hLife最新文献 - Book学术

Rethinking BCG vaccine delivery for enhanced efficacy: Are two distinct routes of BCG administration better than one?

hLife Pub Date : 2025-02-01 DOI: 10.1016/j.hlife.2024.12.002

Raymond Moeketsi Moseki , Melissa Dalcina Chengalroyen

引用次数: 0

Forging paths together: The history of U.S.-China Track II Health Dialogue and the future of Chinese-American health communication

hLife Pub Date : 2025-02-01 DOI: 10.1016/j.hlife.2024.12.001

Qun Yan , Mark McClellan , Gordon G Liu , Stephen Orlins , George Fu Gao

引用次数: 0

Mechanism of microglia-mediated neuroinflammation, associated cognitive dysfunction, and therapeutic updates in Alzheimer's disease

hLife Pub Date : 2025-02-01 DOI: 10.1016/j.hlife.2024.11.006

Arpita Ghimire , Sayed Abdur Rehman , Aleena Subhani , Mansoor A Khan , Ziyaur Rahman , Mohammad Kashif Iqubal , Ashif Iqubal

{"title":"Mechanism of microglia-mediated neuroinflammation, associated cognitive dysfunction, and therapeutic updates in Alzheimer's disease","authors":"Arpita Ghimire , Sayed Abdur Rehman , Aleena Subhani , Mansoor A Khan , Ziyaur Rahman , Mohammad Kashif Iqubal , Ashif Iqubal","doi":"10.1016/j.hlife.2024.11.006","DOIUrl":"10.1016/j.hlife.2024.11.006","url":null,"abstract":"<div><div>Alzheimer's disease (AD) and associated cognitive dysfunction are major healthcare challenges globally. Various mechanisms of pathogenesis and signaling molecules have been studied for their plausible role in disease initiation and progression. Neuroinflammation has been considered a major hallmark of AD. Amyloid beta (Aβ), hyperphosphorylated tau protein, and formed neurofibrillary tangles (NFT) are positively correlated with neuroinflammation. Microglial activation was found to be a key contributor to neuroinflammation, AD pathogenesis, and progression. The mechanism of microglial activation has been studied in detail, and looking into its pivotal role in disease etiology, various drugs have been developed, and many are in the clinical phases of development. These drugs either inhibit the microglial activation or neuroinflammatory event postmicroglial activation. Considering these facts, in the present study, we herein discuss the mechanism of microglial activation and the mechanism of neuroinflammation related to microglial activation and dementia. Here we also discussed the various drugs that either act at tau protein or mitigate neuroinflammation, along with their status in clinical trials. In brief, this review provides an in-depth mechanism of microglial activation and updates on drugs that can inhibit this activation, leading to significant anti-Alzheimer effect and mitigation of cognitive dysfunction.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 2","pages":"Pages 64-81"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143402790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epigenetic regulation of cardiac tissue development by lysine lactylation

hLife Pub Date : 2025-02-01 DOI: 10.1016/j.hlife.2024.12.005

Xiaodong Luan , Runhua Du , Gengchen Su , Cong Yan , Xuelian Ren , Kaide Ju , Ye Jin , Yang An , Dan Guo , Zhuang Tian , He Huang , Shuyang Zhang

{"title":"Epigenetic regulation of cardiac tissue development by lysine lactylation","authors":"Xiaodong Luan , Runhua Du , Gengchen Su , Cong Yan , Xuelian Ren , Kaide Ju , Ye Jin , Yang An , Dan Guo , Zhuang Tian , He Huang , Shuyang Zhang","doi":"10.1016/j.hlife.2024.12.005","DOIUrl":"10.1016/j.hlife.2024.12.005","url":null,"abstract":"<div><div>Heart disease stands as the foremost global cause of mortality. In rodents, the heart possesses the remarkable ability for cardiac regeneration within the first 7 days post-birth. Furthermore, the transition to an oxygen-rich environment and altered nutrient availability trigger a profound shift in cardiac energy metabolism immediately after birth. Lactylation, which translates metabolic adjustments into enduring gene expression patterns, has been recognized for its role in this process. However, its role in heart development has remained unexplored. In this study, we conduct an integrated study combining global proteomics, lactylome, and genome-wide RNA sequencing to elucidate the role of lactylation throughout postnatal heart development. Our findings demonstrate a remarkable increase in non-histone lactylation levels as early as 1 week (1 w) to 6 weeks (6 w) postpartum and remained elevated from 6 months (6 m) onwards. However, the histone lactylation showed the opposite trend. Additionally, we propose that histone 4 lysine 12 lactylation (H4K12la) acts as a pivotal upstream regulatory element in the early postnatal mouse heart, from 1 w to 6 w postpartum. Our findings strongly suggest a significant connection between lactylation and postnatal cardiac development and highlight its involvement in gene expression regulation, thus offering potential mechanisms for targeting heart diseases.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 2","pages":"Pages 82-97"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143402791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lrrk2 promotes M1 macrophage polarization via regulating cytokine (IFN-γ) and TLR4 (LPS)-mediated responses

hLife Pub Date : 2025-02-01 DOI: 10.1016/j.hlife.2024.12.003

Yuchen Kang , Ping Gao , Xiaotong Chen , Xiaoyu Zhai , Xi Wang , Xiaojuan Han , Baoqian Jia , Baidong Hou , Xuyu Zhou , Jian Song , Fuping Zhang

{"title":"Lrrk2 promotes M1 macrophage polarization via regulating cytokine (IFN-γ) and TLR4 (LPS)-mediated responses","authors":"Yuchen Kang , Ping Gao , Xiaotong Chen , Xiaoyu Zhai , Xi Wang , Xiaojuan Han , Baoqian Jia , Baidong Hou , Xuyu Zhou , Jian Song , Fuping Zhang","doi":"10.1016/j.hlife.2024.12.003","DOIUrl":"10.1016/j.hlife.2024.12.003","url":null,"abstract":"<div><div>Leucine-rich repeat kinase 2 (<em>Lrrk2</em>) has received widespread attention as a risk gene associated with Parkinson's disease. As the immune response attributes of Parkinson's disease have been gradually revealed, the link between <em>Lrrk2</em> and the immune system has emerged. Here, we demonstrated that <em>Lrrk2</em> regulates macrophage function by promoting M1 polarization. Transcriptome and immunological analyses revealed that deletion of <em>Lrrk2</em> in macrophages leads to blunted interferon (IFN)-γ and lipopolysaccharide (LPS)-stimulated M1 macrophage-associated gene expression and function. Mechanistically, <em>Lrrk2</em> supports M1-associated immune effector signatures, including chemokines and inducible nitric oxide synthase (iNOS) expression, by enhancing signal transducer and activator of transcription 1 (STAT1) transcription factor signaling. The effect of <em>Lrrk2</em> on macrophages is dependent on its kinase activity. These results revealed a previously uncharacterized role of <em>Lrrk2</em> in M1 macrophage polarization by modulating cellular responses to cytokines and toll-like receptors (TLRs), such as IFN-γ and LPS.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 2","pages":"Pages 98-111"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143402792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diversity of reverse-transcriptase-containing viruses through global metagenomics

hLife Pub Date : 2025-01-01 DOI: 10.1016/j.hlife.2024.10.002

Kaiyang Zheng , Yantao Liang , Yan Zhang , David Páez-Espino , Hongbing Shao , Yeong Yik Sung , Wen Jye Mok , Li Lian Wong , Shi Wang , Andrew McMinn , Min Wang

引用次数: 0

Altitude adaptation: The unseen work of gut microbiota

hLife Pub Date : 2025-01-01 DOI: 10.1016/j.hlife.2024.11.004

Jingling Guo , Runzhou Zhao , Kun Li , Yafang Tan , Likun Wang , Hui Ling , Huan Zhang , Guha Dharmarajan , Yujing Bi , Ruifu Yang

{"title":"Altitude adaptation: The unseen work of gut microbiota","authors":"Jingling Guo , Runzhou Zhao , Kun Li , Yafang Tan , Likun Wang , Hui Ling , Huan Zhang , Guha Dharmarajan , Yujing Bi , Ruifu Yang","doi":"10.1016/j.hlife.2024.11.004","DOIUrl":"10.1016/j.hlife.2024.11.004","url":null,"abstract":"<div><div>High altitudes are one type of extreme environment characterized by hypobaric hypoxia, extreme cold, strong ultraviolet radiation, and low energy availabilty that present tremendous challenges to human and wildlife inhabiting these environs. These extreme environments serve as a unique natural laboratory for delving into the impact of selective pressures on species variation and adaptation. This narrative review compiles the latest research on high-altitude adaptation, with a specific focus on the crucial role of gut microbiota in this process. Evidence indicates that gut microbiota significantly impacts an organism's ability to adapt to high-altitude conditions by adjusting its composition, and hence impacting its function and ability to release microbial metabolites. We explore the link between gut microbiota and high-altitude environments, the microbial signatures, and their effects on adaptation, as well as the potential for targeted modulation of gut microbiota to enhance acclimatization to high altitudes. By examining the interaction between microbiota and host adaptation, this review aims to promote further mechanistic studies and support strategies for improving high-altitude acclimatization through gut microbiota modulation.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 1","pages":"Pages 5-20"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143137025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Drosophila Cul3 contributes to Diap2-mediated innate immune signaling for antimicrobial defense

hLife Pub Date : 2025-01-01 DOI: 10.1016/j.hlife.2024.10.001

Fanrui Kong , Zixuan Wang , Chuchu Zhang , Yihua Xiao , Muhammad Abdul Rehman Saeed , Weini Li , Akira Goto , Qingshuang Cai , Shanming Ji

{"title":"Drosophila Cul3 contributes to Diap2-mediated innate immune signaling for antimicrobial defense","authors":"Fanrui Kong , Zixuan Wang , Chuchu Zhang , Yihua Xiao , Muhammad Abdul Rehman Saeed , Weini Li , Akira Goto , Qingshuang Cai , Shanming Ji","doi":"10.1016/j.hlife.2024.10.001","DOIUrl":"10.1016/j.hlife.2024.10.001","url":null,"abstract":"<div><div>The host antimicrobial immune response relies on a complex interplay of molecular mechanisms to effectively combat microbial infections. Herein, we investigate the functional role of Cullin-3 (Cul3), one critical constituent of Cullin-RING ubiquitin ligases, in the <em>Drosophila melanogaster</em> (fruit fly) antimicrobial immune defense. We show that silencing of <em>Cul3</em> leads to a decreased induction of antimicrobial peptides and high mortality in adult flies after bacterial infection. Through biochemical approaches, we demonstrate that Cul3 predominantly relies on its BTB-binding domain and neddylation domain to physically associate with death-associated inhibitor of apoptosis 2 (Diap2). Importantly, Cul3 ameliorates the Diap2-mediated ubiquitination of death-related ced-3/Nedd2-like caspase (Dredd), a process essential for robust immune deficiency signaling upon bacterial infection. Taken together, our findings highlight a previously unrecognized regulatory axis of Cul3/Diap2/Dredd in the fly antimicrobial immune defense, providing potential insights into therapeutic strategies for combating bacterial infections in humans.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 1","pages":"Pages 38-51"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143137023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Induction of translation-suppressive G3BP1+ stress granules and interferon-signaling cGAS condensates by transfected plasmid DNA

hLife Pub Date : 2025-01-01 DOI: 10.1016/j.hlife.2024.11.005

Vladimir Majerciak, Zhi-Ming Zheng

{"title":"Induction of translation-suppressive G3BP1+ stress granules and interferon-signaling cGAS condensates by transfected plasmid DNA","authors":"Vladimir Majerciak, Zhi-Ming Zheng","doi":"10.1016/j.hlife.2024.11.005","DOIUrl":"10.1016/j.hlife.2024.11.005","url":null,"abstract":"<div><div>Plasmid DNA transfection is one of the fundamental tools of biomedical research. Here, we found that plasmid DNA transfection mediated by liposomes activates multiple innate immune responses in several widely used cell lines. Their activations were visible by the detection of stress granules (SG) and cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-DNA condensates (cGC) in the transfected cells in a plasmid DNA dose-dependent manner. The elevated levels of phosphorylated eukaryotic translation initiation factor 2 subunit alpha (eIF2α), interferon regulatory factor 3 (IRF3), and signal transducer and activator of transcription 1 (STAT1) were induced in plasmid DNA-transfected cells. The formation of SG but not cGC required active transcription and the formation of double-stranded RNA in transfected cells. Plasmid DNA-induced SG or cGC were mutually exclusive because they triggered two distinct pathways. Knockdown (KD) of protein kinase R (PKR) before plasmid DNA transfection led to abolishing SG without affecting cGC formation. Conversely, cGAS KD could prevent cGC without affecting SG formation. In addition, plasmid DNA-induced SG and cGC formation could be prevented, respectively, by co-expression of Kaposi's sarcoma-associated herpesvirus proteins ORF57 (PKR inhibitor) and ORF52 (cGAS inhibitor). Inhibition of SG formation mediated by PKR KD, but not cGC KD, also led to increased expression of transgenes, indicating that PKR activation represents a major roadblock to gene expression. Together, these data indicate that plasmid DNA triggers innate immune responses in the transfected cells and causes a significant cellular perturbation that should be considered during experiment design and data interpretation.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"3 1","pages":"Pages 21-37"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143137024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MicroRNAs unveiled: Nobel recognition of a revolutionary gene regulation mechanism

hLife Pub Date : 2025-01-01 DOI: 10.1016/j.hlife.2024.11.002

Junchao Xue , Gangming Zhang , Enzhi Shen

引用次数: 0