Life medicine最新文献_第2页

Tumor cell-specific exon 3-deleted FOXP3 isoform promotes growth and metastasis via STAT3 in non-small cell lung cancer. 肿瘤细胞特异性外显子3缺失的FOXP3亚型通过STAT3促进非小细胞肺癌的生长和转移。

IF 7.7

Life medicine Pub Date : 2026-07-07 eCollection Date: 2026-08-01 DOI: 10.1093/lifemedi/lnag024

Jia Peng, Yi Liu, Zhongqin Gong, Ming-Yue Li, Hao Jia, Xueqing Zhou, Calvin S H Ng, George G Chen, Shucai Yang

{"title":"Tumor cell-specific exon 3-deleted FOXP3 isoform promotes growth and metastasis via STAT3 in non-small cell lung cancer.","authors":"Jia Peng, Yi Liu, Zhongqin Gong, Ming-Yue Li, Hao Jia, Xueqing Zhou, Calvin S H Ng, George G Chen, Shucai Yang","doi":"10.1093/lifemedi/lnag024","DOIUrl":"10.1093/lifemedi/lnag024","url":null,"abstract":"Forkhead box P3 (FOXP3), the master regulator of regulatory T cells (Tregs), is aberrantly expressed in tumor cells, including lung cancer. Alternative splicing generates multiple isoforms, among which the full-length FOXP3 (FOXP3FL) and exon 3-deleted variant (FOXP3Δ3) are predominant. We identified FOXP3Δ3 as the major isoform in non-small cell lung cancer (NSCLC) tumor cells. FOXP3Δ3 expression was elevated in tumor tissues and correlated with larger tumor size and advanced T stage. Functional assays showed that tumoral FOXP3Δ3 enhanced proliferation, invasion, migration, stemness, and apoptosis resistance in NSCLC cells, exerting stronger effects than FOXP3FL. Knockdown of FOXP3Δ3 in NSCLC cells suppressed tumor growth in nude mice, confirming its oncogenic activity in vivo. Mechanistically, FOXP3Δ3 upregulated phosphorylated STAT3 and mesenchymal markers (N-cadherin, Vimentin, Snail), while reducing epithelial marker E-cadherin compared with FOXP3FL. Coimmunoprecipitation indicated these differences may arise from distinct STAT3 binding affinities. Additionally, FOXP3Δ3 decreased cisplatin-induced apoptosis, suggesting a role in chemoresistance. In summary, FOXP3Δ3 is the predominant oncogenic FOXP3 isoform in NSCLC tumor cells, promoting tumor cell progression and therapy resistance through STAT3 signaling. These findings highlight FOXP3Δ3 as a potential therapeutic target.","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"5 4","pages":"lnag024"},"PeriodicalIF":7.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LoopID reveals condensate-mediated enhancer-promoter interaction regulates cell fate. LoopID揭示凝聚体介导的增强子-启动子相互作用调节细胞命运。

IF 7.7

Life medicine Pub Date : 2026-06-30 eCollection Date: 2026-06-01 DOI: 10.1093/lifemedi/lnag019

Shaoshuai Jiang, Lu Liu, Xinyi Liu, Junjun Ding

引用次数: 0

The ancient viral whispers of ageing: awakening the dark genome. 古老的病毒低语着衰老：唤醒黑暗的基因组。

IF 7.7

Life medicine Pub Date : 2026-06-24 eCollection Date: 2026-08-01 DOI: 10.1093/lifemedi/lnag023

Hui Zhang, Guang-Hui Liu, Jing Qu

引用次数: 0

SIRT1 deacetylates PKM2 to constrain lactate production and protect against premature ovarian insufficiency. SIRT1使PKM2去乙酰化以限制乳酸的产生和防止卵巢功能不全。

IF 7.7

Life medicine Pub Date : 2026-06-09 eCollection Date: 2026-08-01 DOI: 10.1093/lifemedi/lnag022

Xiangrong Cui, Chongyang Han, Puhua Zhang, Ruotong Ju, Ruixiang Zhu, Jiali Luo, Li Peng, Chenyu Jia, Xinyu Zhu, Shu Wang, Huihui Li, Tingting Xue, Meng Zou, Xueqing Wu, Xuan Jing

{"title":"SIRT1 deacetylates PKM2 to constrain lactate production and protect against premature ovarian insufficiency.","authors":"Xiangrong Cui, Chongyang Han, Puhua Zhang, Ruotong Ju, Ruixiang Zhu, Jiali Luo, Li Peng, Chenyu Jia, Xinyu Zhu, Shu Wang, Huihui Li, Tingting Xue, Meng Zou, Xueqing Wu, Xuan Jing","doi":"10.1093/lifemedi/lnag022","DOIUrl":"10.1093/lifemedi/lnag022","url":null,"abstract":"Premature ovarian insufficiency (POI) causes early loss of ovarian function, though its underlying metabolic-epigenetic mechanisms remain unclear. Using ovarian tissues from POI patients and a cisplatin-induced mouse model, we investigated the role of the NAD+-dependent deacetylase Sirtuin 1 (SIRT1) in granulosa cells. We found that SIRT1 expression was markedly downregulated in POI, correlating with hyperacetylation of the glycolytic enzyme pyruvate kinase M2 (PKM2) and pathogenic lactate accumulation. Restoring SIRT1 activity via intra-ovarian AAV-SIRT1 delivery or systemic administration of nicotinamide mononucleotide (NMN) reversed these phenotypes. This intervention improved follicular development, reduced granulosa cell apoptosis, and normalized serum anti-Müllerian hormone and follicle-stimulating hormone levels. Mechanistically, SIRT1 directly interacts with and deacetylates PKM2, suppressing its activity and limiting lactate production. Our work defines a critical SIRT1-PKM2-lactate metabolic axis that maintains ovarian homeostasis. Targeting this axis via NAD+-boosting interventions, such as NMN, presents a promising novel therapeutic strategy for POI.","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"5 4","pages":"lnag022"},"PeriodicalIF":7.7,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The entropic view of aging: from thermodynamics to biology. 衰老的熵观：从热力学到生物学。

IF 7.7

Life medicine Pub Date : 2026-05-26 eCollection Date: 2026-06-01 DOI: 10.1093/lifemedi/lnag020

Zeming Wu, Shuai Ma, Si Wang, Moshi Song, Weiqi Zhang, Jing Qu, Juan Carlos Izpisua Belmonte, Guang-Hui Liu

{"title":"The entropic view of aging: from thermodynamics to biology.","authors":"Zeming Wu, Shuai Ma, Si Wang, Moshi Song, Weiqi Zhang, Jing Qu, Juan Carlos Izpisua Belmonte, Guang-Hui Liu","doi":"10.1093/lifemedi/lnag020","DOIUrl":"10.1093/lifemedi/lnag020","url":null,"abstract":"A growing body of evidence suggests that aging is not simply the accumulation of damage, but a systemic progression of increasing entropy across biological scales. Synthesizing concepts from thermodynamics and information theory, we outline a tentative three-stage entropy model of the lifespan: order-building development, homeostatic adulthood, and disorder-dominant aging. Within this model, we attempt to reframe the established hallmarks of aging as interconnected nodes in an entropy-centered network and detail the multiscale manifestations of disorder from molecules to systems. To quantify this trajectory, we introduce a Multiscale Entropic Aging Index (MEAI) as a proof-of-concept conceptual framework, designed to integrate measurements of disorder across biological levels. This framework seeks to offer a potential unifying, quantitative language for aging research and suggests that entropy reduction could serve as a testable mechanism underlying interventions, laying a principled foundation for the future development of biomarkers and rejuvenative strategies.","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"5 3","pages":"lnag020"},"PeriodicalIF":7.7,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13319325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148371310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

From metaphor to metric: the entropic framework as a unifying theory of aging. 从隐喻到度量：作为老龄化统一理论的熵框架。

IF 7.7

Life medicine Pub Date : 2026-05-26 eCollection Date: 2026-06-01 DOI: 10.1093/lifemedi/lnag021

Yu Chen, Zhiyong Mao

引用次数: 0

TRIM22-mediated ubiquitin-dependent degradation of FLT3-ITD overcomes TKI resistance in acute myeloid leukemia. trim22介导的FLT3-ITD泛素依赖性降解克服急性髓系白血病TKI耐药。

IF 7.7

Life medicine Pub Date : 2026-05-14 eCollection Date: 2026-06-01 DOI: 10.1093/lifemedi/lnag017

Meng Liu, Xiaoqian Wang, Xiaqin He, Xiaoguang Xu, Jing Chen, Juan Liu, Shan Jiang, Sijia Li, Si Wang, Yuanyuan Liu, Jing Feng, Xin Xu, Miaoyin Luo, Zhiyi Li, Yining Zhang, Yingli Wu, Jian Hu, Xiaoqin Wang

{"title":"TRIM22-mediated ubiquitin-dependent degradation of FLT3-ITD overcomes TKI resistance in acute myeloid leukemia.","authors":"Meng Liu, Xiaoqian Wang, Xiaqin He, Xiaoguang Xu, Jing Chen, Juan Liu, Shan Jiang, Sijia Li, Si Wang, Yuanyuan Liu, Jing Feng, Xin Xu, Miaoyin Luo, Zhiyi Li, Yining Zhang, Yingli Wu, Jian Hu, Xiaoqin Wang","doi":"10.1093/lifemedi/lnag017","DOIUrl":"10.1093/lifemedi/lnag017","url":null,"abstract":"FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutations, found in 25%-30% of acute myeloid leukemia (AML) patients, cause poor prognosis and resistance to FLT3 tyrosine kinase inhibitors (TKIs). We show that APG-115 selectively kills FLT3-ITD cells by activating p53. This critically upregulates TRIM22 (Tripartite motif-containing protein 22), an essential E3 ubiquitin ligase that directly binds FLT3-ITD, promotes its polyubiquitination, and induces its proteasomal degradation. This TRIM22-mediated mechanism offers a novel strategy to overcome intrinsic and acquired TKI resistance. Unlike inhibitors such as AC220, which suppress FLT3 signaling but downregulate p53, APG-115 restores p53 function and induces TRIM22, enabling potent synergy with FLT3 inhibitors. TRIM22 is essential for APG-115's suppression of leukemia stem cells, inducing cell cycle arrest, myeloid differentiation, and reduced clonogenic potential. The combination of APG-115 and AC220 significantly enhances apoptosis in FLT3-ITD AML models and primary cells, while sparing normal cells. It shows robust efficacy in preclinical xenograft models, reducing tumor burden and extending survival. This work establishes targeting the p53/TRIM22 axis, reliant on TRIM22's unique activity against FLT3-ITD, as a highly promising therapeutic approach for FLT3-ITD AML, including resistant disease.","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"5 3","pages":"lnag017"},"PeriodicalIF":7.7,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13319326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148371256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Connexins in metabolic control: linking brain cellular communication to systemic homeostasis. 代谢控制中的连接蛋白：将脑细胞通讯与系统稳态联系起来。

IF 7.7

Life medicine Pub Date : 2026-05-11 eCollection Date: 2026-08-01 DOI: 10.1093/lifemedi/lnag018

Yiyi Zhu, Hui Chen, Dan Li, Alexei Verkhratsky, Chenju Yi

{"title":"Connexins in metabolic control: linking brain cellular communication to systemic homeostasis.","authors":"Yiyi Zhu, Hui Chen, Dan Li, Alexei Verkhratsky, Chenju Yi","doi":"10.1093/lifemedi/lnag018","DOIUrl":"10.1093/lifemedi/lnag018","url":null,"abstract":"Connexins, a family of transmembrane proteins, are essential for intercellular communication in the mammalian central nervous system, particularly through their assembly into gap junction channels. This review explores the central role of connexin-mediated signalling in hypothalamic regulation of nutrient metabolism and energy homeostasis, together with the function of connexins in peripheral metabolic organs. Focusing on connexins Cx43 and Cx30, we discuss their specific expression within hypothalamic neuroglial populations, including astrocytes and tanycytes, and their involvement in glucose sensing, metabolic signalling, and neuroendocrine regulation. Functional studies demonstrate that hypothalamic Cx43 is dynamically regulated by metabolic status, while its knockdown impairs glucose-stimulated insulin secretion and systemic energy balance. Tanycytes, interconnected into a Cx43-dependent network, play a critical role in relaying metabolic cues from cerebrospinal fluid and blood to hypothalamic neurons, thereby orchestrating adaptive responses to glycaemic changes. The review further details how the disruption of connexin-mediated coupling in tanycytes leads to impaired glucose sensing, altered neuronal activity, and systemic metabolic disorders. Beyond the hypothalamus, this review also summarizes how connexins in peripheral metabolic organs contribute to metabolic homeostasis, inflammatory regulation, and disease progression. Collectively, these discoveries highlight the fundamental importance of connexins in integrating metabolic signals and maintaining systemic homeostasis.","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"5 4","pages":"lnag018"},"PeriodicalIF":7.7,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Atypical involvement of Alzheimer's tau proteins in diseases beyond tauopathies. 阿尔茨海默氏tau蛋白在tau病以外的疾病中的非典型参与。

IF 7.7

Life medicine Pub Date : 2026-05-11 eCollection Date: 2026-06-01 DOI: 10.1093/lifemedi/lnag016

Jie Meng, Zi-Jie Deng, Jing Zhang, Wenxin Yu, Xiaolei Wu, Peng Lei

{"title":"Atypical involvement of Alzheimer's tau proteins in diseases beyond tauopathies.","authors":"Jie Meng, Zi-Jie Deng, Jing Zhang, Wenxin Yu, Xiaolei Wu, Peng Lei","doi":"10.1093/lifemedi/lnag016","DOIUrl":"10.1093/lifemedi/lnag016","url":null,"abstract":"Tau is a microtubule-associated protein traditionally involved in a collective group of disorders termed \"tauopathy\", including Alzheimer's disease. Tau protein self-aggregates and forms neurofibrillary tangles in neurons, which are considered a pathological hallmark of tauopathies. While the roles of neuronal tau in tauopathies have been extensively investigated, recent studies have shed light on its roles in other diseases without tau pathology and in other cells. In this review, we aim to discuss the \"atypical\" pathological involvement of tau in diseases other than tauopathies, including brain diseases (e.g., amyotrophic lateral sclerosis, multiple sclerosis, and spinal cord injury), vascular diseases (stroke and hypertension), diabetes, and cancers. We have discussed the expression and functions of tau in cell types other than neurons, and have summarized the evidence supporting a role of tau in these diseases. These cross-disease studies collectively suggest that tau protein is more broadly implicated in mechanisms such as axonal instability, dysregulated cell signaling, inflammatory activation, and cell death, independent of its aggregation, contributing to our knowledge of the functions of tau and the myriad ways in which it may be involved in pathological processes.","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"5 3","pages":"lnag016"},"PeriodicalIF":7.7,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13297004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148347635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The metabolic change trajectory of skeletal muscle during the life cycle: arteriovenous metabolomics. 骨骼肌在生命周期中的代谢变化轨迹：动静脉代谢组学。

IF 7.7

Life medicine Pub Date : 2026-04-27 eCollection Date: 2026-06-01 DOI: 10.1093/lifemedi/lnag014

Siyuan Huang, Yuanping Gu, Guogang Xu, Jing Han, Hao Jia, Yifan Wang, Xiao Chen, Ningning Zhang, Xiumeng Hua, Han Mo, Zhe Sun, Fei Dong, Yuan Chang, Hao Cui, Jiangping Song

引用次数: 0