Multicenter Validation of lncRNA and Target mRNA Diagnostic and Prognostic Biomarkers of Acute Ischemic Stroke From Peripheral Blood Leukocytes.

BACKGROUND: Long noncoding RNA (lncRNA) and mRNA profiles in leukocytes have shown potential as biomarkers for acute ischemic stroke (AIS). This study aimed to identify altered lncRNA and target mRNA profiles in peripheral blood leukocytes as biomarkers and to assess the diagnostic value and association with AIS prognosis. METHODS AND RESULTS: Differentially expressed lncRNAs (DElncRNAs) and differentially expressed target mRNAs (DEmRNAs) were screened by RNA sequencing in the discovery set, which consisted of 10 patients with AIS and 20 controls. Validation sets consisted of a multicenter (311 AIS versus 303 controls) and a nested case-control study (351 AIS versus 352 controls). The discriminative value of DElncRNAs and DEmRNAs added to the traditional risk factors was estimated with the area under the curve. NAMPT-AS, FARP1-AS1, FTH1, and NAMPT were identified in the multicenter case-control study (P<0.05). LncRNA NAMPT-AS was associated with cis-target mRNA NAMPT and trans-target mRNA FTH1 in all validation sets (P<0.001). Similarly, AIS cases exhibited upregulated lncRNA FARP-AS1 and FTH1 expression (P<0.001) in the nested case-control study (P<0.001). Furthermore, lncRNA FARP1-AS1 expression was upregulated in AIS patients at discharge with an unfavorable outcome (P<0.001). Positive correlations were found between NAMPT expression level and NIHSS scores of AIS patients (P<0.05). Adding 2 lncRNAs and 2 target mRNAs to the traditional risk factor model improved area under the curve by 22.8% and 5.2% in the multicenter and the nested case-control studies, respectively. CONCLUSIONS: lncRNA NAMPT-AS and FARP1-AS1 have potential as diagnostic biomarkers for AIS and exhibit good performance when combined with target mRNA NAMPT and FTH1.

Diurnal rythm of Nampt is gender and weight dependent.

RESEARCH AIM: Nicotinamide phosphoribosyltransferase (Nampt) is an adipocytokine that is elevated in obesity, type 2 diabetes and increased levels are associated with inflammatory processes. Nampt serum concentrations have been suggested to follow a diurnal rhythm peaking in the afternoon in lean males. However, no data exists regarding the effects of gender and body weight. MATERIAL AND METHODS: We measured Nampt serum levels over 24 h in a cohort of healthy individuals living with either normal weight or obesity. Furthermore, effects of meals, oral glucose tolerance test and physical exercise on Nampt concentrations were evaluated. Correlation analyses to other hormonal- and lab parameters and anthropometric measurements were performed. RESULTS: Nampt showed a diurnal rhythm with increased levels at daytime and a peak in the early afternoon. This diurnal rhythm was significant for all groups but obese males. The Nampt amplitude, measured both relatively and absolutely, was significantly higher in females than in males. Meals did not influence Nampt serum levels, whereas physical exercise and an OGTT did significantly influence Nampt serum levels. CONCLUSION: In conclusion, we found gender specific differences in Nampt amplitude and coefficient variation with both being higher in females. The circadian rhythm of Nampt was independent of gender in healthy lean individuals, whereas it was disturbed in men with obesity.

The interplay between extracellular NAMPT and inflammatory cytokines in preeclampsia.

Preeclampsia (PE) is the major cause of maternal-fetal mortality and morbidity. Its pathophysiology is not elucidated, but there is evidence for the role of visfatin/nicotinamide phosphoribosyl transferase (NAMPT), mainly due to its relation to endothelial dysfunction, a hallmark of PE. However, there is heterogeneous data regarding visfatin/NAMPT in healthy pregnancy (HP) and PE. Therefore, we performed a search on MEDLINE/PubMed using the terms "visfatin and preeclampsia" and "NAMPT and preeclampsia, and we selected 23 original articles: 12 articles reported increased levels in PE compared to HP, only four articles showed lower levels and eight articles did not find differences regarding visfatin/NAMPT in the groups studied. It is widely acknowledged that levels detected in plasma, serum, or placenta can be influenced by the size of the population and sample analyzed, as well as genetic factors. We further discussed the correlations of visfatin/NAMPT with clinical biomarkers in PE and inflammatory pathways. Considering the common inflammatory mechanisms between PE and visfatin/NAMPT, few studies have recently performed serum or plasma dosages. In conclusion, further studies are needed to highlight the potential role of visfatin/NAMPT in the pathophysiology of PE. This will provide comparative evidence to establish it as a biomarker for disease outcomes and treatment.

Mediterranean diet effects on vascular health and serum levels of adipokines and ceramides.

BACKGROUND: A randomized clinical trial to evaluate the effect of a Mediterranean-style diet on vascular health indices such as endothelial function indices, serum lipid and ceramide plasma and some adipokine serum levels. We recruited all consecutive patients at high risk of cardiovascular diseases admitted to the Internal Medicine and Stroke Care ward at the University Hospital of Palermo between September 2017 and December 2020. MATERIALS AND METHODS: The enrolled subjects, after the evaluation of the degree of adherence to a dietary regimen of the Mediterranean-style diet, were randomised to a Mediterranean Diet (group A) assessing the adherence to a Mediterranean-style diet at each follow up visit (every three months) for the entire duration of the study (twelve months) and to a Low-fat diet (group B) with a dietary "counselling" starting every three months for the entire duration of the study (twelve months).The aims of the study were to evaluate: the effects of adherence to Mediterranean Diet on some surrogate markers of vascular damage, such as endothelial function measured by means of the reactive hyperaemia index (RHI) and augmentation index (AIX), at the 6-(T1) and 12-month (T2) follow-ups; the effects of adherence to Mediterranean Diet on the lipidaemic profile and on serum levels of ceramides at T1 and T2 follow-ups; the effects of adherence to Mediterranean Diet on serum levels of visfatin, adiponectin and resistin at the 6- and 12-month follow-ups. RESULTS: A total of 101 patients were randomised to a Mediterranean Diet style and 52 control subjects were randomised to a low-fat diet with a dietary "counselling". At the six-month follow-up (T1), subjects in the Mediterranean Diet group showed significantly lower mean serum total cholesterol levels, and significantly higher increase in reactive hyperaemia index (RHI) values compared to the low-fat diet group. Patients in the Mediterranean Diet group also showed lower serum levels of resistin and visfatin at the six-month follow-up compared to the control group, as well as higher values ​​of adiponectin, lower values of C24:0, higher values of C22:0 and higher values of the C24:0/C16:0 ratio. At the twelve-month follow-up (T2), subjects in the Mediterranean Diet group showed lower serum total cholesterol levels and lower serum LDL cholesterol levels than those in the control group. At the twelve-month follow-up, we also observed a further significant increase in the mean RHI in the Mediterranean Diet group, lower serum levels of resistin and visfatin, lower values of C24:0 and of C:18:0,and higher values of the C24:0/C16:0 ratio. DISCUSSION: The findings of our current study offer a further possible explanation with regard to the beneficial effects of a higher degree of adherence to a Mediterranean-style diet on multiple cardiovascular risk factors and the underlying mechanisms of atherosclerosis. Moreover, these findings provide an additional plausible interpretation of the results from observational and cohort studies linking high adherence to a Mediterranean-style diet with lower total mortality and a decrease in cardiovascular events and cardiovascular mortality. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04873167. https://classic.clinicaltrials.gov/ct2/show/NCT04873167.

Relationship between serum apelin, visfatin levels, and body composition in Polycystic Ovary Syndrome patients.

OBJECTIVE: To investigate the relationship between body composition and serum visfatin and apelin levels in patients with polycystic ovary syndrome (PCOS). METHODS: In this prospective observational study, the differences in body composition, levels of gonadal hormone concentrations, glucose metabolism, apelin, and visfatin were compared between PCOS patients and the control group. PCOS patients were further divided into different subgroups according to different obesity criteria and the differences between serum visfatin and apelin levels in different subgroups were compared. Finally, the correlation of serum visfatin levels and apelin levels with body composition, and metabolism-related indicators in PCOS patients was explored. RESULTS: A total collected 178 cases of PCOS patients and 172 cases of healthy women (control group) between 2020 July and 2021 November. In PCOS patients, their weight, Body Mass Index (BMI), Waist Hip Rate (WHR), Fat-Free Mass Index (FFMI), Percent Body Fat (PBF), Fat mass index (FMI), PBF of Arm, PBF of Leg, PBF of the Trunk, Visceral Fat Level (VFL), fasting insulin (FINS), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and Luteinizing hormone (LH) were significantly higher than in the control group (all P < 0.001), Percent Skeletal Muscle (PSM), PSM of Leg, and PSM of the Trunk were significantly decreased than in the control group (all P < 0.001). The PCOS patients had significantly higher serum visfatin levels and apelin levels compared with the control group (all P < 0.001). In PBF > 35 % PCOS patients, the apelin and visfatin levels were significantly higher than the PBF ≤ 35 % PCOS patients. In WHR ≥ 0.85 and BMI ≥ 24 kg/m2 PCOS patients, the visfatin levels were significantly higher than the WHR < 0.85 and BMI < 24 kg/m2 PCOS patients. Serum apelin and visfatin positively correlated with BMI level, WHR, FFMI, PBF, FMI, PBF of arms, PBF of legs, PBF of the trunk, VFL, FBG, HOMA-IR index and negatively correlated with PSM, PSM of legs, and PSM of the trunk (all P < 0.001). CONCLUSIONS: Compared with healthy women, Patients with PCOS have an increased fat content in various parts of the body, reduced skeletal muscle content, and are often complicated by metabolic abnormalities. Serum visfatin and apelin correlated not only with obesity, fat mass, and fat distribution but also with muscle mass and distribution. It may be possible to reduce the long-term risk of metabolic disease in PCOS through the monitoring and management of the body composition in PCOS patients or to reflect the therapeutic effect of PCOS.

Evaluation of Serum Visfatin as a Biomarker of Lupus Nephritis in Egyptian Patients with Systemic Lupus Erythematosus.

One of the most significant consequences of systemic lupus erythematosus (SLE) is lupus nephritis (LN). Visfatin, an adipokine that is significantly expressed in visceral fat and is a marker of endothelial dysfunction in chronic kidney disease, has multiple proinflammatory actions. We aimed to evaluate the state of serum visfatin in SLE patients and to detect its possible correlation with the disease's activity and effects on the kidney affection. Fifty patients with active LN, 50 patients with inactive lupus, and 50 healthy people had their serum visfatin levels tested. Chemical and immunological markers of SLE and LN were measured. The SLE Disease Activity Index (SLEDAI) was used to measure the disease's activity. Renal biopsies from the LN subgroup were collected and classified using the modified classification of the World Health Organization. The serum visfatin of patients with active LN was significantly greater than that of inactive lupus patients and the healthy controls (20.56 ± 1.07 ng/mL, 16.77 ± 1.02 ng/mL, and 9.96 ± 1.46 ng/mL, P <0.001). SLEDAI and serum visfatin levels were shown to be significantly correlated (P = 0.000057). Serum visfatin levels were likewise significantly correlated with the index of histological activity in the active group (P <0.00001). Serum visfatin was raised in individuals with active LN and was related to the SLEDAI and disease severity scores. Serum visfatin could be utilized as a noninvasive biomarker for evaluating the severity of LN and risk stratification of the risk.

Correlation of serum nicotinamide phosphoribosyl transferase with hypoxia and Framingham risk score in patients with obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is an independent risk factor for atherosclerosis (AS), but the mechanism is different from classical AS risk factors. Nicotinamide phosphoribosyltransferase (NAMPT) is involved in the pathophysiology of AS via multiple pathways, and its expression is closely related to hypoxia. The association of NAMPT with hypoxia and the risk of cardiovascular morbidity in the patients of OSAHS remains to be defined. Therefore, we carried out this study to investigate the association of NAMPT with hypoxia and the risk of early cardiovascular disease [based on the Framingham risk score (FRS)] in patients with OSAHS. METHODS: A total of 82 patients diagnosed with OSAHS were enrolled in this cross-sectional survey design, along with 18 healthy controls who were age- and gender-matched. The general characteristic parameters including height and weight as well as biochemical parameters including blood glucose and lipid were collected from the subjects. The Framingham vascular risk score calculates the risk of developing vascular disease based on the above indicators. Polysomnography was performed in patients with OSAHS, and blood oxygen saturation and apnea-hypopnea index (AHI) were collected, and patients were grouped by disease extent by AHI. The serum NAMPT level of the research subjects was detected using an enzyme-linked immunosorbent assay. Spearman correlation analysis and multiple linear regression to explore the independent correlations of hypoxia on serum NAMPT activity in OSAHS patients. RESULTS: Serum NAMPT level in patients with OSAHS increased with the severity of the disease. Correlation analysis showed that NAMPT was significantly positively correlated with FRS in patients with OSAHS (r=0.829, P<0.05). Multiple linear regression analysis with FRS as the outcome measure showed that NAMPT activity and minimum blood oxygen saturation were independent associated with the risk of developing cardiovascular disease (ß=0.03, P=0.000; ß=-0.13, P=0.034). Univariate and multivariate regression analyses revealed that hypoxia was significantly associated with NAMPT levels in OSAHS patients, and the oxygen desaturation index (ODI) was independent associated with the expression of NAMPT activity (ß=4.09, P=0.000). CONCLUSIONS: In patients with OSAHS, hypoxia is independently associated with NAMPT. NAMPT increases the risk of cardiovascular morbidity in this population may be influenced by hypoxia.

Cord Blood Levels of Spexin, Leptin, and Visfatin in Term Infants Born Small, Appropriate, and Large for Gestational Age and Their Association with Newborn Anthropometric Measurements

Objective: Children born small for gestational age (SGA) are at risk of future obesity and associated comorbidities. Therefore the identification of risk factors and novel biomarkers which are associated with this risk are needed for early detection and to improve preventive strategies. Spexin (SPX), a novel neuropeptide that is involved in the regulation of obesity and fat metabolism, is a candidate biomarker for predicting obesity and related comorbidities at an early age. The aim of this study was to investigate serum levels of SPX in term infants born small, appropriate, and large for gestational age (LGA) and its association with newborn anthropometric measurements. Methods: One hundred and twenty term newborn babies classified as SGA, appropriate for gestational age (AGA), or LGA and their mothers were included. SPX, leptin and visfatin were measured in cord blood and maternal serum by enzyme-linked immunosorbent assay. Results: Fifty-six (46.7%) neonates were girls and 64 (53.3%) were boys. The mean birth weight was 3170.70±663 g, birth length was 48.9±2.79 cm, and head circumference was 34.5±1.67 cm. Birth weights, lengths, and head circumferences of the neonates in the SGA, AGA, and LGA groups were significantly different. Cord blood SPX and leptin levels in the SGA groups were significantly lower than those of both the LGA and AGA groups. Cord blood visfatin levels were significantly lower in the AGA group than the LGA and SGA groups. Maternal SPX levels of SGA babies were significantly lower than those of the mothers in both the LGA and AGA groups, but no significant difference was observed between the SGA and LGA groups. Maternal visfatin levels of the AGA babies were significantly higher than the maternal levels of SGA and LGA groups. There was no difference in terms of maternal leptin levels. Cord blood SPX and leptin levels were positively correlated with birth weight, length and head circumference. Birth weight increased significantly in line with maternal pregestational body mass index. Conclusion: The lowest SPX levels were found in the SGA babies and cord SPX level was significantly correlated with newborn length, weight, and head circumference.

Correlation of Serum Visfatin Level in Non-obese Women with Polycystic Ovary Syndrome and Matched Control.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrinopathy affecting reproductive-age women. Visfatin, an adipocytokine, and insulin resistance (IR) marker in diabetes since PCOS and diabetes share insulin resistance as an etiological factor, this study aimed to investigate visfatin as a predictive marker for IR and hyperandrogenemia in non-obese PCOS women and test its correlation to other parameters. A cross-sectional study conducted at the University Hospital recruited 140 women, divided into two groups. Group I (70/140, study group) was PCOS patients' diagnosis based on 2003 Rotterdam criteria and Group II (70/140, healthy controls). Both were aged, and body mass index (BMI) matched. After a detailed history and general examination, the clinical, demographic, biochemical, hormonal, and metabolic parameters were taken for comparison's sake. PCOS patients were subdivided according to the clinical or hormonal evidence of hyperandrogenemia into two groups: those with hyperandrogenemia and those without. Higher serum visfatin was estimated in the PCOS group (4.4 ± 1.7) versus healthy controls (3.1 ± 0.7) ng/mL, P < 0.0001. Significantly higher visfatin was confirmed in hyperandrogenic PCOS versus non-hyperandrogenic PCOS women (5.69 ± 1.1 vs. 2.76 ± 0.51 ng/mL). A strong correlation was found between visfatin versus hemoglobin A1c and free androgen index (FAI); r = 0.784 and 0.624, respectively. BMI and free testosterone scored a modest correlation. BMI centiles' correlation with serum visfatin revealed no significant effect on serum visfatin, P = 0.62. The ROC calculated visfatin cut-off value; 4.34 ng/mL with 51.4% sensitivity and 100% specificity, and a P-value < 0.001 in discriminating PCOS cases. In conclusion, a strong positive correlation of visfatin with insulin resistance, followed by FAI in PCOS cases irrespective of BMI, suggests the intimate relation of visfatin in PCOS pathophysiology among non-obese women. Further research is warranted to explore this association's therapeutic and prognostic value.

Relationship Of Serum Visfatin Levels With Serum Electrolytes, Liver Profile, Hepatic Enzymes And Anthropometric Parameters In Pregnant Women With Preeclampsia And Eclampsia During 3rd Trimester.

BACKGROUND: Eclampsia and preeclampsia are among the serious complications of gestation and threaten the lives of both mother and foetus. A protein called visfatin, one of these adipokines, is evaluated for its effects on serum electrolytes, lipid profile and hepatic enzymes in preeclamptic and eclamptic patients. METHODS: A sum of 234 pregnant women were enrolled in this crosssectional study and divided in to 2 main groups, i.e., Group A (eclamptic/preeclamptic) Group B (control) pregnant women respectively. Serum visfatin levels (ng/mL), serum electrolytes and liver enzymes were determined for every patient, using relative diagnostic kits. Anthropometric measurements were also noted. RESULTS: A total of 234 women (cases; n=160, controls; n=74) with gestation age of ≥20 weeks participated in this study. Group A had 86 (36.75%) women with preeclampsia and 74 (31.62%) women with eclampsia whereas Group B had 74 (31.62%) normotensive pregnant women. A strong significantly positive association was recorded for systolic (R2=78.78; p-value <0.000) and diastolic blood pressure (BP) (R2=78.52; p-value <0.000). Similar result was obtained for serum sodium ions (R2=3.09; p-value <0.002) and chloride ions (R2=7.36; p-value <0.000). Alkaline phosphatases (ALP) (R2=63.47; p-value <0.000) had also shown a strong positive and statistically significant association with visfatin levels. CONCLUSIONS: Serum visfatin significantly decreased the sodium and chloride levels whereas the levels of potassium remained unaffected. A very strong and positive association of visfatin levels with levels of bilirubin and alkaline phosphatases was also observed (ALP) but it found no effect on aspartate transferases (AST).

Correlation analysis between heart rate variability, epicardial fat thickness, visfatin and AF recurrence post radiofrequency ablation.

BACKGROUND: The aim of the present study is to investigate the possible correlation between heart rate variability (HRV), epicardial fat thickness (EFT), visfatin and AF recurrence post radiofrequency ablation. METHODS: Data of 337 AF patients to whom radiofrequency ablation therapy had been initiated at our hospital over the past three years were evaluated. The patients enrolled were divided into the non-recurrence group (102 patients) and the recurrence group (235 patients) according to AF recurrence in the preceding 12 months. General data in the two groups were collected and HRV, EFT, and visfatin levels were comprehensively compared for each patients of the two groups. RESULTS: The recurrence group showed significantly higher results in rMSSD, PNN50, HF, total EFT, and visfatin but with evidently lower results in LF/HF when comparing the non-recurrence group (P < 0.05). The significantly different general variables in the general data and laboratory parameters, rMSSD, PNN50, HF, total EFT, visfatin, LF/HF were used as independent variables, and AF recurrence post radiofrequency ablation was used as dependent variables. Logistic regression analysis revealed that the risk factors of AF recurrence post radiofrequency ablation were rMSSD, PNN50, HF, total EFT, visfatin, and LF/HF, and the difference was statistically significant (P < 0.05). CONCLUSION: HRV, EFT, visfatin appear to show high association with AF recurrence post radiofrequency ablation.

Analysis of circulating metabolites to differentiate Parkinson's disease and essential tremor.

Parkinson's disease (PD) and essential tremor (ET) are two common adult-onset tremor disorders in which prevalence increases with age. PD is a neurodegenerative condition with progressive disability. In ET, neurodegeneration is not an established etiology. We sought to determine whether an underlying metabolic pattern may differentiate ET from PD. Circulating metabolites in plasma and cerebrospinal fluid (CSF) were analyzed using gas chromatography-mass spectroscopy. There were several disrupted pathways in PD compared to ET plasma including glycolysis, tyrosine, phenylalanine, tyrosine biosynthesis, purine and glutathione metabolism. Elevated α-synuclein levels in plasma and CSF distinguished PD from ET. The perturbed metabolic state in PD was associated with imbalance in the pentose phosphate pathway, deficits in energy production, and change in NADPH, NADH and nicotinamide phosphoribosyltransferase levels. This work demonstrates significant metabolic differences in plasma and CSF of PD and ET patients.

Involvement of eNAMPT/TLR4 signaling in murine radiation pneumonitis: protection by eNAMPT neutralization.

Therapeutic strategies to prevent or reduce the severity of radiation pneumonitis are a serious unmet need. We evaluated extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a damage-associated molecular pattern protein (DAMP) and Toll-Like Receptor 4 (TLR4) ligand, as a therapeutic target in murine radiation pneumonitis. Radiation-induced murine and human NAMPT expression was assessed in vitro, in tissues (IHC, biochemistry, imaging), and in plasma. Wild type C57Bl6 mice (WT) and Nampt+/- heterozygous mice were exposed to 20Gy whole thoracic lung irradiation (WTLI) with or without weekly IP injection of IgG1 (control) or an eNAMPT-neutralizing polyclonal (pAb) or monoclonal antibody (mAb). BAL protein/cells and H&E staining were used to generate a WTLI severity score. Differentially-expressed genes (DEGs)/pathways were identified by RNA sequencing and bioinformatic analyses. Radiation exposure increases in vitro NAMPT expression in lung epithelium (NAMPT promoter activity) and NAMPT lung tissue expression in WTLI-exposed mice. Nampt+/- mice and eNAMPT pAb/mAb-treated mice exhibited significant histologic attenuation of WTLI-mediated lung injury with reduced levels of BAL protein and cells, and plasma levels of eNAMPT, IL-6,  and IL-1ß. Genomic and biochemical studies from WTLI-exposed lung tissues highlighted dysregulation of NFkB/cytokine and MAP kinase signaling pathways which were rectified by eNAMPT mAb treatment. The eNAMPT/TLR4 pathway is essentially involved in radiation pathobiology with eNAMPT neutralization an effective therapeutic strategy to reduce the severity of radiation pneumonitis.

The Physiological Effects of Visfatin on Immune Response and Inflammatory Impacts on Nephropathy.

Obesity triggers the development of adipokines such as leptin, resistin, and visfatin, which have been associated with the development of diabetic nephropathy and other vascular disorders. The main purpose of the current investigation was to identify the physiological impact of visfatin on immunological response and its inflammatory effects on nephropathy. Fifty Iraqi patients with chronic kidney disease (CKD) at various stages, as described by the National Kidney Foundation (NKF) and ranging in age from 48.367.56 to 53.68 8.46 years on average were considered. Prior to the start of the investigation, informed consent was obtained from all participants, and the ethics committee approved the study. Patients were classified into two groups: Group (A) comprised patients with a GFR higher than 60 mL/minute, and Group (B) comprised patients with a GFR of less than 60 mL/min. There was no considerable variance between the groups as regards visfatin, but a highly significant correlation between serum visfatin and CRP was observed. The results of the current investigation indicated that serum visfatin levels are significantly correlated with CRP in CKD patients; it is also correlated with deterioration of kidney function. Moreover, higher visfatin levels were accompanied by increased serum triglyceride and cholesterol levels. These findings would suggest that visfatin may perform an essential function in uremia-related inflammation and may serve as a potential target for treatment and prevention of renal associated complications. Future studies may delineate whether visfatin is a marker of disease activity and severity as well as a predictor of outcome in CKD.

The Association Between Three Adipocytokines (Adiponectin, Resistin and Visfatin) And Thyroid Status in Patients With Type 2 Diabetes Mellitus and Autoimmune Thyroiditis.

Autoimmune thyroiditis (AIT) and type 2 diabetes mellitus (DM2) are the most common endocrinological diseases worldwide. Relation between these diseases explains several hypotheses. One of them is influence of some adipocytokines. This study evaluated association between three adipocytokines (adiponectin, resistin and visfatin) and thyroid and glycid status in patients with DM2 and AIT compared to the control group (CG). The group consisted of four subgroups: patients with DM2 without thyreopathies, patients with AIT on substitution therapy without diabetes and prediabetes, patients with DM2 and AIT on substitution therapy and healthy subjects as the CG. We investigated parameters of thyroid and glucose metabolism and serum levels of three adipocytokines. The mean level of resistin in the group of patients with diabetes and thyroiditis was significantly higher than in patients with thyroiditis without diabetes and than in the CG. We found a weak negative correlation between visfatin and fasting glucose levels in patients with thyroiditis without diabetes. We detected a weak negative correlation between resistin and glycated haemoglobin and a weak negative correlation between visfatin and thyroid gland volume in patients with diabetes without thyroiditis. In the CG we determined a weak positive correlation between visfatin and free thyroxin. Our results are consistent with several studies, which confirmed association between AIT and adipocytokines.

Serum Visfatin as a Diagnostic Marker of Active Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) have been reported to be caused by a complex interplay of immunological, infectious, and genetic factors. Previous studies have suggested that adipokines play a role in IBD by inducing proinflammatory cytokines. We aimed to evaluate the role of visfatin in the diagnosis algorithm of active IBD. METHODS: 85 newly diagnosed IBD patients [56 diagnosed with ulcerative colitis (UC) and 29 with Crohn's disease (CD)] and 30 healthy controls were included. IBD phenotypes were described accordingly to Montreal classification. Hemoglobin, total leucocytic count (TLC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), albumin, fecal calprotectin and serum visfatin were measured. RESULTS: The serum visfatin level was found to be significantly higher in patients with IBD than those in the control group (p<0.001). It was significantly positively correlated with CRP, ESR, and FC in both IBD groups. Receiver operating characteristic curve analysis of visfatin in diagnosis of UC revealed an area under curve of 0.911. At cutoff ≥1.4 ng/ml, the sensitivity was 92.9% and the specificity was 86.7%.. In CD group, at the same cutoff, AUC was 0.974, sensitivity was 96.6% and specificity was 86.7%. There was a statistically significant elevation of serum visfatin in extensive UC (E3) as compared to the other groups. A cutoff ≥3.25 ng/ml revealed 88.9% sensitivity, and 100% specificity in detection of E3 UC. Serum visfatin was significantly increased in CD stricturing phenotype (B2) as compared to non-stricturing non-penetrating CD (B1). A cutoff ≥3.5 ng/ml revealed 83.3% sensitivity, and 100% specificity in detection of B2. CONCLUSIONS: The serum visfatin level were significantly higher in patients with IBD than in controls. Serum visfatin might be a novel noninvasive marker to detect activity in IBD patients and can be used as predictor of disease extension in patients with UC.

Sirtuin 1, Visfatin and IL-27 Serum Levels of Type 1 Diabetic Females in Relation to Cardiovascular Parameters and Autoimmune Thyroid Disease.

The loss of cardioprotection observed in premenopausal, diabetic women may result from the interplay between epigenetic, metabolic, and immunological factors. The aim of this study was to evaluate the concentration of sirtuin 1, visfatin, and IL-27 in relation to cardiovascular parameters and Hashimoto's disease (HD) in young, asymptomatic women with type 1 diabetes mellitus (T1DM). Thyroid ultrasound, carotid intima-media thickness (cIMT) measurement, electrocardiography, and echocardiography were performed in 50 euthyroid females with T1DM (28 with HD and 22 without concomitant diseases) and 30 controls. The concentrations of serum sirtuin 1, visfatin and IL-27 were assessed using ELISA. The T1DM and HD group had higher cIMT (p = 0.018) and lower left ventricular global longitudinal strain (p = 0.025) compared to females with T1DM exclusively. In women with a double diagnosis, the sirtuin 1 and IL-27 concentrations were non-significantly higher than in other groups and significantly positively correlated with each other (r = 0.445, p = 0.018) and thyroid volume (r = 0.511, p = 0.005; r = 0.482, p = 0.009, respectively) and negatively correlated with relative wall thickness (r = -0.451, p = 0.016; r = -0.387, p = 0.041, respectively). These relationships were not observed in the control group nor for the visfatin concentration. These results suggest that sirtuin 1 and IL-27 contribute to the pathogenesis of early cardiac dysfunction in women with T1DM and HD.

eNAMPT Is Localised to Areas of Cartilage Damage in Patients with Hip Osteoarthritis and Promotes Cartilage Catabolism and Inflammation.

Obesity increases the risk of hip osteoarthritis (OA). Recent studies have shown that adipokine extracellular nicotinamide phosphoribosyltransferase (eNAMPT or visfatin) induces the production of IL-6 and matrix metalloproteases (MMPs) in chondrocytes, suggesting it may promote articular cartilage degradation. However, neither the functional effects of extracellular visfatin on human articular cartilage tissue, nor its expression in the joint of hip OA patients of varying BMI, have been reported. Hip OA joint tissues were collected from patients undergoing joint replacement surgery. Cartilage explants were stimulated with recombinant human visfatin. Pro-inflammatory cytokines and MMPs were measured by ELISA and Luminex. Localisation of visfatin expression in cartilage tissue was determined by immunohistochemistry. Cartilage matrix degradation was determined by quantifying proteoglycan release. Expression of visfatin was elevated in the synovial tissue of hip OA patients who were obese, and was co-localised with MMP-13 in areas of cartilage damage. Visfatin promoted the degradation of hip OA cartilage proteoglycan and induced the production of pro-inflammatory cytokines (IL-6, MCP-1, CCL20, and CCL4) and MMPs. The elevated expression of visfatin in the obese hip OA joint, and its functional effects on hip cartilage tissue, suggests it plays a central role in the loss of cartilage integrity in obese patients with hip OA.

Effects of different lipid emulsions on serum adipokines, inflammatory markers and mortality in critically ill patients with sepsis: A prospective observational cohort study.

BACKGROUND & AIMS: Intravenous lipid emulsions in parenteral nutrition may cause different metabolic responses and immune effects in critically ill patients with sepsis. The aim of this study is to investigate the effects of different lipid emulsions on changes in concentrations of adipokine and cytokine and their relationship with mortality in patients. METHODS: Patients enrolled in this prospective, single-center, observational cohort study, were estimated to require more than ten days of parenteral nutrition. They were treated with soybean oil-based or olive oil-based parenteral lipid emulsions. Adipokine and cytokine concentrations of septic patients were determined at enrollment and ten days after, in accordance with the diagnostic criteria of SEPSIS-3. The concentrations levels were measured in an enzyme-linked immunosorbent assay. Mortality was analyzed using the Kaplan-Meier method and Cox regressions. RESULTS: Over a 25-month period, 145 patients were assessed for eligibility and consequently, 40 patients were analyzed. On admission, both groups had comparable physiological scores, comorbidities, malnutrition risk, anthropometric measurements, metabolic/hematologic biomarkers and concentrations of adipokines and cytokines (p > .05). Serum leptin, resistin, and cytokines (IL-6, IL-10, IL-1ß and TNF-α) decreased significantly in the entire cohort over ten days following sepsis (p < .05). Serum resistin decreased in both olive oil-based and soybean oil-based lipid emulsions groups. Serum adiponectin only decreased in soybean oil-based lipid emulsions group (p < .05). There was association between survival and percentage changes in adiponectin, resistin and visfatin concentrations (log rank test: p < .05). CONCLUSION: Adipokine and cytokine responses are affected by medical nutritional therapy in the sepsis process and adipokines may represent functional prognostic biomarkers in critically ill patients with sepsis.

Association between Tumor Prognosis Marker Visfatin and Proinflammatory Cytokines in Hypertensive Patients.

Visfatin has been reported as a risk factor and a potential diagnostic marker in cancer. It is an adipokine, secreted by visceral fat and associated with the pathogenesis of arterial hypertension. We investigated the circulatory levels of visfatin in hypertensive patients with hypertriglyceridemia, which are the risk factors for various cancers and its association with proinflammatory cytokines. A total of 81 (male/female: 33/48) subjects with or without hypertension were enrolled for this study. Group 1 was normotensive, Group 2 hypertensive, and Group 3 with hypertension with hypertriglyceridemia. Data on anthropometric and biochemical data were recorded. Plasma visfatin levels were measured using an ELISA kit. The plasma inflammatory cytokines were estimated using a multiplex bead-based assay. The results revealed that the hypertension with hypertriglyceridemia group has the highest levels of visfatin compared to the hypertension and control groups with a significant difference (p < 0.001). Besides, circulatory visfatin showed the strongest possible correlation with proinflammatory cytokines among hypertensive patients with hypertriglyceridemia. We found a positive correlation between visfatin and diastolic blood pressure as well as high-density lipoproteins. In conclusion, the outcomes of the present study demonstrate that plasma visfatin levels were found to be elevated in hypertensive patients with hypertriglyceridemia and associated with proinflammatory cytokines. Since hypertension has been documented as the most common comorbidity observed in cancer patients, visfatin may be a novel potential therapeutic target for hypertension in cancer patients and survivors.