Global O-glycoproteome enrichment and analysis enabled by a combinatorial enzymatic workflow.

A comprehensive analysis of site-specific protein O-glycosylation is hindered by the absence of a consensus O-glycosylation motif, the diversity of O-glycan structures, and the lack of a universal enzyme that cleaves attached O-glycans. Here, we report the development of a robust O-glycoproteomic workflow for analyzing complex biological samples by combining four different strategies: removal of N-glycans, complementary digestion using O-glycoprotease (IMPa) with/without another protease, glycopeptide enrichment, and mass spectrometry with fragmentation of glycopeptides using stepped collision energy. Using this workflow, we cataloged 474 O-glycopeptides on 189 O-glycosites derived from 79 O-glycoproteins from human plasma. These data revealed O-glycosylation of several abundant proteins that have not been previously reported. Because many of the proteins that contained unannotated O-glycosylation sites have been extensively studied, we wished to confirm glycosylation at these sites in a targeted fashion. Thus, we analyzed selected purified proteins (kininogen-1, fetuin-A, fibrinogen, apolipoprotein E, and plasminogen) in independent experiments and validated the previously unknown O-glycosites.

Reduced hip bone mineral density is associated with high levels of calciprotein particles in patients with Fabry disease.

Calciprotein particles (CPP) are nanoscale mineralo-protein aggregates that help stabilize excess mineral in the circulation. We examined the relationship between CPP and bone mineral density in Fabry disease patients. We found an inverse correlation with total hip and femoral neck density, but none with lumbar spine. PURPOSE: Calciprotein particles (CPP) are colloidal mineral-protein complexes made up primarily of the circulating glycoprotein fetuin-A, calcium, and phosphate. They form in extracellular fluid and facilitate the stabilization, transport, and clearance of excess minerals from the circulation. While most are monomers, they also exist in larger primary (CPP-I) and secondary (CPP-II) form, both of which are reported to be raised in pathological states. This study sought to investigate CPP levels in the serum of patients with Fabry disease, an X-linked systemic lysosomal storage disorder that is associated with generalized inflammation and low bone mineral density (BMD). METHODS: We compared serum CPP-I and CPP-II levels in 59 patients with Fabry disease (37 female) with levels in an age-matched healthy adult cohort (n=28) and evaluated their association with BMD and biochemical data obtained from routine clinical review. RESULTS: CPP-I and CPP-II levels were higher in male Fabry disease patients than female sufferers as well as their corresponding sex- and age-matched controls. CPP-II levels were inversely correlated with BMD at the total hip and femoral neck, but not the lumbar spine. Regression analyses revealed that these associations were independent of common determinants of BMD, but at the femoral neck, a significant association was only found in female patients. CONCLUSION: Low hip BMD was associated with high CPP-II in patients with Fabry disease, but further work is needed to investigate the relevance of sex-related differences and to establish whether CPP measurement may aid assessment of bone disease in this setting.

Does fetuin-A mediate the association between pro-inflammatory diet and type-2 diabetes mellitus risk? / ¿Fetuína-A media en la asociación entre la dieta proinflamatoria y el riesgo de diabetes mellitus tipo 2?

Introduction: recent studies indicate that diet increases T2DM risk via inflammation. Fetuin-A, identified as an acute-phase protein, plays a role in insulin resistance and is an independent predictor of type-2 diabetes. Objectives: the present study aimed to examine the association between diet and T2DM risk, and whether said association is mediated by fetuin-A, and to determine the effect of fetuin-A on T2DM risk. Methods: the case group included 40 individuals with T2DM, whereas 40 individuals without T2DM comprised the control group. The Dietary Inflammatory Index (DII), was used to determine the inflammatory potential of diet. A simple mediation analysis was used to investigate whether diet was associated with T2DM risk and whether the association was mediated by fetuin-A. Results: subjects who consumed a high pro-inflammatory diet had 2.0 times higher risk of developing T2DM (OR = 2.043; 95 % CI: 0.955 to 4.371, p = 0.066). In addition, subjects who had higher levels of fetuin-A had a 1,2 times higher risk of developing T2DM (OR = 1.155; 95 % CI: 1.030 to 1.296, p = 0.014). Both fetuin-A and hs-CRP had a significant full mediator role on the association between DII and HOMA-IR [respectively; β = 0.371 (95 % CI: -0.029-0.770), β = 0.424 (95 % CI: -0.007-0.856)]. Conclusion: these findings suggest that a pro-inflammatory diet, by creating an environment of increased inflammatory markers, affects in particular insulin resistance through these markers and ultimately causes T2DM. In addition, fetuin-A also acts as an important novel mediator between diet and T2DM by inducing insulin resistance (AU)

Introducción: estudios recientes indican que la dieta aumenta el riesgo de T2DM mediante la inflamación. La fetuína-A,identificada como proteína de fase aguda, desempeña un papel en la resistencia a la insulina y es un predictor independiente de la diabetes de tipo 2. Objetivos: el presente estudio pretende examinar la asociación entre la dieta y el riesgo de DMT2 y si la asociación está mediada por la fetuína-A y determinar el efecto de la fetuína-A sobre el riesgo de DMT2. Métodos: en el grupo de casos se incluyeron 40 individuos con DMT2, mientras que 40 individuos sin DMT2 se incluyeron en el grupo de control. El índice de inflamación de la dieta (DII) se usó para determinar el potencial inflamatorio de la dieta. El análisis de mediación simple se usó para investigar si la dieta estaba asociada con el riesgo de DMT2 y si la asociación estaba mediada por la fetuína-A. Resultados: los sujetos que consumieron una dieta más proinflamatoria tuvieron 2 veces más riesgo de desarrollar DMT2. Además, los sujetos que tenían niveles más altos de fetuína-A tuvieron 1,2 veces más riesgo de desarrollar DMT2. Tanto la fetuína-Acomo la hs-CRP tuvieron un papel significativo como mediadores completos sobre la asociación entre DII y HOMA-IR. Conclusión: estos hallazgos sugieren que la dieta proinflamatoria, al crear un ambiente con marcadores inflamatorios aumentados, afecta en particular a la resistencia a la insulina a través de estos marcadores y, finalmente, causa DMT2. Además, la fetuína-A también actúa como mediador novedoso importante entre la dieta y la DMT2 al inducir la resistencia a la insulina (AU)

Lower Serum Fetuin-A Levels are Associated with a Higher Ten-Year Mortality Risk in Patients with ST-Elevation Myocardial Infarction. / Níveis mais Baixos de Fetuína-A Sérica estão Associados a um Maior Risco de Mortalidade em Dez Anos em Pacientes com Infarto do Miocárdio por Supradesnivelamento do Segmento ST.

BACKGROUND: Fetuin-A is an anti-inflammatory and anti-calcification factor involved in the course of coronary artery disease (CAD). In line with these functions, fetuin-A has been investigated as a cardiovascular risk marker in many studies. However, the association between fetuin-A and the prognosis of CAD patients is still controversial. OBJECTIVES: The present study was conducted to identify the association between serum fetuin-A level and long-term cardiovascular disease (CVD) and all-cause mortality of ST-elevation acute myocardial infarction (STEMI). METHODS: One hundred eigthy consecutive patients with STEMI were enrolled in the study. The study population was divided into subgroups (lower, ≤288 µg/ml; and higher, >288 µg/ml) according to the median fetuin-A level. Clinical follow-up data was obtained by annual contact with the patients or family members by telephone. The causes of death were also confirmed by the national health database. Two-sided p-values<0.05 were considered statistically significant. RESULTS: During a median follow-up of 10 years, 71 deaths were recorded , 62 of whom died from CVD. Both CVD and all-cause mortality were found to be significantly higher in the lower fetuin-A group than the higher fetuin-A group (44% vs 24%, p= 0.005; 48% vs 31%, p= 0.022, respectively). In Cox regression proportional hazard analyses, fetuin-A was found to be an independent predictor of CVD and all-cause mortality. CONCLUSIONS: Low fetuin-A concentration is associated with a poor long-term prognosis after STEMI, regardless of the traditional cardiovascular risk factors. Our findings have strengthened previous studies that consistently demonstrate the determining role of anti-inflammatory mediators in acute coronary syndromes.

FUNDAMENTO: A fetuína-A é um fator anti-inflamatório e anticalcificação envolvido no curso da doença arterial coronariana (DAC). Em alinhamento com essas funções, investigou-se a fetuína-A como marcador de risco cardiovascular em vários estudos. Porém, a associação entre a fetuína-A e o prognóstico dos pacientes com DAC ainda é controversa. OBJETIVOS: O presente estudo foi conduzido para identificar a associação entre o nível de fetuína-A sérica e doença cardiovascular (DCV) de longo prazo e a mortalidade global por infarto do agudo do miocárdio por supradesnivelamento do segmento ST (STEMI). MÉTODOS: Foram cadastrados no estudo cento e oitenta pacientes consecutivos com STEMI. A população do estudo foi dividida em subgrupos (mais baixo, ≤288 µg/ml; e mais alto, >288 µg/ml) de acordo com a mediana do nível de fetuína-A. Dados de acompanhamento clínico foram obtidos por contato telefônico anual com pacientes ou familiares. As causas das mortes também foram confirmadas pelo banco de dados de saúde nacional. P-valores bilaterais <0,05 foram considerados estatisticamente significativos. RESULTADOS: Durante um acompanhamento médio de 10 anos, foram registradas 71 mortes, das quais 62 foram devidas a DCV. Identificou-se um índice de mortalidade global e por DCV significativamente mais alto no grupo com nível de fetuína-A mais baixo que no grupo com nível de fetuína-A mais alto (44% versus 24%, p= 0,005; 48% versus 31%, p= 0,022, respectivamente). Nas análises de risco proporcionais por regressão de Cox, detectou-se que a fetuína-A era um preditor independente de mortalidade global e por DCV. CONCLUSÕES: A baixa concentração de fetuína-A está associada ao prognóstico de longo prazo ruim pós-STEMI, independentemente de fatores de risco cardiovascular tradicionais. Nossos achados fortaleceram estudos prévios demonstrando consistentemente o papel determinante dos mediadores anti-inflamatórios em síndromes coronárias agudas.

Fetuin-A and risk of diabetes-related vascular complications: a prospective study.

BACKGROUND: Fetuin-A is a hepatokine which has the capacity to prevent vascular calcification. Moreover, it is linked to the induction of metabolic dysfunction, insulin resistance and associated with increased risk of diabetes. It has not been clarified whether fetuin-A associates with risk of vascular, specifically microvascular, complications in patients with diabetes. We aimed to investigate whether pre-diagnostic plasma fetuin-A is associated with risk of complications once diabetes develops. METHODS: Participants with incident type 2 diabetes and free of micro- and macrovascular disease from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (n = 587) were followed for microvascular and macrovascular complications (n = 203 and n = 60, respectively, median follow-up: 13 years). Plasma fetuin-A was measured approximately 4 years prior to diabetes diagnosis. Prospective associations between baseline fetuin-A and risk of complications were assessed with Cox regression. RESULTS: In multivariable models, fetuin-A was linearly inversely associated with incident total and microvascular complications, hazard ratio (HR, 95% CI) per standard deviation (SD) increase: 0.86 (0.74; 0.99) for total, 0.84 (0.71; 0.98) for microvascular and 0.92 (0.68; 1.24) for macrovascular complications. After additional adjustment for cardiometabolic plasma biomarkers, including triglycerides and high-density lipoprotein, the associations were slightly attenuated: 0.88 (0.75; 1.02) for total, 0.85 (0.72; 1.01) for microvascular and 0.95 (0.67; 1.34) for macrovascular complications. No interaction by sex could be observed (p > 0.10 for all endpoints). CONCLUSIONS: Our data show that lower plasma fetuin-A levels measured prior to the diagnosis of diabetes may be etiologically implicated in the development of diabetes-associated microvascular disease.

Impact of Fetuin-A, Lp(a), matrix gla protein and macrophage density on calcific aortic valve disease: a clinical study.

BACKGROUND: Calcific aortic valve disease (CAVD) has a substantial and increasing burden in the ageing population with occult onset.Present study aimed to assess association of clinical characteristics of these patients and occurrence of CAVD. METHODS: Patients diagnosed with CAVD and those receiving healthy medical examination in our hospital from January 2019 to February 2021 were enrolled in this retrospective study. Clinical characteristics, ultrasonic indicators, serological indicators and histology of CAVD were collected and compared among different groups. Logistic regression and Pearson correlation analysis was used to explore relationship between these indexes and occurrence of CAVD. RESULTS: DBP, SBP, LVESD, LVEDD, IVS, PW, AV Vmax, TC, TG, LDL-C, Fetuin-A, Lp(a) in severe group were higher than mild, moderate and control groups (P<0.05), while those indexes of patients in moderate group were higher than that in mild and controlled groups (P<0.05). Besides, theses indexes of patients in mild group were also higher than that of controlled one (P<0.05). However, LVEF, HDL-C and MGP of patients in severe group was the lowest (P<0.05), while those in moderate group were lower than mild and controlled groups. Moreover, these indexes in mild group were also lower than control group (P<0.05). In Logistic regression analysis, MGP, Fetuin-A and Lp(a) were all independently associated with occurrence of CAVD (P<0.05). In Pearson correlation analysis, Fetuin-A and Lp(a) were positively correlated with progression of the disease, while MGP and macrophage density were negatively correlated with it. CONCLUSIONS: Fetuin-A, MPG and Lp(a) were independently associated with the occurrence of CAVD, and they might be potential predictors for diagnosis of this disease.

Níveis mais Baixos de Fetuína-A Sérica estão Associados a um Maior Risco de Mortalidade em Dez Anos em Pacientes com Infarto do Miocárdio por Supradesnivelamento do Segmento ST / Lower Serum Fetuin-A Levels are Associated with a Higher Ten-Year Mortality Risk in Patients with ST-Elevation Myocardial Infarction

Resumo Fundamento A fetuína-A é um fator anti-inflamatório e anticalcificação envolvido no curso da doença arterial coronariana (DAC). Em alinhamento com essas funções, investigou-se a fetuína-A como marcador de risco cardiovascular em vários estudos. Porém, a associação entre a fetuína-A e o prognóstico dos pacientes com DAC ainda é controversa. Objetivos O presente estudo foi conduzido para identificar a associação entre o nível de fetuína-A sérica e doença cardiovascular (DCV) de longo prazo e a mortalidade global por infarto do agudo do miocárdio por supradesnivelamento do segmento ST (STEMI). Métodos Foram cadastrados no estudo cento e oitenta pacientes consecutivos com STEMI. A população do estudo foi dividida em subgrupos (mais baixo, ≤288 µg/ml; e mais alto, >288 µg/ml) de acordo com a mediana do nível de fetuína-A. Dados de acompanhamento clínico foram obtidos por contato telefônico anual com pacientes ou familiares. As causas das mortes também foram confirmadas pelo banco de dados de saúde nacional. P-valores bilaterais <0,05 foram considerados estatisticamente significativos. Resultados Durante um acompanhamento médio de 10 anos, foram registradas 71 mortes, das quais 62 foram devidas a DCV. Identificou-se um índice de mortalidade global e por DCV significativamente mais alto no grupo com nível de fetuína-A mais baixo que no grupo com nível de fetuína-A mais alto (44% versus 24%, p= 0,005; 48% versus 31%, p= 0,022, respectivamente). Nas análises de risco proporcionais por regressão de Cox, detectou-se que a fetuína-A era um preditor independente de mortalidade global e por DCV. Conclusões A baixa concentração de fetuína-A está associada ao prognóstico de longo prazo ruim pós-STEMI, independentemente de fatores de risco cardiovascular tradicionais. Nossos achados fortaleceram estudos prévios demonstrando consistentemente o papel determinante dos mediadores anti-inflamatórios em síndromes coronárias agudas.

Abstract Background Fetuin-A is an anti-inflammatory and anti-calcification factor involved in the course of coronary artery disease (CAD). In line with these functions, fetuin-A has been investigated as a cardiovascular risk marker in many studies. However, the association between fetuin-A and the prognosis of CAD patients is still controversial. Objectives The present study was conducted to identify the association between serum fetuin-A level and long-term cardiovascular disease (CVD) and all-cause mortality of ST-elevation acute myocardial infarction (STEMI). Methods One hundred eigthy consecutive patients with STEMI were enrolled in the study. The study population was divided into subgroups (lower, ≤288 µg/ml; and higher, >288 µg/ml) according to the median fetuin-A level. Clinical follow-up data was obtained by annual contact with the patients or family members by telephone. The causes of death were also confirmed by the national health database. Two-sided p-values<0.05 were considered statistically significant. Results During a median follow-up of 10 years, 71 deaths were recorded , 62 of whom died from CVD. Both CVD and all-cause mortality were found to be significantly higher in the lower fetuin-A group than the higher fetuin-A group (44% vs 24%, p= 0.005; 48% vs 31%, p= 0.022, respectively). In Cox regression proportional hazard analyses, fetuin-A was found to be an independent predictor of CVD and all-cause mortality. Conclusions Low fetuin-A concentration is associated with a poor long-term prognosis after STEMI, regardless of the traditional cardiovascular risk factors. Our findings have strengthened previous studies that consistently demonstrate the determining role of anti-inflammatory mediators in acute coronary syndromes.

Does fetuin-A mediate the association between pro-inflammatory diet and type-2 diabetes mellitus risk?

Introduction: Introduction: recent studies indicate that diet increases T2DM risk via inflammation. Fetuin-A, identified as an acute-phase protein, plays a role in insulin resistance and is an independent predictor of type-2 diabetes. Objectives: the present study aimed to examine the association between diet and T2DM risk, and whether said association is mediated by fetuin-A, and to determine the effect of fetuin-A on T2DM risk. Methods: the case group included 40 individuals with T2DM, whereas 40 individuals without T2DM comprised the control group. The Dietary Inflammatory Index (DII), was used to determine the inflammatory potential of diet. A simple mediation analysis was used to investigate whether diet was associated with T2DM risk and whether the association was mediated by fetuin-A. Results: subjects who consumed a high pro-inflammatory diet had 2.0 times higher risk of developing T2DM (OR = 2.043; 95 % CI: 0.955 to 4.371, p = 0.066). In addition, subjects who had higher levels of fetuin-A had a 1,2 times higher risk of developing T2DM (OR = 1.155; 95 % CI: 1.030 to 1.296, p = 0.014). Both fetuin-A and hs-CRP had a significant full mediator role on the association between DII and HOMA-IR [respectively; ß = 0.371 (95 % CI: -0.029-0.770), ß = 0.424 (95 % CI: -0.007-0.856)]. Conclusion: these findings suggest that a pro-inflammatory diet, by creating an environment of increased inflammatory markers, affects in particular insulin resistance through these markers and ultimately causes T2DM. In addition, fetuin-A also acts as an important novel mediator between diet and T2DM by inducing insulin resistance.

Introducción: Introducción: estudios recientes indican que la dieta aumenta el riesgo de T2DM mediante la inflamación. La fetuína-A, identificada como proteína de fase aguda, desempeña un papel en la resistencia a la insulina y es un predictor independiente de la diabetes de tipo 2. Objetivos: el presente estudio pretende examinar la asociación entre la dieta y el riesgo de DMT2 y si la asociación está mediada por lafetuína-A, y determinar el efecto de la fetuína-A sobre el riesgo de DMT2. Métodos: en el grupo de casos se incluyeron 40 individuos con DMT2, mientras que 40 individuos sin DMT2 se incluyeron en el grupo de control. El índice de inflamación de la dieta (DII) se usó para determinar el potencial inflamatorio de la dieta. El análisis de mediación simple se usó para investigar si la dieta estaba asociada con el riesgo de DMT2 y si la asociación estaba mediada por la fetuína-A. Resultados: los sujetos que consumieron una dieta más proinflamatoria tuvieron 2 veces más riesgo de desarrollar DMT2. Además, los sujetos que tenían niveles más altos de fetuína-A tuvieron 1,2 veces más riesgo de desarrollar DMT2. Tanto la fetuína-A como la hs-CRP tuvieron un papel significativo como mediadores completos sobre la asociación entre DII y HOMA-IR. Conclusión: estos hallazgos sugieren que la dieta proinflamatoria, al crear un ambiente con marcadores inflamatorios aumentados, afecta en particular a la resistencia a la insulina a través de estos marcadores y, finalmente, causa DMT2. Además, la fetuína-A también actúa como mediador novedoso importante entre la dieta y la DMT2 al inducir la resistencia a la insulina.

Evaluation of the effect of scaling and root planing on salivary and serum fetuin-A levels in patients with Stages II and III periodontitis.

BACKGROUND: Fetuin-A has garnered recognition in the etiopathogenesis of several systemic disorders. It has been recently acknowledged as an anti-inflammatory marker for periodontal disease. This study aimed to compare and correlate salivary and serum fetuin-A levels in health and patients with stages II-III periodontitis along with evaluating the effect of non-surgical periodontal therapy (NSPT) on the same. METHODS: Group 1 comprised of 30 healthy subjects. Group 2 embodied 30 patients with stages II-III periodontitis. Clinical periodontal parameters were recorded. Saliva and serum samples were assembled. Periodontitis patients received non-surgical periodontal treatment. They were recalled after 6 months, and collection of samples and recording of clinical parameters were reiterated. Fetuin-A levels were analyzed using ELISA. RESULTS: Salivary and serum fetuin-A levels were significantly lower in periodontitis patients when compared with the healthy subjects (P < 0.001) at baseline. Their concentrations significantly upregulated 6 months after active periodontal therapy (P < 0.001). Salivary fetuin-A levels revealed a significant positive correlation with their serum levels in Group 1 at baseline (P < 0.001). They also displayed a positive correlation in Group 2 at baseline and 6 months post periodontal therapy, nevertheless failed to establish a statistically significant association. CONCLUSION(S): Our study concluded that salivary and serum fetuin-A levels diminished with increasing severity of periodontal inflammation, and NSPT remarkably improved their levels. They also displayed a significant positive correlation in health, and a non-significant, yet positive correlation in patients with periodontitis.

Fetuin-A in newly detected type 2 diabetes mellitus as a marker of non-alcoholic fatty liver disease.

INTRODUCTION: Fetuin-A has been implicated in the causation of metabolic disorders such as obesity, diabetes, and hepatic steatosis. Numerous studies have shown the association between levels of fetuin-A in type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). The levels of fetuin-A in newly detected type 2 diabetic (NDD) patients and its relationship with the presence of NAFLD have not been studied. OBJECTIVE: To study the fetuin-A levels in patients with NDD and its relationship with NAFLD. METHODS: A total of 60 NDD patients were studied. The diagnosis of NAFLD was made on the basis of transient elastography. Serum fetuin-A and serum fasting insulin were measured along with other investigations. RESULTS: The percentage of patients with NAFLD in NDD was 53.33%. Fetuin-A levels were significantly higher in NDD with NAFLD compared to those without NAFLD. There was no association of fetuin-A with age, systolic and diastolic blood pressure, fasting blood sugar (FBS), hemoglobin (Hb)A1c, fasting insulin, homeostatic model assessment-insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and markers of advanced fibrosis. Fetuin-A levels beyond 1166.5 mcg/mL could predict the development of NAFLD with odds ratio (OR) of 4.33 (95% CI: 1.364-13.77), which remained significant after adjustment for various confounding factors. CONCLUSION: Fetuin-A is a reliable marker of NAFLD in NDD and is positively associated with insulin resistance (IR). The observation in this study suggests that high serum fetuin-A levels in patients with NAFLD do not merely reflect the effects of insulin resistance, but also a more extensive distortion of liver architecture.

The relationship between fetuin-A and coronary atherosclerotic heart disease (CHD) and CHD-related risk factors: A retrospective study.

ABSTRACT: Fetuin-A plays an important role in antivascular calcification and inflammatory response, it is necessary to explore the relationship between fetuin-A and coronary atherosclerotic heart disease (CHD) and CHD-related risk factors.A total of 92 patients with CHD as the research group, and 60 healthy persons as the control group were enrolled from May 2019 to May 2020. Fetuin-A levels were determined by enzyme-linked immunosorbent assay, and the characteristics and clinical data were collected and compared. Logistic regression was used to analyze the factors influencing CHD.The age, proportion of males, patients with hypertension and diabetes, as well as fetuin-A level in the research group were significantly higher than those in the control group, but the high-density lipoprotein cholesterol level was significantly lower than that in the control group (P < .05). Logistic regression analysis and correction showed that gender, age, blood pressure, and diabetes were related to the onset of CHD, and there was a significant correlation between the level of fetuin-A and age (P < .05).Serum fetuin-A was related to the onset risk of CHD, and showed a significant correlation with age.

The Role of Pentraxin-3, Fetuin-A and Sirtuin-7 in the Diagnosis of Prostate Cancer.

PURPOSE: Prostate canceris the most commonly diagnosed type of cancer and one of the leading causes of cancer-related death in men.Numerous efforts have been made to improve existing diagnostic methods and develop a new biomarker to identify patients with prostate cancer. In line with current literature, we preferred new serum-based biochemical markers as Pentraxin-3, Fetuin-A and Sirtuin-7 in the present study. MATERIALS AND METHODS: A total of 174 patients aged 42-76 years were included in the study. Patients with prostate cancer (n=38) were enrolled as Group 1 and patients with benign prostatic hyperplasia (n=136) as Group 2. The serum levels of Pentraxin-3, Fetuin-A and Sirtuin-7 levels were compared between the groups. RESULTS: The mean age of the patients was 61.9±7.6 years (p= .001). The mean serum Prostate Specific Antigen levels 32.0±59.6 (2.6-336) ng/mL and 10.0±11.3 (2.5-77.4) ng/mL in Group 1 and 2, respectively (p= .029). The mean serum levels of Pentraxin-3 and Fetuin-Ain Group 1 were statistically significantlydifferent from Group 2(3.3±4.4 ng/mL vs 1.8±2.4 ng/mL, p= .002 and 466.8±11.0 µg/mL vs 513.3±11.0 µg/mL,p= .041,respectively). There was no significant difference between Group 1 and 2 according to serum levels of Sirtuin-7 (12.7±8.2 ng/mL vs 12.7±12.4 ng/mL respectively, p= .145). CONCLUSION: Pentraxin-3, Fetuin-A and Sirtuin-7 may be effective in the diagnosis of prostate cancerin light of the current literature.In this study, it was found that Pentraxin-3 and Fetuin-A were significantly different in the diagnosis of prostate cancer.Larger-scale prospective studies are needed to determine the importance of Pentraxin-3 and Fetuin-A in the diagnosis of prostate cancer.

The relationship between calcification inhibitor levels in chronic kidney disease and the development of atherosclerosis.

AIM: We aimed to investigate the factors affecting the development of atherosclerosis and the role of calcification inhibitors fetuin-A, matrix-Gla protein (MGP), osteoprotegerin (OPG) in atherosclerosis progress. MATERIAL AND METHODS: The study was planned to investigate the relationship of serum OPG, MGP and fetuin-A levels with the development of atherosclerosis in the stage 2-3-4-5 chronic kidney disease (CKD) patients who did not require dialysis treatment. RESULTS: 32 (17 female, 15 male) healthy individuals and 92 (49 females, 43 males) CKD patients were included. The mean carotid intima-media thickness (CIMT), C-reactive protein (CRP), fetuin-A, OPG and MGP of the two groups were compared statistically. In CKD patients, age, body mass index (BMI), CRP, triglyceride, urea, systolic blood pressure (SBP), fasting blood sugar have a positive linear relationship, fetuin-A, OPG, GFR have a negative linear relationship with CIMT. The mean CIMT, right CIMT, left CIMT, blood urea, CRP, urinary albumin excretion creatinine and age show a negative linear relationship with fetuin-A. CONCLUSION: Fetuin-A levels begin to decline from the early stages of CKD and are significantly lower in patients with atherosclerosis as expressed with CIMT. This suggests that fetuin-A may be used as an early marker in CKD for increased cardiovascular risk. Early recognition of these risk factors is important and large-scale studies on vascular calcification inhibitors are needed.

Independent Dose-Response Associations between Fetuin-A and Lean Nonalcoholic Fatty Liver Disease.

Patients with lean NAFLD make up an increasing subset of liver disease patients. The association between lean NAFLD and feutin-A, which serves as a hepatokine and adipokine, has never been examined. Our study aimed to explore the association of serum fetuin-A among lean and non-lean patients. The study comprised 606 adults from the community, stratified into lean or non-lean (BMI

C-reactive protein, chemerin, fetuin-A and osteopontin as predictors of cardiovascular risks in persons with psoriasis vulgaris.

The study aimed to contribute to understanding the role of CRP, chemerin, fetuin-A and osteopontin and to assess their suitability as biomarkers of early stages of cardiovascular diseases in psoriasis vulgaris. Serum levels measured in 28 patients and 22 controls. Patients: increased levels of CRP (p<0.001), chemerin (p<0.05), osteopontin (p<0.05) and decreased levels of fetuin-A (p<0.05), significant relationships between CRP and fetuin-A (rho=0.530, p<0.01), CRP and chemerin (rho=0.543, p<0.01), CRP and age (rho=0.590, p<0.001), osteopontin and fetuin-A (r=-0.415, p<0.05), chemerin and PASI score (rho=-0.424, p<0.05). We confirmed specific roles of the biomarkers in psoriasis. CRP, fetuin-A and osteopontin could be considered appropriate markers for the detection of early stages of cardiovascular diseases.

On the association between circulating biomarkers and atherosclerotic calcification in a cohort of arterial disease participants.

BACKGROUND AND AIMS: Atherosclerotic calcification is a powerful predictor of cardiovascular disease. This study aims to determine whether circulating levels of a local/systemic calcification inhibitor or a marker of bone formation correlate with measures of coronary or extracoronary calcification. METHODS AND RESULTS: Clinical computed tomography (CT) was performed on 64 arterial disease participants undergoing carotid and lower extremity endarterectomy. Coronary artery calcium (CAC) scores and volumes were acquired from the CT scans (n = 42). CAC scores and volumes were used to derive CAC density scores. Micro-CT was performed on excised carotid (n = 36) and lower extremity (n = 31) plaques to quantify the volume and volume fraction of extracoronary calcification. Circulating levels of dephospho-uncarboxylated Matrix Gla Protein (dp-ucMGP), fetuin-A, carboxylated and uncarboxylated osteocalcin (ucOC) were quantified using commercial immunoassays. Carotid participant CAC density scores were moderately negatively correlated with plasma dp-ucMGP (rs = -0.592, P = 0.008). A weak negative association was found between CAC scores and %ucOC for all participants (rs = -0.335, P = 0.040). Another weak negative correlation was observed between fetuin-A and the volume of calcification within excised carotid specimens (rs = -0.366, P = 0.031). Despite substantial differences in coronary and extracoronary calcium measurements, the levels of circulating biomarkers did not vary significantly between carotid and lower extremity subgroups. CONCLUSION: Correlations identified between circulating biomarkers and measures of coronary and extracoronary calcium were not consistent among participant subgroups. Further research is required to determine the association between circulating biomarkers, coronary and extracoronary calcium.

Evaluation of the pathophysiological role of Fetuin A levels in adolescents with polycystic ovary syndrome.

OBJECTIVES: Polycystic ovary syndrome (PCOS) is an endocrinopathy, in which hyperandrogenism and hyperinsulinism have both occurred. Fetuin-A, a natural inhibitor of tyrosine kinase, leads to insulin resistance. The aim was to evaluate the relationship between fetuin-A and hyperandrogenism and hyperinsulinism and the role of fetuin-A in the pathophysiology of PCOS. METHODS: Thirty-eight cases with PCOS and 40 healthy adolescents were included in the study. PCOS and controls were divided into obese/non-obese subgroups. LH, FSH, total and free testosterone (TT, FT), SHBG, androstenedione, DHEAS were measured in patients with PCOS. Fasting glucose, insulin, lipid profile, AST, ALT, HsCRP, and fetuin levels of PCOS patients and healthy controls were also measured. RESULTS: Fetuin-A levels were higher in PCOS patients than in controls. In the obese-PCOS group, when compared to non-obese PCOS patients; the levels of SHBG and HDL were low while cholesterol, LDL, triglyceride, HOMA-IR, FT, FAI, and HSCRP levels were high, but Fetuin-A levels were similar. In the obese-PCOS group, fetuin-A levels were higher than in obese-controls. HOMA-IR and fetuin-A levels were higher in non-obese PCOS patients than in non-obese controls. In the PCOS group, fetuin-A was positively correlated with TT, FT, FAI and androstenedione and negatively correlated with SHBG. Regression analysis demonstrated that FT, SHBG, and androstenedione significantly predicted fetuin-A levels (R2=54%). In non-obese PCOS patients and controls, fetuin-A was positively correlated with insulin and HOMA-IR. CONCLUSIONS: These results suggest a relationship between androgen levels and fetuin-A in PCOS cases, independent of insulin resistance, and may shed light on further studies.

Association of fetuin-A levels and left ventricular diastolic dysfunction in patients on haemodialysis.

OBJECTIVE: To identify the relationship between serum fetuin-A levels and left ventricular diastolic dysfunction (LVDD) among maintenance haemodialysis patients. METHODS: In a cross-sectional study, 75 dialysis patients with end-stage renal disease (ESRD) were recruited, and fetuin-A levels were detected using an enzyme-linked immunosorbent assay (ELISA). Echocardiography measurements were recorded according to the recommendations of the American Society of Echocardiography. The ratio of early diastolic transmitral inflow velocity (E) to early diastolic annular velocity (E') was measured using tissue Doppler imaging and E/E' > 15 was defined as diastolic dysfunction. The association of serum fetuin-A concentrations with echocardiographic parameters was analysed by calculating the bivariate linear correlation. A binary logistic regression analysis was conducted to determine the variables associated with LVDD. RESULTS: Compared to patients without diastolic dysfunction, patients with diastolic dysfunction were older, a higher percentage had a history of coronary artery disease, and presented with a high systolic pressure, high parathyroid hormone level, high N-terminal pro-brain natriuretic peptide (NT-proBNP) level, high LV mass index, high left atrium diameter, and low serum creatinine and fetuin-A levels. Serum fetuin-A levels showed a negative correlation with E/E' (r = - 0.299, P = 0.009). Fetuin-A levels were considered an independent predictor of diastolic dysfunction. CONCLUSION: A decrease in the serum fetuin-A level is associated with an increased risk of LVDD in patients on haemodialysis.

A pilot study of the effects of chromium picolinate supplementation on serum fetuin-A, metabolic and inflammatory factors in patients with nonalcoholic fatty liver disease: A double-blind, placebo-controlled trial.

BACKGROUND: Evaluating the impact of chromium picolinate supplementation on glycemic status, lipid profile, inflammatory markers and fetuin-A in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: In present research, participants (N = 46) were randomized to (400 mcg/day, n = 23) chromium picolinate and placebo (n = 23) for 3 months. RESULTS: Glucose indices, and lipid profiles, inflammatory biomarker and fetuin-A were measured before and after the intervention. Chromium reduced triglyceride (TG), atherogenic index of plasma (AIP), very-low-density lipoprotein (VLDL), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), high-sensitivity C-reactive protein (hs-CRP), interleukin (IL) -6, tumor necrosis factor-alpha (TNF-α) and fetuin-A significantly compared to placebo group (p < 0.05). Furthermore, chromium significantly increased the quantitative insulin sensitivity check index (QUICKI). There were no significant differences in total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), fasting blood sugar (FBS), Hemoglobin A1c (HbA1C), interleukin (IL)-17 between the two groups (p < 0.05). CONCLUSION: Chromium picolinate significantly decreased TG, insulin, HOMA-IR, fetuin-A, the number of inflammatory factors, and increased QUICKI without changing FBS, HbA1C, TC, LDL, HDL, IL-17 levels and liver steatosis intensity in patients with NAFLD. Further studies by examining the effect of different doses of chromium and mechanisms of cellular action, would help further clarify the subject.

Circulating levels of fetuin-A are associated with moderate-severe hepatic steatosis in young adults.

PURPOSE: The hepatokine fetuin-A might have a role as molecular link between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the association between fetuin-A and the prevalence and severity of NAFLD in a population of young adults. METHODS: Ninety-seven adults (age 35.7 ± 12.4 years, female 64.9%), enrolled in a previous study evaluating NAFLD prevalence in the presence or absence of family history of T2DM, were included. Serum levels of fetuin-A (ELISA BioVendor, Czech Republic) and the main biochemical parameters were assessed. Presence and severity of NAFLD were evaluated by ultrasonography (Toshiba, Japan). A linear regression was run to predict fetuin-A levels and a logistic regression was performed to predict moderate-severe steatosis. RESULTS: Fetuin-A associated inversely with age (ß - 0.12, p = 0.03) and directly with body mass index (BMI) (ß 0.5, p = 0.048), waist circumference (WC) (ß 0.3, p = 0.027), triglycerides (TG) (ß 0.1, p = 0.001) and uric acid (ß 1.7, p = 0.018), after adjustment for age and sex. In a model including age, BMI, WC, TG and uric acid, age (ß - 0.2, p = 0.002) and TG (ß 0.04, p = 0.02) were independent predictors of fetuin-A. Prevalence of steatosis was 66%. The rates of mild and moderate-severe steatosis were 50.5% and 15.5%, respectively. In the logistic model, the independent predictors of moderate-severe steatosis were fetuin-A (OR 1.22, p = 0.036), age (OR 1.17, p = 0.01) and BMI (OR 2.75, p = 0.011). CONCLUSION: In a sample of young adults, circulating levels of fetuin-A correlated with moderate-severe NAFLD, independent of confounders, and with some metabolic parameters. Fetuin-A might be a useful marker to predict NAFLD and metabolic disorders.