Serum fetuin-A Levels Research Articles

The role of Fetuin-A and Leucine-rich α-2-glycoprotein in the diagnosis of prostate cancer - a pilot study.

Prostate cancer (PC) is one of the most frequently diagnosed non-skin solid cancers and is a leading cause of cancer-related death and the incidence increasing. Early diagnosis of the disease improves the outcomes. There is an urgent need for new biomarkers with greater discriminative precision for diagnosis, risk-stratification and treatment. The aim of our study was to evaluate the diagnostic and prognostic potential of Fetuin-A and LRG1 in patients with PC. Serum levels of Fetuin-A and LRG1 were compared in patients with PC (n=46), a control group 1 including young, healthy subjects (n=26) and control group 2 including patients with negative prostate biopsy (n=46). In PC patients, the levels of both biomarkers were compared in subgroups with different tumour characteristics. We demonstrated a statistically significant higher concentrations of Fetuin-A in PC patients compared to control group 2 (439 mg/L vs. 372 mg/L), P<0.001. No statistically significant difference was found between PC patients and control group 1, nor for LRG1 levels between the three groups. In PC patients, higher serum levels of LRG1 were found in M1 patients compared to M0 (98 mg/L vs. 42 mg/L), P=0.059. Fetuin-A levels are significantly higher in patients with prostate cancer than in patients without malignancy but LRG1 levels do not differ between patients with PC and controls.

COVID-19 Recovery and Cardiovascular Health: The Interplay Between Fetuin-A and Blood Pressure.

COVID-19 has been shown to impair cardiovascular function, and further studies have proven that this effect can be long-term on several cardiovascular biomarkers. Fetuin-A, a multifunctional protein involved in calcification and inflammation, has emerged as an important biomarker in this process. This study investigates the relationship between recovery from COVID-19, cardiovascular health, and concentrations of fetuin-A in patients with high blood pressure. Seventy-nine men and 36 women were admitted to the Nasiriyah Heart Center in Iraq between March and August 2023, with ages ranging from 5 to 93 years. Clinical data were collected on admission along with blood samples, and serum levels of fetuin-A were measured using an enzyme-linked immunosorbent assay (ELISA). The results were analyzed using Python libraries Pandas and SciPy to perform independent sample t-tests to determine mean levels of fetuin-A in various patient subgroups. A p-value of less than 0.05 was considered statistically significant. The study showed that patients who had survived COVID-19 had significantly higher levels of fetuin-A compared to healthy controls, with a mean concentration of 103.64 mg/L versus 19.199 mg/L (p < 0.001). Additionally, it was found that patients with high blood pressure had increased levels of fetuin-A compared to those without high blood pressure, with a mean concentration of 109.01 mg/L versus 95.88 mg/L (p = 0.025). These results suggest that COVID-19 may alter the usual relationship between blood pressure and cardiovascular biomarkers. This study emphasizes the complex interaction between recovery from COVID-19 and cardiovascular health, primarily through the levels of fetuin-A. The increase in fetuin-A among hypertensive patients suggests that COVID-19 may enhance cardiovascular risk, highlighting the need for stricter monitoring and tailored treatment strategies. Further studies are needed to elucidate the underlying mechanisms, which will help develop effective clinical guidelines for managing cardiovascular health in COVID-19 survivors.

Enhanced Association of Novel Cardiovascular Biomarkers Fetuin-A and Catestatin with Serological and Inflammatory Markers in Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with increased cardiovascular disease (CVD) risk and mortality. This work aimed to evaluate the serum levels of the novel CV biomarkers fetuin-A (fet-A), Dickkopf-1 (DKK-1), galectin-3 (Gal-3), interleukin-32 (IL-32), and catestatin (CST) in RA patients and their associations with RA parameters and CVD markers. A cohort of 199 RA patients was assessed for traditional CVD risk factors, RA disease activity, and biomarker levels. Carotid ultrasound was used to measure carotid intima-media thickness (cIMT) and carotid plaque presence (cPP). Multivariate analyses examined correlations between biomarkers and RA parameters, serological markers, and CVD markers. Adjusted models showed that elevated CST expression levels were associated with rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) positivity (OR = 2.45, p = 0.0001 and OR = 1.48, p = 0.04, respectively) in the overall cohort and for RF in men and women, respectively. In addition, fet-A concentration was inversely associated with the erythrocyte sedimentation rate (ESR) in the overall cohort (β = -0.15, p = 0.038) and in women (β = -0.25, p = 0.004). Fet-A levels were also negatively correlated with disease activity (DAS28-ESR) scores (β = -0.29, p = 0.01) and fibrinogen concentration (β = -0.22, p = 0.01) in women. No adjusted associations were observed for Gal-3, DKK-1 or IL32 concentration. The study revealed no significant associations between the biomarkers and cIMT or cPP. The measurement of CST and fet-A levels could enhance RA patient management and prognosis. However, the utility of biomarkers for evaluating CV risk via traditional surrogate markers is limited, highlighting the need for continued investigations into their roles in RA.

Serum level of fetuin-A as a biomarker for vascular complications and severity of insulin resistance in individuals with type 2 diabetes

Serum level of fetuin-A as a biomarker for vascular complications and severity of insulin resistance in individuals with type 2 diabetes

Effect of rosuvastatin on sortilin and fetuin-A in type 2 diabetic patients: a randomized controlled trial

Abstract Objective Rosuvastatin is a drug used for decreasing the risk of cardiovascular complications in type 2 diabetes mellitus (T2DM) patients. It is hypothesized that fetuin-A encourages lipid-induced insulin resistance and sortilin may increase the risk of atherosclerotic-related disorders. The aim of this study is to investigate the safety and efficacy of rosuvastatin co-treatment in T2DM patients and its effect on levels of sortilin and fetuin-A. Methods Seventy T2DM patients treated with glimepiride and metformin were randomly assigned to either co-treated with rosuvastatin 10 mg tablets (rosuvastatin group, n = 40), or placebo (placebo group, n = 30) daily for 3 months in a parallel, double-blind randomized controlled trial. Blood was collected for biochemical analysis. Serum sortilin and fetuin-A levels, glycemic and lipid profiles were measured before and 3 months after intervention. Results Fasting blood glucose (FBG, mg/dl) significantly decreased in placebo and rousvastatin groups from (104 ± 7.24 to 96.67 ± 7.14 vs 102.8 ± 6.43 to 93.0 ± 4.71), respectively, compared with baseline (p &lt; 0.05). BMI and HbA1c decreased in placebo vs rosuvastatin group (29.20 ± 3.18 to 28.10 ± 3.08, p=0.08 vs 28.67 ± 3.56 to 27.66 ± 3.16, p = 0.27), and (6.59 ± 0.27 to 6.36 ± 0.27 vs 6.56 ± 0.26 to 6.29 ± 0.25), respectively, compared with baseline (p ≤ 0.001) with no significance difference between both groups (p = 0.58 and p = 0.25, respectively). Sortilin and fetuin-A levels significantly decreased in rosuvastatin vs placebo group from (1.77 ± 0.41 to 0.64 ± 0.37 vs 1.70 ± 0.36 to 1.65 ± 0.36) and from (295.33 ± 52.04 to 179.75 ± 60.22 vs 307.22 ± 50.11 to 288.94 ± 49.53), respectively, compared with baseline with significance difference between both groups (p &lt; 0.001) compared with placebo. Significant positive correlation was found between sortilin with fetuin-A, low-density lipoprotein (LDL-C), and atherogenic index (p &lt; 0.001). Significant positive correlation was observed between fetuin-A with FBG (p &lt; 0.05) and atherogenic index (p &lt; 0.001). Conclusion Rosuvastatin co-treatment in T2DM patients improves glycemic control and aids in decreasing the atherogenic biomarkers sortilin and fetuin-A levels, so it can be considered tolerable and efficient in improving lipid profile and atherogenic index. Trial registration ClinicalTrials.gov identifier (NCT number): NCT03907423, (The registration date: April 9, 2019). https://clinicaltrials.gov/ct2/show/NCT03907423.

Exercise training improves diabetic renal injury by reducing fetuin-A, oxidative stress and inflammation in type 2 diabetic rats

BackgroundDiabetic kidney disease (DKD) stands as a primary contributor to end-stage renal disease, associated with heightened mortality in cardiovascular diseases. This study aimed to explore the impact of an eight-week high-intensity interval training (HIIT) on renal injury in diabetic rats. MethodsTwenty-eight male Wistar rats were randomly allocated into four groups: healthy control (CTL), diabetic control (DC), exercise (EX), and diabetes-exercise (D + EX). Induction of diabetes in the DC and D + EX groups occurred through a two-month high-fat diet followed by a single dose of 35 mg/kg streptozotocin (STZ). Rats in the EX and D + EX groups underwent 4–10 intervals of HIIT (80–100% Vmax) over 8 weeks. Subsequently, pathological and biochemical parameters were assessed in the serum and kidney tissue of the experimental groups. ResultsIn the DC group, diabetes led to elevated kidney damage, glomerulosclerosis, fasting blood glucose (FBG), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index, animal weight, kidney dysfunction, albuminuria, and glomerular filtration rate. Additionally, serum and kidney levels of fetuin-A increased, along with kidney levels of KIM-1. Mechanistically, diabetes induction resulted in kidney inflammation by elevating levels of tumor necrosis factor-alpha (TNF-α), transforming growth factor beta (TGF-β), and interleukin 6 (IL-6), while reducing IL-10 levels and increasing the IL-6/IL-10 ratio. Furthermore, diabetes triggered renal oxidative stress, evidenced by increased Malondialdehyde (MDA) levels and decreased levels of glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD). HIIT mitigated the adverse effects of diabetes in the D + EX group compared to the DC group. ConclusionOur findings suggest that HIIT ameliorates type 2 diabetes (T2D)-induced kidney damage by mitigating inflammation, lowering serum levels of fetuin-A, and bolstering antioxidant defenses. This study highlights the potential of HIIT as a time-efficient intervention for diabetic nephropathy.

Serum fetuin-a and risk of thoracic aortic aneurysms: a two-sample mendelian randomization study.

Recent studies have revealed a significant decrease in serum fetuin-A levels in atherosclerotic aneurysms, indicating that fetuin-A may play a protective role in the progression of arterial calcification. However, the specific mechanism behind this phenomenon remains unclear. We aimed to examine the association between fetuin-A levels in thoracic aortic aneurysms (TAAs) and risk of TAAs and to evaluate whether this association was causal. A total of 26 SNPs were selected as instrumental variables for fetuin-A in 9,055 participants of European ancestry from the CHARGE consortium, and their effects on thoracic aortic aneurysm and decreased descending thoracic aortic diameter were separately estimated in 353,049 and 39,688 individuals from FinnGen consortium. We used two-sample Mendelian randomization (MR) analysis to examine the causal association. At the same time, we employed various methods, including random-effects inverse variance weighting, weighted median, MR Egger regression, and MR PRESSO, to ensure the robustness of causal effects. We assessed heterogeneity using Cochran's Q value and examined horizontal pleiotropy through MR Egger regression and retention analysis. Fetuin-A level was associated with a significantly decreasing risk of thoracic aortic aneurysm (odds ratio (OR) 0.64, 95% CI 0.47 - 0.87, P = 0.0044). Genetically predicted fetuin-A was also correlated with the decreased descending thoracic aortic diameter (β = -0.086, standard error (SE) 0.036, P = 0.017). Serum fetuin-A level was negatively associated with risk of TTAs and correlated with the decreased descending thoracic aortic diameter. Mendelian randomization provides support for the potential causal relationship between fetuin-A and thoracic aortic aneurysm.

Diabetes mellitus modifies the association between chronic kidney disease-mineral and bone disorder biomarkers and aortic stiffness in peritoneal dialysis patients.

This study aimed to investigate the relationship of four chronic kidney disease-mineral and bone disorder (CKD-MBD) biomarkers, including intact parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), soluble klotho, and fetuin-A, with aortic stiffness in peritoneal dialysis (PD) patients, comparing those with and without diabetes mellitus (DM). A total of 213 patients (mean age 58 ± 14years; 81 (38.0%) patients with DM) were enrolled. Their aortic pulse wave velocity (PWV) was measured using pressure applanation tonometry, while serum intact PTH, FGF23, α-klotho, and fetuin-A levels were measured using enzyme-linked immunosorbent assay. Overall, patients with DM had higher aortic PWV than those without (9.9 ± 1.8 vs. 8.6 ± 1.4m/s, p < 0.001). Among the four CKD-MBD biomarkers, FGF23 levels were significantly lower in DM group (462 [127-1790] vs. 1237 [251-3120] pg/mL, p = 0.028) and log-FGF23 independently predicted aortic PWV in DM group (β: 0.61, 95% confidence interval: 0.06-1.16, p = 0.029 in DM group; β: 0.10, 95% confidence interval: - 0.24-0.45, p = 0.546 in nonDM group; interaction p = 0.016). In conclusion, the association between FGF23 and aortic PWV was significantly modified by DM status in PD patients.

Assessing the clinical and biochemical efficacy of alpha-lipoic acid in patients with non-alcoholic fatty liver disease: A randomized placebo-controlled clinical trial

Given the importance of inflammatory and metabolic markers in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), this study was designed to evaluate the effects of alpha-lipoic acid (ALA) supplementation on inflammatory and serum levels of fetuin-A, sirtuin1 (SIRT-1), cytokeratin 18 (CK-18), and hepatic steatosis in patients with NAFLD. In a double-blind, placebo-controlled, randomized clinical trial, 50 patients with NAFLD were randomized to receive daily supplementation with either two capsules of ALA (each capsule containing 600 mg ALA plus 400 mg/day of vitamin E) or two placebo capsules (two placebo capsules plus 400 mg/day of vitamin E) for 12 weeks. Significant reductions in homeostasis model assessment for insulin resistance (HOMA-IR) score and serum levels of insulin and fetuin-A were observed in the ALA group compared to the placebo group (all P < 0.05). ALA supplementation was significantly more effective than placebo in reducing hepatic steatosis by at least one grade.

Serum Levels of Fetuin-A, Ischemia-modified Albumin (IMA), and Ferritin in Hospitalized patients with severe COVID-19. A Case-control Study

Objective: To measure the serum levels of Fetuin-A, ischemia-modified albumin (IMA), and ferritin in hospitalized patients with severe COVID-19in Baghdad, Iraq. Moreover, to determine these biomarkers' cut-off valuesthat differentiate between severely ill patients and control subjects. Methods: This case-control study was done from 15 September to the end of December 2021 and involved a review of the files and collectionof blood samples from patients (n=45, group1) hospitalized in COVID-19 treatment centersbecause of severe symptoms compared tohealthy subjects as controls (n=44, group2). Results: Fetuin-A serum levels were not statistically different between patients and controls. In contrast, IMA and ferritin levels were significantly different between the 2 groups, with patients' levelsbeing greater than control participants' (p 0.05). The critical values for the Fetuin-A, IMA, and ferritin tests were 393.78 mg/L, 59.22 ng/ml, and 126 µg/L, respectively, with concentration curves of 0.58, 0.70, and 0.93 for each. Conclusions: Patients and controls showed no significant difference in Fetuin-A levels in the blood. However, IMA and ferritin levels werehigher in people suffering from acute COVID-19 infection than in controls, with Fetuin-A values less than 393.78 mg/L andIMA and ferritin valueshigher than 59.22 ng/mland 126,000 μg/L, respectively.

The Relationship of Fetuin-A with Coronary Calcification, Carotid Atherosclerosis, and Mortality Risk in Non-Dialysis Chronic Kidney Disease.

This study investigated the relationship of fetuin-A with coronary calcification, carotid atherosclerosis, and mortality risk in non-dialysis chronic kidney disease (CKD). The study included 135 adult patients with CKD at stages 3-5, who were divided into coronary artery calcification (CAC) and non-CAC groups. We excluded current smokers and individuals with diabetes mellitus, inflammatory conditions, liver diseases, acute kidney failure, chronic hemodialysis, and cancer. We conducted kidney function tests, complete blood counts, and measured serum levels of fetuin-A, tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), total cholesterol (TC), total triglycerides (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. Cardiac spiral computed tomography was used to calculate the CAC score, employing the Agatston method. Carotid ultrasonography was performed to assess carotid intima-media thickness (CIMT) and to detect the presence of plaques. CAC patients had considerably higher levels of TNF-α (p<0.001), IL-6 (p<0.001), hs-CRP (p=0.006), TC, TG, parathyroid hormone (PTH) (p<0.001) and phosphorus (p<0.001) than non-CAC patients. They also had significantly lower levels of fetuin-A (p<0.001). Fetuin-A was considerably lower in CKD subgroups as CKD progressed. Fetuin-A (p=0.046), age (p=0.009), TNF-α (p=0.027), IL-6 (p=0.005), TG (p=0.002), PTH (p=0.002), and phosphorus (p=0.004) were significant predictors of CAC. CAC and fetuin-A were strong predictors of all-cause mortality and cardiovascular (CV) mortality. Fetuin-A was a significant predictor of CIMT (p=0.045). Fetuin-A reliably predicted CAC and CIMT. Fetuin-A and CAC emerged as significant risk factors for all-cause and CV mortality in non-dialysis CKD.

Pigment epithelium-derived factor (PEDF) represses the glucose transporter 1 (GLUT1) mRNA expression and may be a potential therapeutic agent in psoriasis: a case–control and experimental study

We investigated the whole blood GLUT1 mRNA expression and serum pigment epithelium-derived factor (PEDF), interleukin-6 (IL-6), fetuin-A, and pentraxin-3 (PTX3) levels in psoriatic patients and tested their correlations with the severity of psoriasis using the psoriasis area and severity index (PASI) score. Also, we tested the GLUT1 mRNA expression after an in vitro treatment of human skin fibroblast (HSF) cell lines with PEDF. The case–control part of the study recruited 74 participants (44 psoriatic patients and 30 healthy volunteers). Whole blood GLUT1 mRNA fold changes were estimated by RT-PCR, and serum PEDF, IL-6, fetuin-A, and PTX3 levels were measured by ELISA kits. In the experimental part, the HSF cell lines were treated with different concentrations of PEDF for different times to test its effect on the GLUT1 mRNA expression. The whole blood GLUT 1 expression significantly increased in psoriatic patients and correlated positively with serum IL-6, fetuin-A, PTX3 levels and with the severity of psoriasis while negatively with serum PEDF levels. The PEDF-treated HSF cell lines showed a time- and dose-dependent decline in the GLUT 1 mRNA expression. The whole blood GLUT 1 mRNA is a non-invasive biomarker that is associated with the severity of psoriasis. PEDF represses GLUT 1 expression and may be a potential therapeutic agent in psoriasis.Trial registration: ClinicalTrials.gov Identifier: NCT04242082.

Relationship of serum Fetuin-A with metabolic and vascular parameters in patients with prediabetes and type 2 diabetes mellitus

Background: Fetuin-A is a multifunctional liver-derived glycoprotein that is associated with insulin resistance and might play a role in the pathogenesis of prediabetes and type 2 diabetes (T2DM). Objective: This study evaluated the relationship of Fetuin-A with metabolic and vascular parameters in patients with prediabetes and T2DM. Materials and methods: total 120 obese patients were included. They were divided into three groups: group 1 – without carbohydrate disturbances, group 2 – with prediabetes and group 3 – with type 2 diabetes mellitus. Results: Higher Fetuin-A serum levels were observed in patients with prediabetes and T2DM compared to those with normoglycemia. Fetuin-A ≥821 mcg/ml increased the risk for T2DM 32-fold. Additionally, we found positive correlations between Fetuin-A, vibration perception threshold and toe-brachial index and a negative correlation with neuropathy disability score. Conclusion: Fetuin-A could be predictive for incidents of prediabetes and T2DM.

The antagonistic relationship of fetuin-A and adiponectin in obese type 2 diabetes mellitus

Fetuin-A and adiponectin display noteworthy affiliations, bolstered by recent prove, with metabolic disorder, obese type 2 diabetes including hyperglycemia, central weight and insulin resistance as the most components, but their natural capacities are inverse. The point of this consider was to confirm the role of fetuin-A and adiponectin are the touchy marker for assessment of obese type 2 diabetes.In this analytical cross-sectional study, 100 control and patients were chosen from the physical examination database. Serum levels of fetuin-A and adiponectin were measured utilizing an enzyme-linked immunosorbent measure (ELISA) method. The Statistical software namely SAS 9.2, SPSS 15.0, Stata10.1, MedCalc 9.0.1 , Systat 12.0 and R environment ver.2.11.1 were used for the analysis of the data and Microsoft word and Excel have been used to generate graphs, tables etc.Compared with fetuin-A or adiponectin was significantly associated with obese type 2 diabetes mellitus (P &amp;#60; 0.001). Fetuin-A or adiponectin are antagonistic linked with each other in obese type 2 diabetes mellitus

Effect of Fetuin-A and oxidative stress on the occurrence of unexplained infertility.

Unexplained infertility refers to a diagnosis in which all standard examinations are usually normal and is statistically seen in approximately 30-40% of infertile couples and endometriosis encountered in 25-50% of patients with unexplained infertility. Unexplained infertility is thought to be closely associated with endometriosis and serum and peritoneal fluid levels of Fetuin-A is increased in patients with endometriosis. Fetuin-A is proposed as a diagnostic marker for endometriosis and has anti-inflammatory effects on several diseases. Oxidative stress also is central to the etiopathogenesis of infertility in women. The aim of this study was to evaluate serum Fetuin-A and oxidative stress parameter concentrations impact on unexplained infertility. In the study, serum Fetuin-A, IL-1β, CA I, TAS, TOS levels, and PON and ARE enzyme activities were measured using the Enzyme-Linked ImmunoSorbent Assay in the sera of diagnosed unexplained infertility females (n=44) and controls (n=41). There was no statistically significant difference between unexplained infertile patients and control groups in terms of serum IL-1β, CA I, OSI, and PON levels (p>0.05). Serum Fetuin-A and ARE levels were significantly higher in unexplained infertility compared with the control, whereas serum TAS and TOS levels were lower (p<0.05, p<0.01, p<0.05, p<0.05, respectively). It is thought that increased Fetuin-A levels may be a response to the inflammatory process and increased ARE activity may be a sign of the impaired oxidant-antioxidant balance in unexplained infertility. This may contribute to the pathogenesis of infertility, and the data obtained will make a significant contribution to new works to be done in this sense.

The usability of MCP-1, fetuin-A, TAS, and TOS levels in the diagnosis of acute myocardial infarction.

Our aims were to determine whether the levels of plasma monocyte chemotactic protein-1 (MCP-1), fetuin-A, serum total antioxidant status (TAS), and serum total oxidant status (TOS) are cardiac biomarkers and to clarify their relationship with each other in acute myocardial infarction (AMI). The study included 90 participants: 60 patients with AMI [30 with and 30 without ST-segment elevation myocardial infarction (STEMI)] and 30 cardiac patients without AMI. The diagnostic values of serum Hs-cTnT, MCP-1, fetuin-A, TAS, and TOS levels in predicting AMI were evaluated statistically. Median levels of MCP-1 [120.10 ng/L (interquartile range: 76.94-230.54 ng/L)] and TOS [2.89 U/MI (IQR: 2.31-3.94 U/Ml)] were statistically higher, and median levels of fetuin-A [433.52 mg/L (IQR: 387.89-584.49 mg/L)] and TAS (3.10 ± 0.86 U/mL) were lower in patients with AMI than in controls. The parameter with the area under the curve (0.815), sensitivity (73.3%), and specificity (66.7%) closest to those of Hs-cTnT was fetuin-A, followed by MCP-1, TOS, and TAS, respectively. A one-unit increase in MCP-1 levels increased the probability of AMI by 1.023 times (p = 0.002). A one-unit increase in fetuin-A levels decreased the probability of AMI by 0.995 times (p = 0.003). A one-unit increase in serum TOS levels was 1.29 times more characteristic of STEMI than of NSTEMI (p = 0.044). MCP-1, oxidative stress parameters, and fetuin-A might support Hs-cTnT levels in the early diagnosis of AMI. Fetuin-A and MCP-1 levels may be independent risk factors for AMI, whereas TOS could be used to distinguish STEMI from NSTEMI.

Can Fetuin-A Deficiency Predict the Severity of COVID-19 Disease in Kidney Transplant Recipients?

BackgroundThis study aims to investigate whether fetuin A deficiency predicts the prognosis of COVID-19 disease in kidney transplant recipients (KTRs). MethodThe study was conducted on 35 hospitalized KTRs with COVID-19 pneumonia between November 2020 and June 2021. Serums were collected for fetuin-A measurement at admission and after six months of follow-up. The demographic and laboratory data of the patients were recorded and analyzed with the appropriate statistical method. ResultsA total of 35 KTRs, 23 of which (65.7%) were men, were included in the study. The mean age of the patients was 51.6 ± 14.0 years. Seventeen (48.6%) patients had severe disease criteria and required intensive care (ICU) support. Biopsy-proven acute rejection developed in 6 (17.1%) patients in the follow-up. At admission, the median fetuin-A value was 173.5 mcg/mL (143.5-199.25) in the moderate disease group and 126.0 mcg/mL (89.4-165.5) in the severe patient group (p = 0.005). While the Median fetuin-A value at the time of diagnosis was 173.5 mcg/mL (143.5-199.25), and in the 6th month was 208 mcg/mL [184-229] (p<0.001). By ROC analysis, the effect of serum fetuin-A level in predicting the severity of COVID-19 disease was significant (AUC: 0.771, p = 0.006, 95% CI: 0.615-0.927). When serum fetuin-A cut-off value was taken as 138 mcg/mL to determine disease severity, it was shown to have 83.3% sensitivity and 64.7% specificity. ConclusionsSerum fetuin-A level can predict disease severity in kidney transplant recipients in the presence of active COVID-19 disease.

Increased UHMWPE Particle-Induced Osteolysis in Fetuin-A-Deficient Mice.

Particle-induced osteolysis is a major cause of aseptic prosthetic loosening. Implant wear particles stimulate tissue macrophages inducing an aseptic inflammatory reaction, which ultimately results in bone loss. Fetuin-A is a key regulator of calcified matrix metabolism and an acute phase protein. We studied the influence of fetuin-A on particle-induced osteolysis in an established mouse model using fetuin-A-deficient mice. Ten fetuin-A-deficient (Ahsg−/−) mice and ten wild-type animals (Ahsg+/+) were assigned to test group receiving ultra-high molecular weight polyethylene (UHMWPE) particle implantation or to control group (sham surgery). After 14 days, bone metabolism parameters RANKL, osteoprotegerin (OPG), osteocalcin (OC), alkaline phosphatase (ALP), calcium, phosphate, and desoxypyridinoline (DPD) were examined. Bone volume was determined by microcomputed tomography (μCT); osteolytic regions and osteoclasts were histomorphometrically analyzed. After particle treatment, bone resorption was significantly increased in Ahsg−/− mice compared with corresponding Ahsg+/+ wild-type mice (p = 0.007). Eroded surface areas in Ahsg−/− mice were significantly increased (p = 0.002) compared with Ahsg+/+ mice, as well as the number of osteoclasts compared with control (p = 0.039). Fetuin-A deficiency revealed increased OPG (p = 0.002), and decreased levels of DPD (p = 0.038), OC (p = 0.036), ALP (p < 0.001), and Ca (p = 0.001) compared with wild-type animals. Under osteolytic conditions in Ahsg−/− mice, OPG was increased (p = 0.013), ALP (p = 0.015) and DPD (p = 0.012) were decreased compared with the Ahsg+/+ group. Osteolytic conditions lead to greater bone loss in fetuin-A-deficient mice compared with wild-type mice. Reduced fetuin-A serum levels may be a risk factor for particle-induced osteolysis while the protective effect of fetuin-A might be a future pathway for prophylaxis and treatment.

Ethyl palmitate ameliorates lethal endotoxemia by inducing hepatic fetuin-A secretion: an in vivo and in vitro experiment.

Ethyl palmitate (EP) is known to promote hepatic fetuin-A production and modulate inflammatory responses, but its potential role in lethal endotoxemia and sepsis remains unclear. This study investigates the plasma fetuin-A levels and further evaluates the impact of hepatic fetuin-A induced by EP on systemic inflammation and macrophage polarization in lethal endotoxemia and sepsis. Blood samples from 55 sepsis patients and 18 non-septic controls with similar age and sex ratio were collected to perform proteomic analyses and identify significantly different proteins. Serum fetuin-A levels in lipopolysaccharide (LPS) induced endotoxemia mice were assayed by enzyme-linked immunosorbent assay (ELISA). The mouse hepatocyte cell (AML-12) was exposed to different concentrations of EP. In vivo experiments were conducted in which adult male C57BL/6J mice were given EP with or without intraperitoneal LPS. Fetuin-A was determined via western blot and immunohistochemical staining. Survival rates, lung and liver injury and levels of pro-inflammatory cytokines were also monitored and assessed using histology, real-time quantitative polymerase chain reaction (RT-qPCR) and ELISA. Additionally, the proportion of macrophages and M1/M2 subtypes in the lung and liver tissues were evaluated by flow cytometry. Our proteomic results revealed that the plasma fetuin-A levels were significantly decreased in sepsis patients compared with non-septic controls. Similarly, the serum fetuin-A levels were also reduced in endotoxemia mice compared with the control group. EP effectively promoted the production of fetuin-A in AML-12 cells and murine liver tissues. Subsequently, activation of fetuin-A by EP dramatically reduced LPS-induced murine mortality, alleviated lung and liver injury, down-regulated pro-inflammatory mediators and macrophage infiltration. Furthermore, EP regulated macrophage polarization from the M1 (CD45+CD11b+F4/80+CD86+) to the M2 (CD45+CD11b+F4/80+CD206+) subtype in murine liver tissue. EP-induced production of fetuin-A prevents sepsis and endotoxemia progression by promoting M2 polarization of macrophages.

Assessment of serum fetuin-A and its gene polymorphism as a marker of insulin resistance in polycystic ovary syndrome

Background/aim Polycystic ovary syndrome (PCOS) is a prevalent endocrine condition affecting 5–10% of reproductive-aged women, the cause of which is unknown. Chronic anovulation, polycystic ovaries, and hyperandrogenism are symptoms of PCOS. It is linked to hirsutism, obesity, and increased probability of cardiovascular disease, metabolic syndrome, and diabetes mellitus. A risk factor for cardiovascular disease is PCOS that is undiagnosed or untreated. Our aim in this study is to investigate serum fetuin-A level and its gene as potential biomarkers for screening of insulin resistance in PCOS. Patients and methods This study involved 100 female participants from outpatient clinic, Department of Obstetrics and Gynecology, Zagazig University Hospital, Egypt. They were split into two groups (each 50). The first group included healthy fertile women without symptoms of hyperandrogenemia as a control. The second group included women with PCOS. Fasting blood sugar levels, cholesterol, high-density lipoprotein cholesterol and triglycerides have been estimated by enzymatic colorimetric technique while low-density lipoprotein cholesterol was calculated. Enzyme-linked immunosorbent assays have been used to measure serum concentrations of luteinizing hormone, follicular-stimulating hormone, testosterone, and fetuin-A, while PCR has been used to extract DNA and genotype common functional polymorphisms in fetuin-A. Results The present results revealed a considerable rise in glucose, insulin, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), cholesterol, triglyceride, low-density lipoprotein cholesterol, luteinizing hormone, testosterone, and fetuin-A and significant decrease in follicular-stimulating hormone and high-density lipoprotein cholesterol in PCOS patients. Also, there was significant higher frequency of the fetuin-A gene variant rs1071592 AA genotype and A allele compared to controls. Conclusions Fetuin-A has a potential diagnostic value as a biomarker for insulin resistance in PCOS associated with metabolic syndrome. Additionally, ‘CG’ allele can be considered a risk factor for PCOS.