The effect of periodontal health and disease on interleukin 1ß and nesfatin-1 levels in gingival crevicular fluid: A cross-sectional study.

Introduction: Periodontitis, a chronic inflammatory disease associated with dental biofilm, poses a significant threat to oral health. This study explores the roles of interleukin 1ß (IL-1ß) and nesfatin-1 in periodontal diseases, aiming to contribute to the molecular understanding of their pathogenesis. Material and methods: A diverse cohort of 62 participants was recruited, spanning ages 20 to 60, and categorized into healthy, gingivitis, and periodontitis groups. Clinical measurements, including plaque index, gingival index, probing pocket depth, and bleeding on probing, were conducted. Gingival crevicular fluid (GCF) samples were collected for IL-1ß and nesfatin-1 analysis using enzyme-linked immunosorbent assay (ELISA). Statistical analysis employed Kruskal-Wallis and Spearman correlation tests. Results: Significant differences in oral hygiene habits were observed among groups, particularly in the 40-60 age range. Clinical indices showed variations, with the highest IL-1ß levels in the periodontitis group and the lowest nesfatin-1 levels. Correlation analysis revealed positive associations between IL-1ß, nesfatin-1, and oral indices. Conclusions: While providing valuable insights, we acknowledge this study's limitations, including a cross-sectional design and a specific age range. Future research should employ longitudinal designs and larger cohorts, and explore broader inflammatory markers, genetic influences, and confounding variables for a more comprehensive understanding of periodontal diseases. The findings underscore the complex interplay between inflammatory markers and periodontal health.

Central NUCB2/nesfatin-1 signaling ameliorates liver steatosis through suppression of endoplasmic reticulum stress in the hypothalamus.

BACKGROUND & AIMS: Nucleobindin-2 (NUCB2)/nesfatin-1, a signal with recognized anorexigenic and insulin-sensitizing properties in peripheral tissues, is expressed within the hypothalamus. However, the potential involvement of central nesfatin-1 signaling in the pathophysiology of hepatic steatosis remains unknown. This study aimed to determine whether and how central NUCB2/nesfatin-1 plays a role in liver steatosis. METHODS: We generated Nucb2 knockout (Nucb2-/-) rats and administered continuous intracerebroventricular (ICV) nesfatin-1 infusion, while observing its effect on liver steatosis. The molecular mechanism of action of nesfatin-1 was elucidated via proteomics, phosphoproteomics and molecular biology methods. RESULTS: Herein, we present compelling evidence indicating diminished NUCB2 expression in the hypothalamus of obese rodents. We demonstrated that chronic ICV infusion of nesfatin-1 mitigated both diet-induced obesity and liver steatosis in high-fat diet (HFD)-fed Nucb2-/- rats by regulating hypothalamic endoplasmic reticulum (ER) stress and Akt phosphorylation. Furthermore, we revealed that the increase in hypothalamic insulin resistance (IR) and ER stress induced by tunicamycin infusion or Ero1α overexpression exacerbated hepatic steatosis and offset the favorable influence of central nesfatin-1 on hepatic steatosis. The metabolic action of central nesfatin-1 is contingent upon vagal nerve transmission to the liver. Mechanistically, nesfatin-1 impedes ER stress and interacts with Ero1α to repress its Ser106 phosphorylation. This leads to the enhancement of Akt activity in the hypothalamus, culminating in the inhibition of hepatic lipogenesis. CONCLUSIONS: These findings underscore the importance of hypothalamic NUCB2/nesfatin-1 as a key mediator in the top-down neural mechanism that combats diet-induced liver steatosis.

Association between serum NUCB2/nesfatin­1 levels and erectile dysfunction.

Erectile dysfunction (ED) is one of the most common complaints in the male sexual health field, with a multifactorial etiology yet to be fully elucidated. Nucleobindin 2 (NUCB2)/nesfatin-1, known for its regulatory role in food intake, can also regulate the vascular, neural and hormonal systems, all of which are of great importance in the etiology of ED. The present study included 43 men with ED and 40 healthy individuals without ED. The participants were assessed using the Turkish version of the International Index of Erectile Function (IIEF-5) to determine the presence and severity of ED. Serum NUCB2/nesfatin-1, total testosterone, fasting blood glucose, hemoglobin A1c, total cholesterol, low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein, triglyceride and total prostate-specific antigen levels were all measured. The mean age of the participants was 46.77±9.87 years with an age range of 25-67 years. The mean ages of the ED and non-ED groups were 47.47±11.19 and 46.03±8.30 years, respectively. Patient age and serum biochemical parameters were found to be comparable between the two groups. The serum NUCB2/nesfatin-1 levels of the ED group were also revealed to be significantly lower compared with those of the non-ED group (P=0.019). There was a weak negative correlation between the serum NUCB2/nesfatin-1 level and the severity of ED according to the IIEF-5 score (r=-0.306; P=0.005). The receiver operating characteristic curve analysis of serum NUCB2/nesfatin-1 revealed a cut-off value of 1.25 ng/ml for distinguishing between the ED and non-ED groups (P=0.019). These findings suggest that reduced serum NUCB2/nesfatin-1 values may be implicated in the etiology of ED. Further studies are required to clarify the effect of NUCB2/nesfatin-1 on vascular physiology and erectile physiology or pathophysiology.

Research progress on the relationship between Nesfatin-1 and glucose metabolism. / Nesfatin-1ä¸Žç³–ä»£è°¢å ³ç³»çš„ç ”ç©¶è¿›å±•.

Nesfatin-1 is a neuropeptide hormone known for its biological functions, including inhibiting food intake, regulating glucose and lipid metabolism, promoting apoptosis, and providing anti-inflammatory and anti-tumor effects. Glucose metabolism is a crucial pathway for the body's energy supply. Current research has demonstrated that Nesfatin-1 can affect glucose metabolism through various mechanisms, such as inhibiting food intake, regulating enzyme activity, and improving insulin resistance, though the findings are not entirely consistent. Investigating the relationship between Nesfatin-1 and glucose metabolism may offer new insights into the diagnosis and treatment of diseases related to glucose metabolism disorders.

Nesfatin-1 is a regulator of inflammation with implications during obesity and metabolic syndrome.

Nesfatin-1, derived from the nucleobindin 2 (NUCB2) precursor, is a potent anorexigenic peptide that was discovered in 2006. Since its identification in the hypothalamus, it has been shown to have wide ranging actions within and outside of the central nervous system. One of these actions is the regulation of inflammation, which could potentially be exploited therapeutically in the context of obesity-associated inflammation in adipose tissue. Here, we review recent advances in our knowledge about the ability of nesfatin-1 to control inflammation by regulating NFκB signaling, which likely attenuates pro-inflammatory cytokine production and inhibits apoptosis.

Nesfatin-1: A Novel Diagnostic and Prognostic Biomarker in Digestive Diseases.

Nesfatin-1, deriving from a precursor protein, NUCB2, is a newly discovered molecule with anti-apoptotic, anti-inflammatory, antioxidant, and anorexigenic effects. It was initially identified in the central nervous system (CNS) and received increasing interest due to its energy-regulating properties. However, research showed that nesfatin-1 is also expressed in peripheral tissues, including the digestive system. The aim of this review is to give a résumé of the present state of knowledge regarding its structure, immunolocalization, and potential implications in diseases with inflammatory components. The main objective was to focus on its clinical importance as a diagnostic biomarker and potential therapeutic molecule in a variety of disorders, among which digestive disorders were of particular interest. Previous studies have shown that nesfatin-1 regulates the balance between pro- and antioxidant agents, which makes nesfatin-1 a promising therapeutic agent. Further in-depth research regarding the underlying mechanisms of action is needed for a better understanding of its effects.

Electroacupuncture negatively regulates the Nesfatin-1/ERK/CREB pathway to alleviate HPA axis hyperactivity and anxiety-like behaviors caused by surgical trauma.

BACKGROUND: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis constitutes a pivotal response by surgical trauma, manifesting as a critical aspect of the acute stress reaction. This hyperactivity resulted in adverse surgical outcomes and is often associated with increased postoperative anxiety. Increased evidence suggests that Nesfatin-1 plays a crucial role in stress responses and stress-related psychiatric disorders. Electroacupuncture (EA) is widely used to alleviate stress responses and anxiety, although its mechanism of action remains unclear. This study aimed to assess the mechanisms by which hypothalamic Nesfatin-1 contribute to the alleviation of HPA axis hyperactivity and anxiety by EA. METHODS: Partial hepatectomy (HT) was performed to simulate surgical trauma, and EA was applied at Zusanli (ST36) and Sanyinjiao (SP6). The levels of hypothalamic Nesfatin-1, c-Fos, and corticotropin-releasing hormone (CRH) were detected, and serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were regarded as indicators of HPA axis activity. Anxiety levels were assessed through open field tests (OFT), elevated plus maze (EPM), and light-dark box tests (LDBT). To investigate the role of Nesfatin-1, its expression was modulated using stereotactic viral injections or plasmid transfections. Transcriptome sequencing was employed to explore the downstream signaling pathways of Nesfatin-1. Additionally, brain cannula implantation was performed to facilitate targeted drug administration. RESULTS: Our findings demonstrated that EA reduced the hypothalamic overexpression of CRH and Nesfatin-1, as well as serum levels of ACTH and CORT. Additionally, it alleviated anxiety-like behaviors resulting from surgical trauma. We observed that overexpression of Nesfatin-1 in the hypothalamic paraventricular nucleus (PVN) triggered hyperactivity of the HPA axis and anxiety. Conversely, knocking down Nesfatin-1 in the PVN reversed these effects caused by surgical trauma. Transcriptome sequencing identified the extracellular regulated protein kinases (ERK)/cAMP-response element binding protein (CREB) pathway as a key mediator in the impacts of surgical trauma and EA on the hypothalamus. Both in vivo and in vitro studies showed that overexpression of Nesfatin-1 activated the ERK/CREB pathway. Furthermore, administering ERK or CREB inhibitors into the PVN mitigated HPA axis hyperactivity and anxiety-like behaviors induced by surgical trauma. Finally, EA was observed to decrease the phosphorylation levels of ERK and CREB in the PVN. CONCLUSION: EA alleviates HPA axis hyperactivity and anxiety-like behaviors caused by surgical trauma through inhibition of Nesfatin-1/ERK/CREB pathway in the hypothalamus.

Nesfatin-1 inhibits cerebral aneurysms by activating Nrf2 and inhibiting NF-κB signaling.

AIMS: Cerebral aneurysm (CA) has been considered one of the most common cerebrovascular diseases, affecting millions of people worldwide. A therapeutic agent is currently missing for the treatment of CA. Nesfatin-1 (Nes-1) is an 82-amino acid adipokine which possesses a wide range of biological functions. However, the physiological function of Nes-1 in CA is still unknown. Here, we aimed to assess the preventive effects of Nes-1 in the pathological development of CA and elucidate the mechanisms behind this. METHODS: We used an elastase-induced CA model, accompanied by a high-salt diet to induce hypertension. Additionally, diverse experimental techniques, including Verhoeff-Van Gieson staining, real time PCR, enzyme-linked immuno sorbent assay (ELISA), and immunofluorescence staining, were employed to assess CA formation, gene and protein expression, as well as the macrophage infiltration. RESULTS: Our results indicate that administration of Nes-1 significantly decreased the aneurysm size. Additionally, Nes-1 prevented inflammatory response by inhibiting the expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein 1 (MCP-1) at both the mRNA and protein levels in the Circle of Willis (COW) region. Also, the increased levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in the COW region were reduced by Nes-1. We found that Nes-1 administration suppressed the invasion of macrophages. Mechanistically, Nes-1 activated Nrf-2 by promoting its nuclear translocation but prevented the activation of the IκBα/NF-κB signaling pathway. CONCLUSION: These findings suggest that Nes-1 might be used as a promising agent for the prevention of CA.

Central thromboxane A2, prostaglandin F2α, prostaglandin E, and prostaglandin D contribute to the cardiovascular effects elicited by nesfatin-1.

Background/aim: Our recent study revealed that the expression of lipoxygenase (LOX) and cyclooxygenase (COX) enzymes in the hypothalamus is activated by nesfatin-1, leading to the liberation of leukotrienes and prostaglandins (PG), respectively. Moreover, our prior report explained that intracerebroventricular (ICV) nesfatin-1 treatment triggers cardiovascular responses mediated by central LOX and COX enzymes. Building upon our prior reports, the present investigation sought to clarify the role of cardiovascularly active central COX products, such as thromboxane (TX) A2, PGF2α, PGE, and PGD, in orchestrating nesfatin-1-evoked reactions in mean arterial pressure (MAP) and heart rate (HR). Materials and methods: The Sprague Dawley rats, which had guide cannula in the lateral ventricle for intracerebroventricular (ICV) injections and catheter in arteria femoralis for monitoring MAP and HR, were underwent central pretreatment with furegrelate (the TXA2 synthase inhibitor), PGF2α-dimethylamine (PGF2α-DA, the PGF2α receptor antagonist), or AH6809 (the PGE and PGD receptor antagonist), 5 min prior to ICV nesfatin-1 administration. The cardiovascular parameters were observed and recorded for 60 min posttreatment. Results: Nesfatin-1 induced cardiovascular responses in rats leading to pressor effect in MAP, and tachycardia following bradycardia in HR. Interestingly, ICV furegrelate, PGF2α-DA, or AH6809 pretreatment partially mitigated the cardiovascular effects revealed by nesfatin-1. Conclusion: The findings illuminate the role of nesfatin-1 in modulating MAP and HR through the central activation of specifically TXA2, PGF2α, PGE, and PGD from COX metabolites. Additionally, the study may also suggest the potential involvement of other central COX or LOX metabolites beyond these COX metabolites in mediating the cardiovascular effects produced by nesfatin-1.

Association of selected adipokines with vitamin D deficiency in children with inflammatory bowel disease.

BACKGROUND: Adipose tissue is significantly involved in inflammatory bowel disease (IBD). Vitamin D can affect both adipogenesis and inflammation. The aim of this study was to compare the production of selected adipokines, potentially involved in the pathogenesis of IBD - adiponectin, resistin, retinol binding protein 4 (RBP-4), adipocyte fatty acid binding protein and nesfatin-1 in children with IBD according to the presence of 25-hydroxyvitamin D (25(OH)D) deficiency. METHODS: The study was conducted as a case-control study in pediatric patients with IBD and healthy children of the same sex and age. In addition to adipokines and 25(OH)D, anthropometric parameters, markers of inflammation and disease activity were assessed in all participants. RESULTS: Children with IBD had significantly higher resistin levels regardless of 25(OH)D levels. IBD patients with 25(OH)D deficiency only had significantly lower RBP-4 compared to healthy controls and also compared to IBD patients without 25(OH)D deficiency. No other significant differences in adipokines were found in children with IBD with or without 25(OH)D deficiency. 25(OH)D levels in IBD patients corelated with RBP-4 only, and did not correlate with other adipokines. CONCLUSIONS: Whether the lower RBP-4 levels in the 25(OH)D-deficient group of IBD patients directly reflect vitamin D deficiency remains uncertain. The production of other adipokines does not appear to be directly related to vitamin D deficiency.

Nesfatin-1 ameliorates pathological abnormalities in Drosophila hTau model of Alzheimer's disease.

In human Alzheimer's disease (AD), the aggregation of tau protein is considered a significant hallmark, along with amyloid-beta. The formation of neurofibrillary tangles due to aberrant phosphorylation of tau disrupts microtubule stability, leading to neuronal toxicity, dysfunction, and subsequent cell death. Nesfatin-1 is a neuropeptide primarily known for regulating appetite and energy homeostasis. However, the function of Nesfatin-1 in a neuroprotective role has not been investigated. In this study, we aimed to elucidate the effect of Nesfatin-1 on tau pathology using the Drosophila model system. Our findings demonstrate that Nesfatin-1 effectively mitigates the pathological phenotypes observed in Drosophila human Tau overexpression models. Nesfatin-1 overexpression rescued the neurodegenerative phenotypes in the adult fly's eye and bristle. Additionally, Nesfatin-1 improved locomotive behavior, neuromuscular junction formation, and lifespan in the hTau AD model. Moreover, Nesfatin-1 controls tauopathy by reducing the protein level of hTau. Overall, this research highlights the potential therapeutic applications of Nesfatin-1 in ameliorating the pathological features associated with Alzheimer's disease.

Nesfatin-1 regulates the phenotype transition of cavernous smooth muscle cells by activating PI3K/AKT/mTOR signaling pathway to improve diabetic erectile dysfunction.

Objective: This study aims to explore the impact of Nesfatin-1 on type 2 diabetic erectile dysfunction (T2DMED) and its underlying mechanism in regulating the phenotypic switching of corpus cavernosum smooth muscle cells (CCSMCs). Methods: Twenty-four 4-week-old male C57 wild-type mice were randomly assigned to the control group, model group, and Nesfatin-1 treatment group. Monitoring included body weight, blood glucose levels, and penile cavernous pressure (ICP). Histochemistry and Western blot analyses were conducted to assess the expressions of α-SMA, OPN, and factors related to the PI3K/AKT/mTOR signaling pathway. CCSMCs were categorized into the control group, high glucose and high oleic acid group (GO group), Nesfatin-1 treatment group (GO + N group), sildenafil positive control group (GO + S group), and PI3K inhibitor group (GO + N + E group). Changes in phenotypic markers, cell morphology, and the PI3K/AKT/mTOR signaling pathway were observed in each group. Results: (1) Nesfatin-1 significantly ameliorated the body size, body weight, blood glucose, glucose tolerance, and insulin resistance in T2DMED mice. (2) Following Nesfatin-1 treatment, the ICP/MSBP ratio and the peak of the ICP curve demonstrated a significant increase. (3) Nesfatin-1 significantly enhanced smooth muscle and reduced collagen fibers in the corpus cavernosum. (4) Nesfatin-1 notably increased α-SMA expression and decreased OPN expression in CCSMCs. (5) Nesfatin-1 elevated PI3K, p-AKT/AKT, and p-mTOR/mTOR levels in penile cavernous tissue. Conclusions: Nesfatin-1 not only effectively improves body weight and blood glucose levels in diabetic mice but also enhances erectile function and regulates the phenotypic switching of corpus cavernosum smooth muscle. The potential mechanism involves Nesfatin-1 activating the PI3K/AKT/mTOR signaling pathway to induce the conversion of CCSMCs to a contractile phenotype.

Nesfatin-1 mitigates calcific aortic valve disease via suppressing ferroptosis mediated by GSH/GPX4 and ZIP8/SOD2 axes.

OBJECTIVE: Calcific aortic valve disease (CAVD) predominantly affects the elderly and currently lacks effective medical treatments. Nesfatin-1, a peptide derived from the cleavage of Nucleobindin 2, has been implicated in various calcification processes, both physiological and pathological. This study explores the impact of Nesfatin-1 on the transformation of aortic valve interstitial cells (AVICs) in CAVD. METHODS AND RESULTS: In vitro experiments showed that Nesfatin-1 treatment mitigated the osteogenic differentiation of AVICs. Corresponding in vivo studies demonstrated a deceleration in the progression of CAVD. RNA-sequencing of AVICs treated with and without Nesfatin-1 highlighted an enrichment of the Ferroptosis pathway among the top pathways identified by the Kyoto Encyclopedia of Genes and Genomes analysis. Further examination confirmed increased ferroptosis in both calcified valves and osteoblast-like AVICs, with a reduction in ferroptosis following Nesfatin-1 treatment. Within the Ferroptosis pathway, ZIP8 showed the most notable modulation by Nesfatin-1. Silencing ZIP8 in AVICs increased ferroptosis and osteogenic differentiation, decreased intracellular Mn2+ concentration, and reduced the expression and activity of superoxide dismutase (SOD2). Furthermore, the silencing of SOD2 exacerbated ferroptosis and osteogenic differentiation. Nesfatin-1 treatment was found to elevate the expression of glutathione peroxidase 4 (GPX4) and levels of glutathione (GSH), as confirmed by Western blotting and GSH concentration assays. CONCLUSION: In summary, Nesfatin-1 effectively inhibits the osteogenic differentiation of AVICs by attenuating ferroptosis, primarily through the GSH/GPX4 and ZIP8/SOD2 pathways.

Evaluating the impact of metabolic and cognitive stress on ghrelin and nesfatin-1 hormones in patients with diabetes and diabetic depression.

Nesfatin-1 and ghrelin, initially recognised as hormones involved in regulating energy, have emerged as crucial players with vital functions in various human body systems. In this study, we conducted a comparative assessment of nesfatin-1 and ghrelin responses in individuals experiencing metabolic stress due to diabetes, those with depressive diabetes characterised by both metabolic and mental stress, and healthy controls. We collected blood samples from a total of 90 participants, consisting of 30 people with type II diabetes mellitus (DM), 30 people with type II DM and major depressive disorders, and 30 healthy individuals. Diabetes was diagnosed based on glycated haemoglobin (HbA1c) levels, while depression was assessed using DSM-V criteria. Insulin resistance (HOMA-IR) was calculated, and serum ghrelin and nesfatin-1 levels were measured using ELISA kits. We observed statistically significant decreases in nesfatin-1 and ghrelin levels in the diabetic group (p < 0.0001). However, in the depressive diabetic group, nesfatin-1 levels increased significantly, while ghrelin levels decreased further. The nesfatin-1 to ghrelin ratio decreased in the diabetic group but increased significantly in the depressive diabetic group (p < 0.0001). Nesfatin-1 and ghrelin hormones exhibit parallel impacts in response to metabolic stress, but nesfatin-1 demonstrates contrasting actions compared to ghrelin when mental stress is added to metabolic stress. The findings of this study suggest that nesfatin-1 and ghrelin hormones may play active roles as protective, prognostic, and even etiological factors in various stress situations, particularly those involving mental stress, in addition to their known functions in regulating energy.

Renoprotective effect of Nesfatin-1 in Adenine-Induced Chronic kidney Disease: An in vitro and in vivo study.

Chronic Kidney Disease (CKD) presents a significant global health challenge with limited treatment options. Nesfatin-1, an anorexigenic peptide, has demonstrated antioxidant, anti-inflammatory, and anti-apoptotic properties in various diseases. However, the role of nesfatin-1 in CKD remains unclear. This study investigates the potential renoprotective effects of nesfatin-1 in adenine-induced CKD mice and in NRK-52E renal epithelial cells. Male C57BL/6J mice and NRK-52E renal epithelial cells were administered adenine to induce CKD. Various aspects of renal function, histopathology, oxidative stress, inflammation, apoptosis, and renal interstitial fibrosis were assessed and downstream pathways were investigated. Adenine-fed mice exhibited reduced nesfatin-1 expression and increased markers of kidney damage, including elevated blood urea nitrogen (BUN), serum creatinine, and histological abnormalities, reactive oxygen species (ROS), inflammation, apoptosis, and fibrosis. Treatment with nesfatin-1 in adenine induced mice significantly reversed these changes. Nesfatin-1 also lowered calcium levels and the expression of inflammatory markers, including IL-1ß, IL-6, TNF-α, and Nf-kB. Furthermore, nesfatin-1 reduced the expression of apoptotic markers (Caspase-3, Caspase-1, Bax/Bcl2 ratio) and restored the balance of Bcl2 and MMP. Lastly, nesfatin-1 attenuated fibrotic markers (Tgf-ß, Smad2/3,4, type IV collagen, α-SMA) in both adenine-induced CKD mice and NRK-52E cells. In conclusion, our results suggest that nesfatin-1 may enhance kidney function in adenine-induced CKD mice and NRK-52E cells. The renoprotective effects of nesfatin-1 are likely associated with its antioxidant, anti-inflammatory, anti-apoptotic, and anti-fibrotic properties.

Dynamics of Serum Inflammatory Markers and Adipokines in Patients: Implications for Monitoring Abnormal Body Weight: Preliminary Research.

This study aimed to investigate the influence of abnormal body weight on inflammatory markers and adipokine levels across varied body mass index (BMI) categories. The cohort included 46 participants categorized into normal BMI (group I; n = 19), overweight (group II; n = 14), and obesity (group III; n = 13). Inflammatory markers (hsCRP and IL-6) and adipokines (Adiponectin, Leptin, Nesfatin-1, and Zinc-α2-glycoprotein) were assessed to discern effective indicators of inflammation in individuals with abnormal body weight. Additionally, the full lipid profile was also assessed (total cholesterol, triglycerides, LDL-C, HDL-C). The results indicated significant biochemical changes, particularly in IL-6 and Leptin levels, in participants with a BMI over 25. The levels of ZAG protein were negatively correlated with the HDL-C and LDC-L levels with statistical significance (Pearson: -0.57, p = 0.001, and Pearson: -0.41, p = 0.029, for HDL-C and LDL-C, respectively), suggesting that the level of ZAG is also inversely proportional to the amount of cholesterol. Statistical analyses revealed decreased Zinc-α2-glycoprotein (ZAG) levels and increased Adiponectin, Leptin, and IL-6 levels in individuals with abnormal body weight. Correlation analyses demonstrated a statistically significant upward trend for IL-6 (p = 0.0008) and Leptin (p = 0.00001), with a similar trend observed for hsCRP without statistical significance (p = 0.113). IL-6 levels in the overweight group were 158.71% higher than in the normal-weight group, while the obese group exhibited a 229.55% increase compared to the normal-weight group. No notable changes have been recorded for the levels of Nesfatin-1. Based on our results, we propose IL-6, Leptin, and ZAG as potential biomarkers for monitoring interventions and assessing patient conditions in those with abnormal BMIs. Further research with a larger patient cohort is warranted to validate these correlations in overweight and obese individuals.

Investigation of the Relationship of Nesfatin-1, Adropin Levels and Claudin-2, Renalase Immunoreactivity with Kidney Function in an Experimental Hypertension Model.

OBJECTIVE: Hypertension is one of the cardiovascular diseases that causes the most mortality, and 95% of the causes are unknown. The aim of the study was to examine the possible correlation of nesfatin-1 levels, adropin levels, claudin-2 immunoreactivity (claudin-2 expression in the renal proximal tubule), and renalase immunoreactivity (renalase expression in the renal proximal tubule) with arterial blood pressure, kidney function, and kidney damage. METHODS: Adult male Sprague Dawley rats were divided into control and hypertension groups (8 per group). Angiotensin II vehicle was given to the control group and angiotensin II (0.7 mg/kg/day) to the hypertension group, both via an osmotic mini pump for 7 days. The animals blood pressures were measured by tail cuff plethysmography on days 1, 3, 5, and 7. On day 7, 24-hour urine, blood, and tissues were collected from the rats. RESULTS: In the hypertension group compared with the control group, there was an increase in systolic blood pressure levels after day 1. While claudin-2 immunoreactivity was reduced in the kidneys, renalase immunoreactivity was increased. There was a decrease in creatinine clearance and an increase in fractional potassium excretion (P < .05). CONCLUSION: Our results showed that claudin-2 and renalase are associated with renal glomerular and tubular dysfunction and may play discrete roles in the pathogenesis of hypertension. We believe that these potential roles warrant further investigation.

Nesfatin-1 alleviates hyperoxia-induced bronchopulmonary dysplasia (BPD) via the nuclear factor-κB (NF-κB) p65 signaling pathway.

Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease in newborns, which severely influences the health of infants and lacks effective clinical treatment strategies. The pathogenesis of BPD is correlated to enhanced inflammation and activated oxidative stress (OS). The application of antioxidants and anti-inflammatory treatment could be hot spots for BPD treatment. Nesfatin-1, a peptide with a suppressive property against inflammation, was tested herein for its potential therapeutic value in BPD. Neonatal SD rats were stimulated with hyperoxia, followed by being intraperitoneally administered with 20 µg/kg/day Nesfatin-1 for 2 weeks. Decreased RAC value in lung tissues, increased wet weight/dry weight (W/D) pulmonary ratio and bronchoalveolar lavage fluid (BALF) proteins, elevated cytokine release in BALF, increased malondialdehyde (MDA) content, and declined superoxide dismutase (SOD) activity were observed in BPD rats, all of which were sharply mitigated by Nesfatin-1. Rat epithelial type II cells (AECIIs) were handled with hyperoxia, and then cultured with 1 and 10 nM Nesfatin-1. Reduced cell viability, elevated lactate dehydrogenase production, elevated cytokine secretion, elevated MDA content, and decreased SOD activity were observed in hyperoxia-handled AECIIs, all of which were markedly alleviated by Nesfatin-1. Furthermore, activated nuclear factor-κB (NF-κB) signaling observed in both BPD rats and hyperoxia-handled AECIIs were notably repressed by Nesfatin-1. Collectively, Nesfatin-1 alleviated hyperoxia-triggered BPD by repressing inflammation and OS via the NF-κB signaling pathway.

The role of adipokines in osteoporosis management: a mini review.

The prevalence of osteoporosis has been on the rise globally. With ageing populations, research has sought therapeutic solutions in novel areas. One such area is that of the adipokines. Current literature points to an important role for these chemical mediators in relation to bone metabolism. Well-established adipokines have been broadly reported upon. These include adiponectin and leptin. However, other novel adipokines such as visfatin, nesfatin-1, meteorin-like protein (Metrnl), apelin and lipocalin-2 are starting to be addressed pre-clinically and clinically. Adipokines hold pro-inflammatory and anti-inflammatory properties that influence the pathophysiology of various bone diseases. Omentin-1 and vaspin, two novel adipokines, share cardioprotective effects and play essential roles in bone metabolism. Studies have reported bone-protective effects of omentin-1, whilst others report negative associations between omentin-1 and bone mineral density. Lipocalin-2 is linked to poor bone microarchitecture in mice and is even suggested to mediate osteoporosis development from prolonged disuse. Nesfatin-1, an anorexigenic adipokine, has been known to preserve bone density. Animal studies have demonstrated that nesfatin-1 treatment limits bone loss and increases bone strength, suggesting exogenous use as a potential treatment for osteopenic disorders. Pre-clinical studies have shown adipokine apelin to have a role in bone metabolism, mediated by the enhancement of osteoblast genesis and the inhibition of programmed cell death. Although many investigations have reported conflicting findings, sufficient literature supports the notion that adipokines have a significant influence on the metabolism of bone. This review aims at highlighting the role of novel adipokines in osteoporosis while also discussing their potential for treating osteoporosis.

Neuropeptides in the rat claustrum - An immunohistochemical detection.

Neuropeptides are involved in numerous brain activities and are responsible for a wide spectrum of higher mental functions. The main purpose of this outline structural qualitative study was to identify the possible immunoreactivity of classical neuropeptides, as well as novel ones such as nesfatin-1, phoenixin (PNX), spexin (SPX), neuromedin U (NMU) and respective receptors within the rat claustrum for the first time. The study shows the novel identification of peptidergic neurotransmission in the rat claustrum which potentially implicates a contribution of this neuropeptide to numerous central neurosecretory mechanisms.