Molecules and Cells最新文献_第4页

Deficient chaperone-mediated autophagy in macrophages aggravates colitis and colitis-associated tumorigenesis in mice 巨噬细胞伴蛋白介导的自噬缺陷加重小鼠结肠炎和结肠炎相关肿瘤发生。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2025-12-01 Epub Date: 2025-11-12 DOI: 10.1016/j.mocell.2025.100298

Weichun Zhu , Zehao Chen , Yunqian Gao , Chungang Zhai , Xia Li , Ning Wang , Kang Fu , Wentao Chen , Jieqiong Peng , Dan Xu , Lei Qiao , Wenqiang Chen

{"title":"Deficient chaperone-mediated autophagy in macrophages aggravates colitis and colitis-associated tumorigenesis in mice","authors":"Weichun Zhu , Zehao Chen , Yunqian Gao , Chungang Zhai , Xia Li , Ning Wang , Kang Fu , Wentao Chen , Jieqiong Peng , Dan Xu , Lei Qiao , Wenqiang Chen","doi":"10.1016/j.mocell.2025.100298","DOIUrl":"10.1016/j.mocell.2025.100298","url":null,"abstract":"<div><div>Chaperone-mediated autophagy (CMA) is a highly selective form of autophagy responsible for the degradation of specific cytosolic proteins within lysosomes. Recent research has established a significant correlation between CMA and colorectal cancer (CRC). However, the majority of current research focuses on tumor parenchymal cells, with limited attention paid to the expression and role of CMA in tumor stromal cells, particularly in tumor-associated macrophages (TAMs). In this study, we generated myeloid-specific LAMP2A-knockout and knock-in mice to investigate the role of macrophage CMA in dextran sodium sulfate (DSS)-induced colitis and azoxymethane/dextran sodium sulfate-induced CRC. Our findings indicated that the expression of LAMP2A, the rate-limiting component of CMA, was reduced in tumor-associated macrophages of both human and mouse CRC tissues. The knockout of LAMP2A in macrophages exacerbated experimentally induced colitis and colitis-related CRC, whereas its overexpression in macrophages alleviated the progression of colitis and CRC in mice. Notably, we observed increased angiogenesis within the tumor mass of CRC tissues from LAMP2A-mØKO mice. Mechanistically, LAMP2A deficiency elevated the protein levels of HIF-1α, thereby enhancing the secretion of its target genes, vascular endothelial growth factor A and IL-1β, which are 2 important proangiogenic cytokines. Our study suggests that the activation of CMA in macrophages may represent a promising therapeutic strategy for the treatment of CRC.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 12","pages":"Article 100298"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523929","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

Response to comments by Kong et al. 对Kong等人评论的回应。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2025-12-01 Epub Date: 2025-10-17 DOI: 10.1016/j.mocell.2025.100288

Hoyun Kwak , Wijin Jeon , Nui Ha , Soon-Gu Kwon , Jae Young Seong

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Brief guide to western blot assays western blot检测的简要指南。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2025-12-01 Epub Date: 2025-11-06 DOI: 10.1016/j.mocell.2025.100297

Seokjun G. Ha, Ji-Hoon Park, Mi-Young Kim, Seung-Jae V. Lee

引用次数: 0

Egr2-dependent Mo-DCs regulate immunosuppressive NK cells, promoting neutrophil-mediated protective immunity against acute Listeria infection egr2依赖性mo - dc调节免疫抑制性NK细胞，促进中性粒细胞介导的抗急性李斯特菌感染的保护性免疫。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2025-12-01 Epub Date: 2025-10-16 DOI: 10.1016/j.mocell.2025.100287

Muhammad Umer Ashraf , Myeong-Ho Kang , Yong Taik Lim , Siyoung Yang , Yong-Soo Bae

{"title":"Egr2-dependent Mo-DCs regulate immunosuppressive NK cells, promoting neutrophil-mediated protective immunity against acute Listeria infection","authors":"Muhammad Umer Ashraf , Myeong-Ho Kang , Yong Taik Lim , Siyoung Yang , Yong-Soo Bae","doi":"10.1016/j.mocell.2025.100287","DOIUrl":"10.1016/j.mocell.2025.100287","url":null,"abstract":"<div><div>The interactions between dendritic cells (DCs) and other innate immune cells during acute bacterial infection remain poorly understood. To investigate this cross-talk, we generated CD11c-cre-mediated early growth response gene-2 knockout (Egr2<sup>cKO</sup>) mice and used an acute <em>Listeria monocytogenes</em> (LM) infection model. In wild-type mice, LM infection induced the generation of monocyte-derived DCs (Mo-DCs), which suppressed the conversion of natural killer (NK) cells into immunosuppressive NK cells, while Mo-DC-derived TNF-α enhanced neutrophil (NP) activity to control infection. In contrast, Egr2<sup>cKO</sup> mice exhibited significantly increased susceptibility to LM infection compared with their Egr2-floxed wild-type littermates, primarily due to a deficiency in Mo-DCs. Instead, monocytes in Egr2<sup>cKO</sup> mice differentiated predominantly into macrophages, which expressed interleukin-15/interleukin-15R and promoted the expansion of immunosuppressive CD11b<sup>low</sup>CD27<sup>+</sup>TIGIT<sup>+</sup> NK cells. These NK cells produced TGF-β, thereby suppressing NP-mediated NETosis. In vivo depletion of NK cells in Egr2<sup>cKO</sup> mice partially restored protective immunity, whereas depletion of NPs further exacerbated susceptibility to LM infection. In conclusion, our study demonstrates that Egr2-dependent Mo-DCs play a pivotal role in host defense against acute LM infection by restraining the expansion of immunoregulatory NK cells and enhancing TNF-α-mediated NPs NETosis. These findings highlight the Mo-DC/NK/NP immune axis as a key element of the innate immune response to acute bacterial infection.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 12","pages":"Article 100287"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318437","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

Ionotropic receptors mediate arachidic acid perception and food avoidance behavior in Drosophila melanogaster 嗜离子受体介导黑腹果蝇花生酸感知和食物回避行为。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2025-12-01 Epub Date: 2025-11-03 DOI: 10.1016/j.mocell.2025.100290

Roshani Nhuchhen Pradhan, Muhammad Atif, Youngseok Lee

引用次数: 0

Letter by Kong et al. Regarding Article, “Is FAM19A5 an adipokine? Peripheral FAM19A5 in wild-type, FAM19A5 knockout, and LacZ knockin mice” Kong等人的信。关于文章《FAM19A5是脂肪因子吗？》外周FAM19A5野生小鼠、FAM19A5敲除小鼠和LacZ敲入小鼠”。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2025-12-01 Epub Date: 2025-10-22 DOI: 10.1016/j.mocell.2025.100289

Wei Kong

引用次数: 0

Approaches to murine T cell isolation and activation 小鼠T细胞的分离和激活方法。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2025-12-01 Epub Date: 2025-10-14 DOI: 10.1016/j.mocell.2025.100286

Sangjun Lim , Sohyun Kum , Jin Ouk Choi , Joonbeom Bae , Soo Seok Hwang

引用次数: 0

THRAISE: An automated and reproducible web platform for RNA-seq analysis THRAISE：用于RNA-seq分析的自动化和可重复的网络平台。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2025-12-01 Epub Date: 2025-11-13 DOI: 10.1016/j.mocell.2025.100299

Hyeon Ho Heo, Soo-Jong Um

引用次数: 0

Recent preclinical and clinical advances in gene therapy for hereditary hearing loss 基因治疗遗传性听力损失的临床前和临床进展。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2025-12-01 Epub Date: 2025-10-12 DOI: 10.1016/j.mocell.2025.100285

Seung Hyun Jang , Hyeong Gi Song , Jinsei Jung , Heon Yung Gee

{"title":"Recent preclinical and clinical advances in gene therapy for hereditary hearing loss","authors":"Seung Hyun Jang , Hyeong Gi Song , Jinsei Jung , Heon Yung Gee","doi":"10.1016/j.mocell.2025.100285","DOIUrl":"10.1016/j.mocell.2025.100285","url":null,"abstract":"<div><div>Hereditary hearing loss is a genetically heterogeneous condition that affects millions of people worldwide and has limited curative treatment options. Recent advancements in gene therapy have opened promising avenues for correcting the underlying genetic defects in the inner ear. This review summarizes the key developments in vector platforms, delivery strategies, target genes, preclinical models, and clinical trials relevant to both gene supplementation and gene editing approaches, as well as future directions. Adeno-associated virus vectors have emerged as the leading platform for inner ear gene transfer, owing to their safety and efficacy. Clinical programs, such as those targeting <em>OTOF</em> variants, are currently underway and are supported by robust preclinical data. Additionally, genome editing technologies, including CRISPR/Cas9-mediated nonhomologous end joining, base editing, and prime editing, offer variant-specific therapeutic potential. Despite these advances, challenges remain in expanding the therapeutic window, ensuring long-term safety, and establishing ethical and regulatory frameworks for their use.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 12","pages":"Article 100285"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292885","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

GOREA: Unbiased Interpretation of Functional Enrichment 基因本体富集的系统和公正解释框架。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2025-11-01 Epub Date: 2025-09-24 DOI: 10.1016/j.mocell.2025.100283

Hojin Lee, Young-In Park, Ina Jeon, Dawon Kang, Harim Chun, Jungmin Choi

{"title":"GOREA: Unbiased Interpretation of Functional Enrichment","authors":"Hojin Lee, Young-In Park, Ina Jeon, Dawon Kang, Harim Chun, Jungmin Choi","doi":"10.1016/j.mocell.2025.100283","DOIUrl":"10.1016/j.mocell.2025.100283","url":null,"abstract":"<div><div>Functional enrichment analysis is essential for extracting biological meaning from gene expression data. Gene set enrichment analysis (GSEA) and over-representation analysis (ORA) are widely used approaches for this purpose. However, interpreting the large number of enriched gene ontology biological process (GOBP) terms remains challenging. Existing tools such as simplifyEnrichment often yield overly general and fragmented keywords, and they do not effectively utilize quantitative metrics such as normalized enrichment scores (NES) or gene overlap proportions, thereby limiting biological interpretation and prioritization. To address these issues, we developed GOREA, an improved tool for summarizing GOBP terms. GOREA improves upon simplifyEnrichment by integrating binary cut and hierarchical clustering, incorporating GOBP term hierarchy to define representative terms, and ranking clusters based on NES or gene overlap proportions. Using ComplexHeatmap R package, GOREA visualizes results as a heatmap accompanied by a panel of broad GOBP terms and representative terms for each cluster, providing both general and specific biological insights. Compared to simplifyEnrichment, GOREA yields more specific and interpretable clusters while significantly reducing computational time. GOREA effectively identified distinct biological processes in immune-related data and revealed substantial overlap between GOBP terms and cancer hallmark gene sets, demonstrating its applicability across diverse biological contexts. These findings suggest that GOREA provides a substantial improvement over existing approaches and offers a scalable and efficient framework for GSEA and ORA across diverse biological contexts.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 11","pages":"Article 100283"},"PeriodicalIF":6.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176824","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