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Erythropoietin improves spatial and nonspatial memory defects by suppressing oxidative damage, inflammation and apoptosis against ethanol neurotoxicity in the developing male rat hippocampus 促红细胞生成素通过抑制乙醇神经毒性对雄性大鼠海马的氧化损伤、炎症和凋亡，改善空间和非空间记忆缺陷

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-02-19 DOI: 10.1016/j.peptides.2025.171368

Raheleh Rafaiee , Fahimeh Mohseni , Mehdi khaksari , Behzad Garmabi , Alireza Masoudi , Zhaleh Jamali , Shima Mohammadi , Alieh Bashghareh

Excessive prenatal exposure to ethanol leads to a condition called fetal alcohol spectrum disorder (FASD). The neurotoxicity of alcohol causes changes in the hippocampus of animals during this time, resulting in impaired hippocampus-related functions, including memory/learning and cognition.The liver and kidneys produce erythropoietin (EPO). The synthesis of EPO by immature neurons also plays a decisive role in the embryonic stage. Also, exogenous EPO exerts its neurocognitive effects in the developing brain under pathophysiological conditions. The aim of this study was to investigate the protective effects of EPO administration after ethanol-induced increased neurodevelopmental toxicity. Male Wistar rat pups were intubated with a dose of 5/27 g/kg/day ethanol from postnatal day 2–10, similar to the last trimester of gestation in humans. Immediately thereafter, EPO (1000 /2000 U/kg, s.c.) were injected. Spatial memory was tested with the Morris water maze (days 36–40) and non-spatial recognition memory with the novel object task (days 39–40). Concentrations of antioxidant enzymes and TNF-α (ELISA) and caspase-3 (immunohistochemical staining) was then performed. The current study shows that EPO administration significantly attenuates spatial and nonspatial memory impairment (P < 0.001). EPO dramatically decreased the amount of caspase 3 positive cells in the CA1 area of the hippocampus (P < 0.01). EPO increased total superoxide dismutase activity (P < 0.05), glutathione concentrations (P < 0.05) and catalase levels (P < 0.001). EPO also attenuated the production of TNF-α and malondialdehyde (P < 0.05). Given EPO's protective effect against ethanol-induced increased neurotoxicity, it is a viable treatment option for FASD, although more research is needed.

产前过量接触乙醇会导致胎儿酒精谱系障碍（FASD）。酒精的神经毒性导致动物海马在这段时间内发生变化，导致海马相关功能受损，包括记忆/学习和认知。肝脏和肾脏产生红细胞生成素（EPO）。未成熟神经元合成EPO在胚胎期也起着决定性作用。此外，在病理生理条件下，外源性EPO在发育中的大脑中发挥其神经认知作用。本研究的目的是研究EPO在乙醇诱导神经发育毒性增加后的保护作用。从出生后2-10天开始，雄性Wistar大鼠幼崽插管5/27 g/kg/天的乙醇剂量，类似于人类妊娠的最后三个月。随后立即注射EPO （1000 /2000 U/kg, s.c）。用Morris水迷宫测试空间记忆（第36-40天），用新物体任务测试非空间识别记忆（第39-40天）。测定抗氧化酶、TNF-α (ELISA)和caspase-3（免疫组化染色）浓度。目前的研究表明，EPO可显著减轻空间和非空间记忆障碍（P <； 0.001）。EPO显著降低海马CA1区caspase 3阳性细胞的数量（P <； 0.01）。EPO增加了总超氧化物歧化酶活性（P <； 0.05）、谷胱甘肽浓度（P <； 0.05）和过氧化氢酶水平（P <； 0.001）。EPO还能减弱TNF-α和丙二醛的产生（P <； 0.05）。考虑到EPO对乙醇诱导的神经毒性增加的保护作用，它是FASD的一种可行的治疗选择，尽管还需要更多的研究。

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引用次数: 0

The role of leptin and ghrelin in the regulation of appetite in obesity 瘦素和胃饥饿素在肥胖患者食欲调节中的作用

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-02-19 DOI: 10.1016/j.peptides.2025.171367

Kinga Skoracka , Szymon Hryhorowicz , Piotr Schulz , Agnieszka Zawada , Alicja Ewa Ratajczak-Pawłowska , Anna Maria Rychter , Ryszard Słomski , Agnieszka Dobrowolska , Iwona Krela-Kaźmierczak

Leptin and ghrelin are two key hormones that play opposing roles in the regulation of appetite and energy balance. Ghrelin stimulates appetite and food intake following binding to receptors and the subsequent activation of orexigenic neurons in the arcuate nucleus. Leptin, conversely, has been demonstrated to suppress appetite and reduce food intake. This occurs through the inhibition of ghrelin-activated neurons, while simultaneously activating those that promote satiety and increase energy expenditure. A lack of biological response despite elevated leptin levels, which is known as leptin resistance, is observed in individuals with excess body weight and represents a significant challenge. As the dysregulation of ghrelin and leptin signalling has been linked to the development of obesity and other metabolic disorders, an in-depth understanding of the genetic determinants affecting these two hormones may facilitate a more comprehensive grasp of the intricate interactions that underpin the pathogenesis of obesity.

瘦素和胃饥饿素是两种关键的激素，在调节食欲和能量平衡方面发挥相反的作用。胃饥饿素在与受体结合后刺激食欲和食物摄入，并随后激活弓状核中的供氧神经元。相反，瘦素已被证明可以抑制食欲，减少食物摄入。这是通过抑制胃饥饿素激活的神经元而发生的，同时激活那些促进饱腹感和增加能量消耗的神经元。尽管瘦素水平升高，但缺乏生物反应，这被称为瘦素抵抗，在体重过重的个体中观察到，这是一个重大挑战。由于胃饥饿素和瘦素信号的失调与肥胖和其他代谢紊乱的发展有关，深入了解影响这两种激素的遗传决定因素可能有助于更全面地掌握支撑肥胖发病机制的复杂相互作用。

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引用次数: 0

Dulaglutide accelerates diabetic wound healing by suppressing Nrf2-dependent ferroptosis in diabetic mice 杜拉鲁肽通过抑制糖尿病小鼠nrf2依赖性铁下垂加速糖尿病伤口愈合。

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-02-13 DOI: 10.1016/j.peptides.2025.171366

Liuqing Xi , Juan Du , Yan Lu , Wen Xue , Yuxuan Xia , Tingxu Chen , Yang Xiao , Nuo Xu , Yansheng Wang , Jianfang Gao , Wenyi Li , Shan Huang

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are frequently utilized to treat type 2 diabetes mellitus (T2DM). Several GLP-1RAs (Exendin-4 and liraglutide) have been shown to accelerate diabetic wound healing. The major aim of the study was to investigate the roles of dulaglutide in wound healing in diabetic mice and identify the underlying mechanism involved. Round-shape, full-thickness wounds were created on the backs of db/db diabetic mice. Subsequently, dulaglutide was delivered via subcutaneous injections surrounding the wound’s perimeter, and the wound closure rates were monitored. In vitro, keratinocytes were treated with dulaglutide under high glucose (HG) conditions, and cell viability was assessed by cell counting kit-8 (CCK-8) and EdU assays. The roles of dulaglutide in ferroptosis were assessed by measuring the levels of Fe^2 + and oxidative stress, as well as the expression of ferroptosis markers. The results demonstrated that dulaglutide treatment increased the expression of vascular endothelial growth factor (VEGF) and the proliferation marker Ki67, thereby accelerating wound healing in diabetic mice. In vitro, dulaglutide promoted HaCaT cell proliferation and migration under HG conditions. Exposure of HaCaT cells to HG resulted in ferroptosis in vivo and in vitro, as evidenced by the significant increase in Fe²⁺, reactive oxygen species (ROS), and malondialdehyde (MDA) levels and the decrease in glutathione (GSH) and superoxide dismutase (SOD) levels. All these effects were reversed by dulaglutide. Mechanistically, dulaglutide activated NFE2-related factor 2 (Nrf2) signaling under HG conditions, which increased glutathione peroxidase (Gpx4) and solute carrier family 7-member 11 (Slc7a11) expression, thereby inhibiting ferroptosis. In summary, these results demonstrate dulaglutide as a promising agent for treating diabetic wounds by regulating Nrf2-dependent ferroptosis.

胰高血糖素样肽-1受体激动剂（GLP-1RAs）常用于治疗2型糖尿病（T2DM）。几种GLP-1RAs （Exendin-4和利拉鲁肽）已被证明可以加速糖尿病伤口愈合。本研究的主要目的是探讨杜拉鲁肽在糖尿病小鼠伤口愈合中的作用，并确定其潜在的机制。在db/db糖尿病小鼠背部制造圆形全层伤口。随后，在伤口周围皮下注射杜拉鲁肽，并监测伤口愈合率。体外，在高糖（HG）条件下用杜拉鲁肽处理角质形成细胞，并通过细胞计数试剂盒-8 （CCK-8）和EdU检测评估细胞活力。通过测定铁2+水平和氧化应激水平以及铁下垂标志物的表达来评估杜拉鲁肽在铁下垂中的作用。结果表明，杜拉鲁肽处理可增加血管内皮生长因子（VEGF）和增殖标志物Ki67的表达，从而促进糖尿病小鼠伤口愈合。在体外，dulaglutide促进HG条件下HaCaT细胞的增殖和迁移。HaCaT细胞暴露于HG后，体内和体外均出现铁下垂，铁下垂表现为Fe2+、活性氧（ROS）和丙二醛（MDA）水平显著升高，谷胱甘肽（GSH）和超氧化物歧化酶（SOD）水平降低。所有这些作用都被杜拉鲁肽逆转了。在机制上，dulaglutide激活了HG条件下nfe2相关因子2 （Nrf2）信号，从而增加谷胱甘肽过氧化物酶（Gpx4）和溶质载体家族7-成员11 （Slc7a11）的表达，从而抑制铁凋亡。总之，这些结果表明杜拉鲁肽通过调节nrf2依赖性铁下垂来治疗糖尿病伤口是一种很有前景的药物。

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引用次数: 0

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