Neuropeptides最新文献_第2页

Pituitary adenylate cyclase-activating polypeptide (PACAP) attenuates diabetic cardiomyopathy via Nrf2/HO-1 antioxidant signaling and NF-κB-mediated inflammation suppression in streptozotocin-treated mice 垂体腺苷酸环化酶激活多肽（PACAP）通过Nrf2/HO-1抗氧化信号和NF-κ b介导的炎症抑制在链脲佐菌素处理小鼠中减轻糖尿病心肌病。

IF 2.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-11-01 DOI: 10.1016/j.npep.2025.102568

Dong Yang , Huozhao Ruan , Liancai Chen , Haonan Zhang , Guiying Liu

Diabetic cardiomyopathy (DCM), characterized by oxidative stress, inflammation, and pathological remodeling, is still a primary cause of death in diabetes. This study examines how pituitary adenylate cyclase-activating polypeptide (PACAP) might treat diabetic heart dysfunction caused by streptozotocin (STZ), with an emphasis on modulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) antioxidant axis and NF-κB-mediated inflammatory signaling. STZ treatment reduced PACAP expression in serum and cardiac tissues, associated with impaired ventricular contractility and hypertrophy. PACAP treatment reversed these effects, restoring heart function, as shown by increased ejection fraction and fractional shortening. PACAP also reduced cardiac hypertrophy, indicated by decreased cardiomyocyte cross-sectional area and heart weight-to-tibia length ratios. Serum markers of myocardial damage (CK-MB, AST, LDH) were elevated in STZ-treated mice but decreased by PACAP. PACAP lowered hemodynamic stress, as shown by reduced mean arterial pressure. PACAP reduced oxidative damage by increasing antioxidant enzyme activity (catalase, SOD, and GPx) and lowering lipid peroxidation, while also inhibiting NADPH oxidase activity. PACAP reduced STZ-induced myocardial inflammation by lowering TNF-α, IL-6, and IL-1β levels and increasing IL-10 levels in cardiac tissue and serum, mitigating systemic inflammation. PACAP restored Nrf2/HO-1 expression and maintained IκBα, which inhibited NF-κB signaling. These findings suggest PACAP's potential to combat oxidative stress and inflammation in STZ-induced DCM, warranting further mechanistic and translational studies.

糖尿病性心肌病（DCM）以氧化应激、炎症和病理性重构为特征，仍然是糖尿病患者死亡的主要原因。本研究探讨垂体腺苷酸环化酶激活多肽（PACAP）对链脲佐素（STZ）引起的糖尿病心功能障碍的作用，重点研究PACAP对核因子红系2相关因子2 (Nrf2)/血红素加氧酶-1 （HO-1）抗氧化轴和NF-κ b介导的炎症信号的调节作用。STZ治疗降低了血清和心脏组织中PACAP的表达，与心室收缩性和肥厚受损有关。PACAP治疗逆转了这些影响，恢复了心脏功能，如射血分数和分数缩短增加所示。PACAP还能减少心肌肥大，表现为心肌细胞横截面积和心脏重量与胫骨长度之比的减少。stz组小鼠血清心肌损伤指标CK-MB、AST、LDH升高，PACAP组降低。PACAP降低了血流动力学压力，如平均动脉压降低所示。PACAP通过增加抗氧化酶活性（过氧化氢酶、SOD和GPx）和降低脂质过氧化作用来减轻氧化损伤，同时抑制NADPH氧化酶活性。PACAP通过降低心肌组织和血清中TNF-α、IL-6和IL-1β水平，增加IL-10水平，减轻全身炎症，减轻stz诱导的心肌炎症。PACAP恢复Nrf2/HO-1表达，维持i -κB α，抑制NF-κB信号转导。这些发现表明PACAP在stz诱导的DCM中具有抗氧化应激和炎症的潜力，值得进一步的机制和转化研究。

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引用次数: 0

Salivary oxytocin responses in mothers and full-term newborns in early skin-to-skin contact for the first 2 hours after birth: Effects of synthetic oxytocin administration and epidural analgesia in labor 母亲和足月新生儿出生后2小时皮肤接触时唾液催产素的反应：人工合成催产素和分娩时硬膜外镇痛的影响

IF 2.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-10-28 DOI: 10.1016/j.npep.2025.102567

Aya Tomita, Kaori Yonezawa, Yuriko Usui, Megumi Haruna

Background

Epidural analgesia with synthetic oxytocin reduces maternal oxytocin levels in the early postpartum period. However, whether maternal and neonatal endogenous oxytocin levels in the first 2 h after birth are affected by drug administration during labor is unknown.

Aim

To determine the effect of drug administration during labor on maternal–newborn salivary oxytocin levels after birth.

Methods

This cohort study was conducted on 62 stable primiparous mother–newborn pairs after vaginal birth. Saliva samples were collected approximately 30 (pre-skin-to-skin contact), 60 (during skin-to-skin contact), and 120 (post-skin-to-skin contact) minutes after birth. Mother–newborn pairs were stratified by medical interventions during labor: non-drug, oxytocin-only, and epidural analgesia-with-oxytocin groups. A mixed-effects model was used to evaluate the log-transformed salivary oxytocin levels among the three groups at each repeated measure.

Results

Maternal oxytocin levels of the epidural analgesia-with-oxytocin group (β = − 0.384, standard error = 0.113) were significantly lower than those of the non-drug group at 30 min (p < 0.001). The group-time interaction analysis showed that the changes in salivary oxytocin levels in the oxytocin-only and epidural analgesia-with-oxytocin groups differed from those in the non-drug group at 60 and 120 min. Newborn oxytocin levels did not significantly differ.

Conclusions

Drug administration during labor may reduce maternal salivary oxytocin levels in the first 2 h after birth. Healthcare professionals should provide information on different approaches, such as a non-pharmacologic approach, for pain relief for primipara during labor.

背景：合成催产素硬膜外镇痛可降低产后早期产妇催产素水平。然而，产妇和新生儿出生后2小时内的内源性催产素水平是否受到分娩期间给药的影响尚不清楚。目的：探讨产程给药对分娩后母婴唾液催产素水平的影响。方法：对62对阴道分娩后稳定的初产妇进行队列研究。唾液样本在出生后大约30分钟（皮肤接触前）、60分钟（皮肤接触期间）和120分钟（皮肤接触后）采集。在分娩过程中，根据医疗干预对母婴进行分层：非药物组、仅使用催产素组和硬膜外使用催产素组。采用混合效应模型评估三组在每次重复测量时的对数转化唾液催产素水平。结果：催产素硬膜外镇痛组30 min时产妇催产素水平（β = - 0.384，标准误差= 0.113）显著低于非药物组(p)。结论：分娩时给药可降低产妇产后前2 h唾液催产素水平。医疗保健专业人员应提供不同方法的信息，如非药物方法，缓解分娩期间初产妇的疼痛。

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引用次数: 0

Ultrastructural characterization of neuropeptide Y synapses in the central inferior colliculus of the Fischer Brown Norway rat Fischer Brown Norway大鼠中央下丘神经肽Y突触的超微结构表征。

IF 2.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-10-13 DOI: 10.1016/j.npep.2025.102566

Laila S. Almassri , Joshua C. Harris , Kristen M. Crane , Andrew P. Ohl , Nick J. Tokar , Brett R. Schofield , Jesse W. Young , Jeffrey G. Mellott

Introduction

The central nucleus of the inferior colliculus (ICc) is the primary target for ascending auditory projections from the lower auditory brainstem nuclei and the main source of ascending projections to the auditory thalamus. The ICc has an extensive network of tonotopically organized neurons, whose classification is a subject of broad interest. In order to understand the extensive microcircuitry of the ICc, it is important to ascertain the synaptic arrangements among molecularly identified neuronal populations. The objective of this study was to describe inhibitory Neuropeptide Y (NPY) synapses in the central nucleus of the IC.

Method

We used electron microscopy (EM) and post-embedding anti-NPY immunogold histochemistry on tissue from adult Fischer Brown Norway rats. Inhibitory NPY synapses were identified by pleomorphic vesicles, symmetric synaptic junctions, and NPY-immunopositive presynaptic boutons.

Results

The data demonstrate that NPY terminals largely (∼75 %) form symmetric synapses with pleomorphic vesicles, mostly target small and medium dendrites, and have larger average bouton areas, active zone lengths, and vesicle pools, as compared to the overall GABAergic population.

Discussion

The subset of GABAergic neurons that co-express NPY feature synaptic characteristics suggesting that NPY neuromodulation has a widespread role in regulating excitation in the ICc.

下丘中央核是来自下听脑干核的上行听觉投射的主要目标，也是听觉丘脑上行投射的主要来源。ICc有一个广泛的拓扑组织神经元网络，其分类是一个广泛感兴趣的主题。为了了解ICc的广泛微电路，确定分子识别的神经元群体之间的突触排列是很重要的。方法：采用电镜和免疫组化方法对成年褐威大鼠组织进行抗神经肽Y （NPY）包埋后免疫组化。抑制性NPY突触通过多形性囊泡、对称突触连接和NPY免疫阳性的突触前钮扣来鉴定。结果：数据表明，NPY末端大部分（~ 75%）形成具有多形性囊泡的对称突触，主要针对中小型树突，并且与总体gaba能群体相比，具有更大的平均钮扣面积，活性区长度和囊泡池。讨论：共同表达NPY的gaba能神经元子集具有突触特征，这表明NPY神经调节在ICc的兴奋调节中具有广泛的作用。

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引用次数: 0

Role of interplay between endocannabinoids and neuropeptides in pathogenesis and therapy of depressive and anxiety disorders 内源性大麻素和神经肽在抑郁和焦虑障碍发病和治疗中的相互作用。

IF 2.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-10-11 DOI: 10.1016/j.npep.2025.102564

Miłosz Gołyszny , Jonasz Dragon , Ewa Obuchowicz

A growing body of evidence suggests the existence of a neurochemical and functional interplay between endocannabinoids and neuropeptides, which are both relevant for the pathomechanism and effects of pharmacotherapy in depressive and anxiety disorders. Here, we review the available data on how endocannabinoids influence the activity of the neuropeptidergic systems and conversely, how neuropeptides affect the endocannabinoid system. The explicit/implicit interactions in the relationship of endocannabinoids-neuropeptides are presented. Our paper focuses on both well-known neuropeptides, i.e., corticotropin-releasing hormone/factor, CRH/CRF; oxytocin, OT; arginine-vasopressin, AVP; neuropeptide Y, NPY; orexins/hypocretins, OXs/HCRTs) and less investigated neuropeptides, i.e., nesfatin-1, NEFA; phoenixin, PNX; spexin, SPX; neuropeptide S, NPS). Of all of the brain regions that have been studied, the direct and indirect bidirectional interactions between endocannabinoids and the neuropeptides has most clearly been established in the hypothalamus. It has been proven that neuropeptides are modulators of the multifaceted effects of the endocannabinoid system, namely, its influence on neuroendocrine (CRH/CRF) and behavioral stress responsivity (CRH/CRF, OXs), sociability (OT), feelings of pleasure (OXs/HCRTs, NPS), appetite control (NPY, OXs/HCRTs, CRH/CRF, NEFA) and nociception (OT). This latter effect has only the desirable support of positive influence of endocannabinoids on emotional homeostasis to some extent. Nowadays, increasing attention is being paid to the interplay between endocannabinoids and the less explored peptides, especially NEFA and NPS. This trend is both desirable and necessary for gaining a better understanding of the neurochemical aspects and for providing new insights into the potential therapeutic implications in the treatment of affective disorders.

越来越多的证据表明，内源性大麻素和神经肽之间存在神经化学和功能上的相互作用，这些相互作用与抑郁症和焦虑症的病理机制和药物治疗效果有关。在这里，我们回顾了关于内源性大麻素如何影响神经肽能系统的活性以及神经肽如何影响内源性大麻素系统的现有数据。介绍了内源性大麻素-神经肽之间的外显/内隐相互作用。我们的论文主要关注两种众所周知的神经肽，即促肾上腺皮质激素释放激素/因子，CRH/CRF；催产素,不;精氨酸抗利尿激素,avon;神经肽Y， NPY；食欲素/下丘脑分泌素（OXs/ hcrt）和较少研究的神经肽，即nesfatin-1， NEFA；phoenixin,非常感谢;spexin SPX;神经肽S （NPS）。在所有已被研究的大脑区域中，内源性大麻素和神经肽之间的直接和间接双向相互作用在下丘脑中得到了最明确的证实。已经证明，神经肽是内源性大麻素系统多方面作用的调节剂，即其对神经内分泌（CRH/CRF）和行为应激反应（CRH/CRF, OXs），社交能力（OT），愉悦感（OXs/HCRTs， NPS），食欲控制（NPY, OXs/HCRTs, CRH/CRF， NEFA）和伤害感觉（OT）的影响。后一种作用在一定程度上只有内源性大麻素对情绪稳态的积极影响的理想支持。目前，人们越来越关注内源性大麻素与较少探索的肽，特别是NEFA和NPS之间的相互作用。这一趋势对于更好地理解神经化学方面以及为情感障碍治疗的潜在治疗意义提供新的见解是可取的和必要的。

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引用次数: 0

Inhibitory modulation of gastrointestinal motility in mice by Tyr-c[D-Lys-Gly-p-F-Phe-Asp]-D-Pro-NH2, a novel cyclic hexapeptide with multifunctional opioid agonism 具有多功能阿片激动作用的新型环六肽Tyr-c[d - lys - gly -p- f - ph - asp]-D-Pro-NH2对小鼠胃肠运动的抑制调节

IF 2.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-10-09 DOI: 10.1016/j.npep.2025.102565

Weifan Ding, Qinqin Zhang, Mengna Zhang, Ning Li, Biao Xu, Yaqi Song, Quan Fang, Nan Zhang

Opioid analgesics are critical for managing moderate-to-severe pain，yet are limited by adverse gastrointestinal (GI) effects, notably constipation. This necessitates developing novel opioid agonists with robust analgesia and reduced GI side effects. The cyclic hexapeptide Tyr-c[D-Lys-Gly-p-F-Phe-Asp]-D-Pro-NH₂ (analog 15), a recently characterized multifunctional agonist of μ-opioid receptor (MOR), κ-opioid receptor (KOR), and δ-opioid receptor (DOR), exhibits potent antinociception following subcutaneous (s.c.) administration with constipation observed only at high doses. To further evaluate its GI impact, we assessed the effects of analog 15 on intestinal motility using in vivo upper GI transit and colonic bead expulsion assays. Our results indicated that fentanyl, analog 15, and its parent peptide analog 0 dose-dependently slowed upper GI transit and colonic expulsion after s.c. administration, with the upper GI tract exhibiting greater sensitivity. Mechanistically, fentanyl inhibited the GI motility via both central and peripheral opioid receptors, whereas analog 15 inhibited upper GI transit exclusively through the peripheral MOR, KOR, and DOR, and suppressed colonic transit via the peripheral MOR and KOR, both effects were independent of the central opioid receptor pathway. In conclusion, we demonstrated that the high doses of analog 15 inhibited GI motility through peripherally restricted activation of multiple opioid receptors. This finding aligns with analog 15's limited blood-brain barrier (BBB) permeability, which explains its reduced constipating effects while preserving potent analgesia, thereby supporting the therapeutic potential of multi-target peripheral opioid agonists.

阿片类镇痛药对于治疗中度至重度疼痛至关重要，但其不良胃肠道（GI）效应（尤其是便秘）有限。这就需要开发具有强大镇痛作用和减少胃肠道副作用的新型阿片类激动剂。环六肽Tyr-c[D-Lys-Gly-p-F-Phe-Asp]-D-Pro-NH2（类似物15）是最近发现的μ-阿片样受体（MOR）、κ-阿片样受体（KOR）和δ-阿片样受体（DOR）的多功能激动剂，在皮下（s.c）给药后显示出有效的抗炎作用，仅在高剂量下观察到便秘。为了进一步评估其对胃肠道的影响，我们通过体内上消化道运输和结肠珠排出试验评估了类似物15对肠道运动的影响。我们的研究结果表明，芬太尼、类似物15及其母体肽类似物0剂量依赖性地减缓了s.c.给药后的上消化道转运和结肠排出，且上消化道表现出更大的敏感性。在机制上，芬太尼通过中枢和外周阿片受体抑制胃肠道运动，而类似物15仅通过外周MOR、KOR和DOR抑制上消化道运输，并通过外周MOR和KOR抑制结肠运输，这两种作用都独立于中枢阿片受体途径。总之，我们证明了高剂量的类似物15通过外周限制多种阿片受体的激活来抑制胃肠道运动。这一发现与类似物15有限的血脑屏障（BBB）渗透性一致，这解释了它在保持有效镇痛的同时减少便秘作用，从而支持多靶点外周阿片受体激动剂的治疗潜力。

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引用次数: 0

Modulation of neuropathological pathways by bioactive peptides and proteins/polypeptides: Targeting oxidative stress in neurodegenerative diseases 生物活性肽和蛋白/多肽对神经病理通路的调节：针对神经退行性疾病中的氧化应激

IF 2.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-09-21 DOI: 10.1016/j.npep.2025.102563

Sushil Giri, Phool Chandra

Neurodegenerative disorders (NDDs) pose a growing global health burden, primarily due to their progressive nature and the limited efficacy of existing treatments. Bioactive peptides and proteins/polypeptides, particularly those derived from dietary and natural sources, show promise in modulating neurobiological pathways central to neurodegeneration. This review aims to critically examine the neuroprotective roles of Bioactive peptides and proteins/polypeptides in NDDs, elucidating their mechanisms of action, potential therapeutic applications in conditions like Alzheimer's, Parkinso's disease, Huntington's disease, and others, as well as the trends in peptide-based therapeutics. Bioactive peptides and proteins/polyspeptides, such as NGF, BDNF, GDNF, Semax, and Exendin-4, have been found to modulate several critical mechanisms, including the reduction of oxidative stress (OS), inhibition of neuroinflammation, preservation of mitochondria, and enhancement of synaptic plasticity. These peptides have demonstrated efficacy in preclinical and early-phase clinical trials across a spectrum of NDDs. Delivery challenges, such as blood-brain barrier (BBB) permeability and enzymatic degradation, have been acknowledged. Ongoing innovations in peptide engineering, nanoparticle-based delivery systems, CRISPR-assisted design, and AI-driven screening are addressing these limitations. By targeting multiple pathogenic mechanisms simultaneously, peptide-based therapeutics present a rational and innovative approach to NDD management. Their multifunctional action profiles and ability to target specific molecular pathways highlight their potential as next-generation neuroprotective agents. However, future clinical validation and advanced strategies are essential for translating these promising molecules into effective treatments.

神经退行性疾病（ndd）造成了日益严重的全球健康负担，主要是由于其进行性和现有治疗方法的有效性有限。生物活性多肽和蛋白质/多肽，特别是来自膳食和天然来源的生物活性多肽，在调节神经退行性变的中枢神经生物学通路方面显示出前景。本综述旨在批判性地研究生物活性肽和蛋白质/多肽在ndd中的神经保护作用，阐明其作用机制，在阿尔茨海默病，帕金森病，亨廷顿病等疾病中的潜在治疗应用，以及基于肽的治疗方法的发展趋势。生物活性肽和蛋白/多肽，如NGF、BDNF、GDNF、Semax和Exendin-4，已被发现可以调节几种关键机制，包括减少氧化应激（OS）、抑制神经炎症、保存线粒体和增强突触可塑性。这些肽已在临床前和早期临床试验中证明了对ndd的有效性。递送挑战，如血脑屏障（BBB）的渗透性和酶降解，已经得到承认。肽工程、基于纳米颗粒的递送系统、crispr辅助设计和人工智能驱动的筛选等方面的持续创新正在解决这些限制。通过同时针对多种致病机制，基于肽的治疗方法为NDD的治疗提供了一种合理和创新的方法。它们的多功能作用特征和靶向特定分子途径的能力突出了它们作为下一代神经保护剂的潜力。然而，未来的临床验证和先进的策略对于将这些有希望的分子转化为有效的治疗方法至关重要。

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引用次数: 0

Kisspeptin-54 ameliorates chondrocyte senescence in osteoarthritis via SIRT3-mediated telomere protection and p53 acetylation inhibition Kisspeptin-54通过sirt3介导的端粒保护和p53乙酰化抑制改善骨关节炎软骨细胞衰老。

IF 2.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-09-19 DOI: 10.1016/j.npep.2025.102562

Zhuobin Yang, Jimo Li, Wenfeng Jin, Dongfeng Cai, Jing Zhang, Song Hong

Background

Osteoarthritis (OA), characterized by chondrocyte senescence and oxidative stress, affects over 300 million people globally. Kisspeptin-54, a neuropeptide with pleiotropic protective effects, was investigated for its role in chondrocyte senescence and its underlying mechanisms.

Methods

Oxidative stress and senescence were induced in primary mouse chondrocytes by treating them with TBHP. Kisspeptin-54 was administered at varying concentrations (10–1000 nM) to assess cytoprotection, while SIRT3 was knocked down using adenoviral shRNA to validate mechanistic pathways. Telomere length, mTERT expression, telomerase activity, and p53 acetylation were evaluated via Southern blot, RT-PCR, and western blot techniques. Furthermore, senescence was evaluated through the application of SA-β-galactosidase staining alongside the measurement of PAI-1 expression.

Results

TBHP induced dose-dependent GPR54 downregulation, oxidative stress (260 % increase in ROS), telomere attrition (41 % reduction in length), and senescence (270 % increase in SA-β-galactosidase-positive cells). Kisspeptin-54 (≤200 nM) rescued cell viability, reduced LDH release (57 % at 200 nM), and mitigated ROS and SOD activity decline. Mechanistically, Kisspeptin-54 restored SIRT3 expression, suppressed p53 acetylation (Acetyl-p53[K382] reduced by 56 % at 200 nM), and preserved telomere function (telomere length restored to 91 % of control). SIRT3 knockdown abrogated these effects, confirming its critical role.

Conclusion

Kisspeptin-54 alleviates chondrocyte senescence via a dual mechanism: (1) SIRT3-mediated restoration of mitochondrial antioxidant capacity and telomere homeostasis; (2) inhibition of p53 hyperacetylation and downstream senescence signaling. These findings establish Kisspeptin-54 as an innovative therapeutic candidate for OA acting through the modulation of the SIRT3/p53 axis to combat oxidative stress and telomere dysfunction.

背景：骨关节炎（OA）以软骨细胞衰老和氧化应激为特征，影响全球超过3亿人。Kisspeptin-54是一种具有多效保护作用的神经肽，研究了其在软骨细胞衰老中的作用及其潜在机制。方法：用三必和必肽诱导小鼠原代软骨细胞氧化应激和衰老。Kisspeptin-54以不同浓度（10-1000 nM）施用以评估细胞保护作用，同时使用腺病毒shRNA敲低SIRT3以验证机制途径。端粒长度、mTERT表达、端粒酶活性和p53乙酰化通过Southern blot、RT-PCR和western blot技术进行评估。此外，通过SA-β-半乳糖苷酶染色和测定PAI-1表达来评估衰老。结果：在SA-β-半乳糖苷酶阳性细胞中，thbhp诱导剂量依赖性GPR54下调、氧化应激（ROS增加260%）、端粒磨损（长度减少41%）和衰老（增加270%）。Kisspeptin-54（≤200 nM）挽救细胞活力，降低LDH释放（200 nM时57%），减轻ROS和SOD活性下降。在机制上，Kisspeptin-54恢复了SIRT3的表达，抑制了p53的乙酰化（Acetyl-p53[K382]在200 nM时减少了56%），并保持了端粒功能（端粒长度恢复到对照组的91%）。SIRT3敲除消除了这些影响，证实了它的关键作用。结论：Kisspeptin-54通过双重机制缓解软骨细胞衰老：(1)sirt3介导的线粒体抗氧化能力和端粒稳态的恢复；(2)抑制p53超乙酰化和下游衰老信号。这些发现表明Kisspeptin-54是一种通过调节SIRT3/p53轴来对抗氧化应激和端粒功能障碍的OA的创新治疗候选药物。

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引用次数: 0

Nesfatin1 attenuates autism-like behavior via antioxidant, anti-inflammatory activities in a prenatal valproic acid-induced rat model of autism 在产前丙戊酸诱导的自闭症大鼠模型中，Nesfatin1通过抗氧化、抗炎活性减弱自闭症样行为

IF 2.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-09-13 DOI: 10.1016/j.npep.2025.102561

Mitra Farbin , Razieh Hajisoltani , Tourandokht Baluchnejadmojarad , Anahita Hejazi , Touqeer Ahmed , Heshmatollah Parsian , Soraya Mehrabi

Nesfatin1, a multifunctional peptide involved in energy homeostasis and neural regulation, has emerged as a promising candidate for modulating neurodevelopmental disorders. The anti-inflammatory, antioxidant, and neuroprotective properties of Nesfatin1 have been proven in the central nervous system (CNS). Therefore, it has emerged as a candidate for targeted therapy of various neurological condition. Autism Spectrum Disorder (ASD) is a significant neurological disorder. Considering the importance of these mechanisms demonstrated by Nefastine1, The current study aimed to investigate the therapeutic potential and mechanisms of Nesfatin1 in a rat model of autism. This study evaluated the therapeutic potential of Nesfatin1 in a rodent model of autism induced by prenatal exposure to valproic acid (VPA). Pregnant Wistar rats received VPA on embryonic day 12.5, and male offspring were subsequently assessed for autism-like behaviors using a comprehensive battery of tests, including the three-chamber social interaction test, marble burying, shuttle box passive avoidance, and the elevated plus maze. Following behavioral testing, rats were euthanized, and blood samples were collected via transcardial perfusion. Serum oxytocin levels were measured, and hippocampal tissues were analyzed for inflammatory markers (IL-6, TNF-α) using ELISA. Additionally, total antioxidant capacity (TAC) and the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were assessed. VPA-exposed rats exhibited significant social deficits, increased repetitive behaviors, and impaired cognitive performance, accompanied by heightened neuroinflammation and oxidative stress. Notably, treatment with Nesfatin1 markedly improved social engagement and preference, reduced anxiety and repetitive behaviors, and restored biochemical parameters toward normal levels. Results showed that possible therapeutic mechanism of Nefastin1 are by decreasing inflammation and reducing markers of oxidative stress, while concurrently elevating levels of oxytocin, in addition to the other unknown mechanisms.

Nesfatin1是一种参与能量稳态和神经调节的多功能肽，已成为调节神经发育障碍的有希望的候选者。Nesfatin1在中枢神经系统（CNS）中已被证实具有抗炎、抗氧化和神经保护特性。因此，它已成为多种神经系统疾病靶向治疗的候选药物。自闭症谱系障碍（ASD）是一种重要的神经系统疾病。考虑到nefatin1所证明的这些机制的重要性，本研究旨在探讨Nesfatin1在自闭症大鼠模型中的治疗潜力和机制。本研究评估了Nesfatin1在产前暴露于丙戊酸（VPA）诱导的自闭症啮齿动物模型中的治疗潜力。怀孕的Wistar大鼠在胚胎期第12.5天接受了VPA治疗，随后通过三室社会互动测试、弹珠掩埋、穿梭箱被动回避和高架迷宫等一系列综合测试来评估雄性后代的自闭症样行为。行为学测试后，对大鼠实施安乐死，经心肌灌注取血。检测血清催产素水平，ELISA法检测海马组织炎症标志物（IL-6、TNF-α）。测定总抗氧化能力（TAC）、谷胱甘肽过氧化物酶（GPx）和超氧化物歧化酶（SOD）活性。暴露于vpa的大鼠表现出明显的社交缺陷，重复性行为增加，认知能力受损，并伴有神经炎症和氧化应激升高。值得注意的是，Nesfatin1治疗显著改善了社会参与和偏好，减少了焦虑和重复行为，并将生化参数恢复到正常水平。结果表明，Nefastin1可能的治疗机制是通过降低炎症和氧化应激标志物，同时提高催产素水平，以及其他未知的机制。

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引用次数: 0

Therapeutic potential of small peptides in Alzheimer's disease: Advances in memory restoration and targeted delivery systems 小肽在阿尔茨海默病中的治疗潜力：记忆恢复和靶向递送系统的进展

IF 2.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-09-05 DOI: 10.1016/j.npep.2025.102559

Poonam Verma , Rubina Khatun , Kiran Anjum Jew , Shakti Ketan Prusty , Shira Knafo

Despite extensive research into Alzheimer's disease (AD), few therapeutic strategies have successfully addressed its core pathology at the synaptic level. Small peptides represent a promising class of therapeutic agents capable of modulating key molecular pathways involved in amyloid toxicity, tau hyperphosphorylation, and synaptic degeneration. Their unique ability to cross biological barriers, interact with intracellular targets, and be modified for enhanced stability positions them as viable candidates for next-generation treatments targeting cognitive decline in AD.Small peptides show strong therapeutic potential yet face challenges in clinical application due to poor bioavailability and rapid enzymatic degradation. To deal with these limitations, various delivery strategies such as intranasal administration, nanoparticle encapsulation, and chemical modification have been developed. When combined with advanced delivery systems, small peptides hold significant promise for mitigating synaptic dysfunction and slowing the progression of Alzheimer's disease. In this review, we examine the mechanisms of action of four small peptides that demonstrate potential in alleviating Alzheimer's-related symptoms. We also evaluate the most effective delivery methods, emphasizing how these approaches enhance the peptides' therapeutic efficacy.

尽管对阿尔茨海默病（AD）进行了广泛的研究，但很少有治疗策略成功地在突触水平上解决其核心病理问题。小肽是一类很有前途的治疗药物，能够调节涉及淀粉样蛋白毒性、tau蛋白过度磷酸化和突触变性的关键分子途径。它们跨越生物屏障、与细胞内靶点相互作用以及通过修饰增强稳定性的独特能力，使它们成为针对AD认知能力下降的下一代治疗的可行候选药物。小肽具有很强的治疗潜力，但由于生物利用度差、酶降解快，在临床应用中面临挑战。为了解决这些限制，各种给药策略，如鼻内给药、纳米颗粒包封和化学修饰已经开发出来。当与先进的递送系统结合时，小肽在减轻突触功能障碍和减缓阿尔茨海默病的进展方面具有重要的前景。在这篇综述中，我们研究了四种具有缓解阿尔茨海默病相关症状潜力的小肽的作用机制。我们还评估了最有效的递送方法，强调这些方法如何增强肽的治疗效果。

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引用次数: 0

The role of salivary neurotensin and oxytocin in emotional responses to stress inoculation 唾液神经紧张素和催产素在应激接种的情绪反应中的作用

IF 2.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-09-05 DOI: 10.1016/j.npep.2025.102560

Matthew Branney , Madison Propp , Dalton Jensen , Anoushka Singh , Mark Payton , Rebecca Ryznar

Neuropeptides comprise a class of signaling molecules that exert direct effects on target tissues and modulatory influences across multiple physiological systems; however, their roles in mediating stress responses remains incompletely characterized. Previous studies have shown that acute stress alters salivary levels of neuropeptides but the extent to which these alterations are associated with mechanisms of stress inoculation and emotional valence requires exploration. This study aimed to examine the relationship between salivary neuropeptides and emotional valence following acute stress in military medical students. Salivary samples for oxytocin, neurotensin and data from two questionnaires, ACE and SPANE, were collected from participants pre- and post-stress inoculation. Spearman rank correlation analysis revealed positive correlations >0.9 for neurotensin and oxytocin at pre- and post-inoculation. Post-inoculation neurotensin showed an inverse correlation with pre-simulation SPANE-P and SPANE-B scores (p = 0.006 and p = 0.009 respectively) and demonstrated a positive correlation with pre-simulation SPANE-N score (p = 0.043). Post-inoculation oxytocin demonstrated a negative correlation with pre-inoculation SPANE-P and SPANE-B scores (p = 0.007 and p = 0.006 respectively). Cohorts were established of participants whose neuropeptide levels increased or decreased during inoculation. Inverse correlations existed between oxytocin post-simulation and post-SPANE positive emotions in the increased oxytocin group (R = −0.4607), and between pre-simulation oxytocin and pre-SPANE positive emotions in the decreased oxytocin group (R = −0.4005). Individual variability in salivary neuropeptide responses to inoculation was inversely associated with positive affect, suggesting these neuropeptides as modulators of affective stress responsivity. Future studies should explore the mechanism of these associations and evaluate the potential of salivary neuropeptides as biomarkers for emotional and stress adaptation.

神经肽包括一类信号分子，对靶组织产生直接作用，并对多个生理系统产生调节作用；然而，它们在介导应激反应中的作用尚未完全确定。先前的研究表明，急性应激会改变唾液中神经肽的水平，但这些改变在多大程度上与应激接种和情绪效价的机制有关，还需要探索。本研究旨在探讨军医学生急性应激后唾液神经肽与情绪效价的关系。研究人员收集了应激接种前后参与者唾液中催产素、神经紧张素的样本，以及ACE和SPANE两份问卷的数据。Spearman秩相关分析显示接种前后神经紧张素和催产素呈正相关>；0.9。接种后神经紧张素与模拟前span - p和span - b评分呈负相关（p = 0.006和p = 0.009），与模拟前span - n评分呈正相关（p = 0.043）。接种后催产素与接种前span - p和span - b评分呈负相关（p = 0.007和p = 0.006）。建立了接种期间神经肽水平升高或降低的参与者的队列。催产素增加组模拟后的催产素与spane后的积极情绪呈负相关（R = - 0.4607），催产素减少组模拟前的催产素与spane前的积极情绪呈负相关（R = - 0.4005）。唾液神经肽对接种反应的个体差异与积极影响呈负相关，表明这些神经肽是情感应激反应的调节剂。未来的研究应该探索这些关联的机制，并评估唾液神经肽作为情绪和应激适应生物标志物的潜力。

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引用次数: 0