首页 > 最新文献

Life sciences最新文献

英文 中文
A dissociated glucocorticoid receptor modulator mitigates glucolipotoxicity in the endocrine pancreas and peripheral tissues: Preclinical data from a mouse model of diet-induced type 2 diabetes 解离糖皮质激素受体调节剂减轻内分泌胰腺和外周组织的糖脂毒性：来自饮食诱导的2型糖尿病小鼠模型的临床前数据。
IF 5.2 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Life sciences
Pub Date : 2025-02-01 DOI: 10.1016/j.lfs.2024.123363
Miranda Sol Orellano , Andrea Scelza-Figueredo , Lucía Lameroli Mauriz , Carolina Sétula , Milagros Argañarás , Catalina Atorrasagasti , Marcelo Javier Perone , Luz Andreone

Aims

Type 2 diabetes (T2D) is a prevalent metabolic disease linked to obesity and metabolic syndrome (MS). The glucolipotoxic environment (GLT) impacts tissues causing low-grade inflammation, insulin resistance and the gradual loss of pancreatic β-cell function, leading to hyperglycemia. We have previously shown that Compound A (CpdA), a plant-derived dissociative glucocorticoid receptor-modulator with inflammation-suppressive activity, displays protective effects on β-cells in type 1 diabetes murine models. This study aimed to evaluate whether the administration of CpdA can attenuate GLT effects and improve pathophysiological parameters in a murine model of T2D/MS.

Main methods

Eight-week-old male C57BL/6NCrl mice were fed either a standard chow diet or a high-fat/high-sucrose diet (HFHS) for 15 weeks. From week 5 of feeding, each group received i.p. injections of CpdA (2.5 μg/g) or vehicle three times a week. We also examined CpdA in vitro effect against GLT using the insulinoma cell line INS-1E and naïve isolated mouse islets.

Key findings

CpdA administration in HFHS fed mice improved glucose homeostasis and insulin sensitivity with no apparent side effects. CpdA treatment also preserved pancreatic islet architecture and insulin expression, while reducing hepatic steatosis and visceral adipose tissue inflammation induced by HFHS diet. In vitro assays in INS-1E cells and naïve isolated mouse islets demonstrated that CpdA counteracted GLT-induced inhibition of glucose-stimulated insulin secretion and supported the expression of key β-cell identity genes under GLT conditions.

Significance

These findings highlight the potential protective effect of CpdA in preserving β-cell functionality and peripheral tissue physiology in the context of T2D/MS.
目的：2型糖尿病（T2D）是一种与肥胖和代谢综合征（MS）相关的普遍代谢性疾病。糖脂毒性环境（GLT）影响组织，引起低度炎症、胰岛素抵抗和胰腺β细胞功能的逐渐丧失，导致高血糖。我们之前已经证明化合物A （CpdA）是一种植物源性解离性糖皮质激素受体调节剂，具有炎症抑制活性，对1型糖尿病小鼠模型中的β细胞具有保护作用。本研究旨在评价CpdA是否能减弱GLT作用，改善小鼠T2D/MS模型的病理生理参数。主要方法：8周龄雄性C57BL/6NCrl小鼠分别饲喂标准饲料和高脂高糖饲料（HFHS） 15周。从饲养第5周开始，各组大鼠ig注射CpdA （2.5 μg/g）或载药，每周3次。我们还使用胰岛素瘤细胞系INS-1E和naïve分离的小鼠胰岛检测了CpdA对GLT的体外作用。主要发现：CpdA能改善HFHS喂养小鼠的葡萄糖稳态和胰岛素敏感性，无明显副作用。CpdA治疗还保留了胰岛结构和胰岛素表达，同时减少HFHS饮食引起的肝脏脂肪变性和内脏脂肪组织炎症。在INS-1E细胞和naïve离体小鼠胰岛的体外实验表明，CpdA可以抵消GLT诱导的葡萄糖刺激胰岛素分泌的抑制，并支持GLT条件下关键β细胞识别基因的表达。意义：这些发现强调了CpdA在T2D/MS背景下在保持β细胞功能和外周组织生理方面的潜在保护作用。
{"title":"A dissociated glucocorticoid receptor modulator mitigates glucolipotoxicity in the endocrine pancreas and peripheral tissues: Preclinical data from a mouse model of diet-induced type 2 diabetes","authors":"Miranda Sol Orellano ,&nbsp;Andrea Scelza-Figueredo ,&nbsp;Lucía Lameroli Mauriz ,&nbsp;Carolina Sétula ,&nbsp;Milagros Argañarás ,&nbsp;Catalina Atorrasagasti ,&nbsp;Marcelo Javier Perone ,&nbsp;Luz Andreone","doi":"10.1016/j.lfs.2024.123363","DOIUrl":"10.1016/j.lfs.2024.123363","url":null,"abstract":"<div><h3>Aims</h3><div>Type 2 diabetes (T2D) is a prevalent metabolic disease linked to obesity and metabolic syndrome (MS). The glucolipotoxic environment (GLT) impacts tissues causing low-grade inflammation, insulin resistance and the gradual loss of pancreatic β-cell function, leading to hyperglycemia. We have previously shown that Compound A (CpdA), a plant-derived dissociative glucocorticoid receptor-modulator with inflammation-suppressive activity, displays protective effects on β-cells in type 1 diabetes murine models. This study aimed to evaluate whether the administration of CpdA can attenuate GLT effects and improve pathophysiological parameters in a murine model of T2D/MS.</div></div><div><h3>Main methods</h3><div>Eight-week-old male C57BL/6NCrl mice were fed either a standard chow diet or a high-fat/high-sucrose diet (HFHS) for 15 weeks. From week 5 of feeding, each group received i.p. injections of CpdA (2.5 μg/g) or vehicle three times a week. We also examined CpdA in vitro effect against GLT using the insulinoma cell line INS-1E and naïve isolated mouse islets.</div></div><div><h3>Key findings</h3><div>CpdA administration in HFHS fed mice improved glucose homeostasis and insulin sensitivity with no apparent side effects. CpdA treatment also preserved pancreatic islet architecture and insulin expression, while reducing hepatic steatosis and visceral adipose tissue inflammation induced by HFHS diet. In vitro assays in INS-1E cells and naïve isolated mouse islets demonstrated that CpdA counteracted GLT-induced inhibition of glucose-stimulated insulin secretion and supported the expression of key β-cell identity genes under GLT conditions.</div></div><div><h3>Significance</h3><div>These findings highlight the potential protective effect of CpdA in preserving β-cell functionality and peripheral tissue physiology in the context of T2D/MS.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123363"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
GLP-1 and IL-6 regulates obesity in the gut and brain GLP-1和IL-6调节肠道和大脑的肥胖。
IF 5.2 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Life sciences
Pub Date : 2025-02-01 DOI: 10.1016/j.lfs.2024.123339
Kun Yang , Yu-ting Wu , Yan He , Jin-xiu Dai , Yu-lu Luo , Jing-hui Xie , Wei-jun Ding
Obesity is a chronic metabolic disease characterized by excessive nutrient intake leading to increased subcutaneous or visceral fat, resulting in pathological and physiological changes. The incidence rate of obesity, an important form of metabolic syndrome, is increasing worldwide. Excess appetite is a key pathogenesis of obesity, and the inflammatory response induced by obesity has received increasing attention. This review focuses on the role of appetite-regulating factor (Glucogan-like peptide 1) and inflammatory factor (Interleukin-6) in the gut and brain in individuals with obesity and draws insights from the current literature.
肥胖是一种慢性代谢性疾病，其特征是营养摄入过多导致皮下或内脏脂肪增加，从而引起病理和生理变化。肥胖症是代谢综合征的一种重要形式，其发病率在全球范围内呈上升趋势。食欲过剩是肥胖的一个重要发病机制，肥胖引起的炎症反应越来越受到人们的关注。本文综述了食欲调节因子（胰高血糖素样肽1）和炎症因子（白细胞介素-6）在肥胖患者肠道和大脑中的作用，并从目前的文献中得出了一些见解。
{"title":"GLP-1 and IL-6 regulates obesity in the gut and brain","authors":"Kun Yang ,&nbsp;Yu-ting Wu ,&nbsp;Yan He ,&nbsp;Jin-xiu Dai ,&nbsp;Yu-lu Luo ,&nbsp;Jing-hui Xie ,&nbsp;Wei-jun Ding","doi":"10.1016/j.lfs.2024.123339","DOIUrl":"10.1016/j.lfs.2024.123339","url":null,"abstract":"<div><div>Obesity is a chronic metabolic disease characterized by excessive nutrient intake leading to increased subcutaneous or visceral fat, resulting in pathological and physiological changes. The incidence rate of obesity, an important form of metabolic syndrome, is increasing worldwide. Excess appetite is a key pathogenesis of obesity, and the inflammatory response induced by obesity has received increasing attention. This review focuses on the role of appetite-regulating factor (Glucogan-like peptide 1) and inflammatory factor (Interleukin-6) in the gut and brain in individuals with obesity and draws insights from the current literature.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123339"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Alternative splicing: Therapeutic target for vasculopathy in diabetic complications 选择性剪接：糖尿病并发症血管病变的治疗靶点。
IF 5.2 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Life sciences
Pub Date : 2025-02-01 DOI: 10.1016/j.lfs.2024.123331
Xiaoyue Li , Dong Zhu , Bingkun Zhao , Qiang Li , Peisheng Jin
It is becoming increasingly evident that diabetic vascular complications seriously threaten human health. The most prevalent microvascular complications include kidney disease, retinal disease, cardiovascular diseases and amputation. Conventional treatments can only relieve the progression of the diseases, and is no longer appropriate for the long-term management of diabetic patients. Exploring a novel therapeutic regimens and improvements in management of Diabetic Complications is required. Alternative splicing has been found to play a crucial role in the occurrence and treatment of diseases, including the destruction and generation of blood vessels in diabetes. Alternative splicing is an important factor in the high complexity of multicellular eukaryotic transcriptome, and angiogenesis, which is an important process controlled by alternative splicing mechanism. This review mainly introduces the current understanding of alternative splicing and the role that alternative splicing plays in the diabetic complications, with a special focus on vascular system. In this study, we summarized alternative splicing in relation to diabetes complications and the pathogenesis of diabetic vasculopathy. It discussed potential treatment strategies for correcting aberrant splicing and suggested novel approaches for addressing diabetes complications.
糖尿病血管并发症对人体健康的严重威胁越来越明显。最常见的微血管并发症包括肾脏疾病、视网膜疾病、心血管疾病和截肢。常规治疗只能缓解病情的进展，不再适合糖尿病患者的长期管理。探索新的治疗方案和改善糖尿病并发症的管理是必要的。选择性剪接已被发现在疾病的发生和治疗中起着至关重要的作用，包括糖尿病血管的破坏和生成。选择性剪接是造成多细胞真核生物转录组高度复杂性的重要因素，而血管生成是由选择性剪接机制控制的重要过程。本文主要介绍了目前对选择性剪接的认识以及选择性剪接在糖尿病并发症中的作用，重点介绍了血管系统。在这项研究中，我们总结了选择性剪接与糖尿病并发症和糖尿病血管病变的发病机制。它讨论了纠正异常剪接的潜在治疗策略，并提出了解决糖尿病并发症的新方法。
{"title":"Alternative splicing: Therapeutic target for vasculopathy in diabetic complications","authors":"Xiaoyue Li ,&nbsp;Dong Zhu ,&nbsp;Bingkun Zhao ,&nbsp;Qiang Li ,&nbsp;Peisheng Jin","doi":"10.1016/j.lfs.2024.123331","DOIUrl":"10.1016/j.lfs.2024.123331","url":null,"abstract":"<div><div>It is becoming increasingly evident that diabetic vascular complications seriously threaten human health. The most prevalent microvascular complications include kidney disease, retinal disease, cardiovascular diseases and amputation. Conventional treatments can only relieve the progression of the diseases, and is no longer appropriate for the long-term management of diabetic patients. Exploring a novel therapeutic regimens and improvements in management of Diabetic Complications is required. Alternative splicing has been found to play a crucial role in the occurrence and treatment of diseases, including the destruction and generation of blood vessels in diabetes. Alternative splicing is an important factor in the high complexity of multicellular eukaryotic transcriptome, and angiogenesis, which is an important process controlled by alternative splicing mechanism. This review mainly introduces the current understanding of alternative splicing and the role that alternative splicing plays in the diabetic complications, with a special focus on vascular system. In this study, we summarized alternative splicing in relation to diabetes complications and the pathogenesis of diabetic vasculopathy. It discussed potential treatment strategies for correcting aberrant splicing and suggested novel approaches for addressing diabetes complications.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123331"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ClC-5 knockout mitigates angiotensin II-induced hypertension and endothelial dysfunction 敲除ClC-5可减轻血管紧张素ii诱导的高血压和内皮功能障碍。
IF 5.2 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Life sciences
Pub Date : 2025-02-01 DOI: 10.1016/j.lfs.2024.123342
Lu Sun , Min Gao , Gui-Yong Yang , Feng-Ting Lu , Zhu-Jun Liang , Kai-Min Guo , Xiao-Fei Lv , Yan-Hua Du , Si-Jia Liang , Yu-Bo Tang , Jia-Guo Zhou , Yong-Yuan Guan , Ming-Ming Ma

Aims

Impairment of nitric oxide (NO) production is a major cause of endothelial dysfunction and hypertension. ClC-5 Cl− channel is abundantly expressed in the vascular endothelium. However, it remains unclear how it regulates endothelial function.

Materials and methods

In this study, we used mice with a knockout of the Clcn5 gene encoding ClC-5 protein globally or specifically in vascular endothelium.

Key findings

ClC-5 knockout globally or specifically in vascular endothelium mitigates the elevation of mean blood pressure and impairment of endothelial dysfunction induced by Angiotensin II. This effect is mediated by the reversal of the impairment of NO production after the stimulation of the Akt/endothelial nitric oxide synthase (eNOS) signal pathway. Application of a low Cl− extracellular solution onto endothelial cells stimulates a ClC-5-dependent current and lowered intracellular Cl− concentration, which activates with-no-lysine (K)-1 (WNK1), a Cl−-sensitive kinase. Silencing ClC-5 or WNK1 expression rescues the impairment of endothelial NO production induced by a low Cl− solution. In contrast, overexpression of ClC-5 or WNK1 led to the opposite results. WNK1, found to be associated with Rho-specific guanine nucleotide dissociation inhibitor (RhoGDI), increases RhoA activity, and thereby inhibits the endothelial Akt/eNOS signaling pathway.

Significance

ClC-5 knockout mitigates Ang II-induced hypertension and endothelial dysfunction by promoting NO production via regulating WNK1/RhoA/Akt/eNOS signaling pathway. The results may be useful for developing novel treatments of endothelial dysfunction associated-diseases.
目的：一氧化氮（NO）生成障碍是内皮功能障碍和高血压的主要原因。clc - 5cl -通道在血管内皮中大量表达。然而，目前尚不清楚它是如何调节内皮功能的。材料和方法：在本研究中，我们使用了在血管内皮中整体或特异性敲除编码ClC-5蛋白的Clcn5基因的小鼠。主要发现：在血管内皮中整体或特异性敲除ClC-5可减轻血管紧张素II诱导的平均血压升高和内皮功能障碍损害。这种作用是通过刺激Akt/内皮型一氧化氮合酶（eNOS）信号通路后一氧化氮生成损伤的逆转而介导的。在内皮细胞上应用低Cl-细胞外溶液刺激clc -5依赖性电流，降低细胞内Cl-浓度，激活-no-赖氨酸(K)-1 (WNK1)，一种Cl-敏感激酶。沉默ClC-5或WNK1表达可挽救低Cl-溶液诱导的内皮细胞NO生成损伤。相反，过表达ClC-5或WNK1导致相反的结果。发现WNK1与RhoA特异性鸟嘌呤核苷酸解离抑制剂（RhoGDI）相关，增加RhoA活性，从而抑制内皮Akt/eNOS信号通路。意义：敲除ClC-5可通过调节WNK1/RhoA/Akt/eNOS信号通路促进NO生成，从而减轻Ang ii诱导的高血压和内皮功能障碍。该结果可能有助于开发内皮功能障碍相关疾病的新治疗方法。
{"title":"ClC-5 knockout mitigates angiotensin II-induced hypertension and endothelial dysfunction","authors":"Lu Sun ,&nbsp;Min Gao ,&nbsp;Gui-Yong Yang ,&nbsp;Feng-Ting Lu ,&nbsp;Zhu-Jun Liang ,&nbsp;Kai-Min Guo ,&nbsp;Xiao-Fei Lv ,&nbsp;Yan-Hua Du ,&nbsp;Si-Jia Liang ,&nbsp;Yu-Bo Tang ,&nbsp;Jia-Guo Zhou ,&nbsp;Yong-Yuan Guan ,&nbsp;Ming-Ming Ma","doi":"10.1016/j.lfs.2024.123342","DOIUrl":"10.1016/j.lfs.2024.123342","url":null,"abstract":"<div><h3>Aims</h3><div>Impairment of nitric oxide (NO) production is a major cause of endothelial dysfunction and hypertension. ClC-5 Cl<sup>−</sup> channel is abundantly expressed in the vascular endothelium. However, it remains unclear how it regulates endothelial function.</div></div><div><h3>Materials and methods</h3><div>In this study, we used mice with a knockout of the <em>Clcn5</em> gene encoding ClC-5 protein globally or specifically in vascular endothelium.</div></div><div><h3>Key findings</h3><div>ClC-5 knockout globally or specifically in vascular endothelium mitigates the elevation of mean blood pressure and impairment of endothelial dysfunction induced by Angiotensin II. This effect is mediated by the reversal of the impairment of NO production after the stimulation of the Akt/endothelial nitric oxide synthase (eNOS) signal pathway. Application of a low Cl<sup>−</sup> extracellular solution onto endothelial cells stimulates a ClC-5-dependent current and lowered intracellular Cl<sup>−</sup> concentration, which activates with-no-lysine (K)-1 (WNK1), a Cl<sup>−</sup>-sensitive kinase. Silencing ClC-5 or WNK1 expression rescues the impairment of endothelial NO production induced by a low Cl<sup>−</sup> solution. In contrast, overexpression of ClC-5 or WNK1 led to the opposite results. WNK1, found to be associated with Rho-specific guanine nucleotide dissociation inhibitor (RhoGDI), increases RhoA activity, and thereby inhibits the endothelial Akt/eNOS signaling pathway.</div></div><div><h3>Significance</h3><div>ClC-5 knockout mitigates Ang II-induced hypertension and endothelial dysfunction by promoting NO production <em>via</em> regulating WNK1/RhoA/Akt/eNOS signaling pathway. The results may be useful for developing novel treatments of endothelial dysfunction associated-diseases.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123342"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
MCP-enhanced SOD3 activity inhibits gastric cancer and potentiate chemotherapy via modulating EGFR signaling mcp增强的SOD3活性通过调节EGFR信号抑制胃癌并增强化疗。
IF 5.2 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Life sciences
Pub Date : 2025-02-01 DOI: 10.1016/j.lfs.2024.123358
Chao Sun , Qiushuang Ma , Liya Feng, Jianbo Ji, Dandan Du, Pengfei Shang, Xiuli Guo

Aims

This study aims to investigate the role of SOD3 in gastric cancer (GC) progression and its impact on chemotherapy efficacy and toxicity. It further seeks to evaluate the therapeutic potential of MCP in enhancing SOD3 activity to improve treatment outcomes and reduce chemotherapy-induced peripheral neurotoxicity (CIPN).

Materials and methods

We used overexpression plasmids and small interfering RNAs (siRNAs) to modulate the expression of SOD3 and Desmocollin2 (DSC2) in gastric cancer cells. Molecular biology experiments were performed to analyze pathway-related protein expression and molecular interactions. In vitro and in vivo experiments were conducted to evaluate the effects of modified citrus pectin (MCP) and oxaliplatin (OXA), individually and in combination, on gastric cancer progression and CIPN.

Key findings

SOD3 inhibited the proliferation, migration, and invasion of GC cells via SOD3/EGFR/PKP3/DSC2 axis. MCP selectively increased SOD3 levels and enhanced its anti-tumor effects. Combined treatment with MCP and OXA synergistically inhibited GC progression in vitro and in vivo, while MCP alleviated CIPN, enabling OXA dose reduction without compromising efficacy.

Significance

The findings revealed that SOD3 played a critical tumor-suppressive role in gastric cancer by modulating the SOD3/EGFR/PKP3/DSC2 axis. MCP, a natural compound that selectively boosted SOD3 levels, enhanced chemotherapy efficacy while reducing peripheral neurotoxicity, providing a promising strategy to improve gastric cancer treatment and mitigate chemotherapy-related side effects.
目的：本研究旨在探讨SOD3在胃癌（GC）进展中的作用及其对化疗疗效和毒性的影响。该研究进一步寻求评估MCP在提高SOD3活性以改善治疗结果和减少化疗诱导的周围神经毒性（CIPN）方面的治疗潜力。材料和方法：我们利用过表达质粒和小干扰rna （sirna）调节胃癌细胞中SOD3和Desmocollin2 （DSC2）的表达。通过分子生物学实验分析通路相关蛋白表达及分子间相互作用。通过体外和体内实验，评价改性柑橘果胶（MCP）和奥沙利铂（OXA）单独或联合使用对胃癌进展和CIPN的影响。主要发现：SOD3通过SOD3/EGFR/PKP3/DSC2轴抑制GC细胞的增殖、迁移和侵袭。MCP选择性提高SOD3水平，增强抗肿瘤作用。MCP和OXA联合治疗在体外和体内协同抑制GC进展，而MCP减轻CIPN，使OXA剂量减少而不影响疗效。意义：研究结果表明SOD3通过调节SOD3/EGFR/PKP3/DSC2轴在胃癌中发挥重要的抑瘤作用。MCP是一种天然化合物，可选择性地提高SOD3水平，增强化疗疗效，同时降低周围神经毒性，为改善胃癌治疗和减轻化疗相关副作用提供了一种有希望的策略。
{"title":"MCP-enhanced SOD3 activity inhibits gastric cancer and potentiate chemotherapy via modulating EGFR signaling","authors":"Chao Sun ,&nbsp;Qiushuang Ma ,&nbsp;Liya Feng,&nbsp;Jianbo Ji,&nbsp;Dandan Du,&nbsp;Pengfei Shang,&nbsp;Xiuli Guo","doi":"10.1016/j.lfs.2024.123358","DOIUrl":"10.1016/j.lfs.2024.123358","url":null,"abstract":"<div><h3>Aims</h3><div>This study aims to investigate the role of SOD3 in gastric cancer (GC) progression and its impact on chemotherapy efficacy and toxicity. It further seeks to evaluate the therapeutic potential of MCP in enhancing SOD3 activity to improve treatment outcomes and reduce chemotherapy-induced peripheral neurotoxicity (CIPN).</div></div><div><h3>Materials and methods</h3><div>We used overexpression plasmids and small interfering RNAs (siRNAs) to modulate the expression of SOD3 and Desmocollin2 (DSC2) in gastric cancer cells. Molecular biology experiments were performed to analyze pathway-related protein expression and molecular interactions. In vitro and in vivo experiments were conducted to evaluate the effects of modified citrus pectin (MCP) and oxaliplatin (OXA), individually and in combination, on gastric cancer progression and CIPN.</div></div><div><h3>Key findings</h3><div>SOD3 inhibited the proliferation, migration, and invasion of GC cells via SOD3/EGFR/PKP3/DSC2 axis. MCP selectively increased SOD3 levels and enhanced its anti-tumor effects. Combined treatment with MCP and OXA synergistically inhibited GC progression in vitro and in vivo, while MCP alleviated CIPN, enabling OXA dose reduction without compromising efficacy.</div></div><div><h3>Significance</h3><div>The findings revealed that SOD3 played a critical tumor-suppressive role in gastric cancer by modulating the SOD3/EGFR/PKP3/DSC2 axis. MCP, a natural compound that selectively boosted SOD3 levels, enhanced chemotherapy efficacy while reducing peripheral neurotoxicity, providing a promising strategy to improve gastric cancer treatment and mitigate chemotherapy-related side effects.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123358"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cadmium-induced augmentation of fungal translocation promotes systemic infection in mice via gut barrier disruption and immune dysfunction 镉诱导的真菌易位增加通过肠道屏障破坏和免疫功能障碍促进小鼠全身感染。
IF 5.2 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Life sciences
Pub Date : 2025-02-01 DOI: 10.1016/j.lfs.2025.123368
Manika Garg , Muskan Verma , Aiysha Siddiq Khan, Pawan Yadav, Saman Saim Rahman, Asghar Ali, Mohan Kamthan
Cadmium (Cd) disrupts the immune system and intestinal barrier, increasing infection risk and gut dysbiosis. Its impact on intestinal fungi, particularly the opportunistic pathogen Candida albicans, which can cause systemic infections in immunocompromised patients, is not well understood. Our study revealed that C. albicans exhibited high tolerance and maintained its morphogenetic switching in response to Cd. As C. albicans is not naturally found in the mouse gut, we attempted intestinal colonization of C. albicans-SC5314 strain using standard procedures. However, the intestinal fungal load decreased and was undetectable by 15th day. To assess the effects of sub-chronic Cd exposure, both oral and intravenous methods were used. Oral exposure to C. albicans (105 CFU/ml) resulted in a 10-fold increase in intestinal translocation in Cd-exposed mice (0.98 mg/kg) compared to controls. Cd exposure also downregulated intestinal tight junction proteins and increased FITC-dextran permeability, indicating that Cd disrupts the intestinal barrier and facilitates C. albicans translocation. Moreover, Cd-exposed mice showed significant morbidity and higher fungal loads in organs after intravenous non-lethal dose of C. albicans, along with a subdued cytokine response. These findings highlight the significant impact of Cd on fungal pathogenicity and immune response, pointing to the broader health risks of Cd exposure.
镉（Cd）破坏免疫系统和肠道屏障，增加感染风险和肠道生态失调。它对肠道真菌的影响，特别是机会致病菌白色念珠菌，在免疫功能低下的患者中可引起全身性感染，目前尚不清楚。我们的研究表明，白色念珠菌对Cd表现出高耐受性，并能维持其形态发生的改变。由于白色念珠菌在小鼠肠道中并不天然存在，我们尝试使用标准程序将白色念珠菌sc5314菌株定殖于肠道。然而，肠道真菌负荷下降，到第15天已检测不到。为了评估亚慢性Cd暴露的影响，采用了口服和静脉注射两种方法。与对照组相比，口服暴露于白色念珠菌（105 CFU/ml）导致cd暴露小鼠肠道易位增加10倍（0.98 mg/kg）。Cd暴露还会下调肠道紧密连接蛋白，增加fitc -葡聚糖通透性，表明Cd破坏肠道屏障，促进白色念珠菌易位。此外，cd暴露小鼠在静脉注射非致死剂量的白色念珠菌后，显示出显著的发病率和更高的器官真菌负荷，同时细胞因子反应减弱。这些发现强调了Cd对真菌致病性和免疫反应的重大影响，指出了Cd暴露的更广泛的健康风险。
{"title":"Cadmium-induced augmentation of fungal translocation promotes systemic infection in mice via gut barrier disruption and immune dysfunction","authors":"Manika Garg ,&nbsp;Muskan Verma ,&nbsp;Aiysha Siddiq Khan,&nbsp;Pawan Yadav,&nbsp;Saman Saim Rahman,&nbsp;Asghar Ali,&nbsp;Mohan Kamthan","doi":"10.1016/j.lfs.2025.123368","DOIUrl":"10.1016/j.lfs.2025.123368","url":null,"abstract":"<div><div>Cadmium (Cd) disrupts the immune system and intestinal barrier, increasing infection risk and gut dysbiosis. Its impact on intestinal fungi, particularly the opportunistic pathogen <em>Candida albicans</em>, which can cause systemic infections in immunocompromised patients, is not well understood. Our study revealed that <em>C. albicans</em> exhibited high tolerance and maintained its morphogenetic switching in response to Cd. As <em>C. albicans</em> is not naturally found in the mouse gut, we attempted intestinal colonization of <em>C. albicans</em>-SC5314 strain using standard procedures. However, the intestinal fungal load decreased and was undetectable by 15th day. To assess the effects of sub-chronic Cd exposure, both oral and intravenous methods were used. Oral exposure to <em>C. albicans</em> (10<sup>5</sup> CFU/ml) resulted in a 10-fold increase in intestinal translocation in Cd-exposed mice (0.98 mg/kg) compared to controls. Cd exposure also downregulated intestinal tight junction proteins and increased FITC-dextran permeability, indicating that Cd disrupts the intestinal barrier and facilitates <em>C. albicans</em> translocation. Moreover, Cd-exposed mice showed significant morbidity and higher fungal loads in organs after intravenous non-lethal dose of <em>C. albicans</em>, along with a subdued cytokine response. These findings highlight the significant impact of Cd on fungal pathogenicity and immune response, pointing to the broader health risks of Cd exposure.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123368"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
G6PD protects against cerebral ischemia-reperfusion injury by inhibiting excessive mitophagy G6PD通过抑制过度的线粒体自噬来预防脑缺血再灌注损伤。
IF 5.2 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Life sciences
Pub Date : 2025-02-01 DOI: 10.1016/j.lfs.2024.123367
Yina Li , Yikun Gao , Guixiang Yu , Yingze Ye , Hua Zhu , Jin Wang , Yilin Li , Lei Chen , Lijuan Gu

Aims

Cerebral ischemia-reperfusion injury (CIRI) exacerbates post-stroke brain damage. We aimed to understand the role of glucose-6-phosphate dehydrogenase (G6PD) in CIRI and mitophagy.

Materials and methods

Lentivirus and small interfering RNA were utilized to suppress G6PD in tissues and cells, leading to the establishment of in vivo and in vitro models of ischemia-reperfusion following middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/ reoxygenation (OGD/R). The expression and function of G6PD were investigated through differential gene analysis and weighted correlation network analysis (WGCNA), immunofluorescence, and western blotting (WB).

Key findings

G6PD mRNA levels increased 3 d after MCAO, and G6PD protein expression was elevated in the ischemic penumbra of mice and HT22 cells following OGD/R. G6PD knockdown increased neural deficits, enlarged infarct volume in mice after CIRI, and reduced HT22 cell survival during OGD/R. WGCNA indicated a correlation between G6PD and mitophagy in CIRI. Following G6PD knockdown, the p-DRP1/DRP ratio increased, the PINK1/Parkin pathway was further activated, and TOMM20 expression was downregulated. The mitophagy inhibitor Mdivi-1 reversed these changes, as well as the nerve damage caused by G6PD knockdown, and alleviated mitochondrial damage in the ischemic penumbra.

Significance

The role of G6PD in CIRI was revealed and its interaction with mitophagy was explored, providing important insights for understanding the molecular mechanism of CIRI and developing new therapeutic strategies.
目的：脑缺血再灌注损伤（CIRI）加重脑卒中后脑损伤。我们旨在了解葡萄糖-6-磷酸脱氢酶（G6PD）在CIRI和线粒体自噬中的作用。材料和方法：利用慢病毒和小干扰RNA抑制组织和细胞中的G6PD，建立大脑中动脉闭塞（MCAO）和氧糖剥夺/再氧合（OGD/R）后缺血再灌注的体内和体外模型。通过差异基因分析、加权相关网络分析（WGCNA）、免疫荧光、western blotting （WB）等方法研究G6PD的表达和功能。关键发现：MCAO后3 d G6PD mRNA水平升高，OGD/R后小鼠缺血半暗区和HT22细胞中G6PD蛋白表达升高。G6PD敲除会增加CIRI后小鼠的神经缺损，增大梗死体积，并降低OGD/R期间HT22细胞的存活率。WGCNA显示G6PD与CIRI的有丝分裂相关。G6PD敲低后，p-DRP1/DRP比值升高，PINK1/Parkin通路进一步激活，TOMM20表达下调。线粒体自噬抑制剂Mdivi-1逆转了这些变化，也逆转了G6PD敲低引起的神经损伤，减轻了缺血半暗区线粒体损伤。意义：揭示G6PD在CIRI中的作用，探讨其与线粒体自噬的相互作用，为了解CIRI的分子机制和制定新的治疗策略提供重要见解。
{"title":"G6PD protects against cerebral ischemia-reperfusion injury by inhibiting excessive mitophagy","authors":"Yina Li ,&nbsp;Yikun Gao ,&nbsp;Guixiang Yu ,&nbsp;Yingze Ye ,&nbsp;Hua Zhu ,&nbsp;Jin Wang ,&nbsp;Yilin Li ,&nbsp;Lei Chen ,&nbsp;Lijuan Gu","doi":"10.1016/j.lfs.2024.123367","DOIUrl":"10.1016/j.lfs.2024.123367","url":null,"abstract":"<div><h3>Aims</h3><div>Cerebral ischemia-reperfusion injury (CIRI) exacerbates post-stroke brain damage. We aimed to understand the role of glucose-6-phosphate dehydrogenase (G6PD) in CIRI and mitophagy.</div></div><div><h3>Materials and methods</h3><div>Lentivirus and small interfering RNA were utilized to suppress G6PD in tissues and cells, leading to the establishment of in vivo and in vitro models of ischemia-reperfusion following middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/ reoxygenation (OGD/R). The expression and function of G6PD were investigated through differential gene analysis and weighted correlation network analysis (WGCNA), immunofluorescence, and western blotting (WB).</div></div><div><h3>Key findings</h3><div>G6PD mRNA levels increased 3 d after MCAO, and G6PD protein expression was elevated in the ischemic penumbra of mice and HT22 cells following OGD/R. G6PD knockdown increased neural deficits, enlarged infarct volume in mice after CIRI, and reduced HT22 cell survival during OGD/R. WGCNA indicated a correlation between G6PD and mitophagy in CIRI. Following G6PD knockdown, the p-DRP1/DRP ratio increased, the PINK1/Parkin pathway was further activated, and TOMM20 expression was downregulated. The mitophagy inhibitor Mdivi-1 reversed these changes, as well as the nerve damage caused by G6PD knockdown, and alleviated mitochondrial damage in the ischemic penumbra.</div></div><div><h3>Significance</h3><div>The role of G6PD in CIRI was revealed and its interaction with mitophagy was explored, providing important insights for understanding the molecular mechanism of CIRI and developing new therapeutic strategies.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123367"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pain in rheumatoid arthritis: Emerging role of high mobility group box 1 protein-HMGB1 类风湿关节炎疼痛：高流动性组框1蛋白hmgb1的新作用。
IF 5.2 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Life sciences
Pub Date : 2025-02-01 DOI: 10.1016/j.lfs.2024.123361
Anithakumari Aswathy Krishna, Beena Levakumar Abhirami, Alaganandam Kumaran
Rheumatoid arthritis (RA) is a chronic inflammatory disease where pain, driven by both inflammatory and non-inflammatory processes, is a major concern for patients. This pain can persist even after joint inflammation subsides. High mobility group box-1 (HMGB1) is a non-histone-DNA binding protein located in the nucleus that plays a key role in processes such as DNA transcription, recombination, and replication. HMGB1 can be released into the extracellular space through both passive and active mechanisms. Extracellular HMGB1 contributes to synovial inflammation, bone degradation, and the production of cytokines in RA by binding to toll-like receptors (TLRs) and receptors for advanced glycation end products (RAGE). It also forms complexes with molecules like lipopolysaccharide (LPS) and IL-1β, amplifying inflammatory responses. Due to its central role in these processes, HMGB1 is considered a promising therapeutic target in RA. It also acts as a nociceptive molecule in mediating pain in diseases such as diabetes and bone cancer. In this review, we explore how HMGB1 contributes to chronic pain in RA, supported by both in vitro and in vivo models. We begin by providing an overview of the mechanisms of pain in RA, the structure of HMGB1, its release mechanisms, and the therapeutic potential of targeting HMGB1 in RA. Following this, we highlight its role in peripheral and central pain sensitization through direct activation of the TLR4/MAPK/NF-κB pathway, as well as indirectly through downstream mediators, underscoring its potential as a target for managing RA pain.
类风湿性关节炎（RA）是一种慢性炎症性疾病，由炎症和非炎症过程驱动的疼痛是患者主要关注的问题。这种疼痛即使在关节炎症消退后也会持续。HMGB1 （High mobility group box-1）是一种位于细胞核中的非组蛋白-DNA结合蛋白，在DNA转录、重组和复制等过程中起关键作用。HMGB1可以通过被动和主动两种机制释放到细胞外空间。细胞外HMGB1通过与toll样受体（TLRs）和晚期糖基化终产物受体（RAGE）结合，参与RA滑膜炎症、骨降解和细胞因子的产生。它还与脂多糖（LPS）和IL-1β等分子形成复合物，放大炎症反应。由于其在这些过程中的核心作用，HMGB1被认为是RA的一个有希望的治疗靶点。在糖尿病和骨癌等疾病中，它还作为一种痛觉分子介导疼痛。在这篇综述中，我们探讨HMGB1如何在体外和体内模型的支持下促进RA的慢性疼痛。我们首先概述了类风湿性关节炎疼痛的机制，HMGB1的结构，其释放机制，以及靶向HMGB1在类风湿性关节炎中的治疗潜力。在此之后，我们强调了它通过直接激活TLR4/MAPK/NF-κB通路以及间接通过下游介质在外周和中枢疼痛致敏中的作用，强调了它作为治疗类风湿性关节炎疼痛的靶点的潜力。
{"title":"Pain in rheumatoid arthritis: Emerging role of high mobility group box 1 protein-HMGB1","authors":"Anithakumari Aswathy Krishna,&nbsp;Beena Levakumar Abhirami,&nbsp;Alaganandam Kumaran","doi":"10.1016/j.lfs.2024.123361","DOIUrl":"10.1016/j.lfs.2024.123361","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic inflammatory disease where pain, driven by both inflammatory and non-inflammatory processes, is a major concern for patients. This pain can persist even after joint inflammation subsides. High mobility group box-1 (HMGB1) is a non-histone-DNA binding protein located in the nucleus that plays a key role in processes such as DNA transcription, recombination, and replication. HMGB1 can be released into the extracellular space through both passive and active mechanisms. Extracellular HMGB1 contributes to synovial inflammation, bone degradation, and the production of cytokines in RA by binding to toll-like receptors (TLRs) and receptors for advanced glycation end products (RAGE). It also forms complexes with molecules like lipopolysaccharide (LPS) and IL-1β, amplifying inflammatory responses. Due to its central role in these processes, HMGB1 is considered a promising therapeutic target in RA. It also acts as a nociceptive molecule in mediating pain in diseases such as diabetes and bone cancer. In this review, we explore how HMGB1 contributes to chronic pain in RA, supported by both in vitro and in vivo models. We begin by providing an overview of the mechanisms of pain in RA, the structure of HMGB1, its release mechanisms, and the therapeutic potential of targeting HMGB1 in RA. Following this, we highlight its role in peripheral and central pain sensitization through direct activation of the TLR4/MAPK/NF-κB pathway, as well as indirectly through downstream mediators, underscoring its potential as a target for managing RA pain.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123361"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Retraction notice to “Cannabinoids as anti-ROS in aged pancreatic islet cells” [Life Sci. 256 (2020) 117969] 引用本文：“大麻素在衰老胰岛细胞中的抗ros作用”[j].中国生物医学工程学报，2016(6):117969。
IF 5.2 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Life sciences
Pub Date : 2025-02-01 DOI: 10.1016/j.lfs.2025.123371
Maryam Baeeri , Mahban Rahimifard , Seyed Mojtaba Daghighi , Fazlullah Khan , Seyed Alireza Salami , Shermineh Moini-Nodeh , Hamed Haghi-Aminjan , Zahra Bayrami , Farhad Rezaee , Mohammad Abdollahi
{"title":"Retraction notice to “Cannabinoids as anti-ROS in aged pancreatic islet cells” [Life Sci. 256 (2020) 117969]","authors":"Maryam Baeeri ,&nbsp;Mahban Rahimifard ,&nbsp;Seyed Mojtaba Daghighi ,&nbsp;Fazlullah Khan ,&nbsp;Seyed Alireza Salami ,&nbsp;Shermineh Moini-Nodeh ,&nbsp;Hamed Haghi-Aminjan ,&nbsp;Zahra Bayrami ,&nbsp;Farhad Rezaee ,&nbsp;Mohammad Abdollahi","doi":"10.1016/j.lfs.2025.123371","DOIUrl":"10.1016/j.lfs.2025.123371","url":null,"abstract":"","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123371"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advances in research on metabolic dysfunction-associated steatotic liver disease 代谢功能障碍相关脂肪变性肝病的研究进展
IF 5.2 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Life sciences
Pub Date : 2025-02-01 DOI: 10.1016/j.lfs.2024.123362
Jiawang Wang , Zhongyu Wang , Yao Yu , Si Cheng , Jianping Wu
The global increase in obesity-related metabolic disorders has led to metabolic dysfunction-associated steatotic liver disease (MASLD) emerging as one of the most prevalent chronic liver disease worldwide. Despite growing concerns, the exact pathogenesis of MASLD remains unclear and no definitive treatments have been made available. Consequently, the need for comprehensive research on MASLD is more critical than ever. Gaining insight into the mechanisms of the disease can lay the groundwork for identifying new therapeutic targets and can facilitate the development of diagnostic tools that enable the early detection and intervention of MASLD. Research has discovered a multifactorial etiology for MASLD, suggesting that potential therapeutic strategies should be considered from a variety of perspectives. This review delves into the pathogenesis of MASLD, current diagnostic approaches, potential therapeutic targets, the status of clinical trials for emerging drugs, and the most promising treatment methods available today. With a focus on therapeutic targets, the aim is to offer fresh insights and guide for future research in the treatment of MASLD.
全球肥胖相关代谢疾病的增加导致代谢功能障碍相关脂肪变性肝病（MASLD）成为全球最普遍的慢性肝病之一。尽管越来越多的关注，MASLD的确切发病机制仍不清楚，也没有明确的治疗方法。因此，对MASLD进行全面研究的必要性比以往任何时候都更加迫切。深入了解这种疾病的机制可以为确定新的治疗靶点奠定基础，并有助于开发能够早期发现和干预MASLD的诊断工具。研究发现了MASLD的多因素病因，提示应该从多种角度考虑潜在的治疗策略。本文将深入探讨MASLD的发病机制、目前的诊断方法、潜在的治疗靶点、新兴药物的临床试验状况以及目前最有希望的治疗方法。以治疗靶点为重点，旨在为MASLD治疗的未来研究提供新的见解和指导。
{"title":"Advances in research on metabolic dysfunction-associated steatotic liver disease","authors":"Jiawang Wang ,&nbsp;Zhongyu Wang ,&nbsp;Yao Yu ,&nbsp;Si Cheng ,&nbsp;Jianping Wu","doi":"10.1016/j.lfs.2024.123362","DOIUrl":"10.1016/j.lfs.2024.123362","url":null,"abstract":"<div><div>The global increase in obesity-related metabolic disorders has led to metabolic dysfunction-associated steatotic liver disease (MASLD) emerging as one of the most prevalent chronic liver disease worldwide. Despite growing concerns, the exact pathogenesis of MASLD remains unclear and no definitive treatments have been made available. Consequently, the need for comprehensive research on MASLD is more critical than ever. Gaining insight into the mechanisms of the disease can lay the groundwork for identifying new therapeutic targets and can facilitate the development of diagnostic tools that enable the early detection and intervention of MASLD. Research has discovered a multifactorial etiology for MASLD, suggesting that potential therapeutic strategies should be considered from a variety of perspectives. This review delves into the pathogenesis of MASLD, current diagnostic approaches, potential therapeutic targets, the status of clinical trials for emerging drugs, and the most promising treatment methods available today. With a focus on therapeutic targets, the aim is to offer fresh insights and guide for future research in the treatment of MASLD.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123362"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
首页 上一页 下一页 尾页
类型
全部 化学•材料 生命科学 医学 物理 工程技术 环境•农林 材料科学 地球科学 法学 管理学 化学 环境科学与生态学 计算机科学 教育学 经济学 农林科学 人文科学 生物学 数学 物理与天体物理 心理学 综合性期刊 其他 工业工程 理学 历史学 农学 文学 信息工程
数据库
全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley
期刊
Life sciences
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
﹀
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整，为了账户安全，请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号：481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们：info@booksci.cn
Book学术提供免费学术资源搜索服务，方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1