Peptides最新文献_第6页

IGF-1 contributes to cardiovascular protection in obesity by upregulating Na+/K+-ATPase activity and modulating key signaling pathways in rats on a high-fat diet 在高脂肪饮食的大鼠中，IGF-1通过上调Na+/K+- atp酶活性和调节关键信号通路，有助于心血管保护

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-08-01 Epub Date: 2025-05-27 DOI: 10.1016/j.peptides.2025.171418

Katarina Banjac , Milan Obradovic , Sonja Zafirovic , Esma R. Isenovic

This study examined the ability of insulin-like growth factor-1 (IGF-1) to improve the expression and function of cardiac sodium/potassium adenosine triphosphatase (Na⁺/K⁺-ATPase) and reduce heart hypertrophy in obese rats. Adult male Wistar rats received a standard diet or a high-fat (HF) diet for 12 weeks. A bolus injection of IGF-1 (50 μg/kg, i.p.) was administered to half of the HF rats 24 hours before euthanasia. IGF-1 treatment increased: the activity of Na⁺/K⁺-ATPase and expression of phosphorylated and total Na⁺/K⁺-ATPase α₁ subunit, the phosphorylation of IGF-1 receptor β /insulin receptor β at Tyr¹¹³¹/Tyr¹¹⁴⁶, insulin receptor substrate-1 (IRS-1) at Tyr¹²²², mammalian target of rapamycin (mTOR) at Ser²⁴⁸¹, protein kinase B (Akt) at Ser⁴⁷³ and the expression of type-2 angiotensin II (AngII) receptor (AT₂R). Conversely, IGF-1 reduced the levels of IRS-1 phosphorylated at Ser³⁰⁷, mTOR at Ser²⁴⁴⁸, ribosomal protein p70 S6 kinase (S6K) at Thr⁴²¹/Ser⁴²⁴, and the expression of type-1 Ang II receptor (AT₁R) in the heart, as well as the serum levels of Ang II in obese rats. IGF-1 treatment reduced cardiac mass and elevated mRNA expression of the α-myosin heavy chain (MHC), and the α/β MHC ratio in the hearts of obese rats. The results of this study suggest that the administration of IGF-1 to obese rats reduces the adverse effects of HF diet, potentially by lowering Ang II-mediated activation of mTOR/S6K and enhancing the IRS-1/Akt pathway, which promotes Na⁺/K⁺-ATPase activity in the heart and diminishes cardiac hypertrophy.

本研究考察了胰岛素样生长因子-1 （IGF-1）改善肥胖大鼠心脏钠/钾腺苷三磷酸酶（Na+/K+- atp酶）的表达和功能，减轻心脏肥厚的能力。成年雄性Wistar大鼠分别饲喂标准饮食和高脂肪饮食12周。在安乐死前24 小时，半数HF大鼠给予IGF-1（50 μg/kg, i.p）。IGF-1处理增加：Na+/K+- atp酶活性、磷酸化和总Na+/K+- atp酶α1亚基的表达、IGF-1受体β /胰岛素受体β Tyr1131/Tyr1146、胰岛素受体底物-1 (IRS-1) Tyr1222、哺乳动物雷帕霉素靶蛋白（mTOR） Ser2481、蛋白激酶B (Akt) Ser473和2型血管紧张素II （AngII）受体（AT2R）的表达。相反，IGF-1降低了Ser307位点磷酸化的IRS-1、Ser2448位点磷酸化的mTOR、Thr421/Ser424位点核糖体蛋白p70 S6激酶（S6K）的水平、心脏中1型Ang II受体（AT1R）的表达以及肥胖大鼠血清中Ang II的水平。IGF-1处理降低肥胖大鼠心脏质量，升高α-肌球蛋白重链（MHC） mRNA表达和α/β MHC比值。本研究结果表明，肥胖大鼠给予IGF-1可减少HF饮食的不良影响，可能是通过降低Ang ii介导的mTOR/S6K激活和增强IRS-1/Akt通路，从而促进心脏Na+/K+- atp酶活性并减轻心脏肥厚。

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引用次数: 0

Whole body distribution of the regulatory peptide 26RFa in male and female mice 调节肽26RFa在雌雄小鼠体内的全身分布。

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-08-01 Epub Date: 2025-05-29 DOI: 10.1016/j.peptides.2025.171417

Marie Picot , Mélodie Devère , Saloua Takhlidjt , Corentin Guillemot , Caroline Lusurier , Gaëtan Prévost , Nicolas Chartrel , David Godefroy

26RFa is a regulatory peptide initially isolated from the brain. 26RFa was found to be involved in the regulation of vital functions such as the regulation of energy and glucose metabolism. However, the whole distribution of 26RFa in the organs/tissues of the organism remains fragmentary although it represents a crucial step to discover novel physiological functions for this regulatory peptide. To this aim, we have generated a mouse line that expresses the fluorescent protein tdTomato in 26RFa-expressing cells, and visualization of tdTomato immunostaining in toto was performed using the tridimensional imaging approach.

Our observations reveal that 26RFa is largely distributed among the organism of male and female mice. 26RFa-expressing cells were notably found in numerous regions of the central nervous system including the olfactory bulbs, the cortex, the hippocampus, the hypothalamus, the cerebellum, the brainstem and the spinal cord. At the periphery, 26RFa-expressing structures were detected all along the gastrointestinal tract, in the liver, the white adipose tissue, the kidney, the adrenal gland, the lungs, the male and female reproductive tracts, the striated muscles, the thymus and a number of exocrine glands such as the salivary glands, the prostate, the seminal vesicles.

In conclusion, the present anatomical observations are in agreement with the main physiological functions previously reported for 26RFa such the regulation of energy and glucose metabolism or the control of the hypothalamo-pituitary-gonadal or adrenal axis. However, 26RFa is present in other organs/tissues in which its physiological relevance is totally unknown opening therefore a new field of research for this regulatory peptide.

26RFa是一种最初从大脑中分离出来的调节肽。rfa被发现参与了一些重要功能的调节，如能量和葡萄糖代谢的调节。然而，26RFa在生物体器官/组织中的整体分布仍然是零碎的，尽管它代表了发现这种调节肽的新生理功能的关键一步。为此，我们在表达26rfa的细胞中产生了表达荧光蛋白tdTomato的小鼠细胞系，并使用三维成像方法可视化tdTomato在toto中的免疫染色。结果表明，26RFa主要分布于雌雄小鼠体内。在中枢神经系统的许多区域，包括嗅球、皮质、海马体、下丘脑、小脑、脑干和脊髓，都发现了表达rfa的细胞。在外周，沿胃肠道、肝脏、白色脂肪组织、肾脏、肾上腺、肺、男性和女性生殖道、横条肌、胸腺以及一些外分泌腺（如唾液腺、前列腺、精囊）均检测到表达26rfa的结构。总之，目前的解剖观察结果与先前报道的26RFa的主要生理功能一致，如调节能量和葡萄糖代谢或控制下丘脑-垂体-性腺或肾上腺轴。然而，26RFa存在于其他器官/组织中，其生理相关性完全未知，因此为这种调节肽开辟了一个新的研究领域。

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引用次数: 0

Acute effects of peripherally administered nicotine on food intake via the central anorectic peptide nesfatin-1/nucleobindin-2 in adult male rats 外周给药尼古丁通过中枢厌食肽nesfatin-1/ nucleobinin -2对成年雄性大鼠食物摄入的急性影响

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-07-01 Epub Date: 2025-05-12 DOI: 10.1016/j.peptides.2025.171409

Reiko Saito , Yukiyo Yamamoto , Reiji Fukano , Masatomo Mori , Takashi Maruyama , Yoichi Ueta

Acute/chronic exposure to nicotine modulates feeding behavior in experimental animals and humans. However, how nicotine modulates food intake remains unclear. This study examined the acute effects of the peripheral administration of nicotine on food intake in adult male rats, focusing on the possible involvement of the anorectic peptide nesfatin-1/nucleobindin-2 (NucB2) in the central nervous system (CNS). Initially, cumulative food intake, but not water intake, was significantly decreased 0.5, 1, and 1.5 h after the intraperitoneal administration of nicotine (0.5 mg/kg) in 24h-fasted rats. Subsequently, the double-labeled immunohistochemical study revealed that nesfatin-1/NucB2-immunoreactive (ir) neurons expressed Fos-ir in various nuclei of the hypothalamic and brainstem areas, including the supraoptic nucleus and ventral tegmental areas, 90 min after the intraperitoneal administration of nicotine. Finally, pretreatment with intracerebroventricular administration of antisense RNA against nesfatin-1/NucB2 significantly attenuated the suppression of food intake induced by intraperitoneal nicotine administration. The results indicated that the acute effects of peripherally administered nicotine on the suppression of food intake may be partially involved in nesfatin-1/NucB2-containing neurons in the CNS in male adult rats.

急性/慢性暴露于尼古丁可调节实验动物和人类的摄食行为。然而，尼古丁如何调节食物摄入仍不清楚。本研究研究了尼古丁外周给药对成年雄性大鼠食物摄入的急性影响，重点研究了中枢神经系统（CNS）中厌食肽nesfatin-1/ nucleobinin -2 （NucB2）的可能参与。最初，禁食24小时的大鼠在腹腔注射尼古丁（0.5 mg/kg） 0.5、1和1.5 h后，累积的食物摄取量显著减少，但水的摄取量没有显著减少。随后，双标记免疫组织化学研究发现，在尼古丁腹腔注射90 min后，nesfatin-1/ nucb2免疫反应性（ir）神经元在下丘脑和脑干区域的各个核（包括视上核和腹侧被盖区）表达Fos-ir。最后，脑室内给予针对nesfatin-1/NucB2的反义RNA预处理可显著减弱尼古丁腹腔给药引起的进食抑制。结果提示，外周给药尼古丁对成年雄性大鼠的急性食物摄取量抑制作用可能部分涉及到CNS内含有nesfatin-1/ nucb2的神经元。

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引用次数: 0

JHP-7 (QLLEELKR), a heptapeptide derived from Jinhua ham, may ameliorate intrauterine adhesion (IUA) via inhibiting inflammatory response and apoptosis 从金华火腿中提取的七肽JHP-7 （QLLEELKR）可能通过抑制炎症反应和细胞凋亡来改善宫内粘连（IUA）

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-06-01 Epub Date: 2025-04-09 DOI: 10.1016/j.peptides.2025.171406

Yixiang Wang , Yang Wu , Luming Wu , Xue Fan , Tong Chen , Jijun Tao , Shiyan Tu , Yiqing Wang , Xuehong Zhang

Objective

This study aimed to investigate the effect of JHP-7(QLLEELKR) derived from Jinhua ham on IUA, in order to provide new methods and new ideas for the clinical treatment of IUA.

Methods

The JHP-7 was synthesized by solid-phase peptide synthesis (SPPS). An in vitro model (human endometrial epithelial cells (HEECs) induced by 10 ng/mL TGF-β1) and an in vivo model (C57BL/6 mice induced by mechanical curettage and LPS stimulation) were used in the study. In vitro, HEEC were co-cultured with TGF-β1with or without JHP-7 (1 μM and 10 μM) for 48 h, followed by RT-qPCR and Western blotting analysis. Meanwhile, the fluorescent ROS probe was employed to assess oxidative stress levels. In vivo, IUA mice were preventively treated with JHP-7 (150 μg/kg/d and 300 μg/kg/d) for 14 days, after which uterine tissues were collected for histopathological evaluation using H&E and Masson staining, as well as molecular analysis via RT-qPCR and Western blotting to measure mRNA and protein expression levels.

Results

In vitro, JHP-7 significantly inhibited the expression of proinflammatory and fibrosis markers, reduced the ROS, and protected endometrial function. Further studies showed that JHP-7 inhibited the apoptosis of TGF-β1-induced HEECs, and reduced the expression of TLR4, p-NF-κB, and p-MAPK. In vivo, JHP-7 significantly improved the uterine morphology and reduced collagen deposition in IUA mice. Reduced expression of TLR4, MyD88, p-NF-κB, p-MAPK and up-regulating expression of Bcl2 were also detected after JHP-7 treatment.

Conclusion

JHP-7 could ameliorate IUA via inhibiting inflammation and apoptosis, which may be related to the TLR4/MyD88/MAPK/NF-κB signaling pathway.

方法采用固相肽合成法（SPPS）合成JHP-7。研究采用了体外模型（10 ng/mL TGF-β1 诱导的人子宫内膜上皮细胞（HEECs））和体内模型（机械刮宫和 LPS 刺激诱导的 C57BL/6 小鼠）。在体外，将 HEEC 与含有或不含 JHP-7（1 μM 和 10 μM）的 TGF-β1 共同培养 48 小时，然后进行 RT-qPCR 和 Western 印迹分析。同时，采用荧光 ROS 探针评估氧化应激水平。在体内，用JHP-7（150 μg/kg/d和300 μg/kg/d）预防性治疗IUA小鼠14天，然后收集子宫组织，用H&E和Masson染色进行组织病理学评估，并通过RT-qPCR和Western印迹进行分子分析，以测量mRNA和蛋白质的表达水平。结果在体外，JHP-7 能显著抑制促炎和纤维化标志物的表达，减少 ROS，保护子宫内膜功能。进一步的研究表明，JHP-7 可抑制 TGF-β1 诱导的 HEECs 的凋亡，并降低 TLR4、p-NF-κB 和 p-MAPK 的表达。在体内，JHP-7 能明显改善 IUA 小鼠的子宫形态并减少胶原沉积。结论 JHP-7可通过抑制炎症和细胞凋亡改善IUA，这可能与TLR4/MyD88/MAPK/NF-κB信号通路有关。

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引用次数: 0

Oxyntomodulin - past, present and future oxyntomodulin -过去，现在和未来。

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-06-01 Epub Date: 2025-04-03 DOI: 10.1016/j.peptides.2025.171393

Jens Juul Holst , Mette M. Rosenkilde

Almost since its discovery, glucagon was suspected to be formed in the gastrointestinal tract, and the L-cells were shown to contain glucagon-like immunoreactivity. This was due to the presence of two peptides that both contained the full glucagon sequence:glicentin of 69 amino acids and oxyntomodulin of 37 amino acids. While glicentin is a part of the glucagon precursor, proglucagon, and probably is inactive, oxyntomodulin, a fragment of glicentin, interacts although weakly with the glucagon as well as the GLP-1 receptor. However, in agreement with these activities, oxyntomodulin inhibited appetite and food intake in humans and inspired development of long acting, potent glucagon-GLP-1 co-agonists. Several such co-agonists are currently in clinical development and show promise because they combine GLP-1 like activities with those of glucagon agonism: additive weight loss and a stimulation of hepatic lipid metabolism with unique effectiveness on hepatic steatosis. They may therefore be effective in the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD).

几乎自胰高血糖素被发现以来，人们就怀疑它是在胃肠道中形成的，并且l细胞显示出含有胰高血糖素样免疫反应性。这是由于两种多肽的存在，它们都含有胰高血糖素的完整序列：由69个氨基酸组成的甘肽肽和由37个氨基酸组成的氧合调节肽。虽然glicentin是胰高血糖素前体，胰高血糖素原的一部分，并且可能是无活性的，但glicentin的一个片段，氧合调节素，虽然与胰高血糖素和GLP-1受体相互作用微弱。然而，与这些活性一致的是，氧调素抑制人类的食欲和食物摄入，并激发了长效、有效的胰高血糖素- glp -1协同激动剂的发展。一些这样的协同激动剂目前正处于临床开发阶段，并显示出前景，因为它们将GLP-1样活性与胰高血糖素激动剂的活性结合起来：增加体重减轻和刺激肝脏脂质代谢，对肝脏脂肪变性具有独特的效果。因此，它们可能对代谢功能障碍相关的脂肪变性肝病（MASLD）的治疗有效。

引用次数: 0

Peptide therapeutics: current status and future opportunity with focus on nose-to-brain delivery☆ 肽疗法：目前的现状和未来的机会，重点是鼻子到大脑的输送☆

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-06-01 Epub Date: 2025-04-11 DOI: 10.1016/j.peptides.2025.171404

Eva-Maria Jülke, Annette G. Beck-Sickinger

Peptide drugs are a highly diverse group of therapeutic agents. Over the last decade, more than 40 peptides have been approved for clinical use. They target different structures, ranging from G protein-coupled receptors (GPCRs) to pathogens and are used to treat a variety of indications, including metabolic disorders, genetic diseases, acute illnesses and more. Structurally, peptide therapeutics are a heterogeneous class. This diversity allows them to bridge the gap between small molecules and biologics. However, limited metabolic stability and bioavailability must be addressed. Strategies to improve the half-life include backbone and sequence modification, cyclization and the addition of stabilizing moieties. Great strides have been made in recent years towards achieving sufficient drug uptake for oral application have been achieved within recent years. However, these methods require specialized peptide design or involve permeabilization of the gastrointestinal tract. Consequently, other routes of administration are being explored. One promising approach is the nasal application of peptides. This method can be used for systemic uptake, but also allows for direct nose-to-brain delivery of compounds. While successful nose-to-brain delivery is already used in the clinic, the underlining mechanisms are poorly understood. Strategies for rational optimization are needed to make this method more applicable to a wider range of compounds. Overall, approved peptide therapeutics cover a wide range of applications and have demonstrated a growing and novel potential in recent drug discovery.

多肽药物是一组高度多样化的治疗药物。在过去的十年中，超过40种多肽被批准用于临床。它们针对不同的结构，从G蛋白偶联受体（gpcr）到病原体，并用于治疗各种适应症，包括代谢紊乱、遗传疾病、急性疾病等。从结构上讲，肽疗法是一个异质性的类别。这种多样性使它们能够弥合小分子和生物制剂之间的差距。然而，有限的代谢稳定性和生物利用度必须解决。改善半衰期的策略包括主链和序列修饰、环化和添加稳定基团。近年来，在实现口服给药的充分吸收方面取得了巨大进展。然而，这些方法需要专门的肽设计或涉及胃肠道渗透。因此，正在探索其他行政途径。一种有前途的方法是多肽的鼻腔应用。这种方法可以用于全身吸收，但也允许直接通过鼻子到大脑给药。虽然临床上已经成功地使用了鼻到脑输送，但其主要机制尚不清楚。为了使该方法适用于更广泛的化合物，需要合理的优化策略。总的来说，已批准的多肽疗法涵盖了广泛的应用，并在最近的药物发现中显示出不断增长的新潜力。

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引用次数: 0

Irisin prevents visceral hypersensitivity and colonic hyperpermeability in a rat model of irritable bowel syndrome 鸢尾素预防肠易激综合征大鼠模型的内脏过敏和结肠高渗透性

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-06-01 Epub Date: 2025-03-26 DOI: 10.1016/j.peptides.2025.171394

Tsukasa Nozu , Saori Miyagishi , Masatomo Ishioh , Kaoru Takakusaki , Toshikatsu Okumura

Visceral hypersensitivity and impaired gut barrier function, accompanied by minor inflammation, are crucial components of the pathophysiology of irritable bowel syndrome (IBS). Research has demonstrated that corticotropin-releasing factor (CRF) and toll-like receptor 4 (TLR4) signaling mutually activate to produce proinflammatory cytokines, which modulate these gastrointestinal changes. Irisin, a myokine, has been shown to inhibit TLR4-proinflammatory cytokine signaling, thereby improving inflammation driven by obesity and metabolic syndrome. Based on this, we hypothesized that irisin could improve visceral hypersensitivity and impaired gut barrier function induced by lipopolysaccharide (LPS) or CRF (IBS rat models), and tested this hypothesis. The visceral pain threshold, triggered by colonic balloon distention, was assessed by electrophysiologically monitoring abdominal muscle contractions in male Sprague-Dawley rats. Colonic permeability was evaluated by measuring the amount of Evans blue dye absorbed within the colonic tissue. Intraperitoneal irisin prevented LPS-induced visceral hypersensitivity and colonic hyperpermeability in a dose-dependent manner. Irisin also prevented CRF-induced gastrointestinal alterations. The beneficial effects of irisin in the LPS model were reversed by compound C, an AMP-activated protein kinase (AMPK) inhibitor; N^G-nitro-L-arginine methyl ester, a nitric oxide (NO) synthesis inhibitor; sulpiride or domperidone, a dopamine D₂ receptor antagonist; atropine and intracisternal injection of SB-334867, a selective orexin 1 receptor antagonist. Overall, these findings suggest that irisin improves visceral sensation and colonic barrier function through AMPK, NO and dopamine D₂, cholinergic and brain orexin signaling in IBS model. Thus, irisin may be a promising therapeutic agent for treating IBS.

内脏过敏和肠道屏障功能受损，伴随着轻微的炎症，是肠易激综合征（IBS）病理生理学的重要组成部分。研究表明，促肾上腺皮质激素释放因子（CRF）和toll样受体4 （TLR4）信号相互激活，产生促炎细胞因子，调节这些胃肠道变化。鸢尾素是一种肌因子，已被证明可以抑制tlr4促炎细胞因子信号，从而改善肥胖和代谢综合征引起的炎症。基于此，我们假设鸢尾素可以改善脂多糖（LPS）或CRF （IBS大鼠模型）引起的内脏超敏反应和肠道屏障功能受损，并对这一假设进行了验证。通过电生理学监测雄性Sprague-Dawley大鼠腹部肌肉收缩，评估由结肠球囊膨胀引发的内脏痛阈。通过测定结肠组织内埃文斯蓝染料的吸收量来评估结肠通透性。鸢尾素以剂量依赖性的方式阻止lps诱导的内脏超敏反应和结肠高渗透性。鸢尾素还能防止crf诱导的胃肠道改变。鸢尾素在LPS模型中的有益作用被化合物C逆转，化合物C是一种amp激活的蛋白激酶（AMPK）抑制剂；NO合成抑制剂ng -硝基- l -精氨酸甲酯；舒必利或多潘立酮，多巴胺D2受体拮抗剂；阿托品和腹腔注射SB-334867，一种选择性食欲素1受体拮抗剂。综上所述，这些发现表明鸢尾素在IBS模型中通过AMPK、NO和多巴胺D2、胆碱能和脑促食欲素信号通路改善内脏感觉和结肠屏障功能。因此，鸢尾素可能是一种很有前途的治疗肠易激综合征的药物。

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引用次数: 0

Spexin expression in the human bile duct and perihilar cholangiocarcinoma Spexin在人胆管和肝门周围胆管癌中的表达。

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-06-01 Epub Date: 2025-04-05 DOI: 10.1016/j.peptides.2025.171405

Sara Huber , Theresia Fitzner , René G. Feichtinger , Theo Kraus , Stefanie Gaisbauer , Sarah Hochmann , Karl Sotlar , Barbara Kofler , Martin Varga

The bile duct transports bile fluid from the liver to the gallbladder and small intestine. It contains bioactive peptides, including galanin (GAL) and its receptors (GAL_1–3-R). Spexin (SPX), a member of the GAL peptide family, activates GAL₂-R and GAL₃-R. Its expression in perihilar bile ducts or in perihilar cholangiocarcinoma (pCCA), the most common biliary cancer, is largely unknown. This study investigated SPX expression in healthy, cholestatic, and malignant bile duct tissues. Immunohistochemistry was used to evaluate SPX in healthy (n = 4), peritumoral (PIT) (n = 23) and pCCA (n = 34) tissues. Score values of SPX expression were calculated and statistically analyzed. In healthy and PIT tissues with or without cholestasis, SPX expression was predominantly observed in cholangiocytes and nerve fibers. In pCCA, tumor cells also expressed SPX. SPX levels were similar across healthy, peritumoral, and cholangiocytes/tumor cells. In a small pCCA patient cohort (n = 19), SPX expression did not correlate with tumor grade or patient survival (p = 0.0838). The substantial expression of SPX in cholangiocytes and nerve fibers in the bile duct indicates that SPX contributes via galaninergic signaling to gall bladder function. The presence of SPX in submucosal nerve fibers suggests a neuromodulatory role, possibly involving bile duct motility. SPX expression did not correlate with survival in pCCA, whereas previous findings on GAL suggest a prognostic value. This highlights the need for joint studies of SPX and GAL in larger cohorts.

胆管将胆汁液从肝脏输送到胆囊和小肠。它含有生物活性肽，包括丙氨酸（GAL）及其受体（GAL1-3-R）。SPX是GAL肽家族的一员，可激活GAL2-R和GAL3-R。它在肝门周围胆管或肝门周围胆管癌（最常见的胆道癌）中的表达在很大程度上是未知的。本研究探讨了SPX在健康、胆汁淤积和恶性胆管组织中的表达。采用免疫组织化学方法评估健康（n = 4）、瘤周（n = 23）和pCCA （n = 34）组织中的SPX。计算SPX表达的评分值并进行统计学分析。在有或没有胆汁淤积的健康和PIT组织中，SPX主要在胆管细胞和神经纤维中表达。在pCCA中，肿瘤细胞也表达SPX。SPX水平在健康细胞、肿瘤周围细胞和胆管细胞/肿瘤细胞中相似。在一个小的pCCA患者队列中（n = 19）， SPX表达与肿瘤分级或患者生存无关（p = 0.0838）。SPX在胆管细胞和神经纤维中的大量表达表明SPX通过半乳糖能信号传导参与胆囊功能。粘膜下神经纤维中SPX的存在提示其具有神经调节作用，可能与胆管运动有关。SPX的表达与pCCA患者的生存无关，而先前关于GAL的研究结果表明其具有预后价值。这突出了在更大的队列中对SPX和GAL进行联合研究的必要性。

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引用次数: 0

Evaluation of plasma arginine vasopressin during hypertonic saline loading: A comparison of radioimmunoassay and liquid chromatography–tandem mass spectrometry 高渗生理盐水负荷期间血浆精氨酸加压素的评价：放射免疫法和液相色谱-串联质谱法的比较。

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-05-01 Epub Date: 2025-03-18 DOI: 10.1016/j.peptides.2025.171392

Narantsatsral Daramjav , Junko Takagi , Fumio Nomura , Kazuo Otake , Akiyoshi Takami

Plasma arginine vasopressin (AVP) measurement is critical for diagnosing central diabetes insipidus (CDI). Conventional radioimmunoassay (RIA) is widely used for AVP quantification, but its limited sensitivity, specificity, and dynamic range have prompted exploration of alternative methods. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has emerged as a promising technique for AVP measurement, offering potential advantages over RIA. This study aimed to evaluate LC-MS/MS performance for AVP quantification during hypertonic saline loading and compare its diagnostic accuracy with that of RIA in differentiating CDI patients from controls. A total of 335 plasma samples were collected from 77 individuals—23 diagnosed with CDI and 54 controls—during hypertonic saline loading. AVP concentrations were measured using both LC-MS/MS and RIA. Statistical analyses included Wilcoxon tests to compare AVP levels, correlation analysis between LC-MS/MS and RIA, and receiver operating characteristic (ROC) curve analysis to assess diagnostic performance. LC-MS/MS demonstrated a lower detection limit (0.3 pg/mL) and a broader quantification range than RIA. Regression analysis showed a strong correlation between LC-MS/MS and RIA in the control group, but no correlation in the CDI group. ROC analysis indicated that LC-MS/MS provided diagnostic accuracy comparable to RIA for distinguishing CDI patients from controls. Bland-Altman analysis showed the agreement between two methods at the low range of AVP. LC-MS/MS offers equivalent specificity and sensitivity to RIA for AVP measurement, while providing added benefits in time efficiency, cost-effectiveness, and differential diagnosis of CDI. These findings suggest that LC-MS/MS is a viable alternative to RIA for clinical AVP quantification.

血浆精氨酸加压素（AVP）测定是诊断中枢性尿崩症（CDI）的关键。传统放射免疫分析法（RIA）被广泛用于AVP定量，但其有限的灵敏度、特异性和动态范围促使人们探索替代方法。液相色谱-串联质谱（LC-MS/MS）已成为一种很有前途的AVP测量技术，与RIA相比具有潜在的优势。本研究旨在评估LC-MS/MS在高渗生理盐水负荷时AVP定量的性能，并比较其与RIA在区分CDI患者和对照组中的诊断准确性。在高渗生理盐水负荷期间，共收集了77名患者的335份血浆样本，其中23名诊断为CDI， 54名对照组。采用LC-MS/MS和RIA检测AVP浓度。统计分析包括比较AVP水平的Wilcoxon检验，LC-MS/MS与RIA的相关性分析，以及评估诊断效果的受试者工作特征（ROC）曲线分析。LC-MS/MS的检出限较低（0.3pg/mL），定量范围较RIA宽。回归分析显示，对照组LC-MS/MS与RIA有较强的相关性，CDI组无相关性。ROC分析表明LC-MS/MS在区分CDI患者和对照组方面具有与RIA相当的诊断准确性。Bland-Altman分析显示两种方法在AVP低范围内一致。LC-MS/MS在AVP测量方面与RIA具有相同的特异性和敏感性，同时在时间效率、成本效益和CDI鉴别诊断方面提供了额外的好处。这些结果表明LC-MS/MS是一种可行的替代RIA的临床AVP定量方法。

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引用次数: 0

A novel regulator of NLRP3 inflammasome: Peptides NLRP3炎性小体的一种新调节剂：多肽

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptides

Pub Date : 2025-05-01 Epub Date: 2025-03-08 DOI: 10.1016/j.peptides.2025.171381

Zhuo Zuo, Yaxing Wang, Yanwei Fang, Mengya Zhao, Zhe Wang, Zhouqi Yang, Bin Jia, Yulong Sun

The NLRP3 inflammasome plays a crucial role as a critical regulator of the immune response and has been implicated in the pathogenesis of numerous diseases. Peptides, known for their remarkable potency, selectivity, and low toxicity, have been extensively employed in disease treatment. Recent research has unveiled the potential of peptides in modulating the activity of the NLRP3 inflammasome. This review begins by examining the structure of the NLRP3 inflammasome, encompassing NLRP3, ASC, and Caspase-1, along with the three activation pathways: canonical, non-canonical, and alternative. Subsequently, we provide a comprehensive summary of peptide modulators targeting the NLRP3 inflammasome and elucidate their underlying mechanisms. The efficacy of these modulators has been validated through in vitro and in vivo experiments on NLRP3 inflammasome regulation. Furthermore, we conduct sequence alignment of the identified peptides and investigate their binding sites on the NLRP3 protein. This work is a foundational exploration for advancing peptides as potential therapeutic agents for NLRP3-related diseases.

NLRP3炎症小体作为免疫反应的关键调节因子起着至关重要的作用，并与许多疾病的发病机制有关。多肽以其显著的效力、选择性和低毒性而闻名，已广泛应用于疾病治疗。最近的研究揭示了多肽在调节NLRP3炎性体活性方面的潜力。本综述首先检查NLRP3炎性小体的结构，包括NLRP3、ASC和Caspase-1，以及三种激活途径：典型、非典型和替代。随后，我们全面总结了针对NLRP3炎性体的肽调节剂，并阐明了它们的潜在机制。这些调节剂对NLRP3炎性小体调控的有效性已通过体内和体外实验得到验证。此外，我们对鉴定的肽进行了序列比对，并研究了它们在NLRP3蛋白上的结合位点。这项工作是推进肽作为nlrp3相关疾病潜在治疗剂的基础探索。

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