Communications Biology最新文献_第9页

Mechanistic insights into alcohol-induced DNA crosslink repair by Slx4-Xpf-Ercc1 nuclease complex in the Fanconi anaemia pathway. 范可尼贫血途径中Slx4-Xpf-Ercc1核酸酶复合体诱导的DNA交联修复机制

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-26 DOI: 10.1038/s42003-025-08769-3

Jana Havlikova, Milan Dejmek, Andrea Huskova, Anthony Allan, Evzen Boura, Radim Nencka, Jan Silhan

{"title":"Mechanistic insights into alcohol-induced DNA crosslink repair by Slx4-Xpf-Ercc1 nuclease complex in the Fanconi anaemia pathway.","authors":"Jana Havlikova, Milan Dejmek, Andrea Huskova, Anthony Allan, Evzen Boura, Radim Nencka, Jan Silhan","doi":"10.1038/s42003-025-08769-3","DOIUrl":"10.1038/s42003-025-08769-3","url":null,"abstract":"Alcohol is broken down in the body into acetaldehyde, a toxic chemical that can damage DNA by creating interstrand crosslinks (AA-ICL). These crosslinks block DNA replication and threaten the stability of the genome. A rare genetic disease, Fanconi anaemia (FA), is marked by extreme sensitivity to DNA crosslinking agents, including acetaldehyde. Although the Fanconi anaemia DNA repair pathway is known to fix this type of damage, exactly how it repairs acetaldehyde crosslinks is not yet understood. Here we show that the FA nuclease Slx4-Xpf-Ercc1 (SXE) plays a key role in the repair of AA-ICL. Using a DNA replication fork with site-specific AA-ICL, we show that SXE specifically excises this crosslink, highlighting its role in the repair of alcohol-induced DNA interstrand crosslinks. Moreover, SXE performs two precise incisions flanking the AA-ICL and can similarly repair a basic-site DNA interstrand crosslink. These results expand our understanding of how the FA pathway resolves alcohol-induced DNA damage. In addition, they suggest that SXE is a versatile nuclease complex and may be involved in repairing other types of crosslinks that may activate the FA pathway.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1374"},"PeriodicalIF":5.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12475018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Multi-omics data reveal the origin of cardiac myxoma. 多组学数据揭示心脏黏液瘤的起源。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-26 DOI: 10.1038/s42003-025-08752-y

Shengzhong Liu, Wanfeng Zhang, Huajun Sun, Chenqing Zheng, Keli Huang, Chengming Fan, Rensheng Lai, Mingzhu Yin, Jie Lan, Xiushan Wu, Longke Ran, Xiaoping Li

{"title":"Multi-omics data reveal the origin of cardiac myxoma.","authors":"Shengzhong Liu, Wanfeng Zhang, Huajun Sun, Chenqing Zheng, Keli Huang, Chengming Fan, Rensheng Lai, Mingzhu Yin, Jie Lan, Xiushan Wu, Longke Ran, Xiaoping Li","doi":"10.1038/s42003-025-08752-y","DOIUrl":"10.1038/s42003-025-08752-y","url":null,"abstract":"Cardiac myxoma, the most common primary heart tumor, remains poorly understood at the molecular level. Here, we combined single-nucleus RNA sequencing, third-generation transcriptomics, and untargeted metabolomics to dissect its origin and pathology. Single-cell analyses demonstrate an endothelial origin driven by aberrant endothelial-to-mesenchymal transition (EndMT), with pseudotime and RNA-velocity tracing a continuum from endothelial-like to mesenchymal-like and metabolically active states. We identify two distinct myxoma subtypes: Subtype 1, marked by MAPK/WNT/EGFR pathway activation, and Subtype 2, characterized by ribosomal and oxidative phosphorylation signatures alongside immune-evasive programs. Third-generation data highlight extracellular matrix remodeling and endothelial signaling, while metabolomics reveal dysregulated purine, nicotinic acid, and nicotinamide metabolism. Notably, MET-PTK2 signaling emerges as a potential driver of tumor initiation and progression. These integrated findings define the cellular architecture and metabolic adaptations of cardiac myxoma and lay the foundation for future interventions.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1373"},"PeriodicalIF":5.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Zingerone treats postmenopausal osteoporosis via increased ferroptosis sensitivity by p53-mediated regulation of SAT1 and GPX4 expression. 姜酮通过p53介导的调节SAT1和GPX4的表达来增加铁下垂敏感性，从而治疗绝经后骨质疏松症。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-26 DOI: 10.1038/s42003-025-08751-z

Hao Li, Fangming Cao, Dian Liu, Lin Tao

{"title":"Zingerone treats postmenopausal osteoporosis via increased ferroptosis sensitivity by p53-mediated regulation of SAT1 and GPX4 expression.","authors":"Hao Li, Fangming Cao, Dian Liu, Lin Tao","doi":"10.1038/s42003-025-08751-z","DOIUrl":"10.1038/s42003-025-08751-z","url":null,"abstract":"Zingerone, a component of dried ginger, has known anti-ulcer and bone growth-promoting effects, but its impact on postmenopausal osteoporosis (PO) is unclear. This study investigates the therapeutic potential and underlying mechanisms of zingerone in PO. A concentration-dependent effect identified on osteoclast precursors: at low concentrations, zingerone maintains low ROS levels, enhance proliferation, and facilitates bone remodelling; at high concentrations, it elevates ROS levels, enhances ferroptosis sensitivity, and suppresses osteoclast formation. Zingerone significantly improves bone mass in an ovariectomised mouse model of PO. Metabolomics identifies 869 differential metabolites linked to glutathione and purine metabolism. Transcriptomics highlights pathways including ferroptosis, leukocyte migration, and cell adhesion. In RAW264.7 cells, zingerone modulates p53, enhances ferroptosis sensitivity, increasing ROS and Fe2+, upregulates Sat1, and downregulates Gpx4, suggesting that zingerone may act via p53-mediated ferroptosis, indicating potential clinical utility. Before clinical application, the dose-dependent effects of zingerone on bone remodelling and its underlying mechanisms warrant further investigation.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1367"},"PeriodicalIF":5.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Immunoproteasome remodeling in senescing human macrophages reveals the loss of PA28αβ capping as a hallmark of immunosenescence. 衰老的人巨噬细胞中的免疫蛋白酶体重塑揭示了PA28αβ帽的丧失是免疫衰老的标志。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-26 DOI: 10.1038/s42003-025-08765-7

Francesca Monittola, Sofia Masini, Mariele Montanari, Maria Gemma Nasoni, Marzia Bianchi, Rita De Matteis, Anastasia Ricci, Daniela Ligi, Francesca Luchetti, Barbara Canonico, Mauro Magnani, Michele Menotta, Alessandra Fraternale, Rita Crinelli

{"title":"Immunoproteasome remodeling in senescing human macrophages reveals the loss of PA28αβ capping as a hallmark of immunosenescence.","authors":"Francesca Monittola, Sofia Masini, Mariele Montanari, Maria Gemma Nasoni, Marzia Bianchi, Rita De Matteis, Anastasia Ricci, Daniela Ligi, Francesca Luchetti, Barbara Canonico, Mauro Magnani, Michele Menotta, Alessandra Fraternale, Rita Crinelli","doi":"10.1038/s42003-025-08765-7","DOIUrl":"10.1038/s42003-025-08765-7","url":null,"abstract":"Aging negatively impacts proteasome activity and/or content, and this impairment contributes to disrupted protein homeostasis and cellular dysfunction. However, little is known about proteasome complex dynamics during aging, particularly in the context of immunosenescence. Indeed, only limited data are available on the immunoproteasome, a specialized variant expressed in immune cells. We establish an in vitro model of monocyte-derived human macrophages that develop a senescence-like phenotype upon long-term culture. Our data demonstrate that immunoproteasome complexes undergo deep structural and functional alterations, with the downregulation of immunosubunit expression at the mRNA and protein level, uncapping of the 20S catalytic particle by the PA28αβ regulator, and loss of activity. Immunosubunits are partly replaced by their constitutive counterparts with a shift toward the building of 19S-capped 20S complexes to maintain proteostasis. Similar proteasome dynamics are found in the lymph nodes of aged C57BL/6 and BTBR mice, the latter of which have a naturally activated immune system. Overall, these findings propose long-term cultures of human monocyte-derived macrophages as a model to study macrophage senescence. They also provide a molecular rationale for immunoproteasome dysfunction with remodeling of the proteasome, indicating that the loss of the PA28αβ regulator is a critical event and a hallmark of immunosenescence.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1371"},"PeriodicalIF":5.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Divergent community assembly processes and multifunctionality contributions of abundant and rare soil bacteria during a 53-year restoration in the Tengger Desert, China. 腾格里沙漠53年恢复过程中丰富和稀有土壤细菌的多样性聚集过程及多功能性贡献

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-26 DOI: 10.1038/s42003-025-08764-8

Qingqing Hou, Rui Xia, Bodong Yuan, Muhammad Aqeel, Ying Sun, Longwei Dong, Abdul Manan, Fan Li, Yan Deng, Xusheng Guo, Guili Wu, Jinzhi Ran, Weigang Hu, Jihua Wu, Xinrong Li, Jianming Deng

{"title":"Divergent community assembly processes and multifunctionality contributions of abundant and rare soil bacteria during a 53-year restoration in the Tengger Desert, China.","authors":"Qingqing Hou, Rui Xia, Bodong Yuan, Muhammad Aqeel, Ying Sun, Longwei Dong, Abdul Manan, Fan Li, Yan Deng, Xusheng Guo, Guili Wu, Jinzhi Ran, Weigang Hu, Jihua Wu, Xinrong Li, Jianming Deng","doi":"10.1038/s42003-025-08764-8","DOIUrl":"10.1038/s42003-025-08764-8","url":null,"abstract":"Soil microbial communities play vital roles in driving ecosystem restoration. However, understanding of the successional dynamics of abundant and rare bacterial subcommunities and their relationships with ecosystem multifunctionality during restoration, particularly in desertified ecosystems, remains limited. Here, we examined the succession of abundant, intermediate, and rare bacterial subcommunities over a 53-year restoration chronosequence following the implementation of straw checkerboard barriers in the Tengger Desert, China. Our findings revealed that the establishment of straw checkerboard barriers significantly increased the richness of abundant, intermediate, and rare taxa over time. However, our results indicated a divergence in ecological processes underpinning the successional dynamics of soil bacterial communities. Stochastic processes and homogeneous selection primarily governed the assembly of abundant and rare subcommunities, respectively, as evidenced by fundamental differences in their niche breadth. More importantly, we further uncovered a dual mechanism underlying the relationships between soil bacterial communities and ecosystem multifunctionality. Abundant taxa were integrally associated with multiple nutrient cycling-related functions simultaneously, likely mediated through coordinated environmental responses or potential interspecies connections, whereas rare taxa were more linked to individual functions independently. These findings deepen our understanding of the successional dynamics of soil microbial communities and the microbe-ecosystem multifunctionality relationships in desert restoration.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1376"},"PeriodicalIF":5.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Demography and adaptation of a species specific pollinator associated with an invasive fig tree. 入侵无花果树特有传粉媒介的人口统计学和适应性。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-26 DOI: 10.1038/s42003-025-08733-1

Li-Hua Wu, Jie Zou, Yu-Ting Jiang, Ling Lu, Kai Jiang, Kai-Jian Zhang, Wei-Chao Liu, Wei-Min Xiang, Gang Wang, Simon T Segar, Simon van Noort, Yuan-Yuan Li, Yuan-Ye Zhang, Xiao-Yong Chen, Stephen G Compton, Rong Wang

{"title":"Demography and adaptation of a species specific pollinator associated with an invasive fig tree.","authors":"Li-Hua Wu, Jie Zou, Yu-Ting Jiang, Ling Lu, Kai Jiang, Kai-Jian Zhang, Wei-Chao Liu, Wei-Min Xiang, Gang Wang, Simon T Segar, Simon van Noort, Yuan-Yuan Li, Yuan-Ye Zhang, Xiao-Yong Chen, Stephen G Compton, Rong Wang","doi":"10.1038/s42003-025-08733-1","DOIUrl":"10.1038/s42003-025-08733-1","url":null,"abstract":"Some fig species introduced outside of their native range have become invasive when colonized by their obligate pollinating wasps, but how these pollinators migrated and adapted to novel environments are less studied. Here, we focus on Eupristina verticillata, the obligate pollinating wasp of an invasive fig tree species (Ficus microcarpa), to uncover its demography and the molecular basis for adaptations to novel environments. We find that only one of the three cryptic species colonized in the sampling locations outside of its native range. This dominant cryptic species migrated simultaneously from the native range to the Americas and to the Mediterranean c. 130 years ago. Moreover, selective sweep analyses reveal several positively selected genes associated with adaptations to the nonnative range. Genome-wide association detect a nonsynonymous substitution in a dopamine N-acetyltransferase gene significantly linked with brood size. Our study outlines the route to colonization and genetic adaptations of an invasive mutualism.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1363"},"PeriodicalIF":5.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12475197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Arabidopsis MYB47 and MYB95 transcription factors regulate jasmonate-inducible ER-body formation. 拟南芥MYB47和MYB95转录因子调控茉莉素诱导的er小体形成。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-26 DOI: 10.1038/s42003-025-08863-6

Jakub Bizan, Shayan Sarkar, Arpan Kumar Basak, Subhankar Bera, Shino Goto-Yamada, Kaichiro Endo, Katarzyna Tarnawska-Glatt, Rituraj Batth, Kritika Bhardwaj, Mohamadreza Mirzaei, Paweł Czerniawski, Paweł Bednarek, Kenji Yamada

{"title":"Arabidopsis MYB47 and MYB95 transcription factors regulate jasmonate-inducible ER-body formation.","authors":"Jakub Bizan, Shayan Sarkar, Arpan Kumar Basak, Subhankar Bera, Shino Goto-Yamada, Kaichiro Endo, Katarzyna Tarnawska-Glatt, Rituraj Batth, Kritika Bhardwaj, Mohamadreza Mirzaei, Paweł Czerniawski, Paweł Bednarek, Kenji Yamada","doi":"10.1038/s42003-025-08863-6","DOIUrl":"10.1038/s42003-025-08863-6","url":null,"abstract":"Endoplasmic reticulum (ER)-derived subcellular structures, namely ER bodies, are involved in glucosinolate-based chemical defense against insect pests and pathogenic fungi in the Brassicaceae family. In Arabidopsis thaliana, treatment of rosette leaves with the wounding hormone jasmonate (JA) induces β-GLUCOSIDASE 18 (BGLU18) and TSK-ASSOCIATING PROTEIN 1 (TSA1) gene expression, whose products accumulate in JA-inducible ER bodies; however, the underlying transcriptional regulatory mechanisms remain unknown. Here, we show that two paralogous Arabidopsis MYBs, namely MYB47 and MYB95, regulate TSA1 and BGLU18 expression and ER-body formation in response to JA. MYB47 and MYB95 bind to and activate the TSA1 promoter. TSA1 and BGLU18 expression levels are reduced in the JA-treated rosette leaves of myb47,95 mutants, suggesting that these MYBs play a key role in the activation of these genes. Transcriptome analysis reveals that MYB47 and MYB95 regulate a subset of JA-responsive genes, including ER-body and defense-related genes. Phylogenetic analysis shows that MYB47 and MYB95 belong to a MYB subfamily unique to the Brassicales order. Together, our findings indicate that MYB47 and MYB95 have evolved to regulate unique downstream target genes in response to JA, which include JA-inducible ER body genes important for protecting plants from fungal and herbivore attacks in Brassicaceae.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1377"},"PeriodicalIF":5.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12475115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Archaic adaptive introgression in modern human reproductive genes. 现代人类生殖基因中古老的适应性渗入。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-26 DOI: 10.1038/s42003-025-08682-9

Christopher Kendall, Amin Nooranikhojasteh, Esteban J Parra, Michael A Schillaci, Bence Viola

{"title":"Archaic adaptive introgression in modern human reproductive genes.","authors":"Christopher Kendall, Amin Nooranikhojasteh, Esteban J Parra, Michael A Schillaci, Bence Viola","doi":"10.1038/s42003-025-08682-9","DOIUrl":"10.1038/s42003-025-08682-9","url":null,"abstract":"Modern humans and archaic hominins, namely Denisovans and Neanderthals, have a long history of admixture. Some of these admixture events have allowed modern humans to adapt to new environments outside of Africa. Little research has been done on the impact of archaic introgression on genes associated with reproduction. In this study we report evidence of adaptive introgression of 118 genes within modern humans that have been previously associated with reproduction in mice or modern humans. We identified 11 archaic core haplotypes, three that have been positively selected, with 327 archaic alleles being genome-wide significant for a variety of traits. Over 300 of these variants were discovered to be eQTLs regulating 176 genes with 81% of the archaic eQTLs overlapping a core haplotype region regulating genes expressed in reproductive tissues. Several of the adaptively introgressed genes in our results are enriched in developmental and cancer pathways, while some have been associated with embryo development and reproductive-inhibiting phenotypes like endometriosis and preeclampsia. Lastly, we find that archaic alleles overlapping an introgressed segment on chromosome 2 are protective against prostate cancer. Our results highlight that archaic alleles show connections with important developmental pathways throughout the lifespan and may help regulate these critical processes.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1365"},"PeriodicalIF":5.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Genetic mapping of complement system proteins for islet autoimmunity in children with high risk of T1D. T1D高危儿童胰岛自身免疫的补体系统蛋白遗传定位

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-26 DOI: 10.1038/s42003-025-08739-9

Xiaowei Hu, Bobbie-Jo M Webb-Robertson, Hemang M Parikh, Ernesto S Nakayasu, Suna Onengut-Gumuscu, Wei-Min Chen, Ashley Frazer-Abel, Thomas O Metz, Stephen S Rich, Marian J Rewers, Ani Manichaikul

{"title":"Genetic mapping of complement system proteins for islet autoimmunity in children with high risk of T1D.","authors":"Xiaowei Hu, Bobbie-Jo M Webb-Robertson, Hemang M Parikh, Ernesto S Nakayasu, Suna Onengut-Gumuscu, Wei-Min Chen, Ashley Frazer-Abel, Thomas O Metz, Stephen S Rich, Marian J Rewers, Ani Manichaikul","doi":"10.1038/s42003-025-08739-9","DOIUrl":"10.1038/s42003-025-08739-9","url":null,"abstract":"Recent studies have reported the involvement of complement system proteins in the initiation and progression of islet autoimmunity (IA) in the study of Type 1 diabetes (T1D). However, the genetic factors of complement system proteins at the time of triggering of IA are unknown. Through complement system protein quantitative trait locus (pQTL) mapping discovery analysis of 170 participants from the Diabetes Autoimmunity Study in the Young (DAISY) and replication analysis of 385 IA cases from The Environment Determinants of Diabetes in the Young (TEDDY) study, we identify 68 significant pQTLs in total for C8A, C8B, CFB, C4A, and MBL2. Furthermore, all replicated pQTLs of CFB and C4A are previously reported to be associated with T1D risk. Our study provides evidence for the potential biological roles of complement system proteins in the etiology of IA and T1D for young children at high risk of developing T1D.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1366"},"PeriodicalIF":5.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12475137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Isolation, characterization and testing of RNA aptamers targeting glutamate receptors in a rat spinal cord injury pain model. 大鼠脊髓损伤疼痛模型中针对谷氨酸受体的RNA适配体的分离、表征和检测。

IF 5.1 1区生物学

Communications Biology Pub Date : 2025-09-26 DOI: 10.1038/s42003-025-08772-8

Stanislava Jergova, Zhen Huang, Chi-Yen Lin, Megumi Akamatsu, Jacqueline Sagen, Li Niu

{"title":"Isolation, characterization and testing of RNA aptamers targeting glutamate receptors in a rat spinal cord injury pain model.","authors":"Stanislava Jergova, Zhen Huang, Chi-Yen Lin, Megumi Akamatsu, Jacqueline Sagen, Li Niu","doi":"10.1038/s42003-025-08772-8","DOIUrl":"10.1038/s42003-025-08772-8","url":null,"abstract":"Spinal cord injury (SCI)-induced neuropathic pain remains difficult to treat. Given the high risk of using opioid analgesics as a primary treatment option, developing non-opioid therapeutic candidates is desirable. Studies in preclinical pain models have shown that antagonists of the ionotropic glutamate receptors (iGluRs) can inhibit pain without abuse potential. Here we report the first study of making and testing a group of RNA aptamers that inhibit iGluRs in a rat SCI pain model. Our results show that aptamers are efficacious in alleviating evoked and ongoing neuropathic symptoms in rats without any significant adverse effects. Furthermore, the antinociceptive efficacy of RNA aptamers on both tactile and cold hypersensitivity becomes steadily strengthened during repeated aptamer administrations and the antinociceptive protection persists for 2-3 extra weeks after the termination of intrathecal injection of aptamers. We also note potential sex differences in aptamer treatment, suggesting the possibility of tailoring the use of aptamers in sex-specific pain treatment. This study demonstrates that developing aptamers targeting iGluRs, especially kainate receptors, as potential analgesic candidates for treatment of SCI-induced pain, is promising.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"1375"},"PeriodicalIF":5.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12475499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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