Peptides最新文献_第7页

The intricate relationship between circadian rhythms and gastrointestinal peptides in obesity 肥胖患者昼夜节律与胃肠肽的复杂关系

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-02-08 DOI: 10.1016/j.peptides.2025.171356

Filipe M. Ribeiro , Luiz Arnaldo , Lana P. Milhomem , Samuel S. Aguiar , Octavio L. Franco

There are different molecular pathways that regulate appetite, particularly the role of the hypothalamus, circadian rhythms, and gastrointestinal peptides. The hypothalamus integrates signals from orexigenic peptides like neuropeptide Y (NPY) and agouti-related protein (AgRP), which stimulate appetite, and anorexigenic peptides such as pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART), which promote satiety. These signals are influenced by peripheral hormones like leptin, ghrelin, insulin, and cortisol, as well as gut peptides including glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and cholecystokinin (CCK). The circadian rhythm, regulated by proteins like circadian locomotor output cycles kaput (CLOCK) and brain and muscle ARNT-like 1 (BMAL1), modulates the secretion of these peptides, aligning feeding behaviors with the sleep-wake cycle. In obesity, these regulatory systems are disrupted, leading to leptin resistance, increased ghrelin sensitivity, and altered gut peptide secretion. This results in heightened appetite and impaired satiety, contributing to overeating and metabolic dysfunction. Additionally, circadian disruptions further impair metabolic processes, exacerbating obesity. The present article underscores the importance of understanding the molecular interplay between circadian rhythms and gastrointestinal peptides, particularly in the context of obesity. While some molecular interactions, such as the regulation of GLP-1 and PYY by reverberation of circadian rhythm α (REV-ERBα) and retinoic acid-related orphan receptor α (RORα), are well-established, clinical studies are scarce. Future research is expected to explore these pathways in obesity management, especially with the rise of incretin-based treatments like semaglutide. A deeper understanding of hypothalamic molecular mechanisms could lead to novel pharmacological and non-pharmacological therapies for obesity.

有不同的分子途径调节食欲，特别是下丘脑，昼夜节律和胃肠道肽的作用。下丘脑整合来自刺激食欲的神经肽Y （NPY）和agouti相关蛋白（AgRP）等厌氧肽和促进饱腹感的促鸦片黑素皮质素（POMC）和可卡因和安非他明调节转录物（CART）等厌氧肽的信号。这些信号受到瘦素、胃饥饿素、胰岛素和皮质醇等外周激素以及胰高血糖素样肽-1 （GLP-1）、YY肽（PYY）和胆囊收缩素（CCK）等肠道肽的影响。昼夜节律由昼夜运动输出周期衰竭（CLOCK）和大脑和肌肉类arnt样1 （BMAL1）等蛋白质调节，调节这些肽的分泌，使摄食行为与睡眠-觉醒周期保持一致。在肥胖中，这些调节系统被破坏，导致瘦素抵抗，胃饥饿素敏感性增加，肠道肽分泌改变。这会导致食欲增加和饱腹感受损，导致暴饮暴食和代谢功能障碍。此外，昼夜节律紊乱会进一步损害代谢过程，加剧肥胖。本文强调了理解昼夜节律和胃肠道肽之间的分子相互作用的重要性，特别是在肥胖的背景下。虽然一些分子相互作用，如通过昼夜节律α (REV-ERBα)和视黄酸相关孤儿受体α (RORα)的混响调节GLP-1和PYY，已经得到证实，但临床研究很少。未来的研究有望在肥胖管理中探索这些途径，特别是随着以肠促胰岛素为基础的治疗方法（如semaglutide）的兴起。对下丘脑分子机制的深入了解可能会导致新的药物和非药物治疗肥胖。

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引用次数: 0

Peptide‑based therapeutic strategies for glioma: Current state and prospects 基于肽的胶质瘤治疗策略：现状和前景

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-02-06 DOI: 10.1016/j.peptides.2025.171354

Yajing Mi , Pengtao Jiang , Jing Luan , Lin Feng , Dian Zhang , Xingchun Gao

Glioma is a prevalent form of primary malignant central nervous system tumor, characterized by its cellular invasiveness, rapid growth, and the presence of the blood-brain barrier (BBB)/blood-brain tumor barrier (BBTB). Current therapeutic approaches, such as chemotherapy and radiotherapy, have shown limited efficacy in achieving significant antitumor effects. Therefore, there is an urgent demand for new treatments. Therapeutic peptides represent an innovative class of pharmaceutical agents with lower immunogenicity and toxicity. They are easily modifiable via chemical means and possess deep tissue penetration capabilities which reduce side effects and drug resistance. These unique pharmacokinetic characteristics make peptides a rapidly growing class of new therapeutics that have demonstrated significant progress in glioma treatment. This review outlines the efforts and accomplishments in peptide-based therapeutic strategies for glioma. These therapeutic peptides can be classified into four types based on their anti-tumor function: tumor-homing peptides, inhibitor/antagonist peptides targeting cell surface receptors, interference peptides, and peptide vaccines. Furthermore, we briefly summarize the results from clinical trials of therapeutic peptides in glioma, which shows that peptide-based therapeutic strategies exhibit great potential as multifunctional players in glioma therapy.

胶质瘤是一种常见的原发性中枢神经系统恶性肿瘤，其特点是细胞侵袭性强，生长迅速，存在血脑屏障(BBB)/血脑肿瘤屏障（BBTB）。目前的治疗方法，如化疗和放疗，在取得显著的抗肿瘤效果方面疗效有限。因此，迫切需要新的治疗方法。治疗肽是一类具有较低免疫原性和毒性的创新药物。它们很容易通过化学手段进行修饰，并具有深层组织渗透能力，从而减少副作用和耐药性。这些独特的药代动力学特征使多肽成为一种快速增长的新疗法，在胶质瘤治疗中取得了重大进展。本文综述了以肽为基础的胶质瘤治疗策略的努力和成就。这些治疗性肽可根据其抗肿瘤功能分为四类：肿瘤归巢肽、靶向细胞表面受体的抑制剂/拮抗剂肽、干扰肽和肽疫苗。此外，我们简要总结了胶质瘤治疗肽的临床试验结果，表明基于肽的治疗策略在胶质瘤治疗中具有巨大的潜力。

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引用次数: 0

Association among nesfatin-1, obesity category, presence of obesity-related complications, and eating patterns in patients with obesity: Results of a single endocrine centre observational study 肥胖患者的nesfatin-1、肥胖类别、肥胖相关并发症和饮食模式之间的关系：一项内分泌中心观察性研究的结果

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-02-05 DOI: 10.1016/j.peptides.2025.171355

Ewa Milewska-Kobos , Ewelina Szczepanek- Parulska , Martyna Marciniak , Elżbieta Wrotkowska , Maja Cieślewicz , Agnieszka Dobrowolska , Marek Ruchala

Since its discovery, nesfatin-1 (N1) has been recognised as an anorexigenic agent potentially related to obesity pathogenesis and development, including its modulatory effect on the brain’s reward system and eating behaviours. As the results from human studies examining the relation between N1 serum levels, body mass index (BMI), and metabolic status are scarce and inconclusive, we aimed to investigate the association between serum N1 levels and obesity categories, obesity-related complications, and disturbed eating behaviour. We studied 110 patients with obesity divided into obesity categories according to their BMI and metabolic status. N1 was measured in a fasting state (N1⁰) and 2 h after a glucose load (N1²) and correlated with anthropometric measurements, serum analysis, and the presence of selected obesity-related complications. Neither N1⁰ nor N1² correlated significantly with obesity; however, N1⁰ tended to be high in patients with a high BMI. A positive correlation was observed among N1², fat-free mass (p = 0.022), and muscle mass (p = 0.02). We found positive correlations between N1⁰ and N1² with aspartate aminotransferase (p = 0.012 and p = 0.022, respectively) and alanine aminotransferase (p = 0.027 and p = 0.006, respectively). Patients with dyslipidaemia had significantly higher N1⁰ (p = 0.03) and N1² (p = 0.049) levels. Neither N1⁰ nor N1² correlated significantly with disturbed eating behaviour; however, low N1⁰ levels were associated with a hedonic eating pattern (p = 0.03). N1 may be involved in the pathogenesis of obesity and obesity-related complications; however, owing to the complex mechanisms of its secretion and action, further clinical and experimental research is needed.

自发现以来，nesfatin-1 （N1）已被认为是一种厌食因子，可能与肥胖的发病和发展有关，包括其对大脑奖励系统和饮食行为的调节作用。由于人类研究N1血清水平、体重指数（BMI）和代谢状态之间关系的结果很少且不确定，因此我们旨在调查血清N1水平与肥胖类别、肥胖相关并发症和饮食行为紊乱之间的关系。我们研究了110例肥胖患者，根据BMI和代谢状况将其分为肥胖类别。N1在空腹状态（N10）和葡萄糖负荷后2 h （N12）测量，并与人体测量、血清分析和选择的肥胖相关并发症的存在相关。N10和N12与肥胖均无显著相关性；然而，N10在BMI高的患者中往往较高。N12、无脂质量（p = 0.022）和肌肉质量（p = 0.02）呈正相关。我们发现N10和N12与天冬氨酸转氨酶（p = 0.012和p = 0.022）和丙氨酸转氨酶（p = 0.027和p = 0.006）呈正相关。血脂异常患者N10 （p = 0.03）和N12 （p = 0.049）水平显著升高。N10和N12与饮食行为紊乱均不显著相关；然而，低N10水平与享乐饮食模式相关（p = 0.03）。N1可能参与肥胖及肥胖相关并发症的发病机制；但由于其分泌和作用机制复杂，需要进一步的临床和实验研究。

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引用次数: 0

Ghrelin promotes chronic diabetic wound healing by regulating keratinocyte proliferation and migration through the ERK1/2 pathway 胃饥饿素通过ERK1/2通路调节角质细胞增殖和迁移，促进慢性糖尿病伤口愈合。

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-02-01 DOI: 10.1016/j.peptides.2025.171350

Yukang Zhang , Yuan Chen , Kailin Li , Cong Chen , Yong Hu , Xian Li

Delayed wound healing is a complication of diabetes mellitus and can lead to infection, sepsis, and amputation. Despite the currently available treatments, the global burden of diabetes-related wounds is growing; thus, more effective therapy for diabetic wounds is urgently needed. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is a 28-amino acid peptide hormone. Some reports have confirmed the therapeutic effects of ghrelin on diabetes mellitus and its complications. However, the effects and corresponding mechanisms of ghrelin on chronic diabetic wounds remain unknown. In this study, we explored the effect of ghrelin on diabetic wound healing and investigated the associated mechanisms. We showed that ghrelin accelerated wound healing in diabetic rats by promoting the proliferation and migration of keratinocytes. Re-epithelialization was accelerated in ghrelin-treated wounds, thicker and longer newly formed epidermis and more dividing keratinocytes were observed. We further confirmed that ghrelin regulated keratinocytes by activating the ERK1/2 pathway through its receptor growth hormone secretagogue receptor 1a (GHSR1a). Ghrelin also significantly reduced the levels of pro-inﬂammatory cytokines and increased the deposition of collagen in diabetic wounds. Our data provides preclinical evidence for the potential application of ghrelin as a compound to promote diabetic wound healing and clarifies the molecular mechanism.

伤口愈合延迟是糖尿病的并发症，可导致感染、败血症和截肢。尽管目前有治疗方法，但糖尿病相关伤口的全球负担正在增加；因此，迫切需要更有效的治疗糖尿病伤口的方法。胃饥饿素是生长激素促分泌素受体的内源性配体，是一种由28个氨基酸组成的肽激素。一些报道证实了胃饥饿素对糖尿病及其并发症的治疗作用。然而，胃饥饿素在慢性糖尿病创面中的作用及其机制尚不清楚。在本研究中，我们探讨了胃饥饿素对糖尿病创面愈合的影响，并探讨了相关机制。我们发现饥饿素通过促进角质形成细胞的增殖和迁移来加速糖尿病大鼠的伤口愈合。胃促生长素处理的创面上皮再生加快，新形成的表皮变厚变长，角化细胞分裂增多。我们进一步证实了ghrelin通过其受体生长激素促分泌受体1a （GHSR1a）激活ERK1/2通路来调节角化细胞。胃饥饿素还显著降低了促炎细胞因子的水平，增加了糖尿病伤口中胶原蛋白的沉积。我们的数据为胃饥饿素作为一种化合物促进糖尿病伤口愈合的潜在应用提供了临床前证据，并阐明了其分子机制。

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引用次数: 0

Effects of irisin on ovariectomy-induced depression, anxiety, and bodyweight growth in female mice 鸢尾素对卵巢切除引起的雌性小鼠抑郁、焦虑和体重增长的影响。

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-02-01 DOI: 10.1016/j.peptides.2025.171349

Xupei Xie , Yanling Zhang , Jianping He

Hormone replacement therapy (HRT) for postmenopausal syndrome (PMS) carries high risks of undesirable side effects. This study explores irisin as a potential alternative to HRT and investigates the underlying mechanisms. Ovariectomized (OVX) female mice was used as an animal model. The experimental mice were divided into sham, OVX, OVX + irisin (1, 3 μg/kg), OVX+ estradiol (0.5 mg/kg), and OVX + irisin + compound C (AMPK inhibitor) groups. Results showed that OVX induced depression, anxiety, and bodyweight growth in female mice. These OVX-induced abnormalities were reversed by irisin treatment, while AMPK inhibitor abolished irisin’s function, indicating that irisin’s therapeutic effects on OVX mice were achieved by activating AMPK. Moreover, irisin could increase pAMPK levels and ameliorate the overexpression of NF-κB and its downstream factors including inflammatory factors (IL-1β, IL-6, and TNF-α) and neurotoxic mediators (COX-2 and iNOS) in the hippocampus, frontal cortex, and serum of the OVX mice. However, irisin did not affect hypothalamus pAMPK level or food intake. These findings indicate that irisin’s therapeutic effects on depression and anxiety may be linked to its inhibition of inflammatory factors and neurotoxic mediators in the serum and brain, occurring through the AMPK/NF-κB pathway. Additionally, irisin’s effect of reducing bodyweight may be associated with an increase in serum pAMPK level, rather than a direct impact on food intake. Further mechanistic exploration revealed that the beneficial effects of irisin, including both the attenuation of bodyweight gain and the improvement of neurological deficits, are attributed to the activation of αVβ5 receptors.

激素替代疗法（HRT）对绝经后综合症（PMS）有很高的不良副作用的风险。本研究探讨鸢尾素作为激素替代疗法的潜在替代品，并探讨其潜在机制。以去卵巢（OVX）雌性小鼠为动物模型。实验小鼠分为假手术组、OVX组、OVX+ 鸢尾素组（1,3 μg/kg）、OVX+ 雌二醇组（0.5 mg/kg）、OVX+ 鸢尾素+ 化合物C （AMPK抑制剂）组。结果显示，OVX诱导雌性小鼠抑郁、焦虑和体重增长。这些OVX诱导的异常被鸢尾素治疗逆转，而AMPK抑制剂则消除了鸢尾素的功能，表明鸢尾素对OVX小鼠的治疗作用是通过激活AMPK来实现的。鸢尾素可提高OVX小鼠海马、额叶皮层和血清中pAMPK水平，改善NF-κB及其下游炎症因子（IL-1β、IL-6和TNF-α）和神经毒性介质（COX-2和iNOS）的过度表达。然而，鸢尾素不影响下丘脑pAMPK水平或食物摄入量。这些发现表明鸢尾素对抑郁和焦虑的治疗作用可能与其通过AMPK/NF-κB通路抑制血清和脑中的炎症因子和神经毒性介质有关。此外，鸢尾素的减肥效果可能与血清pAMPK水平的增加有关，而不是直接影响食物摄入量。进一步的机制探索表明，鸢尾素的有益作用，包括减轻体重增加和改善神经功能缺陷，都归因于αVβ5受体的激活。

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引用次数: 0

Compensatory mechanisms underlying arginine vasopressin regulation in transient polyuria during pregnancy 妊娠期短暂性多尿精氨酸抗利尿素调节的补偿机制。

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-02-01 DOI: 10.1016/j.peptides.2025.171352

Tetsuro Tsumura , Daisuke Hagiwara , Satoshi Naito , Yuichi Kondo , Yohei Kawaguchi , Takashi Miyata , Tomoko Kobayashi , Mariko Sugiyama , Takeshi Onoue , Shintaro Iwama , Hidetaka Suga , Ryoichi Banno , Hiroshi Arima

Transient polyuria during pregnancy is reportedly caused by increased arginine vasopressin (AVP) degradation due to vasopressinase produced by the placenta. The mechanism underlying transient polyuria during pregnancy has not been established. In this study we measured urine volume, urine osmolality, and AVP transcriptional activity during pregnancy in wild-type and familial neurohypophysial diabetes insipidus (FNDI) mice. The FNDI mice were used as a partial AVP deficiency model. Vasopressinase was shown to be present in the placentas of pregnant mice. The Avp hnRNA level in the supraoptic nucleus, which is indicative of AVP transcriptional activity, was upregulated in wild-type and FNDI mice during late pregnancy. FNDI mice, but not wild-type mice, had a significant increase in urine volume and a decrease in urine osmolality during pregnancy. These data suggest that an increase in urine volume during pregnancy only occurs when the compensatory increase in AVP release is insufficient to counteract degradation by vasopressinase.

据报道，妊娠期间短暂性多尿是由胎盘产生的抗利尿酶导致精氨酸抗利尿素（AVP）降解增加引起的。妊娠期短暂性多尿的机制尚未确定。在这项研究中，我们测量了野生型和家族性尿崩症神经垂体性糖尿病（FNDI）小鼠妊娠期间的尿量、尿渗透压和AVP转录活性。以FNDI小鼠作为AVP部分缺乏症模型。抗利尿加压酶被证明存在于怀孕小鼠的胎盘中。野生型和FNDI小鼠在妊娠后期视上核Avp hnRNA水平上调，表明Avp转录活性。FNDI小鼠妊娠期尿量明显增加，尿渗透压明显降低，而野生型小鼠妊娠期尿渗透压明显降低。这些数据表明，怀孕期间尿量的增加只发生在AVP释放的代偿性增加不足以抵消抗利尿加压酶的降解时。

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引用次数: 0

Transcardiac gradients of pro-cholecystokinin, cholecystokinin, and gastrin in patients with and without heart failure with reduced ejection fraction 伴有和不伴有射血分数降低的心力衰竭患者的前胆囊收缩素、胆囊收缩素和胃泌素的经心梯度

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-02-01 DOI: 10.1016/j.peptides.2025.171353

Tania Deis , Benedicte Heegaard , Kasper Rossing , Berit Philbert , Michael Vinther , Niels Risum , Peter Karl Jacobsen , Jens P. Goetze , Finn Gustafsson

Background

Cholecystokinin (CCK) is secreted from the intestines in response to food intake. We previously reported that the CCK gene is also expressed in the mammalian heart, and it has been hypothesized that proCCK could be a novel cardiac biomarker. However, it is not known whether cardiac gene expression leads to secretion in humans.

Purpose

To investigate myocardial secretion of proCCK in patients with heart failure with reduced ejection fraction (HFrEF) or arrythmias.

Methods

A total of 115 patients undergoing invasive cardiac procedures were included: 55 with HFrEF (67 years [interquartile range (IQR) 60–76], 72.7 % male, LVEF 30 % [IQR 20–35]), and 60 without HFrEF (26 with Wolff-Parkinson-White syndrome (WPW) (30 years [IQR 26–39], 61.5 % male), and 34 with atrial fibrillation (AFIB) (66 years [IQR 60–71], 61.8 % male)). Blood was collected from the coronary sinus (CS) as well as the left atrium or femoral artery (A) to determine the transcardiac concentration gradient (TC_proCCK) (CS proCCK concentration - A proCCK concentration). Radioimmunoassays were used for measurements of plasma hormones.

Results

TC_proCCK across failing hearts was 0.05 pmol/l (IQR: −1.49–2.67) (p = 0.365). In non-failing hearts, TC_proCCK was 0.35 pmol/l (IQR: −1.57–1.29) (p = 0.778) for WPW and 0.68 pmol/l (IQR: −1.58–3.28) (p = 0.133) for AFIB. Transcardiac gradients for N-terminal pro B-type natriuretic peptide (NT-proBNP) were observed in all groups.

Conclusions

No evidence of net myocardial secretion of proCCK was found in either failing or structurally normal hearts, questioning its proposed role as a cardiac biomarker.

背景：胆囊收缩素（CCK）是肠道对食物摄入的反应。我们之前报道过CCK基因也在哺乳动物心脏中表达，并假设proCCK可能是一种新的心脏生物标志物。然而，尚不清楚心脏基因表达是否导致人类分泌。目的：探讨心衰伴射血分数降低（HFrEF）或心律失常患者心肌proCCK的分泌情况。方法：共纳入115例接受有创伤心脏手术的患者：55例HFrEF(67岁[四分位间距（IQR） 60-76]， 72%男性，LVEF 30% [IQR 20-35])， 60例无HFrEF(26例沃尔夫-帕金森-怀特综合征（WPW）（30岁[IQR 26-39]， 61.5%男性），34例心房颤动（AFIB）（66岁[IQR 60-71]， 61.8%男性）。取冠状窦（CS）、左心房或股动脉(A)血，测定经心浓度梯度（TCproCCK）（CS proCCK浓度- A proCCK浓度）。放射免疫测定法用于测定血浆激素。结果：衰竭心脏的TCproCCK为0.05 pmol/l (IQR: -1.49 ~ 2.67) （p = 0.365）。在非衰竭心脏中，WPW的TCproCCK为0.35 pmol/l (IQR: -1.57至1.29)(p = 0.778)， AFIB的TCproCCK为0.68 pmol/l (IQR: -1.58至3.28)（p = 0.133）。观察各组n端前b型利钠肽（NT-proBNP）的经心梯度。结论：没有证据表明在衰竭或结构正常的心脏中发现proCCK的净心肌分泌，质疑其作为心脏生物标志物的作用。

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引用次数: 0

Phoenixin's influence on HPG axis and inflammation in elite ice hockey athletes: A cross-sectional analysis 凤凰素对优秀冰球运动员HPG轴和炎症的影响：一项横断面分析。

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-02-01 DOI: 10.1016/j.peptides.2025.171351

Liang Fang , Yixing Chang , Qiuyan Liang , Ruiqi Huang , Xuejie Yi , Tingting Yao

The neuropeptide phoenixin (PNX) may be involved in regulating the hypothalamic-pituitary-gonadal (HPG) axis and inflammatory responses. This study aims to investigate the role of PNX in the regulation of HPG axis function in ice hockey players and its impact on body composition. This cross-sectional study included 65 male ice hockey players aged 18–22, divided into untrained, non-elite athlete, and elite athlete groups. Body composition was assessed using bioelectrical impedance analysis, and plasma levels of PNX, gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), testosterone, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) were measured by enzyme-linked immunosorbent assay. Elite ice hockey players exhibited significantly higher lower limb and core skeletal muscle mass, skeletal muscle index, and testosterone levels, aligning with the high-intensity intermittent nature of hockey training. Compared to the non-training group, ice hockey training groups showed elevated levels of PNX, GnRH, testosterone, and TNF-α, along with reduced levels of LH and IL-6. PNX concentration positively correlated with lean body mass, skeletal muscle mass, skeletal muscle index, serum GnRH, and testosterone levels, and negatively correlated with serum LH and IL-6 levels. In conclusion, PNX may enhance skeletal muscle mass in ice hockey players, particularly in the lower limbs and core muscles, by promoting HPG axis activity while inhibiting inflammatory responses and reducing HPG axis suppression. These findings provide new insights into the physiological adaptation mechanisms of ice hockey players, potentially aiding in the optimization of training strategies and improvement of athletic performance.

神经肽凤凰素（PNX）可能参与调节下丘脑-垂体-性腺（HPG）轴和炎症反应。本研究旨在探讨PNX在冰球运动员HPG轴功能调控中的作用及其对身体成分的影响。这项横断面研究包括65名年龄在18-22岁的男性冰球运动员，分为未经训练的、非精英运动员和精英运动员组。采用生物阻抗分析法评估机体组成，采用酶联免疫吸附法测定血浆PNX、促性腺激素释放激素（GnRH）、促黄体生成素（LH）、睾酮、肿瘤坏死因子-α (TNF-α)、白细胞介素-6 （IL-6）和白细胞介素-10 （IL-10）水平。优秀的冰球运动员表现出更高的下肢和核心骨骼肌质量、骨骼肌指数和睾丸激素水平，这与冰球训练的高强度间歇性性质一致。与非训练组相比，冰球训练组的PNX、GnRH、睾酮和TNF-α水平升高，LH和IL-6水平降低。PNX浓度与瘦体质量、骨骼肌质量、骨骼肌指数、血清GnRH、睾酮水平正相关，与血清LH、IL-6水平负相关。综上所述，PNX可能通过促进HPG轴的活动，抑制炎症反应，减少HPG轴的抑制，从而增加冰球运动员的骨骼肌质量，尤其是下肢和核心肌群。这些发现为冰球运动员的生理适应机制提供了新的见解，可能有助于优化训练策略和提高运动成绩。

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引用次数: 0

Octadecaneuropeptide promotes the migration of astrocyte via ODN metabotropic receptor and calcium signaling pathway 八肽通过ODN代谢受体和钙信号通路促进星形胶质细胞的迁移。

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-01-01 DOI: 10.1016/j.peptides.2024.171338

Sada Al-Mashhadani , Mariem Sallemi , Amira Namsi , Yosra Hamdi , Amine Cherif , Fethia Abidi , Jérôme Leprince , Zekri Sami , David Vaudry , Masmoudi-Kouki Olfa

Migration is an essential characteristic of cells that occurs during many physiological and pathological processes. Astrocytes represent the most abundant cell type in the adult central nervous system (CNS), that play a crucial role in various functions such as guiding and supporting neuronal migration during development and maintaining brain homeostasis at adulthood. Astrocytes specifically synthesize and release endozepines, a family of regulatory peptides, including the octadecaneuropeptide (ODN). ODN is an endogenous ligand for both central-type benzodiazepine receptors and a metabotropic receptor. ODN promotes proliferation and prevents oxidative damage induced apoptosis on both neurons and astrocytes. However, little is known regarding the effect of ODN on cell migration. The purpose of the present study was to investigate the potential effect of ODN on astrocytes migration. Our results show that ODN stimulates astrocytes proliferation and migration at very low concentrations in wound healing assays, that was mimicked by the metabotropic ODN receptor agonist cyclo_1–8 octapeptide (cyclo_1–8OP, 10⁻¹⁴ M to 10⁻¹⁰ M). The effect of ODN on astrocyte migration was abrogated by the metabotropic receptor antagonist, cyclo_1–8[DLeu⁵] OP. Moreover, we have shown that ODN activates the calcium signaling pathway and increases the mammalian target of rapamycin (mTOR) gene transcription, which are both known to promote astrocyte migration. Therefore, the present results suggest that ODN regulates astroglial cell migration through the calcium/mTOR signaling pathway and provide new insight regarding the role of ODN on brain remodling after injury.

迁移是细胞在许多生理和病理过程中发生的基本特征。星形胶质细胞是成人中枢神经系统（CNS）中最丰富的细胞类型，在发育过程中指导和支持神经元迁移以及维持成年期大脑稳态等多种功能中起着至关重要的作用。星形胶质细胞特异性地合成并释放内啡肽，这是一个调节肽家族，包括十八欧肽（ODN）。ODN是中枢型苯二氮卓受体和代谢受体的内源性配体。ODN促进神经元和星形胶质细胞的增殖并防止氧化损伤诱导的细胞凋亡。然而，关于ODN对细胞迁移的影响知之甚少。本研究旨在探讨ODN对星形胶质细胞迁移的潜在影响。我们的研究结果表明，在伤口愈合实验中，ODN在非常低的浓度下刺激星形胶质细胞的增殖和迁移，这是由代谢ODN受体激动剂cyclo1-8八肽（cyclo1-8OP， 10-14M至10-10M）模拟的。ODN对星形胶质细胞迁移的影响被代谢受体拮抗剂cyclo1-8[DLeu5] op所消除。此外，我们已经证明ODN激活钙信号通路并增加哺乳动物雷帕霉素靶基因（mTOR）的转录，这两者都是已知的促进星形胶质细胞迁移的因素。因此，本研究结果提示ODN通过钙/mTOR信号通路调控星形胶质细胞的迁移，并为ODN在损伤后脑重塑中的作用提供了新的认识。

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引用次数: 0

Apelin/APJ increased renal blood flow through endothelial BKCa channel induced p-eNOS and ET-1 in diabetic conditions Apelin/APJ增加通过内皮BKCa通道的肾血流量，诱导糖尿病患者p-eNOS和ET-1。

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-01-01 DOI: 10.1016/j.peptides.2024.171333

Mingcong Huang , Jing Chang , Yu Liu , Jiming Yin , Xiangjun Zeng

Renal hemodynamics damage, an important driving mechanism of diabetic nephropathy (DN), is related to many abnormal endothelial released molecules, such as endothelial nitrogen monoxide synthase (eNOS) and endothelin-1 (ET-1), caused by glomerular endothelial cells dysfunction. Apelin, as the endogenous ligand for APJ, was reported to be associated with endothelial cell dysfunction in diabetes. Therefore, it is hypothesized that apelin/APJ increased renal perfusion in DN through regulating endothelial released molecules. Diabetic models were replicated via injecting STZ intraperitoneally (40 mg/kg/day) for 5 consecutive days. Apelin-13 was infused with micro-osmotic pump at 30 μg/kg/day for 4 weeks. The results showed that apelin increased renal blood flow by increasing phosphorylated eNOS and decreasing ET-1 in diabetic mice, which were cancelled in endothelial-specific APJ knockout mice or whole-body large conductance Ca^2 +-activated K⁺ (BKCa) channel knockout rats. Additionally, apelin/APJ activated BKCa channel via increasing expression of BKCa subunits through PI3K/AKT/GSK-3β/Nrf2 pathway but not increasing intracellular Ca²⁺ concentration under high glucose conditions. In conclusion, this study revealed that apelin/APJ increased renal blood flow in early phase of DN via increasing p-eNOS and decreasing ET-1 in glomerular endothelial cells dependent on PI3K/AKT/GSK-3β/Nrf2 pathway induced expression of BKCa subunits.

肾血流动力学损伤是糖尿病肾病（DN）的重要驱动机制，与肾小球内皮细胞功能障碍引起的内皮一氧化氮合酶（eNOS）、内皮素-1 （ET-1）等内皮释放分子异常有关。据报道，APJ的内源性配体Apelin与糖尿病内皮细胞功能障碍有关。因此，我们假设apelin/APJ通过调节内皮细胞释放的分子增加DN的肾灌注。通过腹腔注射STZ （40mg/kg/天）连续5天复制糖尿病模型。Apelin-13以30μg/kg/d微渗透泵滴注，连续4周。结果表明，在糖尿病小鼠中，apelin通过增加磷酸化的eNOS和降低ET-1来增加肾血流量，而在内皮特异性APJ敲除小鼠或全身大电导Ca2+激活K+ (BKCa)通道敲除大鼠中，这种作用被取消。此外，apelin/APJ通过PI3K/AKT/GSK-3β/Nrf2途径增加BKCa亚基的表达，激活BKCa通道，但在高糖条件下不增加细胞内Ca2+浓度。综上所述，本研究表明apelin/APJ通过PI3K/AKT/GSK-3β/Nrf2通路诱导BKCa亚基的表达，通过增加肾小球内皮细胞的p-eNOS和降低ET-1来增加DN早期肾血流量。

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引用次数: 0