Acta biochimica et biophysica Sinica最新文献

{"title":"The peripheral Atf3 ⁺ neuronal population is responsible for nerve regeneration at the early stage of nerve injury revealed by single-cell RNA sequencing.","authors":"Li Liu, Junhui Chen, Wen Yin, Po Gao, Yinghui Fan, Daxiang Wen, Yingfu Jiao, Weifeng Yu","doi":"10.3724/abbs.2024169","DOIUrl":"10.3724/abbs.2024169","url":null,"abstract":"<p><p>Peripheral nerve injury (PNI) can transform primary somatosensory neurons to a regenerative state. However, the details of the transcriptomic changes associated with the nerve regeneration of somatosensory neurons remain unclear. In this study, single-cell RNA sequencing (scRNA-seq) is conducted on mouse dorsal root ganglion (DRG) cells after the early stage of nerve injury on day 3 after chronic constriction injury (CCI). We observe that a novel CCI-induced neuronal population (CIP) emerge and express high levels of activating transcription factor ( <i>Atf3</i>), a neuronal injury marker. CIP neurons highly express regeneration-associated genes (RAGs) and are enriched in regeneration-related gene ontology (GO) terms, suggesting that these neurons can constitute a pro-regenerative population. Moreover, intercellular communication networks show that CIP neurons closely communicate with satellite glial cells (SGCs) and specifically transmit strong <i>Fgf3</i>- <i>Fgfr1</i> signaling to SGCs, which could initiate regeneration-associated transcriptional changes in SGCs. We also confirm that regenerative progress occurs at the early stage of nerve injury because immunohistochemistry shows that the expression of ATF3 is significantly increased beginning at 3 days post-CCI and decreased at 1 month post-CCI. Our bioinformatics analysis at single-cell resolution advances the knowledge of regenerative dynamic transcriptional changes in DRG cells after injury and the underlying molecular mechanisms involved.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"424-436"},"PeriodicalIF":3.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611934","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":"Repurposed genipin targeting UCP2 exhibits antitumor activity through inducing ferroptosis in glioblastoma.","authors":"Hao Dong, Kaixuan Sun, Xuejie Wang, Meimei Cui, Yaping Ma, Kexin Li, Wanli Duan, Hongxing Zhang, Liying Zhang, Zhimei Sheng, Maotao He, Baogang Zhang","doi":"10.3724/abbs.2024168","DOIUrl":"10.3724/abbs.2024168","url":null,"abstract":"<p><p>Uncoupling protein-2 (UCP2) controls the antioxidant response and redox homeostasis in cancer and is considered a potent molecular target for cancer treatment. However, the specific mechanism of UCP2 inhibition and its role in glioblastoma (GBM) have not yet been elucidated. Here, we attempt to identify a UCP2 inhibitor and study the underlying molecular mechanism in GBM. Bioinformatics analysis and immunohistochemistry are used to validate the high expression of UCP2 in GBM and its prognostic significance. Drug intervention and tumor xenograft experiments are conducted to determine the inhibitory effect of genipin, a UCP2 inhibitor, on UCP2. The mitochondrial membrane potential and key ferroptosis genes are examined to determine the occurrence of ferroptosis. High expression of UCP2 in GBM is associated with poor prognosis, and inhibiting UCP2 can alleviate the malignant behavior of GBM tumors. Genipin can downregulate the expression of GPX4 and upregulate the expression of ACSL4 by inhibiting UCP2, leading to ferroptosis and alleviating the malignant behavior of tumors. In summary, UCP2 is a potential therapeutic target for GBM. Genipin, which targets UCP2, effectively inhibits GBM development by inducing ferroptosis <i>in vivo</i> and <i>in vitro</i>. These findings indicate that genipin treatment based on UCP2 targeting has potential therapeutic applications with a clinical perspective for the treatment of GBM patients.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"403-414"},"PeriodicalIF":3.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611933","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":"SMG-1 serves as a prognostic indicator for the radiotherapy response in head and neck squamous cell carcinoma xenografts and patients.","authors":"Xiaofeng Wang, Yuxia Zou, Ren-Bo Ding, Xueying Lyu, Yuanfeng Fu, Xuejun Zhou, Zhihua Sun, Jiaolin Bao","doi":"10.3724/abbs.2024180","DOIUrl":"10.3724/abbs.2024180","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"1891-1894"},"PeriodicalIF":3.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"R-loop formation contributes to mTORC1 activation-dependent DNA replication stress induced by p53 deficiency.","authors":"Xiaolei Li, Cheng Yang, Xiaohui Zhang, Feiyang Wang, Longhua Sun, Wei Zhang, Xinping Xu","doi":"10.3724/abbs.2024188","DOIUrl":"https://doi.org/10.3724/abbs.2024188","url":null,"abstract":"<p><p>DNA replication stress is a significant contributor to spontaneous DNA damage and genome instability. While the impact of p53 deficiency on increasing DNA replication stress is known, the specific molecular mechanism underlying this phenomenon remains poorly understood. This study explores how p53 deficiency induces DNA replication stress by activating mTORC1 through R-loop formation, which is facilitated by the upregulation of RNR. Research has shown that p53 deficiency results in increased γH2AX expression and a higher mutation rate in the <i>HPRT</i> gene. Interestingly, these effects can be alleviated by rapamycin, an mTORC1 inhibitor. Additionally, rapamycin reduces the abundance of R-loop structures in p53KO cells, which is linked to mTORC1's regulation of ribonucleotide reductase (RNR) level. These findings suggest that p53 deficiency-induced DNA replication stress relies on mTORC1 activation, with the upregulation of RNR expression and R-loop formation. Overall, this study underscores the importance of R-loops in mTORC1 activation-dependent DNA replication stress triggered by p53 deficiency.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724612","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":"R-loop formation contributes to mTORC1 activation-dependent DNA replication stress induced by p53 deficiency.","authors":"Xiaolei Li, Cheng Yang, Xiaohui Zhang, Feiyang Wang, Longhua Sun, Wei Zhang, Xinping Xu","doi":"10.3724/abbs.2024188","DOIUrl":"10.3724/abbs.2024188","url":null,"abstract":"<p><p>DNA replication stress is a significant contributor to spontaneous DNA damage and genome instability. While the impact of p53 deficiency on increasing DNA replication stress is known, the specific molecular mechanism underlying this phenomenon remains poorly understood. This study explores how p53 deficiency induces DNA replication stress by activating mTORC1 through R-loop formation, which is facilitated by the upregulation of RNR. Research has shown that p53 deficiency results in increased γH2AX expression and a higher mutation rate in the <i>HPRT</i> gene. Interestingly, these effects can be alleviated by rapamycin, an mTORC1 inhibitor. Additionally, rapamycin reduces the abundance of R-loop structures in p53KO cells, which is linked to mTORC1's regulation of ribonucleotide reductase (RNR) level. These findings suggest that p53 deficiency-induced DNA replication stress relies on mTORC1 activation, with the upregulation of RNR expression and R-loop formation. Overall, this study underscores the importance of R-loops in mTORC1 activation-dependent DNA replication stress triggered by p53 deficiency.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"1875-1885"},"PeriodicalIF":3.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tanshinone IIA potentiates the therapeutic efficacy of glucocorticoids in lipopolysaccharide-treated HEI-OC1 cells through modulation of the FOXP3/Nrf2 signaling pathway.","authors":"Jie Li, Xiaoyan Zhu, Shiming Ye, Qi Dong, Jie Hou, Jing Liu, Wandong She","doi":"10.3724/abbs.2024194","DOIUrl":"https://doi.org/10.3724/abbs.2024194","url":null,"abstract":"<p><p>Glucocorticoids (GCs) are commonly used to treat sudden sensorineural hearing loss (SSNHL), although some patients are resistant to this therapeutic approach. Clinical studies have demonstrated the efficacy of tanshinone IIA (TA) in combination with GC for managing various human ailments. However, it remains unclear whether TA can mitigate GC resistance in SSNHL. Our aim is to elucidate the role of NRF2-induced transcriptional regulation of HDAC2 in influencing GC resistance and investigate the involvement of TA-related molecular pathways in GC resistance. Here, HEI-OC1 cells are treated with lipopolysaccharide (LPS) to establish an <i>in vitro</i> model for SSNHL. The cells are subsequently treated with dexamethasone (DXE) or DXE+TA. RT-qPCR and western blot analysis are used to measure the mRNA and protein levels of Forkhead box P3 (FOXP3), nuclear factor erythroid 2-related factor 2 (NRF2), and histone deacetylase 2 (HDAC2). Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays are carried out to assess cell proliferation. Flow cytometry analysis is performed to evaluate apoptosis. Mechanistic studies involve chromatin immunoprecipitation (ChIP), luciferase reporter, and DNA pull-down assays. Our results show that treatment with TA+DEX significantly increases proliferation and suppresses apoptosis in LPS-treated HEI-treated OC1 cells. TA upregulates HDAC2 expression by activating NRF2-mediated transcription of HDAC2, with the NRF2-HDAC2 binding site located at bases 419-429 (ATGACACTCCA) in the promoter sequence of <i>HDAC2</i>. Furthermore, TA upregulates FOXP3 expression to activate NRF2 transcription, with the predicted FOXP3-binding site located at bases 864-870 (GCAAACA) in the promoter sequence of <i>NRF2</i>. In summary, these findings suggest that TA enhances the therapeutic effects of GC on the proliferation and apoptosis of HEI OC1 cells by increasing FOXP3/Nrf2 expression. These results indicate that TA may be promising for ameliorating GC resistance in patients with SSNHL.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556870","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>Clitoria ternatea</i> L. flower-derived anthocyanins and flavonoids inhibit bladder cancer growth by suppressing SREBP1 pathway-mediated fatty acid synthesis.","authors":"Chenkai Liu, Jue Liu, Gao Liu, Yusong Song, Xiuyu Yang, Honglei Gao, Cheng Xiang, Jie Sang, Tianrui Xu, Jun Sang","doi":"10.3724/abbs.2024192","DOIUrl":"https://doi.org/10.3724/abbs.2024192","url":null,"abstract":"<p><p><i>Clitoria ternatea</i> L. flowers are used as traditional herbal medicines and are known for their advanced pharmacological activities. Flavonoids and anthocyanins reportedly contribute to the therapeutic properties of <i>C</i>. <i>ternatea</i> flowers; however, their potential anti-bladder cancer effects and molecular mechanisms remain unknown. In this study, flavonoid- and anthocyanin-rich samples from <i>C</i>. <i>ternatea</i> flowers (DDH) are prepared via macroporous resin-based extraction coupled with an efficient and reliable two-dimensional UPLC-DAD-MS/MS method. <i>In vitro</i> and <i>in vivo</i> studies reveal that DDH can inhibit bladder cancer cell growth and enhance the anti-bladder cancer activity of cisplatin. RNA-seq combined with KEGG analysis reveals that fatty acid synthesis is closely related to the anti-bladder cancer effect of DDH. Furthermore, DDH dose-dependently reduces cellular fatty acid levels in bladder cancer cells, and the addition of fatty acids significantly mitigates DDH-induced cell growth inhibition. Subsequent findings reveal that DDH downregulates sterol regulatory element-binding protein 1 (SREBP1), a key transcriptional regulator of <i>de novo</i> fatty acid synthesis in cancer cells, and its downstream targets (FASN, SCD1, and ACC). Additionally, this study demonstrates that gallic acid not only enhances the stability of DDH but also synergistically potentiates its anti-bladder cancer activity. Our study suggests that targeting the SREBP1 pathway is an effective strategy in bladder cancer therapy, and the ability of DDH to induce cell death by inhibiting the SREBP1 pathway and its good tolerance in mice make it a promising strategy for preventing and treating bladder cancer.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520634","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":"Battling pain from osteoarthritis: causing novel cell death.","authors":"Yuheng Zhang, Huaqiang Tao, Liyuan Zhang, Xueyan Li, Yi Shi, Wen Sun, Wenlong Chen, Yuhu Zhao, Liangliang Wang, Xing Yang, Chengyong Gu","doi":"10.3724/abbs.2024189","DOIUrl":"10.3724/abbs.2024189","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a significant contributor to pain and disability worldwide. Pain is the main complaint of OA patients attending the clinic and has a large impact on their quality of life and economic standards. However, existing treatments for OA-related pain have not been shown to achieve good relief. The main focus is on preventing and slowing the progression of OA so that the problem of OA pain can be resolved. Pain caused by OA is complex, with the nature, location, duration, and intensity of pain changing as the disease progresses. Previous research has highlighted the role of various forms of cell death, such as apoptosis and necrosis, in the progression of pain in OA. Emerging studies have identified additional forms of novel cell death, such as pyroptosis, ferroptosis, and necroptosis that are linked to pain in OA. Different types of cell death contribute to tissue damage in OA by impacting inflammatory responses, reactive oxygen species (ROS) production, and calcium ion levels, ultimately leading to the development of pain. Evidence suggests that targeting novel types of cell death could help alleviate pain in OA patients. This review delves into the complex mechanisms of OA pain, explores the relationship between different modes of novel cell death and pain, and proposes novel cell death as a viable strategy for the treatment of these conditions, with the goal of providing scientific references for the development of future OA pain treatments and drugs.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"169-181"},"PeriodicalIF":3.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tim-1-mediated extracellular matrix promotes the development of hepatocellular carcinoma.","authors":"Ruheng Hua, Pengfei Yu, Wanting Zheng, Nuwa Wu, Wangjianfei Yu, Qingyu Kong, Jun He, Lei Qin","doi":"10.3724/abbs.2024191","DOIUrl":"10.3724/abbs.2024191","url":null,"abstract":"<p><p>Tim-1 (T-cell immunoglobulin and mucin domain 1), also known as Kim-1 (kidney injury molecule 1) or hepatitis A virus cellular receptor 1 (HAVCR1), is a transmembrane protein expressed on various immune and epithelial cells. It plays a role in modulating inflammatory and immune responses. In this study, we find that Tim-1 is overexpressed in hepatocellular carcinoma (HCC) samples and that its expression is significantly correlated with postoperative survival. Bulk RNA sequencing reveals a general upregulation of extracellular matrix-related genes in HCC tissues with Tim-1 overexpression. The results of the cell and <i>in vivo</i> experiments reveal that Tim-1 in HCC not only affects biological processes such as the proliferation, migration, and invasion of HCC cells but also broadly promotes extracellular matrix processes by influencing cytokine secretion. Further studies demonstrate that Tim-1 mediates the activation of hepatic stellate cells and upregulates Th1 and Th2 cytokines, thereby promoting HCC progression. Thus, Tim-1 may represent a novel target for future interventions in HCC and liver fibrosis.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"1761-1773"},"PeriodicalIF":3.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircMALAT1 promotes the proliferation and metastasis of intrahepatic cholangiocarcinoma via the miR-512-5p/VCAM1 axis.","authors":"Meixia Zhang, Mingyan He, Liangliang Bai, Fan Du, Yingping Xie, Bimin Li, Yuming Zhang","doi":"10.3724/abbs.2024185","DOIUrl":"10.3724/abbs.2024185","url":null,"abstract":"<p><p>Circular RNAs play a pivotal role in the progression of various cancers. In our previous study, we observed high expression of the circRNA MALAT1 (cMALAT1) in intrahepatic cholangiocarcinoma (ICC) cells co-incubated with activated hepatic stellate cells. This study is designed to explore the roles of cMALAT1 and the underlying mechanisms in ICC. We find that cMALAT1 significantly facilitates the progression of ICC both <i>in vitro</i> and <i>in vivo</i>. The binding between cMALAT1 and miR-512-5p is subsequently confirmed through RNA pull-down experiments. As anticipated, the application of miR-512-5p mimics noticeably reverses the cMALAT1 overexpression-induced malignant phenotypes of ICC cells. Furthermore, <i>VCAM1</i> is identified as a downstream gene of the cMALAT1/miR-512-5p axis. Importantly, silencing of <i>VCAM1</i> not only effectively suppresses the malignant phenotypes of ICC cells but also significantly impairs the functions of cMALAT1. Our study reveals that cMALAT1 promotes the progression of ICC by competitively binding to <i>VCAM1</i> mRNA with miR-512-5p, leading to the upregulation of VCAM1 expression and the activation of the PI3K/AKT signaling pathway.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"223-236"},"PeriodicalIF":3.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}