Molecules and Cells最新文献_第6页

Rationale and emerging evidence for microglial replacement in Alzheimer’s disease 阿尔茨海默病小胶质细胞替代的基本原理和新证据。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2025-10-01 Epub Date: 2025-08-14 DOI: 10.1016/j.mocell.2025.100265

Jee Yoon Bang , Yongjin Yoo

{"title":"Rationale and emerging evidence for microglial replacement in Alzheimer’s disease","authors":"Jee Yoon Bang , Yongjin Yoo","doi":"10.1016/j.mocell.2025.100265","DOIUrl":"10.1016/j.mocell.2025.100265","url":null,"abstract":"<div><div>Microglial biology in Alzheimer’s disease (AD) has become a major focus of investigation, aiming to define how these cells contribute to neurodegeneration and to develop new therapeutic strategies. Once regarded as passive responders, microglia are now recognized as active regulators of brain homeostasis, immune signaling, and synaptic remodeling. Their interactions with genetic risk variants and age-related changes are increasingly understood to play central roles in AD pathogenesis. In this mini-review, we summarize recent progress in identifying microglial contributions to AD through genetic and transcriptomic studies. We discuss how microglia respond to amyloid-β and tau pathology by shifting into diverse functional disease-associated states, which may either protect or harm the brain depending on context and disease stage. We also outline the rationale for targeting microglia through replacement strategies and review emerging approaches using circulation-derived myeloid cells (CDMCs), and human pluripotent stem cell–derived microglia-like cells. These replacement methods have shown potential to rectify microglial functions and modify AD-related pathology in preclinical models, offering a novel therapeutic direction for neurodegenerative diseases.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 10","pages":"Article 100265"},"PeriodicalIF":6.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of a unique subpopulation of mucosal fibroblasts in colorectal cancer with tumor-restraining characteristics 具有肿瘤抑制特征的结直肠癌粘膜成纤维细胞独特亚群的鉴定。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2025-10-01 Epub Date: 2025-08-05 DOI: 10.1016/j.mocell.2025.100263

Jamin Ku , Eunjin Jeong , Jeong-Ryeol Gong , Kwang-Hyun Cho , Chang Ohk Sung , Seok-Hyung Kim

{"title":"Identification of a unique subpopulation of mucosal fibroblasts in colorectal cancer with tumor-restraining characteristics","authors":"Jamin Ku , Eunjin Jeong , Jeong-Ryeol Gong , Kwang-Hyun Cho , Chang Ohk Sung , Seok-Hyung Kim","doi":"10.1016/j.mocell.2025.100263","DOIUrl":"10.1016/j.mocell.2025.100263","url":null,"abstract":"<div><div>While tumor-restraining cancer-associated fibroblasts (Tr-CAFs) have been investigated in various cancers, their existence in colorectal cancer remains unexplored. We performed a comprehensive analysis of diverse colorectal cancer datasets, including single-cell RNA-seq/ATAC-seq data from colorectal samples, TCGA RNA-seq, and histological samples. We identified a fibroblast subpopulation uniquely expressing ADAMDEC1, CXCL14, EDNRB, and PROCR, strongly associated with favorable patient outcomes, implicating their role as Tr-CAFs. Pseudotime trajectory analysis suggested these cells as terminally differentiated mucosal fibroblasts. Pathway analysis indicated that this subpopulation was significantly associated with tumor-suppressive functions, such as reduced extracellular matrix secretion, augmented immune response, and enhanced responsiveness to immunotherapy. Single-cell ATAC-seq analysis revealed that this putative Tr-CAF subset exhibited unique epigenetic profiles characterized by superenhancer-regulated tumor-suppressive genes, thereby supporting its identity as a stable lineage rather than a transient phenotypic state induced by external stimuli. Immunohistochemistry showed that key markers identifying this putative Tr-CAF subset—CXCL14, ADAMDEC1, EDNRB, and PROCR—were predominantly localized to fibroblasts within normal colonic mucosa and less frequently in cancer-associated fibroblasts (CAFs). Their expression levels exhibited statistically significant associations with favorable clinicopathological indicators, including prolonged disease-free survival. Notably, ADAMDEC1 expression in CAFs was significantly correlated with T-cell infiltration within the tumor microenvironment. In conclusion, our investigation elucidates the characteristics and clinical relevance of Tr-CAFs in colorectal cancer, suggesting novel avenues for targeted anti-CAF therapy.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 10","pages":"Article 100263"},"PeriodicalIF":6.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Iron metabolism dysregulation and ferroptosis: Emerging drivers in pulmonary fibrosis pathogenesis and therapy 铁代谢失调和铁下垂：肺纤维化发病机制和治疗的新驱动因素。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2025-10-01 Epub Date: 2025-08-06 DOI: 10.1016/j.mocell.2025.100264

Yawen Jiang , Ligang Zhang , Yuandong Lin , Xiangxing Zhu , Tao Wang , Zhu Zhu , Yingshan Chen , Dongsheng Tang

{"title":"Iron metabolism dysregulation and ferroptosis: Emerging drivers in pulmonary fibrosis pathogenesis and therapy","authors":"Yawen Jiang , Ligang Zhang , Yuandong Lin , Xiangxing Zhu , Tao Wang , Zhu Zhu , Yingshan Chen , Dongsheng Tang","doi":"10.1016/j.mocell.2025.100264","DOIUrl":"10.1016/j.mocell.2025.100264","url":null,"abstract":"<div><div>Ferroptosis is an iron-dependent and regulated form of cell death, characterized by lipid peroxidation and oxidative stress. The progressive development of pulmonary fibrosis (PF) is closely linked to the ferroptosis pathway. Although the underlying mechanisms remain incompletely defined, this field has drawn intense research attention. Notable progress has been made in identifying ferroptosis-related metabolic pathways and key targets during PF development. In this review, we first summarize the basic regulation of iron metabolism in the human lung, iron metabolic imbalance, and the activation of ferroptosis. Second, we focus on elaborating the mechanistic connections between ferroptosis and PF, encompassing the clinical features, pathological manifestations, and core pathogenic mechanisms of PF, as well as the interplay between ferroptosis and 3 specific cell types in PF: alveolar epithelial cells, macrophages, and fibroblasts. Third, the research progress in the pharmacotherapy of PF is categorized into 3 categories: drugs already approved for PF and those under clinical trials; ferroptosis-targeted therapeutic strategies, including inhibitors, natural compounds, gene therapy, and combination strategies. This review, grounded in key metabolic pathways and therapeutic targets, systematically explores the complex relationships among iron metabolic disorders, ferroptosis, and PF progression. Our aim is to provide a theoretical and practical foundation for ferroptosis-targeted PF treatment.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 10","pages":"Article 100264"},"PeriodicalIF":6.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Editorial Board Members/Copyright 编辑委员会成员/版权

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2025-10-01 Epub Date: 2025-09-18 DOI: 10.1016/S1016-8478(25)00104-9

引用次数: 0

Corrigendum to “SKP2 contributes to AKT activation by ubiquitination degradation of PHLPP1, impedes autophagy, and facilitates the survival of thyroid carcinoma” [Molecules and Cells Volume 46, Issue 6, June 2023, 360-373] “SKP2通过PHLPP1的泛素化降解促进AKT活化，阻碍自噬，促进甲状腺癌的存活”[molecular and Cells Volume 46, Issue 6, June 2023, 360-373]的更正。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2025-10-01 Epub Date: 2025-09-16 DOI: 10.1016/j.mocell.2025.100266

Yuan Shao , Wanli Ren , Hao Dai , Fangli Yang , Xiang Li , Shaoqiang Zhang , Junsong Liu , Xiaobao Yao , Qian Zhao , Xin Sun , Zhiwei Zheng , Chongwen Xu

引用次数: 0

Cover and caption 封面及标题

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2025-10-01 Epub Date: 2025-09-18 DOI: 10.1016/S1016-8478(25)00103-7

引用次数: 0

Role of expression quantitative trait loci (eQTL) in understanding genetic mechanisms underlying common complex diseases. 表达数量性状位点（eQTL）在理解常见复杂疾病遗传机制中的作用。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2025-09-01 Epub Date: 2025-07-18 DOI: 10.1016/j.mocell.2025.100256

Sung Eun Hong, Murim Choi, Jeongha Lee

{"title":"Role of expression quantitative trait loci (eQTL) in understanding genetic mechanisms underlying common complex diseases.","authors":"Sung Eun Hong, Murim Choi, Jeongha Lee","doi":"10.1016/j.mocell.2025.100256","DOIUrl":"10.1016/j.mocell.2025.100256","url":null,"abstract":"<p><p>Attaining a complete understanding of the genetic architecture underlying common complex traits is challenging due to the substantial contributions of nongenetic factors and the involvement of numerous influencing genes. Genome-wide association studies (GWAS) have identified novel variants associated with such traits, but our understanding of the molecular genetic mechanisms underlying those associations remains limited. Additionally, variants without significant associations from GWAS can influence gene expression, contributing to individual-level variation in traits. This review summarizes the evolution, advancements in, and practical applications of expression quantitative trait loci analysis. Recent large-scale expression quantitative trait loci studies, often at the single-cell level, provide an opportunity to explain how at least some GWAS variants behave and to elucidate the mechanisms underlying individual-level variations. This approach can further be utilized to identify novel drug targets that are tailored to individuals harboring specific genotypes.</p>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":" ","pages":"100256"},"PeriodicalIF":6.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Crucial roles of calcium ATPases and phosphoinositides: Insights into pathophysiology and therapeutic strategies 钙atp酶和磷酸肌苷的关键作用：病理生理学和治疗策略的见解。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2025-09-01 Epub Date: 2025-07-11 DOI: 10.1016/j.mocell.2025.100254

Hyun-Oh Gu , Seung Wan Noh , Ok-Hee Kim , Byung-Chul Oh

{"title":"Crucial roles of calcium ATPases and phosphoinositides: Insights into pathophysiology and therapeutic strategies","authors":"Hyun-Oh Gu , Seung Wan Noh , Ok-Hee Kim , Byung-Chul Oh","doi":"10.1016/j.mocell.2025.100254","DOIUrl":"10.1016/j.mocell.2025.100254","url":null,"abstract":"<div><div>Calcium (Ca²⁺) serves as a pivotal intracellular messenger, influencing a diverse array of cellular processes, including muscle contraction, neurotransmission, and hormone secretion. It also plays a critical role in the regulation of gene expression. Intracellular Ca²⁺ levels are stringently controlled and maintained within a narrow physiological range, primarily by plasma membrane Ca<sup>2+</sup>-ATPases, sarco-/endoplasmic reticulum Ca<sup>2+</sup>-ATPases, and secretory pathway Ca<sup>2+</sup>-ATPases. These ATPases orchestrate the influx, efflux, and sequestration of Ca²⁺ across cellular compartments, thereby ensuring cellular functionality and survival. This review delves into the intricate interplay between Ca²⁺ and phosphoinositides, essential lipid signaling molecules that modulate Ca<sup>2+</sup>-ATPase activities and link Ca²⁺ signaling to a wide range of cellular functions. By examining the molecular dynamics of Ca<sup>2+</sup>-ATPases and their regulatory interactions with phosphoinositides, we discuss their roles under both physiological and pathological conditions, highlighting how disturbances in these interactions contribute to disease. Furthermore, we explore the potential of targeting these Ca²⁺ regulatory mechanisms as a therapeutic strategy for diseases characterized by Ca²⁺ dysregulation, providing insights into future research directions and clinical applications.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 9","pages":"Article 100254"},"PeriodicalIF":6.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phosphatase regulation in cell division: With emphasis on PP2A-B56. 磷酸酶在细胞分裂中的调控：以PP2A-B56为重点。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2025-09-01 Epub Date: 2025-07-18 DOI: 10.1016/j.mocell.2025.100255

Junsoo Oh, Yeseul Park, Shinae Park, Og-Geum Woo, Jae-Hoon Lee, Jung-Shin Lee, Taekyung Kim

{"title":"Phosphatase regulation in cell division: With emphasis on PP2A-B56.","authors":"Junsoo Oh, Yeseul Park, Shinae Park, Og-Geum Woo, Jae-Hoon Lee, Jung-Shin Lee, Taekyung Kim","doi":"10.1016/j.mocell.2025.100255","DOIUrl":"10.1016/j.mocell.2025.100255","url":null,"abstract":"<p><p>Protein phosphatase 2A-B56 (PP2A-B56) is a key regulator of mitosis, playing an essential role in maintaining chromosomal stability and ensuring the fidelity of cell division. As a component of the PP2A holoenzyme, the B56 regulatory subunit confers substrate specificity, primarily through interactions with the conserved LxxIxE motif on target proteins. This review highlights the molecular mechanisms by which PP2A-B56 regulates key processes in cell division, including chromosome cohesion and condensation, kinetochore-microtubule attachment, spindle assembly checkpoint silencing, and activation of the anaphase-promoting complex/cyclosome. In meiosis, PP2A-B56 safeguards centromeric cohesion and facilitates the transition between divisions, with recruitment strategies that differ across species. Recent studies also emphasize its role in protecting oocyte quality and fertility by maintaining chromosomal stability. Furthermore, the competition among multiple LxxIxE-containing substrates for PP2A-B56 binding introduces an additional layer of temporal and spatial regulation. Finally, we discuss how perturbations in PP2A-B56 activity contribute to chromosomal instability and tumorigenesis. Understanding of PP2A-B56's substrate recognition and regulatory dynamics provides a framework for therapeutic targeting in disorders involving defective cell division.</p>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":" ","pages":"100255"},"PeriodicalIF":6.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A practical guide to ordering C. elegans strains for biological research 生物学研究中秀丽隐杆线虫菌株排序实用指南。

IF 3.7 3区生物学

Molecules and Cells Pub Date : 2025-09-01 Epub Date: 2025-07-02 DOI: 10.1016/j.mocell.2025.100251

Yeon-Ji Park , Kyeong Min Moon , Kyuhyung Kim

引用次数: 0