• home
• Bone Health and Osteoporosis

Osteoporosis is a bone disease characterized by progressive loss of bone density, leading to an increased risk of fractures, particularly in the hip, spine, and wrist. It occurs when the balance between bone resorption and bone formation is disrupted, often due to factors such as aging, hormonal changes (especially post-menopause in women), nutritional deficiencies (such as calcium and vitamin D), sedentarism, and certain medications or medical conditions (1).

The prevalence of osteoporosis among older adults is significant: it is estimated that over 200 million people suffer from osteoporosis worldwide, with about one in three women and one in five men over the age of 50 experiencing an osteoporotic fracture in their lifetime (1). Osteoporosis represents a major public health concern due to its impact on mobility, quality of life, and healthcare costs associated with fracture management and treatment. Surprisingly, in women over 45 years of age, osteoporosis accounts for more days in hospital than may other diseases, including diabetes, myocardial infarction and breast cancer (3).

Bone Health and Osteoporosis

How can Osteoporosis be prevented ?

Regular exercise and a healthy diet, including the intake of key nutrients like Vitamin D and Calcium, are some key factors that can help in preventing the disease (2).

–Calcium: a healthy adult body contains around 1 kg of calcium, 99% of which is deposited in bone and teeth (4). Good sources of calcium include dairy products, leafy green vegetables, fortified foods, and fish with bones (1).

–Vitamin D: vitamin D plays an important role in regulating calcium and maintaining bone health. Although vitamin D influences various aspects of bone and calcium metabolism, one of its most important functions is the regulation of the efficiency of intestinal calcium (Ca) absorption (5).

The primary source of vitamin D is sunlight; it is synthesized in the skin. The form of vitamin D produced in the skin is known as vitamin D3 (cholecalciferol), while the dietary forms can be either vitamin D3 or a closely related plant-derived compound called vitamin D2 (ergocalciferol). Only a limited number of foods are naturally high in vitamin D. Dietary sources include fatty fish like salmon, sardines, and mackerel, as well as eggs, liver, and in some regions, fortified products such as margarine, dairy items, and cereals. For more information on sources on vitamin D and Vitamin D recommendations : https://www.osteoporosis.foundation/vitamin-d-recommendations.

-Other potentially risk factors for osteoporosis are smoking, alcohol consumption, low or excessive phosphorus intake, protein deficiency or a high-protein diet, excessive consumption of coffee, a sedentary lifestyle or lack of mobility, and insufficient exposure to the sun (6). 

Role of the human skeleton

The human skeleton provides support and structure for the body, protecting vital organs like the brain and heart. It is an important component of the musculoskeletal system, enabling movement. The skeleton also produces blood cells in its bone marrow and stores essential minerals like calcium. The skeleton is  constantly remodeled throughout life, with old bone being broken down and replaced by new tissue to maintain bone mass. This ongoing process of bone resorption and growth is called bone metabolism.

Bone remodeling

Bone remodeling is a continuous and regulated process where various specialized cells primarily osteoclasts breaking down old bone tissue, and osteoblasts building new bone, are involved. These cells constantly interact via factors like osteoprotegerin (OPG) and RANKL (receptor activator of nuclear factor kappa-B ligand) to maintain a healthy balance between bone resorption and bone formation. Imbalances in this process can lead to bone diseases like osteoporosis.  

Bone cells act as endocrine cells, influencing other organs. Osteocytes, the most common bone cell type embedded within the bone, are key regulators of bone formation. They play an important role in bone remodelling and release specific biomarkers such as sclerostin (SOST), fibroblast growth factor 23 (FGF23), and Dickkopf-1 (DKK-1).

 

Biomedica offers a range of ELISA kits to measure bone biomarkers in serum, plasma, and cell cultures

SCLEROSTIN (SOST; cat.no. BI-20492)

OPG  (Osteoprotegerin; cat.no. BI-20403)

RANKL  (soluble RANKL; cat.no. BI-20462)

DKK-1  (Dickkopf-1; cat.no. BI-20413)

FGF23 intact (Fibroblast growth factor-23, intact; cat.no. BI-20700)

FGF23 C-terminal  (Fibroblast growth factor-23, C-terminal; cat.no. cat.no. BI-20702)

PERIOSTIN  (POSTN, BI-20433)

 

• TRUSTED – cited in over 1200 publications
• Kit validations follows international quality guidelines
• Developed & manufactured by Biomedica in Austria

 

Literature

1. Assessment of osteoporosis at the primary health-care level. WHO Scientific Group Technical Report. Kanis J. 2007  [Accessed 22.02.2019];
2. The clinician’s guide to prevention and treatment of osteoporosis. LeBoff M et al. Osteoporos Int 33, 2049–2102 (2022).
3. The prevalence of vertebral deformity in european men and women: the European Vertebral Osteoporosis Study. O’Neill TW et al., J Bone Miner Res, 1996. 11(7): p. 1010-8.
4. Physiology of Calcium Homeostasis: An Overview. Matikainen N et al., Endocrinol Metab Clin North Am. 2021; 50(4):575-590. PMID: 34774235.
5. Vitamin D-Mediated Regulation of Intestinal Calcium Absorption . Fleet JC. Nutrients. 2022 Aug 16;14(16):3351. PMID: 36014856.
6. Osteoporosis – risk factors, pharmaceutical and non-pharmaceutical treatment. Tański W et al., Eur Rev Med Pharmacol Sci. 2021; 25(9):3557-3566. PMID: 34002830.

 

The Enzyme Linked Immunosorbent Assay (ELISA) is a widely used laboratory technique designed to detect and quantify proteins, hormones, antibodies, and other molecules in samples such as serum, plasma, saliva, urine, or cell culture supernatants. ELISA assays are used in various fields, including clinical diagnostics and research.  

Selecting the right ELISA kit is an important decision that greatly impacts the results of your experiments. By thoughtfully evaluating factors like sensitivity, dynamic range, precision, and workflow you can make a well-informed decision that aligns with your research objectives. Other parameters that are better indicators of ELISA performance should also be considered. These include type of samples to be measured, recovery, dilution linearity and parallelism (%) to measure the target protein in real samples like plasma, serum, or cell culture media.

ELISA Assay Principle

The main principle of an ELISA involves the binding of an antigen (the target molecule) to a specific antibody. The assay is mostly carried out in a 96-well plate that is coated with capture antibodies specific to the target antigen.

 

ELISA Assay Protocol- Example:

1. Coating: The wells of the 96-well ELISA microplate are coated with a specific capture antibody that binds to the target antigen.
2. Sample Addition: The sample containing the target antigen is added to the wells. Antigen present in the sample binds to coated capture antibody.
3. Detection Antibody: A secondary antibody that is linked to an enzyme, is then added to the wells. It binds specifically to the target antigen, forming a sandwich complex (capture antibody- antigen – secondary antibody).  
4. Substrate Addition: A substrate (e.g. TMB Tetramethylbenzidine) is added to the wells. The enzyme catalyzed color change of the substrate is directly proportional to the amount of target protein present in the sample.
5. Signal Measurement: The color change and the intensity of the color is directly proportional to the amount of target antigen in the samples. It is detectable with a standard microtiter plate ELISA reader (spectrophotometer). A dose response curve of the absorbance (optical density, e.g. OD at 450 nm) versus the standard concentration is generated, using the values obtained from the standards (calibrators).

 

ELISA Assay, 96 well microtiter plate

 

How to select the right ELISA kitBefore purchasing an ELISA assay, always read the kit protocol booklet (package insert). This may help to decide if the kit will be suitable for your needs.

Check as follows:

1. ANALYTE

Which protein biomarker will you be measuring? Be sure to use the correct term during your search. Some biomarker proteins have alternative names (e.g. PERIOSTIN or POSTN ELISA (POSTN is the gene that encodes Periostin).

2. SPECIES – SPECIFICITY – CROSS REACTIVITY

Verify if the assay can be used in the respective model you will be measuring- e.g. human, or preclinical samples such as rat, mouse, monkey. Often ELISA kits can be used for various species, due to high homology between species. As an example the biomarker ELISA kit for NT-proANP was developed for measurements in human samples. Due to the high sequence homology between species, the kit is successfully used to measure NT-proANP as a cardiac safety biomarker in various animal models (rat, mouse, rabbit, monkey). 

3. SAMPLE TYPE

Which sample type (matrix) will you be using (e.g. EDTA-plasma, heparin-plasma, citrate-plasma, serum, cell culture supernatants, urine..) ?

Verify if the assay is compatible for your sample type and check the information in the protocol book. Also check if the assay validation was performed in the respective sample type you will be using. These data can often be found on the website of the assay manufacturer.

Important: the analysis of some biomarkers in the “wrong” sample matrix may lead to “false” results due to a matrix effect.

4. SAMPLE VOLUME

Verify the sample volume that will be required per well, consider duplicates when measuring your samples.

5. SENSITIVTY – BIOMARKER CONCENTRATIONS TO BE EXPECTED

The sensitivity of an ELISA assay refers to the lowest limit of detection (LOD) of the protein that can be detected with the antibody pair used in the ELISA kit. The sensitivity depends mainly on the affinity of the solid phase antibody (coating antibody). Therefore, using a high affinity antibody can increase sensitivity.

-Analytical sensitivity – limit of detection (LOD) is the lowest concentration that can be measured (detected) with statistical significance by means of a given analytical procedure. This concentration is calculated as the background +/- 2 standard deviations.

-Functional Sensitivity –  lower limit of detection (LLOQ) is the lowest concentration at which the analyte can be reliably detected.

How to select the right ELISA kit – before selecting an assay, study the validation data provided in the protocol booklet.

Some companies document the data on their respective website- product page. Documented reference values in an apparently healthy cohort and/or pathological values in serum and/or plasma of the analyte of interest may also be helpful to get an idea in which range sample values can be expected. It will be helpful to know which levels of the target protein can be expected in your respective sample. Sometimes samples require a pre-dilution step to assure that the signal falls within the dynamic range of the assay. Check the information in the protocol booklet if samples require a pre-dilution step and if the dilution buffer is included in the kit.

Of note: assays offering high sensitivity offer a different dynamic range than assays with a lower sensitivity.

    6. DYNAMIC RANGE

The dynamic range if an ELISA refers to the upper and lower range of concentrations of the target protein that the assay can accurately quantify.

Of note: the reported values given for the sensitivity and dynamic range of an assay can be misleading because they are often determined by using the standard protein (calibrators) in a assay buffer. However, this often does not represent the kinetic of detection of an endogenous protein /analyte in the biological sample.

7. ACCURACY / RECOVERY

The accuracy of an ELISA assay correctly identifies the presence or absence of the target protein/antigen (biomarker of interest) in a specific sample, which excludes matrix effects that may interfere with the measurement of the analyte of interest.

The accuracy (% recovery) is determined by spiking a biological sample (= sample matrix: serum, plasma-EDTA, heparin, citrate) with a known amount of the purified target protein. The spiked sample is then measured in the ELISA and the concentration is calculated from the standard curve. This calculated concentration is compared to the known concentration of the protein which is expressed as a percentage of recovery. As an example, a 90% recovery means that the measured concentration in the sample is 10% lower than the actual concentration of spiked protein in the sample. It suggests that the proteins and other molecules in the sample type did not interfere with the quantification of the protein.

8. ASSAY PERFORMANCE – ASSAY VALIDATION

Evaluation of the assay´s performance characteristics is important in choosing an ELISA kit.

Select an assay that has gone through a rigorous validation process. Data on the following performance characteristics should be available:

• Accuracy (% recovery) – detection of a protein biomarker in clinical samples (acceptance criteria: ≥ 80% recovery).
• Dilution linearity and parallelism  – recovery of the analyte of interest in diluted samples (acceptance criteria: ≤ 20% difference from undiluted samples)
• Specificity & cross-reactivity – making sure that you detect only the analyte of interest
• Precision – within-run (intra-assay) precision and in-between run (inter-assay) precision – ensuring precise and reproducible results within an across assay lots (acceptance criteria: ≤ 15%). The CV (%) or coefficient of variability shows how consistent the assay is.
• Calibration – ensures consistent performance over the range of the assay of the calibration curve
• Sample stability – ensures the stability of the analyte of interest (e.g. exposure of real samples to multiple freeze-thaw cycles, stability at room temperature..).
• Sensitivity – depends on the analyte of interest.
• Dynamic range– depends on the analyte of interest.
• Specificity – verify reactivity with highly homologous proteins
• Calibration – ensures consistent performance over the range of the assay of the calibration curve
• Sample stability – ensures the stability of the analyte of interest (e.g. exposure of real samples to multiple freeze-thaw cycles, stability at room temperature..).

 

9. COMPONENTS of the KIT

Verify if the content of the ELISA assay kit includes all the necessary components e.g. controls, assay dilution buffer. Consider storage requirements such as temperature sensitivity and expiration date.

10. REFERENCES &CITATIONS

Verify for available citations of the specific ELISA kit. These publications can usually be found on the manufacturer´s website.  

11. PRODUCT ORIGIN

Check the originator of the ELISA kit – who developed and manufactured the assay?  More and more kits are repacked and are sold under different brands, although it is always the same kit.

The originator of the ELISA kit will more likely give you qualified support as they “know” their product (e.g. availability of additional calibrators, controls, buffers.., technical know-how on the kit..).

12. CUSTOMER SUPPORT

Verify if the kit provider can provide timely and helpful customer service.

 

 

 

 

Literature

Characterization of a sandwich ELISA for the quantification of all human periostin isoforms.Gadermaier E, Tesarz M, Suciu AA, Wallwitz J, Berg G, Himmler G. J Clin Lab Anal. 2018 Feb;32(2):e22252. doi: 10.1002/jcla.22252. Epub 2017 May 11. PMID: 28493527; PMCID: PMC6816904.

 

Make Testing Easy

We at Biomedica offer tailored analytical testing services for ELISA Kits, Luminex Assays, and microRNA Analysis.

Custom Service Measurements for ELISA-Luminex-microRNA

Highlights:

-Professional: all analytics are carried out by experts

-Quality: we pursue excellence in quality

-Flexibility: tailored solutions according to your needs

-Efficient: save your time and budget – fast turnaround time

 

Learn more about the Biomedica Service Measurements  here  

Our measurement services include:

ELISA Assay Kits

We offer services for our proprietary Biomedica ELISA kits (see product list) as well as for ELISA Assays from other providers.

Luminex Technology Multiplex Assays

We utilize Luminex xMAP® (multiple analyte profiling) technology-based immunoassays, enabling the simultaneous detection and quantification of multiple biomarkers.

For more information please see our workflow chart or reach out to us directly to discuss how we can support your specific research project

NEXT-GENERATION SEQUENCING & RT-qPCR MICRORNA SERVICES

We provide a comprehensive range of high-quality RNA services, including RNA extraction, next-generation sequencing (NGS), RT-qPCR, and custom analysis of microRNA signatures, all performed by our experienced laboratory staff. Our services include:

• RNA extraction from biofluids (serum, plasma, extracellular vesicles), cells, and tissues (quality control of total RNA utilizes Bioanalyzer chips)
• Next-generation sequencing (NGS)
• RT-qPCR
• Cell-type specific microRNA/mRNA analysis in complex tissues, along with custom analysis of microRNA signatures

 

For more details about our microRNA services, please visit our website and contact us directly.

 

Literature

Circulating Micro-RNAs in Patients with Hypophosphatasia Results of the first micro-RNA analysis in HPP. Haschka J, Messner Z, Feurstein J, Hadzimuratovic B, Zwerina J, Diendorfer AB, Pultar M, Hackl M, Kuzma M, Payer J, Resch H, Kocijan R.J Clin Endocrinol Metab. 2025 Feb 11:dgaf080. doi: 10.1210/clinem/dgaf080. Epub ahead of print. PMID: 39930630.

Abstract

The EZ4U (easy for you) colorimetric assay from Biomedica (cat. no. BI-5000) is a modified MTT assay for assessing cell metabolic activity.

Assessing metabolic activity of cells

Our EZ4U cell proliferation assay was highlighted in a recent study that investigated the development of novel chemosensitizers targeting therapy-resistant cancer stem cells (CSCs). The study offers an understanding of the structural criteria necessary for optimizing telmisartan, an angiotensin II receptor blocker, and its derivatives as non-toxic chemosensitizers. Furthermore, the findings indicate that these derivatives could be utilized to target and eliminate the cancer stem cell (CSC) population in chronic myeloid leukemia (CML), as well as the therapy-resistant CSCs in solid tumors like ovarian, prostate, lung, and breast cancers.

Learn more: Eradication of Therapy-Resistant Cancer Stem Cells by Novel Telmisartan Derivatives. Schoepf Anna M. et al., J Med Chem. 2025; 68(1):287-306.

Abstract

The present structure-activity relationship study investigates the development of novel chemosensitizers targeting therapy-resistant cancer stem cells (CSCs). We used 4′-((2-propyl-1H-benzo[d]imidazole-1-yl)methyl)-[1,1′-biphenyl]-2-carboxylic acid, derived from the angiotensin II type 1 receptor blocker telmisartan, as a lead structure, demonstrating that the biphenyl moiety is essential for chemosensitizing activity. Introducing a methyl carboxylate or carboxamide instead of the COOH-group significantly enhanced this effect, leading to the development of highly potent compounds. These novel, noncytotoxic chemosensitizers effectively target CSCs and overcome drug resistance by interfering with CSC persistence mechanisms─hyperactivated STAT5 signaling and increased drug transporter activity─with demonstrated efficacy in leukemia, ovarian, and prostate cancers. The carboxamide of telmisartan (telmi-amide, 7c) significantly reduced tumor growth in an imatinib-resistant leukemia xenograft model, both as monotherapy and combined with imatinib, showing promising oral bioavailability and tolerability. In summary, telmisartan derivatives act as effective chemosensitizers and offer an innovative strategy for targeting CSCs in various malignant diseases.

Determination of Metabolic Activity

Brief: ”COS-7 (2 × 10³ cells per well), IGROV-1 SP (2.5 × 10³ cells per well), A2780 V SP (1.5 × 10³ cells per well), PC3-DR (4 × 10³ cells per well), and DU145-DR (3 × 10³ cells per well) cells were seeded in 96-well plates in triplicates and after 24 h, the compounds were added at the respective concentrations. The cells were incubated at 37 °C in a humidified atmosphere (5% CO₂/95% air) for 72 h. A modified MTT colorimetric assay (EZ4U kit, Biomedica) was used to determine the metabolic activity of the tested cells, according to the manufacturer’s instructions. Absorbance was measured and the optical density of the respective FCS-containing medium and of the substrate was subtracted to exclude nonspecific staining. Metabolic activity in the absence of the compounds (CTR, DMSO) was set to 100% as reference. The results of the compounds in all assays are represented by the mean values + SEM of ≥3 independent experiments with three replicates each.”

Assessing metabolic activity of cells:

EZ4U – Cell Proliferation & Cytotoxicity Assay (cat.no. BI-5000)

-Non-radioactive & non-toxic assay

-Reliable & Sensitive

-Convenient single-step incubation  – for use on living cells

-Widely cited in more than 290 publications

 

BROCHURE – EZ4U cell proliferation and cytotoxicity assay

 

Infertility is a worldwide health issue that impacts 17.5% of couples globally (1). Although male infertility is quite prevalent, there are limited treatment options available (2).

RANKL regulates male reproductive function 

A study published by Blomberg Jensen M et al, identified RANKL as a regulator of male reproductive function: RANKL regulates male reproductive function. Nat Commun. 2021; 12(1):2450.

Abstract

Infertile men have few treatment options. Here, we demonstrate that the transmembrane receptor activator of NF-kB ligand (RANKL) signaling system is active in mouse and human testis. RANKL is highly expressed in Sertoli cells and signals through RANK, expressed in most germ cells, whereas the RANKL-inhibitor osteoprotegerin (OPG) is expressed in germ and peritubular cells. OPG treatment increases wild-type mouse sperm counts, and mice with global or Sertoli-specific genetic suppression of Rankl have increased male fertility and sperm counts. Moreover, RANKL levels in seminal fluid are high and distinguishes normal from infertile men with higher specificity than total sperm count. In infertile men, one dose of Denosumab decreases RANKL seminal fluid concentration and increases serum Inhibin-B and anti-Müllerian-hormone levels, but semen quality only in a subgroup. This translational study suggests that RANKL is a regulator of male reproductive function, however, predictive biomarkers for treatment-outcome requires further investigation in placebo-controlled studies.

In a more recent study by Andreassen CH et al , Denosumab, a RANKL inhibitor to treat osteoporosis, showed a beneficial response to treat infertile men in a subgroup of individuals: Denosumab stimulates spermatogenesis in infertile men with preserved Sertoli cell capacity. M.Cell Rep Med. 2024; 5(10):101783.

Summary

Sperm production depends on proper Sertoli-germ cell interaction, and we hypothesized that receptor activator of nuclear factor κB ligand (RANKL) activity in Sertoli cells may influence spermatogenesis. Treatment with the RANKL inhibitor denosumab, normally used to treat osteoporosis, increased testicular weight, inhibin B, and germ cell proliferation in ex vivo testis cultures and in vivo in a humanized RANKL mouse. The effect on germ cell proliferation was positively associated with baseline serum concentrations of anti-müllerian hormone (AMH). In accordance, denosumab increased germ cell proliferation in ex vivo human testis cultures with low/moderate but not severe impairment of Sertoli cell function. In a placebo-controlled randomized clinical trial, denosumab had no effect on semen quality but increased sperm concentration in a subgroup of infertile men with serum AMH ≥38 pmol/L at baseline. In conclusion, high serum AMH may increase the probability of a beneficial response to denosumab treatment in infertile men, thus suggesting a possible venue for precision medicine in male infertility.

The BIOMEDICA soluble RANKL (sRANKL) ELISA assay (cat. no. BI-20462) and Osteoprotegerin – OPG ELISA assay (cat. no. BI-20403) was utilized in both studies to quantify soluble RANKL and OPG levels in human serum and seminal fluid.

 

Key findings

• Infertile men had significant higher seminal sRANKL concentration and lower serum sRANKL levels than healthy men.
• Seminal fluid levels of sRANKL were approx. 100-fold higher than corresponding serum levels.
• High RANKL levels in seminal fluid distinguishes normal from infertile men with higher specificity than total sperm count.
• One dose of Denosumab, a RANKL inhibitor, decreases RANKL seminal fluid concentration.
• Denosumamb treatment in infertile men suggests a potential approach in addressing male infertility.

 

Soluble RANKL HS ELISA assay kit (cat. no. BI-20462)

• High sensitivity – measurable concentrations in healthy subjects
• Only ELISA that measures free, uncomplexed soluble RANKL
• Widely cited in more than 320 publications

 

OSTEOPROTEGERIN (OPG) ELISA assay kit (cat. no. BI-20403)

• Reliable – validated according to international guidelines
• Most referenced human OPG ELISA – 270 citations
• Only 20µl sample volume required 

 

Literature

1. World Health Organization. 2023. Infertility prevalence estimates 1990-2021 .
2. Denosumab stimulates spermatogenesis in infertile men with preserved Sertoli cell capacity. Andreassen CH, Holt R, Juel Mortensen L, Knudsen NK, Nielsen JE, Poulsen NN, Yahyavi SK, Boisen IM, Cui Z, Ongaro L, Hjerresen JP, Toft BG, Hasselager T, Jørgensen NR, Bernard DJ, Juul A, O’Brien C, Jørgensen A, Blomberg Jensen M.Cell Rep Med. 2024 Oct 15;5(10):101783. doi: 10.1016/j.xcrm.2024.101783. PMID: 39383870.
3. RANKL regulates male reproductive function. Blomberg Jensen M, Andreassen CH, Jørgensen A, Nielsen JE, Juel Mortensen L, Boisen IM, Schwarz P, Toppari J, Baron R, Lanske B, Juul A. Nat Commun. 2021 Apr 23;12(1):2450. doi: 10.1038/s41467-021-22734-8. PMID: 33893301; PMCID: PMC8065035.

 

Preterm birth, defined as birth before 37 weeks of gestation, affects around 10.6% of all live births globally (1). Preterm birth has been identified as a significant factor contributing to long-term cardiovascular morbidity and mortality (2). It is associated with an increased risk of elevated blood pressure, hypertension, type 1 and type 2 diabetes, decreased elasticity of the aorta, ischemic heart disease, heart failure, stroke, chronic kidney disease, and cardiovascular mortality during early childhood and young adulthood (3). A recent long-term prospective cohort study has demonstrated a connection between childhood cardiovascular risk factors and adult cardiovascular events (3).

Due to the challenge posed by prematurity and its link to cardiovascular disease, there is a need for biomarkers that can identify individuals at elevated risk, allowing for prompt therapeutic interventions. In adults, fibroblast growth factor-23 (FGF-23) has gained attention as a potential biomarker for cardiovascular disease. Elevated levels of FGF-23 are linked to hypertension, increased left ventricular mass and hypertrophy, as well as a higher incidence of coronary heart disease, heart failure, and overall cardiovascular mortality (4).

In this following pilot study a total number of 26 former very preterm infants (mean gestational age 29.5 weeks) and 21 term-born children (mean gestational age 40.3 weeks), were included. Biomarkers such as FGF23 intact (iFGF23), FGF23 (c-terminal) (cFGF23), Klotho, and HIF-1α were measured in plasma. Significantly higher concentrations were observed only for iFGF-23 and secretoneurin in former very preterm infants in comparison to term-born controls. No differences in HIF-1α, cFGF-23 and α-Klotho were detectable : Young hearts, early risks: novel cardiovascular biomarkers in former very preterm infants at kindergarten age. Mitterer W et al., Pediatr Res. 2024.

 

FGF23 can easily be measured in serum and plasma samples with a conventional ELISA assay:

BIOMEDICA – FGF-23 (intact) ELISA and FGF-23 (C-terminal) multi-matrix ELISA 

 Kit highlights

• Multi-Matrix: works with plasma, serum, and cell culture
• Convenient: 50µl sample/well, all buffers included.
• Reliable: validated quality
• Easy handling: 7 standards and 2 controls
• Comparable: strong correlation with existing methods
• Cited in over 80 publications

 

Literature

1. Global, regional, and national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis. Chawanpaiboon S, Vogel JP, Moller AB, Lumbiganon P, Petzold M, Hogan D, Landoulsi S, Jampathong N, Kongwattanakul K, Laopaiboon M, Lewis C, Rattanakanokchai S, Teng DN, Thinkhamrop J, Watananirun K, Zhang J, Zhou W, Gülmezoglu AM. Lancet Glob Health. 2019 Jan;7(1):e37-e46. doi: 10.1016/S2214-109X(18)30451-0. Epub 2018 Oct 30. PMID: 30389451; PMCID: PMC6293055.
2. Mortality Among Young Adults Born Preterm and Early Term in 4 Nordic Nations. Risnes K, Bilsteen JF, Brown P, Pulakka A, Andersen AN, Opdahl S, Kajantie E, Sandin S.JAMA Netw Open. 2021 Jan 4;4(1):e2032779. doi: 10.1001/jamanetworkopen.2020.32779. Erratum in: JAMA Netw Open. 2021 Feb 1;4(2):e210068. doi: 10.1001/jamanetworkopen.2021.0068. PMID: 33416885; PMCID: PMC7794670.
3. Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events. Jacobs DR Jr, Woo JG, Sinaiko AR, Daniels SR, Ikonen J, Juonala M, Kartiosuo N, Lehtimäki T, Magnussen CG, Viikari JSA, Zhang N, Bazzano LA, Burns TL, Prineas RJ, Steinberger J, Urbina EM, Venn AJ, Raitakari OT, Dwyer T.N Engl J Med. 2022 May 19;386(20):1877-1888. doi: 10.1056/NEJMoa2109191. Epub 2022 Apr 4. PMID: 35373933; PMCID: PMC9563825.
4. Fibroblast growth factor-23 and incident coronary heart disease, heart failure, and cardiovascular mortality: the Atherosclerosis Risk in Communities study. Lutsey PL, Alonso A, Selvin E, Pankow JS, Michos ED, Agarwal SK, Loehr LR, Eckfeldt JH, Coresh J J Am Heart Assoc. 2014 Jun 10;3(3):e000936. doi: 10.1161/JAHA.114.000936. PMID: 24922628; PMCID: PMC4309096.

 

 

Our Osteoprotegerin (OPG) ELISA assay was highlighted in a recent study assessing serum OPG levels during acute inflammatory states induced by a bacterial or viral infection in children. The researchers investigated whether OPG increases during acute inflammatory states and if its levels correlate with other biomarkers. OSTEOPROTEGERIN increases in infection-induced acute inflammation

OPG, a key regulator of bone metabolism (1). OPG suppresses osteoclastogenesis and is expressed in peripheral lymph nodes, osteoblasts, and bone marrow stromal cells. Moreover, OPG is involved in the inflammatory processes of chronic conditions, such as rheumatoid arthritis, ankylosing spondylitis, and Crohn’s disease. The elevated serum levels of OPG observed in these conditions are likely due to the activation of pro-inflammatory proteins like tumor necrosis factor α (TNF-α), which enhances OPG expression (3, 4).

OSTEOPROTEGERIN serum levels increase in infection-induced acute inflammation

Discoveries in recent years have revealed a close relationship between bone biology and immunity. This connection is emphasized by shared regulatory molecules, including cytokines, receptors, and transcription factors. In particular, the receptor activator of nuclear factor NF-kB (RANK) and its ligand (RANKL) are crucial for osteoclast differentiation and the development of immune organs such as the bone marrow, thymus, lymph nodes, and gut-associated lymphoid tissue. The third key element in this system is osteoprotegerin (OPG), a decoy receptor that inhibits RANK signaling by binding to RANKL (2).

Osteoprotegerin (OPG) can reliably be measured with a conventional ELISA assay

 Biomedica OPG ELISA (cat. no. BI-20403)

• Method: Sandwich ELISA, 12×8-well detachable strips
• Sample: Serum, plasma (EDTA, citrate, heparin)
• Sample volume: 20μl / well
• Detection range: 1.25-20 pmol/L (= 25 – 400 pg/mL)
• Sensitivity: 0.07 pmol/L (= 1.4 pg/mL)
• Incubation time: 4 h + 1 h + 30 min (room temperature)
• Precision: In-between-run (n=12): ≤ 5 % CV: Within-run (n=5): ≤ 3 % CV
• Widely cited in over 260 publications!

 

Fully validated Osteoprotegerin ELISA assay – validation data can be found here .

Osteoprotegerin in infection-induced acute inflammatory states in children. Giannakopoulos A et al., 2024.  

Key findings:

-The study provides the proof of concept for an increase of OPG during acute inflammatory states induced only by bacterial infections.

-OPG returns to baseline after resolution of the infection.

-OPG correlates well with CRP only in the group with bacterial infection, although with a lower sensitivity than CRP.

 

Literature

1. Osteoprotegerin in infection-induced acute inflammatory states in children. Giannakopoulos A, Efthymiadou A, Kritikou D, Chrysis D. Heliyon. 2024 Mar 7;10(6):e27565. doi: 10.1016/j.heliyon.2024.e27565. PMID: 38509997; PMCID: PMC10951505.
2. Discovery of the RANKL/RANK/OPG system. Yasuda H. J Bone Miner Metab. 2021 Jan;39(1):2-11. doi: 10.1007/s00774-020-01175-1. Epub 2021 Jan 3. Erratum in: J Bone Miner Metab. 2021 Jan;39(1):12. doi: 10.1007/s00774-021-01203-8. PMID: 33389131.
3. The RANK-RANKL-OPG System: A Multifaceted Regulator of Homeostasis, Immunity, and Cancer. De Leon-Oliva D, Barrena-Blázquez S, Jiménez-Álvarez L, Fraile-Martinez O, García-Montero C, López-González L, Torres-Carranza D, García-Puente LM, Carranza ST, Álvarez-Mon MÁ, Álvarez-Mon M, Diaz R, Ortega MA. Medicina (Kaunas). 2023 Sep 30;59(10):1752. doi: 10.3390/medicina59101752. PMID: 37893470; PMCID: PMC10608105.
4. Interaction between bone and immune cells: Implications for postmenopausal osteoporosis. Fischer V, Haffner-Luntzer M. Semin Cell Dev Biol. 2022 Mar;123:14-21. doi: 10.1016/j.semcdb.2021.05.014. Epub 2021 May 20. PMID: 34024716.

The Biomedica SCLEROSTIN ELISA Assay Kit (cat. no. BI-20492) was utilized in a recent publication identifying high-risk frailty groups (full publication).  

Sclerostin (SOST) ELISA  (cat. no. BI-20492)

• Most referenced Sclerostin ELISA in over 300 citations
• Low sample volume – 20µl / well
• Validation following international guidelines

 

SCLEROSTIN – a biomarker for predicting the onset of frailty

SCLEROSTIN, a protein that is predominantly produced by osteocytes, has gained considerable attention for its role in inhibiting bone formation (1).  In addition to its effects on bone, sclerostin has been shown to have hormonal functions in non-skeletal tissues like adipocytes, blood vessels, muscles, and kidneys, where it plays a role in endothelial function, energy balance, glucose metabolism, physical performance, and kidney health (2-4). This broader systemic involvement highlights its potential effects on overall health.

Sclerostin circulates in the blood as a secreted protein and can easily be measured by ELISA assay technology, making it a promising biomarker for various age-related conditions, such as osteoporosis, sarcopenia, and cardiovascular diseases. The link between serum Sclerostin levels and frailty has not yet been studied. In a recent clinical study the relationship between circulating sclerostin levels and frailty, using both the phenotypic frailty model and the frailty index in a group of older adults has been investigated.

SCLEROSTIN – a biomarker for predicting the onset of frailty

Elevated Circulating Sclerostin Levels in Frail Older Adults: Implications beyond Bone Health. Baek JY et al., Endocrinol Metab (Seoul). 2025; 40(1):73-81. doi: 10.3803/EnM.2024.2100. PMCID: PMC11898323.

“Methods: We collected blood samples from 244 older adults who underwent comprehensive geriatric assessments. Sclerostin levels were quantified using an enzyme-linked immunosorbent assay. Frailty was assessed using two validated approaches: the phenotypic model by Fried and the deficit accumulation frailty index (FI) by Rockwood.

Results: After controlling for sex, age, and body mass index, we found that serum sclerostin levels were significantly elevated in frail individuals compared to their robust counterparts (P<0.001). There was a positive correlation between serum sclerostin concentrations and the FI (P<0.001). Each standard deviation increase in serum sclerostin was associated with an odds ratio of 1.87 for frailty (P=0.003). Moreover, participants in the highest quartile of sclerostin levels had a significantly higher FI and a 9.91-fold increased odds of frailty compared to those in the lowest quartile (P=0.003 and P=0.039, respectively).

Conclusion: These findings, which for the first time explore the association between circulating sclerostin levels and frailty, have significant clinical implications, positioning sclerostin as one of potential blood-based biomarkers for frailty that captures the comprehensive physical, mental, and social aspects of the elderly, extending beyond its traditional role in bone metabolism.”

 

Literature

1. Role of Wnt signaling and sclerostin in bone and as therapeutic targets in skeletal disorders. Marini F, Giusti F, Palmini G, Brandi ML.Osteoporos Int. 2023 Feb;34(2):213-238. doi: 10.1007/s00198-022-06523-7. Epub 2022 Aug 18. PMID: 35982318.
2. Sclerostin: From Molecule to Clinical Biomarker. Omran A, Atanasova D, Landgren F, Magnusson P. Int J Mol Sci. 2022 Apr 26;23(9):4751. doi: 10.3390/ijms23094751. PMID: 35563144; PMCID: PMC9104784.
3. Role of Sclerostin in Cardiovascular Disease. Golledge J, Thanigaimani S. Arterioscler Thromb Vasc Biol. 2022 Jul;42(7):e187-e202. doi: 10.1161/ATVBAHA.122.317635. Epub 2022 May 12. PMID: 35546488.
4. Exploring the Role of Sclerostin as a Biomarker of Cardiovascular Disease and Mortality: A Scoping Review. Sanabria-de la Torre R, González-Salvatierra S, García-Fontana C, Andújar-Vera F, García-Fontana B, Muñoz-Torres M, Riquelme-Gallego B. Int J Environ Res Public Health. 2022 Nov 30;19(23):15981. doi: 10.3390/ijerph192315981. PMID: 36498053; PMCID: PMC9739125.

Our Fibroblast Growth Factor-23 (FGF-23) C-terminal ELISA assay was highlighted in a recent clinical study in hypertensive patients. The researchers evaluated whether individuals with “functional vitamin D deficiency” significantly benefit from vitamin D supplementation. As of now, there is no widely accepted definition of functional vitamin D deficiency. Thus, the authors explored the hypothesis that a specific definition of functional vitamin D deficiency could help identify individuals who would significantly benefit from vitamin D supplementation.

The authors concluded that the criteria for functional vitamin D deficiency indicate that patients with vitamin D deficiency do not experience significant improvements in bone markers or cardiovascular risk factors following vitamin D supplementation. Furthermore, additional research is needed to determine whether measuring vitamin D metabolites alongside 25(OH)D is beneficial for accurately classifying vitamin D status and identifying individuals who would particularly benefit from vitamin D treatment.

Classification of Vitamin D status based on its metabolism

Classification of Vitamin D Status Based on Vitamin D Metabolism: A Randomized Controlled Trial in Hypertensive Patients. Zelzer S, Meinitzer A, Enko D, Keppel MH, Herrmann M, Theiler-Schwetz V, Trummer C, Schmitt L, Tomaschitz A, Sadoghi P, Dierkes J, Pludowski P, Zittermann A, März W, Pilz S. Nutrients. 2024 Mar 14;16(6):839. doi: 10.3390/nu16060839. PMID: 38542750; PMCID: PMC10975656.

Abstract

Circulating 25-hydroxyvitamin D (25(OH)D) is the generally accepted indicator of vitamin D status. Since hydroxylation of 25(OH)D to 24-25-dihydroxyvitamin D (24,25(OH)2D) is the first step of its catabolism, it has been suggested that a low 24,25(OH)D level and a low vitamin D metabolite ratio (VMR), i.e., 24,25(OH)2D divided by 25(OH)D, may indicate high vitamin D requirements and provide additional diagnostic information beyond serum 25(OH)D. We, therefore, evaluated whether the classification of “functional vitamin D deficiency”, i.e., 25(OH)D below 50 nmol/L, 24,25(OH)2D below 3 nmol/L and a VMR of less than 4%, identifies individuals who benefit from vitamin D supplementation. In participants of the Styrian Vitamin D Hypertension trial, a randomized controlled trial (RCT) in 200 hypertensive patients with serum 25(OH)D below 75 nmol/L, who received either 2.800 international units of vitamin D per day or placebo over 8 weeks, 51 participants had functional vitamin D deficiency. In these individuals, there was no treatment effect of vitamin D supplementation on various parameters of bone metabolism and cardiovascular risk except for a significant effect on parathyroid hormone (PTH) and expected changes in vitamin D metabolites. In conclusion, a low vitamin D metabolite profile did not identify individuals who significantly benefit from vitamin D supplementation with regard to bone markers and cardiovascular risk factors. The clinical significance of functional vitamin D deficiency requires further evaluation in large vitamin D RCTs.

BIOMEDICA provides two distinct ELISA assays to reliably quantify FGF23 concentrations in human serum and plasma.

 FGF23 intact ELISA (cat. no. BI-20700)

 FGF23 (C-terminal) ELISA (cat. no. BI-20702)

Features and benefits  

• MULTI-MATRIX: for plasma, serum, cell-culture

• CONVENIENT: 50 µl sample/well, all buffers included

• RELIABLE: validated following quality guidelines

• COMPARABLE: good correlation with existing kits

• EASY HANDLING: 7 prediluted standards, 2 controls

• TRUSTED: cited in more than 80 publications

All Assays are Developed & Manufactured by Biomedica

Biomarkers have long been used as indicators of biological changes. In the context of drug development, they serve two key functions: predicting drug efficacy and detecting potential toxicity.

Cardiotoxicity is a significant reason for the failure of preclinical safety tests during the drug development process. Consequently, monitoring cardiac toxicity through biomarkers is a crucial component of drug development.

Cardiac Safety Biomarkers for Toxicity Testing

The biomarkers NT-proANP and NT-proBNP are cardiac hormones released when the heart muscle is stretched. They are part of the natriuretic peptides family and serve as cardiac biomarkers in both human studies and in animal studies (1-4).

In preclinical settings, they have been effectively utilized to identify cardiotoxicity (3). NT-proBNP and NT-proANP have proven to be valuable tools that enhance the early detection of cardiovascular injury during drug development (4). NT-proANP has also been measured to study Heart Failure with preserved Ejection Fraction (HFpEF) in a mouse model to probe preload-dependency (5). Furthermore, N-terminal pro-atrial natriuretic peptide (NT-proANP) was also quantified to assess left ventricular (LV) function in a rat model of cardiac arrest (CA) (6).

Biomedica provides reliable ELISA kits for the quantification of NT-proBNP and NT-proANP in samples from humans and rodents.

Rat NT-proBNP ELISA (cat. no. BI-1204R)

• Sample type: rat serum, plasma
• Sample volume: 10 µL/well
• Sensitivity: LOD 21 pg/ml
• Standard curve range: 0 – 3200 pg/ml (0 / 100 / 200 / 400 / 800 / 1600 / 3200 pg/ml)
• Assay time: 3.5 hours
• Protocol booklet click here – reference values provided

 

NT-proBNP ELISA (cat.no. SK-1204) – for human serum and plasma samples

• CE marked for IVD use in the EU
• Proficiency testing , saliva protocol
• Widely cited

 

NT-proANP ELISA (Cat. No. BI-20892)

Due to the high sequence homology of NT-proANP among species the assay has also been used in rodent (rat, mouse) rabbit, and dog samples.

• Sample types: Serum, plasma, urine, cell culture supernatant (human, rat, mouse, rabbit samples)
• Sample volume: 10 µL/well
• Sensitivity: LOD 0.05 nmol/l (= 0.64 ng/ml)
• Standard curve range: 0 – 10 nmol/l (= 0 – 127 ng/ml)
• Assay time: 3.5 hours
• Citations all , citations with use of rat/mouse samples
• Protocol Booklet click here

 

Literature

1. Circulating N-terminal pro-atrial natriuretic peptide is an independent predictor of left ventricular hypertrophy in the general population. The Tromsø Study. Schirmer H and Omland T. Eur Heart J. 1999; 20(10):755-63. doi: 10.1053/euhj.1998.1396. Erratum in: Eur Heart J 1999 Oct;20(19):1439. PMID: 10329067.
2.  Biomarkers for the diagnosis and management of heart failure. Castiglione V et al., Heart Fail Rev. 2022; 27(2):625-643. PMID: 33852110.
3.  Cardiac Hypertrophy Working Group of the Predictive Safety Testing Consortium. Serum Natriuretic Peptides as Differential Biomarkers Allowing for the Distinction between Physiologic and Pathologic Left Ventricular Hypertrophy. Dunn ME et al., Toxicol Pathol. 2017; 45(2):344-352. PMID: 27102652.
4.  Integrated approach to early detection of cardiovascular toxicity induced by a ghrelin receptor agonist. Stokes AH et al., Int J Toxicol. 2015; 34(2):151-61. PMID: 25722321.
5. Preload dependence in an animal model of mild heart failure with preserved ejection fraction (HFpEF). Jacobsen JCBet al., Acta Physiol (Oxf). 2024; 240(3):e14099. PMID: 38230889.
6. Post-cardiac arrest temporal evolution of left ventricular function in a rat model: speckle-tracking echocardiography and cardiac circulating biomarkers. De Giorgio Det al., Eur Heart J Imaging Methods Pract. 2024; 2(1):qyae006. doi: 10.1093/ehjimp/qyae006. PMID: 39045191.

The BIOMEDICA cardiac biomarker kits NT-proBNP and NT-proANP were used in a recent study exploring the potential for increased cardiovascular complications due to radioactive iodine treatment (RAI) effects in patients with differentiated thyroid cancer (DTC) with or without type 2 diabetes.

The Interplay Between High Cumulative Doses of Radioactive Iodine and Type 2 Diabetes Mellitus: A Complex Cardiovascular Challenge. Stanciu AE et al., Int J Mol Sci. 2024; 26(1):37. PMC11720250.

Abstract

Starting from the metabolic profile of type 2 diabetes mellitus (T2DM), we hypothesized that the mechanisms of ¹³¹I-induced cardiotoxicity differ between patients diagnosed with differentiated thyroid cancer (DTC) with/without T2DM, with metformin potentially acting as a cardioprotective agent by mitigating inflammation in patients with T2DM. To address this hypothesis, we quantified, using ELISA, the serum concentration of several key biomarkers that reflect cardiac injury (NT-proBNP, NT-proANP, ST2/IL-33R, and cTn I) in 74 female patients with DTC/-T2DM and 25 with DTC/+T2DM treated with metformin. All patients received a cumulative oral dose of ¹³¹I exceeding 150 mCi (5.55 GBq) over approximately 53 months.

The results showed the following:

-In DTC/-T2DM patients, high-cumulative ¹³¹I doses promote a pro-inflammatory state that accelerates the development of cardiotoxicity. Monitoring NT-proBNP, ST2/IL-33R, and cTn I in these patients may help identify those at risk of developing cardiac complications.

– In patients with DTC/+T2DM, high-cumulative ¹³¹I doses lead to the release of NT-proANP (r = 0.63), which signals that the atria are under significant stress.

-In patients with DTC/+T2DM, metformin suppresses inflammation, leading to a dose-dependent reduction in cTn I (r = -0.59). Monitoring cTn I and NT-proANP, and considering the use of metformin as part of the therapeutic strategy, could help manage cardiotoxicity in T2DM patients undergoing ¹³¹I therapy.

NT-proANP – a Biomarker for Cardiac Risk

Biomedica NT-proANP (cat. no. BI-20892) and NT-proBNP (cat. no. SK-1204) ELISA Assay Kits

• Trusted – widely cited in over 300 publications
• Quality – fully validated assays following international quality guidelines
• Convenient – kits include pre-diluted calibrators and 2 controls

 

Related publications

Biomarkers for predicting atrial fibrillation: An explorative sub-analysis of the randomised SCREEN-AF trial. Schmalstieg-Bahr K, Gladstone DJ, Hummers E, Suerbaum J, Healey JS, Zapf A, Köster D, Werhahn SM, Wachter R. Eur J Gen Pract. 2024 Dec;30(1):2327367. doi: 10.1080/13814788.2024.2327367. Epub 2024 Mar 18. PMID: 38497412; PMCID: PMC10949835.

Evaluation of left atrial volume and functions by 3D echocardiography in patients with prediabetes and investigation of its correlation with NT-pro ANP levels. Eyyupkoca, Hidayet, Özyalın, Bayramoğlu, Altıntaş, Yağmur, Northwestern Med J (2022) 2 (1), 40-50 DOI: 10.54307/nwmj.2022.33043

Relationship of Natriuretic Peptides with Left Atrial Structure and Function within 1 Month after Electrical Cardioversion in Patients with Persistent Atrial Fibrillation. Karaliute R, Jureviciute J, Jurgaityte J, Stanaitiene G, Mizariene V, Kazakevicius T, Urboniene D, Kavoliuniene A. Biomed Res Int. 2019 Mar 17;2019:7636195. doi: 10.1155/2019/7636195. PMID: 31008112; PMCID: PMC6441525.

Natriuretic peptides are a group of hormones that play a crucial role in regulating blood pressure, blood volume, and fluid balance in the body. They are primarily produced by the heart in response to increased blood volume and pressure. The main types of natriuretic peptides include:

1. B-Type Natriuretic Peptide (BNP): Primarily produced by the ventricles of the heart, BNP also promotes natriuresis and diuresis (increased urine production) and is a marker used in diagnosing and assessing heart failure (1). Elevated levels of BNP in the blood can indicate heart strain or underlying heart failure. Measurement of BNP or NT-proBNP (the inactive fragment of pro-BNP) levels is commonly used in clinical settings to evaluate patients with suspected heart failure or to monitor the severity of heart disease.

Both BNP (B-type natriuretic peptide) and NT-proBNP (N-terminal pro b-type natriuretic peptide) are important biomarkers used in the assessment of heart failure and other cardiovascular conditions. However, measuring NT-proBNP has some advantages:

-Stability in Blood Samples: NT-proBNP is more stable than BNP in blood samples. NT-proBNP levels remain stable for a longer time, making it more reliable for laboratory handling and storage conditions. BNP, on the other hand, has a shorter half-life and is more susceptible to degradation.

-Longer Half-Life: NT-proBNP has a longer half-life compared to BNP (approximately 60-120 minutes for NT-proBNP vs. 20 minutes for BNP). This longer half-life allows for more consistent detection in patients, especially in acute settings.

 

2. Atrial Natriuretic Peptide (ANP): Secreted by the atria of the heart, ANP helps to lower blood pressure by promoting the excretion of sodium (natriuresis) and water by the kidneys. It also inhibits the renin-angiotensin-aldosterone system (RAAS), which is responsible for increasing blood volume and pressure. Studies have shown that NT-proANP levels are higher in individuals with atrial fibrillation (AF) than in controls (2).

 

 3. C-Type Natriuretic Peptide (CNP): CNP is primarily produced in the endothelial cells and has a role in vascular biology, promoting vasodilation and inhibiting smooth muscle proliferation. CNP is a cardioprotective peptide with high affinity for the ectoenzyme neutral endopeptidase (neprilysin). A recent study investigated if an angiotensin receptor-neprilysin inhibitor treatment acutely affects circulating concentrations of bioactive CNP and its molecular amino-terminal precursor (NT-proCNP). The results of the study showed that Sacubitril/valsartan treatment leads to an increase of  circulating concentrations of both bioactive CNP and NT-proCNP in healthy young men (3).

 

Top quality ELISA kits for your clinical & preclinical research

•  NT-proBNP – human (CE-marked in EU) (cat. no. SK-1204)
• NT-proBNP – rat (new!)  (cat. no. BI-1204R)
• NT-proANP – human, rodent (cat. no. BI-20892) citations rat/mouse
• NT-proCNP- human (cat. no. BI-20812)

 

• widely cited in over 450 publications
• kit validation follows international quality guidelines

 

 

Literature

1. Practical algorithms for early diagnosis of heart failure and heart stress using NT-proBNP: A clinical consensus statement from the Heart Failure Association of the ESC. Bayes-Genis A, Docherty KF, Petrie MC, Januzzi JL, Mueller C, Anderson L, Bozkurt B, Butler J, Chioncel O, Cleland JGF, Christodorescu R, Del Prato S, Gustafsson F, Lam CSP, Moura B, Pop-Busui R, Seferovic P, Volterrani M, Vaduganathan M, Metra M, Rosano G.Eur J Heart Fail. 2023 Nov;25(11):1891-1898. doi: 10.1002/ejhf.3036. Epub 2023 Sep 26. PMID: 37712339.
2. NT-proANP levels in peripheral and cardiac circulation. J Interv Card Electrophysiol. Büttner P, Seewöster T, Obradovic D, Hindricks G, Thiele H, Kornej J.2022 Mar;63(2):409-415. doi: 10.1007/s10840-021-01020-z. Epub 2021 Jun 25. PMID:
3. Circulating Concentrations of C-Type Natriuretic Peptides Increase with Sacubitril/Valsartan Treatment in Healthy Young Men. Thonsgaard S, Prickett TCR, Hansen LH, Wewer Albrechtsen NJ, Andersen UØ, Terzic D, Plomgaard P, Gustafsson F, Goetze JP, Mark PD. Clin Chem. 2022 May 18;68(5):713-720. doi: 10.1093/clinchem/hvac005. PMID: 35175317.

February is designated as “Heart Month,” focusing on raising awareness about heart disease. Advances in biomarker research have transformed the diagnosis and treatment of heart conditions. Current studies on novel exploratory protein biomarkers may provide insight into the intricate mechanisms that underlie the disease process.

Novel Biomarker Assays for Heart Disease

BIG ENDOTHELIN-1, ENDOSTATIN, FGF23, LRG

Big Endothelin-1 (Big ET-1)  is a precursor to the potent vasoconstrictor peptide Endothelin-1 (ET-1), produced by endothelial cells. While ET-1 plays a crucial role in regulating vascular tone and blood pressure, Big ET-1 itself is biologically inactive and serves mainly as a reservoir for ET-1. Big ET-1 has a longer half-life than ET-1 and circulates in equimolar amounts as ET-1, making it a more reliable biomarker.Elevated levels of Big ET-1 can indicate vascular dysfunction and are associated with cardiovascular diseases like hypertension and heart failure (1).

Endostatin  is a naturally occurring protein and a fragment of collagen XVIII that has potent anti-angiogenic properties, inhibiting the formation of new blood vessels. Endostatin has gained attention in the context of heart disease due to its role in modulating angiogenesis and vascular health. In cardiovascular conditions, such as heart failure and ischemic heart disease, endostatin may help regulate the formation of new blood vessels, potentially improving blood flow to damaged heart tissue. Elevated levels of endostatin have been associated with adverse cardiac outcomes (2), suggesting it could serve as a biomarker for heart disease severity.

Fibroblast growth factor-23 (FGF23)  is a hormone primarily produced by osteocytes in bone that plays a significant role in phosphate metabolism and vitamin D regulation. In the context of heart disease, elevated levels of FGF23 have been linked to an increased risk of cardiovascular events and poor outcomes in patients with chronic kidney disease, heart failure, and other cardiovascular conditions. FGF23’s actions can promote left ventricular hypertrophy and contribute to arterial stiffness, which are important factors in heart disease progression. Its rise in response to phosphate overload and inflammation signifies a potential pathophysiological link between mineral metabolism and cardiovascular health.

Leucine-riche alpha-2-glyoprotein (LRG) is a protein involved in the inflammatory response and has emerged as a marker for various cardiovascular diseases. Elevated levels of LRG have been associated with a higher risk of heart disease, including conditions like heart failure and myocardial infarction. This protein is thought to play a role in the pathophysiology of heart disease by influencing inflammation and fibrosis in cardiac tissue. Its presence in the bloodstream may reflect underlying systemic inflammation, which is a crucial factor in the development and progression of cardiovascular disorders (5-7).

NOVEL BIOMARKERS FOR HEART DISEASE

Biomedica offers a range of top-quality ELISA Assay kits for your clinical & preclinical research.

-Big Endothelin-1 (cat. no. BI-20082H)

-Endostatin (cat. no. BI-20742)

-FGF23 intact (cat. no. BI-20700)

-FGF23 c-terminal (cat. no. BI-20702)

-LRG (cat. no. BI-LRG)

 

LITERATURE

1. Plasma concentration of big endothelin-1 and its relation with plasma NT-proBNP and ventricular function in heart failure patients. Rivera M et al., Rev Esp Cardiol. 2005;  58(3):278-84.
2. Endostatin in Renal and Cardiovascular Diseases. Li M et al., Kidney Dis. 2021; 9;7(6):468-481.
3. Circulating endostatin and the incidence of heart failure. Ruge T et al., 2018; 52(5):244-249.
4. FGF23 and Cardiovascular Risk. Prié D. Ann Endocrinol (Paris). 2021 ; 82(3-4):141-143. PMID: 32950228.
5. Leucine-Rich Alpha-2-Glycoprotein: A Novel Predictor of Diastolic Dysfunction. Biomedicines. Loch A, Tan KL, Danaee M, Idris I, Ng ML. 2023 Mar 20;11(3):944. doi: 10.3390/biomedicines11030944. PMID: 36979923; PMCID: PMC10045934.
6. Proteomic analysis of coronary sinus serum reveals leucine-rich α2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure. Watson CJ et al., Circ Heart Fail. 2011; 4(2):188-97.
7. Serum biomarker discovery related to pathogenesis in acute coronary syndrome by proteomic approach  Shin M et al.,Biosci Rep. 2021; 25;41(6):BSR20210344.

 

World Cancer Day is a campaign to promote global awareness of cancer and to encourage its prevention, detection, and treatment. The day was initiated by the Union for International Cancer Control (UICC) in 2000 serving as a platform to promote research, improve education, and increase funding for cancer treatment and care.

World Cancer Day 

Key Statistics: The Global Impact of Cancer

Cancer is one of the foremost causes of mortality around the globe. In 2022, there were nearly 20 million new cases, and 9.7 million deaths attributed to cancer worldwide. Projections indicate that by 2040, the annual number of new cancer cases could reach 29.9 million, with cancer-related deaths increasing to 15.3 million.

In general, cancer rates tend to be highest in countries where populations enjoy greater life expectancy, educational attainment, and living standards. However, certain types of cancer, such as cervical cancer, show a contrasting trend, with the highest incidence found in countries where these measures are lower (1, 2).

Discover BIOMEDICA´s Biomarker ELISA kits for cancer research

Neuropilin-1, Periostin, Semaphorin 4D, Osteoprotegerin, RANKL, LRG1,  and others

 

Advantages of Biomedica ELISA assay kits

• RELIABLE – full validation package
  • CONVENIENT – assay range optimized for clinical samples
  • EASY – ready to use prediluted calibrators & controls
  • LOW sample volumes
  • TRUSTED – widely cited

 

Literature

1. https://www.cancer.gov/about-cancer/understanding/statistics
2. Cancer statistics for the year 2020: An overview. Int J Cancer. Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, Bray F. 2021 Apr 5. doi: 10.1002/ijc.33588. Epub ahead of print. PMID: 33818764.

 

Further reading

Influence of Diet and Nutrition on Prostate Cancer. Matsushita M, Fujita K, Nonomura N. Int J Mol Sci. 2020 Feb 20;21(4):1447. doi: 10.3390/ijms21041447. PMID: 32093338; PMCID: PMC7073095.

Abstract

The incidence of prostate cancer (PCa) displays widespread regional differences, probably owing to differences in dietary habits. Nutrients, including fat, protein, carbohydrates, vitamins (vitamin A, D, and E), and polyphenols, potentially affect PCa pathogenesis and progression, as previously reported using animal models; however, clinical studies have reported controversial results for almost all nutrients. The effects of these nutrients may be manifested through various mechanisms including inflammation, antioxidant effects, and the action of sex hormones. Dietary patterns including the Western and Prudent patterns also influence the risk of PCa. Recent studies reported that the gut microbiota contribute to tumorigenesis in some organs. Diet composition and lifestyle have a direct and profound effect on the gut bacteria. Human studies reported an increase in the abundance of specific gut bacteria in PCa patients. Although there are few studies concerning their relationship, diet and nutrition could influence PCa, and this could be mediated by gut microbiota. An intervention of dietary patterns could contribute to the prevention of PCa. An intervention targeting dietary patterns may thus help prevent PCa.

Breast cancer: A review of risk factors and diagnosis. Medicine (Baltimore). Obeagu EI, Obeagu GU 2024 Jan 19;103(3):e36905. doi: 10.1097/MD.0000000000036905. PMID: 38241592; PMCID: PMC10798762.

Abstract

Breast cancer remains a complex and prevalent health concern affecting millions of individuals worldwide. This review paper presents a comprehensive analysis of the multifaceted landscape of breast cancer, elucidating the diverse spectrum of risk factors contributing to its occurrence and exploring advancements in diagnostic methodologies. Through an extensive examination of current literature, various risk factors have been identified, encompassing genetic predispositions such as BRCA mutations, hormonal influences, lifestyle factors, and reproductive patterns. Age, family history, and environmental factors further contribute to the intricate tapestry of breast cancer etiology. Moreover, this review delineates the pivotal role of diagnostic tools in the early detection and management of breast cancer. Mammography, the cornerstone of breast cancer screening, is augmented by emerging technologies like magnetic resonance imaging and molecular testing, enabling improved sensitivity and specificity in diagnosing breast malignancies. Despite these advancements, challenges persist in ensuring widespread accessibility to screening programs, particularly in resource-limited settings. In conclusion, this review underscores the importance of understanding diverse risk factors in the development of breast cancer and emphasizes the critical role of evolving diagnostic modalities in enhancing early detection. The synthesis of current knowledge in this review aims to contribute to a deeper comprehension of breast cancer’s multifactorial nature and inform future directions in research, screening strategies, and preventive interventions.

Sclerostin and Periostin associated with vascular risk scales in type 2 diabetes

Exciting research news! The BIOMEDICA bioactive Sclerostin and Periostin ELISA kits were used in a groundbreaking study evaluating the association of these bone proteins related to cardiovascular disease (CVD), with the main vascular risk scales in patients with type 2 diabetes.

All Biomedica ELISA assays are fully validated following international quality guidelines.

Bioactive Sclerostin ELISA (cat. no. BI-20472)

• CHARACTERIZED ANTIBODIES – targeting the receptor binding region
• LOW sample volume – 20µl sample /well 

 

Sclerostin ELISA (cat. no. BI-20492)

• TRUSTED – most referenced Sclerostin ELISA (+280 citations)
• LOW sample volume – 20µl sample /well

 

Periostin ELISA (cat. no. BI-20433)

• LOW sample volume – 20µl sample /well
• SPECIFIC – Characterized, epitope mapped capture and detection antibodies:

Characterization of a sandwich ELISA for the quantification of all human periostin isoforms. Gadermaier, E et al.

 

Sclerostin and Periostin associated with vascular risk scales in type 2 diabetes

Type 2 diabetes is linked to an elevated risk of cardiovascular disease (CVD), affecting approximately 35% of patients with the condition (1). As a result, assessing cardiovascular risk is essential for effective disease management in individuals with type 2 diabetes. Various risk scores have been developed to estimate CVD in the general population, including the Framingham Risk Score (FRS), the REGICOR and more recently, the SCORE2-Diabetes was introduced, specifically tailored for individuals with type 2 diabetes (2).

While these computational tools are utilized in clinical practice, there remains a need to investigate new biomarkers that could enhance cardiovascular risk stratification for patients with type 2 diabetes.

Typical bone proteins, including Sclerostin and Periostin, have been linked to cardiovascular disease (CVD). Concurrently, various risk scores have been created to forecast CVD in the general population. The objective of the following study was to examine the relationship between these bone proteins connected to CVD and key vascular risk scales:

Bone proteins are associated with cardiovascular risk according to the SCORE2-Diabetes algorithm. González-Salvatierra S et al., Cardiovasc Diabetol. 2024.  

Key findings:

• Sclerostin and Periostin are associated with vascular risk in the SCORE2-Diabetes algorithm.
• This suggests that Sclerostin and Periostin may serve as useful diagnostic biomarkers for vascular risk in patients with type 2 diabetes.
• Future prospective studies are needed to validate the significance of these bone proteins in assessing vascular risk in the diabetic population.

 

Abstract

Background: Typical bone proteins, such as sclerostin and periostin, have been associated with cardiovascular disease (CVD). Simultaneously, several risk scores have been developed to predict CVD in the general population. Therefore, we aimed to evaluate the association of these bone proteins related to CVD, with the main vascular risk scales: Framingham Risk Score (FRS), REGICOR and SCORE2-Diabetes, in patients with type 2 diabetes. We focus in particular on the SCORE2-Diabetes algorithm, which predicts 10-year CVD risk and is specific to the study population.

Methods: This was a cross-sectional study including 104 patients with type 2 diabetes (62 ± 6 years, 60% males). Clinical data, biochemical measurements, and serum bioactive sclerostin and periostin levels were collected, and different risk scales were calculated. The association between bioactive sclerostin or periostin with the risk scales was analyzed.

Results: A positive correlation was observed between circulating levels of bioactive sclerostin (p < 0.001) and periostin (p < 0.001) with SCORE2-Diabetes values. However, no correlation was found with FRS or REGICOR scales. Both serum bioactive sclerostin and periostin levels were significantly elevated in patients at high-very high risk of CVD (score ≥ 10%) than in the low-moderate risk group (score < 10%) (p < 0.001 for both). Moreover, analyzing these proteins to identify patients with type 2 diabetes at high-very high vascular risk using ROC curves, we observed significant AUC values for bioactive sclerostin (AUC = 0.696; p = 0.001), periostin (AUC = 0.749; p < 0.001), and the model combining both (AUC = 0.795; p < 0.001). For diagnosing high-very high vascular risk, serum bioactive sclerostin levels > 131 pmol/L showed 51.6% sensitivity and 78.6% specificity. Similarly, serum periostin levels > 1144 pmol/L had 64.5% sensitivity and 76.2% specificity.

Conclusions: Sclerostin and periostin are associated with vascular risk in the SCORE2-Diabetes algorithm, opening a new line of investigation to identify novel biomarkers of cardiovascular risk in the type 2 diabetes population.

 

Literature

1. Cardiovascular disease in type 2 diabetes mellitus: progress toward personalized management. Ma CX, Ma XN, Guan CH, Li YD, Mauricio D, Fu SB. Cardiovasc Diabetol. 2022 May 14;21(1):74. doi: 10.1186/s12933-022-01516-6. PMID: 35568946.
2. Bone proteins are associated with cardiovascular risk according to the SCORE2-Diabetes algorithm. González-Salvatierra S, García-Martín A, García-Fontana B, Martínez-Heredia L, García-Fontana C, Muñoz-Torres M. Cardiovasc Diabetol. 2024 Aug 24;23(1):311. doi: 10.1186/s12933-024-02406-9. PMID: 39182106.

 

 

Heart failure (HF) is a clinical condition caused by structural and/or functional abnormalities of the heart. Increased filling pressure in the heart´s left ventricle (LV) indicates diastolic dysfunction. The golden standard for diagnosis is the measurement of LV end-diastolic pressure (LVEDP) obtained through cardiac catheterization. However, this procedure is invasive. The objective of the following study was to explore the relationship between LVEDP and cardiac serum biomarkers, including including N-terminal prohormone B-type natriuretic peptide (NT-proBNP) and soluble ST2.

Natriuretic peptides and soluble ST2 improves echocardiographic diagnosis of elevated left ventricular filling pressures. Călburean Paet al., Sci Rep. 2024 Sep 27;14(1):22171. doi: 10.1038/s41598-024-73349-0. PMID: 39333652; PMCID: PMC11436802.

 

Abstract

Elevated filling pressure of the left ventricle (LV) defines diastolic dysfunction. The gold standard for diagnosis is represented by the measurement of LV end-diastolic pressure (LVEDP) during cardiac catheterization, but it has the disadvantage of being an invasive procedure. This study aimed to investigate the correlation between LVEDP and cardiac serum biomarkers such as natriuretic peptides (mid-regional pro-atrial natriuretic peptide [MR-proANP], B-type natriuretic peptide [BNP], and N-terminal prohormone BNP [NT-proBNP]), soluble ST2 (sST2), galectin-3 and mid-regional pro-adrenomedullin (MR-proAMD). Consecutive patients hospitalized in a tertiary center and undergoing left cardiac catheterization were included in the study. Diastolic dysfunction was considered present if the end-expiratory LVEDP was ≥ 15 mmHg. Cardiac biomarkers were determined from pre-procedural peripheral venous blood samples. A total of 110 patients were included, of whom 76 (69.0%) were males, with a median age of 65 (55-71) years. Median LVEDP was 13.5 (8-19) mmHg and diastolic dysfunction was present in 50 (45.4%) of the patients. LVEDP correlated with BNP (p < 0.0001, r = 0.39 [0.20-0.53]), NT-proBNP (p < 0.0001, r = 0.40 [0.22-0.55]), MR-proANP (p = 0.001, r = 0.30 [0.11-0.46]), sST2 (p < 0.0001, r = 0.47 [0.30-0.60]), but not with MR-proAMD (p = 0.77) or galectin-3 (p = 0.76). In the final stepwise multivariable binary logistic regression model, diastolic dysfunction was predicted by NT-proBNP, mitral average E/e’, sST2, atrial fibrillation, and left atrium reservoir strain. BNP, NT-proBNP, MR-proANP, and sST2 had predictive value for diastolic dysfunction. In contrast, galectin-3 and MR-proAMD were not associated with increased filling pressures. Furthermore, NT-proBNP and sST2 significantly improved diastolic dysfunction prediction in the final multivariable mode.

Diagnosis of Diastolic Heart Failure with NT-proBNP

NT-proBNP ELISA (cat. no. SK-1204)

√  CONVENIENT – can be used in every lab
√  RELIABLE – Full validation package
√  CE registered – for IVD use in EU
√  Widely cited in more than 130 publications 

 

 

Quantification and Clinical Relevance of Oxidized Low-Density Lipoprotein (oLAb) Antibodies

Oxidized LDL contains a vast and currently unknown variety of epitopes that trigger the production of antibodies against these molecules (1). Since the mid-1990s, we at BIOMEDICA have been a leader in developing the “oLAb” ELISA assay, designed to measure IgG antibodies to oxidized LDL, based on the research of Tatzber and Esterbauer from 1995 (2). Utilizing this methodology, numerous studies have been conducted over the past several decades, yielding insights into the immunological aspects of oxidative stress in various diseases, contributing to advancements in medicine and human health (1-5).  Oxidized LDL antibodies (oLAb) have been regarded as indicators of the immune response to the oxidation of low density lipoprotein (oxLDL). Investigators have discussed that measuring oxLDL antibodies might provide a more accurate reflection of oxidative stress levels than measuring oxidized LDL itself (6).

More about Oxidative Stress and Oxidized Low-Density Lipoprotein (oLAb) Antibodies

Oxidative Stress is an imbalance between reactive oxygen species (ROS) production and the body’s ability to neutralize them, leading to cellular damage. It arises from both internal (e.g., mitochondrial respiration, metabolic processes) and external (e.g., pollution, UV radiation, poor diet) sources. The consequences include cellular damage, inflammation, and aging, contributing to diseases like cardiovascular illness, cancer, neurodegenerative disorders, and diabetes. The body employs enzymatic (e.g., superoxide dismutase, catalase) and non-enzymatic (e.g., vitamins C and E, glutathione) antioxidants to combat oxidative stress, which is crucial for maintaining health.

Autoantibodies against Oxidized LDL are antibodies produced by the immune system that specifically target oxidized low-density lipoprotein (LDL). Oxidized LDL plays a significant role in atherosclerosis and cardiovascular diseases, as it contributes to the formation of fatty plaques in arteries. The presence of these autoantibodies can indicate an autoimmune response and may serve as a biomarker for cardiovascular risk. They can also have protective or detrimental effects, depending on their concentration and context, influencing lipid metabolism and inflammation. Understanding these autoantibodies is crucial for developing potential diagnostic and therapeutic strategies in cardiovascular disease management.

Oxidized Low-Density Lipoprotein (oLAb) Antibodies

Autoantibodies targeting oxidatively modified LDL particles can easily be measured in serum with a commercial and standardized ELISA assay.

Anti-Oxidized LDL Antibody ELISA (oLAB) Assay (cat. no. BI-20032)

Features

• Standardized method with over 30 years’ experience in oLAB ELISA production
• Widely referenced

• Results in 2,5 hours
• 2 controls included

 

 

Conclusion

Over the last thirty years, the clinical significance and understanding of antibodies against oxidized low-density lipoproteins has evolved, offering valuable insights into their impact on cardiovascular health and disease. Progress in ELISA technology has been crucial for this research, facilitating in-depth analysis of these antibodies and paving the way for potential advancements in diagnostic and therapeutic approaches. As our understanding of oLAb continues to grow, their application in clinical practice and patient management remains a critical area of focus within cardiovascular research.

 

Related products

OxyStat Assay | BI-5007

Oxystat Oxidative Stress Test highlights:

• Determination of total oxidant capacity/status (TOC/TOS)
• Quick and easy assay to measure total peroxides in biological fluids

 

Literature

1. Antibodies against oxidized LDL-theory and clinical use. Steinerová A, Racek J, Stozický F, Zima T, Fialová L, Lapin A. Physiol Res. 2001;50(2):131-41. PMID: 11522041.
2. Transient reduction of autoantibodies against oxidized LDL in patients with acute myocardial infarction. Schumacher M, Eber B, Tatzber F, Kaufmann P, Halwachs G, Fruhwald FM, Zweiker R, Esterbauer H, Klein W. Free Radic Biol Med. 1995 Jun;18(6):1087-91. doi: 10.1016/0891-5849(94)00216-7. PMID: 7628731.
3. Overview of Clinical Relevance of Antibodies Against Oxidized Low-Density Lipoprotein (oLAb) Within Three Decades by ELISA Technology. Wonisch, W.; Tatzber, F.; Lindschinger, M.; Falk, A.; Resch, U.; Mörkl, S.; Zarkovic, N.; Cvirn, G. Antioxidants 2024, 13, 1560.
4. Antibodies against oxidized low density lipoproteins in pregnant women. Fialová L, Mikulíková L, Malbohan I, Benesová O, Stípek S, Zima T, Zwinger A. Physiol Res. 2002;51(4):355-61. PMID: 12449433.
5. Increased circulating oxidised low-density lipoprotein and antibodies to oxidised low-density lipoprotein in preeclampsia. Arifin R, Kyi WM, Che Yaakob CA, Yaacob NM. J Obstet Gynaecol. 2017 Jul;37(5):580-584. doi: 10.1080/01443615.2016.1269227. Epub 2017 Mar 30. PMID: 28358592.
6. Low-density lipoprotein oxidation biomarkers in human health and disease and effects of bioactive compounds. Winklhofer-Roob BM, Faustmann G, Roob JM. Free Radic Biol Med. 2017 Oct;111:38-86. doi: 10.1016/j.freeradbiomed.2017.04.345. Epub 2017 Apr 26. PMID: 28456641.

 

Our EZ4U (Easy for You) cell proliferation and cytotoxicity MTT assay was applied in a recent study exploring the role of pertuzumab, a monoclonal antibody that targets HER2, in disrupting the transactivation between the epidermal growth factor receptor (EGFR) and HER2 in HER2-positive cancers. The research focuses on understanding how this disruption could predict therapeutic outcomes based on the quantitative analysis of EGFR signaling input (1).

Measuring cell metabolic activity with EZ4U – MTT assay

 

EZ4U  Cell Viability & Cytotoxicity Assay (cat.no. BI-5000)

EASY FOR YOU (EZ4U)

• Non-radioactive & non-toxic
• Convenient single-step incubation  – for use on living cells
• Widely cited in more than 280 publications

 

1. Disrupting EGFR-HER2 Transactivation by Pertuzumab in HER2-Positive Cancer: Quantitative Analysis Reveals EGFR Signal Input as Potential Predictor of Therapeutic Outcome. Ujlaky-Nagy L, Szöllősi J, Vereb G. Int J Mol Sci. 2024 May 29;25(11):5978. doi: 10.3390/ijms25115978. PMID: 38892166.

 

Abstract

 

Related publications

Targeted therapeutic options and future perspectives for HER2-positive breast cancer. Wang J, Xu B. Signal Transduct Target Ther. 2019 Sep 13;4:34. doi: 10.1038/s41392-019-0069-2. PMID: 31637013.

 

 

for  ELISA and Luminex Assays and microRNA Analysis

With more than 30 years of expertise in the development and manufacturing of ELISA assay kits, Biomedica offers analytical testing services tailored for universities, clinical centers, as well as pharmaceutical and biotechnology industries. Our comprehensive range of analytical solutions ensures that we can provide exceptional service for your research or product development needs.

Biomarker Testing Service from Biomedica

Our highly trained staff will help you to achieve your specified goals and requirements. Biomedica has established a systematic process that guarantees results aligned with your exact specifications. Client satisfaction is our top priority. Having contributed to numerous successful research projects and publications, you will benefit from our expertise in analytical testing, paired with a customer-focused approach.

We offer:

• CUSTOMIZED Services – flexibility to meet your project needs
• EXPERTISE – trained and experienced laboratory staff
• QUALITY ASSURANCE – quality equipment adhering to strict quality guidelines
• TIMELINESS – rapid turn-around times to meet your deadlines
• RELIABILITY – verified and comprehensive results presented in an analytical report

 

Quality Assurance
We are committed to achieving the highest quality standards, recognizing that this is essential for both your success and ours. Our robust quality assurance system, quality control procedures, and testing methods clearly reflect this commitment. We hold ISO 9001:2015 quality management system and with 30 years of experience in the development and manufacturing of immunoassays, we offer expert knowledge and techniques that align with European quality standards.

Our Quality Assurance (QA) system is founded on comprehensive and well-structured standard operating procedures, ensuring that all analyses are traceable from the receipt of samples to the reporting of results. Regular inspections by regulatory bodies further affirm our strong compliance with current regulations.

• Routine internal audits and inspections
• Data assessed for traceability, integrity, and reliability
• Inspections to ensure adherence to protocols and laboratory SOPs

 

Find out more about our workflow for ELISA and Luminex and microRNA Services

Our analytical services include:  

ELISA (Enzyme Linked Immunabsorbent Assay) Kits

We offer services for our proprietary Biomedica assays (product catalogue) as well as ELISA Assay Kits from other suppliers, covering a wide range of biomarker analytes.

LUMINEX Technology Multiplex Assays

We utilize Luminex xMAP® (multiple analyte profiling) technology-based immunoassays to measure your samples, enabling the simultaneous detection and quantification of multiple biomarkers.

For additional details, please refer to our workflow chart or reach out to us directly to discuss how we can support your specific research project. 

NEXT-GENERATION SEQUENCING & RT-qPCR MICRO RNA SERVICES

We provide a comprehensive range of high-quality RNA services, including RNA extraction, next-generation sequencing (NGS), RT-qPCR, and custom analysis of microRNA signatures, all performed by our experienced laboratory staff. Our services include:

• RNA extraction from biofluids (serum, plasma, extracellular vesicles), cells, and tissues (quality control of total RNA utilizes Bioanalyzer chips).
• Next-generation sequencing (NGS).
• RT-qPCR
• Cell-type specific microRNA/mRNA analysis in complex tissues, along with custom analysis of microRNA signatures.

 

Share the details of your project with us!

For more details about our microRNA services, please visit our website or contact us directly (info.at.bmgrp.com).

 

Further reading

High-throughput proteomics: a methodological mini-review. Cui M, Cheng C, Zhang L. Lab Invest. 2022 Nov;102(11):1170-1181. doi: 10.1038/s41374-022-00830-7. Epub 2022 Aug 3. PMID: 35922478; PMCID: PMC9362039.

Circulating miRNAs in bone health and disease. Grillari J, Mäkitie RE, Kocijan R, Haschka J, Vázquez DC, Semmelrock E, Hackl M. Bone. 2021 Apr;145:115787. doi: 10.1016/j.bone.2020.115787. Epub 2020 Dec 8. PMID: 33301964.

C4d and graft loss in KTR with IgAN (abbrev. KTR: kidney transplant recipients, IgAN: IgA nephropathy)

C4d analysis has become an important diagnostic tool used in the evaluation of kidney transplant recipients (1). C4d is a fragment of the complement component C4 that is produced during the activation of the complement system. In the context of kidney transplantation, the presence of C4d in peritubular capillaries can indicate antibody-mediated injury and help assess the immune status of the transplanted kidney (2).

Our Anti-C4d Antibody (FITC)  has recently been used in a study evaluating whether recurrent IgA deposition, which is common after kidney transplantation, is associated with an increased risk of graft failure (1).

IgA nephropathy (IgAN) is the most prevalent type of kidney disorder. It can occur at any age but is more frequently diagnosed in young adults and adolescents (3). IgAN is marked by the deposition of immunoglobulin A (IgA) in the glomeruli, the filtering units of the kidney. The deposition of IgA, particularly in the mesangial cells of the glomeruli, leads to inflammation and kidney damage (4). The exact cause of IgAN is not fully understood, but it is believed to involve abnormal IgA production and a dysregulation of the immune system. IgA nephropathy (IgAN) has been shown to be associated with a risk for posttransplant recurrence (5, 6).

 C4d and graft loss in KTR with IgAN

The study involved sixty-seven kidney transplant recipients (KTR) of which 37% had recurrent IgA deposition (1). The results showed that “there were no clinical differences between KTR with and without recurrent IgA deposition. C4d was present in 48% of the biopsies. During a median follow-up of 9.6 [4.8-14] years, 18 (27%) KTR developed death-censored graft failure. Recurrent IgA deposition was not associated with graft failure. Of the evaluated complement factors, only C4d staining was associated with graft failure in KTR with recurrent IgA deposition” .  

The authors concluded that “ recurrent IgA deposition was not associated with graft failure in itself. C4d, when present, is strongly associated with graft loss in KTR with recurrent IgA deposition, suggesting a pathogenic role for the lectin pathway in recurrent IgAN.” (1).

Our C4d antibodies are used to identify the human complement split product C4d in paraffin and frozen sections as well as by flow cytometry.

 Anti-C4d Antibody | BI-RC4D

• widely cited in 100 publications
• for immunohistochemistry on paraffin embedded tissue and frozen sections
• use in kidney, heart, liver and other transplants

Anti-C4d Antibody (FITC) | BI-RC4D-FITC

• detection of cell- or solid-phase bound C4d and C4d split product by flow cytometry using FlowPRA® Class I and II screening test beads from One Lambda.

 

Literature

1. C4d, rather than C3d and C5b-9, is associated with graft loss in recurrent IgA deposition after kidney transplantation. Alkaff FF, Uffing A, Tiller G, Lammerts RGM, van den Heuvel MC, Bajema IM, Daha MR, van den Born J, Berger SP. Am J Nephrol. 2024 Aug 17. doi: 10.1159/000540986. Epub ahead of print. PMID: 39154645.
2. The diagnostic significance of C4d deposits, as an immunohistochemical proof of complement activation, in kidney glomerular pathologies and kidney transplantation. Hresko S, Madarova M, Dobosova M, Palusekova N, Niznerova P, Ziaran S, Varga I. Bratisl Lek Listy. 2024;125(5):275-280. doi: 10.4149/BLL_2024_41. PMID: 38624051.
3. Significance of C4d expression in peritubular capillaries concurrent with microvascular inflammation in for-cause biopsies of ABO-incompatible renal allografts. Cho H, Baek CH, Park SK, Kim H, Go H. Kidney Res Clin Pract. 2024 Jan;43(1):82-92. doi: 10.23876/j.krcp.22.221. Epub 2023 May 12. PMID: 37448281; PMCID: PMC10846988.
4. Complement Activation Is Associated With Crescents in IgA Nephropathy. Wang Z, Xie X, Li J, Zhang X, He J, Wang M, Lv J, Zhang H. Front Immunol. 2021 Sep 14;12:676919. doi: 10.3389/fimmu.2021.676919. PMID: 34594322; PMCID: PMC8477028.
5. Risk for graft loss in pediatric and young adult kidney transplant recipients due to recurrent IgA nephropathy. Engen RM, Bartosh SM, Smith JM, Perkins JD, Harshman LA.Am J Transplant. 2024 Jan;24(1):37-45. doi: 10.1016/j.ajt.2023.08.007. Epub 2023 Aug 16. PMID: 37595842.
6. Recurrence of IgA Nephropathy after Kidney Transplantation in Adults. Uffing A, Pérez-Saéz MJ, Jouve Tet al.,. Clin J Am Soc Nephrol. 2021 Aug;16(8):1247-1255. doi: 10.2215/CJN.00910121. PMID: 34362788; PMCID: PMC8455056.

Big ENDOTHELIN-1 a prognostic marker in CAD.  Endothelin-1 (ET-1) is the most potent vasoconstrictor peptide. This 21 amino acid peptide is the biologically active from that is rapidly cleared from the circulation. Its low concentrations and short half-life make it challenging to detect in serum and plasma samples. Big-Endothelin-1 (BigET-1) is the precursor peptide in the synthesis of Endothelin-1 (ET-1).  It circulates in higher concentrations  and also has a much longer half-life than ET-1. Therefore, measurement of plasma BigET-1 levels are an alternative approach for the indirect estimation of ET-1 release (1).

BigET-1 is primarily produced by endothelial cells and is produced through cleavage of “preproendothelin”, a larger precurser protein. The conversion of BigET-1 to the biologically active 21 amino acid ET-1, is a result the proteolytic cleavage by endothelin-converting enzymes (ECEs) (2). Big-ET-1 has been reported as an independent predictor of cardiovascular mortality in patients with chronic heart failure as determined in a large cohort study in more than 2800 individuals (3). In addition, Big ET-1 has been shown to be a strong and independent predictor of mortality in patients with moderate to severe light chain cardiac amyloidosis (AL-CA) , which may indicate a possible role for risk stratification in patients with this disease (4).

Big ENDOTHELIN-1 can easily be measured in serum and plasma samples.

Biomedica Big Endothelin ELISA Assay 

• EASY – can be used in every lab
• ROBUST & fully VALIDATED (following international quality guidelines)
• HIGHLY SENSTIVE – 0.02 pmol/l (= 0.086 pg/ml)
• GOOD ANALYTE STABILITY in serum and plasma

 

Download your protocol booklet  here

Big ENDOTHELIN-1 a prognostic marker in CAD

The Biomedica BigET-1 ELISA assay was highlighted in this large cohort study of nearly 8000 prediabetic and diabetic patients with stable Coronary Artery Disease (CAD): Prognostic Value of Plasma Endothelin-1 in Predicting Worse Outcomes in Patients with Prediabetes and Diabetes and Stable Coronary Artery Diseases. Yang C et al., Diabetes Metab J. 2024. 

Key findings

• Plasma BigET-1 level is an independent predictor of #cardiovascular events (CVEs) in patients with stable CAD. 

• BigET-1 remains independently associated with worse cardiovascular outcomes in prediabetic and diabetic patients but not in patients with normoglycemia.

• Patients with diabetes and high BigET-1 levels were associated with the highest risk of CVEs in patients with stable CAD.
• Targeting ET-1 pathways may help manage CAD in individuals with dysglycemia.

 

Literature

1. Biomarkers and Precision Medicine in Heart Failure . Nasrien E. Ibrahim et al., Heart Failure: a Companion to Braunwald’s Heart Disease (Fourth Edition), 2020.
2. Endothelin-1 levels and cardiovascular events. Jankowich M, Choudhary G. Trends Cardiovasc Med. 2020 Jan;30(1):1-8. doi: 10.1016/j.tcm.2019.01.007.PMID: 30765295.
3. Propeptide big-endothelin, N-terminal-pro brain natriuretic peptide and mortality. The Ludwigshafen risk and cardiovascular health (LURIC) study. Gergei I, Krämer BK, Scharnagl H, Stojakovic T, März W, Mondorf U. Biomarkers. 2017; 22(3-4):315-320. doi: 10.1080/1354750X.2016.1252969. PMID: 27788598.
4. Prognostic value of plasma big endothelin-1 in patients with light chain cardiac amyloidosis. Chen Z, Shi A, Wang Z, Chen Y, Lin Y, Su M, Dong H, Laptseva N, Hu Y, Flammer AJ, Duru F, Jin W, Chen L. Heart. 2024; 26;110(18):1124-1132. doi: 10.1136/heartjnl-2024-324000. PMID: 39084705.
5. Prognostic Value of Plasma Endothelin-1 in Predicting Worse Outcomes in Patients with Prediabetes and Diabetes and Stable Coronary Artery Diseases. Yang C, Zhu CG, Guo YL, Wu NQ, Dong Q, Xu RX, Wu YJ, Qian J, Li JJ. Diabetes Metab J. 2024 Sep;48(5):993-1002. doi: 10.4093/dmj.2023.0410. Epub 2024 Aug 21. PMID: 39165112.

 

Further reading

• Plasma concentration of big endothelin-1 and its relation with plasma NT-proBNP and ventricular function in heart failure patients. Rivera M, Cortés R, Portolés M, Valero R, et al., Rev Esp Cardiol. 2005 Mar;58(3):278-84. Spanish. PMID: 15766450.

• Endothelin: 30 Years From Discovery to Therapy. Barton M, Yanagisawa M. Hypertension. 2019; 74(6):1232-1265.

 

VANIN-1 a biomarker for survival in PAD – Peripheral artery disease (PAD) is a condition characterized by the narrowing of the peripheral arteries, often due to atherosclerosis, which reduces blood flow to the limbs, particularly the legs (1). This can lead to symptoms such as leg pain, cramping, and weakness during physical activity. In more severe cases, PAD can result in critical limb ischemia, ulcers, or even gangrene. It is closely associated with cardiovascular conditions and risk factors, including high blood pressure, diabetes, and chronic kidney disease.

Chronic kidney disease (CKD) significantly increases the risk of developing peripheral artery disease (PAD) and is also a common co-morbidity factor that is associated with PAD (2). Despite its clinical significance, there is currently no specific marker available for conducting a functional risk assessment of kidney disease patients suffering from peripheral artery disease (PAD), particularly in the early stages.

VANIN-1 a biomarker for survival in PAD 

In search of novel biomarkers that may serve as tools of risk assessment, Zierfuss B. and colleagues investigated the relationship between urinany Vanin-1 (uVNN-1) as a marker of kidney disease and PAD severity (3). The study included patients with stable PAD (n = 304) who were followed up for up to 10 years. Urinary Vanin-1 (uVNN1) was measured by an enzyme-linked immunosorbent assay (ELISA) from Biomedica. Urinary Vanin-1 (uVNN1) concentration were normalized to urine creatinine levels (uVNN1/Cr).

The results of the study demonstrate that uVNN-1 is an independent link to both all-cause and cardiovascular mortality in patients with peripheral artery disease (PAD). As a result, uVNN1/Cr may serve as a practical and accessible marker for risk stratification in early kidney disease patients with PAD, aiding in the identification of those patients who are at high risk for fatal events.

Human VANIN -1 (urine) ELISA Assay Kit  (cat. no. BI-VNN1)

• The assay is optimized for human urine samples
• Characterized antibodies enable high SPECIFICITY
• Rigorously validated assay following international quality guidelines
• Easy and quick one-step ELISA

 

 

Related products

-Mouse/rat Vanin-1 ELISA

-Nephrology and Transplant: FGF23, Endostatin, Anti C4d

-Cardiovascular: NT-proBNP, Endothelins, proANP, NT-proCNP

 

About Vanin-1 (VNN1)

Vascular non-inflammatory molecule-1 or VANIN-1 (VNN1) is a protein that is part of the Vanin family of enzymes that possesses pantetheinase activity and primarily carries out its physiological functions through the products of its enzyme catalysis, such as pantothenic acid and cysteamine. VNN1 is involved in various biological processes, including inflammation, oxidative stress, and tissue repair (4). Vanin-1 is primarily expressed in certain tissues, such as the liver, kidneys, and immune cells. The capacity of  VNN1 to influence various metabolic pathways and its role in oxidative stress in either worsening or alleviating pathological processes, has led to the hypothesis that it is a crucial factor in disease progression (5).

The potential of Vanin-1 as a marker of acute kidney injury and as a predictor of acute pyelonephritis in young children with urinary tract infection has been investigated, particularly as urinary VNN1 concentrations are higher in these patients (6, 7).

Literature

1. Peripheral Artery Disease: A Comprehensive Updated Review. Shamaki GR, Markson F, Soji-Ayoade D, Agwuegbo CC, Bamgbose MO, Tamunoinemi BM. Curr Probl Cardiol. 2022; 47(11):101082. doi: 10.1016/j.cpcardiol.2021.101082. PMID: 34906615.
2. The Impact of Chronic Kidney Disease on Peripheral Artery Disease and Peripheral Revascularization. Serra R, Bracale UM, Ielapi N, Del Guercio L, Di Taranto MD, Sodo M, Michael A, Faga T, Bevacqua E, Jiritano F, Serraino GF, Mastroroberto P, Provenzano M, Andreucci M.Int J Gen Med. 2021; 14:3749-3759. doi: 10.2147/IJGM.S322417. PMID: 34326661.
3. Urinary vanin-1 as a novel biomarker for survival in peripheral artery disease. Zierfuss B, Karlinger A, Bojic M, Koppensteiner R, Schernthaner GH, Höbaus C. Vasc Med. 2024; 29(4):390-397. doi: 10.1177/1358863X241240428. PMID: 38607943.
4. Vanin 1: Its Physiological Function and Role in Diseases. Bartucci R, Salvati A, Olinga P, Boersma YL. Int J Mol Sci. 2019; 20(16):3891. doi: 10.3390/ijms20163891. PMID: 31404995.
5. Vanin1 (VNN1) in chronic diseases: Future directions for targeted therapy. Yu H, Cui Y, Guo F, Zhu Y, Zhang X, Shang D, Dong D, Xiang H. Eur J Pharmacol. 2024; 962:176220. doi: 10.1016/j.ejphar.2023.176220. PMID: 38042463.
6. Urinary vanin-1 for predicting acute pyelonephritis in young children with urinary tract infection: a pilot study. Krzemień G, Pańczyk-Tomaszewska M, Górska E, Szmigielska A Biomarkers. 2021; 26(4):318-324. doi: 10.1080/1354750X.2021.1893813. PMID: 33656956
7. A Novel Biomarker for Acute Kidney Injury, Vanin-1, for Obstructive Nephropathy: A Prospective Cohort Pilot Study. Washino S, Hosohata K, Oshima M, Okochi T, Konishi T, Nakamura Y, Saito K, Miyagawa T. Int J Mol Sci. 2019; 20(4):899. doi: 10.3390/ijms20040899. PMID: 30791405.

November is Diabetes Awareness Month bringing attention to diabetes and its impact on millions of individuals.

Diabetes mellitus has emerged as the third most significant non-communicable disease, following cardiovascular diseases and cancer. This condition encompasses a group of metabolic disorders marked by chronic hyperglycemia resulting from various causes, along with inadequate insulin secretion and impaired insulin action. According to the most recent statistics from the International Diabetes Federation, the global number of individuals with diabetes reached 530 million in 2021, with projections suggesting it could exceed 780 million by 2045. Due to the long-term nature of the disease, diabetes can lead to damage across multiple body systems or organs, resulting in various complications (1, 2). Beyond the more commonly known complications of diabetes such as heart disease, diabetes can also affect the skeletal system. This severe complication of diabetes leads to bone loss potentially resulting in osteoporosis and increased fracture risk.

Identifying biomarkers that may predict fracture risk in individuals with diabetes is crucial for improving patient care.

Sclerostin and Fracture Risk Prediction in Diabetes

Sclerostin (SOST) is a bone-related protein that is mainly produced by osteocytes, bone cells embedded in the bone matrix. Sclerostin is considered to be one of the major regulators of bone formation. It is a soluble antagonist of the Wnt signaling pathway and its inactivation leads to bone degradation, while the  of Wnt signaling promotes bone formation (3). Sclerostin has been a target of therapeutic antibodies for osteoporosis treatment due to its role in inhibiting bone formation.

Bone as an endocrine organ

Research indicates that bone, which is involved in lipid and glucose metabolism, is increasingly recognized as an endocrine organ. Recent findings suggest that sclerostin contributes to disorders related to lipid and glucose metabolism (4). Studies have shown that Sclerostin levels are increased in individuals with prediabetes and correlated with insulin resistance in the skeletal muscle, liver, and adipose tissue (5). In addition, Sclerostin levels have been shown to be negatively associated with insulin sensitivity in obese but not in lead woman (6).

Further studies have revealed that increased serum Sclerostin levels are associated with vertebral fractures in patients with type 2 diabetes mellitus (7, 8). Sclerostin, has also been suggested to have predictive value for fracture risk in patients with diabetes (9).

Sclerostin – a promising circulating marker of diabetic bone disease

Sclerostin has emerged as a promising circulating marker of diabetic bone disease. It may not only reflect the degree of osteocyte dysfunction and the suppression of bone formation that occurs in this disease, but it may also potentially reflect the vascular alterations that are associated with specific bone alterations such as cortical porosity (10).

Additional research is essential to enhance the understanding of biochemical markers in the assessment of diabetic bone disease. Specifically, the ability of bone markers to forecast fracture risk needs further examination.

Circulating Sclerostin levels can reliably be measured in human serum and plasma samples with a conventional SCLEROSTIN ELISA Assay Kit.

Sclerostin ELISA (cat. no. BI-20492)

• MOST referenced in more than 300 citations
• LOW sample volume – 20µl sample /well
• For SERUM & PLASMA samples
• RELIABLE – full validation package

 

Bioactive Sclerostin ELISA (cat. no. BI-20472)

• CHARACTERIZED ANTIBODIES – targeting the receptor binding region
• RIGOROUSLY validated for clinical samples
• LOW sample volume – 20µl sample /well
• RELIABLE – full validation package

 

Literature

1. International Diabetes Federation – Facts and Figures
2. Diabetes mellitus, the fastest growing global public health concern: Early detection should be focused. Hossain MJ, Al-Mamun M, Islam MR. Health Sci Rep. 2024; 7(3):e2004. doi: 10.1002/hsr2.2004. PMID: 38524769.
3. Role of Wnt signaling and sclerostin in bone and as therapeutic targets in skeletal disorders. Marini F, Giusti F, Palmini G, Brandi ML. Osteoporos Int. 2023; 34(2):213-238. doi: 10.1007/s00198-022-06523-7. PMID: 35982318.
4. The role of sclerostin in lipid and glucose metabolism disorders. Jiang H, Li D, Han Y, Li N, Tao X, et al., Biochem Pharmacol. 2023; 215:115694. doi: 10.1016/j.bcp.2023.115694. PMID: 37481136.
5. Sclerostin and Insulin Resistance in Prediabetes: Evidence of a Cross Talk Between Bone and Glucose Metabolism. Daniele G, Winnier D, Mari A, Bruder J, Fourcaudot M, Pengou Z, Tripathy D, Jenkinson C, Folli F. Diabetes Care. 2015; 38(8):1509-17. doi: 10.2337/dc14-2989. PMID: 26084344.
6. Serum sclerostin is negatively associated with insulin sensitivity in obese but not lean women. Aznou A, Meijer R, van Raalte D, den Heijer M, Heijboer A, de Jongh R. Endocr Connect. 2021; 10(2):131-138. doi: 10.1530/EC-20-0535. PMID: 33480863.
7. Increased serum sclerostin and decreased serum IGF-1 are associated with vertebral fractures among postmenopausal women with type-2 diabetes. M.S. Ardawi, D.H. Akhbar, A. Alshaikh, M.M. Ahmed, M.H. Qari, A.A. Rouzi, et al. Bone, 56 (2013), pp. 355-362
8. Elevated sclerostin levels are associated with vertebral fractures in patients with type 2 diabetes mellitus. Yamamoto M, Yamauchi M, Sugimoto T. J Clin Endocrinol Metab. 2013; 98(10):4030-7. doi: 10.1210/jc.2013-2143. PMID: 23894157.
9. Fracture risk assessment in diabetes mellitus. Front Endocrinol (Lausanne). Chen W, Mao M, Fang J, Xie Y, Rui Y. 2022; 13:961761. doi: 10.3389/fendo.2022.961761. PMID: 36120431.
10. Biochemical Markers of Bone Fragility in Patients with Diabetes. A Narrative Review by the IOF and the ECTS. Meier C, Eastell R, Pierroz DD, Lane NE, Al-Daghri N, Suzuki A, Napoli N, Mithal A, Chakhtoura M, El-Hajj Fuleihan G, Ferrari S. J Clin Endocrinol Metab. 2023; 108(10):e923–36. doi: 10.1210/clinem/dgad255. PMID: 37155585.

 

 

Detectable values in serum and plasma samples

We´re thrilled to offer our customers a SIGNIFICANT PRICE DROP of minus 15% !!!

on our human Interleukin-6 ELISA assay kit.

Quality, fully validated kit, ready to use reagents for affordable and efficient research!

Biomedica´s human Interleukin-6 (IL-6) ELISA is highly sensitive with measurable values in serum and in plasma samples.

Features include:

• Standardized– use of WHO intern. standards for kit calibration & harmonization 
• High Specificity – using characterized epitope-mapped antibodies
• User-Friendly – ready to use color coded, prediluted standards & controls

 

Human IL-6 ELISA Assay Kit (cat. no. BI-IL6)

Contact us or your local representative click here

Just use Promotion Code: BCIL62024 on your order.

Human IL-6 ELISA Assay Kit (cat. no. BI-IL6)

• Format: 12×8 wells
• Detection limit/Sensitivity: 0.28 pg/ml
• Assay – Dynamic Range: 0 – 200 pg/ml
• Incubation Time: 4 hours 30 minutes
• Sample Type: Serum, Plasma, Cell Culture Supernatants, Urine
• Sample Volume: 100 µl
• Alternative Name: Interleukin 6

 

Links to IL-6 ELISA : Protocol Booklet,  Validation Data File, Material Safety Data Sheet MSDS

The Human IL-6 High Sensitivity ELISA Assay is Developed and Manufactured in Austria by Biomedica

 Assay Principle

The Human IL-6 High Sensitivity ELISA Assay Kit is a sandwich enzyme immunoassay that has been optimized and fully validated for the quantitative determination of human IL-6 in serum, EDTA-plasma, citrate plasma, and heparin plasma. Validation experiments have been performed according to international quality guidelines (ICH/ FDA/ EMEA). Cell culture supernatant and urine samples are compatible with this ELISA. The IL-6 ELISA assay recognizes both natural and recombinant human IL-6. The assay employs highly purified epitope mapped antibodies as well as human serum-based standards and controls. The figure below explains the principle of the human IL-6 sandwich ELISA:

First, STD/sample/CTRL are pipetted into wells. The wells are precoated with a recombinant anti-human IL-6 antibody. The soluble IL-6 that is present in the sample binds to the pre-coated anti-IL-6 antibody in the well. After an incubation step, the microtiter plate is washed where all non-specific unbound material is removed. In the next step, the biotinylated anti-IL-6 antibody is pipetted into the wells. This antibody reacts with the IL-6 present in the sample and forms a so-called sandwich. During the next washing step all unbound antibody is removed. After washing, the conjugate (streptavidin-HRPO) is added to the wells that reacts with the biotinylated anti-IL-6 antibody. After a further washing step, the substrate (tetramethylbenzidine; TMB) is pipetted into the wells. The enzyme catalyzed color change of the substrate is directly proportional to the amount of IL-6 present in the sample which is detectable with a standard microtiter plate ELISA reader. Thereafter, a dose response curve of the absorbance (optical density, OD at 450 nm) versus standard concentration is generated, using the values obtained from the standards. The concentration of soluble IL-6 in the sample is determined directly from the dose response curve.

Learn more about our validation process and our quality guidelines

Related ELISA kits

Human VEGF, human Angiopoietin-2, mouse/rat Angiopoietin-2

 

About Interleukin-6 (IL- 6)

Il-6 is a cytokine which acts as a type of signaling molecule that plays a critical role in the immune response, inflammation, and metabolism. It is produced by various types of cells, including macrophages, T cells, and fibroblasts, and acts on multiple cell types to modulate immune functions and systemic responses.

Key Functions of IL-6

1. Role in Inflammation: IL-6 is involved in the acute phase response to inflammation and infection. It stimulates the production of acute-phase proteins by the liver, such as C-reactive protein (CRP).
2. Immune Regulation: This cytokine influences the differentiation of T cells and B cells, enhancing the body’s ability to respond to pathogens. It also promotes the growth and differentiation of specific immune cells.
3. Metabolism: IL-6 plays a role in metabolic processes, including glucose metabolism and lipid metabolism. Dysregulation of IL-6 signaling is linked to metabolic disorders such as obesity and type 2 diabetes.
4. Bone Metabolism: IL-6 is involved in bone remodeling. It can stimulate the formation of osteoclasts, the cells responsible for bone resorption, potentially contributing to conditions such as osteoporosis.
5. Chronic Conditions: Elevated levels of IL-6 are associated with chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, and certain malignancies. It is also implicated in the cytokine storm seen in severe cases of COVID-19.

 

Clinical Relevance

Due to its central role in inflammation and immune response, IL-6 has become a target for therapeutic interventions in various conditions. Several IL-6 inhibitors, such as tocilizumab, are used in the treatment of autoimmune diseases and other inflammatory conditions. Monitoring IL-6 levels can also provide insights into disease progression and response to treatment in conditions characterized by inflammation.

Conclusion:

IL-6 is a multifaceted cytokine with critical roles in immune responses, inflammation, and metabolism. Its dysregulation can contribute to various diseases, making it an important focus in both research and clinical settings. Understanding its mechanisms and effects can help in developing targeted therapies for inflammatory and metabolic disorders.

Literature

• Interleukin 6: at the interface of human health and disease. Grebenciucova E, VanHaerents S. Front Immunol. 2023 Sep 28;14:1255533. doi: 10.3389/fimmu.2023.1255533. PMID: 37841263; PMCID: PMC10569068.
• Interleukin-6 signalling in health and disease. Rose-John S. F1000Res. 2020 Aug 20;9:F1000 Faculty Rev-1013. doi: 10.12688/f1000research.26058.1. PMID: 32864098; PMCID: PMC7443778.
• Recent advances in the role of interleukin-6 in health and disease. Peppler WT, Townsend LK, Wright DC. Curr Opin Pharmacol. 2020 Jun;52:47-51. doi: 10.1016/j.coph.2020.04.010. Epub 2020 Jun 18. PMID: 32563931.

Sepsis is a life-threatening medical condition that arises when the body’s response to an infection triggers widespread inflammation, leading to tissue damage and organ dysfunction. Early recognition and prompt treatment are crucial as sepsis can result in multi-organ failure and death (1). Timely administration of antibiotics and supportive care significantly improve outcomes, highlighting the importance of awareness and rapid intervention in managing this critical condition.

For sepsis, a range of biomarkers exist but have not been completely effective identifying patients at the onset of sepsis or in predicting their prognosis and the anticipated severity of organ failure. Furthermore, the mechanisms underlying the uncontrolled infection, dysregulated immune response, and subsequent organ failure remain unclear, highlighting the need for further research.

A recent study by Hohlstein P and colleagues (2) explores the role of soluble Neuropilin-1 (sNRP-1) in critical illness and sepsis and evaluates its potential as a biomarker in this context.

Key findings of the study:

• Critically ill and septic patients exhibit higher levels of circulating sNRP-1.
• sNRP-1 levels correlate with organ failure, particularly hepatic and kidney function impairment.
• Long-term survivors have lower levels of sNRP-1 upon admission to the ICU.

soluble NEUROPILIN-1 in sepsis correlates with organ dysfunction

Soluble Neuropilin-1 (sNRP-1) was measured in human serum samples with the

Biomedica soluble Neuropilin-1 ELISA assay (cat. no. BI-20409)

Assay Highlights:

• Only assay that detects free and ligand-bound soluble Neuropilin-1
• Highly specific and epitope mapped antibodies 
• Extensively validated according to FDA/ICH/EMEA guidelines

 

Links to the  Protocol Booklet and Validation Data

 

Soluble Neuropilin-1 Is Elevated in Sepsis and Correlates with Organ Dysfunction and Long-Term Mortality in Critical Illness. 

Abstract

Critical illness and sepsis may cause organ failure and are recognized as mortality drivers in hospitalized patients. Neuropilin-1 (NRP-1) is a multifaceted transmembrane protein involved in the primary immune response and is expressed in immune cells such as T and dendritic cells. The soluble form of NRP-1 (sNRP-1) acts as an antagonist to NRP-1 by scavenging its ligands. The aim of this study was to determine the value of sNRP-1 as a biomarker in critical illness and sepsis. We enrolled 180 critically ill patients admitted to a medical intensive care unit and measured serum sNRP-1 concentrations at admission, comparing them to 48 healthy individuals. Critically ill and septic patients showed higher levels of sNRP-1 compared to healthy controls (median of 2.47 vs. 1.70 nmol/L, p < 0.001). Moreover, sNRP-1 was also elevated in patients with sepsis compared to other critical illness (2.60 vs. 2.13 nmol/L, p = 0.01), irrespective of disease severity or organ failure. In critically ill patients, sNRP-1 is positively correlated with markers of kidney and hepatic dysfunction. Most notably, critically ill patients not surviving in the long term (one year after admission) showed higher concentrations of sNRP-1 at the time of ICU admission (p = 0.036), with this association being dependent on the presence of organ failure. Critically ill and septic patients exhibit higher serum concentrations of circulating sNRP-1, which correlates to organ failure, particularly hepatic and kidney dysfunction.

Keywords: Neuropilin-1; critical illness; human; immune system; inflammation; intensive care unit; mortality; prognosis; sepsis; survival

Literature

1. Sepsis and septic shock. Cecconi M, Evans L, Levy M, Rhodes A. Lancet. 2018 Jul 7;392(10141):75-87. doi: 10.1016/S0140-6736(18)30696-2. Epub 2018 Jun 21. PMID: 29937192.
2. Soluble Neuropilin-1 Is Elevated in Sepsis and Correlates with Organ Dysfunction and Long-Term Mortality in Critical Illness. Hohlstein P, Schumacher E, Abu Jhaisha S, Adams JK, Pollmanns MR, Schneider CV, Hamesch K, Horvathova K, Wirtz TH, Tacke F, Trautwein C, Weiskirchen R, Koch A. Int J Mol Sci. 2024 May 16;25(10):5438. doi: 10.3390/ijms25105438. PMID: 38791476.

 

Kidney dysfunction causes disruptions in bone and mineral metabolism and changes in the regulators of the renal-bone axis through various mechanisms. Studies have demonstrated that fibroblast growth factor 23 (FGF23) and inflammatory markers rise, while iron status may decline (1, 2). In healthy individuals, FGF23 is regulated by phosphate, Vitamin D (1,25(OH)₂D), and parathyroid hormone (PTH). However in the early stages of chronic kidney disease (CKD), FGF23 levels begin to increase even before plasma phosphate levels increase (3).

Thus, CKD causes disruptions in bone and mineral metabolism that also includes the regulatory hormones, resulting chronic kidney disease-mineral bone disorder (CKD-MBD).

Bone biomarkers in early renal impairment

A recent study investigated the effects of Vitamin D supplementation in a cohort of healthy community-dwelling older people. Baseline blood concentrations of bone regulatory markers including Sclerostin (SOST), Dickkopf-related Protein 1 (DKK1); Osteoprotegerin (OPG) and soluble RANKL (sRANKL), Fibroblast growth factor 23 (intact and c-terminal FGF23) and TNF-alpha, Interleukin-6 (IL-6) were analysed. The results showed that SOST, cFGF23, iFGF23, PTH and TNF-alpha were elevated in the group of individuals with early kidney impairment compared to those with normal kidney function. Following Vitamin D supplementation, only cFGF23, 25(OH)D, and IL-6 showed differences between the groups.

The study identified alterations in the renal bone-axis that occur prior to clinical monitoring of patients. Early diagnosis in the initial stages of renal impairment may offer opportunities for preventing the progression of renal disease and chronic kidney disease-mineral bone disorder (CKD-MBD).

Learn more: Alterations in regulators of the renal-bone axis, inflammation and iron status in older people with early renal impairment and the effect of vitamin D supplementation. Christodoulou M et al., Age Ageing. 2024; 53(5):afae096. doi: 10.1093/ageing/afae096. PMID: 38770543.

Bone biomarkers in early renal impairment

Biomedica offers quality ELISA Assay Kits for bone regulatory biomarkers

Sclerostin (SOST; cat.no. BI-20492)

Bioactive Sclerostin (bioSOST; cat. no. BI-20472)

OPG  (Osteoprotegerin; cat.no. BI-20403)

RANKL (soluble RANKL; cat.no. BI-20462)

DKK-1  (Dickkopf-1; cat.no. BI-20413)

FGF23 intact  (Fibroblast growth factor-23 intact; cat.no. BI-20700)

FGF23 C-terminal  (Fibroblast growth factor-23 C-terminal; cat.no. cat.no. BI-20702)

 

Key Features

• TRUSTED – cited in over 1000 publications
• Kit validations follows international quality guidelines
• Ready to use standards and controls included
• Developed & manufactured by Biomedica in Austria

 

Literature

1. Iron Deficiency Anemia in Chronic Kidney Disease. Gafter-Gvili A, Schechter A, Rozen-Zvi B. Acta Haematol. 2019;142(1):44-50. doi: 10.1159/000496492. Epub 2019 Apr 10. PMID: 30970355.
2. Iron-Deficiency Anemia in CKD: A Narrative Review for the Kidney Care Team. Hain D, Bednarski D, Cahill M, Dix A, Foote B, Haras MS, Pace R, Gutiérrez OM. Kidney Med. 2023 May 25;5(8):100677. doi: 10.1016/j.xkme.2023.100677. PMID: 37415621; PMCID: PMC10319843.
3. The bone-renal axis in early chronic kidney disease: an emerging paradigm. Danziger J. Nephrol Dial Transplant. 2008 Sep;23(9):2733-7. doi: 10.1093/ndt/gfn260. Epub 2008 May 9. PMID: 18469306.

 

Breast cancer is the most prevalent cancer among women globally. Enhancing our knowledge of how breast cancer develops, progresses, and metastasizes could aid in decreasing the risk and impact of the disease. Circulating proteins in serum or plasma can serve as biomarkers of cancer progression and prognosis while also serving as potential therapeutic targets. Enhancing our understanding on how cancers originate, grow and spread could aid in lowering the risk and impact of the disease. Recent research on cancer markers has highlighted novel protein biomarkers and promising therapeutic targets in breast cancer:

PERIOSTIN, NEUROPILIN-1, SEMAPHORIN 4D, and LEUCINE-RICH ALPHA-2-GLYCOPROTEIN. These proteins can be easily detected in human serum and plasma using ELISA assays.

Novel Biomarkers in Breast Cancer

PERIOSTIN (alternative names: POSTN, OSF-2, OSF2, PDLPN, PN)

Periostin is a matricellular protein that plays a significant role in various physiological and pathological processes, including tissue remodeling, inflammation, and wound healing. In the context of breast cancer, periostin has garnered attention due to its involvement in tumorigenesis, progression, and the tumor microenvironment.

Role of Periostin in Breast Cancer

Tumor Microenvironment: Periostin is often overexpressed in the extracellular matrix (ECM) of breast tumors (1). It interacts with various cells in the tumor microenvironment, including cancer-associated fibroblasts, immune cells, and endothelial cells, promoting tumor growth and metastasis. A recent study has demonstrated that Periostin drives extracellular matrix degradation, stemness, and chemoresistance in triple-negative breast cancer cells by activating specific signaling pathways (2).

Cell Signaling: Periostin can activate multiple signaling pathways that contribute to cancer progression. It is known to bind to integrins on the surface of cancer cells, which can lead to enhanced cell survival, proliferation, and migration. This signaling also supports processes such as epithelial-to-mesenchymal transition (EMT), a critical step in cancer metastasis.

Metastasis: Elevated levels of periostin have been associated with increased metastasis in breast cancer. Studies have indicated that higher periostin expression correlates with the aggressive behavior of breast cancer cells, particularly in triple-negative breast cancer (TNBC), which is known for its poor prognosis (3).

Periostin as a Potential Biomarker: Due to its association with poor outcomes and aggressive disease, periostin has been investigated as a potential biomarker for breast cancer. Its expression levels in tumor tissues or serum may provide insights into disease progression and treatment responses. Epithelial periostin expression is correlated with poor survival in patients with invasive breast carcinoma (3). High serum levels of Periostin have been demonstrated to be associated with poor survival in breast cancer (4).

Therapeutic Target: Given its role in promoting cancer progression, periostin presents a potential therapeutic target. Inhibition of periostin signaling may offer a novel strategy for treating aggressive breast cancer subtypes by disrupting the supportive tumor microenvironment (5).

Conclusion: Periostin plays a multifaceted role in breast cancer, affecting tumor growth, metastasis, and the tumor microenvironment. Its involvement in key molecular pathways and its potential utility as a biomarker make it a significant focus of ongoing research. Targeting periostin could open new avenues for therapy, particularly in aggressive forms of breast cancer, ultimately aiming to improve patient outcomes. Further studies are needed to fully elucidate its mechanisms and to evaluate its efficacy as a therapeutic target in clinical settings.

Periostin can reliably be measured in human blood samples with a conventional ELISA assay developed and manufactured by BIOMEDICA.

PERIOSTIN ELISA (cat. no. BI-20433)

• EASY – ready to use calibrators & controls included
• RELIABLE – validated according to international quality guidelines
• LOW sample volume- 10 µl / sample
• TRUSTED – widely cited

 

An in-depth characterization of the Biomedica Periostin ELISA has been published here: Characterization of a sandwich ELISA for the quantification of all human periostin isoforms. Gadermaier E et al., J Clin Lab Anal. 2018; 32(2):e22252.

 

Novel Biomarkers in Breast Cancer

NEUROPILIN-1 (alternative names: NRP1, BDCA4, CD304, NP1, NRP, VEGF165R)

Neuropilin-1 (NRP1) is a transmembrane protein that has emerged as an important player in breast cancer biology. It is involved in various cellular processes, including cell signaling, survival, and migration, and has been implicated in cancer progression and metastasis (6).

Role of Neuropilin-1 in Breast Cancer

Tumor Growth and Survival: Neuropilin-1 (NRP1) is expressed in both cancer cells and the surrounding stromal cells within the tumor microenvironment. It has been linked to enhanced cell survival and proliferation, contributing to tumor growth. Elevated NRP1 expression has been associated with aggressive breast cancer subtypes, such as triple-negative breast cancer (TNBC) (6). A recent study has demonstrated that high NRP1 expression is associated with shorter relapse- and metastasis-free survival specifically in ER-negative BrCa cohorts (7).

Angiogenesis: NRP1 plays a critical role in angiogenesis, the formation of new blood vessels from existing ones, which is crucial for tumor growth and metastasis. By interacting with vascular endothelial growth factor (VEGF) and its receptors, NRP1 promotes endothelial cell proliferation and migration, facilitating the tumor’s ability to establish a blood supply (8).

Metastasis: Neuropilin-1 expression has been shown to be associated with lymph node metastasis in breast cancer tissues (9). Increased levels of NRP1 in breast cancer have been correlated with a higher propensity for metastasis. Studies have shown that NRP1 facilitates the migration of cancer cells to distant sites, contributing to the spread of the disease and poorer patient outcomes.

Potential Biomarker: In breast cancer patients, soluble Neuropilin-1 has shown to be an independent marker of poor prognosis in early breast cancer (10). In addition NRP-1 has also been shown to be a potential biomarker of prognosis and invasive-related parameters in other cancers such as liver and colorectal cancer (11).

Therapeutic Target: Given its involvement in tumor growth, angiogenesis, and metastasis, NRP1 is being explored as a therapeutic target. Strategies to inhibit NRP1 function or block its signaling pathways could offer new avenues for breast cancer treatment, particularly for patients with aggressive or metastatic disease (12).

Conclusion: Neuropilin-1 is a significant factor in the biology of breast cancer, influencing tumor growth, metastasis, and interactions within the tumor microenvironment. Its role in promoting angiogenesis and facilitating aggressive cellular behaviors makes it an important target for ongoing research. Targeting NRP1 could provide new therapeutic approaches for breast cancer, potentially improving outcomes for patients, especially those with more aggressive forms of the disease. Further studies are needed to clarify its mechanisms and evaluate targeted therapies in clinical settings.

Neuropilin-1 (NRP1) can reliably be measured in human blood samples with a conventional ELISA assay developed and manufactured by BIOMEDICA.

Total soluble NEUROPILIN-1 ELISA (cat. no. BI-20409)

• EASY – ready to use calibrators & controls included
• RELIABLE – validated according to international quality guidelines
• LOW sample volume- 10 µl / sample
• TRUSTED – for citations click here

 

The Biomedica human NRP-1 ELISA is described in this following publication: Characterization of a sandwich ELISA for quantification of total human soluble neuropilin-1. Gadermaier E, Tesarz M, Wallwitz J, Berg G, Himmler G. J Clin Lab Anal. 2019; 33(7):e22944. doi: 10.1002/jcla.22944. PMID: 31219204.

 

Novel Biomarkers in Breast Cancer

SEMAPHORIN 4D (alternative names: Sema4D, C9orf164, SEMAJ, CD100, BB18, GR3, CD100, COLL4)

Semaphorin 4D (Sema4D) is a member of the semaphorin family of proteins, which are known for their roles in cell signaling, axon guidance, and immune regulation (13). In the context of breast cancer, Sema4D has garnered attention for its involvement in tumor growth, metastasis, and the tumor microenvironment.

About Semaphorin 4D in Breast Cancer

Tumor Growth and Progression: Sema4D can influence the behavior of cancer cells, promoting survival and proliferation. It may also aid in the establishment of a supportive tumor microenvironment. In a study researchers have shown that Sema4D was expressed at higher levels in breast cancer cell lines compared with the normal human breast epithelial cell lines (14).

Angiogenesis: Sema4D is involved in the formation of new blood vessels (angiogenesis), which is vital for tumor growth. It can modulate the activity of endothelial cells, thereby supporting the vascularization of tumors (14).

Immune Evasion: Sema4D can affect the immune response to tumors. It may contribute to the suppression of T-cell responses, allowing cancer cells to evade immune detection and destruction.

Metastasis: The expression of Sema4D has been linked to increased metastatic potential in breast cancer. It may facilitate the migration and invasion of cancer cells to distant sites in the body. In a recent study researchers have found that Semaphorin 4D promotes skeletal metastasis in breast cancer (15).

A decreased expression of semaphorin 4D and plexin-B in breast cancer has been shown to be associated with recurrence and poor prognosis in a breast cancer cohort (16).

Biomarker Potential: Research suggests that Sema4D levels could serve as a potential biomarker for breast cancer progression and prognosis, although further studies would be needed to establish its clinical utility.

The potential link between Sema4D and estrogen receptor signaling was proposed in a study measuring circulating Sema4D plasma levels at primary diagnosis and in a follow-up sample 12 months after surgery in a cohort of 46 pre- and postmenopausal women with primary estrogen receptor positive breast cancer receiving adjuvant tamoxifen. The finding potentially represents an additional mechanism of the bone-protective properties of tamoxifen (17).

Therapeutic Targeting:  Due to its involvement in various aspects of cancer biology, Sema4D is being explored as a potential therapeutic target. Inhibiting its function might help in reducing tumor growth and improving the effectiveness of existing treatments. A study demonstrated that a Sema4D antibody in combination with either CTLA-4 or PD-1 blockade enhanced rejection of tumors or tumor growth delay, resulting in prolonged survival with either treatment (18).

Conclusion: Sema4D plays a multifaceted role in breast cancer pathology, influencing tumor growth, metastasis, and immune interactions. Ongoing research is essential to fully understand its mechanisms and to explore its potential as a target for therapeutic intervention.

Soluble SEMAPHORIN 4D ELISA (cat. no. BI-20405)

• EASY – ready to use calibrators & controls included
• RELIABLE – first validated according to international quality guidelines
• LOW sample volume- 10 µl / sample – no predilution!
• Reference values for healthy individuals provided

 

An in-depth characterization of the Biomedica Semaphorin 4D ELISA has been published here: A high-sensitivity enzyme immunoassay for the quantification of soluble human semaphorin 4D in plasma. Laber, A., Gadermaier, E., Wallwitz, J., Berg, G., Himmler, G., 2019. Anal. Biochem. 574, 15–22.  PMID: 30879960

 

Novel Biomarkers in Breast Cancer

LEUCINE-RICH ALPHA-2-GLYCOPROTEIN (alternative names: LRG, LRG1, HMFT1766) 

Leucine-rich alpha-2-glycoprotein (LRG) is a protein that has been studied in various diseases, including cancer. It is known for its involvement in inflammation and immune responses. In the context of breast cancer, LRG has attracted interest for its potential role as a biomarker and its involvement in the tumor microenvironment. For more information on LRG-1 as a prognostic marker for breast cancer survival please click here

LRG ELISA Assay Highlights (cat. no. BI-LRG)

• CONVENIENT – ready to use reagents and controls included
• RELIABLE – rigorously validated following international quality guidelines
• EASY – results available in 3 hours

 

Related products

DKK-1 (Dickkopf-1) ELISA kit (cat. no. BI-20413) 

• Direct measurement – no sample pre-dilution
• Day test – all reagents included
• Widely cited +180 references!

 

Literature 

1.  Expression of periostin in breast cancer cells. Ratajczak-Wielgomas K, Grzegrzolka J, Piotrowska A, Matkowski R, Wojnar A, Rys J, Ugorski M, Dziegiel P. Int J Oncol. 2017; 51(4):1300-1310. doi: 10.3892/ijo.2017.4109.
2. Periostin drives extracellular matrix degradation, stemness, and chemoresistance by activating the MAPK/ERK signaling pathway in triple-negative breast cancer cells. Wu J, Li J, Xu H, Qiu N, Huang X, Li H. Lipids Health Dis. 2023; 16;22(1):153. doi: 10.1186/s12944-023-01912-1.
3. Epithelial periostin expression is correlated with poor survival in patients with invasive breast carcinoma. Kim GE, Lee JS, Park MH, Yoon JH. PLoS One. 2017; 21;12(11):e0187635. doi: 10.1371/journal.pone.0187635. PMID: 29161296..
4. High serum levels of periostin are associated with a poor survival in breast cancer. Rachner TD et al., Breast Cancer Res Treat. 2020; 180(2):515-524.
5. Development of an engineered peptide antagonist against periostin to overcome doxorubicin resistance in breast cancer. Oo KK, Kamolhan T, Soni A, Thongchot S, Mitrpant C, O-Charoenrat P, Thuwajit C, Thuwajit P. BMC Cancer. 2021; 14;21(1):65. doi: 10.1186/s12885-020-07761-w.
6. Neuropilin1, a novel independent prognostic factor and therapeutic target in triple-negative breast cancer. Wang H, Zhang YN, Xu DQ, Huang JG, Lv D, Shi XY, Liu JY, Ren HW, Han ZX. Neoplasma. 2020; 67(6):1335-1342. doi: 10.4149/neo_2020_191127N1223. PMID: 32657612.
7. Neuropilin-1 is over-expressed in claudin-low breast cancer and promotes tumor progression through acquisition of stem cell characteristics and RAS/MAPK pathway activation. Tang YH, Rockstroh A, Sokolowski KA, Lynam LR, Lehman M, Thompson EW, Gregory PA, Nelson CC, Volpert M, Hollier BG. Breast Cancer Res. 2022; 25;24(1):8. doi: 10.1186/s13058-022-01501-7. PMID: 35078508.
8. Endothelial VEGFR Coreceptors Neuropilin-1 and Neuropilin-2 Are Essential for Tumor Angiogenesis. Benwell CJ, Johnson RT, Taylor JAGE, Price CA, Robinson SD. Cancer Res Commun. 2022 Dec 14;2(12):1626-1640. doi: 10.1158/2767-9764.CRC-22-0250. PMID: 36970722; PMCID: PMC10036134.
9. Neuropilin-1 expression is associated with lymph node metastasis in breast cancer tissues. Seifi-Alan M, Shams R, Bandehpour M, Mirfakhraie R, Ghafouri-Fard S. Cancer Manag Res. 2018 Jul 11;10:1969-1974. doi: 10.2147/CMAR.S169533. PMID: 30022855; PMCID: PMC6045910.
10. Soluble Neuropilin-1 is an independent marker of poor prognosis in early breast cancer. Rachner TD, Kasimir-Bauer S, Goebel A, Erdmann K, Hoffmann O, Rauner M, Hofbauer LC, Kimmig R, Bittner AK. J Cancer Res Clin Oncol. 2021; 147(8):2233-2238. doi: 10.1007/s00432-021-03635-1. PMID: 33884469.
11. Neuropilin-1 as a Potential Biomarker of Prognosis and Invasive-Related Parameters in Liver and Colorectal Cancer: A Systematic Review and Meta-Analysis of Human Studies. Fernández-Palanca P, Payo-Serafín T, Fondevila F, Méndez-Blanco C, San-Miguel B, Romero MR, Tuñón MJ, Marin JJG, González-Gallego J, Mauriz JL. Cancers (Basel). 2022 Jul 15;14(14):3455. doi: 10.3390/cancers14143455. PMID: 35884516.
12. SPECT and near-infrared fluorescence imaging of breast cancer with a neuropilin-1-targeting peptide. Feng GK, Liu RB, Zhang MQ, Ye XX, Zhong Q, Xia YF, Li MZ, Wang J, Song EW, Zhang X, Wu ZZ, Zeng MS.J Control Release. 2014; 28;192:236-42. doi: 10.1016/j.jconrel.2014.07.039. PMID: 25058570.
13. Semaphorin 4D as a guidance molecule in the immune system. Kuklina E. Int Rev Immunol. 2021;40(4):268-273. doi: 10.1080/08830185.2021.1905807. PMID: 33787446.
14. The role of semaphorin 4D in tumor development and angiogenesis in human breast cancer. Jiang H, Chen C, Sun Q, Wu J, Qiu L, Gao C, Liu W, Yang J, Jun N, Dong J. Onco Targets Ther. 2016 Sep 26;9:5737-5750. doi: 10.2147/OTT.S114708. PMID: 27729799; PMCID: PMC5045906.
15. Semaphorin 4D Promotes Skeletal Metastasis in Breast Cancer. Yang YH, Buhamrah A, Schneider A, Lin YL, Zhou H, Bugshan A, Basile JR.PLoS One. 2016; 11(2):e0150151. doi: 10.1371/journal.pone.0150151. PMID: 26910109.
16. Reduced expression of semaphorin 4D and plexin-B in breast cancer is associated with poorer prognosis and the potential linkage with oestrogen receptor. Malik MF, Ye L, Jiang WG. Oncol Rep. 2015 Aug;34(2):1049-57. doi: 10.3892/or.2015.4015. Epub 2015 May 28. PMID: 26035216.
17. Plasma levels of Semaphorin 4D are decreased by adjuvant tamoxifen but not aromatase inhibitor therapy in breast cancer patients. Göbel, A., Kuhlmann, J.D., Link, T., Wimberger, P., Link-Rachner, C., Thiele, S., Dell’Endice, S., Furesi, G., Breining, D., Rauner, M., Hofbauer, L.C., Rachner, T.D., 2019. Journal of Bone Oncology, 16: 100237. PMID: 31011525
18. Semaphorin4D Inhibition Improves Response to Immune-Checkpoint Blockade via Attenuation of MDSC Recruitment and Function. Clavijo PE, Friedman J, Robbins Y, Moore EC, Smith E, Zauderer M, Evans EE, Allen CT. Cancer Immunol Res. 2019; 7(2):282-291. doi: 10.1158/2326-6066.CIR-18-0156. PMID: 30514791.

Leucine-rich alpha-2-glycoprotein (LRG or syn. LRG1) is a glycoprotein that has gained attention in the context of various cancers, including breast cancer. It is encoded by the LRG1 gene and is known for its role in the immune response and its involvement in various biological processes, including inflammation and tissue repair (1, 2).

In patients diagnosed with early breast cancer (BC), elevated levels of intratumoral LRG-1 protein expression are linked to decreased survival rates (3). In a recent study by Göbel A et al., serum LRG-1 levels were assessed in 509 patients with primary early BC (4). The study explored the correlation of LRG with the presence of disseminated tumor cells (DTCs) in the bone marrow as well as survival outcomes.

LRG-1 a prognostic marker for breast cancer survival

The LRG ELISA assay from BIOMEDICa has been utilized in this study (4) demonstrating that serum levels of leucine-rich α-2 glycoprotein serve as an independent prognostic indicator for breast cancer-specific survival. This discovery could lead to novel diagnostic approaches, particularly given that serum sample analyses in cancer patients are readily available, cost-effective, and can be easily integrated into standard clinical practices.

High serum levels of leucine-rich α-2 glycoprotein 1 (LRG-1) are associated with poor survival in patients with early breast cancer. Göbel A,et al., Arch Gynecol Obstet 2024; 309(6):2789-2798. 

 

ROLE OF LRG-1 in BREAST CANCER

Biomarker Potential: LRG has been investigated as a potential biomarker for breast cancer. Studies have indicated that LRG levels is elevated in the serum of breast cancer patients compared to healthy controls (4). This suggests that LRG could potentially be used as a diagnostic or prognostic marker, providing insights into disease presence and progression. 

Tumor Microenvironment: LRG is thought to play a role in modulating the tumor microenvironment. It may influence the behavior of cancer cells and the surrounding stromal cells, thereby impacting tumor growth and metastasis. Its interactions with various cytokines and immune cells can affect inflammation and immune evasion, which are critical components of cancer progression.

Mechanisms of Action: The exact mechanisms by which LRG influences breast cancer are still being unraveled. There is evidence suggesting that LRG can modulate the signaling pathways involved in cancer cell proliferation and survival. Its leucine-rich regions are known to interact with a variety of proteins, possibly contributing to the malignancy of breast cancer cells.

Therapeutic Implications: Given its involvement in tumor progression and immune regulation, LRG is being explored as a potential therapeutic target. Strategies aimed at modulating LRG levels or blocking its actions could offer new avenues for treatment, particularly in patients with aggressive or metastatic breast cancer.

Research Directions: Ongoing research is focused on further elucidating the role of LRG in breast cancer. This includes understanding its function in different breast cancer subtypes (e.g., triple-negative breast cancer) and its interactions within the immune system. The potential for LRG to serve as a target for immunotherapy or be a part of combination therapies is also an area of ongoing investigation.

Conclusion: LRG is emerging as an important player in the context of breast cancer, both as a potential biomarker and as a target for therapeutic interventions. While more research is needed to fully understand its role and mechanisms, the current findings highlight its significance in the pathophysiology of breast cancer and its potential utility in improving cancer diagnosis and treatment outcomes. The continued exploration of LRG may pave the way for advancements in personalized medicine strategies for breast cancer patients.

LRG ELISA Assay Highlights (cat. no. BI-LRG)

• SPECIFIC – characterized antibodies – epitope mapped
• CONVENIENT – ready to use reagents and controls included
• RELIABLE – rigorously validated following international quality guidelines
• EASY – results available in 3 hours
• Protocol booklet, instructions for use- click here

 

For detailed information please click on the link: Leucine-rich alpha-2-glycoprotein (LRG) ELISA | BI-LRG

Literature

1. Research Progress on Leucine-Rich Alpha-2 Glycoprotein 1: A Review. Zou Y, Xu Y, Chen X, Wu Y, Fu L, Lv Y. Front Pharmacol. 2022 Jan 5;12:809225. doi: 10.3389/fphar.2021.809225. PMID: 35095520; PMCID: PMC8797156.
2. Intracellular leucine-rich alpha-2-glycoprotein-1 competes with Apaf-1 for binding cytochrome c in protecting MCF-7 breast cancer cells from apoptosis. Jemmerson R, Staskus K, Higgins L, Conklin K, Kelekar A Apoptosis. 2021 Feb;26(1-2):71-82. doi: 10.1007/s10495-020-01647-9. PMID: 33386492; PMCID: PMC7904597.
3. The role of leucine-rich alpha-2-glycoprotein-1 in proliferation, migration, and invasion of tumors. Lin M, Liu J, Zhang F, Qi G, Tao S, Fan W, Chen M, Ding K, Zhou F. J Cancer Res Clin Oncol. 2022 Feb;148(2):283-291. doi: 10.1007/s00432-021-03876-0. PMID: 35037101.
4. High serum levels of leucine-rich α-2 glycoprotein 1 (LRG-1) are associated with poor survival in patients with early breast cancer. Göbel A, Rachner TD, Hoffmann O, Klotz DM, Kasimir-Bauer S, Kimmig R, Hofbauer LC, Bittner AK.Arch Gynecol Obstet. 2024 Jun;309(6):2789-2798. doi: 10.1007/s00404-024-07434-0. PMID: 38413424; PMCID: PMC11147863.

 

Breast Cancer Awareness Month is a global health initiative celebrated every October. Its purpose is to raise awareness about screening and prevention for a disease that impacts 2.3 million women worldwide.

Breast cancer (BC) is the most prevalent cancer among women and ranks as the most common cancer overall. While it predominantly affects women, men can also develop breast tissue that becomes malignant. Male breast cancers are uncommon, accounting for only 1% of all cases, yet men are frequently diagnosed at more advanced stages. This delay in seeking medical care often leads to later presentations and poorer outcomes.

Breast Cancer Awareness Month – October 2024

Several risk factors can increase the likelihood of developing breast cancer, including:

• Gender: Being female is the primary risk factor.
• Age: The risk increases with age, particularly for women over 55.
• Family History: Genetics can play a role; individuals with a family history of breast cancer may have mutations in genes such as BRCA1 and BRCA2.
• Personal History: Those who have had breast cancer or certain benign breast conditions are at a higher risk.
• Lifestyle Factors: Factors such as obesity, lack of physical activity, alcohol consumption, and smoking can contribute to the risk.

 

Early detection through regular screening improves outcomes significantly. The prognosis for breast cancer varies significantly depending on several factors, including the type of cancer, the stage at diagnosis, and how well the cancer responds to treatment.

Prevention and Awareness

While it’s not possible to prevent breast cancer entirely, certain lifestyle choices can help reduce risk, such as maintaining a healthy weight, exercising regularly, moderating alcohol intake, and avoiding tobacco. Organizations worldwide promote Breast Cancer Awareness Month in October, highlighting the importance of early detection, education, and support resources for those affected by the disease.

Further reading

• Breast Cancer Screening and Prevention. Farkas AH, Nattinger AB. Ann Intern Med. 2023 Nov;176(11):ITC161-ITC176. doi: 10.7326/AITC202311210. Epub 2023 Nov 14. PMID: 37956433.

 

• Breast cancer highlights from 2023: Knowledge to guide practice and future research. Cardoso MJ, Poortmans P, Senkus E, Gentilini OD, Houssami N.Breast. 2024 Apr;74:103674. doi: 10.1016/j.breast.2024.103674. Epub 2024 Jan 27. PMID: 38340683; PMCID: PMC10869942.

 

• Male Breast Cancer (MBC) – A Review. AlFehaid M. Pol Przegl Chir. 2023 Dec 30;95(6):24-30. PMID: 38058163.

 

Biomedica´s Oncology Product Line

 

Join us at the ASBMR (American Society of Bone and Mineral Research) Conference at booth number 145. The annual meeting is taking place in Toronto, ON, Canada from September 27-30, 2024.

The American Society of Bone and Mineral Research (ASBMR) meeting is considered to be the largest event worldwide covering fields in bone, mineral and musculoskeletal research. The meeting attracts over 2,500 participants across the globe, including both clinicians and researchers working in different disciplines and at all career levels. The meeting provides attendees with exciting opportunities to exchange knowledge and to learn about the latest scientific and medical advances in the field.

Discover some of our biomarker assays for clinical research in bone and mineral disorders

–FGF23 intact and c-terminal

–Sclerostin and bioactive Sclerostin

–Osteoprotegerin(OPG)  and soluble RANKL

–Dickkopf-1 and Periostin

 

 

Exploring Biomarkers in Bone Biology

During the process of bone remodeling, bone cells release biomarkers that can aid in the evaluation of bone diseases and serve as valuable therapeutic targets. These bone biomarkers can be readily detected in serum and plasma samples using immunoassays.

A recent review by Nicolas H Hart et al., provides researchers and clinicians involved in bone and mineral metabolism with a comprehensive contemporary update on the Biological basis of bone strength: anatomy, physiology and measurement. J Musculoskelet Neuronal Interact. 2020; ;20(3):347-371.

Abstract

Understanding how bones are innately designed, robustly developed and delicately maintained through intricate anatomical features and physiological processes across the lifespan is vital to inform our assessment of normal bone health, and essential to aid our interpretation of adverse clinical outcomes affecting bone through primary or secondary causes. Accordingly this review serves to introduce new researchers and clinicians engaging with bone and mineral metabolism, and provide a contemporary update for established researchers or clinicians. Specifically, we describe the mechanical and non-mechanical functions of the skeleton; its multidimensional and hierarchical anatomy (macroscopic, microscopic, organic, inorganic, woven and lamellar features); its cellular and hormonal physiology (deterministic and homeostatic processes that govern and regulate bone); and processes of mechanotransduction, modelling, remodelling and degradation that underpin bone adaptation or maladaptation. In addition, we also explore commonly used methods for measuring bone metabolic activity or material features (imaging or biochemical markers) together with their limitations.