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1.
PLoS One ; 19(9): e0304485, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39226294

RESUMO

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.


Assuntos
Disfunção Erétil , Miócitos de Músculo Liso , Nucleobindinas , Pênis , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Masculino , Disfunção Erétil/metabolismo , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/etiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Camundongos , Miócitos de Músculo Liso/metabolismo , Nucleobindinas/metabolismo , Pênis/metabolismo , Fenótipo , Camundongos Endogâmicos C57BL , Osteopontina/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Actinas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicações , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicações
2.
Gen Physiol Biophys ; 43(5): 457-467, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39140686

RESUMO

In this study, we investigated the effects of peripheral nesfatin-1 on basal brain activity and 4-aminopyridine (4-AP)-induced epileptiform activity, and its relationship with the electrocorticogram (ECoG) power spectrum and EEG bands. Forty-nine male Wistar rats were divided into seven groups: control sham, 4-AP (2.5 mg/kg i.p.), Nesfatin-1 (1, 2, and 4 µg/kg i.p.), Nesfatin-1 (2 µg/kg) post-treatment, and Nesfatin-1 (2 µg/kg) pre-treatment. Recordings were conducted for 70 min under ketamine/xylazine (90/10 mg/kg) anesthesia. In the post-treatment group, nesfatin-1 was injected 20 min after 4-AP induction. In the pre-treatment groups, nesfatin-1 was administered following basal recordings and before 4-AP injection. 4-AP induced epileptiform activity in all animals, peaking at 30 min. Nesfatin-1 (2 µg/kg) reduced basal brain activity (p < 0.05) and decreased alpha, delta, and theta bands in ECoG. Post-treatment of nesfatin-1 did not affect 4-AP-induced activity (p > 0.05) but increased gamma band activity (p > 0.05). Pre-treatment of nesfatin-1 reduced epileptiform activity between 50 and 60 min (p < 0.05), decreased delta bands, and increased gamma bands (p > 0.05). We conclude that peripheral nesfatin-1 modulates normal brain activity but has limited effects on abnormal discharges.


Assuntos
Encéfalo , Epilepsia , Nucleobindinas , Ratos Wistar , Animais , Masculino , Ratos , Epilepsia/fisiopatologia , Epilepsia/induzido quimicamente , Epilepsia/sangue , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Proteínas de Ligação a DNA/administração & dosagem , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/administração & dosagem , Eletroencefalografia , Proteínas do Tecido Nervoso/administração & dosagem , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/farmacologia , Resultado do Tratamento , Anticonvulsivantes/farmacologia , Anticonvulsivantes/administração & dosagem
3.
CNS Neurosci Ther ; 30(8): e14864, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39097921

RESUMO

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.


Assuntos
Aneurisma Intracraniano , Fator 2 Relacionado a NF-E2 , NF-kappa B , Nucleobindinas , Transdução de Sinais , Animais , Masculino , Ratos , Aneurisma Intracraniano/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
4.
Biochem Biophys Res Commun ; 727: 150311, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950494

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 , Longevidade
5.
Turk J Med Sci ; 54(3): 598-606, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39049997

RESUMO

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 fármacos
6.
BMC Pediatr ; 24(1): 426, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961351

RESUMO

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/complicações
7.
Free Radic Biol Med ; 222: 149-164, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38851518

RESUMO

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.


Assuntos
Estenose da Valva Aórtica , Valva Aórtica , Calcinose , Ferroptose , Nucleobindinas , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Superóxido Dismutase , Ferroptose/genética , Nucleobindinas/metabolismo , Nucleobindinas/genética , Animais , Valva Aórtica/patologia , Valva Aórtica/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Calcinose/metabolismo , Calcinose/patologia , Calcinose/genética , Estenose da Valva Aórtica/metabolismo , Estenose da Valva Aórtica/patologia , Estenose da Valva Aórtica/genética , Superóxido Dismutase/metabolismo , Superóxido Dismutase/genética , Humanos , Proteínas de Transporte de Cátions/metabolismo , Proteínas de Transporte de Cátions/genética , Glutationa/metabolismo , Masculino , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Camundongos , Ratos , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteoblastos/efeitos dos fármacos , Modelos Animais de Doenças , Diferenciação Celular , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/genética
8.
Sci Rep ; 14(1): 11261, 2024 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760405

RESUMO

Here, we focused on the role of Nucleobindin 2 (NUCB2), a multifunctional protein, in gastric carcinoma (GC) progression. NUCB2 expression was investigated in 150 GC cases (20 non-invasive (pT1) and 130 invasive (pT2/pT3/pT4) tumors) by immunohistochemistry (IHC), and in situ hybridization for detection of the mRNA in 21 cases. Using GC cell lines, we determined whether NUCB2 expression was associated with specific cellular phenotypes. In GC clinical samples, NUCB2 was transcriptionally upregulated when compared to normal tissues. High NUCB2 expression was associated with clinicopathological factors including deep tumor invasion, lymphovascular invasion, lymph node metastasis, and advanced clinical stages, and was a significant independent predictor of unfavorable progression-free survival in 150 non-invasive and invasive GC patients. Similar findings were also evident in 72 invasive GC cases in which patients received post-operative chemotherapy, but not in 58 invasive tumors from patients who did not receive the chemotherapy. In cell lines, NUCB2 knockout inhibited proliferation, susceptibility to apoptosis, and migration capability by inducting cellular senescence; this was consistent with higher proliferation and apoptotic indices in the NUCB2 IHC-high compared to NUCB2 IHC-low GC cases. NUCB2-dependent inhibition of senescence in GC engenders aggressive tumor behavior by modulating proliferation, apoptosis, and migration.


Assuntos
Senescência Celular , Nucleobindinas , Neoplasias Gástricas , Feminino , Humanos , Masculino , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Nucleobindinas/metabolismo , Prognóstico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo
9.
Commun Biol ; 7(1): 623, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802487

RESUMO

Nesfatin-1 (NESF-1) has been shown to modulate lipid metabolism. We have identified a nesfatin-1-like-peptide (NLP) processed from a related precursor nucleobindin 1 (NUCB1). Here we determined if NLP, like NESF-1, regulates lipid accumulation in vitro, and tested if the disruption of nucb1 gene affects hepatic lipid metabolism genes in mice. Hepatocytes (HepG2/C3A cells) express NLP and NESF-1 and both peptides significantly reduced lipogenic enzyme mRNAs and enhanced beta-oxidation enzyme mRNAs. Lipid contents in oleic acid induced HepG2/C3A cells were attenuated by NESF-1 and NLP. The inhibitory effect on cellular lipid content was blocked by compound C, an inhibitor of AMPK. The disruption of nucb1 gene affected lipid metabolism-related enzyme mRNAs, endogenous nucb2 mRNA and AMPK phosphorylation. The lipid-lowering effects identified here highlights the potential of nucleobindins and peptides processed from them to address lipid disorders, and its possible benefits in metabolic disease management.


Assuntos
Proteínas de Ligação ao Cálcio , Proteínas de Ligação a DNA , Hepatócitos , Metabolismo dos Lipídeos , Proteínas do Tecido Nervoso , Nucleobindinas , Nucleobindinas/metabolismo , Nucleobindinas/genética , Animais , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Camundongos , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Células Hep G2 , Masculino , Camundongos Endogâmicos C57BL
10.
Cell Commun Signal ; 22(1): 298, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38812013

RESUMO

BACKGROUND: Nucleobindin-2 (Nucb2) and nesfatin-1 (N1) are widely distributed hormones that regulate numerous physiological processes, from energy homeostasis to carcinogenesis. However, the role of nesfatin-2 (N2), the second product of Nucb2 proteolytic processing, remains elusive. To elucidate the relationship between the structure and function of nesfatins, we investigated the properties of chicken and human homologs of N1, as well as a fragment of Nucb2 consisting of N1 and N2 conjoined in a head-to-tail manner (N1/2). RESULTS: Our findings indicate that Zn(II) sensing, in the case of N1, is conserved between chicken and human species. However, the data presented here reveal significant differences in the molecular features of the analyzed peptides, particularly in the presence of Zn(II). We demonstrated that Zn(II) has a Janus effect on the M30 region (a crucial anorexigenic core) of N1 and N1/2. In N1 homologs, Zn(II) binding results in the concealment of the M30 region driven by a disorder-to-order transition and adoption of the amyloid fold. In contrast, in N1/2 molecules, Zn(II) binding causes the exposure of the M30 region and its destabilization, resulting in strong exposure of the region recognized by prohormone convertases within the N1/2 molecule. CONCLUSIONS: In conclusion, we found that Zn(II) binding is conserved between chicken and human N1. However, despite the high homology of chicken and human N1, their interaction modes with Zn(II) appear to differ. Furthermore, Zn(II) binding might be essential for regulating the function of nesfatins by spatiotemporally hindering the N1 anorexigenic M30 core and concomitantly facilitating N1 release from Nucb2.


Assuntos
Galinhas , Nucleobindinas , Zinco , Nucleobindinas/metabolismo , Zinco/metabolismo , Humanos , Animais , Sequência de Aminoácidos , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/química , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/genética , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/química , Proteínas de Ligação ao Cálcio/genética
11.
Biochem Pharmacol ; 225: 116284, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38750903

RESUMO

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.


Assuntos
Adenina , Insuficiência Renal Crônica , Animais , Masculino , Camundongos , Ratos , Adenina/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Camundongos Endogâmicos C57BL , Nucleobindinas , Estresse Oxidativo/efeitos dos fármacos , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia
12.
Cancer Lett ; 591: 216893, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38636892

RESUMO

The oncogenic properties of Nucleobindin2 (NUCB2) have been observed in various cancer types. Nevertheless, the precise understanding of the biological functions and regulatory mechanisms of NUCB2 in osteosarcoma remains limited. This investigation reported that NUCB2 was significantly increased upon glucose deprivation-induced metabolic stress. Elevated NUCB2 suppressed glucose deprivation-induced cell death and reactive oxygen species (ROS) increase. Depletion of NUCB2 resulted in a reduction in osteosarcoma cell proliferation as well as metastatic potential in vitro and in vivo. Mechanically, NUCB2 ablation suppressed C-X-C Motif Chemokine Ligand 8 (CXCL8) expression which then reduced programmed cell death 1 ligand 1 (PD-L1) expression and stimulated anti-tumor immunity mediated through cytotoxic T cells. Importantly, a combination of NUCB2 depletion with anti-PD-L1 treatment improved anti-tumor T-cell immunity in vivo. Moreover, we further demonstrated that NUCB2 interacted with NUCKS1 to inhibit its degradation, which is responsible for the transcriptional regulation of CXCL8 expression. Altogether, the outcome emphasizes the function of NUCB2 in osteosarcoma and indicates that NUCB2 elevates osteosarcoma progression and immunosuppressive microenvironment through the NUCKS1/CXCL8 pathway.


Assuntos
Neoplasias Ósseas , Proteínas de Ligação ao Cálcio , Progressão da Doença , Interleucina-8 , Nucleobindinas , Osteossarcoma , Microambiente Tumoral , Animais , Humanos , Camundongos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/patologia , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/genética , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/genética , Linhagem Celular Tumoral , Proliferação de Células , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Regulação Neoplásica da Expressão Gênica , Interleucina-8/metabolismo , Interleucina-8/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Osteossarcoma/imunologia , Osteossarcoma/patologia , Osteossarcoma/metabolismo , Osteossarcoma/genética , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Linfócitos T Citotóxicos/imunologia , Microambiente Tumoral/imunologia , Nucleobindinas/genética , Nucleobindinas/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo
13.
Int J Food Sci Nutr ; 75(4): 445-448, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38659170

RESUMO

Nesfatin concentrations are positively correlated with beta cell function. However, it is unclear whether diet composition mediates this relationship. We recruited 27 overweight individuals who practiced Orthodox fasting (OF), a subset of the Mediterranean diet (MedDiet), for 7 weeks. Fourteen overweight people who practiced 16:8 time-restricted eating served as control group. Anthropometric parameters, biochemical data and adipokine levels were evaluated at baseline and after the end of the diet period (7 weeks from baseline). Subsequently, participants were asked to return to their usual eating plans, and an additional evaluation was performed 5 weeks after the end of the research diets (12 weeks from baseline). We observed a significant and negative correlation between HOMA-B and nesfatin values at 12 weeks, only in the OF group (r = -0.455, p = 0.01). In conclusion, returning to normal eating habits after 7 weeks of strict adherence to MedDiet affects the homeostatic balance between insulin secretion and nesfatin.


Assuntos
Dieta Mediterrânea , Jejum , Células Secretoras de Insulina , Nucleobindinas , Sobrepeso , Humanos , Masculino , Sobrepeso/metabolismo , Feminino , Adulto , Células Secretoras de Insulina/metabolismo , Pessoa de Meia-Idade , Insulina/sangue , Resistência à Insulina , Comportamento Alimentar , Índice de Massa Corporal , Proteínas do Tecido Nervoso , Proteínas de Ligação ao Cálcio/metabolismo
14.
Bioelectromagnetics ; 45(5): 209-217, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38369591

RESUMO

In recent years exposure of living beings to radiofrequency radiation (RFR) emitted from wireless equipment has increased. In this study, we investigated the effects of 3.5-GHz RFR on hormones that regulate energy metabolism in the body. Twenty-eight rats were divided into four groups: healthy sham (n = 7), healthy RFR (n = 7), diabetic sham (n = 7), and diabetic RFR (n = 7). Over a month, each group spent 2 h/day in a Plexiglas carousel. The rats in the experimental group were exposed to RFR, but the sham groups were not. At the end of the experiment, blood and adipose tissues were collected from euthanized rats. Total antioxidant, total oxidant, hydrogen peroxide, ghrelin, nesfatin-1, and irisin were determined. Insulin expression in pancreatic tissues was examined by immunohistochemical analysis. Whole body specific absorption rate was 37 mW/kg. For the parameters analyzed in blood and fat, the estimated effect size varied within the ranges of 0.215-0.929 and 0.503-0.839, respectively. The blood and adipose nesfatin-1 (p = 0.002), blood and pancreatic insulin are decreased, (p = 0.001), gherelin (p = 0.020), irisin (p = 0.020), and blood glucose (p = 0.040) are increased in healthy and diabetic rats exposed to RFR. While nesfatin-1 are negatively correlated with oxidative stress, hyperglycemia and insulin, ghrelin and irisin are positively correlated with oxidative stress and hyperglycemia. Thus, RFR may have deleterious effects on energy metabolism, particularly in the presence of diabetes.


Assuntos
Tecido Adiposo , Fibronectinas , Grelina , Insulina , Nucleobindinas , Ondas de Rádio , Animais , Ondas de Rádio/efeitos adversos , Grelina/sangue , Grelina/metabolismo , Nucleobindinas/metabolismo , Masculino , Fibronectinas/metabolismo , Fibronectinas/sangue , Ratos , Tecido Adiposo/metabolismo , Tecido Adiposo/efeitos da radiação , Insulina/metabolismo , Insulina/sangue , Antioxidantes/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/sangue , Metabolismo Energético/efeitos da radiação , Proteínas de Ligação ao Cálcio/metabolismo , Peróxido de Hidrogênio/metabolismo , Estresse Oxidativo/efeitos da radiação , Ratos Wistar
15.
J Chem Neuroanat ; 136: 102400, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38342331

RESUMO

Neuropeptides are involved in numerous brain activities being responsible for a wide spectrum of higher mental functions. The purpose of this concise, structural and qualitative investigation was to map the possible immunoreactivity of the novel regulatory peptides: spexin (SPX) and nesfatin-1 within the human claustrum. SPX is a newly identified peptide, a natural ligand for the galanin receptors (GALR) 2/3, with no molecular structure similarities to currently known regulatory factors. SPX seems to have multiple physiological functions, with an involvement in reproduction and food-intake regulation recently revealed in animal studies. Nesfatin-1, a second pleiotropic neuropeptide, which is a derivative of the nucleobindin-2 (NUCB-2) protein, is characterized by a wide distribution in the brain. Nesfatin-1 is a substance with a strong anorexigenic effect, playing an important role in the neuronal circuits of the hypothalamus that regulate food intake and energy homeostasis. On the other hand, nesfatin-1 may be involved in several important brain functions such as sleep, reproductive behaviour, cognitive processes, stress responses and anxiety. For the first time we detected and described a population of nesfatin-1 and SPX expressing neurons in the human claustrum using immunohistochemical and fluorescent methods. The study presents the novel identification of SPX and nesfatin-1 immunopositive neurons in the human claustrum and their assemblies show similar patterns of distribution in the whole structure.


Assuntos
Claustrum , Neuropeptídeos , Animais , Humanos , Masculino , Nucleobindinas/metabolismo , Claustrum/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neuropeptídeos/metabolismo , Neurônios/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo
16.
Int J Mol Sci ; 25(3)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38339201

RESUMO

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/metabolismo
17.
Neurochem Res ; 49(1): 38-51, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37740893

RESUMO

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 farmacológico
18.
Neuropeptides ; 103: 102401, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38157780

RESUMO

Nesfatin-1 is an anorexigenic peptide suppressing food intake and is synthesized and secreted by neurons located in the hypothalamus. Our study was aimed to demonstrate the effect of excitatory and inhibitory neurotransmitters on NUCB2/nesfatin-1 neurons. In this context, dual peroxidase immunohistochemistry staining was performed using NUCB2/nesfatin-1 primary antibody with each of the primary antibodies of vesicular transporter proteins applied as markers for neurons using glutamate, acetylcholine, and GABA as neurotransmitters. In double labeling applied on floating sections, the NUCB2/nesfatin-1 reaction was determined in brown color with diaminobenzidine, while vesicular carrier proteins were marked in black. Slides were analyzed to determine the ratio of nesfatin-1 neurons in the three hypothalamic nucleus in contact with a relevant vesicular carrier protein. The ratios of NUCB2/nesfatin-1 neurons with the innervation were compared among neurotransmitters. In addition, possible gender differences between males and females were examined. The difference in the number of VGLUT2-contacting NUCB2/nesfatin-1 neurons was significantly higher in males when compared to females. When both genders were compared in different nuclei, it was seen that there was no statistical significance in terms of the percentage of NUCB2/nesfatin-1 neuron apposition with VGLUT3. The statistical evaluation showed that number of NUCB2/nesfatin-1 neurons receiving GABAergic innervation is higher in males when compared to females (*p ≤ 0.05; p = 0.045). When the axonal contact of vesicular neurotransmitter transporter proteins was compared between the neurotransmitters, it was determined that the most prominent innervation is GABAergic. In the supraoptic region, no contacts of VAChT-containing axons were found on NUCB2/nesfatin-1 neurons in both female and male subjects. In conclusion, it is understood that both excitatory and inhibitory neurons can innervate the NUCB2/nesfatin-1 neurons and the glutamatergic system is effective in the excitatory innervation while the GABAergic system plays a role in the inhibitory mechanism.


Assuntos
Proteínas de Ligação ao Cálcio , Proteínas de Ligação a DNA , Feminino , Masculino , Humanos , Nucleobindinas , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Axônios/metabolismo , Neurotransmissores/metabolismo
19.
Georgian Med News ; (343): 107-110, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38096526

RESUMO

Nesfatin-1 reduces body weight and the intake of food, it is also tangled in setting insulin release. This study aims at comparing the levels of serum of Nesfatin-1 with the insulin resistance in obese adolescent of iraqi population with other nations around the world predicating development of diabetes mellitus later. 90 participants were needed for this cross-sectional study, including 30 control participants (17 men and 13 women) and 60 obese adolescents (36 men and 24 women). Serum glucose, insulin, and glycated hemoglobin in starved participants were estimated, using an ELISA kit, the serum level of Nesfatin-1 was measured, and insulin resistance was calculated. Obese adolescents aged 12 to 18 and the control group, who were between 13 and 18 years old. The level of nesfatin-1 was significantly lower in the group of obese adolescents than in the controls. The ranges of Nesfatin-1 were (1.22±0.39 n/ml vs 2.54±0.64 n/m P = 0.001). In the control and obese groups respectively. In comparison to the results of the non-obese adolescent group, the obese group has significantly lower insulin sensitivity. Serum Nesfatin-1 is negatively associated with insulin sensitivity, lipid profile, and body mass index. In general, our study revealed that there is no effect of food culture and eating intake on the role of Nesfatin -1 inducing obesity.


Assuntos
Resistência à Insulina , Obesidade Infantil , Masculino , Humanos , Adolescente , Feminino , Nucleobindinas , Estudos Transversais , Iraque , Proteínas de Ligação ao Cálcio , Proteínas de Ligação a DNA , Insulina
20.
Cell Biochem Funct ; 41(8): 1016-1030, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37909689

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/genética
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