Human molecular genetics最新文献_第3页

Editorial: recent advances in molecular genetics shine new light on immune disorders and infection. 社论：分子遗传学的最新进展为免疫疾病和感染提供了新的线索。

IF 3.2 2区生物学

Human molecular genetics Pub Date : 2025-10-07 DOI: 10.1093/hmg/ddaf105

Michaela U Gack, Thirumala-Devi Kanneganti

引用次数: 0

The dynamic interactions between virus infections and nonsense-mediated decay. 病毒感染与无义介导的衰变之间的动态相互作用。

IF 3.2 2区生物学

Human molecular genetics Pub Date : 2025-10-07 DOI: 10.1093/hmg/ddae151

Teun van der Klugt, Michiel van Gent

引用次数: 0

An overview of host immune responses against Leishmania spp. infections. 宿主对利什曼原虫感染的免疫反应综述。

IF 3.2 2区生物学

Human molecular genetics Pub Date : 2025-10-07 DOI: 10.1093/hmg/ddaf043

Hanna Paton, Prabuddha Sarkar, Prajwal Gurung

引用次数: 0

Recent insights into the role of innate immunity in lupus. 先天免疫在狼疮中的作用。

IF 3.2 2区生物学

Human molecular genetics Pub Date : 2025-10-07 DOI: 10.1093/hmg/ddaf066

Lauren A Robinson, Virginia Pascual

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Three decades of caspases and RIPKs in life and death. 30年来半胱天冬酶和RIPKs的生死关系。

IF 3.2 2区生物学

Human molecular genetics Pub Date : 2025-10-07 DOI: 10.1093/hmg/ddaf106

R K Subbarao Malireddi, Thirumala-Devi Kanneganti

{"title":"Three decades of caspases and RIPKs in life and death.","authors":"R K Subbarao Malireddi, Thirumala-Devi Kanneganti","doi":"10.1093/hmg/ddaf106","DOIUrl":"10.1093/hmg/ddaf106","url":null,"abstract":"Caspases and RIPKs are critical regulators of life and death. These molecules have roles in innate immunity and cell death that drive host defense, development, and tumor immunity, but their activation can also contribute to aberrant inflammation and inflammatory disease. This review revisits three decades of genetic studies that have elucidated the critical functions of caspases and RIPKs, synthesizing seminal findings in development, lytic cell death pathways, inflammation, disease pathology, and therapeutic innovation. These studies have led to the paradigm-shifting concept of PANoptosis, defined as an innate immune, inflammatory cell death pathway initiated by innate immune sensors and driven by caspases and RIPKs through PANoptosome complexes. PANoptosis can occur in response to pathogens, pathogen- and damage-associated molecular patterns, homeostatic alterations, cytokines, and the lytic cell death of surrounding cells. Caspase-8 has emerged as a critical core component of PANoptosomes, with other caspases and RIPKs also being key to the molecular activation of PANoptosis. Further genetic studies have established the significance of caspases and RIPKs, including their role in PANoptosis, across the disease spectrum, in infections, inflammatory conditions, cytokine storm, and cancer. Collectively, genetic and biochemical evidence suggests that targeting PANoptosome pathway molecules, including innate immune sensors, caspases, and RIPKs, provides a promising therapeutic strategy for a wide range of conditions, such as neurodegeneration, metabolic disorders, cancers, and chronic inflammatory or autoimmune diseases.","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"R121-R136"},"PeriodicalIF":3.2,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12393794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Dual faces of itaconate and its derivatives: exploring diverse biological functions in immunity and infectious diseases. 衣康酸及其衍生物的双重面目：探索免疫和传染病的多种生物学功能。

IF 3.2 2区生物学

Human molecular genetics Pub Date : 2025-10-07 DOI: 10.1093/hmg/ddae177

Cecilie Poulsen, Dominic G Roy, David Olagnier

引用次数: 0

Mouse models of type I interferonopathies. ⅰ型干扰素病变的小鼠模型。

IF 3.2 2区生物学

Human molecular genetics Pub Date : 2025-10-07 DOI: 10.1093/hmg/ddae187

Domnica Luca, Hiroki Kato

引用次数: 0

Macrophages: sentinels, warriors, and healers. 巨噬细胞：哨兵、战士和治疗者。

IF 3.2 2区生物学

Human molecular genetics Pub Date : 2025-10-07 DOI: 10.1093/hmg/ddaf087

Eduardo D Bernier, Eric Bartnicki, Kamal M Khanna

{"title":"Macrophages: sentinels, warriors, and healers.","authors":"Eduardo D Bernier, Eric Bartnicki, Kamal M Khanna","doi":"10.1093/hmg/ddaf087","DOIUrl":"10.1093/hmg/ddaf087","url":null,"abstract":"Macrophages are versatile innate immune cells that act as sentinels, warriors, and healers in virtually every tissue. This review synthesizes current insights into their developmental origins and the organ-specific cues that imprint diverse tissue-resident and monocyte-derived programs. We detail how pattern-recognition pathways, metabolic and epigenetic rewiring, and environmental signals govern macrophage plasticity, steering transitions between pro-inflammatory and reparative phenotypes during homeostasis, infection, and sterile injury. Dysregulated macrophage responses drive chronic inflammatory, autoimmune, metabolic, neurodegenerative, and neoplastic diseases; inter-individual variability rooted in genetic polymorphisms and enhancer landscapes further modulates susceptibility. Advances in single-cell and spatial multi-omics are redefining macrophage subsets and exposing disease-associated states, while approaches such as checkpoint blockade, chimeric antigen receptor macrophages, nanoparticles, metabolic modulators, and pro-resolving mediators showcase the therapeutic promise of re-programming these cells. Remaining challenges include integrating the layered genetic, metabolic, and microenvironmental inputs that dictate macrophage fate. Addressing these gaps will unlock precision strategies that harness macrophage plasticity to combat infection, resolve inflammation, repair tissue, and augment anti-tumor immunity.","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"R110-R120"},"PeriodicalIF":3.2,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Spatiotemporal regulation of neutrophil heterogeneity in health and disease. 中性粒细胞异质性在健康和疾病中的时空调节。

IF 3.2 2区生物学

Human molecular genetics Pub Date : 2025-10-07 DOI: 10.1093/hmg/ddaf008

Jingu Lee, Bo-Ram Jin, Jaehyung Cho

引用次数: 0

A synonymous single nucleotide variant on the FAM20C gene causes non-lethal Raine syndrome. FAM20C基因上的同义单核苷酸变异导致非致命性雷恩综合征。

IF 3.2 2区生物学

Human molecular genetics Pub Date : 2025-10-05 DOI: 10.1093/hmg/ddaf129

Bayram Toraman, İdris Er, Burak Kaan Kasap, Ümit Uzun, Tuba Dinçer, Gökhan Yıldız, Gülay Karagüzel, Saadettin Kayipmaz, Ersan Kalay

{"title":"A synonymous single nucleotide variant on the FAM20C gene causes non-lethal Raine syndrome.","authors":"Bayram Toraman, İdris Er, Burak Kaan Kasap, Ümit Uzun, Tuba Dinçer, Gökhan Yıldız, Gülay Karagüzel, Saadettin Kayipmaz, Ersan Kalay","doi":"10.1093/hmg/ddaf129","DOIUrl":"10.1093/hmg/ddaf129","url":null,"abstract":"Raine syndrome (RNS) is an autosomal recessive neonatal osteosclerotic bone dysplasia that usually results in death in the postnatal period. Patients present with abnormal craniofacial features and widespread periosteal osteosclerosis affecting the ribs, skull, and long bones. Nonlethal forms of RNS have recently been reported. Biallelic mutations in the FAM20C gene, which encodes a Golgi serine/threonine protein kinase that phosphorylates secretory pathway proteins, are responsible for RNS. In this study, we examined a Turkish family consisting of three patients by exome sequencing and found that the homozygous c.1071A > G transition at the second-to-last position of the 5' end of exon 5 gave rise to a synonymous variant (p.P357P) in FAM20C. Subsequent mRNA (cDNA) sequencing of FAM20C showed that the c.1071A > G substitution disrupted the splice junction and directed the splicing to a new location in intron 5, resulting in an in-frame 12 amino acid insertion into the protein. FAM20C is a serine/threonine protein kinase that localizes to the Golgi apparatus by forming a homo- or hetero-dimer and/or is secreted from the cell to phosphorylate secretory proteins. Functional analysis showed that the identified insertion did not disrupt either homo- or hetero-dimerization of the FAM20C protein. However, this variant protein failed to localize properly to the Golgi apparatus and exhibited poor secretion from the cell. All these findings suggest that the identified variant causing the 12 amino acid insertion is responsible for the nonlethal form of RNS in the family and provides mechanistic insight into the molecular pathogenesis of RNS.","PeriodicalId":13070,"journal":{"name":"Human molecular genetics","volume":" ","pages":"1693-1704"},"PeriodicalIF":3.2,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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