RESUMO
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.
Assuntos
Doença de Alzheimer , Modelos Animais de Doenças , Nucleobindinas , Proteínas tau , Animais , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Nucleobindinas/metabolismo , Nucleobindinas/genética , Proteínas tau/metabolismo , Proteínas tau/genética , Humanos , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/genética , Junção Neuromuscular/metabolismo , Junção Neuromuscular/patologia , Animais Geneticamente Modificados , Drosophila , Locomoção , LongevidadeRESUMO
Nesfatin-1 is a novel adipocytokine consisting of 82 amino acids with anorexic and anti-hyperglycemic properties. Further studies of nesfatin-1 have shown it to be closely associated with neurological disorders. Changes in nesfatin-1 levels are closely linked to the onset, progression and severity of neurological disorders. Nesfatin-1 may affect the development of neurological disorders and can indicate disease evolution and prognosis, thus informing the choice of treatment options. In addition, regulation of the expression or level of nesfatin-1 can improve the level of neuroinflammation, apoptosis, oxidative damage and other indicators. It is demonstrated that nesfatin-1 is involved in neuroprotection and may be a therapeutic target for neurological disorders. In this paper, we will also discuss the role of nesfatin-1 as a biomarker in neurological diseases and its potential mechanism of action in neurological diseases, providing new ideas for the diagnosis and treatment of neurological diseases.
Assuntos
Proteínas de Ligação ao Cálcio , Doenças do Sistema Nervoso , Humanos , Nucleobindinas , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação a DNA/metabolismo , Biomarcadores/metabolismo , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/tratamento farmacológicoRESUMO
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.
Assuntos
Displasia Broncopulmonar , Hiperóxia , Animais , Humanos , Recém-Nascido , Ratos , Animais Recém-Nascidos , Displasia Broncopulmonar/tratamento farmacológico , Displasia Broncopulmonar/etiologia , Displasia Broncopulmonar/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Hiperóxia/metabolismo , Inflamação/metabolismo , Pulmão/metabolismo , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Superóxido Dismutase/metabolismoRESUMO
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.
Assuntos
Adipocinas , Deficiência de Vitamina D , Vitamina D , Humanos , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/sangue , Masculino , Feminino , Criança , Estudos de Casos e Controles , Adipocinas/sangue , Adolescente , Vitamina D/sangue , Vitamina D/análogos & derivados , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Proteínas Plasmáticas de Ligação ao Retinol/análise , Resistina/sangue , Nucleobindinas/sangue , Adiponectina/sangue , Adiponectina/deficiência , Proteínas de Ligação ao Cálcio/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Proteínas de Ligação a DNA/sangue , Biomarcadores/sangue , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/complicaçõesRESUMO
Nesfatin-1 has recently emerged as a modulator of ovarian functions in mammals. Studies in non-mammalian vertebrates, though limited and majorly restricted to fishes, have evidenced a role of this peptide in the regulation of ovarian steroidogenesis and oocyte maturation. Interestingly, nesfatin-1 remains completely unexplored in reptiles. Therefore, the present study aimed to identify nesfatin-1 and elucidate its role and regulation in the ovary of Hemidactylus flaviviridis. Ovarian expression of nucb2/nesfatin-1 was highest during late recrudescence and breeding while it was lowest during regression. Follicular stage-dependent expression analysis showed significantly high expression of nucb2/nesfatin-1 in previtellogenic follicles. Further, in vitro treatment of recrudescent wall lizard ovaries with nesfatin-1 resulted in increased expression of anti-apoptotic gene, bcl-2, along with a concomitant decline in the pro-apoptotic gene, caspase-3. In addition, proliferation/differentiation markers like scf, c-kit, pcna, and bmp-15 were stimulated in ovaries incubated with the peptide. Ovarian steroidogenesis was also positively influenced by nesfatin-1 as treatment with the peptide resulted in heightened star expression as well as increased estradiol and progesterone production. Also, all concentrations of nesfatin-1 stimulated glucose uptake and metabolism in wall lizard ovary. Our observations provide the first evidence of ovarian functions of nesfatin-1 in a reptile. Further, ovarian nucb2/nesfatin-1 was differentially regulated by gonadotropin and sex steroids wherein its expression was stimulated by dihydrotestosterone (DHT) and 17ß-estradiol (E2) but inhibited by follicle-stimulating hormone (FSH). In summary, this is the first report of the presence, reproductive stage-dependent expression, role, and regulation of ovarian nucb2/nesfatin-1 in H. flaviviridis.
Assuntos
Lagartos , Ovário , Feminino , Animais , Ovário/metabolismo , Estradiol/metabolismo , Hormônio Foliculoestimulante/metabolismo , Reprodução , MamíferosRESUMO
Previous studies have shown that nuclear binding protein 2 (NUCB2) is expressed in the human placenta and increases with an increase in the syncytialization of trophoblast cells. This study aimed to investigate the role of NUCB2 in the differentiation and fusion of trophectoderm cells. In this study, the expression levels of NUCB2 and E-cadherin in the placentas of rats at different gestation stages were investigated. The results showed that there was an opposite trend between the expression of placental NUCB2 and E-cadherin in rat placentas in different trimesters. When primary human trophoblast (PHT) and BeWo cells were treated with high concentrations of Nesfatin-1, the trophoblast cell syncytialization was significantly inhibited. The effects of NUCB2 knockdown in BeWo cells and Forskolin-induced syncytialization were investigated. These cells showed a significantly decreased cell fusion rate. The mechanism underlying NUCB2-regulated trophoblast cell syncytialization was explored using RNA-Seq and the results indicated that the epidermal growth factor receptor (EGFR)-phospholipase C gamma 1 (PLCG1)-calmodulin-dependent protein kinase IV (CAMK4) pathway might be involved. The results suggested that the placental expression of NUCB2 plays an important role in the fusion of trophoblasts during differentiation via the EGFR-PLCG1-CAMK4 pathway.
Assuntos
Nucleobindinas , Placenta , Placentação , Trofoblastos , Animais , Feminino , Gravidez , Ratos , Caderinas/metabolismo , Proteína Quinase Tipo 4 Dependente de Cálcio-Calmodulina/metabolismo , Proteínas de Transporte/metabolismo , Fusão Celular , Receptores ErbB/metabolismo , Proteínas Nucleares/metabolismo , Fosfolipase C gama/metabolismo , Placenta/metabolismo , Trofoblastos/metabolismo , Nucleobindinas/metabolismoRESUMO
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.
Assuntos
Nucleobindinas , Ratos Sprague-Dawley , Tromboxano A2 , Animais , Nucleobindinas/farmacologia , Ratos , Masculino , Tromboxano A2/metabolismo , Dinoprosta/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Dinoprostona/farmacologia , Dinoprostona/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/farmacologia , Pressão Sanguínea/efeitos dos fármacosRESUMO
BACKGROUND: Reprogramming lipid metabolism for tumor metastasis is essential in breast cancer, and NUCB2/Nesfatin-1 plays a crucial role in regulating energy metabolism. Its high expression is associated with poor prognosis in breast cancer. Here, we studied whether NUCB2/Nesfatin-1 promotes breast cancer metastasis through reprogramming cholesterol metabolism. METHODS: ELISA was employed to measure the concentration of Nesfatin-1 in the serum of breast cancer patients and the control group. Database analysis suggested that NUCB2/Nesfatin-1 might be acetylated in breast cancer, which was confirmed by treating the breast cancer cells with acetyltransferase inhibitors. Transwell migration and Matrigel invasion assays were conducted, and nude mouse lung metastasis models were established to examine the effect of NUCB2/Nesfatin-1 on breast cancer metastasis in vitro and in vivo. The Affymetrix gene expression chip results were analyzed using IPA software to identify the critical pathway induced by NUCB2/Nesfatin-1. We evaluated the effect of NUCB2/Nesfatin-1 on cholesterol biosynthesis through the mTORC1-SREBP2-HMGCR axis by utilizing mTORC1 inhibitor and rescue experiments. RESULTS: NUCB2/Nesfatin-1 was found to be overexpressed in the breast cancer patients, and its overexpression was positively correlated with poor prognosis. NUCB2 was potentially acetylated, leading to high expression in breast cancer. NUCB2/Nesfatin-1 promoted metastasis in vitro and in vivo, while Nesfatin-1 rescued impaired cell metastasis induced by NUCB2 depletion. Mechanistically, NUCB2/Nesfatin-1 upregulated cholesterol synthesis via the mTORC1 signal pathway, contributing to breast cancer migration and metastasis. CONCLUSIONS: Our findings demonstrate that the NUCB2/Nesfatin-1/mTORC1/SREBP2 signal pathway is critical in regulating cholesterol synthesis, essential for breast cancer metastasis. Thus, NUCB2/Nesfatin-1 might be utilized as a diagnostic tool and also used in cancer therapy for breast cancer in the future.
Assuntos
Neoplasias da Mama , Proteínas de Ligação ao Cálcio , Animais , Camundongos , Proteínas de Ligação ao Cálcio/metabolismo , Colesterol , Proteínas de Ligação a DNA/metabolismo , Nucleobindinas/genética , Nucleobindinas/metabolismo , Regulação para Cima , Humanos , Feminino , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologiaRESUMO
Bronchopulmonary dysplasia (BPD) is a pulmonary disease commonly observed in premature infants and it is reported that oxidative stress is a critical induction factor in BPD and is considered as a promising target for treating BPD. Nesfatin-1 is a brain-gut peptide with inhibitory effects on food intake, which is recently evidenced to show suppressive effect on oxidative stress. The present study aims to explore the therapeutic effect and mechanism of Nesfatin-1 in BPD mice. AECIIs were extracted from newborn rats and exposed to hyperoxia for 24 h, followed by treatment with 5 and 10 nM Nesfatin-1. Declined cell viability, increased apoptotic rate, upregulated Bax, downregulated Bcl-2, increased release of ROS and MDA, and suppressed SOD activity were observed in hyperoxia-treated AECIIs, which were extremely reversed by Nesfatin-1. Newborn rats were exposed to hyperoxia, followed by treated with 10 µg/kg Nesfatin-1 and 20 µg/kg Nesfatin-1. Severe pathological changes, elevated MDA level, and declined SOD activity were observed in lung tissues of BPD mice, which were rescued by Nesfatin-1. Furthermore, the protective effect of Nesfatin-1 on hyperoxia-challenged AECIIs was abolished by silencing SIRT1. Collectively, Nesfatin-1 alleviated hyperoxia-induced lung injury in newborn mice by inhibiting oxidative stress through regulating SIRT1/PGC-1α pathway.
Assuntos
Displasia Broncopulmonar , Hiperóxia , Nucleobindinas , Displasia Broncopulmonar/etiologia , Displasia Broncopulmonar/terapia , Hiperóxia/complicações , Animais , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Nucleobindinas/farmacologia , Nucleobindinas/uso terapêutico , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Superóxido Dismutase/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Malondialdeído/metabolismo , Ratos Sprague-Dawley , Masculino , FemininoRESUMO
PURPOSE: The association of NUCB-2/Nesfatin-1 with nasopharyngeal carcinoma (NPC) remains unclear. We clarified the role of NUCB-2/Nesfatin-1 in the development, progression and diagnosis of NPC. MATERIALS AND METHODS: In nasopharyngeal carcinoma cell lines (5-8 F, 6-10B, CNE1, CNE2 and NP69), western blotting, MTT, EdU and other techniques were performed to investigate the role of NUCB-2 in nasopharyngeal carcinoma. 70 tissue samples (39 NPC and 31 rhinitis) and 140 serum samples (including NPC, rhinitis, other head and neck tumors and healthy control) were included to explore the expression of NUCB-2 and its metabolite Nesfatin-1 in tissues or serum of patients with nasopharyngeal carcinoma. RESULTS: NUCB-2 level in NPC tissue was higher than that in rhinitis tissue (P < 0.05). Suppression of NUCB-2 in the NPC cell line CNE2 inhibited proliferation and clone formation of the cells; on the contrary, improvement of NUCB-2 in the NPC cell line CNE1 promoted cell propagation and clone development. An elevated serum level of NUCB-2 in NPC patients was detected, compared to that in patients with other head and neck tumors, rhinitis or healthy donors. Determination of nesfatin-1 combined with EA-IgA, VCA-IgA and Rta-IgG in serum samples for NPC diagnosis reached a sensitivity of 93.6% and a specificity of 94.5%, while the positive and negative predictive value of this diagnostic model was 89.8% and 96.6%, and the accuracy yielded 94.2%. CONCLUSION: This study revealed that NUCB-2 could enhance proliferation of NPC cells and NUCB-2/nesfatin-1 has the potential to be a serological marker to aid early diagnosis of nasopharyngeal carcinoma.
RESUMO
The aim of this rapid review is to examine the research evidence that presents the effects of physical activity and exercise on Nucleobindin-2 (NUCB2) gene expression and Nesfatin-1 concentration. Five databases (PubMed, Science Direct, Springer, Wiley, and Google Scholar) were searched for eligible studies from the earliest available date to August 2023. In human studies, Nesfatin-1 concentration either remains unchanged or increases after exercise training. It appears that higher exercise intensity and longer duration of training accentuate the increase of blood Nesfatin-1 concentration. The few human studies that have examined the acute response of exercise on Nesfatin-1 concentration from blood draws show conflicting results. There is a severe lack of biopsy studies in humans which warrants attention. All published animal studies have used the mouse model. The majority show that regular exercise training increases tissue NUCB2/Nesfatin-1. In some animal studies, where the effects of exercise on tissue Nesfatin-1 concentration has been seen as significant, there has been no significant effect of exercise on plasma Nesfatin-1 concentration. All animal studies evaluated the effect of endurance training except one which used resistance training. No animal studies have investigated the effects of acute exercise, which warrants investigation. In conclusion, human and animal studies have shown that physical training can increase NUCB2/Nesfatin-1, but research evidence examining the effect of acute exercise is in its infancy. In addition, future comparative studies are needed to compare the effects of different training protocols on NUCB2/Nesfatin-1 in humans and animals.
Assuntos
Proteínas de Ligação ao Cálcio , Proteínas de Ligação a DNA , Exercício Físico , Animais , Humanos , Camundongos , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Expressão Gênica , Nucleobindinas/genéticaRESUMO
Nesfatin-1 is a pleiotropic hormone implicated in various physiological functions including reproduction. Studies though limited, have established an important role of the peptide in regulation of testicular functions in mammals and fishes. However, role of nesfatin-1 in regulation of spermatogenesis and testicular steroidogenesis remains completely unexplored in reptiles. Therefore, present study aimed to develop an insight into reproductive phase-dependent testicular expression, function and regulation of nucb2/nesfatin-1 in a reptile, Hemidactylus flaviviridis. Expression of nucb2/nesfatin-1 in testis of wall lizard varied significantly depending upon reproductive phase, being highest in the active phase while lowest during regressed phase. Further, in vitro treatment of wall lizard testis with nesfatin-1 showed a concentration- and time-dependent stimulatory effect of the peptide on expression of cell proliferation and differentiation markers like scf, c-kit and pcna suggesting a spermatogenic role of nesfatin-1 in wall lizard. Also, nesfatin-1 stimulated the anti-apoptotic marker, bcl-2 while inhibited the apoptotic marker, caspase-3, suggesting its role as an inhibitor of apoptosis of testicular cells. Further, treatment with nesfatin-1 resulted in significantly higher expression of star along with a concomitant increase in testosterone production by the lizard testis. The present study also demonstrates hormonal regulation of testicular nucb2/nesfatin-1 wherein follicle-stimulating hormone (FSH) inhibited while sex steroids like dihydrotestosterone (DHT) and 17ß-estradiol-3-benzoate (E2) stimulated the mRNA expression of nesfatin-1. Observations from the current study for the first time provide comprehensive evidence of spermatogenic and steroidogenic role of nesfatin-1 as well as its hormonal regulation in the testis of a reptile, H. flaviviridis.
Assuntos
Lagartos , Testículo , Masculino , Animais , Testículo/metabolismo , Testosterona/farmacologia , Testosterona/metabolismo , Espermatogênese/fisiologia , Lagartos/metabolismo , Hormônio Foliculoestimulante/metabolismo , Mamíferos/metabolismoRESUMO
Background/aim: Due to the increasing mortality and morbidity rates in diabetes mellitus (DM), which is one of the biggest health problems of our age, many treatment modalities are still being tried. The positive effects of metformin (MET) and physical exercise (EXE) on the pathophysiology of diabetes are well known. In this study, it was aimed to detail these positive effects of MET and EXE in combination on the basis of inflammation, apoptosis mechanisms, and endogen nesfatin-1 (NES-1) synthesis. Materials and methods: Twenty-seven type 2 DM (DM-2) male Wistar Albino rats were divided into 4 groups, as the high-fat diet (HFD), MET, EXE, and MET+EXE groups. The total duration of the study was 3 months. At the end of the experiment, blood glucose and lipid profiles were measured. Histopathological evaluation was performed on the cardiac and aortic tissues and apoptotic markers were evaluated immunohistochemically. Inflammatory markers and NES-1 levels were analyzed by enzyme-linked immunosorbent assay. Results: The plasma glucose, homeostatic model evaluation-insulin resistance (HOMA-IR), low-density lipoprotein (LDL) levels increased, and high-density lipoprotein (HDL) levels decreased significantly in the HFD group. In the treatment groups, the glucose, HOMA-IR, LDL, NES-1 levels in the plasma, as well as tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), IL-6, caspase-3 (Cas-3), Bcl-2-associated X protein (Bax), and histopathological findings of inflammation in tissues were decreased. Additionally, there was an increase in plasma insulin, HDL, and tissue B-cell lymphoma-2 and levels. Conclusion: It was observed that the MET and EXE treatments in the DM-2 model reduced cellular damage mechanisms such as inflammation and apoptosis. The decrease in NES-1 levels was thought to be secondary to this antiinflammatory effect. In conclusion, the results demonstrated the effectiveness of EXE in reducing DM-2 and the NES-1 levels. Further studies are needed to evaluate the effect in different EXE models and treatment durations.
Assuntos
Diabetes Mellitus Tipo 2 , Dieta Hiperlipídica , Metformina , Proteínas Proto-Oncogênicas c-bcl-2 , Ratos Wistar , Transdução de Sinais , Natação , Proteína X Associada a bcl-2 , Animais , Metformina/farmacologia , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Ratos , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Natação/fisiologia , Proteína X Associada a bcl-2/metabolismo , Obesidade/complicações , Condicionamento Físico Animal/fisiologia , Hipoglicemiantes/farmacologia , Apoptose/efeitos dos fármacos , Aorta/efeitos dos fármacos , Nucleobindinas , Diabetes Mellitus Experimental/complicaçõesRESUMO
OBJECTIVE: The aim: To study the nesfatin-1 activity in the blood serum of patients with chronic heart failure (CHF) of ischemic origin against the background of such metabolic disorders as type 2 diabetes mellitus (T2DM) and obesity. PATIENTS AND METHODS: Materials and methods: 154 patients with CHF were examined, and divided into 4 groups, according to the presence of metabolic disorders. Group 1 included patients with CHF on the background of coronary heart disease (CHD) and T2DM and obesity (n=42). The second group consisted of patients with heart failure on the background of CHD with concomitant T2DM (n=46), the third group - with concomitant obesity (n=36), the fourth group was formed from patients with signs of heart failure of ischemic origin without metabolic disorders (n=30). The control group (CG) included 30 practically healthy persons of comparable age. RESULTS: Results: The mean level of serum nesfatin-1 was 1.64±0.27 ng/mL in the СHF group, 0.342±0.19 ng/mL in the CHF + T2DM + obesity group, 1.06±0.36 ng/ mL in the obese + CHF group, 0.96±0.27 ng/mL in the CHF + T2DM group and 2.98±0.38 ng/mL in the CG. Significant correlation was found between the serum nesfatin-1 level and BMI (r=-0.34, p<0.05), HOMA (r=-0.54, p<0.05), insulin (r=-0.41, p<0.05). No significant correlation was found between the serum nesfatin-1 level and blood glucose level (r=0.13, p=0.65). CONCLUSION: Conclusions: Thus, nesfatin-1 may play a significant role in the pathogenesis of both weight-related abnormalities and type 2 diabetes mellitus in patients with chronic heart failure of ischemic origin.
Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Humanos , Nucleobindinas , Diabetes Mellitus Tipo 2/complicações , Proteínas de Ligação ao Cálcio , Proteínas de Ligação a DNA , Soro , Obesidade/complicações , Insuficiência Cardíaca/complicaçõesRESUMO
Background: Recent changes in dietary habits have resulted in increased intake of advanced glycation end products (AGEs), which are known to have a predominant contribution to the pathogenesis and complications of coronary artery disease (CAD). AGEs are also thought to induce weight gain by affecting appetite, energy expenditure, and brown adipose tissue (BAT). Here, we investigated whether the restriction of dietary AGEs could affect appetite, body composition, anthropometric indices, and BAT-derived markers in CAD patients treated with angioplasty. Materials and Methods: Forty-two stented CAD patients were randomly allocated into two groups that received either a low-AGEs or a control diet for 12 weeks. At baseline and postintervention, fasting blood samples were analyzed for total AGEs, nesfatin-1, and BAT-derived markers (fibroblast growth factor 21 and neuregulin 4). Subjective appetite ratings and body composition were evaluated using the Visual Analog Scale (VAS) and bioelectric impedance analysis. Anthropometric indices, including fat mass index (FMI), abdominal volume index (AVI), and body adiposity index (BAI), were calculated through the relevant formula. Results: Restricting dietary AGEs for 12 weeks could cause a significant reduction in weight, FMI, AVI, and BAI (P < 0.05) compared to the comparison group. In addition, VAS data analyses indicated a significant decrease in the sense of hunger and prospective food intake (P < 0.05) in the intervention group compared to the comparison group. No significant difference was seen in the measured biochemical markers between the two groups. Conclusion: This study indicated that the low-AGEs diet could decrease appetite, weight, and anthropometric indices in stented CAD patients.
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Nesfatin-1, a newly discovered adipokine derived from nucleobindin-2 (NUCB2), has been described as a new prognostic marker in cancers. This study aimed to explore the functional role of NUCB2/nesfatin-1 in the cell proliferation, migration and invasion in gastric carcinoma (GC). The expressions of NUCB2/nesfatin-1 in GC tissues and normal adjacent tissues (NATs) were compared, and the effect of inhibition of NUCB2/nesfatin-1 on the cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in GC cell line SGC-7901 was investigated. Cell transfection was conducted to inhibit NUCB2/nesfatin-1 by short hairpin RNA. Cell proliferation, migration and invasion abilities were determined using cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), wound healing and transwell assays, respectively. The expressions of EMT markers E-Cadherin and N-Cadherin were determined using western blotting. The expression of NUCB2/nesfatin-1 protein in GC tissues was significantly increased compared with that in NATs. Consistently, the serum concentrations of NUCB2/nesfatin-1 were significantly higher in patients with GC as compared with those in the control group. Moreover, the results of CCK-8 assay and EdU assay indicated that knockdown of NUCB2/nesfatin-1 could markedly decrease SGC-7901 proliferation. Furthermore, the results of wound healing assay and transwell assay demonstrated that knockdown of NUCB2/nesfatin-1 significantly suppressed SGC-7901 migration and invasion abilities. Additionally, knockdown of NUCB2/nesfatin-1 decreased the expressions of N-Cadherin and increased the expressions of E-Cadherin in SGC-7901 cells. These findings suggest that knockdown of NUCB2/nesfatin-1 suppressed the proliferation, migration, invasion and EMT of SGC-7901 cells, suggesting a potentially promising therapeutic target for GC.
Assuntos
Carcinoma , Neoplasias Gástricas , Adipocinas/metabolismo , Caderinas/genética , Caderinas/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Proliferação de Células/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Transição Epitelial-Mesenquimal/genética , Humanos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Nucleobindinas , RNA Interferente Pequeno , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologiaRESUMO
Nesfatin-1 and -2 are produced from a reaction in which the N-terminus of human Nucleobindin-2 undergoes proteolytical processing. To date, Nucleobindin-2 and/or nesfatin-1 have only been shown to act as peptide hormones. On the other hand, the purpose of nesfatin-2 remains unknown. Since Nucleobindin-2/nesfatin-1 is thought impact the control of a wide range of physiological processes, including energy homeostasis, neurodegenerative processes and carcinogenesis, its ligands/interactions deserve special studies and attention. However, there are no reports about the molecular properties of the proteolytical products of human Nucleobindin-2 in the literature. Hence, this study aimed to analyze the effect of Zn(II) and Ca(II) on human nesfatin-1, -2, and -1/2 structures. Herein, we report that human nesfatin-1 is a member of the intrinsically disordered protein family, as indicated by circular dichroism and analytical ultracentrifugation experiments. In contrast, we found that the human nesfatin-2 and nesfatin-1/2 structures were globular with intrinsically disordered regions. Under Zn(II) treatment, we observed concentration-dependent structurization and compaction of intrinsically disordered nesfatin-1 and its propensity for oligomerization, as well as destabilization of both nesfatin-2 and nesfatin-1/2. Furthermore, dissociation constants for Zn(II) binding by nesfatin-1, nesfatin-2, and nesfatin-1/2 were also reported. Moreover, structurally distinct nesfatin-1 and -2 seem to be interdependent when linked together, as indicated by the observed molecular properties of nesfatin-1/2, which in turn are not a simple sum of the properties exhibited by the former peptides. Thus, herein, we shed new light on the molecular behavior of human nesfatins, which might help to elucidate the complex function of those peptides. Video abstract.
Assuntos
Proteínas Intrinsicamente Desordenadas , Hormônios Peptídicos , Humanos , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas Intrinsicamente Desordenadas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Nucleobindinas , Hormônios Peptídicos/metabolismoRESUMO
BACKGROUND: Nesfatin-1 (NES-1), an anorexigenic peptide, was reported to have anti-inflammatory and anti-apoptotic actions in several inflammation models. METHODS: To elucidate potential renoprotective effects of NES-1, unilateral ureteral obstruction (UUO) was induced in male Sprague Dawley rats by ligating left ureters. The rats were injected intraperitoneally with either saline (SL) or NES-1 (10 µg/kg/day) for 7 or 14 days (n = 8 in each group). On the 7th or 14th day, obstructed kidneys were removed for the isolation of leucocytes for flow-cytometric analysis and the assessments of biochemical and histopathological changes. RESULTS: Opposite to glutathione levels, renal myeloperoxidase activity in the SL-treated UUO group was significantly increased compared with the sham-operated group, while NES-1 treatment abolished the elevation. The percentages of CD8+/CD4+ T-lymphocytes infiltrating the obstructed kidneys were increased in the SL-treated groups but treatment with NES-1 did not prevent lymphocyte infiltration. Elevated tumour necrosis factor-alpha (TNF-α) levels in SL-treated UUO group were decreased with NES-1. Although total degeneration scores were similarly increased in all UUO groups, tubular dilatation scores were significantly increased in UUO groups and lowered by NES-1 only in the 7-day treated group. Elevated interstitial fibrosis scores in the SL-treated groups were decreased in both 7- and 14-day NES-1 treated groups, while alpha-smooth muscle actin (α-SMA) and apoptosis scores were depressed in both NES-1 treated groups. CONCLUSION: The present data demonstrate that UUO-induced renal fibrosis is ameliorated by NES-1, which appears to involve the inhibition of neutrophil infiltration and thereby amelioration of oxidative stress and inflammation. These data suggest that NES-1 may have a regulatory role in protecting the kidneys against obstruction-induced renal injury.
Assuntos
Nefropatias , Obstrução Ureteral , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Fibrose , Humanos , Inflamação/patologia , Rim/patologia , Nefropatias/tratamento farmacológico , Nefropatias/etiologia , Nefropatias/prevenção & controle , Masculino , Ratos , Ratos Sprague-Dawley , Obstrução Ureteral/complicações , Obstrução Ureteral/patologiaRESUMO
PURPOSE: Reducing the mean age of puberty onset in recent years has crucial public health, clinical, and social implications. This study aimed to evaluate the serum levels of appetite-related peptides (leptin, ghrelin, nesfatin-1, and orexin-A) and anthropometric data in girls with premature thelarche (PT). METHODS: We enrolled 44 girls aged 4-8 years diagnosed with PT and 33 age-matched healthy girls as controls. The demographic data of the girls were obtained using a questionnaire. Anthropometric data were measured and fasting blood samples were collected. RESULTS: Body weight, height, body mass index (BMI), body fat mass, and basal metabolic rate (BMR) were higher in the PT group than in the control group (p < 0.05). Serum leptin (p < 0.001), nesfatin-1 (p = 0.001), and orxein-A (p < 0.001) levels were significantly higher in the PT group than in healthy controls. However, there were no significant differences in the serum ghrelin levels between the groups (p > 0.05). The results of multivariate logistic regression revealed that serum leptin level (OR (95% CI): 42.0 (10.91, 173.06), p < 0.001), orexin-A (OR (95% CI): 1.14 (1.04, 1.24), p = 0.006), and BMI for age z-score (OR (95% CI): 6.97 (1.47, 33.4), p = 0.014) elevated the risk of incidence of PT at 4-8 girls. CONCLUSION: These results suggest that in addition to serum leptin levels, serum orexin-A and nesaftin-1 can take part in the initiation of PT. Few studies have investigated the relationship between nesfatin-1 and orexin-A levels and age at onset of puberty; hence, it should be a subject for future studies.
Assuntos
Leptina , Puberdade Precoce , Índice de Massa Corporal , Feminino , Grelina , Humanos , OrexinasRESUMO
OBJECTIVE: Nesfatin-1 plays an important role in regulating metabolism, appetite, gut motility, and eating behavior. It is suspected that abnormalities in nesfatin-1 secretion may be involved in the development of anorexia nervosa, and as such, this study aims to investigate the "circumstances of" nesfatin-1 in patients with functional hypothalamic amenorrhea (FHA). MATERIALS AND METHODS: One hundred and forty-seven patients with FHA were enrolled to the present study. A control group consisting of 88 healthy, age-matched subjects was used. Both study and control groups had blood samples drawn to establish baseline serum concentrations of luteinizing hormone, follicle-stimulating hormone, estradiol, prolactin, thyroid-stimulating hormone, fT4, morning cortisol, dehydroepiandrosterone sulfate, testosterone, glucose, and insulin. Nesfatin-1 was also measured with the use of enzyme-linked immunosorbent assay. RESULTS: Patients with FHA were found to have a significantly decreased concentration of serum nesfatin-1 when compared to healthy controls (6.21 ± 4.79 vs. 8.64 ± 6.63 respectively, p = 0.005). No statistically significant difference in nesfatin-1 levels was found between patients with normal and decreased BMI in the FHA group. Significant positive correlation was observed between serum nesfatin-1 concentration and 17-ß-estradiol, while a significant negative correlation was observed between serum nesfatin-1 concentration and patient age, fasting glucose, and HDL levels. CONCLUSIONS: This is the first known study to examine nesfatin-1 concentration in the context of clinical FHA. Patients with FHA were found to have decreased serum nesfatin-1 concentrations. This finding may prove instrumental in our future approach managing patients with FHA.