Acta biochimica et biophysica Sinica最新文献

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A visualized and quercetin-optimized three-dimensional culture model of mouse ovaries derived from fetal gonads. 基于胚胎性腺的小鼠卵巢三维可视化培养模型。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-06-03 DOI: 10.3724/abbs.2025084
Manman Cui, Ziye Zheng, Shiyu Bai, Zhaoxiang Ouyang, Jun Chen, Xinyan Yang, Cong Wan, Yi Zheng, Jiexiang Zhao, Gang Chang, Xiao-Yang Zhao
{"title":"A visualized and quercetin-optimized three-dimensional culture model of mouse ovaries derived from fetal gonads.","authors":"Manman Cui, Ziye Zheng, Shiyu Bai, Zhaoxiang Ouyang, Jun Chen, Xinyan Yang, Cong Wan, Yi Zheng, Jiexiang Zhao, Gang Chang, Xiao-Yang Zhao","doi":"10.3724/abbs.2025084","DOIUrl":"https://doi.org/10.3724/abbs.2025084","url":null,"abstract":"<p><p>The <i>in vitro</i> culture of ovarian tissue is emerging as a popular technology to study female reproductive medicine. However, standard <i>in vitro</i> culture conditions usually increase the level of reactive oxygen species (ROS), hindering ovarian development. Here, we establish an <i>in vitro</i> visualized mouse ovarian explant 3D culture model with the GFP-BVSC reporter system and obtain the early follicle pool from fetal female gonads. This model recapitulates <i>in vivo</i> ovarian characteristics and allows non-invasive monitoring of ovarian development. Importantly, supplementation with quercetin, a plant-derived natural antioxidant, increases the tissue area and total follicle count in cultured ovaries by protecting mitochondria and reducing ROS, thus more closely mimicking <i>in vivo</i> growth conditions. Finally, this visualized and optimized ovarian explant culture platform has been proven to be effective in modelling female ovarian diseases, such as the fetal reproductive aberrations of female offspring affected by gestational diabetes mellitus (GDM). Overall, our work extends the understanding of ovarian biology and creates an efficient and simplified platform for the morphological monitoring of ovarian development, as well as for drug screening and the clinical treatment of ovarian hypofunction.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immune signatures of megakaryocytes in persistent inflammation-immunosuppression and catabolism syndrome. 巨核细胞在持续性炎症-免疫抑制和分解代谢综合征中的免疫特征。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-05-30 DOI: 10.3724/abbs.2025087
Xingfeng Sun, Ke Nan, Ziwen Zhong, Zhiqiang Liu, Changhong Miao
{"title":"Immune signatures of megakaryocytes in persistent inflammation-immunosuppression and catabolism syndrome.","authors":"Xingfeng Sun, Ke Nan, Ziwen Zhong, Zhiqiang Liu, Changhong Miao","doi":"10.3724/abbs.2025087","DOIUrl":"https://doi.org/10.3724/abbs.2025087","url":null,"abstract":"<p><p>Persistent inflammation-immunosuppression and catabolism syndrome (PICS) is a severe condition that may follow sepsis and is characterized by ongoing inflammation and immune suppression, diminishing quality of life and potentially causing death. The role of megakaryocytes (MKs) in PICS, despite their association with thrombopoiesis, is not well understood. In this study, we use single-cell RNA sequencing to profile MKs in peripheral blood mononuclear cell samples obtained from 11 patients, including six with PICS, five with sepsis, and five healthy controls, to determine the diversity and molecular signatures of the MKs. Five subgroups of MKs are identified (MK1-MK5), and their proportions vary across the groups. MK1 and MK2 are predominant in PICS. Gene Ontology analysis shows that genes related to antigen processing and presentation and IL-17 signaling are enriched in MK1, whereas genes associated with platelet degranulation and neutrophil activation are enriched in MK2. Moreover, the expression level of CCL5 is markedly increased in MKs. Ligand-receptor analysis reveals dynamic interactions among MKs and T cells, B cells, natural killer cells, monocytes, and macrophages, suggesting a broad role of MKs in immune homeostasis. In PICS model mice, MKs regulate systemic inflammation by reducing the levels of the proinflammatory cytokines TNF-α and IL-17A and promoting lung tissue repair. Our findings establish MKs as essential components of the immune system in PICS and provide new insights into their potential as therapeutic targets for post-sepsis immune dysfunction.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ATRX ADD domain is a versatile module for recognizing macroH2A, H3, and beyond. ATRX ADD域是一个多功能模块,用于识别macroH2A, H3等。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-05-30 DOI: 10.3724/abbs.2025085
Shukun Yan, Xiaoman Wang, Kexue Ge, Duo Wang, Yong Chen
{"title":"ATRX ADD domain is a versatile module for recognizing macroH2A, H3, and beyond.","authors":"Shukun Yan, Xiaoman Wang, Kexue Ge, Duo Wang, Yong Chen","doi":"10.3724/abbs.2025085","DOIUrl":"https://doi.org/10.3724/abbs.2025085","url":null,"abstract":"<p><p>Alpha Thalassemia/Mental developmental retardation, X-linked (ATRX) is an important heterochromatin regulator, frequent mutated in ATR-X syndrome and various cancers. ATRX binds a histone variant macroH2A, forming a functional axis crucial for transcription regulation and genome stability. However, the molecular mechanism underlying the ATRX-macroH2A interaction remains obscure. Here we demonstrate that the ADD domain of ATRX (ATRX <sub>ADD</sub>) specifically binds the histone-fold domain of macroH2A, but not the canonical H2A. The binding specificity is mediated by a D/E-rich loop of ATRX <sub>ADD</sub> and the L <sub>12</sub> loop of macroH2A. A swapping mutation in the L <sub>12</sub> loop of macroH2A disrupts ATRX binding, whereas the reverse mutation in H2A confers binding capacity with ATRX. Notably, ATRX <sub>ADD</sub> employs a conserved interface to recognize both macroH2A and H3, leading to competition between macroH2A and H3 for ATRX binding. Furthermore, affinity purification and mass spectrometry identify NuRD components as the potential ATRX <sub>ADD</sub>-associating proteins, with CDH4 mimicking H3 in its direct interaction with ATRX <sub>ADD</sub>. These findings elucidate the molecular basis of ATRX's interaction with macroH2A and NuRD, and also demonstrate the versatility of ATRX <sub>ADD</sub> in recognizing diverse chromatin regulators, providing insights into ATRX's multifaceted roles in epigenetic regulation and pathogenesis.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
LM2I leads to CAD ubiquitination and liver cancer suppression through activation of ASS1. LM2I通过激活ASS1导致CAD泛素化和肝癌抑制。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-05-30 DOI: 10.3724/abbs.2025083
Zhengnan Ming, Tiao Luo, Zizheng Zou, Wensong Luo, Xiyuan Hu, Ling Chen, Jiang Zhou, Xiaohe Liu, Mingquan Liu, Jijia Li, Dayou Ma, Suyou Liu, Zhiyong Luo
{"title":"LM2I leads to CAD ubiquitination and liver cancer suppression through activation of ASS1.","authors":"Zhengnan Ming, Tiao Luo, Zizheng Zou, Wensong Luo, Xiyuan Hu, Ling Chen, Jiang Zhou, Xiaohe Liu, Mingquan Liu, Jijia Li, Dayou Ma, Suyou Liu, Zhiyong Luo","doi":"10.3724/abbs.2025083","DOIUrl":"https://doi.org/10.3724/abbs.2025083","url":null,"abstract":"<p><p>The urea cycle occurs mainly in the liver and undergoes changes during hepatocarcinogenesis. Argininosuccinate synthase 1 (ASS1) is a key enzyme in the urea cycle and is expressed at low levels in certain cancers. LM2I, a specific activator of ASS1, exhibits significant antitumor activity. However, the antitumor mechanism of LM2I in liver cancer remains unclear. In this study, we find that LM2I is more effective for liver cancer cells with low ASS1 expression. The results of the IP-LC/MS experiments reveal that ASS1 interacts with CAD. The expressions of ASS1 and CAD in liver cancer tissues and cells are negatively correlated. LM2I promotes the ubiquitination of CAD protein through ASS1. LM2I inhibits the proliferation of liver cancer cells <i>in vivo</i> and <i>in vitro</i>. However, its efficacy is weak in liver cancer cells stably overexpressing CAD. The H&E staining results reveal that LM2I has no toxicity in mice. In terms of metabolism, LM2I increases the urea content and decreases the pyrimidine content in liver cancer cells. Overexpression of CAD can reduce the inhibitory effect of LM2I on pyrimidine. Pyrimidine supplementation facilitates the proliferation of liver cancer cells, particularly when they are treated with LM2I. In summary, ASS1 interacts with CAD, and LM2I enhances CAD degradation through the activation of ASS1, consequently inhibiting pyrimidine synthesis and the progression of liver cancer.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A simple, rapid, and transgene-free strategy for the generation of transgenic pigs via precise editing of monoclonal porcine fetal fibroblasts. 通过对单克隆猪胎儿成纤维细胞进行精确编辑,获得一种简单、快速、无转基因的转基因猪策略。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-05-29 DOI: 10.3724/abbs.2025044
Kun Liu, Nan Huang, Chuanxiang Ding, Qiaoli Lang, Hongyu Chen, Hao Liang, Rendong Fang, Liangpeng Ge, Xi Yang
{"title":"A simple, rapid, and transgene-free strategy for the generation of transgenic pigs via precise editing of monoclonal porcine fetal fibroblasts.","authors":"Kun Liu, Nan Huang, Chuanxiang Ding, Qiaoli Lang, Hongyu Chen, Hao Liang, Rendong Fang, Liangpeng Ge, Xi Yang","doi":"10.3724/abbs.2025044","DOIUrl":"https://doi.org/10.3724/abbs.2025044","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Andrographolide prevents necroptosis by suppressing the generation of reactive oxygen species. 穿心莲内酯通过抑制活性氧的产生来防止坏死性下垂。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-05-28 DOI: 10.3724/abbs.2025077
Na Lu, Qing Li, Linghan Duan, Rong Xu, Yaping Li, Fuli Shi, Zhiya Zhou, Yingqing Gan, Bo Hu, Jinhua Li, Xianhui He, Dongyun Ouyang, Qingbing Zha
{"title":"Andrographolide prevents necroptosis by suppressing the generation of reactive oxygen species.","authors":"Na Lu, Qing Li, Linghan Duan, Rong Xu, Yaping Li, Fuli Shi, Zhiya Zhou, Yingqing Gan, Bo Hu, Jinhua Li, Xianhui He, Dongyun Ouyang, Qingbing Zha","doi":"10.3724/abbs.2025077","DOIUrl":"https://doi.org/10.3724/abbs.2025077","url":null,"abstract":"<p><p>Andrographolide (Andro), a natural product extracted from the Chinese traditional medicine herb <i>Andrographis paniculata</i>, has been applied for the treatment of diverse inflammatory diseases. However, its effects on necroptosis, a lytic form of cell death implicated in various inflammatory diseases, remain uncharacterized. In the present study, we investigate whether Andro and its derivatives can suppress necroptosis. Our results demonstrate that Andro notably inhibits necroptosis in the <i>in vitro</i> cellular models induced by either lipopolysaccharide (LPS) plus IDN-6556 or a combination of TNF-α, LCL-161 (Smac mimetic) and IDN-6556. In these cellular models, Andro inhibits the phosphorylation of receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL), as well as the formation of necrosomes. Specifically, Andro reduces the levels of intracellular reactive oxygen species (ROS) and mitochondrial superoxide (mtROS), preserves the mitochondrial membrane potential during necroptotic induction, and activates the antioxidant transcription factor nuclear factor E2-related factor 2 (Nrf2). Upon necroptotic stimulation, some mitochondrial proteins, such as Bcl-2 and Bak, oligomerize and co-localize with RIPK1, RIPK3, and phosphorylated MLKL (p-MLKL) in necrosomes. However, this process of necrosome formation can be prevented by Andro. In contrast, derivatives, including dehydroandrographolide, neoandrographolide, 14-deoxy-11,12-didehydroandrographolide, and 14-deoxyandrographolide, have no anti-necroptotic effects and fail to upregulate Nrf2. Collectively, our findings demonstrate that Andro specifically inhibits the RIPK1/RIPK3/MLKL signaling axis to suppress necroptosis, highlighting its therapeutic potential against necroptosis-related disorders.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Vesicle-mediated transport-related gene SEC23A promotes cell proliferation by regulating cell cycle leading to gastric cancer progression. 囊泡介导的转运相关基因SEC23A通过调节细胞周期促进细胞增殖,从而导致胃癌的进展。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-05-22 DOI: 10.3724/abbs.2025051
Kang Wang, Shihao Rao, Xujin Wei, Wen Xie, Zhijun Hong, Jia Cheng, Xin Chen, Jingjing Hou, Huiqin Zhuo
{"title":"Vesicle-mediated transport-related gene SEC23A promotes cell proliferation by regulating cell cycle leading to gastric cancer progression.","authors":"Kang Wang, Shihao Rao, Xujin Wei, Wen Xie, Zhijun Hong, Jia Cheng, Xin Chen, Jingjing Hou, Huiqin Zhuo","doi":"10.3724/abbs.2025051","DOIUrl":"https://doi.org/10.3724/abbs.2025051","url":null,"abstract":"<p><p>Gastric cancer (GC) is a highly prevalent and lethal gastrointestinal cancer. Dysregulation of vesicle-mediated transport-related genes (VMTRGs) is closely associated with tumorigenesis and disease progression. However, the prognostic value of VMTRGs in GC remains unclear. In this study, on the basis of our proteomics data and public databases, we identify differentially expressed VMTRGs in infiltrative-type GC with more metastases and recurrences identified by Ming's classification. Least absolute shrinkage and selection operator (LASSO) regression identifies 3 VMTRGs ( <i>SEC23A</i>, <i>RAB31</i>, and <i>GABARAPL2</i>) from 41 infiltrative-associated VMTRGs, based on which a risk model Vesicle-Infiltrative Lasso System (VILS) is constructed, and its effectiveness and potential importance are validated by immune microenvironment analysis and functional enrichment analysis. As an independent prognostic factor for GC, VILS, combined with other clinically independent prognostic factors to form a nomogram, is effective in predicting GC prognosis. The VILS high-risk group has higher M2 macrophage and cancer-associated fibroblast infiltration, and lower infiltration of Th1 cells and natural killer cells. SEC23A is highly expressed in GC tissues and cells. The importance of SEC23A in GC cells is evaluated by <i>in vitro</i> assays including colony formation assay and CCK-8 assay, and by <i>in vivo</i> assay using a subcutaneous xenograft mouse model. The results show that SEC23A promotes GC cell proliferation and tumor growth through regulation of the cell cycle <i>in vitro</i> and <i>in vivo</i>. VILS provides excellent prognostic prediction for GC patients and is correlated with antitumor immune cell infiltration. <i>SEC23A</i>, the dominant gene of VILS, is highly expressed in GC and promotes GC growth and malignant progression through various molecular mechanisms. Our study reveals the effect of SEC23A on the proliferation of gastric cancer cells for the first time. Therefore, SEC23A has the potential to be a new therapeutic target for the diagnosis and treatment of GC.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integrated multi-omics and experimental approaches identify fascin actin-bundling protein 1 as an unfavorable prognostic biomarker in adrenocortical carcinoma. 综合多组学和实验方法确定了筋膜蛋白肌动蛋白捆绑蛋白1是肾上腺皮质癌的不利预后生物标志物。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-05-19 DOI: 10.3724/abbs.2025067
Pingkaiqi He, Yihao Chen, Ming Xi, Shanshan Mo, Jiahong Chen, Chuanfan Zhong, Fengping Liu, Weide Zhong, Le Zhang, Junhong Deng, Jianming Lu, Chao Cai
{"title":"Integrated multi-omics and experimental approaches identify fascin actin-bundling protein 1 as an unfavorable prognostic biomarker in adrenocortical carcinoma.","authors":"Pingkaiqi He, Yihao Chen, Ming Xi, Shanshan Mo, Jiahong Chen, Chuanfan Zhong, Fengping Liu, Weide Zhong, Le Zhang, Junhong Deng, Jianming Lu, Chao Cai","doi":"10.3724/abbs.2025067","DOIUrl":"https://doi.org/10.3724/abbs.2025067","url":null,"abstract":"<p><p>Adrenocortical carcinoma (ACC) is a rare epithelial tumor originating from adrenal cortical cells, notable for its high degree of malignancy and poor prognosis. Owing to heterogeneity, patient outcomes vary significantly. Current biomarkers for ACC risk stratification have notable limitations. However, with the advancement of multi-omics sequencing technology, we can utilize multi-omics data to explore the heterogeneity of ACC, thereby identifying novel biomarkers. In this study, we establish multicenter transcriptomics and ATAC-seq data from the TCGA and GEO databases to perform weighted gene coexpression network analysis (WGCNA) clustering and conduct comprehensive analyses of various ACC samples. These findings are integrated with univariate Cox regression, receiver operating characteristic (ROC) curve analysis, and survival analysis to identify potential biomarkers. We establish FSCN1 as an independent risk factor associated with poor ACC prognosis. ATAC-seq data demonstrate higher chromatin accessibility of FSCN1 in ACC patients with progressive disease. Immunohistochemical analysis confirms the expression of FSCN1 at the protein level, while functional cell assays reveal its role in promoting tumor invasion and proliferation. Functional enrichment analyses highlight the biological characteristics of FSCN1, and estimation of TME-infiltrating cells suggests that FSCN1 expression contributes to poor prognosis by inhibiting CD8 <sup>+</sup> T-cell infiltration within the ACC microenvironment. Finally, multi-omics analyses elucidate the role of FSCN1 at the mutation level. Taken together, our findings highlight FSCN1 as a promising novel biomarker and potential therapeutic target, underscoring its value in guiding the strategic management of ACC.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A modified system to promote stemness of mouse intestinal stem cells by activating Nrf2 and α2-adrenergic receptor signaling pathway. 通过激活Nrf2和α2-肾上腺素能受体信号通路促进小鼠肠道干细胞干性的改良系统。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-05-19 DOI: 10.3724/abbs.2025078
Xingyu Zhou, Li Yang, Sentao Song, Xiaolei Yin
{"title":"A modified system to promote stemness of mouse intestinal stem cells by activating Nrf2 and α2-adrenergic receptor signaling pathway.","authors":"Xingyu Zhou, Li Yang, Sentao Song, Xiaolei Yin","doi":"10.3724/abbs.2025078","DOIUrl":"https://doi.org/10.3724/abbs.2025078","url":null,"abstract":"<p><p>Intestinal stem cells (ISCs) maintain epithelial homeostasis through continuous self-renewal and differentiation, but their regulatory mechanisms remain incompletely understood. Using a simplified culture system, we identify two novel pathways that synergistically enhance stem cell characteristics: antioxidant signaling through 2-phospho-L-ascorbic acid (pVc) and α2-adrenergic receptor (α2-AR) activation by dexmedetomidine (Dex). Mechanistic studies reveal that pVc promotes stem cell maintenance through Nrf2-mediated antioxidant responses, while α2-AR activation functions through suppression of cAMP signaling. <i>In vivo</i> administration of these compounds enhances intestinal epithelial renewal while maintaining proper stem cell positioning and identity. Notably, α2-AR activation promotes regeneration after radiation injury by enhancing proliferation of stem cells produced by Bmi1 <sup>+</sup> cells in the post-injury process, demonstrating therapeutic potential. These findings advance our understanding of ISC regulation and suggest new strategies for protecting intestinal integrity during injury or disease.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Resident CD24 +LCN2 + LPCs aggravate fibrosis and inflammatory progression via the recruitment of TPPP3 +COL10A1 + macrophages in NASH. 在NASH中,常驻CD24 +LCN2 + LPCs通过募集TPPP3 +COL10A1 +巨噬细胞加重纤维化和炎症进展。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-05-16 DOI: 10.3724/abbs.2025081
Min Ding, Xiaoshu Qi, Weijian Huang, Yan Lin, Hexin Yan
{"title":"Resident CD24 <sup>+</sup>LCN2 <sup>+</sup> LPCs aggravate fibrosis and inflammatory progression via the recruitment of TPPP3 <sup>+</sup>COL10A1 <sup>+</sup> macrophages in NASH.","authors":"Min Ding, Xiaoshu Qi, Weijian Huang, Yan Lin, Hexin Yan","doi":"10.3724/abbs.2025081","DOIUrl":"https://doi.org/10.3724/abbs.2025081","url":null,"abstract":"<p><p>Resident CD24 <sup>+</sup>LCN2 <sup>+</sup> liver progenitor cells (LPCs) reportedly contribute to the expanding ductular reaction and macrophage-mediated inflammation associated with chronic liver damage. Both ductular reactions and macrophage-driven inflammation are associated with liver fibrosis and injury in various mouse liver disorders. This study aims to investigate the molecular phenotypes of LPCs and their regulatory mechanisms in humans with non-alcoholic steatohepatitis (NASH). Single-cell RNA sequencing (scRNA-seq) datasets are used to characterize the status and molecular phenotypes of LPCs in clinical NASH samples. To elucidate the regulatory mechanisms of LPCs, CellChat and NicheNet are employed to assess cell-cell communication between LPCs and other cell types. The findings are validated using RNA sequencing datasets associated with NASH progression, NASH mouse models (CDAHFD and HFD), and human NASH liver samples. Results show that resident CD24 <sup>+</sup>LCN2 <sup>+</sup> LPCs are identified and found to be significantly enriched in NASH patients. Cell communication analyses predict strong interactions between LPCs and proinflammatory macrophage subtypes. Additionally, in NASH, the liver recruits peripheral blood mononuclear cell (PBMC)-derived macrophages and polarizes them into proinflammatory subtypes. The macrophage subtype MP-2 is identified as the primary recipient of LPC-derived signals, exhibiting marked hyperactivation of the NF-κB pathway and a strong association with liver fibrosis. Finally, the MP-2 markers COL10A1 and TPPP3 are characterized and validated. In summary, this study reveals that resident CD24 <sup>+</sup>LCN2 <sup>+</sup> LPCs are activated in NASH and contribute to fibrosis progression by promoting the activation of the proinflammatory COL10A1 <sup>+</sup>TPPP3 <sup>+</sup> macrophage subtype.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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