Molecules and Cells最新文献

英文中文

Cover and caption 封面及标题

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-08-20 DOI: 10.1016/S1016-8478(25)00091-3

引用次数: 0

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 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-08-14 DOI: 10.1016/j.mocell.2025.100265

Jee Yoon Bang , Yongjin Yoo

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.

阿尔茨海默病（AD）的小胶质细胞生物学已成为研究的主要焦点，旨在确定这些细胞如何促进神经退行性变并制定新的治疗策略。小胶质细胞曾经被认为是被动应答者，现在被认为是大脑稳态、免疫信号和突触重塑的主动调节者。它们与遗传风险变异和年龄相关变化的相互作用在AD发病机制中起着越来越重要的作用。在这篇综述中，我们总结了通过遗传和转录组学研究确定小胶质细胞对阿尔茨海默病的贡献的最新进展。我们讨论了小胶质细胞如何通过转变成不同的功能疾病相关状态来响应淀粉样蛋白-β和tau病理，这可能根据环境和疾病阶段保护或损害大脑。我们还概述了通过替代策略靶向小胶质细胞的基本原理，并回顾了使用循环来源的髓样细胞和人类多能干细胞来源的小胶质样细胞的新兴方法。这些替代方法在临床前模型中显示出矫正小胶质细胞功能和改变ad相关病理的潜力，为神经退行性疾病的治疗提供了新的方向。

{"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":"2025-08-14","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

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 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub 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

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.

铁下垂是一种铁依赖性和受调节的细胞死亡形式，以脂质过氧化和氧化应激为特征。肺纤维化（PF）的进展与铁下垂途径密切相关。尽管潜在的机制尚未完全确定，但这一领域已经引起了广泛的研究关注。在确定铁衰相关的代谢途径和PF发育过程中的关键靶点方面取得了显著进展。本文首先综述了人体肺铁代谢的基本调控、铁代谢失衡和铁下沉的激活。其次，我们重点阐述了铁沉与PF之间的机制联系，包括PF的临床特征、病理表现和核心致病机制，以及铁沉与PF中三种特定细胞类型：肺泡上皮细胞、巨噬细胞和成纤维细胞之间的相互作用。第三，将PF药物治疗的研究进展分为三类：已获批的PF药物和正在临床试验的PF药物；针对死铁的治疗策略，包括抑制剂、天然化合物、基因治疗和联合策略。本文以关键代谢途径和治疗靶点为基础，系统地探讨了铁代谢紊乱、铁下垂和PF进展之间的复杂关系。我们的目的是为针对铁中毒的PF治疗提供理论和实践基础。

{"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":"2025-08-06","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

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 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub 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

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.

虽然肿瘤抑制癌相关成纤维细胞（Tr-CAFs）在各种癌症中已被研究，但它们在结直肠癌中的存在仍未被探索。我们对不同的结直肠癌数据集进行了综合分析，包括来自结直肠癌样本的单细胞RNAseq/ATACseq数据、TCGA RNAseq数据和组织学样本。我们发现了一个独特表达ADAMDEC1、CXCL14、EDNRB和PROCR的成纤维细胞亚群，与良好的患者预后密切相关，暗示了它们作为Tr-CAFs的作用。伪时间轨迹分析提示这些细胞为终末分化的粘膜成纤维细胞。途径分析表明，该亚群与肿瘤抑制功能显著相关，如细胞外基质分泌减少、免疫反应增强和对免疫治疗的反应性增强。单细胞ATAC-seq分析显示，这个假定的Tr-CAF亚群表现出独特的表观遗传特征，其特征是超增强子调节的肿瘤抑制基因，从而支持其作为稳定谱系的身份，而不是由外部刺激诱导的短暂表型状态。免疫组织化学表明，鉴定这一推测的Tr-CAF亚群的关键标志物cxcl14、ADAMDEC1、EDNRB和procr主要定位于正常结肠黏膜内的成纤维细胞，而在癌症相关成纤维细胞（CAFs）中较少出现。它们的表达水平与有利的临床病理指标（包括延长无病生存期）有统计学上的显著相关性。值得注意的是，ADAMDEC1在CAFs中的表达与肿瘤微环境中的t细胞浸润显著相关。总之，我们的研究阐明了结直肠癌中Tr-CAFs的特征和临床相关性，为靶向抗caf治疗提供了新的途径。

{"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":"2025-08-05","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

Multifaceted role of serine hydroxymethyltransferase in health and disease 丝氨酸羟甲基转移酶在健康和疾病中的多方面作用。

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-07-28 DOI: 10.1016/j.mocell.2025.100262

Jing Zhang , Seong Eun Lee , Jiyeon Yoon , Bon Jeong Ku , Junyoung O. Park , Da Hyun Kang , Jun Young Heo , Yea Eun Kang

Serine hydroxymethyltransferase (SHMT) is a key enzyme in 1-carbon metabolism, a biochemical pathway critical for cellular growth, proliferation, and survival. One-carbon metabolism integrates the folate and methionine cycles to produce essential intermediates necessary for nucleotide synthesis, methylation reactions, and redox homeostasis. SHMT exists in 2 isoforms, SHMT1, which is localized in the cytoplasm, and SHMT2, which is localized in the mitochondria. SHMT1 and SHMT2 have distinct yet complementary functions. Both are involved in serine and glycine metabolism, ensuring a continuous supply of the 1-carbon units required for biosynthetic and epigenetic processes. SHMT dysregulation has been implicated in cancer progression and metabolic disorders, including cardiovascular diseases, diabetes, and neurological abnormalities. In cancer, the abnormal expression of SHMT has been associated with tumor growth, metabolic reprogramming, and treatment resistance, and has also been shown to correlate with poor patient outcomes. Considering its critical role in both cancer and metabolic diseases, SHMT has emerged as a potential therapeutic target in cancer. Recent studies have shown that SHMT inhibitors can reduce tumor proliferation and restore metabolic homeostasis. This review provides a comprehensive overview of the role of SHMT in the regulation of metabolic pathways and its role in tumor progression and metabolic diseases. In this review, we aimed to highlight the therapeutic potential of targeting SHMT and offer insights into the development of innovative treatment strategies in oncology and metabolic medicine. These insights support the hypothesis that targeting SHMT, particularly isoform-specific inhibition, may provide novel therapeutic avenues in both oncology and metabolic medicine.

丝氨酸羟甲基转移酶（SHMT）是单碳代谢（OCM）的关键酶，OCM是细胞生长、增殖和生存的重要生化途径。OCM整合叶酸和蛋氨酸循环，产生核苷酸合成、甲基化反应和氧化还原稳态所必需的中间体。SHMT存在两种亚型，定位于细胞质的SHMT1和定位于线粒体的SHMT2。SHMT1和SHMT2具有不同但互补的功能。两者都参与丝氨酸和甘氨酸的代谢，确保生物合成和表观遗传过程所需的单碳单位的持续供应。SHMT失调与癌症进展和代谢紊乱有关，包括心血管疾病、糖尿病和神经异常。在癌症中，SHMT的异常表达与肿瘤生长、代谢重编程和治疗耐药性有关，也被证明与不良患者预后相关。考虑到其在癌症和代谢性疾病中的重要作用，SHMT已成为癌症的潜在治疗靶点。最近的研究表明，SHMT抑制剂可以减少肿瘤增殖，恢复代谢稳态。本文综述了SHMT在调节代谢途径中的作用及其在肿瘤进展和代谢性疾病中的作用。在这篇综述中，我们旨在强调靶向SHMT的治疗潜力，并为肿瘤学和代谢医学的创新治疗策略的发展提供见解。这些见解支持了针对SHMT的假设，特别是同种异型特异性抑制，可能为肿瘤学和代谢医学提供新的治疗途径。

{"title":"Multifaceted role of serine hydroxymethyltransferase in health and disease","authors":"Jing Zhang , Seong Eun Lee , Jiyeon Yoon , Bon Jeong Ku , Junyoung O. Park , Da Hyun Kang , Jun Young Heo , Yea Eun Kang","doi":"10.1016/j.mocell.2025.100262","DOIUrl":"10.1016/j.mocell.2025.100262","url":null,"abstract":"<div><div>Serine hydroxymethyltransferase (SHMT) is a key enzyme in 1-carbon metabolism, a biochemical pathway critical for cellular growth, proliferation, and survival. One-carbon metabolism integrates the folate and methionine cycles to produce essential intermediates necessary for nucleotide synthesis, methylation reactions, and redox homeostasis. SHMT exists in 2 isoforms, SHMT1, which is localized in the cytoplasm, and SHMT2, which is localized in the mitochondria. SHMT1 and SHMT2 have distinct yet complementary functions. Both are involved in serine and glycine metabolism, ensuring a continuous supply of the 1-carbon units required for biosynthetic and epigenetic processes. SHMT dysregulation has been implicated in cancer progression and metabolic disorders, including cardiovascular diseases, diabetes, and neurological abnormalities. In cancer, the abnormal expression of SHMT has been associated with tumor growth, metabolic reprogramming, and treatment resistance, and has also been shown to correlate with poor patient outcomes. Considering its critical role in both cancer and metabolic diseases, SHMT has emerged as a potential therapeutic target in cancer. Recent studies have shown that SHMT inhibitors can reduce tumor proliferation and restore metabolic homeostasis. This review provides a comprehensive overview of the role of SHMT in the regulation of metabolic pathways and its role in tumor progression and metabolic diseases. In this review, we aimed to highlight the therapeutic potential of targeting SHMT and offer insights into the development of innovative treatment strategies in oncology and metabolic medicine. These insights support the hypothesis that targeting SHMT, particularly isoform-specific inhibition, may provide novel therapeutic avenues in both oncology and metabolic medicine.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 9","pages":"Article 100262"},"PeriodicalIF":6.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753855","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

Cover and caption 封面及标题

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-07-18 DOI: 10.1016/S1016-8478(25)00082-2

引用次数: 0

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

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-07-18 DOI: 10.1016/S1016-8478(25)00083-4

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 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-07-11 DOI: 10.1016/j.mocell.2025.100254

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

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 Ca²⁺-ATPases, sarco-/endoplasmic reticulum Ca²⁺-ATPases, and secretory pathway Ca²⁺-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 Ca²⁺-ATPase activities and link Ca²⁺ signaling to a wide range of cellular functions. By examining the molecular dynamics of Ca²⁺-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.

钙（Ca 2 +）是一种关键的细胞内信使，影响多种细胞过程，包括肌肉收缩、神经传递和激素分泌。它在基因表达调控中也起着至关重要的作用。细胞内Ca2+水平被严格控制并维持在狭窄的生理范围内，主要由质膜Ca2+-ATPases、sarco/内质网Ca2+-ATPases和分泌途径Ca2+-ATPases控制。这些atp酶协调ca2 +在细胞间的内流、外排和隔离，从而确保细胞功能和存活。这篇综述深入研究了Ca2+和磷酸肌苷（PIPs）之间复杂的相互作用，磷酸肌苷是调节Ca2+- atp酶活性的必需脂质信号分子，并将Ca2+的信号传导与广泛的细胞功能联系起来。通过研究Ca2+- atp酶的分子动力学及其与pip的调节相互作用，我们讨论了它们在生理和病理条件下的作用，强调了这些相互作用中的干扰如何导致疾病。此外，我们探索了靶向这些Ca 2 +调节机制作为Ca 2 +失调疾病的治疗策略的潜力，为未来的研究方向和临床应用提供了见解。

{"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":"2025-07-11","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

Tumor-derived CD84 promotes growth of acute myeloid leukemia cells via regulating nonhomologous DNA end-joining pathway 肿瘤源性CD84通过调节非同源DNA末端连接途径促进急性髓系白血病细胞生长。

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-07-07 DOI: 10.1016/j.mocell.2025.100253

Xiang Li , Bo Chen , Jiajing Zhou , Chunling Li , Yue Yu , Erdi Zhao , Xingli Wu , Changzhu Jin , Minjing Li , Jiankai Feng , Leilei Lin , Yancun Yin

CD84, a member of the signaling lymphocyte activation molecule immunoglobulin superfamily, has been identified as playing a significant role in regulating various immune cell activities. However, its intrinsic role in cancer cells remains largely unknown. We aim to explore the direct role of CD84 in acute myeloid leukemia (AML) progression and to clarify the underlying molecular mechanisms involved in nonhomologous end-joining (NHEJ) repair. Herein, we found that CD84 is frequently upregulated in various types of AML and leukemia initiation cells (LICs)-enriched cells. Knockdown or blocking of CD84 significantly inhibits the growth and induces the apoptosis of AML cells. Moreover, knockdown of CD84 significantly delays AML progression and prolongs the survival of the xenografted mice in vivo. Mechanistically, CD84 promotes the expression of NHEJ core factors by recruiting SAP and activating the AKT signaling pathway. Knockdown of CD84 inhibits NHEJ repair in AML cells via regulating the expression of NHEJ core factors, including PRKDC, LIG4, XRCC5, and DCLRE1C. Subsequently, this leads to double-strand breaks accumulation and cell apoptosis. Importantly, CD84 is required for the proliferation and self-renewal of human LICs. In conclusion, CD84 plays important roles in AML growth and progression through promoting NHEJ repair. Targeting CD84 may be a potential approach for inhibiting AML development and eliminating LICs.

CD84是信号淋巴细胞激活分子（signaling lymphocyte activation molecule， SLAM）免疫球蛋白超家族的一员，在调节多种免疫细胞活性中发挥着重要作用。然而，它在癌细胞中的内在作用在很大程度上仍然未知。我们的目的是探索CD84在急性髓性白血病（AML）进展中的直接作用，并阐明参与非同源末端连接（NHEJ）修复的潜在分子机制。在这里，我们发现CD84在各种类型的AML和白血病起始细胞（lic）富集的细胞中经常上调。敲低或阻断CD84可显著抑制AML细胞的生长并诱导细胞凋亡。此外，敲低CD84可显著延缓AML的进展，延长异种移植小鼠的体内存活时间。机制上，CD84通过募集SAP和激活AKT信号通路促进NHEJ核心因子的表达。敲低CD84通过调节NHEJ核心因子（包括PRKDC、LIG4、XRCC5和DCLRE1C）的表达抑制AML细胞的NHEJ修复。随后，这导致双链断裂（DSBs）积累和细胞凋亡。重要的是，CD84是人类LICs增殖和自我更新所必需的。综上所述，CD84通过促进NHEJ修复在AML的生长和进展中发挥重要作用。靶向CD84可能是抑制AML发展和消除LICs的潜在途径。

{"title":"Tumor-derived CD84 promotes growth of acute myeloid leukemia cells via regulating nonhomologous DNA end-joining pathway","authors":"Xiang Li , Bo Chen , Jiajing Zhou , Chunling Li , Yue Yu , Erdi Zhao , Xingli Wu , Changzhu Jin , Minjing Li , Jiankai Feng , Leilei Lin , Yancun Yin","doi":"10.1016/j.mocell.2025.100253","DOIUrl":"10.1016/j.mocell.2025.100253","url":null,"abstract":"<div><div>CD84, a member of the signaling lymphocyte activation molecule immunoglobulin superfamily, has been identified as playing a significant role in regulating various immune cell activities. However, its intrinsic role in cancer cells remains largely unknown. We aim to explore the direct role of CD84 in acute myeloid leukemia (AML) progression and to clarify the underlying molecular mechanisms involved in nonhomologous end-joining (NHEJ) repair. Herein, we found that CD84 is frequently upregulated in various types of AML and leukemia initiation cells (LICs)-enriched cells. Knockdown or blocking of CD84 significantly inhibits the growth and induces the apoptosis of AML cells. Moreover, knockdown of <em>CD84</em> significantly delays AML progression and prolongs the survival of the xenografted mice in vivo. Mechanistically, CD84 promotes the expression of NHEJ core factors by recruiting SAP and activating the AKT signaling pathway. Knockdown of <em>CD84</em> inhibits NHEJ repair in AML cells via regulating the expression of NHEJ core factors, including <em>PRKDC</em>, <em>LIG4</em>, <em>XRCC5</em>, and <em>DCLRE1C.</em> Subsequently, this leads to double-strand breaks accumulation and cell apoptosis. Importantly, CD84 is required for the proliferation and self-renewal of human LICs. In conclusion, CD84 plays important roles in AML growth and progression through promoting NHEJ repair. Targeting CD84 may be a potential approach for inhibiting AML development and eliminating LICs.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 9","pages":"Article 100253"},"PeriodicalIF":3.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601023","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

Cyclotides as novel plant-derived scaffolds for orally active cyclic peptide therapeutics 环肽作为口服活性环肽治疗的新型植物源支架。

IF 3.7 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-07-04 DOI: 10.1016/j.mocell.2025.100252

Youbong Hyun

Cyclotides are a group of plant-derived small peptides, characterized by a head-to-tail cyclic backbone and 3 conserved cysteine knots. The unique structure endows cyclotides with exceptional chemical stability and intrinsic cell-penetrating capacities, allowing them to serve as orally active agents for host defense. These properties also position cyclotides as ideal scaffolds for the design of novel edible drugs. This review provides a comprehensive overview of the discovery, distribution, and evolutionary divergence of cyclotides in flowering plants, while also discussing their classification and applications in structure-based engineering for various purposes. Additionally, recent advancements in the biological and pharmaceutical activities of both naturally occurring and synthetic “designer” cyclotides are summarized. The complexities of the cyclotide biosynthetic pathway have posed challenges for their synthesis in non-native organisms. Thus, the article concludes by exploring the latest strategies for large-scale cyclotide production in plants, highlighting Viola species as rich sources for future cyclotide engineering.

环肽是一组源自植物的小肽，其特征是一个首尾相连的环状主链和三个保守的半胱氨酸结。独特的结构赋予环核苷酸特殊的化学稳定性和内在的细胞穿透能力，使它们能够作为宿主防御的口服活性剂。这些特性也使环聚糖成为设计新型可食用药物的理想支架。本文综述了开花植物中环核苷酸的发现、分布和进化分化，并讨论了环核苷酸的分类及其在结构工程中的应用。此外，总结了天然存在的和合成的“设计”环核苷酸的生物和药物活性的最新进展。环肽生物合成途径的复杂性给其在非原生生物中的合成带来了挑战。因此，本文最后探讨了在植物中大规模生产环肽的最新策略，强调堇菜属是未来环肽工程的丰富来源。

{"title":"Cyclotides as novel plant-derived scaffolds for orally active cyclic peptide therapeutics","authors":"Youbong Hyun","doi":"10.1016/j.mocell.2025.100252","DOIUrl":"10.1016/j.mocell.2025.100252","url":null,"abstract":"<div><div>Cyclotides are a group of plant-derived small peptides, characterized by a head-to-tail cyclic backbone and 3 conserved cysteine knots. The unique structure endows cyclotides with exceptional chemical stability and intrinsic cell-penetrating capacities, allowing them to serve as orally active agents for host defense. These properties also position cyclotides as ideal scaffolds for the design of novel edible drugs. This review provides a comprehensive overview of the discovery, distribution, and evolutionary divergence of cyclotides in flowering plants, while also discussing their classification and applications in structure-based engineering for various purposes. Additionally, recent advancements in the biological and pharmaceutical activities of both naturally occurring and synthetic “designer” cyclotides are summarized. The complexities of the cyclotide biosynthetic pathway have posed challenges for their synthesis in non-native organisms. Thus, the article concludes by exploring the latest strategies for large-scale cyclotide production in plants, highlighting <em>Viola</em> species as rich sources for future cyclotide engineering.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 9","pages":"Article 100252"},"PeriodicalIF":3.7,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575904","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

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

Molecules and Cells

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.

﹀