Yiqing Guo, Yuxuan Bao, Zhichao Chen, Zhiheng Rao, Yongde Luo, Sheng Ye, Si Liu
{"title":"Novel FGF21 analogues through structure-based optimization for therapeutic development.","authors":"Yiqing Guo, Yuxuan Bao, Zhichao Chen, Zhiheng Rao, Yongde Luo, Sheng Ye, Si Liu","doi":"10.3724/abbs.2024227","DOIUrl":"https://doi.org/10.3724/abbs.2024227","url":null,"abstract":"<p><p>Fibroblast growth factor 21 (FGF21) plays a pivotal role in regulating metabolic processes and energy homeostasis, making it a promising therapeutic avenue for various obesity-related conditions. However, its therapeutic efficacy faces challenges due to its suboptimal pharmacokinetics and bioactivity. To overcome these limitations, we adapt a strategy in which key amino acid residues responsible for enhanced activity are pinpointed through sequence alignment and comparative analysis to develop long-acting FGF21 analogs. The mutant FGF21 analogs are fused with the Fc fragment. Here, we report the design, identification, and characterization of two distinct Fc-fused FGF21 analogs, Fc-FGF21(P119R) and Fc-FGF21(H125R), with significantly augmented potency. These findings hold promise for clinical applications, offering potential interventions for obesity-related metabolic disorders.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885103","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}
Hongjiao Xu, Zhuang Yu, Jun Zhu, Haoran Liu, Xiangyuan Chen, Jihong Jiang, Minmin Zhu, Jinbao Li
{"title":"Types of cell death in diabetic cardiomyopathy: insights from animal models.","authors":"Hongjiao Xu, Zhuang Yu, Jun Zhu, Haoran Liu, Xiangyuan Chen, Jihong Jiang, Minmin Zhu, Jinbao Li","doi":"10.3724/abbs.2024213","DOIUrl":"https://doi.org/10.3724/abbs.2024213","url":null,"abstract":"<p><p>Approximately one-tenth of the global population is affected by diabetes mellitus, and its incidence continues to rise each year. In China, 1.4 million patients die from diabetes-related complications every year. Additionally, approximately 26% of patients with diabetes develop diabetic cardiomyopathy, with heart failure being one of the main causes of death in these patients. However, early detection of diabetic cardiomyopathy has proven to be difficult in a clinical setting; furthermore, there are limited guidelines and targeted means of prevention and treatment for this disease. In recent years, several studies have provided evidence for the occurrence of various forms of regulated cell death in diabetic myocardial cells, including apoptosis, necroptosis, ferroptosis, and cuproptosis, which are closely linked to the pathological progression of diabetic cardiomyopathy. Although most research on diabetic cardiomyopathy is currently in the animal trial phase, the inhibition of these regulatory cell death processes can limit or slow down the progression of diabetic cardiomyopathy. Therefore, this review discusses the appropriate animal experimental models currently available for diabetic cardiomyopathy and evaluates the roles of apoptosis, necroptosis, ferroptosis, and cuproptosis in diabetic cardiomyopathy. We hope to provide new methods and ideas for future research in diabetic cardiomyopathy.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885120","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":"Structure-based design of covalent nanobody binders for a thermostable green fluorescence protein.","authors":"Zhihao Yue, Yanfang Li, Hongmin Cai, Hebang Yao, Dianfan Li, Aimin Ni, Tingting Li","doi":"10.3724/abbs.2024233","DOIUrl":"https://doi.org/10.3724/abbs.2024233","url":null,"abstract":"<p><p>The use of green fluorescence protein (GFP) has advanced numerous areas of life sciences. An ultra-thermostable GFP (TGP), engineered from a coral GFP, offers potential advantages over traditional jellyfish-derived GFP because of its high stability. However, owing to its later discovery, TGP lacks the extensive toolsets available for GFP, such as heavy chain-only antibody binders known as nanobodies. In this study, we report the crystal structure of TGP in complex with Sb92, a synthetic nanobody identified from a previous <i>in vitro</i> screening, revealing Sb92's precise three-dimensional epitope. This structural insight, alongside the previously characterized Sb44-TGP complex, allows us to rationally design disulfide bonds between the antigen and the antibody for tighter interactions. Using biochemical analysis, we identify two bridged complexes (TGP A18C-Sb44 V100C and TGP E118C-Sb92 S57C), with the TGP-Sb92 disulfide pair showing high resistance to reducing agents. Our study expands the toolkit available for TGP and should encourage its wider applications.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885111","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 host gene <i>CSTF2</i> regulates HBV replication via HBV PRE-induced nuclear export.","authors":"Jinyu Wang, Jing Li, Wentao Xie, Zhongliang Shen, Jingwen Wu, Richeng Mao, Mengji Lu, Jiming Zhang","doi":"10.3724/abbs.2024216","DOIUrl":"https://doi.org/10.3724/abbs.2024216","url":null,"abstract":"<p><p>The persistent global burden of hepatitis B virus (HBV) infection has prompted ongoing investigations into host determinants of viral control. In this study, we investigate the regulatory influence of the host gene cleavage stimulation factor subunit 2 (CSTF2) on HBV replication dynamics. We demonstrate differential CSTF2 expression across the spectrum of HBV infection phases, with upregulated expression noted during the immune-reactive and inactive carrier states compared with the immune-tolerant phase. Notably, dose-responsive attenuation of HBV DNA, as well as surface and core protein levels, is observed subsequent to CSTF2 overexpression, whereas HBV RNA levels remain unaffected. Upon HBV transfection, a notable alteration in CSTF2 subcellular localization is discerned, suggesting active relocalization to the cytoplasm, potentially mediated through interaction with the HBV posttranscriptional regulatory element (PRE). This interaction appears to impede the nuclear export of HBV RNA. Additionally, distinct antiviral efficacies are attributed to the functional domains of the CSTF2 protein, indicating a multifaceted host defense mechanism. These insights increase the understanding of host-virus interplay and identify CSTF2 as a candidate for antiviral therapeutic strategies.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891260","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}
Wentao Liu, Yuan He, Kunlun Chen, Jianwen Ye, Long Yu, Chuang Zhou, Wenlong Zhai
{"title":"YTHDF2 influences hepatic fibrosis by regulating ferroptosis in hepatic stellate cells by mediating the expression of ACSL4 in an m <sup>6</sup>A-dependent manner.","authors":"Wentao Liu, Yuan He, Kunlun Chen, Jianwen Ye, Long Yu, Chuang Zhou, Wenlong Zhai","doi":"10.3724/abbs.2024162","DOIUrl":"https://doi.org/10.3724/abbs.2024162","url":null,"abstract":"<p><p>Hepatic fibrosis (HF) is an abnormal reparative response of the liver to chronic injury and is histologically reversible. In recent years, increasing interest has been given to changes in m <sup>6</sup>A in liver disease. In this study, we explore the role of the m <sup>6</sup>A-modified reading protein YTHDF2 in HF and its regulatory mechanism. The HF mouse model is generated through CCl <sub>4</sub> injection, and the cell model is via TGF-β stimulation. The liver tissues are subjected to hematoxylin-eosin, Masson, and α-SMA immunohistochemical staining. Reactive oxygen species (ROS) and iron levels are examined via relevant kits. Quantitative real-time PCR, immunofluorescence staining, and western blot analysis were conducted to measure the YTHDF2 and ACSL4 levels. RNA immunoprecipitation, methylated RNA immunoprecipitation, RNA pull-down, and polysome fractionation were performed to understand the regulatory mechanism by which YTHDF2 affects ACSL4. The results show that YTHDF2 is highly expressed after HF induction, and the inhibition of YTHDF2 reduces fibrosis as well as ROS and iron levels. <i>In vitro</i>, overexpression of YTHDF2 increases hepatic stellate cell activation, as well as ROS and iron levels, and this effect is blocked by the silencing of <i>ACSL4</i>. YTHDF2 acts as a regulator of ACSL4 expression and is involved in m <sup>6</sup>A modification. In addition, <i>in vivo</i> experiments indicate that overexpression of ACSL4 reverses the attenuating effect of YTHDF2 interference on HFs. Therefore, YTHDF2 mediates the expression of the ferroptosis marker protein ACSL4 in an m <sup>6</sup>A-dependent manner, thereby affecting HF.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881018","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}
Xuewei Li, Jinghui Feng, Haiqin Cheng, Ning Jin, Shanshan Jin, Zhizhen Liu, Jun Xu, Jun Xie
{"title":"Human umbilical cord mesenchymal stem cells enhance liver regeneration and decrease collagen content in fibrosis mice after partial hepatectomy by activating Wnt/β-catenin signaling.","authors":"Xuewei Li, Jinghui Feng, Haiqin Cheng, Ning Jin, Shanshan Jin, Zhizhen Liu, Jun Xu, Jun Xie","doi":"10.3724/abbs.2024207","DOIUrl":"https://doi.org/10.3724/abbs.2024207","url":null,"abstract":"<p><p>Liver fibrosis is a critical stage in the progression of various chronic liver diseases to cirrhosis and liver cancer. Early inhibition of liver fibrosis is crucial for the treatment of liver disease. Hepatectomy, a common treatment for liver-related diseases, promotes liver regeneration. However, in the context of liver fibrosis, liver regeneration is hindered. Many studies have shown that mesenchymal stem cells (MSCs) can promote liver regeneration after partial hepatectomy (PH). However, there are few reports on the impact of MSC therapy on liver regeneration post-PH in the context of hepatic fibrosis. The objective of this study is to examine the impact of MSCs on liver regeneration following PH in the fibrotic liver and uncover the related molecular mechanisms. This study reveals that MSC therapy significantly enhances liver function and mitigates liver inflammation after PH in the context of hepatic fibrosis. MSCs also significantly promote liver regeneration and alleviate liver fibrosis. In addition, this study identifies the role of MSCs in promoting liver regeneration and alleviating liver fibrosis via the activation of Wnt/β-catenin signaling. The combination of MSCs with hepatectomy may offer a novel approach for the treatment of liver fibrotic diseases.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881016","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":"Cellular functions and biomedical applications of circular RNAs.","authors":"Zheyu Zhang, Zefeng Wang","doi":"10.3724/abbs.2024241","DOIUrl":"10.3724/abbs.2024241","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) have emerged as a large class of stable and conserved RNAs that are derived primarily from back-splicing of pre-mRNAs and expressed in a cell- and tissue-specific fashion. Recent studies have indicated that a subset of circRNAs may undergo translation through cap-independent pathways mediated by internal ribosome entry sites (IRESs), m6A modifications, or IRES-like short elements. Considering the stability and low immunogenicity of circRNAs, <i>in vitro</i> transcribed circRNAs hold great promise in biomedical applications. In this review, we briefly discuss the noncoding and coding functions of circRNAs in cells, as well as the methods for the <i>in vitro</i> synthesis of circRNAs and current advances in the applications of circRNAs in biomedicine.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"157-168"},"PeriodicalIF":3.3,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885095","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}
Yingying Guo, Panpan Zhang, Zhixing Gao, Xiaotian Liu, Chen Su, Su Chen, Tao An, Jingjing Hou
{"title":"Inhibition of USP22 by miR-200b-5p represses gastric cancer cell proliferation and migration by targeting the NF-κB signaling pathway.","authors":"Yingying Guo, Panpan Zhang, Zhixing Gao, Xiaotian Liu, Chen Su, Su Chen, Tao An, Jingjing Hou","doi":"10.3724/abbs.2024231","DOIUrl":"https://doi.org/10.3724/abbs.2024231","url":null,"abstract":"<p><p>Gastric cancer (GC) is an aggressive tumor type with an intricate pathogenesis and limited therapeutic options. Ubiquitin-specific protease 22 (USP22) is a protein implicated in cell proliferation, metastasis, and tumorigenesis. However, the regulatory mechanisms governing USP22 in GC are still not fully understood. In this study, we perform bioinformatics analysis to identify conserved miRNA recognition sites for miR-200b-5p within the 3'UTR of <i>USP22</i>. Validation via luciferase reporter assay confirms the transcriptional regulation of <i>USP22</i> by miR-200b-5p. Overexpression of miR-200b-5p markedly inhibits the proliferation and migration of GC cells <i>in vitro</i> and suppresses tumor growth <i>in vivo</i>. Conversely, ectopic expression of USP22 reversed this effect by modulating the NF-κB signaling pathway. Additionally, qPCR analysis reveals an inverse correlation between the miR-200b-5p level and USP22 expression in GC. Collectively, our findings indicate that miR-200b-5p-mediated inhibition of USP22 attenuates cell proliferation by targeting the NF-κB signaling pathway in GC, suggesting that miR-200b-5p and USP22 could serve as potential diagnostic or therapeutic targets for gastric cancer and other related human diseases.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875725","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}
Wangwen Wang, Xi Lu, Chengjun Zhu, Jie Li, Yue Liu, Zhangchao Yao, Xiaolin Li
{"title":"O-GlcNAcylation-related genes mediate tumor microenvironment characteristics and prediction of immunotherapy response in gastric cancer.","authors":"Wangwen Wang, Xi Lu, Chengjun Zhu, Jie Li, Yue Liu, Zhangchao Yao, Xiaolin Li","doi":"10.3724/abbs.2024222","DOIUrl":"https://doi.org/10.3724/abbs.2024222","url":null,"abstract":"<p><p>We aim to identify molecular clusters related to O-GlcNAcylation and establish a novel scoring system for predicting prognosis and immunotherapy efficacy in patients with gastric cancer (GC). The transcriptomic and clinical data are obtained from XENA-UCSC and GEO databases. The O-GlcNAcylation-related genes are obtained from the GSEA database. Consensus clustering analysis is employed to identify O-GlcNAcylation-related molecular clusters, and principal component analysis (PCA) is utilized to develop a novel prognostic scoring system for predicting GC outcomes and immunotherapy efficacy. The prognostic accuracy of the scoring system is assessed across five real-world cohorts. The biological function of actin alpha 2, smooth muscle (ACTA2) in GC is determined through experimental verification. Using 34 O-GlcNAcylation-related genes associated with prognosis in GC patients, these individuals are divided into two distinct subgroups characterized by different outcomes, tumor microenvironment profiles, and clinical case characteristics. The DEGs between the two subgroups are subsequently used to further divide the GC patients into two subgroups by consensus cluster analysis. PCA is used to construct a prognostic scoring system, which reveal that patients in the low-score subgroup have a better prognosis and greater benefit from immunotherapy. The accuracy of the scoring system is confirmed through validation in a cohort of patients receiving immunotherapy in the real world. ACTA2 promotes proliferation and inhibits apoptosis in GC cells. These findings suggest that we successfully establish molecular clusters associated with O-GlcNAcylation and develop a scoring system that demonstrates strong performance in predicting the prognosis of patients with GC and the effect of immunotherapy interventions.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852020","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}