Journal of Biomedical Science最新文献

筛选
英文 中文
USP24 upregulation stabilizes PKA-Cα to promote lipogenesis, inflammation, and fibrosis during MASH progression. USP24上调稳定PKA-Cα,促进MASH进展过程中的脂肪生成、炎症和纤维化。
IF 9 2区 医学
Journal of Biomedical Science Pub Date : 2025-05-30 DOI: 10.1186/s12929-025-01148-4
Beh Ning, Shao-An Wang, Ming-Jer Young, Yung-Ching Chen, Yun Hung, Tran Thu Huong, Wen-Chang Chang, Yi-Ching Wang, Ming-Lung Yu, Kai-Cheng Hsu, Jan-Jong Hung
{"title":"USP24 upregulation stabilizes PKA-Cα to promote lipogenesis, inflammation, and fibrosis during MASH progression.","authors":"Beh Ning, Shao-An Wang, Ming-Jer Young, Yung-Ching Chen, Yun Hung, Tran Thu Huong, Wen-Chang Chang, Yi-Ching Wang, Ming-Lung Yu, Kai-Cheng Hsu, Jan-Jong Hung","doi":"10.1186/s12929-025-01148-4","DOIUrl":"10.1186/s12929-025-01148-4","url":null,"abstract":"<p><strong>Background: </strong>Ubiquitin-specific peptidase 24 (USP24), a deubiquitinating enzyme, regulates protein stability by removing ubiquitin. This study investigates the role of UPS24 in lipid metabolism, inflammation, and fibrosis. It also explores the effect of targeting USP24 on metabolic disorders, focusing on high-fat diet (HFD)-induced obesity and liver diseases.</p><p><strong>Methods: </strong>This study utilized CRISPR/Cas9 to create functional knockout mice (USP24<sup>C1695A</sup>) and treated HFD-fed mice with USP24 inhibitor (USP24-i-101). The effects of USP24 inhibition or knockout on 3T3-L1 derived adipocytes, primary hepatocytes, hepatic stellate cells, and murine hepatocyte cell line AML12 (alpha mouse liver 12) cells were assessed with RNA-sequencing. Molecular mechanisms and the interaction between USP24 and PKA-Cα were studied with co-immunoprecipitation. Downstream signaling pathways involving CREB, SREBP1, PPARγ, and C/EBPβ, as well as USP24 role in liver inflammation and fibrosis, were studied using western blot and real-time PCR. Clinical and animal tissue samples were examined with immunohistochemistry to identify the correlations between USP24 and metabolic-associated liver diseases.</p><p><strong>Results: </strong>Knockout or inhibition of USP24 reduced body weight, lipid accumulation, inflammation, and fibrosis in HFD-fed mice. The expression of genes related to lipogenesis, inflammation, and fibrosis was downregulated in USP24<sup>C1695A</sup> mice and those treated with USP24 inhibitor (USP24-i-101). USP24 inhibition decreased lipid droplet accumulation in adipocytes and hepatocytes, suppressed inflammation in hepatocytes and AML12 cells, and reduced fibrosis in hepatic stellate cells. Mechanistically, USP24 expression was upregulated by PKA activation during adipocyte differentiation, leading to increased PKA-Cα stability and CREB phosphorylation, which promoted lipogenic gene expression. Free fatty acids (FFA) increased USP24 expression, activating NF-κB and TGFβ pathways to induce inflammation (Cox2) and fibrosis (α-SMA). USP24 was highly expressed in patients with metabolic dysfunction-associated steatohepatitis (MASH) and correlated with Cox2 and α-SMA levels.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"54"},"PeriodicalIF":9.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
AbOmpA in Acinetobacter baumannii: exploring virulence mechanisms of outer membrane-integrated and outer membrane vesicle-associated AbOmpA and developing anti-infective agents targeting AbOmpA. 鲍曼不动杆菌中的AbOmpA:探索外膜整合和外膜囊泡相关的AbOmpA的毒力机制,并开发针对AbOmpA的抗感染药物。
IF 9 2区 医学
Journal of Biomedical Science Pub Date : 2025-05-27 DOI: 10.1186/s12929-025-01147-5
Man Hwan Oh, Md Minarul Islam, Nayeong Kim, Chul Hee Choi, Minsang Shin, Woo Shik Shin, Je Chul Lee
{"title":"AbOmpA in Acinetobacter baumannii: exploring virulence mechanisms of outer membrane-integrated and outer membrane vesicle-associated AbOmpA and developing anti-infective agents targeting AbOmpA.","authors":"Man Hwan Oh, Md Minarul Islam, Nayeong Kim, Chul Hee Choi, Minsang Shin, Woo Shik Shin, Je Chul Lee","doi":"10.1186/s12929-025-01147-5","DOIUrl":"10.1186/s12929-025-01147-5","url":null,"abstract":"<p><p>Acinetobacter baumannii is notorious for its antimicrobial resistance and its potential to cause epidemics in hospital settings, which pose a global health threat. Although this microorganism is traditionally considered a low-virulence pathogen, extensive research has been conducted on its virulence and pathogenesis in recent years. Advances in understanding the virulence mechanisms of A. baumannii have prompted a shift in the development of anti-infective agents. The outer membrane protein A (AbOmpA) of A. baumannii is a key virulence factor both in vitro and in vivo. AbOmpA exists in three forms: outer membrane-integrated AbOmpA, outer membrane vesicle (OMV)-associated AbOmpA, and free proteins. Given that outer membrane-integrated AbOmpA has been implicated in the virulence and antimicrobial resistance of A. baumannii, many studies have focused on outer membrane-integrated AbOmpA as a therapeutic target for combating drug-resistant A. baumannii, and have led to the discovery of small molecules, polypeptides, and antimicrobial peptides targeting AbOmpA. However, the pathophysiological role of OMV-associated AbOmpA and its impact on AbOmpA-targeting agents remain unclear. This review summarizes the current knowledge of AbOmpA and critically discusses OMV-associated AbOmpA in relation to virulence and its potential impact on AbOmpA-targeted therapies to provide a better understanding of AbOmpA for the development of novel therapeutics against A. baumannii.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"53"},"PeriodicalIF":9.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Adjunctive beneficial effect of c-di-GMP, a STING agonist, in enhancing protective efficacy of TLR4-adjuvanted tuberculosis subunit vaccine formulations. STING激动剂c-di-GMP在增强tlr4佐剂结核亚单位疫苗制剂保护效果中的辅助有益作用
IF 9 2区 医学
Journal of Biomedical Science Pub Date : 2025-05-26 DOI: 10.1186/s12929-025-01144-8
Kee Woong Kwon, Eunsol Choi, Hagyu Kim, Hyeong Woo Kim, Sangwon Choi, Seunghyun Lee, Sang-Jun Ha, Sung Jae Shin
{"title":"Adjunctive beneficial effect of c-di-GMP, a STING agonist, in enhancing protective efficacy of TLR4-adjuvanted tuberculosis subunit vaccine formulations.","authors":"Kee Woong Kwon, Eunsol Choi, Hagyu Kim, Hyeong Woo Kim, Sangwon Choi, Seunghyun Lee, Sang-Jun Ha, Sung Jae Shin","doi":"10.1186/s12929-025-01144-8","DOIUrl":"10.1186/s12929-025-01144-8","url":null,"abstract":"<p><strong>Background: </strong>Effective subunit vaccine development requires selecting appropriate adjuvant formulations to trigger desired adaptive immune responses. This study explores the immunogenicity and tuberculosis (TB) vaccine potential of antigens (Ags) combined with Toll-like receptor 4 (TLR4) adjuvants and a stimulator of interferon genes (STING) agonist.</p><p><strong>Methods: </strong>In this work, we investigated the combination of Ags with TLR4 adjuvants (monophosphoryl lipid A / dimethyldioctadecylammonium bromide; MPL/DDA or glucopyranosyl lipid adjuvant-stable emulsion; GLA-SE) and a STING agonist, c-di-GMP (CDG). Mice were immunized three times by intramuscular injections at 3-week intervals. The effects of integrating Ags in these adjuvant formulations on the immune response were evaluated, focusing on the generation of Th1-biased, polyfunctional Ag-specific CD4<sup>+</sup> T cells and their localization in the lung and spleen. To assess protection, immunized mice were aerogenically challenged with either conventional or ultra-low doses of Mycobacterium tuberculosis (Mtb) 4 weeks after the last immunization. Subsequently, bacterial load and pulmonary inflammation were assessed.</p><p><strong>Results: </strong>Integrating ESAT6 Ag in TLR4 and CDG adjuvant formulations remarkably boosted Th1-biased, polyfunctional ESAT6-specific CD4<sup>+</sup> T cells in the lungs and spleen, providing durable protection against Mtb infection. The inclusion of CDG promoted mucosal localization of ESAT6-specific CD4<sup>+</sup> T cells resembling resident memory phenotypes in the lung parenchyma and increased Ag-specific CD4<sup>+</sup> T cells in lung vasculature. Immunization with another vaccine Ag candidate, Ag85B, in GLA-SE plus CDG similarly increased Ag85B-specific CD4<sup>+</sup> T cells in the spleen and both lung compartments. Following ultra-low dose Mtb challenge, ESAT6 or Ag85B/GLA-SE/CDG immunizations significantly reduced bacterial loads compared to non-, Bacillus Calmette-Guérin (BCG)-, and ESAT6 or Ag85B/GLA-SE-immunized groups. Importantly, the inclusion of CDG decreased killer cell lectin-like receptor subfamily G member 1 (KLRG1) expression among Ag-specific CD4<sup>+</sup> T cells in the lung, correlating with enhanced lung-homing evidenced by expanded lung parenchyma Ag-specific CD4<sup>+</sup> T cells, including less-differentiated Th1 cells.</p><p><strong>Conclusions: </strong>This study highlights that CDG, when used in combination with TLR4 adjuvants, enhances long-term protective immunity, offering a promising strategy for subunit TB vaccine development.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"52"},"PeriodicalIF":9.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Meta-epigenetic shifts in T cell aging and aging-related dysfunction. T细胞衰老和衰老相关功能障碍的后表观遗传改变。
IF 9 2区 医学
Journal of Biomedical Science Pub Date : 2025-05-23 DOI: 10.1186/s12929-025-01146-6
Lorène Rousseau, Karina L Hajdu, Ping-Chih Ho
{"title":"Meta-epigenetic shifts in T cell aging and aging-related dysfunction.","authors":"Lorène Rousseau, Karina L Hajdu, Ping-Chih Ho","doi":"10.1186/s12929-025-01146-6","DOIUrl":"10.1186/s12929-025-01146-6","url":null,"abstract":"<p><p>Epigenetic regulation, including DNA methylation and histone modifications, play a pivotal role in shaping T cell functionality throughout life. With aging, these epigenetic changes profoundly affect gene expression, altering T cell plasticity, activation, and differentiation. These modifications contribute significantly to immunosenescence, increasing susceptibility to infections, cancer, and autoimmune diseases. In CD8⁺ T cells, chromatin closure at key regulatory regions suppresses activation and migration, while chromatin opening in pro-inflammatory gene loci amplifies inflammation. These changes drive terminal differentiation, characterized by increased expression of senescence-associated markers, impaired migration and loss of epigenetic plasticity. CD4⁺ T cells experience fewer but critical epigenetic alterations, including disrupted pathways, a skewed Th1/Th2 balance, and reduced Treg functionality. These epigenetic changes, compounded by metabolic dysfunctions, such as mitochondrial deficiency and oxidative stress, impair T-cell adaptability and resilience in the aging organism. Therefore, understanding the interplay between epigenetic and metabolic factors in T cell aging offers promising therapeutic opportunities to mitigate immunosenescence and enhance immune function in aging populations. This review explores the interplay between DNA methylation, histone alterations, and metabolic changes underlying T cell aging.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"51"},"PeriodicalIF":9.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Exploring the genomic and transcriptomic profiles of glycemic traits and drug repurposing. 探索血糖特征和药物再利用的基因组和转录组学特征。
IF 9 2区 医学
Journal of Biomedical Science Pub Date : 2025-05-21 DOI: 10.1186/s12929-025-01137-7
Min-Rou Lin, Cheng-Lin Tsai, Cai-Sian Liao, Chun-Yu Wei, Wan-Hsuan Chou, Tzu-Hung Hsiao, Wei-Chiao Chang
{"title":"Exploring the genomic and transcriptomic profiles of glycemic traits and drug repurposing.","authors":"Min-Rou Lin, Cheng-Lin Tsai, Cai-Sian Liao, Chun-Yu Wei, Wan-Hsuan Chou, Tzu-Hung Hsiao, Wei-Chiao Chang","doi":"10.1186/s12929-025-01137-7","DOIUrl":"10.1186/s12929-025-01137-7","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes is an increasingly prevalent metabolic disorder with moderate to high heritability. Glycemic indices are crucial for diagnosing and monitoring the disease. Previous genome-wide association study (GWAS) have identified several risk loci associated with type 2 diabetes, but data from the Taiwanese population remain relatively sparse and primarily focus on type 2 diabetes status rather than glycemic trait levels.</p><p><strong>Methods: </strong>We conducted a comprehensive genome-wide meta-analysis to explore the genetics of glycemic traits. The study incorporated a community-based cohort of 145,468 individuals and a hospital-based cohort of 35,395 individuals. The study integrated genetics, transcriptomics, biological pathway analyses, polygenic risk score calculation, and drug repurposing for type 2 diabetes.</p><p><strong>Results: </strong>This study assessed hemoglobin A1c and fasting glucose levels, validating known loci (FN3K, SPC25, MTNR1B, and FOXA2) and discovering new genes, including MAEA and PRC1. Additionally, we found that diabetes, blood lipids, and liver- and kidney-related traits share genetic foundations with glycemic traits. A higher PRS was associated with an increased risk of type 2 diabetes. Finally, eight repurposed drugs were identified with evidence to regulate blood glucose levels, offering new avenues for the management and treatment of type 2 diabetes.</p><p><strong>Conclusions: </strong>This research illuminates the unique genetic landscape of glucose regulation in Taiwanese Han population, providing valuable insights to guide future treatment strategies for type 2 diabetes.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"50"},"PeriodicalIF":9.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Gemcitabine resistance by CITED4 upregulation via the regulation of BIRC2 expression in pancreatic cancer. 胰腺癌中通过BIRC2表达调控CITED4上调吉西他滨耐药
IF 9 2区 医学
Journal of Biomedical Science Pub Date : 2025-05-19 DOI: 10.1186/s12929-025-01140-y
Eun-Jeong Jeong, Yuna Roh, Eunsun Jung, Jin-Seong Hwang, Taesang Son, Hyun Seung Ban, Tae-Su Han, Young-Kug Choo, Jang-Seong Kim
{"title":"Gemcitabine resistance by CITED4 upregulation via the regulation of BIRC2 expression in pancreatic cancer.","authors":"Eun-Jeong Jeong, Yuna Roh, Eunsun Jung, Jin-Seong Hwang, Taesang Son, Hyun Seung Ban, Tae-Su Han, Young-Kug Choo, Jang-Seong Kim","doi":"10.1186/s12929-025-01140-y","DOIUrl":"10.1186/s12929-025-01140-y","url":null,"abstract":"<p><strong>Background: </strong>Gemcitabine (GEM) is used as a first-line therapy for patients diagnosed with any stage of pancreatic cancer (PC); however, patient survival is poor because of GEM resistance. Thus, new approaches to overcome GEM resistance in PC are urgently needed. Here, we aimed to establish an in vivo drug-resistant PC model and identify genes involved in GEM resistance. We focused on one of these factors, CITED4, and elucidated its mechanisms of action in GEM resistance in PC.</p><p><strong>Methods: </strong>L3.6pl, a GEM-sensitive PC cell line, was orthotopically injected into the pancreas of BALB/c nude mice to establish a GEM-resistant PC animal model. Transcriptomic data from control or GEM-resistant tumor-derived cells were analyzed. GEM resistance was evaluated using cell viability, clonogenicity, and apoptosis assays. An apoptosis array was used to identify genes downstream of CITED4. A CITED4 knockout-mediated GEM sensitivity assay was performed in an orthotopic xenograft mouse model using PANC-1 cells, which are GEM-resistant cells.</p><p><strong>Results: </strong>From the RNA sequencing data of isolated GEM-resistant PC cells and The Cancer Genome Atlas dataset, 15 GEM resistance-related genes were found to be upregulated, including CITED4, the gene encoding a type of CBP/p300-interacting transactivator implicated in several cancers. CITED4 knockdown in drug-resistant cells reduced cell proliferation and migration but increased apoptosis. To identify the molecular mechanism underlying CITED4-mediated induction of GEM resistance, alterations in Baculoviral IAP Repeat Containing 2 (BIRC2) levels were observed using an apoptosis array. BIRC2 expression was downregulated following CITED4 knockdown in GEM-resistant PC cell lines. Furthermore, chromatin immunoprecipitation and promoter assays showed that BIRC2 was directly regulated by CITED4. Consistent with the CITED-knockdown experiments, silencing of BIRC2 increased the sensitivity of L3.6pl-GEM-resistant and PANC-1 cell lines to GEM. Furthermore, CITED4 knockout using the CRISPR-Cas9 system in PANC-1 cells increased the sensitivity to GEM in orthotopic mice. Moreover, elevated CITED4 and BIRC2 expression levels were associated with poorer outcomes in human PC clinical samples.</p><p><strong>Conclusions: </strong>Collectively, these results indicate that CITED4 regulates GEM resistance via inhibition of apoptosis by upregulating BIRC2 expression in PC cells. Therefore, CITED4 may serve as a valuable diagnostic marker and therapeutic target for GEM-resistant PC.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"49"},"PeriodicalIF":9.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 innate lymphoid cells and innate-like lymphocytes in asthma: pathways to mechanisms and therapies. 解码先天淋巴样细胞和先天淋巴细胞在哮喘:途径,机制和治疗。
IF 9 2区 医学
Journal of Biomedical Science Pub Date : 2025-05-12 DOI: 10.1186/s12929-025-01142-w
Christina Li-Ping Thio, Jheng-Syuan Shao, Chia-Hui Luo, Ya-Jen Chang
{"title":"Decoding innate lymphoid cells and innate-like lymphocytes in asthma: pathways to mechanisms and therapies.","authors":"Christina Li-Ping Thio, Jheng-Syuan Shao, Chia-Hui Luo, Ya-Jen Chang","doi":"10.1186/s12929-025-01142-w","DOIUrl":"10.1186/s12929-025-01142-w","url":null,"abstract":"<p><p>Asthma is a chronic inflammatory lung disease driven by a complex interplay between innate and adaptive immune components. Among these, innate lymphoid cells (ILCs) and innate-like lymphocytes have emerged as crucial players in shaping the disease phenotype. Within the ILC family, group 2 ILCs (ILC2s), in particular, contribute significantly to type 2 inflammation through their rapid production of cytokines such as IL-5 and IL-13, promoting airway eosinophilia and airway hyperreactivity. On the other hand, innate-like lymphocytes such as invariant natural killer T (iNKT) cells can play either pathogenic or protective roles in asthma, depending on the stimuli and lung microenvironment. Regulatory mechanisms, including cytokine signaling, metabolic and dietary cues, and interactions with other immune cells, play critical roles in modulating their functions. In this review, we highlight current findings on the role of ILCs and innate-like lymphocytes in asthma development and pathogenesis. We also examine the underlying mechanisms regulating their function and their interplay with other immune cells. Finally, we explore current therapies targeting these cells and their effector cytokines for asthma management.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"48"},"PeriodicalIF":9.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Keratin 6A promotes skin inflammation through JAK1-STAT3 activation in keratinocytes. 角蛋白6A通过激活角化细胞中的JAK1-STAT3促进皮肤炎症。
IF 9 2区 医学
Journal of Biomedical Science Pub Date : 2025-05-09 DOI: 10.1186/s12929-025-01143-9
Mengting Chen, Yaling Wang, Mei Wang, San Xu, Zixin Tan, Yisheng Cai, Xin Xiao, Ben Wang, Zhili Deng, Ji Li
{"title":"Keratin 6A promotes skin inflammation through JAK1-STAT3 activation in keratinocytes.","authors":"Mengting Chen, Yaling Wang, Mei Wang, San Xu, Zixin Tan, Yisheng Cai, Xin Xiao, Ben Wang, Zhili Deng, Ji Li","doi":"10.1186/s12929-025-01143-9","DOIUrl":"https://doi.org/10.1186/s12929-025-01143-9","url":null,"abstract":"<p><strong>Background: </strong>Skin barrier dysfunction and immune activation are hallmarks of inflammatory skin diseases such as rosacea and psoriasis, suggesting shared pathogenic mechanisms. While barrier disruption may trigger or exacerbate skin inflammation, the precise underlying mechanisms remain unclear. Notably, epidermal barrier compromise leads to a marked increase in barrier alarmin expression. Among these, keratin 6A (KRT6A) plays a role in maintaining skin barrier integrity.</p><p><strong>Methods: </strong>We treated mouse skin and human keratinocytes, with and without KRT6A expression, with LL37/TNF-α and assessed the severity of inflammation. The specific mechanism by which KRT6A promotes skin inflammation was investigated using mass spectrometry and immunoprecipitation assays.</p><p><strong>Results: </strong>KRT6A expression was elevated in lesional skin from patients and mouse models of rosacea and psoriasis. In mice with LL37-induced rosacea-like and imiquimod (IMQ)-induced psoriasis-like skin inflammation, KRT6A knockdown alleviated inflammation, whereas KRT6A overexpression exacerbated inflammatory responses. Mechanistically, KRT6A activated signal transducer and activator of transcription 3 (STAT3) and enhanced proinflammatory cytokine expression in keratinocytes by reducing Janus kinase 1 (JAK1) ubiquitination. This occurred through inhibition of ring finger protein 41 (RNF41)-mediated JAK1 binding.</p><p><strong>Conclusions: </strong>Our findings indicate that KRT6A expression increases following epidermal barrier disruption and contributes to exacerbated skin inflammation in disease conditions. Targeting KRT6A may represent a novel therapeutic approach for inflammatory skin diseases associated with epidermal dysfunction.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"47"},"PeriodicalIF":9.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Accelerating antibody discovery and optimization with high-throughput experimentation and machine learning. 通过高通量实验和机器学习加速抗体发现和优化。
IF 9 2区 医学
Journal of Biomedical Science Pub Date : 2025-05-09 DOI: 10.1186/s12929-025-01141-x
Ryo Matsunaga, Kouhei Tsumoto
{"title":"Accelerating antibody discovery and optimization with high-throughput experimentation and machine learning.","authors":"Ryo Matsunaga, Kouhei Tsumoto","doi":"10.1186/s12929-025-01141-x","DOIUrl":"https://doi.org/10.1186/s12929-025-01141-x","url":null,"abstract":"<p><p>The integration of high-throughput experimentation and machine learning is transforming data-driven antibody engineering, revolutionizing the discovery and optimization of antibody therapeutics. These approaches employ extensive datasets comprising antibody sequences, structures, and functional properties to train predictive models that enable rational design. This review highlights the significant advancements in data acquisition and feature extraction, emphasizing the necessity of capturing both sequence and structural information. We illustrate how machine learning models, including protein language models, are used not only to enhance affinity but also to optimize other crucial therapeutic properties, such as specificity, stability, viscosity, and manufacturability. Furthermore, we provide practical examples and case studies to demonstrate how the synergy between experimental and computational approaches accelerates antibody engineering. Finally, this review discusses the remaining challenges in fully realizing the potential of artificial intelligence (AI)-powered antibody discovery pipelines to expedite therapeutic development.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"46"},"PeriodicalIF":9.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Impact of large language model (ChatGPT) in healthcare: an umbrella review and evidence synthesis. 大语言模型(ChatGPT)在医疗保健中的影响:概括性回顾和证据综合。
IF 9 2区 医学
Journal of Biomedical Science Pub Date : 2025-05-07 DOI: 10.1186/s12929-025-01131-z
Usman Iqbal, Afifa Tanweer, Annisa Ristya Rahmanti, David Greenfield, Leon Tsung-Ju Lee, Yu-Chuan Jack Li
{"title":"Impact of large language model (ChatGPT) in healthcare: an umbrella review and evidence synthesis.","authors":"Usman Iqbal, Afifa Tanweer, Annisa Ristya Rahmanti, David Greenfield, Leon Tsung-Ju Lee, Yu-Chuan Jack Li","doi":"10.1186/s12929-025-01131-z","DOIUrl":"10.1186/s12929-025-01131-z","url":null,"abstract":"<p><strong>Background: </strong>The emergence of Artificial Intelligence (AI), particularly Chat Generative Pre-Trained Transformer (ChatGPT), a Large Language Model (LLM), in healthcare promises to reshape patient care, clinical decision-making, and medical education. This review aims to synthesise research findings to consolidate the implications of ChatGPT integration in healthcare and identify research gaps.</p><p><strong>Main body: </strong>The umbrella review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Cochrane Library, PubMed, Scopus, Web of Science, and Google Scholar were searched from inception until February 2024. Due to the heterogeneity of the included studies, no quantitative analysis was performed. Instead, information was extracted, summarised, synthesised, and presented in a narrative form. Two reviewers undertook title, abstract, and full text screening independently. The methodological quality and overall rating of the included reviews were assessed using the A Measurement Tool to Assess systematic Reviews (AMSTAR-2) checklist. The review examined 17 studies, comprising 15 systematic reviews and 2 meta-analyses, on ChatGPT in healthcare, revealing diverse focuses. The AMSTAR-2 assessment identified 5 moderate and 12 low-quality reviews, with deficiencies like study design justification and funding source reporting. The most reported theme that emerged was ChatGPT's use in disease diagnosis or clinical decision-making. While 82.4% of studies focused on its general usage, 17.6% explored unique topics like its role in medical examinations and conducting systematic reviews. Among these, 52.9% targeted general healthcare, with 41.2% focusing on specific domains like radiology, neurosurgery, gastroenterology, public health dentistry, and ophthalmology. ChatGPT's use for manuscript review or writing was mentioned in 17.6% of reviews. Promising applications include enhancing patient care and clinical decision-making, though ethical, legal, and accuracy concerns require cautious integration.</p><p><strong>Conclusion: </strong>We summarise the identified areas in reviews regarding ChatGPT's transformative impact in healthcare, highlighting patient care, decision-making, and medical education. Emphasising the importance of ethical regulations and the involvement of policymakers, we urge further investigation to ensure the reliability of ChatGPT and to promote trust in healthcare and research.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"32 1","pages":"45"},"PeriodicalIF":9.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信