Cell Reports Medicine最新文献_第9页

Impact of antimicrobials on penile HIV susceptibility and immunology in uncircumcised men: A randomized phase 1/2 clinical trial. 抗菌药物对未行包皮环切术男性阴茎 HIV 易感性和免疫学的影响：1/2期随机临床试验。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-09-17 Epub Date: 2024-08-29 DOI: 10.1016/j.xcrm.2024.101705

Ronald M Galiwango, Brenda Okech, Daniel E Park, Lane Buchanan, Zhongtian Shao, Bernard Bagaya, Juliet Mpendo, Vineet Joag, Sergey Yegorov, Annet Nanvubya, Victoria M Biribawa, Teddy Namatovu, Charles Kato, Barbara Kawoozo, Ali Ssetaala, Moses Muwanga, Maliha Aziz, Tony Pham, Sanja Huibner, Aaron A R Tobian, Cindy M Liu, Jessica L Prodger, Rupert Kaul

{"title":"Impact of antimicrobials on penile HIV susceptibility and immunology in uncircumcised men: A randomized phase 1/2 clinical trial.","authors":"Ronald M Galiwango, Brenda Okech, Daniel E Park, Lane Buchanan, Zhongtian Shao, Bernard Bagaya, Juliet Mpendo, Vineet Joag, Sergey Yegorov, Annet Nanvubya, Victoria M Biribawa, Teddy Namatovu, Charles Kato, Barbara Kawoozo, Ali Ssetaala, Moses Muwanga, Maliha Aziz, Tony Pham, Sanja Huibner, Aaron A R Tobian, Cindy M Liu, Jessica L Prodger, Rupert Kaul","doi":"10.1016/j.xcrm.2024.101705","DOIUrl":"10.1016/j.xcrm.2024.101705","url":null,"abstract":"Within the penile microbiome, bacteria associated with seroconversion, immunology, and cells (BASIC species) enhance HIV susceptibility in heterosexual uncircumcised men by inducing foreskin inflammation and HIV target cell recruitment. This phase 1/2 clinical trial randomizes HIV-uninfected Ugandan men (n = 125) to either oral tinidazole, topical metronidazole, topical clindamycin, or topical hydrogen peroxide to define impact on ex vivo foreskin HIV susceptibility, penile immunology, and BASIC species density. Antimicrobials are well tolerated, and 116 (93%) participants complete the protocol. Topical metronidazole and oral tinidazole reduce the inner foreskin tissue density of HIV-susceptible CD4+ T cells (predefined primary endpoint). Antimicrobials also have varying but substantial effects on reducing prepuce inflammation and BASIC species density, reducing density of foreskin T cell subsets, and increasing foreskin epithelial integrity. Immune alterations correlate strongly with changes in the abundance of BASIC species. Clinical interventions targeting the penile microbiota, particularly topical metronidazole, may reduce HIV susceptibility in uncircumcised men.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrating amyloid and tau imaging with proteomics and genomics in Alzheimer’s disease 将淀粉样蛋白和 tau 成像与阿尔茨海默病的蛋白质组学和基因组学相结合

IF 14.3 1区医学

Cell Reports Medicine Pub Date : 2024-09-17 DOI: 10.1016/j.xcrm.2024.101735

Gabriele Vilkaite, Jacob Vogel, Niklas Mattsson-Carlgren

引用次数: 0

Transforming hypercholesterolemia management: Spotlight on PCSK9 peptide vaccines 改变高胆固醇血症的管理：聚焦 PCSK9 肽疫苗

IF 14.3 1区医学

Cell Reports Medicine Pub Date : 2024-09-17 DOI: 10.1016/j.xcrm.2024.101726

Amirhossein Sahebkar, Maciej Banach

引用次数: 0

Human milk microbiota, oligosaccharide profiles, and infant gut microbiome in preterm infants diagnosed with necrotizing enterocolitis. 确诊为坏死性小肠结肠炎的早产儿的母乳微生物群、寡糖谱和婴儿肠道微生物群。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-09-17 Epub Date: 2024-08-30 DOI: 10.1016/j.xcrm.2024.101708

Andrea C Masi, Lauren C Beck, John D Perry, Claire L Granger, Alice Hiorns, Gregory R Young, Lars Bode, Nicholas D Embleton, Janet E Berrington, Christopher J Stewart

{"title":"Human milk microbiota, oligosaccharide profiles, and infant gut microbiome in preterm infants diagnosed with necrotizing enterocolitis.","authors":"Andrea C Masi, Lauren C Beck, John D Perry, Claire L Granger, Alice Hiorns, Gregory R Young, Lars Bode, Nicholas D Embleton, Janet E Berrington, Christopher J Stewart","doi":"10.1016/j.xcrm.2024.101708","DOIUrl":"10.1016/j.xcrm.2024.101708","url":null,"abstract":"Necrotizing enterocolitis (NEC) is a severe intestinal disease of very preterm infants with mother's own milk (MOM) providing protection, but the contribution of the MOM microbiota to NEC risk has not been explored. Here, we analyze MOM of 110 preterm infants (48 NEC, 62 control) in a cross-sectional study. Breast milk contains viable bacteria, but there is no significant difference in MOM microbiota between NEC and controls. Integrative analysis between MOM microbiota, human milk oligosaccharides (HMOs), and the infant gut microbiota shows positive correlations only between Acinetobacter in the infant gut and Acinetobacter and Staphylococcus in MOM. This study suggests that NEC protection from MOM is not modulated through the MOM microbiota. Thus, \"'restoring\" the MOM microbiota in donor human milk is unlikely to reduce NEC, and emphasis should instead focus on increasing fresh maternal human milk intake and researching different therapies for NEC prevention.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Five miRNAs identified in fucosylated extracellular vesicles as non-invasive diagnostic signatures for hepatocellular carcinoma. 在岩藻糖基化细胞外囊泡中发现的五种 miRNA 是肝细胞癌的非侵入性诊断特征。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-09-17 Epub Date: 2024-09-05 DOI: 10.1016/j.xcrm.2024.101716

Boan Li, Kun Hao, Mengyang Li, Ailan Wang, Huixue Tang, Lida Xu, Cuidie Ma, Wenqian Du, Lijuan Sun, Xufeng Hou, Tianye Jia, Aixia Liu, Qi Gao, Zhiming Zhao, Ronghua Jin, Ruifu Yang

{"title":"Five miRNAs identified in fucosylated extracellular vesicles as non-invasive diagnostic signatures for hepatocellular carcinoma.","authors":"Boan Li, Kun Hao, Mengyang Li, Ailan Wang, Huixue Tang, Lida Xu, Cuidie Ma, Wenqian Du, Lijuan Sun, Xufeng Hou, Tianye Jia, Aixia Liu, Qi Gao, Zhiming Zhao, Ronghua Jin, Ruifu Yang","doi":"10.1016/j.xcrm.2024.101716","DOIUrl":"10.1016/j.xcrm.2024.101716","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a prevalent and aggressive cancer that presents significant challenges for early detection. This study introduces the GlyExo-Capture method for isolating fucosylated extracellular vesicles (Fu-EVs) from serum. We analyze microRNA (miRNA) profiles from Fu-EVs in 88 HCC patients and 179 non-HCC controls using next-generation sequencing (NGS) and identify five miRNAs (hsa-let-7a, hsa-miR-21, hsa-miR-125a, hsa-miR-200a, and hsa-miR-150) as biomarkers for HCC diagnosis. The five-miRNA panel demonstrates exceptional HCC diagnostic performance, with a sensitivity of 0.90 and specificity of 0.92 in a combined cohort of 194 HCC and 412 non-HCC controls, significantly surpassing the performance of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP). Notably, the miRNA model achieves recall rates of 85.7% and 90.8% for stage 0 and stage A early-stage HCC, respectively, identifies 88.1% of AFP-negative HCC cases, and effectively differentiates HCC from other cancers. This study provides a high-throughput, rapid, and non-invasive approach for early HCC detection.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Decoding the diabetic bone paradox: How AGEs sabotage skeletal integrity 解密糖尿病骨骼悖论：AGE 如何破坏骨骼完整性

IF 14.3 1区医学

Cell Reports Medicine Pub Date : 2024-09-17 DOI: 10.1016/j.xcrm.2024.101693

Juan Wang, Wenguo Cui

引用次数: 0

Glycan-specific IgM is critical for human immunity to Staphylococcus aureus 糖蛋白特异性 IgM 对人类免疫金黄色葡萄球菌至关重要

IF 14.3 1区医学

Cell Reports Medicine Pub Date : 2024-09-17 DOI: 10.1016/j.xcrm.2024.101734

Astrid Hendriks, Priscilla F. Kerkman, Meri R.J. Varkila, Jelle L.G. Haitsma Mulier, Sara Ali, Thijs ten Doesschate, Thomas W. van der Vaart, Carla J.C. de Haas, Piet C. Aerts, Olaf L. Cremer, Marc J.M. Bonten, Victor Nizet, George Y. Liu, Jeroen D.C. Codée, Suzan H.M. Rooijakkers, Jos A.G. van Strijp, Nina M. van Sorge

{"title":"Glycan-specific IgM is critical for human immunity to Staphylococcus aureus","authors":"Astrid Hendriks, Priscilla F. Kerkman, Meri R.J. Varkila, Jelle L.G. Haitsma Mulier, Sara Ali, Thijs ten Doesschate, Thomas W. van der Vaart, Carla J.C. de Haas, Piet C. Aerts, Olaf L. Cremer, Marc J.M. Bonten, Victor Nizet, George Y. Liu, Jeroen D.C. Codée, Suzan H.M. Rooijakkers, Jos A.G. van Strijp, Nina M. van Sorge","doi":"10.1016/j.xcrm.2024.101734","DOIUrl":"https://doi.org/10.1016/j.xcrm.2024.101734","url":null,"abstract":"Staphylococcus aureus is a major human pathogen, yet the immune factors that protect against infection remain elusive. High titers of opsonic IgG antibodies, achieved in preclinical animal immunization studies, have consistently failed to provide protection in humans. Here, we investigate antibody responses to the conserved S. aureus surface glycan wall teichoic acid (WTA) and detect the presence of WTA-specific IgM and IgG antibodies in the plasma of healthy individuals. Functionally, WTA-specific IgM outperforms IgG in opsonophagocytic killing of S. aureus and protects against disseminated S. aureus bacteremia through passive immunization. In a clinical setting, patients with S. aureus bacteremia have significantly lower WTA-specific IgM but similar IgG levels compared to healthy controls. Importantly, low WTA-IgM levels correlate with disease mortality and impaired bacterial opsonization. Our findings may guide risk stratification of hospitalized patients and inform future design of antibody-based therapies and vaccines against serious S. aureus infection.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Uncovering therapeutic targets for macrophage-mediated T cell suppression and PD-L1 therapy sensitization. 发现巨噬细胞介导的 T 细胞抑制和 PD-L1 治疗增敏的治疗靶点。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-09-17 Epub Date: 2024-08-23 DOI: 10.1016/j.xcrm.2024.101698

Sushil Kumar, Dhanir Tailor, Arpit Dheeraj, Wenqi Li, Kirsten Stefan, Jee Min Lee, Dylan Nelson, Bailey F Keefe, Pepper Schedin, Shivaani Kummar, Lisa M Coussens, Sanjay V Malhotra

{"title":"Uncovering therapeutic targets for macrophage-mediated T cell suppression and PD-L1 therapy sensitization.","authors":"Sushil Kumar, Dhanir Tailor, Arpit Dheeraj, Wenqi Li, Kirsten Stefan, Jee Min Lee, Dylan Nelson, Bailey F Keefe, Pepper Schedin, Shivaani Kummar, Lisa M Coussens, Sanjay V Malhotra","doi":"10.1016/j.xcrm.2024.101698","DOIUrl":"10.1016/j.xcrm.2024.101698","url":null,"abstract":"Tumor-associated macrophages (TAMs) and other myelomonocytic cells are implicated in regulating responsiveness to immunotherapies, including immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis. We have developed an ex vivo high-throughput approach to discover modulators of macrophage-mediated T cell suppression, which can improve clinical outcomes of ICIs. We screened 1,430 Food and Drug Administration (FDA)-approved small-molecule drugs using a co-culture assay employing bone-marrow-derived macrophages (BMDMs) and splenic-derived T cells. This identified 57 compounds that disrupted macrophage-mediated T cell suppression. Seven compounds exerted prominent synergistic T cell expansion activity when combined with αPD-L1. These include four COX1/2 inhibitors and two myeloid cell signaling inhibitors. We demonstrate that the use of cyclooxygenase (COX)1/2 inhibitors in combination with αPD-L1 decreases tumor growth kinetics and enhances overall survival in triple-negative breast cancer (TNBC) tumor models in a CD8+ T cell-dependent manner. Altogether, we present a rationalized approach for identifying compounds that synergize with ICI to potentially enhance therapeutic outcomes for patients with solid tumors.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mother's milk microbiota is associated with the developing gut microbial consortia in very-low-birth-weight infants. 母乳微生物群与极低出生体重婴儿肠道微生物群的发育有关。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-09-17 Epub Date: 2024-09-06 DOI: 10.1016/j.xcrm.2024.101729

Sara Shama, Michelle R Asbury, Alex Kiss, Nicole Bando, James Butcher, Elena M Comelli, Julia K Copeland, Adrianna Greco, Akash Kothari, Philip M Sherman, Alain Stintzi, Amel Taibi, Christopher Tomlinson, Sharon Unger, Pauline W Wang, Deborah L O'Connor

{"title":"Mother's milk microbiota is associated with the developing gut microbial consortia in very-low-birth-weight infants.","authors":"Sara Shama, Michelle R Asbury, Alex Kiss, Nicole Bando, James Butcher, Elena M Comelli, Julia K Copeland, Adrianna Greco, Akash Kothari, Philip M Sherman, Alain Stintzi, Amel Taibi, Christopher Tomlinson, Sharon Unger, Pauline W Wang, Deborah L O'Connor","doi":"10.1016/j.xcrm.2024.101729","DOIUrl":"10.1016/j.xcrm.2024.101729","url":null,"abstract":"Mother's milk contains diverse bacterial communities, although their impact on microbial colonization in very-low-birth-weight (VLBW, <1,500 g) infants remains unknown. Here, we examine relationships between the microbiota in preterm mother's milk and the VLBW infant gut across initial hospitalization (n = 94 mother-infant dyads, 422 milk-stool pairs). Shared zero-radius operational taxonomic units (zOTUs) between milk-stool pairs account for ∼30%-40% of zOTUs in the VLBW infant's gut. We show dose-response relationships between intakes of several genera from milk and their concentrations in the infant's gut. These relationships and those related to microbial sharing change temporally and are modified by in-hospital feeding practices (especially direct breastfeeding) and maternal-infant antibiotic use. Correlations also exist between milk and stool microbial consortia, suggesting that multiple milk microbes may influence overall gut communities together. These results highlight that the mother's milk microbiota may shape the gut colonization of VLBW infants by delivering specific bacteria and through intricate microbial interactions.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Acutely blocking excessive mitochondrial fission prevents chronic neurodegeneration after traumatic brain injury. 急性阻断线粒体过度分裂可预防脑外伤后的慢性神经退行性变。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-09-17 Epub Date: 2024-09-05 DOI: 10.1016/j.xcrm.2024.101715

Preethy S Sridharan, Yeojung Koh, Emiko Miller, Di Hu, Suwarna Chakraborty, Sunil Jamuna Tripathi, Teresa R Kee, Kalyani Chaubey, Edwin Vázquez-Rosa, Sarah Barker, Hui Liu, Rose A León-Alvarado, Kathryn Franke, Coral J Cintrón-Pérez, Matasha Dhar, Min-Kyoo Shin, Margaret E Flanagan, Rudolph J Castellani, Tamar Gefen, Marina Bykova, Lijun Dou, Feixiong Cheng, Brigid M Wilson, Hisashi Fujioka, David E Kang, Jung-A A Woo, Bindu D Paul, Xin Qi, Andrew A Pieper

{"title":"Acutely blocking excessive mitochondrial fission prevents chronic neurodegeneration after traumatic brain injury.","authors":"Preethy S Sridharan, Yeojung Koh, Emiko Miller, Di Hu, Suwarna Chakraborty, Sunil Jamuna Tripathi, Teresa R Kee, Kalyani Chaubey, Edwin Vázquez-Rosa, Sarah Barker, Hui Liu, Rose A León-Alvarado, Kathryn Franke, Coral J Cintrón-Pérez, Matasha Dhar, Min-Kyoo Shin, Margaret E Flanagan, Rudolph J Castellani, Tamar Gefen, Marina Bykova, Lijun Dou, Feixiong Cheng, Brigid M Wilson, Hisashi Fujioka, David E Kang, Jung-A A Woo, Bindu D Paul, Xin Qi, Andrew A Pieper","doi":"10.1016/j.xcrm.2024.101715","DOIUrl":"10.1016/j.xcrm.2024.101715","url":null,"abstract":"Progression of acute traumatic brain injury (TBI) into chronic neurodegeneration is a major health problem with no protective treatments. Here, we report that acutely elevated mitochondrial fission after TBI in mice triggers chronic neurodegeneration persisting 17 months later, equivalent to many human decades. We show that increased mitochondrial fission after mouse TBI is related to increased brain levels of mitochondrial fission 1 protein (Fis1) and that brain Fis1 is also elevated in human TBI. Pharmacologically preventing Fis1 from binding its mitochondrial partner, dynamin-related protein 1 (Drp1), for 2 weeks after TBI normalizes the balance of mitochondrial fission/fusion and prevents chronically impaired mitochondrial bioenergetics, oxidative damage, microglial activation and lipid droplet formation, blood-brain barrier deterioration, neurodegeneration, and cognitive impairment. Delaying treatment until 8 months after TBI offers no protection. Thus, time-sensitive inhibition of acutely elevated mitochondrial fission may represent a strategy to protect human TBI patients from chronic neurodegeneration.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0