Acta Pharmaceutica Sinica. B最新文献

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Design, synthesis, and antitumor activity of novel thioheterocyclic nucleoside derivatives by suppressing the c-MYC pathway 新型硫杂环核苷衍生物通过抑制c-MYC通路的设计、合成和抗肿瘤活性
IF 14.7 1区 医学
Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.05.008
Xian-Jia Li , Ke-Xin Huang , Ke-Xin Wang , Ru Liu , Dong-Chao Wang , Yu-Ru Liang , Er-Jun Hao , Yang Wang , Hai-Ming Guo
{"title":"Design, synthesis, and antitumor activity of novel thioheterocyclic nucleoside derivatives by suppressing the c-MYC pathway","authors":"Xian-Jia Li ,&nbsp;Ke-Xin Huang ,&nbsp;Ke-Xin Wang ,&nbsp;Ru Liu ,&nbsp;Dong-Chao Wang ,&nbsp;Yu-Ru Liang ,&nbsp;Er-Jun Hao ,&nbsp;Yang Wang ,&nbsp;Hai-Ming Guo","doi":"10.1016/j.apsb.2025.05.008","DOIUrl":"10.1016/j.apsb.2025.05.008","url":null,"abstract":"<div><div>Eightly-four novel thioheterocyclic nucleoside derivatives were designed, synthesized, and evaluated for antitumor activity <em>in vitro</em> and <em>in vivo</em>. Most of the compounds inhibited the growth of HCT116 and HeLa cancer cells <em>in vitro</em>, among them <strong>33a</strong> and <strong>36b</strong> exhibited potent activity against HCT116 cells (IC<sub>50</sub> = 0.27 and 0.49 μmol/L, respectively). Both compounds <strong>33a</strong> and <strong>36b</strong> inhibited cell metastasis, arrested the cell cycle in the G<sub>2</sub>/M phase, and induced apoptosis <em>in vitro</em>. Mechanistic studies revealed that <strong>33a</strong> and <strong>36b</strong> increased ROS levels, led to DNA damage, ER stress, and mitochondrial dysfunction, and inhibited autophagy in HCT116 cells. Biological information analysis, RNA-sequencing, Gene Set Enrichment Analysis (GSEA), drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and SPR experiments identified that compounds <strong>33a</strong> and <strong>36b</strong> showed antitumor activity by suppressing the c-MYC pathway. <em>c-MYC</em> silencing assays indicated that c-MYC proteins participated in <strong>33a</strong>-mediated anticancer activities in HCT116 cells. More importantly, compound <strong>33a</strong> presented favorable pharmacokinetic properties in mice (<em>T</em><sub>1/2</sub> = 6.8 h) and showed significant antitumor efficacy <em>in vivo</em> without obvious toxicity, showing promising potential for further clinical development.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3685-3707"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Traditional Chinese medicine in the early prevention of colorectal cancer from the perspective of tumor microenvironment 中医药在结直肠癌早期预防中的肿瘤微环境视角
IF 14.7 1区 医学
Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.06.020
Huan Tang, Jigang Wang
{"title":"Traditional Chinese medicine in the early prevention of colorectal cancer from the perspective of tumor microenvironment","authors":"Huan Tang,&nbsp;Jigang Wang","doi":"10.1016/j.apsb.2025.06.020","DOIUrl":"10.1016/j.apsb.2025.06.020","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3829-3830"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Autonomous drug delivery and scar microenvironment remodeling using micromotor-driven microneedles for hypertrophic scars therapy 利用微电机驱动的微针自主给药和疤痕微环境重塑治疗增生性疤痕
IF 14.7 1区 医学
Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.05.017
Ting Wen , Yanping Fu , Xiangting Yi , Ying Sun , Wanchen Zhao , Chaonan Shi , Ziyao Chang , Beibei Yang , Shuling Li , Chao Lu , Tingting Peng , Chuanbin Wu , Xin Pan , Guilan Quan
{"title":"Autonomous drug delivery and scar microenvironment remodeling using micromotor-driven microneedles for hypertrophic scars therapy","authors":"Ting Wen ,&nbsp;Yanping Fu ,&nbsp;Xiangting Yi ,&nbsp;Ying Sun ,&nbsp;Wanchen Zhao ,&nbsp;Chaonan Shi ,&nbsp;Ziyao Chang ,&nbsp;Beibei Yang ,&nbsp;Shuling Li ,&nbsp;Chao Lu ,&nbsp;Tingting Peng ,&nbsp;Chuanbin Wu ,&nbsp;Xin Pan ,&nbsp;Guilan Quan","doi":"10.1016/j.apsb.2025.05.017","DOIUrl":"10.1016/j.apsb.2025.05.017","url":null,"abstract":"<div><div>Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO<sub>2</sub> bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. <em>In vitro</em> studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-<em>β</em>1 (TGF-<em>β</em>1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3738-3755"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
A high clinically translatable strategy to anti-aging using hyaluronic acid and silk fibroin co-crosslinked hydrogels as dermal regenerative fillers 使用透明质酸和丝素蛋白共交联水凝胶作为皮肤再生填充剂的高临床可翻译的抗衰老策略
IF 14.7 1区 医学
Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.04.020
Jialing Cheng , Zhiyang Chen , Demin Lin , Yanfang Yang , Yanjing Bai , Lingshuang Wang , Jie Li , Yuchen Wang , Hongliang Wang , Youbai Chen , Jun Ye , Yuling Liu
{"title":"A high clinically translatable strategy to anti-aging using hyaluronic acid and silk fibroin co-crosslinked hydrogels as dermal regenerative fillers","authors":"Jialing Cheng ,&nbsp;Zhiyang Chen ,&nbsp;Demin Lin ,&nbsp;Yanfang Yang ,&nbsp;Yanjing Bai ,&nbsp;Lingshuang Wang ,&nbsp;Jie Li ,&nbsp;Yuchen Wang ,&nbsp;Hongliang Wang ,&nbsp;Youbai Chen ,&nbsp;Jun Ye ,&nbsp;Yuling Liu","doi":"10.1016/j.apsb.2025.04.020","DOIUrl":"10.1016/j.apsb.2025.04.020","url":null,"abstract":"<div><div>An ideal dermal filler should integrate filling, repair, and anti-aging effects, with immediate tissue augmentation, slow degradation, and progressive stimulation of collagen regeneration. However, commonly used hyaluronic acid (HA) hydrogels, while effective for rapid filling, suffer from limited duration of support, weak cell adhesion, and an inability to promote collagen regeneration. Silk fibroin (SF), a natural protein from silkworm cocoons, is known for its excellent cell adhesion and collagen-stimulating abilities. However, its limited gelation capability restricts its potential application as a standalone injectable hydrogel. Based on a complementary strategy, this study combines the rapid gelling properties of HA with the collagen regenerative properties of SF to create a co-crosslinked HA-SF hydrogel. The composite hydrogel merges HA's rapid filling effect with SF's strong tissue adhesion and collagen-stimulating abilities. The formulation, physicochemical properties, degradation, biocompatibility, and filling effects of the HA-SF hydrogel were systematically investigated. HA-SF hydrogel exhibits excellent mechanical properties and ensures long-term support while maintaining injectability. Interestingly, after intradermal injection in the UVB-induced photoaging model, HA-SF hydrogel not only enhances hydrogel–cell interaction but also continues to stimulate collagen regeneration, especially type III collagen. This dual action achieves the biological effects of repair and anti-aging while maintaining the filling effect. Proteomic analysis confirms that repair and anti-aging effects are enhanced by the regulation of skin fibroblasts and modulation of amino acid and lipid metabolism. This composite hydrogel holds strong promise for clinical applications, offering a safer, long-lasting, and more natural injectable filler that combines filling, repair, and anti-aging into one system.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3767-3787"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
RXRα modulates hepatic stellate cell activation and liver fibrosis by targeting CaMKKβ–AMPKα axis RXRα通过靶向CaMKKβ-AMPKα轴调控肝星状细胞活化和肝纤维化
IF 14.7 1区 医学
Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.05.023
Lijun Cai , Meimei Yin , Shuangzhou Peng , Fen Lin , Liangliang Lai , Xindao Zhang , Lei Xie , Chuanying Wang , Huiying Zhou , Yunfeng Zhan , Gulimiran Alitongbieke , Baohuan Lian , Zhibin Su , Tenghui Liu , Yuqi Zhou , Zongxi Li , Xiaohui Chen , Qi Zhao , Ting Deng , Lulu Chen , Xiao-Kun Zhang
{"title":"RXRα modulates hepatic stellate cell activation and liver fibrosis by targeting CaMKKβ–AMPKα axis","authors":"Lijun Cai ,&nbsp;Meimei Yin ,&nbsp;Shuangzhou Peng ,&nbsp;Fen Lin ,&nbsp;Liangliang Lai ,&nbsp;Xindao Zhang ,&nbsp;Lei Xie ,&nbsp;Chuanying Wang ,&nbsp;Huiying Zhou ,&nbsp;Yunfeng Zhan ,&nbsp;Gulimiran Alitongbieke ,&nbsp;Baohuan Lian ,&nbsp;Zhibin Su ,&nbsp;Tenghui Liu ,&nbsp;Yuqi Zhou ,&nbsp;Zongxi Li ,&nbsp;Xiaohui Chen ,&nbsp;Qi Zhao ,&nbsp;Ting Deng ,&nbsp;Lulu Chen ,&nbsp;Xiao-Kun Zhang","doi":"10.1016/j.apsb.2025.05.023","DOIUrl":"10.1016/j.apsb.2025.05.023","url":null,"abstract":"<div><div>Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXR<em>α</em>), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXR<em>α</em> exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase <em>β</em> (CaMKK<em>β</em>)-mediated activation of AMP-activated protein kinase-alpha (AMPK<em>α</em>). In addition, we demonstrate that K-80003, which binds RXR<em>α</em> by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl<sub>4</sub> and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPK<em>α</em> activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPK<em>α</em> by inducing RXR<em>α</em> to form condensates with CaMKK<em>β</em> and AMPK<em>α via</em> a two-phase process. The formation of RXR<em>α</em> condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKK<em>β</em>. Our results reveal a crucial role of RXR<em>α</em> in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXR<em>α</em> modulators hold promise as therapeutic agents for fibrosis-related diseases.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3611-3631"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Anacyphrethines A and B as potent analgesics: Multiple ion channel inhibitors with an unprecedented chemical architecture 磺胺甲醚A和B作为强效镇痛药:具有前所未有化学结构的多离子通道抑制剂
IF 14.7 1区 医学
Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.04.032
Hui Chen , Hanqi Zhang , Chao Niu , Bianlin Wang , Biao Gao , Zhijun Liu , Guangmin Yao , Haji Akber Aisa
{"title":"Anacyphrethines A and B as potent analgesics: Multiple ion channel inhibitors with an unprecedented chemical architecture","authors":"Hui Chen ,&nbsp;Hanqi Zhang ,&nbsp;Chao Niu ,&nbsp;Bianlin Wang ,&nbsp;Biao Gao ,&nbsp;Zhijun Liu ,&nbsp;Guangmin Yao ,&nbsp;Haji Akber Aisa","doi":"10.1016/j.apsb.2025.04.032","DOIUrl":"10.1016/j.apsb.2025.04.032","url":null,"abstract":"<div><div>Multi-target analgesics with minimal side effects and high efficacy are a key research focus in addressing the global pain crisis. Using a molecular networking approach, five pairs of potent analgesic alkaloid enantiomers were isolated from the roots of <em>Anacyclus pyrethrum</em> (<em>A</em>. <em>pyrethrum</em>). Their structures were elucidated by comprehensive spectroscopic data analysis, including LR-HSQMBC and <sup>1</sup>H–<sup>15</sup>N HMBC, quantum <sup>13</sup>C NMR DP4+ and ECD calculations, and single-crystal X-ray diffraction analysis. Anacyphrethines A (<strong>1</strong>) and B (<strong>2</strong>) are highly conjugated and polymethylated 6/6/6/6/5/7/5/5-fused octacyclic tetraazabic alkaloids possessing an unprecedented 8,14,18,24-tetraaza-octacyclo[16.8.2.1<sup>1,23</sup>.0<sup>4,28</sup>.0<sup>5,17</sup>.0<sup>9,16</sup>.0<sup>11,15</sup>.0<sup>21,27</sup>] nonacosane motif. Their biosynthetic pathways are proposed involving key aldol, hydroamination, and Schiff base reactions. All isolates showed potent analgesic effects <em>in vivo</em>. Even at a lower dose of 0.2 mg/kg, (±)-<strong>1</strong> and (+)-<strong>1</strong> still exhibited more potent analgesic activities than morphine. Interestingly, the racemic mixture (±)-<strong>1</strong> showed stronger analgesic effect than either pure enantiomer alone at higher doses of 5 and 1 mg/kg; while, (±)-<strong>1</strong> showed significant analgesic activities comparable to (+)-<strong>1</strong> at lower doses of 0.2 and 0.04 mg/kg. (+)-<strong>1</strong> had stronger analgesic effect than (−)-<strong>1</strong> at five tested does. Further tests on 44 analgesic-related targets demonstrated that (+)-<strong>1</strong> showed significant inhibitory effects against many ion channels such as TRPM8, Kv1.2, Kv1.3, and Ca<sub>v</sub>2.1 with IC<sub>50</sub> values of 1.10 ± 0.26, 4.20 ± 0.07, 2.20 ± 0.24, and 10.40 ± 0.69 μmol/L, respectively, while (−)-<strong>1</strong> primarily inhibited TRPC6, Kv1.2, and Kv1.3 ion channels with IC<sub>50</sub> values of 0.81 ± 0.05, 0.91 ± 0.04, and 1.50 ± 0.13 μmol/L, respectively, without affecting the opioid receptors, suggesting their non-opioid analgesic potentials. The molecular dockings provided structural guidance to develop potent non-opioid analgesics.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3725-3737"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
A transformer-based strategy to develop RP20 as a potent RIPK2 inhibitor for acetaminophen-induced acute liver injury 基于变压器的策略开发RP20作为对乙酰氨基酚诱导的急性肝损伤的有效RIPK2抑制剂
IF 14.7 1区 医学
Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.06.003
Liang Ouyang
{"title":"A transformer-based strategy to develop RP20 as a potent RIPK2 inhibitor for acetaminophen-induced acute liver injury","authors":"Liang Ouyang","doi":"10.1016/j.apsb.2025.06.003","DOIUrl":"10.1016/j.apsb.2025.06.003","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3831-3832"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Melatonin receptor 1a alleviates sleep fragmentation-aggravated testicular injury in T2DM by suppression of TAB1/TAK1 complex through FGFR1 褪黑激素受体1a通过FGFR1抑制TAB1/TAK1复合物,减轻T2DM患者睡眠片段加重的睾丸损伤
IF 14.7 1区 医学
Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.05.018
Xiaohui Zhang , Xinyu Tang , Ting Gao , Yuanfang Guo , Guangping Lu , Qingbo Liu , Jiahao Li , Jie Wang , Mingrui Liu , Dongmei Zhang , Yufeng Tang , Junlian Gu
{"title":"Melatonin receptor 1a alleviates sleep fragmentation-aggravated testicular injury in T2DM by suppression of TAB1/TAK1 complex through FGFR1","authors":"Xiaohui Zhang ,&nbsp;Xinyu Tang ,&nbsp;Ting Gao ,&nbsp;Yuanfang Guo ,&nbsp;Guangping Lu ,&nbsp;Qingbo Liu ,&nbsp;Jiahao Li ,&nbsp;Jie Wang ,&nbsp;Mingrui Liu ,&nbsp;Dongmei Zhang ,&nbsp;Yufeng Tang ,&nbsp;Junlian Gu","doi":"10.1016/j.apsb.2025.05.018","DOIUrl":"10.1016/j.apsb.2025.05.018","url":null,"abstract":"<div><div>A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in <em>Fgfr1</em> knockout (<em>Fgfr1-KO</em><sup><em>+/–</em></sup>) diabetic mice. Meanwhile, testicular-specific overexpression of <em>Tak1</em> abolished the protective effect of FGF1<sup>mut</sup> on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3591-3610"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Trends in intestinal aging: From underlying mechanisms to therapeutic strategies 肠道衰老的趋势:从潜在机制到治疗策略
IF 14.7 1区 医学
Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.05.011
Yajun Wang , Xueni Zhang , Mengli Qing , Wen Dang , Xuemei Bai , Yingjie Wang , Di Zhou , Lingjuan Zhu , Degang Qing , Juan Zhang , Gang Chen , Ning Li
{"title":"Trends in intestinal aging: From underlying mechanisms to therapeutic strategies","authors":"Yajun Wang ,&nbsp;Xueni Zhang ,&nbsp;Mengli Qing ,&nbsp;Wen Dang ,&nbsp;Xuemei Bai ,&nbsp;Yingjie Wang ,&nbsp;Di Zhou ,&nbsp;Lingjuan Zhu ,&nbsp;Degang Qing ,&nbsp;Juan Zhang ,&nbsp;Gang Chen ,&nbsp;Ning Li","doi":"10.1016/j.apsb.2025.05.011","DOIUrl":"10.1016/j.apsb.2025.05.011","url":null,"abstract":"<div><div>Intestinal aging is central to systemic aging, characterized by a progressive decline in intestinal structure and function. The core mechanisms involve dysregulation of epithelial cell renewal and gut microbiota dysbiosis. In addition to previous results in model organisms like <em>Drosophila melanogaster</em>, recent studies have shown that in mammalian models, aging causes increased intestinal permeability and intestinal-derived systemic inflammation, thereby affecting longevity. Therefore, anti-intestinal aging can be an important strategy for reducing frailty and promoting longevity. There are three key gaps remaining in the study of intestinal aging: (1) overemphasis on aging-related diseases rather than the primary aging mechanisms; (2) lack of specific drugs or treatments to prevent or treat intestinal aging; (3) limited aging-specific dysbiosis research. In this review, the basic structures and renewal mechanisms of intestinal epithelium, and mechanisms and potential therapies for intestinal aging are discussed to advance understanding of the causes, consequences, and treatments of age-related intestinal dysfunction.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3372-3403"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Indoleamine-2,3-dioxygenase: An important controller in maintaining mesenchymal stem cell-mediated immunomodulatory homeostasis 吲哚胺-2,3-双加氧酶:维持间充质干细胞介导的免疫调节稳态的重要控制者
IF 14.7 1区 医学
Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.04.022
Yufei Hui , Xue Jiao , Li Yang , Dejin Lu , Yanbo Han , Wen Yang , Yanli Cao , Yuxi Miao , Shiqiang Gong , Minjie Wei
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