Evaluation of seminal plasma levels of vaspin and visfatin in infertile males with elevated sperm DNA fragmentation index: a comparative study.

BACKGROUND: Sperm DNA fragmentation (SDF) can significantly impact male fertility, especially in cases where there is a substantial level of DNA damage. We aimed in the current study to assess seminal plasma (SP) levels of vaspin and visfatin in infertile men with an elevated SDF index (SDFI ≥ 30%) compared to infertile males with a normal SDFI (SDFI < 30%). RESULTS: Groups with good and medium DNA integrity exhibited significantly higher total motile sperm count and sperm motility in comparison to the group with poor DNA integrity. Significant negative correlations were noticed between SDF index (SDFI) and numerous semen parameters. Similarly, a significant negative correlation was observed between SDFI and SP vaspin. On the other hand, a significant positive correlation was found between SDFI and abnormal forms percentage. A statistically significant negative correlation was identified SP vaspin with age (r = -0.305, P = 0.006) and infertility duration (r = -0.263, P = 0.019). Statistically significant negative correlation was also identified between SP visfatin and abnormal forms percentage (r = -0.239, P = 0.034). The receiver operating characterisitic curve for predicting poor DNA integrity (SDFI ≥ 30%) revealed fair discriminative power for SP vaspin, with a cutoff value of < 0.55 ng/ml. It demonstrated a sensitivity of 58.8% and a specificity of 64.5% (area under the cureve (AUC) 0.685, p = 0.008). Meanwhile, SP visfatin had little discriminative power (AUC 0.562, p = 0.408). Finally, the results of a linear regression analysis indicated that sperm motility and SP vaspin were significant independent predictors of poor DNA integrity (SDFI ≥ 30%). The analysis was done with a 95% confidence interval and showed upper and lower bounds of -0.302 and -0.623, and -1.362 and -16.101, p < 0.001, p = 0.021, respectively. CONCLUSION: SP Level of vaspin had shown promise as potential biomarkers for sperm DNA integrity. However, vaspin appeared to have greater specificity than visfatin in this point. Future studies are required to validate these findings, evaluate the role of SP vaspin in maintaining sperm DNA integrity, and investigate the potential relationship between SP adipocytokines and other clinical-demographic variables.

RéSUMé: CONTEXTE: La fragmentation de l'ADN des spermatozoïdes (SDF) peut avoir un impact significatif sur la fertilité masculine. Dans cette étude, nous avons cherché à évaluer les niveaux de vaspine et de visfatine dans le plasma séminal (PS) chez les hommes infertiles présentant un indice SDF élevé (SDFI≥30%) par rapport aux hommes infertiles présentant un SDFI normal (SDFI <30%). RéSULTATS: Les patients dont l'intégrité de l'ADN spermatique était bonne ou moyenne présentaient un nombre total de spermatozoïdes mobiles et une mobilité significativement plus élevés par rapport au groupe dont l'intégrité de l'ADN était mauvaise. Des corrélations négatives significatives ont été observées entre l'indice SDF (SDFI) et plusieurs paramètres du sperme. De même, une corrélation négative significative a été observée entre le SDFI et le niveau de vaspin dans le PS. Par ailleurs, une corrélation positive significative a été trouvée entre le SDFI et le pourcentage de formes anormales. Une corrélation négative statistiquement significative a été identifiée entre le niveau de vaspin dans le PS et l'âge (r= -0,305, p=0,006) et la durée de l'infertilité (r= -0,263, p=0,019). Une corrélation négative statistiquement significative a également été identifiée entre le niveau de visfatine dans le PS et le pourcentage de formes anormales (r= -0,239, P=0,034). La courbe ROC prédit une mauvaise intégrité de l'ADN spermatique (sensibilité 58,8%, spécificité 64,5%, aire sous la courbe 0,685, p=0.008) lorsque la teneur en vaspine dans le PS est inférieure à 0,55 ng/ml. En revanche, la teneur du PS en visfatine s'est avérée avoir un faible pouvoir discriminant (AUC 0,562, p = 0,408). Enfin, les résultats d'une analyse de régression linéaire ont indiqué que la mobilité des spermatozoïdes et le niveau de  vaspine dans le PS étaient des prédicteurs indépendants significatifs d'une mauvaise intégrité (SDFI ≥ 30 %) de l'ADN spermatique. L'analyse a été réalisée avec un intervalle de confiance de 95 % et a montré des limites supérieures et inférieures de -0,302 et -0,623, et de -1,362 et -16,101, p<0,001, p=0,021, respectivement. CONCLUSION: Les niveaux de vaspin dans le PS se sont révélés prometteurs en tant que biomarqueurs potentiels de l'intégrité de l'ADN des spermatozoïdes. Toutefois, la vaspine semble avoir une plus grande spécificité que la visfatine sur ce point. De futures études sont nécessaires pour valider ces résultats, évaluer le rôle de la vaspine SP dans le maintien de l'intégrité de l'ADN des spermatozoïdes et étudier la relation potentielle entre les adipocytokines du plasma séminal et d'autres variables cliniques et démographiques.

Comparative Effects of Candesartan Versus Enalapril on Apelin, Visfatin, and Lipid Levels in Non-obese Hypertensive Patients.

Objective: Apelin and visfatin are adipokines secreted from adipose tissue that play important roles in regulating blood pressure. Therefore, the current study aimed to investigate the effects of candesartan versus enalapril on apelin, visfatin, and lipid profiles in hypertensive patients. Methods: In this case-control study, 120 participants were enrolled in four groups; Healthy people, newly diagnosed hypertensive patients, and enalapril- and candesartan-treated patients. Results: Serum apelin levels were significantly lower and visfatin levels were significantly higher in newly diagnosed hypertensive patients compared with the control group (p=0.0015, p=0.0175 respectively). Moreover, apelin levels were higher and visfatin levels were lower in the candesartan-treated patients compared with the newly diagnosed group (p=0.0487, p<0.0001 respectively). Interestingly, apelin levels were non-significantly higher and visfatin levels were significantly lower in enalapril-treated patients compared with the newly diagnosed group (p<0.0001). Conclusions: Lower apelin and higher visfatin levels are associated with newly diagnosed patients with hypertension. Interestingly, the findings suggest that ACE inhibition and angiotensin receptor blockade by enalapril and candesartan, respectively, positively regulate apelin and visfatin levels in hypertension. Specifically, candesartan regulates these adipokine to a greater extent than enalapril.

Amphiregulin Upregulation in Visfatin-Stimulated Colorectal Cancer Cells Reduces Sensitivity to 5-Fluororacil Cytotoxicity.

Colorectal cancer (CRC) has become a prevalent and deadly malignancy over the years. Drug resistance remains a major challenge in CRC treatment, significantly affecting patient survival rates. Obesity is a key risk factor for CRC development, and accumulating evidence indicates that increased secretion of adipokines, including Visfatin, under obese conditions contributes to the development of resistance in CRC to various therapeutic methods. Amphiregulin (AREG) is a member of the epidermal growth factor (EGF) family, which activates the EGF receptor (EGFR), influencing multiple tumorigenic characteristics of cancers. Abnormal expression levels of AREG in cancer cells have been associated with resistance to anti-EGFR therapy in patients. However, it remains unclear whether this abnormal expression also impacts CRC resistance to other chemotherapeutic drugs. The aim of this study is to examine whether AREG expression levels could be affected in CRC cells under Visfatin stimulation, thereby initiating the development of resistance to 5-fluororacil (5-FU). Through our results, we found that Visfatin indeed increases AREG expression, reducing the sensitivity of HCT-116 CRC cells to 5-FU cytotoxicity. Moreover, AREG upregulation is regulated by STAT3-CREB transcription factors activated by JNK1/2 and p38 signaling. This study highlights the significant role of AREG upregulation in CRC cells in initiating chemotherapeutic resistance to 5-FU under Visfatin stimulation. These findings provide a deeper understanding of drug resistance development in CRC under obese conditions and offer new insights into the correlation between an abnormal increase in AREG levels and the development of 5-FU-resistance in CRC cells, which should be considered in future clinical applications.

Genetic associations of visfatin polymorphisms with clinicopathologic characteristics of prostate cancer in Taiwanese males.

The most general cancer in men is prostate cancer (PCa), with its risk increasing due to age and obesity. Visfatin, a member of adipokines, is related to cancer progression and metastasis, but its relationship in PCa remains undetermined. In addition, no knowledge is available regarding relations between visfatin polymorphisms and clinicopathological characteristics in PCa. We sought to investigate the functions of four visfatin gene polymorphisms and clinicopathological characteristics on the hazard of developing PCa in 695 Taiwanese males with PCa. Carriers of the GA+AA heterozygote of SNP rs61330082 were at a markedly higher risk of biochemical recurrence than those with the GG genotype. Visfatin rs61330082 and rs11977021 were related with a high risk of perineural invasion, lymphovascular invasion, and biochemical recurrence in prostate-specific antigen (PSA) > 10 PCa patients. The Cancer Genome Atlas database noted that visfatin mRNA level did not prominently differ with pathological T/N stage and overall survival. This finding is the first to document a connection between visfatin polymorphisms and clinicopathological characteristics of PCa in Taiwanese males.

Qing-Luo-Yin Eased Adjuvant-Induced Arthritis by Inhibiting SIRT1-Controlled Visfatin Production in White Adipose Tissues.

Background: Nicotinamide adenine dinucleotide (NAD)-dependent deacetylase SIRT1 regulates both metabolism and immune functions. This study investigated if SIRT1 inhibitory property of herbal formula Qing-Luo-Yin (QLY) contributed to its anti-rheumatic effects. Methods: Adjuvant-induced arthritis (AIA) rats were treated by QLY and nicotinamide mononucleotide (NMN, a biosynthesis precursor of NAD) for 38 days. After sacrifice, blood, paws, liver and white adipose tissues (WAT) were collected. Pre-adipocytes were cultured by the rats' serum. The medium was used for monocytes culture. Some pre-adipocytes were treated by QLY-derived SIRT1 inhibitors. SIRT1 was silenced or overexpressed beforehand. The samples were subjected to kits-based quantification, polymerase-chain reaction, western-blot, immunofluorescence, and histology experiments. Results: AIA rats experienced significant fat loss in liver and WAT. Expression of many SIRT1-related signals like PPARγ, PGC-1α, HSL, ATGL and CPT-1A were altered. QLY attenuated all these abnormalities and joint injuries. By pan-acetylation up-regulation, visfatin was obviously reduced in QLY-treated AIA rats' blood (from 191.8 to 127.0 pg/mL). NMN sustained SIRT1 activation by replenishing NAD, and weakened these effects. QLY-containing serum and the related compounds showed similar impacts on pre-adipocytes, resembling the changes in QLY-treated AIA rats' WAT. These treatments suppressed AIA serum-induced visfatin secretion (from 49.3 to 36.1 and 30.7 pg/mL). This effect was impaired by SIRT1 overexpression. The medium from the compounds-treated pre-adipocytes impaired NF-κB activation in AIA serum-cultured monocytes. Conclusion: Besides fat depletion, SIRT1 up-regulation in rheumatic subjects' WAT promotes visfatin production, and exacerbates inflammation. SIRT1 inhibition in WAT is an anti-rheumatic way of QLY independent of immune regulation.

Intra-testicular visfatin inhibition disrupts androgen and estrogen signalling in the mouse testis.

Visfatin is expressed in the testis of chicken, humans and rodents; however, direct role of visfatin in the adult testis has not been studied. We investigated testicular responses after intra-testicular injection of FK866. The effects of visfatin inhibition were accessed at 24 hrs and 1 week post FK866 treatment. The testicular histoarchitecture were degenerated after 24 hrs of FK866 treatment along with supressed testosterone and proliferating markers and resumption in these parameters showed after 1 week. The expression of AR and ERα were down-regulated after 1 week of FK866 treatment. The expression of BCl2 was down-regulated along with a slight elevation of caspase3 after 24 hrs; however, both proteins still showed suppressed expression after 1 week. Furthermore, ERß expression, 3ßHSD, and 17ßHSD were down-regulated in both groups compared to the control. Despite the down-regulation of some factors, the testicular proliferation and histoarchitecture showed resumption in the testis after 1 week of FK866 treatment. This could be due to increased testosterone secretion by suppressing aromatase expression. In conclusion, our result is the first report on the direct role of visfatin in the adult testis. Visfatin has a stimulatory role in testosterone synthesis and proliferation in the testis. Moreover, some deregulated factors in the testis after 1 week of FK866 treatment, despite normal histoarchitecture treatment, could be a compensatory mechanism after visfatin inhibitions.

Bariatric Surgery in Obesity: Metabolic Quality Analysis and Comparison of Surgical Options.

Obesity is a constantly growing health problem which reduces quality of life and life expectancy. Bariatric surgery (BS) for obesity is considered when all other conservative treatment modalities have failed. Comparison of the multidisciplinary programs with BS regarding to the weight loss showed that substantial and durable weight reduction have been achieved only with bariatric surgical treatments. Although laparoscopic sleeve gastrectomy is the most popular BS, it has high long-term failure rates, and it is claimed that one of every three patients will undergo another bariatric procedure within a 10-year period. Although BS provides weight loss and improvement of metabolic comorbidities, in long-term follow-up, weight gain is observed in half of the patients, while decrease in bone mass and nutritional deficiencies occur in up to 90%. Moreover, despite significant weight loss, several psychological aspects of patients are worsened in comparison to preoperative levels. Nearly one-fifth of postoperative patients with "Loss-of-eating control" meet food addiction criteria. Therefore, the benefits of weight loss following bariatric procedures alone are still debated in terms of the proinflammatory and metabolic profile of obesity.

Evaluation of Serum Adipokine Levels in Girls With Central Precocious Puberty.

PURPOSE: Adipose tissue has an important endocrine function by secreting a variety of hormones known as adipokines, such as Visfatin, Omentin-1 and Chemerin. On the other hand, these hormones are also secreted from places other than fatty tissues in the girl's genital system. The goal of this study was to demonstrate the secretory status of adipokines in patients with central precocious puberty (CPP) and their utility in the diagnosis of precocious puberty. METHOD: A total of 105 patients were included in the study (53 in the CPP group and 52 in the control group). The following were used as the CPP diagnostic criteria; breast development, basal LH measurement higher than 0.3 IU/L, peak LH level ≥ 5 IU/L, peak LH/FSH ratio ≥ 0.66 (after 0.1 mg GnRH stimulation test) and a difference of at least 1 year between bone and chronological age. RESULTS: A statistically significant difference was detected between the groups in serum Omentin-1 and Chemerin levels, and no significant differences were detected between the groups in Visfatin values. The cut-off values for the diagnosis of CPP were calculated as ≤ 48.9 with 81% sensitivity and 54% specificity for Omentin-1, and as ≥ 417 with 85% sensitivity and 60% specificity for Chemerin. CONCLUSION: In our study, we found that Omentin-1 level decreased and Chemerin level increased in lean girls with CPP. More studies are needed to elucidate how adipokines play roles in explaining the onset of CPP, and whether they may be used as a reliable marker for the diagnosis of CPP.

Relationship between adipokines and androgens in children and young adults with congenital adrenal hyperplasia.

Introduction: Children and young adults with congenital adrenal hyperplasia (CAH) are at increased risk of obesity and insulin resistance. There is evidence that children with CAH have increased visceral adiposity, which has been linked to metabolic syndrome and cardiovascular disease (CVD). The adipokine adiponectin has been shown to correlate with reduced metabolic risk, whereas the adipokines visfatin and leptin have been linked to visceral fat and adipocyte inflammation and can serve as biomarkers of increased metabolic risk. Few studies to date have characterized adipokine levels in children and young adults with congenital adrenal hyperplasia. We sought to investigate the relationship between adiponectin, leptin and visfatin levels to metabolic risk factors and androgen levels in children and young adults with CAH. Methods: Fasting blood was obtained for visfatin, leptin, adiponectin, glucose, insulin, CRP, lipid panel, total cholesterol (TC), triglycerides (TG) and HbA1c, as well as standard laboratory tests to assess adrenal control, from children with CAH due to 21-hydroxylase deficiency. HOMA-IR was calculated based on fasting glucose and insulin. Anthropomorphic measurements of BMI and waist-to-hip ratio were also obtained. Results: Adiponectin and androstenedione were inversely correlated (R = -0.57, p =0.016). There was a positive correlation between leptin and BMI percentile (R = 0.63, p <0.001) as well as leptin and HOMA-IR (R = 0.63, p <0.01). Glucocorticoid dose had a positive correlation with HOMA-IR (R=0.56, p = 0.021). Visfatin was inversely correlated with HDL cholesterol (R = -0.54, p = 0.026) and total cholesterol (R = -0.49, p <0.05). Overweight children and young adults had a significantly higher leptin (p = 0.02) and HOMA-IR (p=0.001) than non-overweight children and young adults. Conclusion: The inverse relationship between adiponectin and androstenedione suggests that better CAH control can reduce the risk of insulin resistance and metabolic syndrome. However, a high glucocorticoid dose appears to increase the risk of insulin resistance, underscoring the delicate balance required when treating CAH.

Changes in Circulating Adipokine Levels in COVID-19 Patients.

Objective: The COVID-19 pandemic has posed significant global health challenges. Despite extensive research efforts, the inflammatory response triggered by SARS-CoV-2 remains to be further explored and understood. Our study aims to examine the changes in serum concentrations of pro-inflammatory adipokines-visfatin and leptin-in COVID-19 patients in relation to a healthy control group. Patients/Materials/Subjects and Methods: The study consisted of forty COVID-19 patients and twenty-four healthy patients in the control group. Two serum samples were collected: upon admission and on the seventh day of hospitalization. Concentrations of visfatin and leptin in the serum, alongside routine biochemical parameters, were measured using enzyme immunoassay or enzyme-linked immunosorbent assay kits. The Shapiro-Wilk test was used to assess normality. Differences between independent groups were compared using the Mann-Whitney U test and Kruskal-Wallis ANOVA. Correlations were evaluated with Spearman's rank correlation coefficient. Results: Our findings revealed significantly lower visfatin levels in COVID-19 patients compared to the control group upon admission (4.29 ng/mL, (3.0-6.88 ng/mL) vs. 37.16 ng/mL (24.74-50.12 ng/mL), p < 0.001 for visfatin 1 and 52.05 ng/mL, (31.2-69.66 ng/mL) vs. 37.16 ng/mL (24.74-50.12 ng/mL), p = 0.048 for visfatin 2). The visfatin level of COVID-19 patients returned to the normal levels, established in the control group. However, there was no significant difference in leptin levels between the two groups (p = 0.270 for leptin 1 and p = 0.129 for leptin 2). There was a positive correlation between BMI and leptin concentration (r = 0.66 and p = 0.00). Moreover, it was discovered that COVID-19 independently reduces visfatin levels during the first day of illness. Conclusions: The results of our research suggest that the onset of COVID-19 infection is correlated to visfatin levels. Association with leptin levels remains inconclusive. Further research is imperative to elucidate the intricate role of visfatin and leptin in SARS-CoV-2 infection and their potential as biomarkers for COVID-19 severity and prognosis.

Exploring the potential roles of apelin, visfatin, and irisin in energy regulation in farm animals: an overview.

Adipose tissue, both intricate and fundamental to physiological functions, comprises cell types, including adipocytes, pivotal in secreting bioactive peptides known as 'adipokines.' Apelin (APLN), Visfatin (VSFTN), and Irisin (IRSN) are novel adipokines involved in regulating energy, carbohydrate, protein, and lipid metabolism. APLN acts as an endogenous ligand for G-protein-coupled receptors, VSFTN is essential in nicotinamide adenine dinucleotide (NAD) biosynthesis, and IRSN is released from skeletal muscle and adipose tissues. Their influence spans various physiological domains, including insulin resistance and sensitivity, cardiovascular functions, angiogenesis, and reproductive systems. This review focuses on the potential roles of APLN, VSFTN, and IRSN in energy regulation mechanisms related to farm animal production. Despite accumulating evidence of their significance, comprehensive understanding is still emerging, with most studies based on model organisms. Thus, there's a pressing need for targeted research on farm animals. Addressing these knowledge gaps could pave the way for improved health strategies, reproductive efficiency, and productivity in farm animals. Future research should focus on understanding the multifaceted interactions of these adipokines and their implications for promoting sustainable and effective animal production.

Visfatin (NAMPT) affects global gene expression in porcine anterior pituitary cells during the mid-luteal phase of the oestrous cycle.

BACKGROUND: The pituitary belongs to the most important endocrine glands involved in regulating reproductive functions. The proper functioning of this gland ensures the undisturbed course of the oestrous cycle and affects the female's reproductive potential. It is believed that visfatin, a hormone belonging to the adipokine family, may regulate reproductive functions in response to the female's metabolic state. Herein we verified the hypothesis that suggests a modulatory effect of visfatin on the anterior pituitary transcriptome during the mid-luteal phase of the oestrous cycle. RESULTS: RNA-seq analysis of the porcine anterior pituitary cells revealed changes in the expression of 202 genes (95 up-regulated and 107 down-regulated in the presence of visfatin, when compared to the non-treated controls), assigned to 318 gene ontology terms. We revealed changes in the frequency of alternative splicing events (235 cases), as well as long noncoding RNA expression (79 cases) in the presence of the adipokine. The identified genes were associated, among others, with reproductive system development, epithelial cell proliferation, positive regulation of cell development, gland morphogenesis and cell chemotaxis. CONCLUSIONS: The obtained results indicate a modulatory influence of visfatin on the regulation of the porcine transcriptome and, in consequence, pituitary physiology during the mid-luteal phase of the oestrous cycle.

Correlation Between Body Mass Index and Periodontitis: A Clinical and Biochemical Analysis.

Introduction Obesity is the excessive deposition of body fat in relation to lean body mass. In this research, its relation to periodontitis has been analysed using clinical and biochemical parameters. The current study assessed the correlation between body mass index (BMI) and periodontitis using salivary visfatin levels. Materials and methods Sixty participants (33 males and 27 females) were categorised into three different groups according to BMI: group 1: normal weight (n=20); group 2: overweight (n=20); and group 3: obese (n=20). Clinical parameters such as probing pocket depth (PPD) and clinical attachment level (CAL) were recorded. Salivary samples were collected and assessed for salivary visfatin levels with the aid of a human visfatin enzyme-linked immunosorbent assay (ELISA) kit. The results were assessed using IBM SPSS Statistics for Windows, Version 23.0 (Released 2015; IBM Corp., Armonk, New York, United States). Results The PPD, CAL, and salivary visfatin levels were higher in group 3, followed by groups 2 and 1, and were statistically significant (p=0.000). The correlation between visfatin and PPD (r=0.962) and visfatin and CAL (r=0.978) was strongly positive and statistically significant. Conclusion This study demonstrates a strong positive correlation between BMI and periodontitis. Moreover, salivary visfatin can be considered a diagnostic marker for periodontal diseases.

Comparative Effects of Gymnema sylvestre and Berberine on Adipokines, Body Composition, and Metabolic Parameters in Obese Patients: A Randomized Study.

Gymnema sylvestre (GS) and berberine (BBR) are natural products that have demonstrated therapeutic potential for the management of obesity and its comorbidities, as effective and safe alternatives to synthetic drugs. Although their anti-obesogenic and antidiabetic properties have been widely studied, comparative research on their impact on the gene expression of adipokines, such as resistin (Res), omentin (Ome), visfatin (Vis) and apelin (Ap), has not been reported. METHODOLOGY: We performed a comparative study in 50 adult Mexican patients with obesity treated with GS or BBR for 3 months. The baseline and final biochemical parameters, body composition, blood pressure, gene expression of Res, Ome, Vis, and Ap, and safety parameters were evaluated. RESULTS: BBR significantly decreased (p < 0.05) body weight, blood pressure and Vis and Ap gene expression and increased Ome, while GS decreased fasting glucose and Res gene expression (p < 0.05). A comparative analysis of the final measurements revealed a lower gene expression of Ap and Vis (p < 0.05) in patients treated with BBR than in those treated with GS. The most frequent adverse effects in both groups were gastrointestinal symptoms, which attenuated during the first month of treatment. CONCLUSION: In patients with obesity, BBR has a better effect on body composition, blood pressure, and the gene expression of adipokines related to metabolic risk, while GS has a better effect on fasting glucose and adipokines related to insulin resistance, with minimal side effects.

Serum visfatin level in ß-thalassemia and its correlation with disease severity.

Thalassemia is a group of genetic hematological conditions characterized by the defective synthesis of one or more hemoglobin chains. This genetic anomaly alters globin chain balance, causing hemolysis, ineffective erythropoiesis, and chronic inflammatory diseases. The proinflammatory adipocytokine visfatin is predominantly produced in visceral adipose tissue. Its evaluation in individuals with thalassemia may provide valuable insights into the assessment of disease severity. The aim of this study was to investigate the potential role of visfatin in the development of ß-thalassemia and its association with the severity of the illness. The study included 40 patients with ß-thalassemia and ten healthy individuals matched by age and sex. Serum visfatin level was measured using ELISA. We found that individuals with ß-thalassemia major had significantly higher levels of serum visfatin than those with ß-thalassemia minor and the control group (P < 0.001). A receiver operating characteristic curve revealed that serum visfatin levels were different in the three groups. Our results suggest that the serum level of visfatin is significantly correlated with the severity of ß-thalassemia.

eNAMPT is a novel therapeutic target for mitigation of coronary microvascular disease in type 2 diabetes.

AIMS/HYPOTHESIS: Individuals with diabetes are at high risk of cardiovascular complications, which significantly increase morbidity/mortality. Coronary microvascular disease (CMD) is recognised as a critical contributor to the increased cardiac mortality observed in people with diabetes. Therefore, there is an urgent need for treatments that are specific to CMD. eNAMPT (extracellular nicotinamide phosphoribosyltransferase) is a damage-associated molecular pattern and TLR4 ligand, whose plasma levels are elevated in people with diabetes. This study was thus designed to investigate the pathogenic role of intracellular nicotinamide phosphoribosyltransferase (iNAMPT) and eNAMPT in promoting the development of CMD in a preclinical murine model of type 2 diabetes. METHODS: An inducible type 2 diabetic mouse model was generated by a single injection of low-dose streptozocin (75 mg/kg, i.p.) combined with a high-fat diet for 16 weeks. The in vivo effects of i/eNAMPT inhibition on cardiac endothelial cell (CEC) function were evaluated by using Nampt+/- heterozygous mice, chronic administration of eNAMPT-neutralising monoclonal antibody (mAb) or use of an NAMPT enzymatic inhibitor (FK866). RESULTS: As expected, diabetic wild-type mice exhibited significantly lower coronary flow velocity reserve (CFVR), a determinant of coronary microvascular function, compared with control wild-type mice. eNAMPT plasma levels or expression in CECs were significantly greater in diabetic mice than in control mice. Furthermore, in comparison with diabetic wild-type mice, diabetic Nampt+/- heterozygous mice showed markedly improved CFVR, accompanied by increased left ventricular capillary density and augmented endothelium-dependent relaxation (EDR) in the coronary artery. NAMPT inhibition by FK866 or an eNAMPT-neutralising mAb significantly increased CFVR in diabetic mice. Furthermore, administration of the eNAMPT mAb upregulated expression of angiogenesis- and EDR-related genes in CECs from diabetic mice. Treatment with either eNAMPT or NAD+ significantly decreased CEC migration and reduced EDR in coronary arteries, partly linked to increased production of mitochondrial reactive oxygen species. CONCLUSIONS/INTERPRETATION: These data indicate that increased i/eNAMPT expression contributes to the development of diabetic coronary microvascular dysfunction, and provide compelling support for eNAMPT inhibition as a novel and effective therapeutic strategy for CMD in diabetes.

Visfatin impact on the proteome of porcine luteal cells during implantation.

Visfatin (VIS) is a hormone belonging to the adipokines' group secreted mainly by the adipose tissue. VIS plays a crucial role in the control of energy homeostasis, inflammation, cell differentiation, and angiogenesis. VIS expression was confirmed in the hypothalamic-pituitary-gonadal (HPG) axis structures, as well as in the uterus, placenta, and conceptuses. We hypothesised that VIS may affect the abundance of proteins involved in the regulation of key processes occurring in the corpus luteum (CL) during the implantation process in pigs. In the present study, we performed the high-throughput proteomic analysis (liquid chromatography with tandem mass spectrometry, LC-MS/MS) to examine the in vitro influence of VIS (100 ng/mL) on differentially regulated proteins (DRPs) in the porcine luteal cells (LCs) on days 15-16 of pregnancy (implantation period). We have identified 511 DRPs, 276 of them were up-regulated, and 235 down-regulated in the presence of VIS. Revealed DRPs were assigned to 162 gene ontology terms. Western blot analysis of five chosen DRPs, ADAM metallopeptidase with thrombospondin type 1 motif 1 (ADAMTS1), lanosterol 14-α demethylase (CYP51A1), inhibin subunit beta A (INHBA), notch receptor 3 (NOTCH3), and prostaglandin E synthase 2 (mPGES2) confirmed the veracity and accuracy of LC-MS/MS method. We indicated that VIS modulates the expression of proteins connected with the regulation of lipogenesis and cholesterologenesis, and, in consequence, may be involved in the synthesis of steroid hormones, as well as prostaglandins' metabolism. Moreover, we revealed that VIS affects the abundance of protein associated with ovarian cell proliferation, differentiation, and apoptosis, as well as CL new vessel formation and tissue remodelling. Our results suggest important roles for VIS in the regulation of ovarian functions during the peri-implantation period.

Insulin resistance-related circulating predictive markers in the metabolic syndrome: a systematic review in the Iranian population.

Background: Specific biomarkers for metabolic syndrome (MetS) may improve diagnostic specificity for clinical information. One of the main pathophysiological mechanisms of MetS is insulin resistance (IR). This systematic review aimed to summarize IR-related biomarkers that predict MetS and have been investigated in Iranian populations. Methods: An electronic literature search was done using the PubMed and Scopus databases up to June 2022. The risk of bias was assessed for the selected articles using the instrument suggested by the Joanna Briggs Institute (JBI). This systematic review protocol was registered with PROSPERO (registration number CRD42022372415). Results: Among the reviewed articles, 46 studies investigated the association between IR biomarkers and MetS in the Iranian population. The selected studies were published between 2009 and 2022, with the majority being conducted on adults and seven on children and adolescents. The adult treatment panel III (ATP III) was the most commonly used criteria to define MetS. At least four studies were conducted for each IR biomarker, with LDL-C being the most frequently evaluated biomarker. Some studies have assessed the diagnostic potency of markers using the area under the curve (AUC) with sensitivity, specificity, and an optimal cut-off value. Among the reported values, lipid ratios and the difference between non-HDL-C and LDL-C levels showed the highest AUCs (≥ 0.80) for predicting MetS. Conclusions: Considering the findings of the reviewed studies, fasting insulin, HOMA-IR, leptin, HbA1c, and visfatin levels were positively associated with MetS, whereas adiponectin and ghrelin levels were negatively correlated with this syndrome. Among the investigated IR biomarkers, the association between adiponectin levels and components of MetS was well established. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01347-6.

Effect of non-surgical periodontal therapy on salivary and gingival crevicular fluid concentration of visfatin in periodontal health and disease.

Background and objective: Visfatin, a pleotropic mediator mostly produced by visceral fat, is crucial in controlling the immunological and defensive systems. It serves the roles of a cytokine, an enzyme involved in energy metabolism, and a growth factor. The objective of the present study was to assess the impact of non-surgical periodontal therapy (scaling and root planing) on visfatin concentrations in saliva and gingival crevicular fluid in individuals with Periodontitis (stage-II grade-A). Materials and methods: 54 individuals were divided into Group A (Periodontally Healthy) and Group B1(Periodontitis baseline) based on periodontal parameters including plaque index (PI), gingival index (GI), probing pocket depth (PPD), clinical attachment level (CAL), and radiographic parameters. After NSPT (SRP), Group B1 patients were recalled after 4 weeks, constituting Group B2 (post NSPT group B1). At baseline and 4 weeks after non-surgical periodontal therapy (SRP), all clinical parameters, salivary and GCF samples were recorded. An ELISA kit was used to measure the levels of visfatin. Using the paired t-test, unpaired t-test, and Pearson's correlation coefficient, data were analysed using SPSS 15. Results: After non-surgical periodontal treatment (SRP), the mean salivary and gingival crevicular fluid concentration of visfatin considerably decreased to a level comparable to periodontal health. In all groups, GCF visfatin concentration was higher than salivary concentration of visfatin. In periodontitis patients, visfatin concentration in GCF was 1.5 times higher than in saliva. Conclusion: The results of this investigation suggest a direct correlation between salivary and gingival crevicular fluid visfatin concentration and periodontal tissue inflammation and disease activity.

An oncolytic HSV-1 armed with Visfatin enhances antitumor effects by remodeling tumor microenvironment against murine pancreatic cancer.

Oncolytic viruses (OVs) have shown potential in converting a "cold" tumor into a "hot" one and exhibit effectiveness in various cancer types. However, only a subset of patients respond to oncolytic virotherapy. It is important to understand the resistance mechanisms to OV treatment in pancreatic ductal adenocarcinoma (PDAC) to engineer oncolytic viruses. In this study, we used transcriptome RNA sequencing (RNA-seq) to identify Visfatin, which was highly expressed in the responsive tumors following OV treatment. To explore the antitumor efficacy, we modified OV-mVisfatin, which effectively inhibited tumor growth. For the first time, we revealed that Visfatin promoted the antitumor efficacy of OV by remodeling the tumor microenvironment, which involved enhancing CD8+ T cell and DC cell infiltration and activation, repolarizing macrophages towards the M1-like phenotype, and decreasing Treg cells using single-cell RNA sequencing (scRNA-seq) and flow cytometry. Furthermore, PD-1 blockade significantly enhanced OV-mVisfatin antitumor efficacy, offering a promising new therapeutic strategy for PDAC.