The International Day of Happiness has been initiated by the United Nations to spread awareness of the importance of happiness in the lives of people around the world (1). Happiness and health are closely tied together and affect one another.
Happiness and Health
Numerous studies have found that happiness is linked to a strong immune system and a better general health (2). Reducing risk factors e.g., tobacco, alcohol, low-nutrition foods and beverages are only some strategies to reduce disease burden (3).
Studying biomarkers may help to understand the mechanism on how the disease originates and could improve diagnosis and disease prognosis (4).
BIOMEDICA specializes on the development of cutting-edge biomarker assays for clinical research.
Biomedica ELISA kits by research area
- Bone Metabolism
- Cardiovascular
- Cell Proliferation
- Immunology
- Infectious Disease
- Metabolic Disease
- Infection
- Nephrology and Transplant
- Neurology
- Oncology
- Oxidative Stress
- Cytokines
High quality ELISA kits- developed and manufactured by Biomedica
References
- International Day of Happiness – the United Nations
- Happiness and Health Annu Rev Public Health. Steptoe A. 2019 Apr 1;40:339-359. doi: 10.1146/annurev-publhealth-040218-044150. Epub 2019 Jan 2. PMID: 30601719. Full text review
Abstract
Research into the relationship between happiness and health is developing rapidly, exploring the possibility that impaired happiness is not only a consequence of ill-health but also a potential contributor to disease risk. Happiness encompasses several constructs, including affective well-being (feelings of joy and pleasure), eudaimonic well-being (sense of meaning and purpose in life), and evaluative well-being (life satisfaction). Happiness is generally associated with reduced mortality in prospective observational studies, albeit with several discrepant results. Confounding and reverse causation are major concerns. Associations with morbidity and disease prognosis have also been identified for a limited range of health conditions. The mechanisms potentially linking happiness with health include lifestyle factors, such as physical activity and dietary choice, and biological processes, involving neuroendocrine, inflammatory, and metabolic pathways. Interventions have yet to demonstrate substantial, sustained improvements in subjective well-being or direct impact on physical health outcomes. Nevertheless, this field shows great potential, with the promise of establishing a favorable effect on population health.
- Association of Healthy Lifestyle With Years Lived Without Major Chronic Diseases.Nyberg ST, Singh-Manoux A, Pentti J, .. Batty GD, Kivimäki M. JAMA Intern Med. 2020 May 1;180(5):760-768. doi: 10.1001/jamainternmed. 2020.0618. PMID: 32250383; PMCID: PMC7136858.
- Role of Biomarkers in Health Care. Jain KK. The Handbook of Biomarkers. 2010 Jan 20:115–88. doi: 10.1007/978-1-60761-685-6_5. PMCID: PMC7123449.
World Kidney Day – March 9, 2023 – raising awareness of the importance of our kidneys
Around 1 in 10 people suffer from chronic kidney disease (CKD), with more than 800 million individuals being affected worldwide. CKD is a progressive disease in which the kidneys gradually lose their function over time. If detected early, medication and changes in lifestyle may help to prevent or slow down CKD progression.
What are the risk factors for CKD?
Older age (+60 years), diabetes, high blood pressure, heart disease, obesity and some medications are some known risk factors for kidney disease.
How can we keep our kidneys healthy?
Nutrition, exercise, sufficient fluid intake are only some examples on how to keep our kidneys healthy. Valuable information can be found on the following websites :
“The International Society of Nephrology – ISN”
“International Federation of Kidney Foundations – IFKF”
BIOMEDICA – Biomarker ELISA kits for clinical research in kidney disease
check out our Brochure – Biomarkers in Clinical Nephrology
ROBUST & RELIABLE ASSAYS
- Fully validated according to international quality guidelines
- Widely cited in over 1500 publications
FGF23 (Fibroblast growth factor 23) Vanin-1, Endostatin, Sclerostin, Osteoprotegerin, Angiopoietin-2, IL-6, VEGF
Biomedica Quality ELISA kits
LITERATURE
Plant-based diets for prevention and management of chronic kidney disease. Joshi S, Hashmi S, Shah S, Kalantar-Zadeh K. Curr Opin Nephrol Hypertens. 2020 Jan;29(1):16-21. doi: 10.1097/MNH.0000000000000574. PMID: 31725014.
Abstract
Purpose of review: Plant-based diets have been used with growing popularity for the treatment of a wide range of lifestyle-related diseases, including diabetes, hypertension, and obesity. With the reinvigoration of the dietary management of chronic kidney disease (CKD) and the use of low protein diets for secondary prevention of CKD to delay or prevent dialysis therapy, there is an increasing interest in the potential role of plant-based diets for these patients.
Recent findings: Recently, a body of evidence related to the role of plant-based diets in preventing CKD has reemerged. Several observational studies have shown that red and processed meat have been associated with increased risk of CKD as well as faster progression in those with preexisting CKD. In several substitution analyses, replacement of one serving of red and/or processed meat has been linked with sizable reductions in CKD risk. Although limited, experimental trials for the treatment of metabolic acidosis in CKD with fruits and vegetables show outcomes comparable to oral bicarbonate. The use of plant-based diets in CKD may have other benefits in the areas of hypertension, weight, hyperphosphatemia, reductions in hyperfiltration, and, possibly, mortality. The risk of potassium overload from plant-based diets appears overstated, mostly opinion-based, and not supported by the evidence. Plant-based diets are generally well tolerated and provide adequate protein intake, including essential amino acids as long as the diet is correctly implemented.
Summary: Plant-based diets should be recommended for both primary and secondary prevention of CKD. Concerns of hyperkalemia and protein inadequacy related to plant-based diets may be outdated and unsupported by the current body of literature. Healthcare providers in general medicine and nephrology can consider plant-based diets as an important tool for prevention and management of CKD.
Exercise and Kidney Disease Prevention: Walk This Way. Seliger S, Weiner DE. Am J Kidney Dis. 2022 Oct;80(4):552-554. doi: 10.1053/j.ajkd.2022.07.001. Epub 2022 Jul 21. PMID: 35872228.
Raising awareness, screening and prevention of chronic kidney disease: It takes more than a village. Hsiao LL. Nephrology (Carlton). 2018 Oct;23 Suppl 4:107-111. doi: 10.1111/nep.13459. PMID: 30298651.
Abstract
Chronic kidney disease (CKD) is a major public health problem worldwide. Its prevalence and incidence are increasing, particularly among the ethnic minority populations. Diabetes, hypertension and obesity have been the three major aetiologies for CKD in all developed countries. While diabetes and hypertension remain the major causes of CKD in developing countries, environmental pollution, pesticides, water, analgesic abuse and herbal medications are common causes in these regions. Rapid urbanization and globalization are thought to be the contributing factors to rising prevalence and incidents of CKD. Despite the rising prevalence of CKD, disease awareness remains profoundly low. Worldwide, only 6% of the general population and 10% of the high-risk population are aware of their CKD statuses. Health screenings have been shown to be effective in improving the incidence of ESRD. However, currently there is no effective tool to assess and evaluate the awareness objectively.
Microbiome-metabolome reveals the contribution of gut-kidney axis on kidney disease. Chen YY, Chen DQ, Chen L, Liu JR, Vaziri ND, Guo Y, Zhao YY. J Transl Med. 2019 Jan 3;17(1):5. doi: 10.1186/s12967-018-1756-4. PMID: 30602367; PMCID: PMC6317198.
Acute kidney injury (AKI) – also called acute renal failure – occurs when the kidneys suddenly fail to function due to an injury medication, or an infection. It happens within a few hours or days and is usually accompanied with other medical conditions e.g. blood vessel blockage, diabetes, heart failure, kidney and liver disease, hospitalization (ICU) and other.
FGF23 in Acute Kidney Injury
Fibroblast growth factor 23 (FGF23) is a bone derived hormone that regulates renal phosphate excretion in the kidney. In kidney disease, when the function of the kidney declines, serum phosphate levels rise which subsequently leads to the secretion of FGF-23. High phosphate levels are also common in patients with acute kidney injury (AKI) (1).
FGF23 marker of adverse outcomes in acute kidney injury
Fibroblast growth factor 23 (FGF23) levels rise rapidly with acute kidney injury and are associated with the requirement for renal replacement therapy (1-4). FGF-23 levels also have prognostic utility as shown in a large study in over 1500 patients with AKI (3).
Most studies measuring elevated FGF23 levels in AKI patients are performed using FGF23 (C-terminal) assays, which detect intact and C-terminal FGF23. Although the results mirror an increase of FGF23 production they may not necessarily reflect the bioactivity of FGF23 (5).
Quantifying circulating FGF23 levels
Circulating FGF23 levels include the bioactive intact hormone (iFGF23) and the inactive N-terminal and C-terminal fragments. FGF23 can be measured with two commercially available assay types (6). The C-terminal FGF23 assay captures both intact and the c-terminal fragments of FGF23, which result after cleavage. The intact FGF23 assay utilizes antibodies that are located in the N-terminal and in the C-terminal region of the FGF23 hormone, thus capturing only biologically active intact FGF23.
Learn more: FGF23 – an Overview
BIOMEDICA offers quality FGF23 assays for serum & plasma samples
FGF23 (c-terminal) ELISA, cat. no. BI-20702
FGF23 intact ELISA, cat no. BI-20700
- developed & manufactured by Biomedica , Austria
- fully validated
- numerous top journal citations
Literature
- Fibroblast Growth Factor 23 and Klotho in AKI. Christov M, Neyra JA, Gupta S, Leaf DE. Semin Nephrol. 2019 Jan;39(1):57-75. doi: 10.1016/j.semnephrol.2018.10.005. PMID: 30606408.
- Fibroblast Growth Factor 23 Regulation and Acute Kidney Injury. Zhou W, Simic P, Rhee EP. Nephron. 2022;146(3):239-242. doi: 10.1159/000517734. Epub 2021 Jul 20. PMID: 34284404; PMCID: PMC8770696.
- Fibroblast growth factor 23 associates with death in critically ill patients. Leaf DE, Siew ED, Eisenga MF, Singh K, Mc Causland FR, Srivastava A, Ikizler TA, Ware LB, Ginde AA, Kellum JA, Palevsky PM, Wolf M, Waikar SS, Am Clin J Am Soc Nephrol. 2018. 13(4):531–41.
- FGF-23 levels in patients with AKI and risk of adverse outcomes. Leaf DE, Wolf M, Waikar SS, Chase H, Christov M, Cremers S, Stern L. Clin J Am Soc Nephrol. 2012. 7(8):1217-23.
- Fibroblast Growth Factor 23 and αKlotho in Acute Kidney Injury: Current Status in Diagnostic and Therapeutic Applications. Neyra JA, Hu MC, Moe OW. Nephron. 2020;144(12):665-672. doi: 10.1159/000509856. Epub 2020 Aug 25. PMID: 32841947; PMCID: PMC7708396.
- The Measurement and Interpretation of Fibroblast Growth Factor 23 (FGF23) Concentrations. Heijboer AC, Cavalier E. Calcif Tissue Int. 2023. 112(2):258-270.
NEW – Rat NT-proBNP ELISA assay
quantitative, reliable and robust for translational research and drug discovery.
Rat NT-proBNP ELISA assay │ BI-1204R
features & benefits
- 10 µl / well, serum or plasma
- kit control included
- sample values provided
NT-proANP ELISA assay │BI-20892
features & benefits
- 10 µl / well, serum or plasma
- widely cited as cardiovascular safety biomarker in rats
“cross-laboratory comparison study detecting serum NT-proANP in rats with the Biomedica NT-proANP ELISA to be technically adequate with acceptable intra- and inter-assay and inter-laboratory precision and accuracy (Vinken et al., 2016).”
All assays are developed and manufactured by Biomedica!
NT-proBNP & NT-proANP in drug-induced cardiac hypertrophy
The cardiac biomarkers NT-proBNP and NT-proANP are predictive of left ventricular hypertrophy (LVH) and systolic dysfunction in humans (1, 2).
In preclinical settings they have successfully been used to detect cardiotoxicity (3). NT-proBNP and NT-proANP have shown to be useful tools that help to improve the detection of cardiovascular injury early in drug development (4).
REFERENCES
- Circulating N-terminal pro-atrial natriuretic peptide is an independent predictor of left ventricular hypertrophy in the general population. The Tromsø Study. Schirmer H, Omland T. Eur Heart J. 1999 May;20(10):755-63. doi: 10.1053/euhj.1998.1396. Erratum in: Eur Heart J 1999 Oct;20(19):1439. PMID: 10329067.
- An association between N-terminal pro-brain natriuretic protein level and risk of left ventricular hypertrophy in patients without heart failure. Huang L, Huang L, Yu J, Wu X, Zhao J Exp Ther Med. 2020 May;19(5):3259-3266. doi: 10.3892/etm.2020.8598. Epub 2020 Mar 12. PMID: 32266021; PMCID: PMC7132238.
- 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, Manfredi TG, Agostinucci K, Engle SK, Powe J, King NM, Rodriguez LA, Gropp KE, Gallacher M, Vetter FJ, More V, Shimpi P, Serra D, Colton HM Toxicol Pathol. 2017 Feb;45(2):344-352. doi: 10.1177/0192623316634231. Epub 2016 Jul 11. PMID: 27102652.
- Integrated approach to early detection of cardiovascular toxicity induced by a ghrelin receptor agonist. Stokes AH, Falls JG, Yoon L, Cariello N, Faiola B, Colton HM, Jordan HL, Berridge BR. Int J Toxicol. 2015 Mar-Apr;34(2):151-61. doi: 10.1177/1091581815573029. Epub 2015 Feb 26. PMID: 25722321.
Valvular heart disease is a leading cause of cardiovascular morbidity. Transcatheter aortic valve replacement (TAVR) is a minimally invasive procedure that replaces the aortic valve in patients with aortic stenosis. Mineral homeostasis, the process that regulates the body’s levels of calcium and phosphorus, plays an important role in the progression of cardiovascular diseases, including calcific aortic valve stenosis. FGF23 is a bone-derived phosphotropic hormone that regulates phosphate and vitamin D metabolism. FGF23 has been shown to be an independent risk factor for CV morbidity and mortality.
FGF23 is a novel risk factor for patients undergoing TAVR
A study by Mirna et al. evaluated the predictive potential of both C-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) for adverse outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) with regard to renal function. Patients were followed up at 12 months.
The authors demonstrated:
- significant association of high cFGF23 levels with mortality in patients with an estimated glomerular filtration rate (eGFR) ≥45 ml/min/1.73m².
- patients with cFGF23 levels above the cut-off of 6.82 pmol/l had a worse 1-year-mortality
- cFGF23 could be a novel risk factor for patients undergoing TAVR with eGFR ≥45ml/min/1.73m².
FGF23 (C-terminal) and FGF23 intact were both measured with an ELISA assay from BIOMEDICA.
Assay Highlights
- full validation package
- for serum and plasma
- +50 international references
LITERATURE
Mirna M, Lauten A, Jirak P, Rezar R, Wernly B, Paar V, Felder TK, Hoppe UC, Motloch LJ, Jung C, Alushi B, Lichtenauer M, Salmhofer H. Eur J Intern Med. 2021. 85:98-107. doi: 10.1016/j.ejim.2020.09.022. Epub 2020 Nov 13. PMID: 33191056.
Abstract
Introduction: Serum levels of FGF23 have been associated with adverse outcomes in cardiovascular diseases in patients with and without impaired renal function. Hence, this study aimed to explore the prognostic relevance of intact FGF23 (iFGF23) and its derivate C-terminal FGF23 (cFGF23) in patients undergoing transcatheter aortic valve replacement (TAVR) with regard to renal function.
Methods: A total of 274 patients undergoing transfemoral TAVR were enrolled in this study. Blood samples were obtained preinterventionally and analyzed for iFGF23 and cFGF23 by means of enzyme linked immunosorbent assay (ELISA). Follow-up was obtained for 12 months.
Results: Serum levels of cFGF23 and iFGF23 both correlated positively with serum creatinine and inversely with estimated glomerular filtration rate (eGFR). Cox regression analysis revealed a significant association of cFGF23 with 1-year-mortality in patients with eGFR ≥45ml/min/1.73m², but not in patients with an eGFR <45ml/min/1.73m². A cut-off was calculated for cFGF23 (6.82 pmol/l) and patients with eGFR ≥45ml/min/1.73m² were retrospectively divided into two groups (above/below cut-off). Patients above the cut-off had a significantly worse 1-year-mortality than patients below the cut-off (33.3% vs. 19.6%; OR 2.05 (95%CI 1.03-4.07), p= 0.038). The association of cFGF23 with 1-year-mortality in patients with eGFR ≥45ml/min/1.73m² remained statistically significant even after correction for possible confounders in a multivariate Cox regression analysis.
Conclusion: cFGF23 could be an individual risk factor for mortality in patients undergoing TAVR with an eGFR ≥45ml/min/1.73m².
The natriuretic peptides NT-proBNP & NT-proANP
Cardiac Biomarkers – kits for clinical & preclinical use
NT-proBNP is released in the heart in response to cardiac wall stretch or pressure overload. It is considered as the gold standard in heart failure and is useful for both diagnosis and prognosis (1).
NT-proANP is synthesized and stored in atrial myocytes in response to increased intra-atrial pressure. Elevated circulating levels of NT-proANP are associated with heart failure resulting from increased mechanical stress in the heart during hypertension. In population-based studies, elevated plasma NT-pro-ANP levels predicted the risk of cardiovascular events and death ( 2).
Cardiac Biomarkers – kits for clinical & preclinical use
Natriuretic peptides in pre-clinical models as cardiac toxicity biomarkers
Biomarkers are also a valuable tool to explore drug effects in pre-clinical models. The natriuretic peptide NT-proANP has successfully been validated as a cardiovascular safety biomarker in rodents (3). An additional cardiac toxicity biomarker in drug development is NT-proBNP supporting the use of natriuretic peptides to investigate drug-induced cardiac hypertrophy (4, 5).
Biomedica offers a range of top quality ELISA kits for your clinical & preclinical research
- NT-proBNP – human (CE-marked in EU) (#SK-1204)
- NT-proBNP – rat (new!) (#BI-1204R)
- NT-proANP – human, rodent (#BI-20892) citations rat/mouse
- widely cited in over 400 publications
- kit validation follows international quality guidelines
LITERATURE
- NT-proBNP: The Gold Standard Biomarker in Heart Failure. McKie PM, Burnett JC Jr. J Am Coll Cardiol. 2016; 6;68(22):2437-2439.
- Plasma natriuretic peptide levels and the risk of cardiovascular events and death. Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Omland T, Wolf PA, Vasan RS. N Engl J Med. 2004; 12;350(7):655-63.
- Cross-laboratory analytical validation of the cardiac biomarker NT-proANP in rat. Vinken P, Reagan WJ, Rodriguez LA, Buck WR, Lai-Zhang J, Goeminne N, Barbacci G, Liu R, King NM, Engle SK, Colton H. Pharmacol Toxicol Methods. 2016; 77:58-65.
- Evaluation of Cardiac Toxicity Biomarkers in Rats from Different Laboratories. Kim K, Chini N, Fairchild DG, Engle SK, Reagan WJ, Summers SD, Mirsalis JC – Cardiac Hypertrophy Working Group of the Predictive Safety Testing Consortium. Toxicol Pathol. 2016; 44(8):1072-1083.
- Serum Natriuretic Peptides as Differential Biomarkers Allowing for the Distinction between Physiologic and Pathologic Left Ventricular Hypertrophy. Dunn ME, Manfredi TG, Agostinucci K, Engle SK, Powe J, King NM, Rodriguez LA, Gropp KE, Gallacher M, Vetter FJ, More V, Shimpi P, Serra D, Colton HM – Cardiac Hypertrophy Working Group of the Predictive Safety Testing Consortium. Toxicol Pathol. 2017; 45(2):344-352.
For use in preclinical models – cardiotoxicity biomarkers
Rat NT-proBNP ELISA , cat. no. BI-1204R
NT-proANP ELISA independently validated for rat, cat. no. BI-20892
February is “Heart Month” raising awareness about heart disease. Biomarker research has revolutionized on how heart diseases are diagnosed and treated. Ongoing research on newer exploratory protein biomarkers may shed light into the complex mechanisms that drive the disease process.
Novel Biomarkers for Heart Disease
BIG ENDOTHELIN-1, ENDOSTATIN, FGF23, LRG
Big Endothelin-1 (Big ET-1) is a vasoconstrictor peptide and is the precursor of Endothelin-1 (ET-1) the biologically active form. Elevated concentrations provide an independent indicator of heart failure in congestive heart disease (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.
Endostatin is a degradation product of collagen XVIII and is an extracellular matrix protein. Endostatin plays an essential role in the pathogenesis of chronic kidney and heart diseases (2). A study in two community-based cohorts of elderly showed an association of high serum endostatin levels with left ventricular dysfunction and an increased heart failure risk (3).
Fibroblast growth factor-23 (FGF23) is a hormone that regulates phosphate metabolism. FGF23 has been suggested as a novel candidate biomarker of cardiovascular risk. High circulating FGF23 levels have been associated with adverse cardiovascular outcomes such as heart failure and arrhythmias (4).
Leucine-riche alpha-2-glyoprotein (LRG) is a secreted protein that plays an important role in pathogenic ocular neovascularization. LRG is also involved in multiple conditions including cardiovascular disease, diabetes, inflammatory disorders, and cancer. A recent study demonstrated that LRG accurately identify patients with heart failure stronger than BNP, independent of age, sex, and creatinine (5, 6).
NOVEL BIOMARKERS FOR HEART DISEASE
Biomedica offers a range of top quality ELISA kits for your clinical & preclinical research.
-Big Endothelin-1 (#BI-20082H)
-Endostatin (#BI-20742)
-Endostatin mouse/rat (#BI-20742MR)
-FGF23 intact (#BI-20700)
-FGF23 c-terminal (#BI-20702)
-LRG (#BI-LRG)
|
LITERATURE
- 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.
- Endostatin in Renal and Cardiovascular Diseases. Li M et al., Kidney Dis. 2021; 9;7(6):468-481.
- Circulating endostatin and the incidence of heart failure. Ruge T et al., 2018; 52(5):244-249.
- Fibroblast Growth Factor 23 and Long-Term Cardiac Function: The Multi-Ethnic Study of Atherosclerosis. Patel RB et al., Cardiovasc Imaging. 2020; 13(11):e011925.
- 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.
- Serum biomarker discovery related to pathogenesis in acute coronary syndrome by proteomic approach Shin M et al.,Biosci Rep. 2021; 25;41(6):BSR20210344.
Widely cited non-radioactive EZ4U – Cell Proliferation & Cytotoxicity Assay – single step incubation for use on living cells
The Biomedica EZ4U cell proliferation and cytotoxicity assay was highlighted in a recent study investigating the cytotoxicity of drug combinations tested against different pancreatic cell lines. Learn more: Cytotoxicity of combinations of the pan-KRAS SOS1 inhibitor BAY-293 against pancreatic cancer cell lines.
Pancreatic ductal adenocarcinomas (PDACs), the most prevalent pancreatic cancer, is highly aggressive with a 5-year overall survival rate of less than 8%. Late detection, it´s metastatic spread and the resistance to chemotherapy are among some of the factors responsible for poor patient outcome. The PDAC incidence rate is increasing and is particularly related to the general aging of our society. Furthermore, life style habits that include abuse of alcohol and tobacco as well as obesity and type 2 diabetes increases the risk for various types of cancer including PDAC.
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 230 publications
BROCHURE – EZ4U cell proliferation and cytotoxicity assay
FURTHER READING
Pancreatic ductal adenocarcinoma: Treatment hurdles, tumor microenvironment and immunotherapy.
World J Gastrointest Oncol. Sarantis P, Koustas E, Papadimitropoulou A, Papavassiliou AG, Karamouzis MV. 2020 Feb 15;12(2):173-181. doi: 10.4251/wjgo.v12.i2.173. PMID: 32104548; PMCID: PMC7031151.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases, with an average 5-year survival rate of less than 10%. Unfortunately, the majority of patients have unresectable, locally advanced, or metastatic disease at the time of diagnosis. Moreover, traditional treatments such as chemotherapy, surgery, and radiation have not been shown to significantly improve survival. Recently, there has been a swift increase in cancer treatments that incorporate immunotherapy-based strategies to target all the stepwise events required for tumor initiation and progression. The results in melanoma, non-small-cell lung cancer and renal cell carcinoma are very encouraging. Unfortunately, the application of checkpoint inhibitors, including anti-CTLA4, anti-PD-1, and anti-PD-L1 antibodies, in pancreatic cancer has been disappointing. Many studies have revealed that the PDAC microenvironment supports tumor growth, promotes metastasis and consists of a physical barrier to drug delivery. Combination therapies hold great promise for enhancing immune responses to achieve a better therapeutic effect. In this review, we provide an outline of why pancreatic cancer is so lethal and of the treatment hurdles that exist. Particular emphasis is given to the role of the tumor microenvironment, and some of the latest and most promising studies on immunotherapy in PDAC are also presented.
Orth M, Metzger P, Gerum S, Mayerle J, Schneider G, Belka C, Schnurr M, Lauber K. Radiat Oncol. 2019 Aug 8;14(1):141. doi: 10.1186/s13014-019-1345-6. PMID: 31395068; PMCID: PMC6688256.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with poor prognosis and rising incidence. Late detection and a particularly aggressive biology are the major challenges which determine therapeutic failure. In this review, we present the current status and the recent advances in PDAC treatment together with the biological and immunological hallmarks of this cancer entity. On this basis, we discuss new concepts combining distinct treatment modalities in order to improve therapeutic efficacy and clinical outcome – with a specific focus on protocols involving radio(chemo)therapeutic approaches.
Pancreatic ductal adenocarcinomas (PDACs), the most prevalent pancreatic cancer, is highly aggressive with a 5-year overall survival rate of less than 8%. Late detection, it´s metastatic spread and the resistance to chemotherapy are among some of the factors responsible for poor patient outcome. The PDAC incidence rate is increasing and is particularly related to the general aging of our society. Furthermore, life stye habits that include abuse of alcohol and tobacco as well as obesity and type 2 diabetes increases the risk for various types of cancer including PDAC.
Do you need support in meeting your research goals? We can help! We offer custom analytical service measurements for ELISA Kits, Luminex Assays, or microRNA Analysis .
GET IN TOUCH at Biomedica for your custom analytical testing service.
Custom Analytical Service Measurements for ELISA, Luminex, microRNA
Why choose Biomedica Services?
• Expertise – experienced laboratory staff
• Quality – highest quality equipment
• Flexibility – customized according to your project needs and budget
• Speed – rapid turn-around time to meet your deadlines
• Results – verified and comprehensive results presented in an analytical report
Click here for detailed information on our Service Measurements
RELATED PUBLICATIONS
Comprehensive Characterization of Platelet-Enriched MicroRNAs as Biomarkers of Platelet Activation.
Krammer TL, Zeibig S, Schrottmaier WC, Pirabe A, Goebel S, Diendorfer AB, Holthoff HP, Assinger A, Hackl M. Cells. 2022 Apr 7;11(8):1254. doi: 10.3390/cells11081254. PMID: 35455934; PMCID: PMC9030873.
Abstract
Dysregulation of platelet function is causally connected to thrombus formation and cardiovascular diseases. Therefore, assessing platelet reactivity is crucial. However, current platelet function tests come with pitfalls, limiting clinical use. Plasma miRNA signatures have been suggested as novel biomarkers for predicting/diagnosing cardiovascular diseases and monitoring antiplatelet therapy. Here, we provide results from a comprehensive study on the feasibility of using circulatory platelet miRNAs as surrogate markers of platelet activation. We performed small RNA-Seq on different blood cell types to confirm known and identify novel platelet-enriched miRNAs and validated a panel of 16 miRNAs using RT-qPCR. To identify the main carrier of these blood-based platelet miRNAs, we enriched and analyzed distinct microvesicle populations. Platelets were stimulated with GPVI and P2Y12 agonists in vitro to monitor the release of the selected miRNAs following activation. Finally, the miRNA panel was also measured in plasma from mice undergoing the Folts intervention (recurrent thrombus formation in the carotid artery). Applying an unbiased bioinformatics-supported workflow to our NGS data, we were able to confirm a panel of previously established miRNA biomarker candidates and identify three new candidates (i.e., miR-199a-3p, miR-151a-5p, and miR-148b-3p). Basal levels of platelet-derived miRNAs in plasma were mainly complexed with proteins, not extracellular vesicles. We show that changes in miRNA levels due to platelet activation are detectable using RT-qPCR. In addition, we highlight limitations of studying the in vitro release of miRNAs from platelets. In vivo thrombosis resulted in significant elevations of platelet-derived miRNA levels in mice. In conclusion, we provide in-depth evidence that activated platelets release miRNAs, resulting in measurable changes in circulatory miRNA levels, rendering them promising biomarker candidates.
Multiplex Soluble Biomarker Analysis from Pleural Effusion.
Biomolecules. Javadi J, Dobra K, Hjerpe A. 2020 Jul 28;10(8):1113. doi: 10.3390/biom10081113. PMID: 32731396; PMCID: PMC7464384.
Abstract
Malignant pleural mesothelioma (MPM) is a highly aggressive and therapy resistant pleural malignancy that is caused by asbestos exposure. MPM is associated with poor prognosis and a short patient survival. The survival time is strongly influenced by the subtype of the tumor. Dyspnea and accumulation of pleural effusion in the pleural cavity are common symptoms of MPM. The diagnostic distinction from other malignancies and reactive conditions is done using histopathology or cytopathology, always supported by immunohistochemistry, and sometimes also by analyses of soluble biomarkers in effusion supernatant. We evaluated the soluble angiogenesis related molecules as possible prognostic and diagnostic biomarkers for MPM by Luminex multiplex assay. Pleural effusion from 42 patients with malignant pleural mesothelioma (MPM), 36 patients with adenocarcinoma (AD) and 40 benign (BE) effusions were analyzed for 10 different analytes that, in previous studies, were associated with angiogenesis, consisting of Angiopoietin-1, HGF, MMP-7, Osteopontin, TIMP-1, Galectin, Mesothelin, NRG1-b1, Syndecan-1 (SDC-1) and VEGF by a Human Premixed Multi-Analyte Luminex kit. We found that shed SDC-1 and MMP-7 levels were significantly lower, whereas Mesothelin and Galectin-1 levels were significantly higher in malignant mesothelioma effusions, compared to adenocarcinoma. Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1, NRG1-β1, VEGF and TIMP-1 were significantly higher in malignant pleural mesothelioma effusions compared to benign samples. Moreover, there is a negative correlation between Mesothelin and shed SDC-1 and positive correlation between VEGF, Angiopoietin-1 and shed SDC-1 level in the pleural effusion from malignant cases. Shed SDC-1 and VEGF have a prognostic value in malignant mesothelioma patients. Collectively, our data suggest that MMP-7, shed SDC-1, Mesothelin and Galectin-1 can be diagnostic and VEGF and SDC-1 prognostic markers in MPM patients. Additionally, Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1 and TIMP-1 can be diagnostic for malignant cases.
Biomarkers & Bone Health – ELISA Kits for Clinical Research
Bone remodeling is a continuous process that removes bone and replaces it with newly synthesized bone. This bone turnover process preserves the mechanical function of the human skeleton.
Bone turnover biomarkers, e.g. markers of bone formation and bone resorption, have been used during the last decade to monitor bone diseases and to monitor their treatment.
Many of these markers are secreted by osteoblasts and osteoclasts and include regulators of bone turnover e.g. receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG).
Though RANKL and OPG play an integral role in bone turnover, they do not reflect the activity of osteocytes, the most abundant cell type in the bone.
Osteocytes are cells that regulate bone remodeling. They secrete proteins – bone regulation markers – that include Sclerostin (SOST), Dickkopf-1 (DKK-1), and Fibroblast growth factor (FGF23). These markers reflect the osteocyte activity.
The above listed biomarkers circulate and can be measured in serum and plasma allowing the investigation of complex interactions between the bone and their relationship with other organs.
BIOMEDICA ELISA KITS – Biomarkers & Bone Health
check out our Bone Biomarker Brochure
ELISA Assay Kit Highlights
+ EASY – ready to use calibrators & controls included (color-coded reagents)
+FULL VALIDATION PACKAGE – assays are optimized for clinical samples
+ HIGH QUALITY GUARANTEED – results you can rely on
+ WIDELY CITED in 1500 + publications
Biomedica – Complete ready-to-use ELISA kits for superior performance and reproducibility
RELATED PRODUCTS
Osteoprotegerin (OPG) ELISA , soluble RANKL ELISA, Periostin ELISA, DKK-1 ELISA , Sclerostin ELISA
FGF23 ELISA , IL-6 ELISA , VEGF ELISA , Angiopoietin-2 ELISA
osteomiR®– bone miRNA biomarkers highlights:
- Novel minimally invasive biomarkers to detect high imminent fracture-risk in osteoporosis
- 19 individual bone-related biomarkers with distinct information content
RELATED PUBLICATIONS
Novel biological markers of bone: from bone metabolism to bone physiology. Rheumatology (Oxford). Chapurlat RD, Confavreux CB. 2016; 55(10):1714-25.
Abstract
Biochemical markers of bone turnover have been used for decades in the management of bone diseases, to assess the prognosis of these conditions and to monitor treatments. The new markers, however, also reflect specific physiological mechanisms in the bone or other organs. Periostin may be more specific to the periosteum; cathepsin K is an osteoclastic enzyme that may be involved in the cardiovascular system and joints; Dickkopf-1 is involved in bone formation and vascular calcification; sclerostin is a major regulator of bone formation in response to mechanical loading and may also play a role in chronic kidney disease bone and mineral disorder; sphingosine-1-phosphate is a lipid mediator interacting with bone resorption. Some of the bone markers are in fact hormones produced by the bone that affect various physiological and pathological functions in other organs. Thus, osteocalcin is produced by osteoblasts and participates in the regulation of insulin sensitivity and fertility in men. Fibroblast growth factor 23 is produced by osteocytes to regulate phosphorus and 1,25(OH)2D3, but it also plays a major role in the adverse consequences of declining renal function, in particular with respect to the myocardium. Micro RNAs are single-stranded RNAs that regulate several pathways, including the development timing, organogenesis, cell apoptosis, proliferation and differentiation. Their serum concentration may reflect the links between bone physiology and certain conditions in other organs, for example, the cardiovascular system.
Bones have many important biological functions. Bone biomarkers have gained attention in clinical research for the assessment of bone-related diseases. Some of the biomarker proteins have been found to represent useful targets for therapeutic antibodies.
Biomarkers in Bone Biology
Function of the human skeleton
The human skeletal system gives the body it´s structure and helps to protect and support the internal organs. It forms a part of the muscular-skeletal systems that helps the body to move. Throughout our lifetime, the human skeleton undergoes constant remodeling. This dynamic process, degrading bone and replacing it with new tissue maintains bone mass. The continuous cycle of bone resorption and bone growth is also known as bone metabolism.
Bone remodeling
Bone remodeling is a tightly regulated process performed by hormones, cell-signaling molecules, and bone cells. These specific bone cells are osteoclasts, osteoblasts, and osteocytes. The cells are in constant communication with each other through secreted factors, such as osteoprotegerin, RANKL, and sclerostin. These regulatory systems keep the bone remodeling balanced. Imbalances in bone metabolism can lead to bone diseases.
Role of RANKL, RANK, and OPG in bone biology |
Bones are broken down by osteoclasts and rebuilt by osteoblasts.
RANKL receptor activator is a mediator of bone resorption and OPG acts as a decoy receptor.
Osteoprotegerin (OPG) is produced by osteoblasts, cells that synthesize bone. OPG is a decoy receptor and binds to RANKL, antagonizing its binding to RANK.
RANKL (receptor activator of nuclear factor kappa-B ligand) is secreted by osteoblasts and binds to the RANK receptor on osteoclast precursor and mature osteoclast cells. RANKL stimulates bone resorption.
Role of Sclerostin, FGF23, DKK-1, and Periostin in bone biology
Biomarkers in Bone Biology
Bone cells have been reported to have endocrine functions that affect multiple organs. The most abundant cell type in the bone are osteocytes residing within the bone matrix and comprising 90% to 95% of the bone cells. Osteocytes play a significant role in the regulation of osteogenesis, releasing osteocyte-related biomarkers such as sclerostin (SOST), fibroblast growth factor 23 (FGF23), and Dickkopf-1 (DKK-1).
Sclerostin (SOST) is mainly produced by osteocytes and is considered as the major regulator of bone formation. More recently, Sclerostin has been shown to stimulate the osteocyte synthesis of fibroblast growth factor-23, potentially contributing to the regulation of phosphate homeostasis.
Fibroblast growth factor 23 (FGF23) is a hormone that is mainly secreted by osteocytes and osteoblasts. It regulates phosphate and vitamin D levels and functions as a central endocrine hormone regulating phosphate balance.
Dickkopf-1 (DKK-1) is an extracellular protein. DKK-1 plays a role in the regulation of bone metabolism, as it inhibits the differentiation of osteoblasts.
Periostin (POSTN) is an extracellular matrix protein that is preferentially expressed in the periosteum, a membrane covering the outer surface of bones which is responsible for growth. Periostin has functions in osteology, tissue repair, oncology, cardiovascular and respiratory diseases, and in a variety of inflammatory settings (e.g. asthma).
BIOMEDICA OFFERS HIGH QUALITY ELISA KITS FOR BONE BIOMARKERS
|
|
Sclerostin ELISA (cat.no. BI-20492)
OPG ELISA (cat.no. BI-20403)
RANKL ELISA (cat.no. BI-20462)
FGF23 intact ELISA (cat.no. BI-20700)
FGF23 C-terminal ELISA (cat.no. BI-20702)
DKK-1 ELISA (cat.no. BI-20413)
PERIOSTIN ELISA (cat.no. BI-20433)
RELATED LITERATURE
A Review of the Potential Application of Osteocyte-Related Biomarkers, Fibroblast Growth Factor-23, Sclerostin, and Dickkopf-1 in Predicting Osteoporosis and Fractures. Ramli FF, Chin KY. Diagnostics (Basel). 2020 Mar 6;10(3):145. doi: 10.3390/diagnostics10030145. PMID: 32155909; PMCID: PMC7151094.
Sclerostin Directly Stimulates Osteocyte Synthesis of Fibroblast Growth Factor-23. Wijenayaka AR, Yang D, Ormsby RT, Bonewald LF, Atkins GJ. Calcif Tissue Int. 2021 Jul;109(1):66-76. doi: 10.1007/s00223-021-00823-6. Epub 2021 Feb 22. PMID: 33616712.
Biology of the RANKL-RANK-OPG System in Immunity, Bone, and Beyond. Front Immunol. Walsh MC, Choi Y.2014 Oct 20;5:511. doi: 10.3389/fimmu.2014.00511. PMID: 25368616; PMCID: PMC4202272.
The Osteocyte: New Insights. Robling AG, Bonewald LF. Annu Rev Physiol. 2020 Feb 10;82:485-506. doi: 10.1146/annurev-physiol-021119-034332. PMID: 32040934; PMCID: PMC8274561.
Sema4D induces cartilage destruction
Semaphorin 4D destroys cartilage: Semaphorin 4D (Sema 4D) has been identified as an inflammatory cytokine that promotes cartilage destruction. This finding was recently published by Murakami T and colleagues. In a mouse model of inflammatory arthritis, the researchers demonstrated that Sema4D was increased in synovial fluid and loss of Sema4D protected against cartilage degeneration. Click here to learn more.
What is cartilage?
Cartilage is a type of strong and flexible tissue that is found throughout the body. It is a connective tissue that exists in our joints, bones, spine, ears and nose. It protects our joints and our bones, absorbing impact, reducing friction and helping our joints to move smoothly.
If cartilage is degraded, movements will cause friction and pain, leading to swelling and stiffness. Cartilage degradation can be caused through direct injury, osteoarthritis, and aging.
Semaphorin 4D destroys cartilage
Murakami T, Takahata Y, Hata K, Ebina K, Hirose K, Ruengsinpinya L, Nakaminami Y, Etani Y, Kobayashi S, Maruyama T, Nakano H, Kaneko T, Toyosawa S, Asahara H, Nishimura R. Sci Signal. 2022 Nov;15(758):eabl5304. doi: 10.1126/scisignal.abl5304. Epub 2022 Nov 1. PMID: 36318619.
Abstract
Proinflammatory cytokines play critical roles in the pathogenesis of joint diseases. Using a mass spectrometry-based cloning approach, we identified Semaphorin 4D (Sema4D) as an inflammatory cytokine that directly promoted cartilage destruction. Sema4d-deficient mice showed less cartilage destruction than wild-type mice in a model of rheumatoid arthritis. Sema4D induced a proinflammatory response in mouse articular chondrocytes characterized by the induction of proteolytic enzymes that degrade cartilage, such as matrix metalloproteinases (MMPs) and aggrecanases. The activation of Mmp13 and Mmp3 expression in articular chondrocytes by Sema4D did not depend on RhoA, a GTPase that mediates Sema4D-induced cytoskeletal rearrangements. Instead, it required NF-κB signaling and Ras-MEK-Erk1/2 signaling downstream of the receptors Plexin-B2 and c-Met and depended on the transcription factors IκBζ and C/EBPδ. Genetic and pharmacological blockade of these Sema4D signaling pathways inhibited MMP induction in chondrocytes and cartilage destruction in femoral head organ culture. Our results reveal a mechanism by which Sema4D signaling promotes cartilage destruction.
SEMA4D ELISA kit highlights
|
|
|
|
RELATED PUBLICATIONS
Inhibition of Semaphorin 4D/Plexin-B1 signaling inhibits the subchondral bone loss in early-stage osteoarthritis of the temporomandibular joint. Zhang Z, Lu L, Ye T, Yu S, Zhang J, Zhang M, He F, Liu Q, Yang H, Feng J.Arch Oral Biol. 2022 Mar;135:105365. doi: 10.1016/j.archoralbio.2022.105365. Epub 2022 Feb 2. PMID: 35151027.
Abstract
Objective: The aim of this study was to demonstrate the biological function of Semaphorin 4D (Sema4D)/Plexin-B1 in the bone formation features of osteoblasts in early-stage temporomandibular joint (TMJ) osteoarthritis.
Design: Sema4D/Plexin-B1, expressed by osteoclasts/osteoblasts, plays a balancing role in bone formation and resorption. However, previous studies have mainly focused on bone resorption by osteoclasts in early-stage osteoarthritis. This study used our reported experimental unilateral anterior crossbite (UAC) mouse model to explore subchondral bone changes, which were assessed by micro-CT analysis. The changes in osteoblasts were investigated after the inhibition of Sema4D by BMA-12 injection with the detection of bone formation-related markers. A Transwell migration assay was performed to reveal the specific impact of Sema4D on osteoblasts in vitro.
Results: The data demonstrated that subchondral bone loss in early-stage TMJ osteoarthritis was accompanied by the upregulated expression of Sema4D in cartilage and subchondral bone and Plexin-B1 in subchondral bone. Reducing Sema4D levels could inhibit subchondral bone loss and cartilage degeneration in early-stage TMJ osteoarthritis. In vitro, the results revealed that Sema4D could reduce the expression of osteocalcin and alkaline phosphatase and increase the migrating capability of Plexin-B1-positive osteoblasts.
Conclusions: Our results revealed that elevated Sema4D expression in early-stage TMJ osteoarthritis might decrease the bone formation activity of osteoblasts in the subchondral bone by binding to Plexin-B1 expressed by osteoblasts. Inhibiting Sema4D/Plexin-B1 signaling in early-stage osteoarthritis represents a promising strategy for new therapeutic approaches to osteoarthritis.
Compliance of NT-proBNP test in accredited cardiac marker survey
NT-proBNP ELISA test successfully passed accredited cardiac marker survey: Biomedica participated in an accredited international ring trial program for the cardiac biomarker NT-proBNP. The results demonstrate that the CE-marked NT-proBNP ELISA assay successfully passed the QC circle in the cardiac marker survey.
NT-proBNP ELISA test successfully passed cardiac marker survey
The results comply with strict quality standards confirmed by RfB, an international provider for proficiency testing.
NT-proBNP ELISA assay kit (cat. no. SK-1204)
√ CE-marked – for IVD use in the EU
√ Flexible – can be run in every lab
√ Two controls included
√ Simple 2 step protocol
√ Reliable – full validation
√ Widely cited in more than 100 publications
Developed & manufactured by Biomedica right in the heart of Europe
What is proficiency testing?
Proficiency Testing provides a report that shows how laboratories can compare their own data to data to data from other laboratories around the world.
The testing, carried out in a ring trial program, is performed by an accredited laboratory specialist in proficiency testing. Proficiency testing monitors the performance of individual laboratories for specific tests e.g. cardiac biomarker assays.
LITERATURE
Monitoring of NT-proBNP – predicting risk of cardiovascular events from anti-inflammatory drugs (Non-Steroid Anti-Inflammatory Drugs)
N-terminal pro-B-type natriuretic peptide concentrations predict the risk of cardiovascular adverse events from antiinflammatory drugs: a pilot trial. Brune K, Katus HA, Moecks J, Spanuth E, Jaffe AS, Giannitsis E. Clin Chem. 2008 Jul;54(7):1149-57. doi: 10.1373/clinchem.2007.097428. Epub 2008 May 1. PMID: 18451314.
Safety of Oral Non-Selective Non-Steroidal Anti-Inflammatory Drugs in Osteoarthritis: What Does the Literature Say? Cooper C, Chapurlat R, Al-Daghri N, Herrero-Beaumont G, Bruyère O, Rannou F, Roth R, Uebelhart D, Reginster JY.Drugs Aging. 2019 Apr;36(Suppl 1):15-24. doi: 10.1007/s40266-019-00660-1. PMID: 31073921; PMCID: PMC6509083.
Cardio-renal safety of non-steroidal anti-inflammatory drugs. Radi ZA, Khan KN. J Toxicol Sci. 2019;44(6):373-391. doi: 10.2131/jts.44.373. PMID: 31168026.
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used therapeutic class in clinical medicine. These are sub-divided based on their selectivity for inhibition of cyclooxygenase (COX) isoforms (COX-1 and COX-2) into: (1) non-selective (ns-NSAIDs), and (2) selective NSAIDs (s-NSAIDs) with preferential inhibition of COX-2 isozyme. The safety and pathophysiology of NSAIDs on the renal and cardiovascular systems have continued to evolve over the years following short- and long-term treatment in both preclinical models and humans. This review summarizes major learnings on cardiac and renal complications associated with pharmaceutical inhibition of COX-1 and COX-2 with focus on preclinical to clinical translatability of cardio-renal data.
Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. Trelle S, Reichenbach S, Wandel S, Hildebrand P, Tschannen B, Villiger PM, Egger M, Jüni P.BMJ. 2011 Jan 11;342:c7086. doi: 10.1136/bmj.c7086. PMID: 21224324; PMCID: PMC3019238.
Pathogenic contribution of LRG1 to vascular retinopathies
Globally, 2.2 billion people are estimated to have a vision impairment. Eye diseases are on the rise due to an ageing population and an increase of diabetes. The classical therapy involves the blockage of vascular endothelial growth factor (VEGF). However, a high rate of patient non-response and loss of efficacy over time are major challenges.
Evaluating new treatments with better efficiency are moving forward. One novel therapeutic target is leucine-rich α-2 glycoprotein 1 (LRG1). It is an emerging key player in vascular dysfunction, inflammation, and fibrosis.
LRG1 as a novel therapeutic target in eye disease
The uncontrolled formation of new blood vessels in the eye (ocular angiogenesis) is one of the major causes of eye diseases and blindness.
The blood protein LRG1 plays a central role in the progression of eye diseases and is thus a promising novel therapeutic target.
In searching for mediators of vascular remodeling in the diseased and damaged retina, researchers discovered that leucine-rich α-2 glycoprotein 1 (LRG1) is a novel regulator of TGFß signaling. The study published in Nature in 2013 by Wang X et al., revealed that LRG1 is a novel regulator of angiogenesis that mediates its effect through modulating TGFβ signaling. The researchers showed that LRG1 expression in the retina is predominantly vascular and is increased during neovascular growth. Their study in mice supported the hypothesis that LRG1 is necessary for robust vascular growth and its inhibition has potential as a therapeutic target. Based on their studies, the authors suggested that LRG1 is not only a promising target for controlling pathogenic angiogenesis in eye diseases but could potentially also be used in other diseases such as cancer and atherosclerosis.
WHAT IS LRG1 (leucine-rich α-2 glycoprotein 1)
The mature 38,2 kDa glyocoprotein LRG contains 347 amino acids (Uniprot entry Leucine-rich alpha-2-glycoprotein). It belongs to the family of LRG proteins characterized through leucine-rich repeats in its amino acid sequence. LRG1 (also named LRG) is involved in protein-protein interactions, signal transduction, and development. Studies have shown that LRG plays a role in physiological processes of the nervous system including synapse formation and growth. It is also implied in cell proliferation, in immune responses, in cell migration, in neovascularization, and in apoptosis.
Alternative titles: LRG – OMIM Entry leucine-rich α-2 glycoprotein (LRG)
HOW CAN YOU MEASURE LRG1?
LRG1 can reliably be measured in human serum and plasma with the Biomedica LRG ELISA (cat. no. BI-LRG).
-
Sample volume: 5µl
-
Assay range: 2-64 ng/ml
-
Easy protocol – day test
The validation of the LRG1 ELISA kit has been performed following international quality guidelines. Download the validation data here.
RELATED PUBLICATIONS
LRG1 as a novel therapeutic target in eye disease.
De Rossi G, Da Vitoria Lobo ME, Greenwood J, Moss SE. Eye (Lond). 2022 Feb;36(2):328-340. doi: 10.1038/s41433-021-01807-4. Epub 2022 Jan 5. Erratum in: Eye (Lond). 2022 Feb 28;: PMID: 34987199; PMCID: PMC8807626.
Abstract
Retinal and choroidal diseases are major causes of blindness and visual impairment in the developed world and on the rise due to an ageing population and diabetes epidemic. Standard of care is centred around blockade of vascular endothelial growth factor (VEGF), but despite having halved the number of patients losing sight, a high rate of patient non-response and loss of efficacy over time are key challenges. Dysregulation of vascular homoeostasis, coupled with fibrosis and inflammation, are major culprits driving sight-threatening eye diseases. Improving our knowledge of these pathological processes should inform the development of new drugs to address the current clinical challenges for patients. Leucine-rich α-2 glycoprotein 1 (LRG1) is an emerging key player in vascular dysfunction, inflammation and fibrosis. Under physiological conditions, LRG1 is constitutively expressed by the liver and granulocytes, but little is known about its normal biological function. In pathological scenarios, such as diabetic retinopathy (DR) and neovascular age-related macular degeneration (nvAMD), its expression is ectopically upregulated and it acquires a much better understood pathogenic role. Context-dependent modulation of the transforming growth-factor β (TGFβ) pathway is one of the main activities of LRG1, but additional roles have recently been emerging. This review aims to highlight the clinical and pre-clinical evidence for the pathogenic contribution of LRG1 to vascular retinopathies, as well as extrapolate from other diseases, functions which may be relevant to eye disease. Finally, we will provide a current update on the development of anti-LRG1 therapies for the treatment of nvAMD..
LRG1 promotes angiogenesis by modulating endothelial TGF-β signalling.
Wang X, Abraham S, McKenzie JAG, Jeffs N, Swire M, Tripathi VB, Luhmann UFO, Lange CAK, Zhai Z, Arthur HM, Bainbridge J, Moss SE, Greenwood J.Nature. 2013 Jul 18;499(7458):306-11. doi: 10.1038/nature12345. PMID: 23868260; PMCID: PMC3836402.
High big ET-1 levels are associated with risk of all–cause death in diabetes patients with CAD
Big Endothelin-1 associated with all-cause death in diabetes patients with CAD
A clinical study in 8550 patients investigated the association between the cardio-vascular marker big endothelin-1 (big ET-1) and long-term all-cause death in patients with coronary artery disease (CAD) and impaired glucose metabolism.
Patients were categorized into both glucose status (diabetes mellitus, pre-diabetes mellitus, normalglycemia) and big ET-1 level groups. Primary endpoint was all-cause death. The data indicate that baseline big ET-1 levels were independently associated with the long-term mortality in diabetes patients with CAD.
Read more Big Endothelin-1 associated with all-cause death in diabetes patients with CAD.
What is Big Endothelin-1 (Big ET-1) ?
Big ET-1 is a 38 amino acid peptide and is the precursor of Endothelin-1 (ET-1). ET-1 is a potent vasoconstrictor secreted by endothelial cells. It acts as the counterpart of the vasodilator nitric oxide (NO).
-
ET-1 is cleaved from Big ET-1 by the ET converting enzyme -1 (ECE-1).
-
Both the precursor Big ET-1 and the shorter 21 aminoacid vasoactive form Endothelin-1 circulate in blood.
-
ET-1, the biologically active form, is rapidly cleared and has a short half-life.
-
ET-1 and big ET-1 are found in equimolar concentrations in the plasma.
-
Thus, the longer half-life of big ET-1, its slower clearance and the findings that increased plasma levels of ET-1 in patients with heart failure are mainly due to an increase in big ET-1 concentrations, offers an analytical window for the measurement of Big ET-1 .
How can you measure Big ET-1?
Big ET-1 can easily be measured using in serum and plasma with only 50µl sample volume.
Biomedica’s Big ET-1 ELISA cat. no. BI-20082H
√ Direct measurement – highly sensitive
√ Full validation package
√ Widely cited +75 publications
check out the customer review on Biocompare
Related publications – Citations Big ET-1 ELISA – Biomedica
The Biomedica Big Endothelin-1 (Big ET-1) ELISA kit was utilized in the following studies:
Xu N, Zhu P, Yao Y, Jiang L, Jia S, Yuan D, Xu J, Wang H, Song Y, Gao L, Gao Z, Song L, Zhao X, Chen J, Yang Y, Xu B, Gao R, Yuan J. Nutr Metab Cardiovasc Dis. 2022 Sep;32(9):2147-2156. doi: 10.1016/j.numecd.2022.06.002. Epub 2022 Jun 11. PMID: 35843800.
Abstract
Background and aims: The present study aimed to examine the association between big endothelin-1 (big ET-1) and long-term all-cause death in patients with coronary artery disease (CAD) and different glucose metabolism status.
Methods and results: We consecutively enrolled 8550 patients from January 2013 to December 2013. Patients were categorized according to both status of glucose metabolism status [Diabetes Mellitus (DM), Pre-Diabetes (Pre-DM), Normoglycemia (NG)] and big ET-1 levels. Primary endpoint was all-cause death. During a median of 5.1-year follow-up periods, 301 all-cause deaths occurred. Elevated big ET-1 was significantly associated with long-term all-cause death (adjusted HR: 2.230, 95%CI 1.629-3.051; p < 0.001). Similarly, patients with DM, but not Pre-DM, had increased risk of all-cause death compared with NG group (p < 0.05). When patients were categorized by both status of glucose metabolism and big ET-1 levels, high big ET-1 were associated with significantly higher risk of all-cause death in Pre-DM (adjusted HR: 2.442, 95% CI 1.039-5.740; p = 0.041) and DM (adjusted HR: 3.162, 95% CI 1.376-7.269; p = 0.007). The Kaplan-Meier curve indicated that DM patients with the highest big ET-1 levels were associated with the greatest risk of all-cause death (p < 0.05).
Conclusions: The present data indicate that baseline big ET-1 levels were independently associated with the long-term all-cause death in DM and Pre-DM patients with CAD undergoing PCI, suggesting that big ET-1 may be a valuable marker in patients with impaired glucose metabolism.
Predictive Value of Plasma Big Endothelin-1 in Adverse Events of Patients With Coronary Artery Restenosis and Diabetes Mellitus: Beyond Traditional and Angiographic Risk Factors. Ma Y, Tian T, Wang T, Wang J, Guan H, Yuan J, Song L, Yang W, Qiao S. Front Cardiovasc Med. 2022 May 26;9:854107. doi: 10.3389/fcvm.2022.854107. PMID: 35694656; PMCID: PMC9177997.
Big Endothelin-1 and long-term all-cause death in patients with coronary artery disease and prediabetes or diabetes after percutaneous coronary intervention . Xu N, Zhu P, Yao Y, Jiang L, Jia S, Yuan D, Xu J, Wang H, Song Y, Gao L, Gao Z, Song L, Zhao X, Chen J, Yang Y, Xu B, Gao R, Yuan J. Nutr Metab Cardiovasc Dis. 2022 Sep;32(9):2147-2156. doi: 10.1016/j.numecd.2022.06.002. Epub 2022 Jun 11. PMID: 35843800.
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, Sancho-Tello MJ, Martínez-Dolz L, Sevilla B, Taléns-Visconti R, Jordán A, Miró V, Pérez-Boscá JL, Marín F, Climent V, García de Burgos F, Payá R, Sogorb F, Bertomeu V, Salvador A. Rev Esp Cardiol. 2005 Mar;58(3):278-84. Spanish. PMID: 15766450.
Plasma big endothelin-1 concentrations in congestive heart failure patients with or without systemic hypertension. Pacher R, Bergler-Klein J, Globits S, Teufelsbauer H, Schuller M, Krauter A, Ogris E, Rödler S, Wutte M, Hartter E. Am J Cardiol. 1993 Jun 1;71(15):1293-9. doi: 10.1016/0002-9149(93)90543-l. PMID: 8498369.
Plasma big endothelin-1 levels at admission and future cardiovascular outcomes: A cohort study in patients with stable coronary artery disease. Zhou BY, Guo YL, Wu NQ, Zhu CG, Gao Y, Qing P, Li XL, Wang Y, Dong Q, Liu G, Xu RX, Cui CJ, Sun J, Li JJ. Int J Cardiol. 2017 Mar 1;230:76-79. doi: 10.1016/j.ijcard.2016.12.082. Epub 2016 Dec 21. PMID: 28038820.
Background: Big endothelin-1 (ET-1) has been proposed as a novel prognostic indicator of acute coronary syndrome, while its predicting role of cardiovascular outcomes in patients with stable coronary artery disease (CAD) is unclear.
Methods and results: A total of 3154 consecutive patients with stable CAD were enrolled and followed up for 24months. The outcomes included all-cause death, non-fatal myocardial infarction, stroke and unplanned revascularization (percutaneous coronary intervention and coronary artery bypass grafting). Baseline big ET-1 was measured using sandwich enzyme immunoassay method. Cox proportional hazard regression analysis and Kaplan-Meier analysis were used to evaluate the prognostic value of big ET-1 on cardiovascular outcomes. One hundred and eighty-nine (5.99%) events occurred during follow-up. Patients were divided into two groups: events group (n=189) and non-events group (n=2965). The results indicated that the events group had higher levels of big ET-1 compared to non-events group. Multivariable Cox proportional hazard regression analysis showed that big ET-1 was positively and statistically correlated with clinical outcomes (Hazard Ratio: 1.656, 95% confidence interval: 1.099-2.496, p=0.016). Additionally, the Kaplan-Meier analysis revealed that patients with higher big ET-1 presented lower event-free survival (p=0.016).
Conclusions: The present study firstly suggests that big ET-1 is an independent risk marker of cardiovascular outcomes in patients with stable CAD. And more studies are needed to confirm our findings.
Superiority of big endothelin-1 and endothelin-1 over natriuretic peptides in predicting survival in severe congestive heart failure: a 7-year follow-up study. Van Beneden R, Gurné O, Selvais PL, Ahn SA, Robert AR, Ketelslegers JM, Pouleur HG, Rousseau MF. J Card Fail. 2004 Dec;10(6):490-5. doi: 10.1016/j.cardfail.2004.04.001. PMID: 15599839.
Try Biomedica’s Cytokine ELISA Kits for free!
Annoyed wasting valuable resources by inefficient tests?
Order your free trial Cytokine ELISA kit – offer valid until 12/31/22.
Contact us at Biomedica: info@bmgrp.com
Discover Biomedica’s Cytokine Kits – Use code: Biomedica FREE CytELISA Promotion – CN040010:
Discover Biomedica’s Cytokine Kits
Full validation package- assays are optimized for clinical samples
developed & manufactured by Biomedica. Austrian Quality.
IL-6 (Interleukin-6) high sensitivity
VEGF low sample volume – 10µl
ANGIOPOIETIN-2 optimized assay range
All kits include color coded, ready to use prediluted standards and controls.
Citations
Ana-Maria Suciu Andreea, Jacqueline Wallwitz, Berg Gabriela, Maria Laber Anna, Himmler Gottfried. Nephrology Dialysis Transplantation, Volume 34, Issue Supplement_1, June 2019, gfz103.SP339, https://doi.org/10.1093/ndt/gfz103.SP339
Click here to view poster: ERA-EDTA Poster 2019 Human Angiopoietin-2
Abstract
INTRODUCTION: Angiopoietin-2 (Ang-2) is an important regulator of the angiopoietin-1/Tie-2 receptor signaling system on endothelial cells during angiogenesis. Disruption of this signaling leads to the loss of endothelial integrity and renders the endothelium response towards a variety of pro-inflammatory cytokines and growth factors. Thus, Ang-2 might lead to vascular micro-inflammation in patients with CKD (chronic kidney disease). Ang-2 levels increase with CKD stage, are associated with fluid overload and abnormal cardiac structure and predict mortality in patients with CKD stages 4–5. Although Ang-2 levels return toward normal after successful kidney transplantation, Ang-2 remains a putative cardiovascular risk factor in this population.
METHODS: An enzyme-linked immunosorbent assay for the detection of all three angiopoietin-2 isoforms in human serum and plasma was developed. Two high quality antibodies are combined in a sandwich test format: As capturing antibody a recombinant monoclonal antibody is used. A biotin-labeled polyclonal affinity-purified antibody serves for detection of the analyte. High resolution epitope mapping of the antibodies via peptide microarray technology allowed the identification of linear antibody epitopes. Technical performance and accuracy of the assay were assessed according to ICH/EMEA guidelines.
RESULTS: Microarray data illustrate the binding of the polyclonal detection antibody to human angiopoietin-2 spotted on a chip. Altogether, seven linear epitopes located N-terminal/at the center of angiopoietin-2 were detected. Most relevant linear epitopes are epitope e2 in the super clustering region and e6 near the fibrinogen-like domain, displaying a twofold higher fluorescent signal than the remaining epitopes. For the recombinant monoclonal antibody no fluorescence was recorded. This antibody recognizes a structural epitope within the C-terminus of angiopoietin-2, which covers the bioactive receptor-binding site of the protein. We expect to detect all described angiopoietin-2 isoforms, as the receptor-binding site is conserved and the majority of the polyclonal antibody epitopes are present in all isoforms. This assay is in conformance with ICH/EMEA/FDA guidelines. Validation data demonstrate its applicability in nephrological disorders including chronic kidney disease. Here we compare an apparently healthy population to chronic kidney disease samples on haemodialysis and kidney transplant samples.
CONCLUSIONS: This new angiopoietin-2 ELISA enables a quick and accurate quantification of all human angiopoietin-2 isoforms that are bioactive in chronic kidney disease and other nephrological disorders.
RELATED LITERATURE
- Molnar et al. (2014): Circulating angiopoietin-2 levels predict mortality in kidney transplant recipients: a 4-year prospective case–cohort study. Transplant International, 27 (6): 541-52. 2. David et al. (2010): Circulating angiopoietin-2 levels increase with progress of chronic kidney disease. Nephrol. Dial. Transplant, 25: 2571-2579,
- Tsai et al. (2017): The interaction between fluid status and angiopoietin-2 in adverse renal outcomes of chronic kidney disease. PLoS One, 12 (3): e173906.
- Tsai et al. (2016): Angiopoietin-2, Angiopoietin-1 and subclinical cardiovascular disease in Chronic Kidney Disease. Scientific Reports, 6:39400
Circulating DKK-1 levels predict disease outcomes and mirror metabolic adaptations in patients with Covid-19
Individuals with low serum levels of DKK1 (Dickkopf-1) are twice as likely to die from Covid-19 than those with high levels according to new research published by Nikolai Jaschke and colleagues in the Journal of Clinical Endocrinology & Metabolism.
The researchers found that circulating DKK1 levels vary in humans and change as a function of time during SARS-CoV-2 infection. The infection promotes metabolic adaptations that resembles fasting, which are mirrored by circulating DKK1 levels. DKK-1 levels predict disease outcomes in Covid-19 individuals.
The results of the study suggest a potential clinical use of measuring circulating DKK1 as an indicator of disease severity in COVID-19 patients.
Circulating DKK1 levels were measured with the DKK-1 ELISA kit from Biomedica
Biomedica, Vienna, Austria, DKK-1 ELISA, catalog #BI-20413, RRID: AB_2922680
Highlights – DKK-1 ELISA (cat. no. BI-20413)
- Small sample volume – 20µl serum/well
- Reliable –international validation guidelines
- Easy – direct measurement
- Widely cited in +170 publications
Circulating Dickkopf1 parallels metabolic adaptations and predicts disease trajectories in patients with Covid-19. Full text link
Jaschke NP, Funk AM, Jonas S, Riffel RM, Sinha A, Wang A, Pählig S, Hofmann M, Altmann H, Von Bonin S, Koch T, Spieth P, Tausche K, Akgün K, Rauner M, Kronstein-Wiedemann R, Odendahl M, Tonn T, Göbel A, Hofbauer LC, Rachner TD. J Clin Endocrinol Metab. 2022 Sep 8:dgac514. doi: 10.1210/clinem/dgac514. Epub ahead of print. PMID: 36071553; PMCID: PMC9494396.
Abstract
Context and aims: Coronavirus disease 19 (COVID-19) trajectories show high interindividual variability, ranging from asymptomatic manifestations to fatal outcomes, the latter of which may be fueled by immunometabolic maladaptation of the host. Reliable identification of patients who are at risk of severe disease remains challenging. We hypothesized that serum concentrations of Dickkopf1 (DKK1) indicate disease outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals.
Methods: We recruited hospitalized patients with PCR-confirmed SARS-CoV-2 infection and included 80 individuals for whom blood samples from 2 independent time points were available. DKK1 serum concentrations were measured by ELISA in paired samples. Clinical data were extracted from patient charts and correlated with DKK1 levels. Publicly available datasets were screened for changes in cellular DKK1 expression on SARS-CoV-2 infection. Plasma metabolites were profiled by nuclear magnetic resonance spectroscopy in an unbiased fashion and correlated with DKK1 data. Kaplan-Meier and Cox regression analysis were used to investigate the prognostic value of DKK1 levels in the context of COVID-19.
Results: We report that serum levels of DKK1 predict disease outcomes in patients with COVID-19. Circulating DKK1 concentrations are characterized by high interindividual variability and change as a function of time during SARS-CoV-2 infection, which is linked to platelet counts. We further find that the metabolic signature associated with SARS-CoV-2 infection resembles fasting metabolism and is mirrored by circulating DKK1 abundance. Patients with low DKK1 levels are twice as likely to die from COVID-19 than those with high levels, and DKK1 predicts mortality independent of markers of inflammation, renal function, and platelet numbers.
Conclusion: Our study suggests a potential clinical use of circulating DKK1 as a predictor of disease outcomes in patients with COVID-19. These results require validation in additional cohorts.
Decrease of bone biomarker Sclerostin in women with anorexia nervosa during nutrition therapy – indication of reduced bone loss
Anorexia nervosa (AN) is an eating disorder and has one of the highest mortality rates of any mental illness. It affects roughly 2.9 million people and many experience bone loss and increased fracture risk. In a 3-year prospective study, Swedish researchers looked into the long-term effects of nutrition therapy. They investigated bone and mineral metabolism and biomarkers young women with AN. Their results showed that body mass index (BMI) and fat mass was increased. The regulatory bone biomarker Sclerostin decreased during nutrition therapy and further over 3 years, indicating reduced bone loss.
Read more: Bone mass and biomarkers in young women with anorexia nervosa: a prospective 3-year follow-up study.
Biomedica Sclerostin ELISA kit
- The internationally most referenced Sclerostin ELISA with more than 270 citations!
- Rigorously validated according to international quality guidelines
- Low sample volume
Bone mass and biomarkers in young women with anorexia nervosa: a prospective 3-year follow-up study.
Svedlund A, Pettersson C, Tubic B, Ellegård L, Elfvin A, Magnusson P, Swolin-Eide D. J Bone Miner Metab. 2022 Aug 12. doi: 10.1007/s00774-022-01359-x. Epub ahead of print. PMID: 35960382.
Abstract
Introduction: Anorexia nervosa (AN) increases the risk of impaired bone health, low areal bone mineral density (aBMD), and subsequent fractures. This prospective study investigated the long-term effects of bone and mineral metabolism on bone and biomarkers in 22 women with AN.
Materials and methods: Body composition and aBMD were measured by dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography. Total and free 25-hydroxyvitamin D (25OHD), C-terminal collagen cross-links (CTX), osteocalcin, bone-specific alkaline phosphatase (BALP), leptin, sclerostin, and oxidized/non-oxidized parathyroid hormone (PTH) were analyzed before and after 12 weeks of intensive nutrition therapy and again 3 years later. An age-matched comparison group of 17 healthy women was recruited for the 3-year follow-up.
Results: Body mass index (BMI) and fat mass increased from baseline to 3 years in women with AN. Sclerostin decreased during nutrition therapy and further over 3 years, indicating reduced bone loss. CTX was elevated at baseline and after 12 weeks but decreased over 3 years. BALP increased during nutrition therapy and stabilized over 3 years. Free 25OHD was stable during treatment but decreased over 3 years. Non-oxidized PTH was stable during treatment but increased over 3 years. Trabecular volumetric BMD in AN patients decreased during the first 12 weeks and over 3 years despite stable BMI and bone biomarkers implying increased BMD.
Conclusion: Our findings highlight the importance of early detection and organized long-term follow-up of bone health in young women with a history of AN.
Keywords: DXA; Eating disorder; Osteoporosis; Sclerostin; Vitamin D
Related publications
Anorexia nervosa: 30-year outcome.
Dobrescu SR, Dinkler L, Gillberg C, Råstam M, Gillberg C, Wentz E. Br J Psychiatry. 2020 Feb;216(2):97-104. doi: 10.1192/bjp.2019.113. PMID: 31113504; PMCID: PMC7557598.
Abstract
Background: Little is known about the long-term outcome of anorexia nervosa.
Aims: To study the 30-year outcome of adolescent-onset anorexia nervosa.
Method: All 4291 individuals born in 1970 and attending eighth grade in 1985 in Gothenburg, Sweden were screened for anorexia nervosa. A total of 24 individuals (age cohort for anorexia nervosa) were pooled with 27 individuals with anorexia nervosa (identified through community screening) who were born in 1969 and 1971-1974. The 51 individuals with anorexia nervosa and 51 school- and gender-matched controls were followed prospectively and examined at mean ages of 16, 21, 24, 32 and 44. Psychiatric disorders, health-related quality of life and general outcome were assessed.
Results: At the 30-year follow-up 96% of participants agreed to participate. There was no mortality. Of the participants, 19% had an eating disorder diagnosis (6% anorexia nervosa, 2% binge-eating disorder, 11% other specified feeding or eating disorder); 38% had other psychiatric diagnoses; and 64% had full eating disorder symptom recovery, i.e. free of all eating disorder criteria for 6 consecutive months. During the elapsed 30 years, participants had an eating disorder for 10 years, on average, and 23% did not receive psychiatric treatment. Good outcome was predicted by later age at onset among individuals with adolescent-onset anorexia nervosa and premorbid perfectionism.
Conclusions: This long-term follow-up study reflects the course of adolescent-onset anorexia nervosa and has shown a favourable outcome regarding mortality and full symptom recovery. However, one in five had a chronic eating disorder.
Mitchell JE, Peterson CB. N Engl J Med. 2020 Apr 2;382(14):1343-1351. doi: 10.1056/NEJMcp1803175. PMID: 32242359.
Osteoporosis Awareness –
Worldwide around 200 million women have osteoporosis. Osteoporosis is a disease that weakens bone. Bones become fragile and porous. From the outside, the osteoporotic bone is shaped like normal bone. However, the inside of the bone loses density and becomes weak. The risk of fractures become greater with age, due to the loss of minerals like calcium and phosphate. Osteoporosis most often affects bones in the hip, the spine and the wrist. Factors that influence bone health are nutrition, exercise and hormonal factors. Osteoporosis cannot be cured but delayed through early intervention and biomarker research has identified proteins that may help to identify patients at risk.
BIOMEDICA offers ELISA kits to measure Bone Biomarkers in human serum or plasma samples:
Osteoprotegerin (OPG) ELISA , DKK-1 ELISA , Sclerostin ELISA , soluble RANKL ELISA and others…
IL-6 ELISA , VEGF ELISA , Angiopoietin-2 ELISA
How can you prevent Osteoporosis?
Osteoporosis prevention includes a balanced diet, containing sufficient amounts of calcium and vitamin D and regular exercise.
Exercises to protect or reduce your chance of fracture include regular weight-bearing exercise (eg. weight lifting or resistance training) or any kind of activity that carries your own body weight (e.g. walking, running, climbing stairs, dancing).
A healthy and balanced diet with the recommended daily amounts of calcium are important for bone health. Read more about “Good for your bone foods .
Related literature
The Effectiveness of Physical Exercise on Bone Density in Osteoporotic Patients.
Benedetti MG, Furlini G, Zati A, Letizia Mauro G. Biomed Res Int. 2018. 23;2018:4840531. PMID: 30671455. Link to full text
Abstract
Physical exercise is considered an effective means to stimulate bone osteogenesis in osteoporotic patients. The authors reviewed the current literature to define the most appropriate features of exercise for increasing bone density in osteoporotic patients. Two types emerged: (1) weight-bearing aerobic exercises, i.e., walking, stair climbing, jogging, and Tai Chi. Walking alone did not appear to improve bone mass; however it is able to limit its progressive loss. In fact, in order for the weight-bearing exercises to be effective, they must reach the mechanical intensity useful to determine an important ground reaction force. (2) Strength and resistance exercises: these are carried out with loading (lifting weights) or without (swimming, cycling). For this type of exercise to be effective a joint reaction force superior to common daily activity with sensitive muscle strengthening must be determined. These exercises appear extremely site-specific, able to increase muscle mass and BMD only in the stimulated body regions. Other suggested protocols are multicomponent exercises and whole body vibration. Multicomponent exercises consist of a combination of different methods (aerobics, strengthening, progressive resistance, balancing, and dancing) aimed at increasing or preserving bone mass. These exercises seem particularly indicated in deteriorating elderly patients, often not able to perform exercises of pure reinforcement. However, for these protocols to be effective they must always contain a proportion of strengthening and resistance exercises. Given the variability of the protocols and outcome measures, the results of these methods are difficult to quantify. Training with whole body vibration (WBV): these exercises are performed with dedicated devices, and while it seems they have effect on enhancing muscle strength, controversial findings on improvement of BMD were reported. WBV seems to provide good results, especially in improving balance and reducing the risk of falling; in this, WBV appears more efficient than simply walking. Nevertheless, contraindications typical of senility should be taken into account.
Exercise for the prevention of osteoporosis in postmenopausal women: an evidence-based guide to the optimal prescription.
Daly RM, Dalla Via J, Duckham RL, Fraser SF, Helge EW.Braz J Phys Ther. 2019.23(2):170-180. PMID: 30503353. Full text link
Abstract
Background: Osteoporosis and related fragility fractures are a global public health problem in which pharmaceutical agents targeting bone mineral density (BMD) are the first line of treatment. However, pharmaceuticals have no effect on improving other key fracture risk factors, including low muscle strength, power and functional capacity, all of which are associated with an increased risk for falls and fracture, independent of BMD. Targeted exercise training is the only strategy that can simultaneously improve multiple skeletal and fall-related risk factors, but it must be appropriately prescribed and tailored to the desired outcome(s) and the specified target group.
Objectives: In this review, we provide an overview of the general principles of training and specific loading characteristics underlying current exercise guidelines for the prevention of osteoporosis, and an update on the latest scientific evidence with regard to the type and dose of exercise shown to positively influence bone mass, structure and strength and reduce fracture risk in postmenopausal women.
The bone metabolism mediators RANK (receptor activator of nuclear factor κB), RANKL (receptor activator of nuclear factor κB ligand) and OPG (osteoprotegerin) have been linked to breast cancer tumorgenesis. The dysregulation of RANK signaling is involved in the pathogenesis of BRCA1 associated breast cancer.
Experimental studies have shown that OPG (the decoy receptor for RANKL) protein levels are significantly lower in BRCA1 mutation carriers, inhibiting RANK signaling. Thus, OPG may serve as a potential biomarker of breast cancer risk.
Learn more: Delineating the role of osteoprotegerin as a marker of breast cancer risk among women with a BRCA1 mutation. Park SS et al., 2022.
Osteoprotegerin a potential biomarker of breast cancer risk
OPG can reliably be measured by ELISA analysis with only 20µl of serum or plasma.
The Biomedica OPG ELISA is the most referenced human OPG ELISA.
- Widely cited in more than 240 publications
Delineating the role of osteoprotegerin as a marker of breast cancer risk among women with a BRCA1 mutation.
Park SS, Uzelac A, Kotsopoulos J Hered Cancer Clin Pract. 2022 Apr 13;20(1):14. doi: 10.1186/s13053-022-00223-3. PMID: 35418083; PMCID: PMC9008947. Read full publication
Abstract
Women with a pathogenic germline mutation in the BRCA1 gene face a very high lifetime risk of developing breast cancer, estimated at 72% by age 80. Prophylactic bilateral mastectomy is the only effective way to lower their risk; however, most women with a mutation opt for intensive screening with annual MRI and mammography. Given that the BRCA1 gene was identified over 20 years ago, there is a need to identify a novel non-surgical approach to hereditary breast cancer prevention. Here, we provide a review of the emerging preclinical and epidemiologic evidence implicating the dysregulation of progesterone-mediated receptor activator of nuclear factor κB (RANK) signaling in the pathogenesis of BRCA1-associated breast cancer. Experimental studies have demonstrated that RANK inhibition suppresses Brca1-mammary tumorigenesis, suggesting a potential target for prevention. Data from studies conducted among women with a BRCA1 mutation further support this pathway in BRCA1-associated breast cancer development. Progesterone-containing (but not estrogen-alone) hormone replacement therapy is associated with an increased risk of breast cancer in women with a BRCA1 mutation. Furthermore, BRCA1 mutation carriers have significantly lower levels of circulating osteoprotegerin (OPG), the decoy receptor for RANK-ligand (RANKL) and thus endogenous inhibitor of RANK signaling. OPG levels may be associated with the risk of disease, suggesting a role of this protein as a potential biomarker of breast cancer risk. This may improve upon current risk prediction models, stratifying women at the highest risk of developing the disease, and further identify those who may be targets for anti-RANKL chemoprevention. Collectively, the evidence supports therapeutic inhibition of the RANK pathway for the primary prevention of BRCA1-associated breast cancer, which may generate unique prevention strategies (without prophylactic surgery) and enhance quality of life.
Related publications
Plasma osteoprotegerin and breast cancer risk in BRCA1 and BRCA2 mutation carriers.
Odén L, Akbari M, Zaman T, Singer CF, Sun P, Narod SA, Salmena L, Kotsopoulos J. Oncotarget. 2016. 27;7(52):86687-86694. doi: 10.18632/oncotarget.13417. PMID: 27893411; PMCID: PMC5349945.
Abstract
Emerging evidence suggests a role of receptor activator of nuclear factor κB (RANK)/RANK ligand (RANKL) signaling in breast cancer development. Lower osteoprotegerin (OPG) levels, the endogenous decoy receptor for RANKL which competes with RANK for binding of RANKL, has been reported among BRCA mutation carriers. Whether low OPG levels contribute to the high breast cancer risk in this population is unknown. OPG concentrations were measured in plasma of 206 cancer-free BRCA mutation carriers using an enzyme-linked immunosorbent assay. Subjects were categorized as high vs. low based on the median of the entire cohort (95 ng/mL) and followed for a new diagnosis of breast cancer. Cumulative incidence by baseline plasma OPG concentration was estimated using Kaplan-Meier survival analysis. Cox proportional hazards models were used to estimate the adjusted hazard ratios for the association between plasma OPG and breast cancer risk. Over a mean follow-up period of 6.5 years (range 0.1-18.8 years), 18 incident breast cancer cases were observed. After ten years of follow-up, the cumulative incidence of breast cancer among women with low OPG was 21%, compared to 9% among women with high OPG (P-log rank = 0.046). After multivariate adjustment, women with high plasma OPG had a significantly decreased risk of developing breast cancer, compared to women with low OPG (HR = 0.25; 95%CI 0.08-0.78; P = 0.02). These data suggest that low OPG levels are associated with an increased risk of BRCA-associated breast cancer. Targeting RANK signalling may represent a plausible, non-surgical prevention option for BRCA mutation carriers.
Human plasma Osteoprotegerin (OPG) was quantified using the Biomedica OPG ELISA – cat. no. BI-20403 .
Breast Cancer – the most common cancer worldwide
Breast cancer (BC) is the most commonly occurring cancer in women and the most common cancer overall. Although it is mostly found in women, it can affect men as well. Breast tissue in men can also become malignant. Though male BCs are rare and occur in 1% of all BCs, men are often diagnosed at a more advanced stage. The delay in seeking medical attention often results in late presentation and poor prognosis.
October is breast cancer month – raising global awareness on risks, the importance of screenings, and the options of treatment.
Related links
Further readings
Wilkinson L et al., Br J Radiol. 2022. PMID: 34905391; PMCID. Full text
Abstract
Breast cancer is now the most commonly diagnosed cancer in the world. The most recent global cancer burden figures estimate that there were 2.26 million incident cases in 2020 and the disease is the leading cause of cancer mortality in women worldwide. The incidence is strongly correlated with human development, with a large rise in cases anticipated in regions of the world that are currently undergoing economic transformation. Survival, however, is far less favourable in less developed regions. There are a multitude of factors behind disparities in the global survival rates, including delays in diagnosis and lack of access to effective treatment. The World Health Organization’s new Global Breast Cancer Initiative was launched this year to address this urgent global health challenge. It aims to improve survival across the world through three pillars: health promotion, timely diagnosis, and comprehensive treatment and supportive care.
Trapani D et al., Cancer Treat Rev. 2022. PMID: 35074727.
Cancer research
Prognostic exploratory biomarkers
Circulating biomarkers have the potential to provide valuable insight into disease progression.
Discover Biomarker ELISA kits for cancer research – developed and manufactured by Biomedica
regulator of tumor biology – expressed by endothelial cells – isoform-specific receptors for VEGF – checkpoint target – association with poor prognosis in BC patients.
extracellular matrix protein – novel therapeutic target – marker of glioma malignancy and potential tumor recurrence – high serum levels associated with a poor survival in BC patients.
glycoprotein – emerging clinical biomarker and therapeutic target in cancer – association with cancer progression and the bone metastases.
contribution to development of bone metastases an –in earlier stages of cancer influence on tumor biology.
Leucine-rich alpha-2-glycoprotein 1 – LRG1 – involved in pathogenic angiogenesis in cancer – wide spread in the microenvironment of numerous tumors – contributes to vascular dysfunction – potential therapeutic target.
ANG2 – ANGPT2 – glycoprotein – drives vessel growth – immune target – involved in resistance to anti-VEGF therapy – possible predictive and prognostic biomarker for immune checkpoint therapy.
important cytokine during breast cancer progression – IL6 triggers activation of STAT2 in breast tumors – soluble factor IL6 could be used for early diagnosis of BC or prevent development of metastasis to the bone.
Vascular growth factor – potent cytokine that induces tumor angiogenesis – subtype VEGFA and VEGF Receptor -2 are therapeutical targets.
Further information on our products can be found on our website
International agency for research on cancer – WHO
BIOMEDICA & QUALITY
Looking for a reliable ELISA kit for your research?
Use Biomedica kits as your new standard for trustworthy results.
Reliable ELISA kits
From product development to manufacturing, Biomedica ELISA kits go through a complete validation process.
Contact us for your special evaluation discount by email info@bmgrp.com or call us at our headquarter in Vienna / Austria: +43 1 29107 45 .
We validate our ELISA assays according to international quality standards
The international recognized regulatory forces that issue technical quality guidelines for the validation of bioanalytical methods are:
- FDA (US Food and Drug Administration)
- EMEA (European Medicines Agency)
- ICH (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use)
Their main objective is to demonstrate the reliability of a test to determine the concentration of an analyte in a specific biological matrix (e.g. serum, plasma, urine).
Reliable ELISA kits for your research
All Biomedica immunoassays are validated for multiple sample matrices according to above quality guidelines. Our validation experiments include:
- Accuracy
- Dilution linearity – parallelism
- Specificity
- Cross-reactivity
- Sensitivity
- Precision
- Calibration
- Stability
We Guarantee the Performance of our Products – reliable ELISA kits
Understanding the importance of high quality, we at Biomedica we offer fully validated ELISA kits for your research.
- We optimize all our ELISA kits for reliability, sensitivity, precision, and ease-of-use.
- Our development, production and customer service teams consist of doctorate-level and industry-trained scientists with long-standing research experience.
- Biomedica’s manufacturing process conforms to the ISO 9001:2015 certified quality management system.
To ensure continued customers’ satisfaction, we strive to meet the highest quality standards and continuously work on improving both our products and manufacturing process.
For further details on our validation process come and visit our quality site.
Test our high-quality ELISA kits for your research and ask for your special evaluation discount.
Contact us by email info@bmgrp.com or call us at our office in Vienna – Austria: +43 1 29107 45 .
Cancer research for the prevention and early recognition of cancer
Promoting cancer research to beat cancer: prevention and early detection of cancer is essential to control the disease. Understanding the causes of cancer and the ability to detect cancer sooner has a great impact on the survival and the outcome of patients.
Subsequently, early detection strategies and progress in diagnostic procedures will help to develop treatments to control the disease.
Promoting cancer research:
Exploring new biomarkers may help to identify the disease early.
Biomedica offers a range of novel biomarker ELISA kits for your cancer research.
Novel research biomarkers for cancer research include: Periostin, Neuropilin-1, Semaphorin 4D
A range of cytokine ELISA kits complete the panel: Interleukin-6, VEGF, Angiopoietin-2 .
See our comprehensive “Oncology Biomarker Brochure “ for more information or contact us directly info@bmgrp.com .
We will be glad to meet you.
RELATED LITERATURE:
Promoting Cancer Early Diagnosis – https://www.who.int
“Early diagnosis of cancer focuses on detecting symptomatic patients as early as possible so they have the best chance for successful treatment. When cancer care is delayed or inaccessible there is a lower chance of survival, greater problems associated with treatment and higher costs of care. Early diagnosis improves cancer outcomes by providing care at the earliest possible stage and is therefore an important public health strategy in all settings…” Read more
Pelosi E, Castelli G, Testa U.Ann Ist Super Sanita. 2019 Oct-Dec;55(4):371-379. doi: 10.4415/ANN_19_04_11. PMID: 31850865.
Abstract
The burden of cancer is increasing worldwide, with a continuous rise of the annual total cases. Although mortality rates due to cancer are declining in developed countries, the total number of cancer deaths continues to rise due to the increase in the number of aged people. Three main causes of cancer have been described, represented by environmental factors, hereditary factors and random factors related to defects originated during cell replication. The frequency of cancers is very different for the various tissues and there is great debate on the extent of the specific contribution of environmental factors and random factors (due to “bad luck”) to cancer development. However, there is consensus that about 50% of all cases of cancer are related to environment and are preventable. Although a part of cancers is related to intrinsic mechanisms non preventable of genetic instability, it is evident that implementation of primary and secondary prevention measures is the only affordable strategy to meet from a medical and economic point of view the tremendous pressure created on healthcare structures by the increased cancer burden. It is time to bypass the paradox of disease prevention: celebrated in principle, resisted in practice.
Ovarian Cancer Biomarkers: Moving Forward in Early Detection
Bonifácio VDB. Adv Exp Med Biol. 2020;1219:355-363. doi: 10.1007/978-3-030-34025-4_18. PMID: 32130708.
Abstract
Ovarian cancer is a silent cancer which rate survival mainly relays in early stage detection. The discovery of reliable ovarian cancer biomarkers plays a crucial role in the disease management and strongly impact in patient’s prognosis and survival. Although having many limitations CA125 is a classical ovarian cancer biomarker, but current research using proteomic or metabolomic methodologies struggles to find alternative biomarkers, using non-invasive our relatively non-invasive sources such as urine, serum, plasma, tissue, ascites or exosomes. Metabolism and metabolites are key players in cancer biology and its importance in biomarkers discovery cannot be neglected. In this chapter we overview the state of art and the challenges facing the use and discovery of biomarkers and focus on ovarian cancer early detection.
Keywords: Cancer biomarkers; Early detection; Metabolomics; Ovarian cancer; Proteomics; Urine biomarkers.
Back to school – sports training has positive outcomes
Strength training for children and adolescents enhances bone health
Strength training for children and adolescents is becoming more important as part of sport training and after-school fitness programs. Consequently, health problems due to inactivity, sedentary lifestyle and being overweight have resulted in increased interest in strength and resistance training (1). Today there is ample evidence that youth resistance training is safe and effective and improves motor skills, reduces fat mass, and enhances bone health. In addition, various performance markers such as muscle strength, power and overall health also improve (2-5). In adults, weight-bearing impact exercise such as jumping or hopping in addition to strength training can improve bone health. Among these, resistance training is the most promising intervention to maintain or increase bone mass and density (5, 6).
Subsequently, measuring serum bone related biomarkers can be helpful in understanding normal and pathological processes that reflect bone cell activities in the skeleton.
Check out Biomedica´s high quality bone marker ELISA kits: Sclerostin, RANKL, OPG, DKK-1, FGF23 (C-terminal), FGF23 intact and other
RELIABLE MANUFACTURING ENSURES CONSISTENT RESULTS
√ The internationally most referenced Sclerostin ELISA!
√ Extensively validated according to international quality guidelines
√ Only 20µl sample / well – low sample volume
References on strength training for children and adoloscents
- Resistance Training for Children and Adolescents.
Stricker PR, Faigenbaum AD, McCambridge TM; COUNCIL ON SPORTS MEDICINE AND FITNESS Pediatrics. 2020. 145(6):e20201011. doi: 10.1542/peds.2020-1011. - Performance – and health-related benefits of youth resistance training – Leistungs- und gesundheitsbezogene Wirkungen von Krafttraining mit Heranwachsenden.
H.Chaabene H et al., 2020. Sports Orthopaedics and Traumatology; 36: 231-240. - Strength training for children and adolescents: benefits and risks.
Barbieri D, Zaccagni L. Coll Antropol. 2013. 37 Suppl 2:219-25. PMID: 23914510. - Strength training for children and adolescents.
Faigenbaum A. 2000. Clinics in Sports Medicine; 593-619. - Exercise and Sports Science Australia (ESSA) position statement on exercise prescription for the prevention and management of osteoporosis.
Beck BR, Daly RM, Singh MA, Taaffe DR. J Sci Med Sport. 2017;20:438–445. - Effects of Resistance Exercise on Bone Health.
Hong AR, Kim SW. Endocrinol Metab (Seoul). 2018. 33(4):435-444. doi: 10.3803/EnM.2018.33.4.435. PMID: 30513557; PMCID: PMC6279907.
RELATED LITERATURE
Youth Resistance Training: The Good, the Bad, and the Ugly-The Year That Was 2017.
Faigenbaum AD. Pediatr Exerc Sci. 2018. 1;30(1):19-24. doi: 10.1123/pes.2017-0290. PMID: 29424264.
Abstract
The good news is that a growing body of evidence recognizes resistance training as foundational to long-term physical development. Original research and reviews published in 2017 conclude that early exposure to developmentally appropriate resistance training can improve markers of health, increase muscular fitness, enhance physical literacy, and reduce the risk of injury in young athletes. Although the papers discussed in the commentary add to our understanding of the pleiotropic benefits of youth resistance training, they also raise concerns. As measures of muscular strength and power have been found to track from childhood to adulthood, the bad news is that youth with low levels of muscular fitness tend to become weak adults who are at increased risk for functional limitations and adverse health outcomes. Furthermore, global participation in youth resistance training is falling far short of public health recommendations, and these ugly trends will likely impact the health and well-being of future generations. A change in current attitudes and common practices is urgently needed to educate parents, practitioners, and clinicians about the potential benefits of resistance training for all children and adolescents, not only young athletes.
Leister KR, Cilhoroz BT, Rosenberg J, Brown EC, Kim JY Diabetes Metab Syndr. 2022. 16(6):102530. doi: 10.1016/j.dsx.2022.102530. PMID: 35709585.
Watch this on how kids can get stronger muscles: “Top 10 Kids Exercises To Get Stronger Muscles”
Strength training for children and adolescents enhances bone health
FGF23 is a cardiovascular toxin in CKD
Chronic kidney disease (CKD) is a serious health problem that involves gradual loss of kidney function. The major cause of death in CKD patients is cardiovascular disease is triggered by the cardiovascular toxins fibroblast growth factor (FGF23) and phosphate.
Declining kidney function leads to elevated serum phosphate levels which are regulated by the phophaturic hormone FGF23 in CKD patients. In later stages of chronic kidney disease, access FGF23 and phosphate levels lead to increased cardiovascular disease and mortality. Ongoing experimental studies are identifying novel therapeutic strategies in order to prevent toxicity of FGF23 and hyperphosphatemia in CKD patients.
FGF23 is a cardiovascular toxin in chronic kidney disease
FGF23 and Phosphate-Cardiovascular Toxins in CKD.
Vogt I, Haffner D, Leifheit-Nestler M. Toxins (Basel). 2019 Nov 6;11(11):647. doi: 10.3390/toxins11110647. PMID: 31698866; PMCID: PMC6891626.
Biomedica offers ready to use FGF23 (C-terminal) and FGF23 intact ELISA kits
√ HIGH QUALITY – assay validation with clinical samples – IHC precision and reproducibility
√ USER FRIENDLY kits – ready to use standards and controls
√ Multi-matrix use in SERUM & PLASMA samples
FGF23 and Phosphate-Cardiovascular Toxins in CKD full text link
Abstract
Elevated levels of fibroblast growth factor 23 (FGF23) and phosphate are highly associated with increased cardiovascular disease and mortality in patients suffering from chronic kidney disease (CKD). As the kidney function declines, serum phosphate levels rise and subsequently induce the secretion of the phosphaturic hormone FGF23. In early stages of CKD, FGF23 prevents the increase of serum phosphate levels and thereby attenuates phosphate-induced vascular calcification, whereas in end-stage kidney disease, FGF23 fails to maintain phosphate homeostasis. Both hyperphosphatemia and elevated FGF23 levels promote the development of hypertension, vascular calcification, and left ventricular hypertrophy by distinct mechanisms. Therefore, FGF23 and phosphate are considered promising therapeutic targets to improve the cardiovascular outcome in CKD patients. Previous therapeutic strategies are based on dietary and pharmacological reduction of serum phosphate, and consequently FGF23 levels. However, clinical trials proving the effects on the cardiovascular outcome are lacking. Recent publications provide evidence for new promising therapeutic interventions, such as magnesium supplementation and direct targeting of phosphate and FGF receptors to prevent toxicity of FGF23 and hyperphosphatemia in CKD patients.
RELATED PUBLICATIONS
Fibroblast Growth Factor-23-A Potential Uremic Toxin.
Kuczera P, Adamczak M, Wiecek A Toxins (Basel). 2016 Dec 8;8(12):369. doi: 10.3390/toxins8120369. PMID: 27941640; PMCID: PMC5198563.
Abstract
Fibroblast growth factor-23 (FGF23) is a circulating member of the FGF family produced mainly by the osteocytes and osteoblasts that can act as a hormone. The main action of FGF23 is to lower phosphatemia via the reduction of urinary phosphate reabsorption and the decrease of 1,25(OH)₂-D generation in the kidney. In the course of chronic kidney disease (CKD), plasma FGF23 concentration rises early, most probably to compensate the inability of the deteriorating kidneys to excrete an adequate amount of phosphate. However, this comes at the cost of FGF23-related target organ toxicity. Results of clinical studies suggest that elevated plasma FGF23 concentration is independently associated with the increased risk of CKD progression, occurrence of cardio-vascular complications, and mortality in different stages of CKD. FGF23 also contributes to cardiomyocyte hypertrophy, vascular calcification, and endothelial dysfunction. The impact of FGF23 on heart muscle is not dependent on Klotho, but rather on the PLCγ-calcineurin-NFAT (nuclear factor of activated T-cells) pathway. Among the factors increasing plasma FGF23 concentration, active vitamin D analogues play a significant role. Additionally, inflammation and iron deficiency can contribute to the increase of plasma FGF23. Among the factors decreasing plasma FGF23, dietary phosphate restriction, some intestinal phosphate binders, cinacalcet (and other calcimimetics), and nicotinamide can be enumerated. Anti-FGF23 antibodies have also recently been developed to inhibit the action of FGF23 in target organs. Still, the best way to normalize plasma FGF23 in maintenance hemodialysis patients is restoring kidney function by successful kidney transplantation.
Zhao SJ, Wang ZX, Chen L, Wang FX, Kong LD. Ann Palliat Med. 2022 Apr;11(4):1264-1277. doi: 10.21037/apm-21-1943. Epub 2021 Nov 2. PMID: 34775773.
Courbon G, Martinez-Calle M, David V. Curr Opin Nephrol Hypertens. 2020 Jul;29(4):359-366. doi: 10.1097/MNH.0000000000000614. PMID: 32452919; PMCID: PMC7769207.
Leucine-rich alpha-2 glycoprotein – an inflammation marker
LRG – a biomarker of fetal infection: Infections during pregnancy could harm the pregnant mother and the developing baby and remain a substantial clinical problem. Findings suggest that certain biomarkers have diagnostic value when maternal infection is suspected. Researchers from Japan recently identified the inflammatory protein leucine-rich alpha-2 glycoprotein (LRG) as a biomarker of fetal infection. Read more: Evaluation of leucine-rich alpha-2 glycoprotein as a biomarker of fetal infection.
LRG can reliably be measured by ELISA assay in serum, plasma, urine or cell culture supernatants.
√ TRUSTED – full validation package
√ CONVENIENT – optimized for clinical samples
√ EASY – results in 3 h, all reagents included
Developed & manufactured by Biomedica – Austria.
Check out the LRG ELISA assay validation data
RELATED PUBLICATIONS
Evaluation of leucine-rich alpha-2 glycoprotein as a biomarker of fetal infection.
Kajimoto E, Endo M, Fujimoto M, Matsuzaki S, Fujii M, Yagi K, Kakigano A, Mimura K, Tomimatsu T, Serada S, Takeuchi M, Yoshino K, Ueda Y, Kimura T, Naka T.
PLoS One. 2020, 19;15(11):e0242076. doi: 10.1371/journal.pone.0242076. PMID: 33211747; PMCID: PMC7676652. PubMed
Abstract
This study aimed to determine the association between umbilical cord leucine-rich alpha-2 glycoprotein (LRG) and fetal infection and investigate the underlying mechanism of LRG elevation in fetuses. We retrospectively reviewed the medical records of patients who delivered at Osaka University Hospital between 2012 and 2017 and selected those with histologically confirmed chorioamnionitis (CAM), which is a common pregnancy complication that may cause neonatal infection. The participants were divided into two groups: CAM with fetal infection (CAM-f[+] group, n = 14) and CAM without fetal infection (CAM-f[-] group, n = 31). Fetal infection was defined by the histological evidence of funisitis. We also selected 50 cases without clinical signs of CAM to serve as the control. LRG concentrations in sera obtained from the umbilical cord were unaffected by gestational age at delivery, neonatal birth weight, nor the presence of noninfectious obstetric complications (all, p > 0.05). Meanwhile, the LRG levels (median, Interquartile range [IQR]) were significantly higher in the CAM-f(+) group (10.37 [5.21-13.7] μg/ml) than in the CAM-f(-) (3.61 [2.71-4.65] μg/ml) or control group (3.39 [2.81-3.93] μg/ml; p < 0.01). The area under the receiver operating characteristic (ROC) curve of LRG for recognizing fetal infection was 0.92 (optimal cutoff, 5.08 μg/ml; sensitivity, 86%; specificity, 88%). In a mouse CAM model established by lipopolysaccharide administration, the fetal LRG protein in sera and LRG mRNA in the liver were significantly higher than those in phosphate-buffered saline (PBS)-administered control mice (p < 0.01). In vitro experiments using a fetal liver-derived cell line (WRL68) showed that the expression of LRG mRNA was significantly increased after interleukin (IL)-6, IL-1β, and tumor necrosis factor- alpha (TNF-α) stimulation (p < 0.01); the induction was considerably stronger following IL-6 and TNF-α stimulation (p < 0.01). In conclusion, LRG is an effective biomarker of fetal infection, and fetal hepatocytes stimulated with inflammatory cytokines may be the primary source of LRG production in utero.
Recognising the burden of maternal infection worldwide.
Seale AC. Lancet Glob Health. 2020. 8(5):e615-e616. doi: 10.1016/S2214-109X(20)30126-1. PMID: 32353299.
Oben AG, Johnson BM, Tita ATN, Andrews WW, Hibberd PL, Subramaniam A, Sinkey RG. Int J Gynaecol Obstet. 2022.157(1):42-50. doi: 10.1002/ijgo.13747. PMID: 33999419.
An update on COVID-19 and pregnancy.
Jamieson DJ, Rasmussen SA. Am J Obstet Gynecol. 2022. 226(2):177-186. doi: 10.1016/j.ajog.2021.08.054. PMID: 34534497; PMCID: PMC8438995.
Developed & manufactured by Biomedica – Biomarkers for Cancer Research
The identification and validation of biomarkers in cancer is essential to improve our understanding of the disease. The emergence of novel cancer biomarkers continues to grow as scientists strive to find promising novel therapeutic targets and new prognostic and predictive markers to fight the disease.
Discover Biomedica Biomarker Assays for Cancer Research – we offer a range of unique biomarker ELISAs for your research.
Advantages of Biomedica ELISA 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
High specificity – known target binding sites through mapping data
The unique specificity of the proprietary antibodies used in the Biomedica ELISA kits ensure that the assays only measure the analyte of interest.
Discover Biomedica´s Biomarker ELISA kits for cancer research
Neuropilin-1, Periostin, Semaphorin 4D, Osteoprotegerin, RANKL, LRG1, IL-6, VEGF, Angiopoietin-2 and other
Biomarkers for Cancer Research – Learn more about the markers
The transmembrane protein Neuropilin-1 (NRP1) regulates tumor biology and has been identified as a checkpoint target (1). High tissue NRP-1 levels are associated with a poor prognosis in breast cancer patients. In a recent study (2), German researchers have shown that circulating soluble NRP1 serum levels are an independent marker for poor prognosis in early breast cancer. Soluble Neuropilin-1 was quantified in serum with the highly specific NRP1 ELISA from Biomedica. Therapeutic areas of NRP1.
The secreted extracellular matrix protein Periostin has evolved as a novel therapeutic target and is a robust marker of glioma malignancy and potential tumor recurrence. It has also been implicated in the pathogenesis of breast cancer as high serum levels of periostin are associated with a poor survival in breast cancer patients (3). Periostin was quantified in serum with the well characterized Biomedica Periostin ELISA that has been published (4). Therapeutic areas of Periostin.
Semaphorin 4D (Sema4D) is a glycoprotein that is emerging as clinical biomarker and as therapeutic target in cancer. It has been associated with cancer progression and the occurrence of bone metastases (5, 6). Therapeutic areas of Sema4D.
Leucine-rich alpha-2-glycoprotein 1 (LRG1) is a protein that is an important factor involved in pathogenic angiogenesis in cancer. It is abundantly present in the microenvironment of many tumors contributing to vascular dysfunction and thus serving as a potential therapeutic target (7). Therapeutic areas of LRG 1.
The RANKL/RANK/OPG system contributes to the development of bone metastases and influences tumor biology in earlier stages of cancer (9). Dysregulation has been widely documented in the context of metastatic bone disease (10). The Biomedica OPG and RANKL ELISA kits have been widely used in the respective studies.
Literature
1. Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy. Chuckran CA et al., J Immunother Cancer. 2020. 8(2):e000967.
2. Soluble Neuropilin-1 is an independent marker of poor prognosis in early breast cancer. Rachner TD et al., J Cancer Res Clin Oncol. 2021. 147(8):2233-2238.
3. High serum levels of periostin are associated with a poor survival in breast cancer. Rachner TD et al., 2020. 180(2):515-524.
4. Characterization of a sandwich ELISA for the quantification of all human periostin isoforms. Gadermaier E J Clin Lab Anal. 2018. 32(2):e22252.
5. Plasma levels of Semaphorin 4D are decreased by adjuvant tamoxifen but not aromatase inhibitor therapy in breast cancer patients. Göbel A J Bone Oncol. 2019. 4;16:100237.
6. Semaphorins as emerging clinical biomarkers and therapeutic targets in cancer. Mastrantonio R et al., Theranostics. 202. 15;11(7):3262-3277.
7. Leucine-rich alpha-2-glycoprotein 1 (LRG1) as a novel ADC target. Javaid F et al., RSC Chem Biol. 2021. 31;2(4):1206-1220.
8. RANKL/RANK/OPG system beyond bone remodeling: involvement in breast cancer and clinical perspectives. Infante M J Exp Clin Cancer Res. 2019. 8;38(1):12.
9. Serum receptor activator of nuclear factor κB ligand (RANKL) levels predict biochemical recurrence in patients undergoing radical prostatectomy. Todenhöfer T, BJU Int. 2014. 113(1):152-9.
10. Prognostic Value of RANKL/OPG Serum Levels and Disseminated Tumor Cells in Nonmetastatic Breast Cancer. Rachner TD et al., Clin Cancer Res. 2019. 15;25(4):1369-1378.
Try our unique CYTOKINE ELISA Kits
ELISA Kits for affordable and efficient research : Use promo code BIcytELISA. Valid until 12/31/22
√ Human IL-6 ELISA – high sensitivity & detectable IL-6 levels
√ Human VEGF ELISA – only 10µl of serum or plasma sample
√ Human Angiopoietin-2 ELISA – immediate results-optimized for clinical samples
All kits include color coded, ready to use prediluted standards and controls.
Contact us NOW for your promotion discount info@bmgrp.com
ELISA Kits for affordable and efficient research
We validate all the BIOMEDICA ELISA assays according to international quality standards and follow guidelines of ICH, EMEA and FDA. Thus, you can find the validation data of every assay on the respective product pages on our website. Specifically, the data include spike-recovery and parallelism, dilution linearity experiments including precision and accuracy testing. In addition, every analyte is tested on its stability in the respective sample matrix, including long term stability. Finally, the antibodies utilized in the BIOMEDICA Elisa kits are characterized and epitope mapped. Click here to upload the validation data file on our human Interleukin-6 (IL-6) ELISA assay kit.
We Guarantee the Performance of our Products
Related Posts – on Biomedica Quality Cytokine Kits
All our ELISA kits undergo a stringent quality control process, ensuring reliable and consistent results. We are located right in the heart of Europe. developed & manufactured by Biomedica.
Report on novel prostate tumor cell targets
The Biomedica EZ4U – Cell Proliferation & Cytotoxicity Kit was cited in a high tier journal studying novel prostate tumor endothelial cell targets. The study highlights CXCR4/CXCL12 interaction as a potential novel target to interfere with tumor angiogenesis:
EZ4U Cell Proliferation & Cytotoxicity Assay
- Use of non-radioactive & non-toxic substances
- Easy one-step procedure on living cells
- Cited in more than 225 publications
More information can be found in our brochure: EZ4U – cat. no. BI-5000
Comprehensive characterization of the prostate tumor microenvironment identifies CXCR4/CXCL12 crosstalk as a novel antiangiogenic therapeutic target in prostate cancer.
Heidegger I, Fotakis G, Offermann A, Goveia J, Daum S, Salcher S, Noureen A, Timmer-Bosscha H, Schäfer G, Walenkamp A, Perner S, Beatovic A, Moisse M, Plattner C, Krogsdam A, Haybaeck J, Sopper S, Thaler S, Keller MA, Klocker H, Trajanoski Z, Wolf D, Pircher A. Mol Cancer. 2022 Jun 18;21(1):132. doi: 10.1186/s12943-022-01597-7. PMID: 35717322; PMCID: PMC9206324. Full text
Abstract
Background: Crosstalk between neoplastic and stromal cells fosters prostate cancer (PCa) progression and dissemination. Insight in cell-to-cell communication networks provides new therapeutic avenues to mold processes that contribute to PCa tumor microenvironment (TME) alterations. Here we performed a detailed characterization of PCa tumor endothelial cells (TEC) to delineate intercellular crosstalk between TEC and the PCa TME.
Methods: TEC isolated from 67 fresh radical prostatectomy (RP) specimens underwent multi-omic ex vivo characterization as well as orthogonal validation of both TEC functions and key markers by immunohistochemistry (IHC) and immunofluorescence (IF). To identify cell-cell interaction targets in TEC, we performed single-cell RNA sequencing (scRNA-seq) in four PCa patients who underwent a RP to catalogue cellular TME composition. Targets were cross-validated using IHC, publicly available datasets, cell culture experiments as well as a PCa xenograft mouse model.
Results: Compared to adjacent normal endothelial cells (NEC) bulk RNA-seq analysis revealed upregulation of genes associated with tumor vasculature, collagen modification and extracellular matrix remodeling in TEC. PTGIR, PLAC9, CXCL12 and VDR were identified as TEC markers and confirmed by IF and IHC in an independent patient cohort. By scRNA-seq we identified 27 cell (sub)types, including endothelial cells (EC) with arterial, venous and immature signatures, as well as angiogenic tip EC. A focused molecular analysis revealed that arterial TEC displayed highest CXCL12 mRNA expression levels when compared to all other TME cell (sub)populations and showed a negative prognostic role. Receptor-ligand interaction analysis predicted interactions between arterial TEC derived CXCL12 and its cognate receptor CXCR4 on angiogenic tip EC. CXCL12 was in vitro and in vivo validated as actionable TEC target by highlighting the vessel number- and density- reducing activity of the CXCR4-inhibitor AMD3100 in murine PCa as well as by inhibition of TEC proliferation and migration in vitro.
Conclusions: Overall, our comprehensive analysis identified novel PCa TEC targets and highlights CXCR4/CXCL12 interaction as a potential novel target to interfere with tumor angiogenesis in PCa.
Procedure of the EZ4U colorimetric test
The cell proliferation Assay kit EZ4U is non-toxic and non-radioactive that is based on the reduction of tetrazolium salt to colored formazan in living cells. Thus, the assay discriminates between living and dead cells since the process requires functional mitochondria. The assay is very easy to perform – add EZ4U reagent directly to the cells cultured, incubate and detect absorbance of the supernatant by a reader. The assay has been applied in numerous cells as reported in more than 225 publications e.g.
Fasting improves therapeutic response in hepatocellular carcinoma through p53-dependent metabolic synergism. Krstic J et al., Sci Adv. 2022. 21;8(3):eabh2635.
“Cell viability was analyzed using EZ4U assay (Biomedica Immunoassays) according to the manufacturer’s instructions. Briefly, at the end of treatment, the medium was replaced with fresh GM (200 μl per well) and 20 μl per well of EZ4U working solution. After 2 hours of incubation at 37°C, the absorbance was measured at 492 nm with a reference wavelength of 620 nm (Spark 10M multimode microplate reader).”
Syndecan-4 Is a Key Facilitator of the SARS-CoV-2 Delta Variant’s Superior Transmission. Hudák A et al., Int J Mol Sci. 2022. 12;23(2):796.
“Cell Viability Measurements: The effect of the applied spike proteins on cell viability was assessed with the EZ4U cell proliferation assay (Biomedica Gmbh, Vienna, Austria, cat. no. BI-5000), according to the instructions of the manufacturer. Absorbance was measured with a BioTek Cytation 3 multimode microplate reader.”
Method
- Water-soluble tetrazolium compound penetrates cell membrane
- In mitochondria reduction takes place and results in intense colored formazan which is water-soluble
- The reagent Formazan is secreted into culture medium and measured with an ELISA reader at 450 nm or 492 nm
Protocol
- Sample type – culture medium
- Sample size – 200 µl / test
- Detection limit – depends on respective cell line. Some xamples are shown in the product insert
- Incubation time – between 2-5 hours
What does the EZ4U kit include?
The reagents supplied per kit are sufficient for testing 10 x 96 well microtiter plates and contain:
- Substrate – lyophilized 10 vials
- Activator solution – ready to use 1 x 30 ml
Examples of cell types used in the EZ4U assay
– Endothelial cells (primary isolated from biopsies or cell-lines)
– Peripheral blood mononuclear cells (PBMCsec)
– HeLa (human cervical cancer) and HEK293A (human embryonic kidney) cell lines
– Human aortic smooth muscle cells (HAoSMCs)
– Huh7 (human liver carcinoma, CLS Cell Lines)
– Colon carcinoma cell models SW480
– CLC CTC cell lines (BHGc7, BHGc10, BHGc16, BHGc26 and UHGc5)
– CRC cell line HT29, DLD-1, HCT116,primary CRC cell line CG08
– HepG2 and Huh6 clone 5 cell lines
– Primary human skin cells – keratinocytes and fibroblasts
– Bovine mammary epithelial cells (MAC-T)
– Human primary chondrocytes
– HL-60 leukemia cells
– A172 and T98G glioblastoma cells
– Clonal preosteoblastic cell line MC3T3-E1-derived from newborn mouse calvaria
– Osteocyte-like MLO-Y4 cell line
– Preosteoclastic, macrophage-like RAW 264.7 cell line
– Primary HUVECs – human vascular endothelial cells
– MCF-7, T47D and MDA-MB-231 breast cancer cell lines
and many more..
Baseline Ang-2 plasma levels are an independent prognostic biomarker in refractory metastatic colorectal cancer
Chemorefractory is a term that is used to describe a cancer that does not respond to chemotherapy. Currently, no biomarkers are available to predict the efficacy of chemotherapy in chemorefractory metastatic colorectal cancer. Researchers from Italy have shown that circulating biomarker levels of Angiopoietin-2 (ANG2) increases early and predicts outcome with regorafenib but not with trifluridine/tipiracil treatment. Thus, baseline Ang-2 plasma levels are an independent prognostic biomarker in chemorefractory metastatic colorectal cancer. Read more: Early modulation of Angiopoietin-2 plasma levels predicts benefit from regorafenib in patients with metastatic colorectal cancer
Easy measurement of Angiopoietin-2 (ANG-2) in blood samples with only 20µl sample volume.
Check out the Biomedica ANGIOPOIETIN-2 (ANG2) ELISA kit
√ Full validation package – the assay is optimized for clinical samples
√ Kit includes ready to use standards and controls
√ HIGH QUALITY GUARANTEED
Related publications
Antoniotti C, Marmorino F, Boccaccino A, Martini S, Antista M, Rossini D, Zuco V, Prisciandaro M, Conca V, Zucchelli G, Borelli B, Cosentino P, Germani MM, Bosco MF, Carullo M, Vetere G, Moretto R, Giordano M, Masi G, Pietrantonio F, Zaffaroni N, Cremolini C. Eur J Cancer. 2022. 165:116-124. doi: 10.1016/j.ejca.2022.01.025. PMID: 35231767.
Abstract
Background: No biomarkers are currently available to predict the efficacy of trifluridine/tipiracil (FTD/TPI) in chemorefractory metastatic colorectal cancer. The multicohort REGOLAND study aims at exploring and validating circulating markers potentially able to predict benefit from regorafenib in this setting. Material and methods: In the retrospective ‘regorafenib exploratory cohort’, including 105 patients treated with regorafenib, baseline (d1) plasma levels of angiogenesis-related biomarkers and their early modulation after 15 days (d15) of treatment were investigated for correlation with clinical outcome. Based on a pre-specified statistical hypothesis, main retrospective findings were prospectively challenged in the ‘regorafenib validation cohort’, including 100 patients treated with regorafenib. Prospectively validated putative biomarkers were then assessed in the control ‘FTD/TPI cohort’, including 93 patients treated with FTD/TPI. Results: In the ‘regorafenib exploratory cohort’, the early (d15) increase of Angiopoietin-2 (Ang-2) was associated with longer progression-free survival (HR:0.57 [95%CI:0.38-0.88], P = 0.004) and a trend towards longer OS (HR:0.74 [95%CI:0.48-1.14], P = 0.165), than the early decrease. Similar results were prospectively confirmed in the ‘regorafenib validation cohort’ (HR for progression-free survival:0.72 [95%CI:0.48-1.08], P = 0.095; HR for OS:0.77 [95%CI:0.51-1.16], P = 0.204). No predictive impact was shown for the early modulation of Ang-2 in the ‘FTD/TPI cohort’. High baseline Ang-2 levels predict poor prognosis in all the investigated cohorts, independently of other clinical prognostic variables. Conclusions: The early modulation of circulating Ang-2 predicts the efficacy of regorafenib. Baseline Ang-2 plasma levels are an independent prognostic biomarker in chemorefractory metastatic colorectal cancer.
Angiopoietin-2 as a Prognostic Factor in Patients with Incurable Stage IV Colorectal Cancer.
Munakata S, Ueyama T, Ishihara H, Komiyama H, Tsukamoto R, Kawai M, Takahashi M, Kojima Y, Tomiki Y, Sakamoto K. J Gastrointest Cancer. 2021.52(1):237-242. PMID: 32166589.