Acta biochimica et biophysica Sinica最新文献

{"title":"Using transcription and translation regulators to improve recombinant protein expression in CHO cells.","authors":"Shaolei Geng, Chunliu Mi, Chong Wang, Jiayue Li, Qiuli Sun, Weidong Li, Tianyun Wang","doi":"10.3724/abbs.2025160","DOIUrl":"https://doi.org/10.3724/abbs.2025160","url":null,"abstract":"<p><p>Chinese hamster ovary (CHO) cells are the predominant platform for the production of recombinant therapeutic proteins (RTPs). Over the past two decades, numerous strategies have focused on increasing the growth, titer and quality of RTPs in CHO cells and concomitantly reducing production costs. Transcription and translation are continuous processes that are crucial for RTP production. Transcription factors (TFs) are predominantly involved in the regulation of growth, metabolism, and endoplasmic reticulum function, and TF engineering has been demonstrated to be an efficacious strategy for enhancing RTP expression, enabling the design of customized TFs and promoters. Translation regulators encompass translation, folding, secretion, and post-translational modifications and involve a multitude of key genes and signaling pathways, which are vital for the immunogenicity of RTPs. Novel synthetic biology methods and advancements in genomics have played significant roles in the design of specific TFs and the selection of translation factors. This review summarizes the strategies for increasing RTP expression in CHO cells via TFs and translation factors. We also propose methods to further optimize protein expression strategies and develop more efficient CHO cell lines by leveraging advancements in genomics and synthetic biology research.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079460","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}

{"title":"Exosomal miR-146a-3p modulates neural stem cell fate through UCHL1 downregulation in spinal cord injury: implications for neuroregeneration.","authors":"Ying Gao, Ziwen Shi, Suhe Zhang, Zhiqiang Wu, Tao Zhou, Pinghui Zhou, Weiwei Chu, Xuyi Wang","doi":"10.3724/abbs.2025131","DOIUrl":"https://doi.org/10.3724/abbs.2025131","url":null,"abstract":"<p><p>Spinal cord injury (SCI) poses a substantial challenge within the field of regenerative medicine, primarily because of its high incidence of disability and the paucity of effective therapeutic interventions. This study explores the involvement of cerebrospinal fluid (CSF) exosomes in the differentiation of neural stem cells (NSCs) following SCI, with a particular emphasis on the miR-146a-3p/UCHL1 signaling axis. Using an SCI animal model, we analyze the molecular composition of CSF and its influence on NSC fate through bioinformatics approaches, dual-luciferase reporter assays, and <i>in vitro</i> differentiation experiments. Differential expression analyses reveal a significant upregulation of miR-146a-3p in CSF-derived exosomes post-SCI, which directly targets and suppresses UCHL1, a pivotal regulator of neuronal differentiation. Overexpression of UCHL1 facilitates the differentiation of NSCs into neurons and enhances functional recovery, whereas its downregulation leads to increased astrocytic differentiation and fibrotic scar formation. These findings are corroborated through immunofluorescence, western blot analysis, and behavioral assessments. In summary, our study identifies miR-146a-3p as a critical regulator in SCI, offering novel insights into the role of microRNAs in modulating neural stem cell fate and promoting neuronal regeneration. Our study highlights the pivotal role of CSF exosomal miRNAs in determining NSC fate, paving the way for systemic interventions in injured spinal cord injury repair. These findings underscore the importance of exosomal miRNAs in modulating the spinal cord microenvironment, potentially leading to novel strategies for enhancing functional recovery in SCI patients.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051672","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}

{"title":"Angptl4 is upregulated by microenvironmental factors during the wound healing process and promotes epidermal stem cell proliferation via PRL8a6.","authors":"Siyuan Yu, Pengxiang Ji, Ting Du, Zuohua Liu, Yuan Yang, Zhenkun Lv, Lei Xu, Qianheng Jin, Weijuan Gong, Yingying Le, Yi Fu, Ruixing Hou","doi":"10.3724/abbs.2025145","DOIUrl":"https://doi.org/10.3724/abbs.2025145","url":null,"abstract":"<p><p>Angiopoietin-like 4 (ANGPTL4) expression is increased in wound tissue and contributes to wound healing. However, the underlying mechanisms are not fully understood. Here, we demonstrate that ANGPTL4 expression is significantly increased in epidermal stem cells (EpSCs) in the periwound epidermis during wound healing in mice. Increased Angptl4 expression is positively correlated with increased expressions of tumor growth factor-α, interleukin-1β, epidermal growth factor, nerve growth factor, fibroblast growth factor 7, and transforming growth factor-β1. Each of these molecules induces Angptl4 expression in mouse EpSCs. RNA sequencing of EpSCs derived from wild-type and Angptl4 knockout (Angptl4 ^-/-) mice reveals altered expressions of genes involved in the cell cycle and cell proliferation in Angptl4 ^-/- EpSCs, including a decrease in cyclin E2/A2/B1 and cyclin-dependent kinase 1 ( <i>Cdk1</i>) expression; an increase in Cdk inhibitor 2a ( <i>Cdkn2a</i>) and <i>Cdkn2b</i> expression; and a decrease in the prolactin (PRL) family members <i>Prl2a1</i>, <i>Prl8a1</i>, <i>Prl8a9</i>, and <i>Prl8a6</i>. Mechanistic studies reveal that ANGPTL4 stimulates EpSC proliferation via PRL8a6-mediated upregulation of cyclins A2/E2/B1 and Cdk1, downregulation of Cdkn2a, and acceleration of cell cycle progression from the G1 to the S and G2 phases. <i>In vivo</i> studies demonstrate that <i>Prl8a6</i> mRNA is upregulated by ANGPTL4 in mouse periwound tissue during skin wound healing. Knockdown of <i>Angptl4</i> or <i>Prl8a6</i> in periwound skin tissue impairs EpSC proliferation and delays wound re-epithelialization. In conclusion, our study demonstrates that, after skin injury, elevated levels of proinflammatory cytokines and growth factors in periwound tissue stimulate <i>Angptl4</i> expression in EpSCs and that ANGPTL4 promotes EpSC proliferation by increasing Prl8a6 expression, thereby accelerating wound re-epithelialization.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051654","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}

{"title":"The E2F1‒KIF14 axis drives focal adhesion formation and promotes colorectal cancer metastasis.","authors":"Yajie Wang, Xinyue Wu, Xiaofeng Li, Xiaoying Lian, Jiao An, Wenhua Cai, Jing Jia, Changjun Zhu","doi":"10.3724/abbs.2025158","DOIUrl":"https://doi.org/10.3724/abbs.2025158","url":null,"abstract":"<p><p>Kinesin family member 14 (KIF14) has been implicated in the progression of multiple cancer types, yet its role in colorectal cancer (CRC) metastasis remains undefined. Here, we assesse KIF14 expression in CRC specimens and explore its clinical and functional significance. KIF14 upregulation is frequently observed in CRC tissues and is correlated with advanced tumor stage and reduced overall survival. Functional assays reveal that KIF14 depletion in CRC cells inhibits migration, invasion, and <i>in vivo</i> metastatic colonization, whereas KIF14 overexpression induces the opposite effects. Transcriptomic and pathway enrichment analyses reveal that KIF14 functions as a critical regulator of focal adhesion and cell-matrix adhesion signaling. This finding is further supported by experimental evidence showing that KIF14 overexpression promotes focal adhesion assembly, whereas <i>KIF14</i> knockdown disruptes this process. Mechanistically, we demonstrate that KIF14 binds directly to the focal adhesion protein vinculin and mediates its delivery to the leading edge of migrating cells. Moreover, bioinformatics prediction and chromatin immunoprecipitation confirm that E2F1 directly binds the <i>KIF14</i> promoter to drive its transcription. Rescue experiments reveal that ectopic KIF14 expression restores the prometastatic phenotypes suppressed by <i>E2F1</i> silencing, indicating that the effects of E2F1 are mediated by the E2F1‒KIF14 axis. Collectively, our findings reveal a novel E2F1-KIF14-vinculin signaling axis that drives CRC metastasis by modulating focal adhesion dynamics, highlighting KIF14 as a potential therapeutic target.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032364","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}

{"title":"Lysyl oxidase exacerbates rheumatoid arthritis through promoting angiogenesis and the proliferation of fibroblast-like synoviocytes.","authors":"Hong Deng, Yanmeng Li, Tai Teng, Kaibo Wang, Chen Ji, Lijuan Yang, Shuming Zhang, Yanbin Tian, Mei Han","doi":"10.3724/abbs.2025162","DOIUrl":"https://doi.org/10.3724/abbs.2025162","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is an autoimmune disorder characterized by synovial hyperplasia and pannus formation, which serves as its primary pathological feature and may ultimately result in joint deformities. Lysyl oxidase (LOX) is involved in the formation and remodeling of the extracellular matrix, but its role in RA is not yet clear. This study aims to investigate the mechanism of lysyl oxidase (LOX) in synovial hyperplasia and pannus formation associated with rheumatoid arthritis (RA). Synovial, serum, and synovial fluid samples are collected from RA, osteoarthritis (OA), and knee injury patients and subsequently analyzed via HE staining, immunohistochemistry, and ELISA. Compared with those of the OA and injury groups, the RA synovium presents increased thickness, disorganized cell layers, increased microvascular density (MVD), and elevated LOX expression. Moreover, LOX levels are positively correlated with the MVD. Both synovial fluid and fibroblast-like synoviocytes (FLSs) derived from RA patients present significantly elevated concentrations of LOX. <i>In vitro</i> experiments reveal that LOX dose-dependently promotes the proliferation of FLSs derived from both RA patients and healthy individuals (MH7A/HFLS) by accelerating S/M-phase cell cycle progression while simultaneously stimulating angiogenesis in human umbilical vein endothelial cells (HUVECs). In contrast, the LOX inhibitor BAPN suppresses these effects. Mechanistic analysis further reveals that LOX increases the phosphorylation of the PI3K-AKT signaling pathway, an effect that is reversible by BAPN. In conclusion, LOX may induce abnormal fibroblast proliferation and endothelial neovascularization via activation of the PI3K/AKT pathway, thus aggravating synovial hyperplasia and pathological membrane formation in RA. These findings provide a theoretical foundation for the development of targeted LOX treatments for RA.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022557","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}

{"title":"Intestinal epithelial C/EBPβ deficiency impairs colitis-associated tumorigenesis by disrupting CXCL1/CXCL2/CXCL5-CXCR2-mediated neutrophil infiltration.","authors":"Mingyue Li, Xintong Wang, Wenjie Hu, Xiaohui Cheng, Qi Sun, Yongjie Wu, Zhen Huang, Jiangning Chen","doi":"10.3724/abbs.2025119","DOIUrl":"https://doi.org/10.3724/abbs.2025119","url":null,"abstract":"<p><p>Dysregulated transcription factors critically link chronic inflammation to oncogenesis in colitis-associated colorectal cancer (CAC), but their mechanistic roles remain incompletely understood. By integrating microarray and transcriptome sequencing data from ulcerative colitis (UC), colitis-associated cancer (CAC), and colorectal cancer (CRC) patients, we identify C/EBPβ as a key transcriptional regulator whose elevated expression inversely correlates with survival. In azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC models, intestinal epithelial C/EBPβ is upregulated during tumor progression, which is correlated with exacerbated tumor burden and neutrophil infiltration. Mice with intestinal epithelial-specific <i>Cebpb</i> deletion ( <i>Cebpb</i> ^ΔIEC) are resistant to carcinogenesis, accompanied by reduced neutrophil infiltration and tumor growth. Mechanistically, C/EBPβ transcriptionally activates CXCR2 ligands (CXCL1, CXCL2, and CXCL5) to drive neutrophil recruitment. Pharmacological inhibition of CXCR2 phenocopies the anti-tumor effects of <i>Cebpb</i> ^ΔIEC deletion, further validating this axis as a therapeutic target. Correlation analysis of patient tissues confirms positive relationships between C/EBPβ, CXCR2 ligands, and neutrophil infiltration, suggesting that targeting the C/EBPβ-CXCL1/2/5-CXCR2 axis may constitute a novel strategy for treating CAC.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022518","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}

{"title":"ADD domain added new binding partners for the nuclear hub protein ATRX.","authors":"Yan Chen, Yang Luo, Jielin Sun, Shouhua Wang, Bingbing Wan","doi":"10.3724/abbs.2025140","DOIUrl":"https://doi.org/10.3724/abbs.2025140","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022584","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}

{"title":"The SRC-TOPK positive feedback loop promotes RB1 phosphorylation and drives the development of lung squamous cell carcinoma.","authors":"Xiaofei Zeng, Longzhen Cui, Beibei Tang, Fei Wang, Hua He, Feng Zhu, Minjie Ma, Chang Chen","doi":"10.3724/abbs.2025149","DOIUrl":"https://doi.org/10.3724/abbs.2025149","url":null,"abstract":"<p><p>Lung squamous cell carcinoma (LUSC) is a common subtype of non-small cell lung cancer, with limited treatment options and poor patient prognosis. Currently, common driver mutations in lung adenocarcinoma rarely occur in LUSC; the mutated genes found in LUSCs lack corresponding targeted drugs. Therefore, it is necessary to discover new therapeutic targets for LUSC and provide patients with more treatment options. By analyzing different databases and tissue microarray immunohistochemistry staining, we firstly find that the expression of SRC/TOPK is elevated and positively correlated in LUSC and that patients with high SRC/TOPK expression have shorter survival time. Changing the expression levels of SRC/TOPK in LUSC cells can affect cell growth and colony formation, as there is a positive feedback loop between SRC and TOPK that regulates the transcription factor RB1, thereby altering the expressions of key factors in some growth-related signaling pathways. These inhibitors can synergistically promote apoptosis and have been validated <i>in vivo</i>. Therefore, the positive feedback loop between SRC and TOPK promotes tumorigenicity by inhibiting RB1 function, and has the potential to become a precise therapeutic target for LUSC, providing new possibilities for targeted therapy.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999440","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}

{"title":"Intestinal aging-related immune dysfunction: mechanisms and interventions.","authors":"Xin Shen, Xianzhi Gao, Lie Wang","doi":"10.3724/abbs.2025157","DOIUrl":"https://doi.org/10.3724/abbs.2025157","url":null,"abstract":"<p><p>Intestinal immunosenescence, a hallmark of organismal aging, has emerged as a critical biological process impacting the health of elderly individuals. This review systematically examines the core mechanisms underlying intestinal immunosenescence, including immune cell dysfunction, imbalances in immune-microbiota interactions, and impaired barrier function. We analyze its associations with infectious diseases, chronic inflammation, and neurodegenerative disorders, summarizing recent advances in dietary interventions, microecological therapy, and other emerging strategies. By integrating cutting-edge technologies, we prospect the development of precision interventions aimed at delaying intestinal immunosenescence, thereby providing a theoretical basis for improving the healthspan of the aging population.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999453","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}

{"title":"The ACSS2-PPARD-BCAT1 axis synchronously regulates branched-chain amino acid metabolism and development in pancreatic cancer.","authors":"Haidi Chen, Zeng Ye, Lijun Liu, Wenyan Xu, Yihua Shi, Shunrong Ji, Xiaowu Xu, Xianjun Yu, Sen Hou, Yi Qin, Chenjie Zhou","doi":"10.3724/abbs.2025111","DOIUrl":"https://doi.org/10.3724/abbs.2025111","url":null,"abstract":"<p><p>The characteristics of the tumor microenvironment (TME) of pancreatic cancer include an abundant stroma, hypoxia, insufficient blood supply and high degree of immunosuppression. Therefore, overcoming the TME conditions to reach a hypermetabolic state is a concern for the treatment of pancreatic cancer. Previous studies have demonstrated that tumor cells adapt to the TME by activating or increasing the expression level of ACSS2 under metabolic stress. Our study focuses mainly on the relationship between ACSS2 and amino acid metabolism. We find that ACSS2 is generally highly expressed and promotes the proliferation and invasiveness of pancreatic cancer. Knockout of <i>ACSS2</i> reduces the catabolism of branched chain amino acids (BCAAs) by inhibiting the transcription of <i>BCAT1</i>. ACSS2 participates in the regulation of histone and transcription factor acetylation. Mechanistically, ACSS2 promotes acetylation at the H3K27 site in the <i>PPARD</i> promoter region to increase the transcription of <i>BCAT1</i> and ultimately alters the metabolic status of BCAAs. Moreover, the proliferation and invasion status induced by ACSS2 can be partly reversed by BCAT1 in pancreatic cancer cells. In summary, we believe that targeting the ACSS2-PPARD-BCAT1 axis has certain clinical value and can provide a new therapeutic strategy for the comprehensive treatment of pancreatic cancer.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999430","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}