Elevated serum growth differentiation factor 15 in multiple system atrophy patients:A case control study

BACKGROUND Multiple system atrophy(MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15(GDF15) is involved in the differentiation and progression of the central nervous system, and is widely distributed in peripheral blood, which may be a novel biomarker for MSA.AIM To determine serum GDF15 levels, related factors and their potential diagnostic value in MSA patients, compared with Parkinson’s disease(PD) patients and healthy controls.METHODS A case-control study was conducted, including 49 MSA patients, 50 PD patients and 50 healthy controls. Serum GDF15 levels were measured by human enzymelinked immunosorbent assay, and the differences between the MSA, PD and control groups were analyzed. Further investigations were performed in different MSA subgroups according to age of onset, sex, clinical subtypes, diagnostic criteria, and disease duration. Receiver-operating characteristic curve analysiswas used to evaluate the diagnostic value of GDF15, especially for the differential diagnosis between MSA and PD.RESULTS Serum GDF15 levels were significantly higher in MSA patients than in PD patients and healthy controls(P = 0.000). Males and those with a disease duration of more than three years showed higher serum GDF15 levels(P = 0.043 and 0.000;respectively). Serum GDF15 levels may be a potential diagnostic biomarker for MSA patients compared with healthy controls and PD patients(cutoff: 470.42 pg/m L, sensitivity: 85.7%, specificity: 88.0%;cutoff: 1075.91 pg/m L, sensitivity:51.0%, specificity: 96.0%;respectively).CONCLUSION Serum GDF15 levels are significantly higher in MSA patients and provide suggestions on the etiology of MSA.

Growth differentiation factor 15 as an emerging novel biomarker in SARS-CoV-2 infection

BACKGROUND Growth differentiation factor(GDF)-15 is a member of a transforming growth factor-βcytokine superfamily that regulates metabolism and is released in response to inflammation,hypoxia and tissue injury.It has evolved as one of the most potent cytokines for predicting the severity of infections and inflammatory conditions,such as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.AIM To investigate the utility of GDF-15 in predicting the severity of SARS-CoV-2 infection.METHODS PubMed,Reference Citation Analysis,CNKI,and Goggle Scholar were explored by using related MeSH keywords and data such as the first author’s name,study duration,type and place of study,sample size and subgroups of participants if any,serum/plasma GDF-15 level in pg/mL,area under the curve and cut-off value in receiver operating characteristic analysis,method of measurement of GDF-15,and the main conclusion were extracted.RESULTS In all studies,the baseline GDF-15 level was elevated in SARS-CoV-2-infected patients,and it was significantly associated with severity,hypoxemia,viral load,and worse clinical consequences.In addition,GDF-15 levels were correlated with C-reactive protein,D-dimer,ferritin and procalcitonin,and it had superior discriminatory ability to detect severity and in-hospital mortality of SARS-CoV-2 infection.Hence,GDF-15 might be used to predict the severity and prognosis of hospitalized patients with SARS-CoV-2.CONCLUSION Serial estimation of GDF-15 levels in hospitalized patients with SARS-CoV-2 infection appeared to have useful prognostic value and GDF-15 can be considered a clinically prominent sepsis biomarker for SARS-CoV-2 infection.

Association between plasma growth differentiation factor 15 levels and pre-eclampsia in China

Background Growth differentiation factor-15(GDF-15)is a stress response protein and is related to cardiovascular diseases(CVD).This study aimed to investigate the association between GDF-15 and pre-eclampsia(PE).Method The study involved 299 pregnant women,out of which 236 had normal pregnancies,while 63 participants had PE.Maternal serum levels of GDF-15 were measured by using enzyme-linked immunosorbent assay kits and then translated into multiple of median(MOM)to avoid the influence of gestational week at blood sampling.Logistic models were performed to estimate the association between GDF-15 MOM and PE,presenting as odd ratios(ORs)and 95%confidence intervals(CIs).Results MOM of GDF-15 in PE participants was higher compared with controls(1.588 vs.1.000,p<0.001).In the logistic model,pregnant women with higher MOM of GDF-15(>1)had a 4.74-fold(95%CI=2.23–10.08,p<0.001)increased risk of PE,adjusted by age,preconceptional body mass index,gravidity,and parity.Conclusions These results demonstrated that higher levels of serum GDF-15 were associated with PE.GDF-15 may serve as a biomarker for diagnosing PE.

Cardioprotective Effect of Growth Differentiation Factor 15 Against Isoproterenol-Induced Cardiomyocyte Apoptosis via Regulation of the Mitochondrial Fusion

Objective:Pressure overload-induced myocardial apoptosis is a critical pathologically initiated process leading to heart failure(HF).Growth differentiation factor 15(GDF15)dramatically increases during cardiac hypertrophy and dysfunction,but its functions and mechanisms are barely known.This study aims to elucidate the role and mechanism of GDF15 in HF.Methods:Between January 2017 and August 2018,57 patients diagnosed with chronic HF(aged>18 years,with left ventricular ejection fraction(LVEF)35%)and 57 non-HF patients(aged>18 years,LVEF>35%)were prospectively enrolled in this study based on the balance of the baseline characteristics.Other acute or chronic diseases and pregnant/lactating women were excluded.The serum concentrations of GDF15 were detected.Isoproterenol(ISO)-induced HF mouse model was established by pumping with ISO(30mg/(kg·day))for 4 weeks,and the GDF15 expression in serum and heart tissue was evaluated in vivo.Primary cardiomyocytes were cultured and treated with ISO to induce cardiomyocytes damage.The apoptosis of cardiomyocytes and the effect of GDF15 on ISO-induced cardiomyocytes injury was evaluated in vitro.Results:After adjusting the baseline characteristic,serum levels of GDF15 were significantly higher in HF subjects than in non-HF patients.Similarly,in the ISO-induced HF mouse model,the significant increase in GDF15 was associated with the process of HF in vivo.Moreover,the elevation of GDF15 occurred prior to heart remodeling in the ISO-induced HF mouse model.Furthermore,using primary cardiomyocytes,we demonstrated that the GDF15 was remarkably enhanced in serum from pathological HF patients and cardiac tissue from the ISO-induced mouse model.Reducing GDF15 exaggerated the ISO-induced cell apoptosis by blocking mitochondrial fusion and increasing oxidative stress.In contrast,the silence of GDF15 aggravated the ISO-induced cardiomyocytes damage.Conclusions:GDF15 acts as a protective factor against cardiomyocyte apoptosis by improving mitochondria fusion during HF.These findings indicate that GDF15 may be a potential therapeutic target for HF.

GDF-15 Level Correlates with CMKLR1 and VEGF-A in Tumor-free Margin in Colorectal Cancer

Colorectal cancer(CRC)is the third most frequently diagnosed cancer worldwide,responsible for over 880000 deaths each year.Growth/differentiation factor 15(GDF-15)is reported to be a promising diagnostic and prognostic factor in CRC.It induces pleiotropic effects in tumor cells:proliferation,sternness,invasion and metastasis.Some studies indicate that GDF-15 may stimulate angiogenesis in malignant neoplasms.However,it has not been investigated in CRC yet.The aim of our study was to determine the level of GDF-15 and the concentrations of hypoxia-inducible factor-la(HIF-1α),VEGF-A and chemokine-like receptor 1(CMKLR1)in tumor and margin specimens of CRC in relation to histological grade and TNM staging.The study comprised 33 samples of tumor and margin tissues obtained from CRC patients.To assess the concentration of GDF-15,HIF-1α,VEGF-A and CMKLR1,commercially available enzyme-linked immunosorbent assay(ELISA)kits were used.We found significantly increased levels of GDF-15 and CMKLR1 in tumor tissue compared to margin tissue and higher concentrations of HIF-1α and VEGF-A in margin tissue than in tumor tissue.The levels of GDF-15 and HIF-1α were significantly correlated with VEGF-A and CMKLR1 in margin tissue.In CRC,the increased level of GDF-15 might stimulate angiogenesis through upregulation of HIF-1α,VEGF A and CMKLR1 expression.Our study is the first one to reveal the correlation between the levels of GDF-15 and CMKLR1 in CRC.The elevated levels of HIF-1α and VEGF-A in tumor-free margin tissues suggest that noncancer cells in the tumor microenvironment are an important source of proangiogenic factors.

The energetics of cellular life transitions

Major life transitions are always difficult because change costs energy.Recent findings have demonstrated how mitochondrial oxidative phosphorylation(OxPhos)defects increase the energetic cost of living and that excessive integrated stress response(ISR)signaling may prevent cellular identity transitions during development.In this perspective,we discuss general bioenergetic principles of life transitions and the costly molecular processes involved in reprograming the cellular hardware/software as cells shift identity.The energetic cost of cellular differentiation has not been directly quantified,representing a gap in knowledge.We propose that the ISR is an energetic checkpoint evolved to(i)prevent OxPhos-deficient cells from engaging in excessively costly transitions and(ii)allow ISR-positive cells to recruit systemic energetic resources by signaling via GDF15 and the brain.