Yuan Wang, Haokun Yuan, Ruiqin Fang, Ran Zhang, Wei-Jia Wang
{"title":"Unveiling the cytotoxicity of a new gold(I) complex towards hepatocellular carcinoma by inhibiting TrxR activity.","authors":"Yuan Wang, Haokun Yuan, Ruiqin Fang, Ran Zhang, Wei-Jia Wang","doi":"10.3724/abbs.2024155","DOIUrl":"https://doi.org/10.3724/abbs.2024155","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC), the predominant type of liver cancer, is an aggressive malignancy with limited therapeutic options. In this study, we assess a collection of newly designed gold(I) phosphine complexes. Remarkably, the compound GC002 exhibits the greatest toxicity to HCC cells and outperforms established medications, such as sorafenib and auranofin, in terms of antitumor efficacy. GC002 triggers irreversible necroptosis in HCC cells by increasing the intracellular accumulation of reactive oxygen species (ROS). Mechanistically, GC002 significantly suppresses the activity of thioredoxin reductase (TrxR), which plays a crucial role in regulating redox homeostasis and is often overexpressed in HCC by binding directly to the enzyme. Our <i>in vivo</i> xenograft study confirms that GC002 possesses remarkable antitumor activity against HCC without severe side effects. These findings not only highlight the novel mechanism of controlling necroptosis via TrxR and ROS but also identify GC002 as a promising candidate for the further development of antitumor agents targeting HCC.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306914","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":"<i>UHRF1</i> knockdown induces cell cycle arrest and apoptosis in breast cancer cells through the ZBTB16/ANXA7/Cyclin B1 axis.","authors":"Di Liu, Qin Du, Yuxuan Zhu, Yize Guo, Ya Guo","doi":"10.3724/abbs.2024148","DOIUrl":"https://doi.org/10.3724/abbs.2024148","url":null,"abstract":"<p><p>Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) is involved in tumorigenicity through DNA methylation in various cancers, including breast cancer. This study aims to investigate the regulatory mechanisms of UHRF1 in breast cancer progression. Herein, we show that UHRF1 is upregulated in breast cancer tissues and cell lines as measured by western blot analysis and immunohistochemistry. Breast cancer cells are transfected with a UHRF1 overexpression plasmid (pcDNA-UHRF1) or short hairpin RNA targeting UHRF1 (sh-UHRF1), followed by detection of cell proliferation, invasion, apoptosis, and cell cycle. UHRF1 overexpression promotes proliferation and invasion and attenuates cell cycle arrest and apoptosis in breast cancer cells, while <i>UHRF1</i> knockdown shows the opposite effect. Moreover, methylation-specific PCR and ChIP assays indicate that UHRF1 inhibits zinc finger and BTB domain containing 16 (ZBTB16) expression by promoting ZBTB16 promoter methylation via the recruitment of DNA methyltransferase 1 (DNMT1). Then, a co-IP assay is used to verify the interaction between ZBTB16 and the annexin A7 (ANXA7) protein. ZBTB16 promotes ANXA7 expression and subsequently inhibits Cyclin B1 expression. Rescue experiments reveal that <i>ZBTB16</i> knockdown reverses the inhibitory effects of <i>UHRF1</i> knockdown on breast cancer cell malignancies and that <i>ANXA7</i> knockdown abolishes the inhibitory effects of ZBTB16 overexpression on breast cancer cell malignancies. Additionally, <i>UHRF1</i> knockdown significantly inhibits xenograft tumor growth <i>in vivo</i>. In conclusion, <i>UHRF1</i> knockdown inhibits proliferation and invasion, induces cell cycle arrest and apoptosis in breast cancer cells via the ZBTB16/ANXA7/Cyclin B1 axis, and reduces xenograft tumor growth <i>in vivo</i>.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278636","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":"Label-free and rapid mechanics of single cells under high-density co-culture conditions by deep learning image recognition-assisted atomic force microscopy.","authors":"Xuliang Yang,Mi Li","doi":"10.3724/abbs.2024158","DOIUrl":"https://doi.org/10.3724/abbs.2024158","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142266081","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":"miR-155 induces sepsis-associated damage to the intestinal mucosal barrier via sirtuin 1/nuclear factor-κB-mediated intestinal pyroptosis.","authors":"Zhihua Li,Yi Wang,Weiwei Huang,Xingyu Shi,Tao Ma,Xiangyou Yu","doi":"10.3724/abbs.2024124","DOIUrl":"https://doi.org/10.3724/abbs.2024124","url":null,"abstract":"Sepsis is a life-threatening state of organ dysfunction caused by systemic inflammation and a dysfunctional response to host infections that can induce severe intestinal mucosal damage. Pyroptosis is mediated by the activated NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome after stimulation by various inflammatory factors during sepsis. The inflammatory response is a major driver of intestinal damage during sepsis. Intestinal mucosal barrier dysfunction in sepsis is associated with pyroptosis, a type of programmed inflammatory cell death. Several studies have confirmed the role of miR-155 in sepsis and other diseases. However, the effect of miR-155 on intestinal pyroptosis in the context of intestinal mucosal barrier dysfunction during sepsis remains unclear. Thus, a model of sepsis in Sprague-Dawley rats is established using cecal ligation and puncture (CLP), and a series of molecular biological methods are used in this study. The results show that the expression of miR-155 is increased and that of sirtuin 1 (SIRT1) is decreased in the intestinal tissues of patients with sepsis. miR-155 expression is negatively correlated with SIRT1 expression. Increased miR-155 expression significantly inhibits SIRT1 activity and upregulates the expressions of NOD-like receptor family pyrin domain-containing 3 (NLRP3), caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC), interleukin-1β (IL-1β) and interleukin-18 (IL-18) to promote pyroptosis. The inhibition of miR-155 expression is associated with increased SIRT1 expression, promotes the deacetylation of p65, and significantly downregulates p65 acetylation. Herein, we propose that miR-155 induces pyroptosis in the intestine partly by regulating SIRT1, thereby reducing the deacetylation of the nuclear factor (NF)-κB subunit p65 and increasing NF-κB signaling activity in sepsis, leading to intestinal barrier damage.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202358","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}
Li Zhang,Yingmei Chen,Quanrong Pan,Shizheng Fang,Zhongjian Zhang,Jia Wang,Yongjian Yang,Dachun Yang,Xiongshan Sun
{"title":"Silencing of PCK1 mitigates the proliferation and migration of vascular smooth muscle cells and vascular intimal hyperplasia by suppressing STAT3/DRP1-mediated mitochondrial fission.","authors":"Li Zhang,Yingmei Chen,Quanrong Pan,Shizheng Fang,Zhongjian Zhang,Jia Wang,Yongjian Yang,Dachun Yang,Xiongshan Sun","doi":"10.3724/abbs.2024154","DOIUrl":"https://doi.org/10.3724/abbs.2024154","url":null,"abstract":"The pathological proliferation and migration of vascular smooth muscle cells (VSMCs) are key processes during vascular neointimal hyperplasia (NIH) and restenosis. Phosphoenolpyruvate carboxy kinase 1 (PCK1) is closely related to a variety of malignant proliferative diseases. However, the role of PCK1 in VSMCs has rarely been investigated. This study aims to examine the role of PCK1 in the proliferation and migration of VSMCs and vascular NIH after injury. In vivo, extensive NIH and increased expression of PCK1 within the neointima are observed in injured arteries. Interestingly, the administration of adeno-associated virus-9 (AAV-9) carrying Pck1 short hairpin RNA (sh Pck1) significantly attenuates NIH and stenosis of the vascular lumen. In vitro, Pck1 small interfering RNA (si Pck1)-induced PCK1 silencing inhibits VSMC proliferation and migration. Additionally, silencing of PCK1 leads to reduced expression of dynamin-related protein 1 (DRP1) and attenuated mitochondrial fission. Lentivirus-mediated DRP1 overexpression markedly reverses the inhibitory effects of PCK1 silencing on VSMC proliferation, migration, and mitochondrial fission. Finally, PCK1 inhibition attenuates the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Activation of STAT3 abolishes the suppressive effects of PCK1 silencing on DRP1 expression, mitochondrial fission, proliferation, and migration in VSMCs. In conclusion, PCK1 inhibition attenuates the mitochondrial fission, proliferation, and migration of VSMCs by inhibiting the STAT3/DRP1 axis, thereby suppressing vascular NIH and restenosis.","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202359","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}
Rengui Jiang, Xuyu He, Weidong Chen, Huoying Cai, Zhaohai Su, Zheng Xie, Bilong Zhang, Jiangyong Yang, Yueting Wang, Ling Huang, Gang Cao, Xiutong Zhong, Hui Xie, Hengqing Zhu, Jun Cao, Weiling Lu
{"title":"lncRNA H19 facilitates vascular neointima formation by targeting miR-125a-3p/FLT1 axis.","authors":"Rengui Jiang, Xuyu He, Weidong Chen, Huoying Cai, Zhaohai Su, Zheng Xie, Bilong Zhang, Jiangyong Yang, Yueting Wang, Ling Huang, Gang Cao, Xiutong Zhong, Hui Xie, Hengqing Zhu, Jun Cao, Weiling Lu","doi":"10.3724/abbs.2024087","DOIUrl":"https://doi.org/10.3724/abbs.2024087","url":null,"abstract":"<p><p>The aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the development of neointima formation in vascular restenosis. This study aims to explore the function of the long noncoding RNA H19 in neointima formation. A mouse carotid ligation model was established, and human vascular smooth muscle cells (VSMCs) were used as a cell model. lncRNA H19 overexpression promoted VSMC proliferation and migration. Moreover, miR-125a-3p potentially bound to lncRNA H19, and Fms-like tyrosine kinase-1 (FLT1) might be a direct target of miR-125a-3p in VSMCs. Upregulation of miR-125a-3p alleviated lncRNA H19-enhanced VSMC proliferation and migration. Furthermore, rescue experiments showed that enhanced expression of miR-125a-3p attenuated lncRNA H19-induced FLT1 expression in VSMCs. In addition, the overexpression of lncRNA H19 significantly exacerbated neointima formation in a mouse carotid ligation model. In summary, lncRNA H19 stimulates VSMC proliferation and migration by acting as a competing endogenous RNA (ceRNA) of miR-125a-3p. lncRNA H19 may be a therapeutic target for restenosis.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138968","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}
Jiazheng Liu, Limei Lin, Lina Zhang, Hongtu Ma, Xi Chen, Keliang Pang, Linlin Li, Hua Han
{"title":"Three-dimensional reconstruction of rat sperm using volume electron microscopy.","authors":"Jiazheng Liu, Limei Lin, Lina Zhang, Hongtu Ma, Xi Chen, Keliang Pang, Linlin Li, Hua Han","doi":"10.3724/abbs.2024144","DOIUrl":"https://doi.org/10.3724/abbs.2024144","url":null,"abstract":"<p><p>Three-dimensional (3D) reconstruction serves as a crucial instrument for the analysis of biological structures. In particular, a comprehensive and accurate 3D ultrastructural examination of rat sperm is vital for understanding and diagnosing male fertility issues and the underlying causes of infertility. In this study, we utilize the automated tape-collecting ultramicrotome scanning electron microscopy (ATUM-SEM) imaging technique, which is a highly effective method for 3D cellular ultrastructural analysis. Our findings reveal that during spermiogenesis, the volume of the nucleus significantly decreases, shrinking to just 10% of its original size. The acrosomal vesicles derived from the Golgi apparatus converge and elongate along the spermatid nucleus. These vesicles then attach to the nucleus via a cap-like structure, thereby defining the head side of the spermatozoa. In the initial stages of spermiogenesis, the mitochondria in spermatids are distributed beneath the cell membrane. As the process progresses, these mitochondria gradually migrate to the sperm tail, where they form the mitochondrial sheath. This sheath plays a crucial role in providing the energy required for the movement of the sperm. In addition, we reconstruct the mRNA-stroring structure-chromatoid body in sperm cells, which are cloud-like or net-like structures in the cytoplasm. The precise and comprehensive nature of 3D ultrastructural examination allows for a deeper understanding of the morphological process of spermiogenesis, thereby contributing to our knowledge of male fertility and the causes of infertility. Our research has significantly advanced the understanding of the 3D ultrastructure of sperm more comprehensively than ever before.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144913","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":"Structures and mechanisms of the RNA m <sup>6</sup>A writer.","authors":"Ting Deng, Jinbiao Ma","doi":"10.3724/abbs.2024152","DOIUrl":"https://doi.org/10.3724/abbs.2024152","url":null,"abstract":"<p><p><i>N</i> <sup>6</sup>-methyladenosine (m <sup>6</sup>A) is the most prevalent epigenetic modification found in eukaryotic mRNAs and plays a crucial role in regulating gene expression by influencing numerous aspects of mRNA metabolism. The m <sup>6</sup>A writer for mRNAs and long non-coding RNAs consists of the catalytic subunit m <sup>6</sup>A-METTL complex (MTC) (including METTL3/METTL14) and the regulatory subunit m <sup>6</sup>A-METTL-associated complex (MACOM) (including HAKAI, WTAP, VIRMA, ZC3H13, and RBM15/15B). In this review, we focus on recent advances in our understanding of the structural and functional properties of m <sup>6</sup>A writers and the possible mechanism by which they recognize RNA substrates and perform selective m <sup>6</sup>A modifications.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138969","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":"Nuclear mRNA export.","authors":"Suli Chen, Qingyi Jiang, Jing Fan, Hong Cheng","doi":"10.3724/abbs.2024145","DOIUrl":"https://doi.org/10.3724/abbs.2024145","url":null,"abstract":"<p><p>In eukaryotic cells, gene expression begins with transcription in the nucleus, followed by the maturation of messenger RNAs (mRNAs). These mRNA molecules are then exported to the cytoplasm through the nuclear pore complex (NPC), a process that serves as a critical regulatory phase of gene expression. The export of mRNA is intricately linked to precursor mRNA (pre-mRNA) processing, ensuring that only properly processed mRNA reaches the cytoplasm. This coordination is essential, as recent studies have revealed that mRNA export factors not only assist in transport but also influence upstream processing steps, adding a layer of complexity to gene regulation. Furthermore, the export process competes with RNA processing and degradation pathways, maintaining a delicate balance vital for accurate gene expression. While these mechanisms are generally conserved across eukaryotes, significant differences exist between yeast and higher eukaryotic cells, particularly due to the more genome complexity of the latter. This review delves into the current research on mRNA export in higher eukaryotic cells, focusing on its role in the broader context of gene expression regulation and highlighting how it interacts with other gene expression processes to ensure precise and efficient gene functionality in complex organisms.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144912","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}