Molecular biomedicine最新文献

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Oncolytic adenovirus encoding decorin and CD40 ligand inhibits tumor growth and liver metastasis via immune activation in murine colorectal tumor model. 在小鼠结直肠肿瘤模型中,编码Decolin和CD40配体的溶瘤腺病毒通过免疫激活抑制肿瘤生长和肝转移。
IF 6.3
Molecular biomedicine Pub Date : 2024-09-22 DOI: 10.1186/s43556-024-00202-1
Yejing Rong, Yingjun Ning, Jianping Zhu, Pei Feng, Weixin Zhu, Xin Zhao, Zi Xiong, Chunyan Ruan, Jiachang Jin, Hua Wang, Ting Cai, Shun Zhang, Yuefeng Yang
{"title":"Oncolytic adenovirus encoding decorin and CD40 ligand inhibits tumor growth and liver metastasis via immune activation in murine colorectal tumor model.","authors":"Yejing Rong, Yingjun Ning, Jianping Zhu, Pei Feng, Weixin Zhu, Xin Zhao, Zi Xiong, Chunyan Ruan, Jiachang Jin, Hua Wang, Ting Cai, Shun Zhang, Yuefeng Yang","doi":"10.1186/s43556-024-00202-1","DOIUrl":"10.1186/s43556-024-00202-1","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the second common cause of cancer mortality worldwide, and it still lacks effective approaches for relapsed and metastatic CRC. Recently, oncolytic virus has been emerged as a promising immune therapeutic strategy. In this study, we develop a novel oncolytic adenovirus, rAd.mDCN.mCD40L, which drive oncolytic activity by telomerase reverse transcriptase promoter (TERTp). rAd.mDCN.mCD40L expressed both mouse genes of decorin (mDCN) and CD40 ligand (mCD40L), and produced effective cytotoxicity in both human and mouse CRC cells. Moreover, oncolytic adenovirus mediated mDCN over-expression inhibited Met expression in vitro. In CT26 subcutaneous tumor model, intratumorally delivery of oncolytic adenoviruses could inhibit tumor growth and liver metastasis, while mDCN and/or mCD40L armed oncolytic adenoviruses produced much more impressive responses. No obvious toxicity was detected in lung, liver and spleen. Moreover, mDCN and/or mCD40L armed oncolytic adenoviruses altered the immune state to activate anti-tumor responses, including increasing CD8<sup>+</sup> T effector cells and CD4<sup>+</sup> memory T cells, reducing MDSCs and Tregs in peripheral blood. Furthermore, mDCN and/or mCD40L armed oncolytic adenoviruses mediated mDCN and/or mCD40L expression in tumors, and up-regulated Th1 cytokines and reduced Th2 cytokines in tumors, which will be benefit for remodeling tumor microenvironment. Importantly, rAd.mDCN.mCD40L and rAd.mCD40L prevented tumor liver metastasis much more effectively than rAd.Null and rAd.mDCN. Therefore, rAd.mDCN.mCD40L and rAd.mCD40L are promising approaches for CRC therapy.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"39"},"PeriodicalIF":6.3,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The dual role of SOX17 in the occurrence and development of early colorectal cancer. SOX17 在早期结直肠癌的发生和发展中的双重作用。
IF 6.3
Molecular biomedicine Pub Date : 2024-09-16 DOI: 10.1186/s43556-024-00201-2
Xinming Su, Jianqiao Shentu, Ruixiu Chen, Shiwei Duan
{"title":"The dual role of SOX17 in the occurrence and development of early colorectal cancer.","authors":"Xinming Su, Jianqiao Shentu, Ruixiu Chen, Shiwei Duan","doi":"10.1186/s43556-024-00201-2","DOIUrl":"10.1186/s43556-024-00201-2","url":null,"abstract":"","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"38"},"PeriodicalIF":6.3,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gut microbiome influences efficacy of Endostatin combined with PD-1 blockade against colorectal cancer. 肠道微生物组影响内司他丁联合 PD-1 阻断剂对结直肠癌的疗效。
IF 6.3
Molecular biomedicine Pub Date : 2024-09-10 DOI: 10.1186/s43556-024-00200-3
Jie Xu, Yaomei Tian, Binyan Zhao, Die Hu, Siwen Wu, Jing Ma, Li Yang
{"title":"Gut microbiome influences efficacy of Endostatin combined with PD-1 blockade against colorectal cancer.","authors":"Jie Xu, Yaomei Tian, Binyan Zhao, Die Hu, Siwen Wu, Jing Ma, Li Yang","doi":"10.1186/s43556-024-00200-3","DOIUrl":"10.1186/s43556-024-00200-3","url":null,"abstract":"<p><p>The combination of anti-angiogenic drugs and immune checkpoint inhibitors (ICIs) in the treatment of tumors is emerging as a way to improve ICIs-resistant tumor therapy. In addition, gut microbes (GMs) are involved in angiogenesis in the tumor microenvironment and are also associated with the antitumor function of immune checkpoint inhibitors. However, it is unclear whether gut microbes have a role in anti-tumor function in the combination of anti-angiogenic drugs and immune checkpoint inhibitors for cancer treatment. Endostatin, an angiogenesis inhibitor, has been widely used as an antiangiogenic therapy for cancer. We showed that combined therapy with an adenovirus encoding human endostatin, named Ad-E, and PD-1 blockade dramatically abrogated MC38 tumor growth. The structure of intestinal microbes in mice was changed after combination treatment. We found that the antitumor function of combination therapy was inhibited after the elimination of intestinal microbes. In mice with depleted microbiota, oral gavage of Bacteroides fragilis salvaged the antitumor effects of combination Ad-E and αPD-1 monoclonal antibody (mAb) to a certain extent. Further, Bacteroides fragilis could improve CD3<sup>+</sup>T cells, NK cells, and IFNγ<sup>+</sup>CD8<sup>+</sup> T cells in the tumor microenvironment to inhibit tumor growth. Besides, Bacteroides fragilis might restore antitumor function by down-regulating isobutyric acid (IBA). Our results suggested that GMs may be involved in the combination of Ad-E and αPD-1 mAb for cancer treatment, which has oncological implications for tumor growth dynamics and cancer immune surveillance.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"37"},"PeriodicalIF":6.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11383918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SOX7 inhibits the malignant progression of bladder cancer via the DNMT3B/CYGB axis. SOX7 通过 DNMT3B/CYGB 轴抑制膀胱癌的恶性进展。
IF 6.3
Molecular biomedicine Pub Date : 2024-09-04 DOI: 10.1186/s43556-024-00198-8
Jingcheng Zhang, Wentao Zhang, Ji Liu, Yuchao Liu, Yufeng Jiang, Ailiyaer Ainiwaer, Hanyang Chen, Zhuoran Gu, Haotian Chen, Shiyu Mao, Yadong Guo, Tianyuan Xu, Yunfei Xu, Yuan Wu, Xudong Yao, Yang Yan
{"title":"SOX7 inhibits the malignant progression of bladder cancer via the DNMT3B/CYGB axis.","authors":"Jingcheng Zhang, Wentao Zhang, Ji Liu, Yuchao Liu, Yufeng Jiang, Ailiyaer Ainiwaer, Hanyang Chen, Zhuoran Gu, Haotian Chen, Shiyu Mao, Yadong Guo, Tianyuan Xu, Yunfei Xu, Yuan Wu, Xudong Yao, Yang Yan","doi":"10.1186/s43556-024-00198-8","DOIUrl":"10.1186/s43556-024-00198-8","url":null,"abstract":"<p><p>Bladder cancer (BCa) stands out as a highly prevalent malignant tumor affecting the urinary system. The Sex determining region Y-box protein family is recognized for its crucial role in BCa progression. However, the effect of Sex determining region Y-box 7 (SOX7) on BCa progression has not been fully elucidated. Herein, RNA-sequencing, western blot (WB), immunohistochemistry (IHC), immunofluorescence (IF) and tissue microarray were utilized to assess SOX7 expression in vitro and in vivo. Additionally, SOX7 expression, prognosis, and SOX7 + cytoglobin (CYGB) score were analyzed using R software. In vitro and vivo experiments were performed with BCa cell lines to validate the effect of SOX7 knockdown and overexpression on the malignant progression of BCa. The results showed that SOX7 exhibits low expression in BCa. It functions in diverse capacities, inhibiting the proliferative, migratory, and invasive capabilities of BCa. In addition, the experimental database demonstrated that SOX7 binds to the promoter of DNA methyltransferase 3 beta (DNMT3B), leading to the transcriptional inhibition of DNMT3B. This subsequently results in a reduced methylation of CYGB promoter, ultimately inhibiting the tumor progression of BCa. SOX7 + CYGB scores were significantly linked to patient prognosis. In conclusion, SOX7 inhibits the malignant progression of BCa via the DNMT3B/CYGB axis. Additionally, the SOX7 + CYGB score is capable of predicting the prognostic outcomes of BCa patients. Therefore, SOX7 and CYGB may play an important role in the progression of bladder cancer, and they can be used as prognostic markers of bladder cancer patients.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"36"},"PeriodicalIF":6.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A review of HSV pathogenesis, vaccine development, and advanced applications. HSV 发病机制、疫苗开发和先进应用综述。
IF 6.3
Molecular biomedicine Pub Date : 2024-08-29 DOI: 10.1186/s43556-024-00199-7
Lan Bai, Jiuzhi Xu, Linghui Zeng, Long Zhang, Fangfang Zhou
{"title":"A review of HSV pathogenesis, vaccine development, and advanced applications.","authors":"Lan Bai, Jiuzhi Xu, Linghui Zeng, Long Zhang, Fangfang Zhou","doi":"10.1186/s43556-024-00199-7","DOIUrl":"10.1186/s43556-024-00199-7","url":null,"abstract":"<p><p>Herpes simplex virus (HSV), an epidemic human pathogen threatening global public health, gains notoriety for its complex pathogenesis that encompasses lytic infection of mucosal cells, latent infection within neurons, and periodic reactivation. This intricate interplay, coupled with HSV's sophisticated immune evasion strategies, gives rise to various diseases, including genital lesions, neonatal encephalitis, and cancer. Despite more than 70 years of relentless research, an effective preventive or therapeutic vaccine against HSV has yet to emerge, primarily due to the limited understanding of virus-host interactions, which in turn impedes the identification of effective vaccine targets. However, HSV's unique pathological features, including its substantial genetic load capacity, high replicability, transmissibility, and neurotropism, render it a promising candidate for various applications, spanning oncolytic virotherapy, gene and immune therapies, and even as an imaging tracer in neuroscience. In this review, we comprehensively update recent breakthroughs in HSV pathogenesis and immune evasion, critically summarize the progress made in vaccine candidate development, and discuss the multifaceted applications of HSV as a biological tool. Importantly, we highlight both success and challenges, emphasizing the critical need for intensified research into HSV, with the aim of providing deeper insights that can not only advance HSV treatment strategies but also broaden its application horizons.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"35"},"PeriodicalIF":6.3,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pan-cancer analysis identifies venous thromboembolism-related genes F3, PLAT, and C1S as potential prognostic biomarkers for glioblastoma and lower grade glioma. 泛癌症分析发现静脉血栓栓塞相关基因F3、PLAT和C1S是胶质母细胞瘤和低级别胶质瘤的潜在预后生物标志物。
IF 6.3
Molecular biomedicine Pub Date : 2024-08-24 DOI: 10.1186/s43556-024-00197-9
Jing Zhang, Qian Zhao, Yun Du, Wannan Wang, Cuiqing Liu
{"title":"Pan-cancer analysis identifies venous thromboembolism-related genes F3, PLAT, and C1S as potential prognostic biomarkers for glioblastoma and lower grade glioma.","authors":"Jing Zhang, Qian Zhao, Yun Du, Wannan Wang, Cuiqing Liu","doi":"10.1186/s43556-024-00197-9","DOIUrl":"10.1186/s43556-024-00197-9","url":null,"abstract":"<p><p>Venous thromboembolism (VTE) is a prevalent complication among patients with cancer, contributing significantly to morbidity and mortality. However, the relationship between VTE-related genes (VRGs) and their potential impact on prognosis, immune response, and therapeutic targets in various cancer types remains unclear. Based on the coagulation and complement pathways, we identified hub VRGs that play a role in regulating the immune response in cancer. Specifically, coagulation factor III (F3), plasminogen activator (PLAT) and complement C1s (C1S) were identified as genes that exhibit high expression levels, positively correlating with tumor stemness and copy number variations, while inversely correlating with methylation levels, in particular cancer types. Pan-cancer survival analysis revealed detrimental effects of these VRGs in several cancer types, notably in glioblastoma and lower grade glioma (GMBLGG). Further analysis using receiver operating characteristic (ROC) curves demonstrated a high accuracy of F3, PLAT and C1S in predicting outcomes in GBMLGG, with area under the curve (AUC) values ranging from 0.78 to 0.9. Validation of the prognostic value of these three genes in GMBLGG was conducted using an independent Gene Expression Omnibus (GEO) dataset. Additionally, gene-drug association analysis identified ciclosporin, ouabain and 6- mercaptopurine, which all exhibit immunosuppressive properties, as potential therapeutic options for tumor patients exhibiting high F3, PLAT or C1S expression, respectively. In summary, our findings provide a bioinformatics perspective on VRGs in pan-cancer, highlighting the pivotal roles of F3, PLAT and C1S, which could potentially be therapeutically exploited and targeted in several cancers, especially in GBMLGG.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"34"},"PeriodicalIF":6.3,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11343955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
METTL Family in Healthy and Disease. 健康和疾病中的 METTL 家族
IF 6.3
Molecular biomedicine Pub Date : 2024-08-19 DOI: 10.1186/s43556-024-00194-y
Jiejie He, Fengchen Hao, Shiqi Song, Junli Zhang, Hongyu Zhou, Jun Zhang, Yan Li
{"title":"METTL Family in Healthy and Disease.","authors":"Jiejie He, Fengchen Hao, Shiqi Song, Junli Zhang, Hongyu Zhou, Jun Zhang, Yan Li","doi":"10.1186/s43556-024-00194-y","DOIUrl":"10.1186/s43556-024-00194-y","url":null,"abstract":"<p><p>Transcription, RNA splicing, RNA translation, and post-translational protein modification are fundamental processes of gene expression. Epigenetic modifications, such as DNA methylation, RNA modifications, and protein modifications, play a crucial role in regulating gene expression. The methyltransferase-like protein (METTL) family, a constituent of the 7-β-strand (7BS) methyltransferase subfamily, is broadly distributed across the cell nucleus, cytoplasm, and mitochondria. Members of the METTL family, through their S-adenosyl methionine (SAM) binding domain, can transfer methyl groups to DNA, RNA, or proteins, thereby impacting processes such as DNA replication, transcription, and mRNA translation, to participate in the maintenance of normal function or promote disease development. This review primarily examines the involvement of the METTL family in normal cell differentiation, the maintenance of mitochondrial function, and its association with tumor formation, the nervous system, and cardiovascular diseases. Notably, the METTL family is intricately linked to cellular translation, particularly in its regulation of translation factors. Members represent important molecules in disease development processes and are associated with patient immunity and tolerance to radiotherapy and chemotherapy. Moreover, future research directions could include the development of drugs or antibodies targeting its structural domains, and utilizing nanomaterials to carry miRNA corresponding to METTL family mRNA. Additionally, the precise mechanisms underlying the interactions between the METTL family and cellular translation factors remain to be clarified.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"33"},"PeriodicalIF":6.3,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of HOX family regulator-mediated modification patterns and immunity characteristics on tumor-associated cell type in endometrial cancer. HOX家族调控因子介导的修饰模式和免疫特征对子宫内膜癌肿瘤相关细胞类型的影响
IF 6.3
Molecular biomedicine Pub Date : 2024-08-14 DOI: 10.1186/s43556-024-00196-w
JiaoLin Yang, JinPeng Li, SuFen Li, YuTong Yang, HuanCheng Su, HongRui Guo, Jing Lei, YaLin Wang, KaiTing Wen, Xia Li, SanYuan Zhang, Zhe Wang
{"title":"Effects of HOX family regulator-mediated modification patterns and immunity characteristics on tumor-associated cell type in endometrial cancer.","authors":"JiaoLin Yang, JinPeng Li, SuFen Li, YuTong Yang, HuanCheng Su, HongRui Guo, Jing Lei, YaLin Wang, KaiTing Wen, Xia Li, SanYuan Zhang, Zhe Wang","doi":"10.1186/s43556-024-00196-w","DOIUrl":"10.1186/s43556-024-00196-w","url":null,"abstract":"<p><p>Endometrial cancer (UCEC) is one of three major malignant tumors in women. The HOX gene regulates tumor development. However, the potential roles of HOX in the expression mechanism of multiple cell types and in the development and progression of tumor microenvironment (TME) cell infiltration in UCEC remain unknown. In this study, we utilized both the The Cancer Genome Atlas (TCGA) database and International Cancer Genome Consortium (ICGC) database to analyze transcriptome data of 529 patients with UCEC based on 39 HOX genes, combing clinical information, we discovered HOX gene were a pivotal factor in the development and progression of UCEC and in the formation of TME diversity and complexity. Here, a new scoring system was developed to quantify individual HOX patterns in UCEC. Our study found that patients in the low HOX score group had abundant anti-tumor immune cell infiltration, good tumor differentiation, and better prognoses. In contrast, a high HOX score was associated with blockade of immune checkpoints, which enhances the response to immunotherapy. The Real-Time quantitative PCR (RT-qPCR) and Immunohistochemistry (IHC) exhibited a higher expression of the HOX gene in the tumor patients. We revealed that the significant upregulation of the HOX gene in the epithelial cells can activate signaling pathway associated with tumour invasion and metastasis through single-cell RNA sequencing (scRNA-seq), such as nucleotide metabolic proce and so on. Finally, a risk prognostic model established by the positive relationship between HOX scores and cancer-associated fibroblasts (CAFs) can predict the prognosis of individual patients by scRNA-seq and transcriptome data sets. In sum, HOX gene may serve as a potential biomarker for the diagnosis and prediction of UCEC and to develop more effective therapeutic strategies.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"32"},"PeriodicalIF":6.3,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11322468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhibition of Sesn2 has negative regulatory effects on the myogenic differentiation of C2C12 myoblasts. 抑制 Sesn2 会对 C2C12 肌母细胞的成肌分化产生负面调节作用。
IF 6.3
Molecular biomedicine Pub Date : 2024-08-09 DOI: 10.1186/s43556-024-00193-z
Zubiao Song, Qing Lin, Jiahui Liang, Weixi Zhang
{"title":"Inhibition of Sesn2 has negative regulatory effects on the myogenic differentiation of C2C12 myoblasts.","authors":"Zubiao Song, Qing Lin, Jiahui Liang, Weixi Zhang","doi":"10.1186/s43556-024-00193-z","DOIUrl":"10.1186/s43556-024-00193-z","url":null,"abstract":"<p><p>Sestrin2 (Sesn2) has been previously confirmed to be a stress-response molecule. However, the influence of Sesn2 on myogenic differentiation remains elusive. This study was conducted to analyze the role of Sesn2 in the myogenic differentiation of C2C12 myoblasts and related aspects in mdx mice, an animal model of Duchenne muscular dystrophy (DMD). Our results showed that knockdown of Sesn2 reduced the myogenic differentiation capacity of C2C12 myoblasts. Predictive analysis from two databases suggested that miR-182-5p is a potential regulator of Sesn2. Further experimental validation revealed that overexpression of miR-182-5p decreased both the protein and mRNA levels of Sesn2 and inhibited myogenesis of C2C12 myoblasts. These findings suggest that miR-182-5p negatively regulates myogenesis by repressing Sesn2 expression. Extending to an in vivo model of DMD, knockdown of Sesn2 led to decreased Myogenin (Myog) expression and increased Pax7 expression, while its overexpression upregulated Myog levels and enhanced the proportion of slow-switch myofibers. These findings indicate the crucial role of Sesn2 in promoting myogenic differentiation and skeletal muscle regeneration, providing potential therapeutic targets for muscular dystrophy.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"31"},"PeriodicalIF":6.3,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in immunocompromised AG129 mice. 寨卡病毒的接种剂量会影响免疫力低下的 AG129 小鼠的病毒复制动态、细胞因子反应和存活率。
IF 6.3
Molecular biomedicine Pub Date : 2024-08-03 DOI: 10.1186/s43556-024-00195-x
Yuhuan Yan, Hao Yang, Yun Yang, Junbin Wang, Yanan Zhou, Cong Tang, Bai Li, Qing Huang, Ran An, Xiaoming Liang, Dongdong Lin, Wenhai Yu, Changfa Fan, Shuaiyao Lu
{"title":"The inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in immunocompromised AG129 mice.","authors":"Yuhuan Yan, Hao Yang, Yun Yang, Junbin Wang, Yanan Zhou, Cong Tang, Bai Li, Qing Huang, Ran An, Xiaoming Liang, Dongdong Lin, Wenhai Yu, Changfa Fan, Shuaiyao Lu","doi":"10.1186/s43556-024-00195-x","DOIUrl":"10.1186/s43556-024-00195-x","url":null,"abstract":"<p><p>Zika virus, a mosquito-borne arbovirus, has repeatedly caused large pandemics with symptoms worsening from mild and self-limiting diseases to Guillain-Barré syndrome in adults and fetal microcephaly in newborns. In recent years, Zika virus diseases have posed a serious threat to human health. The shortage of susceptible small animal models makes it difficult to study pathogenic mechanisms and evaluate potential therapies for Zika virus infection. Therefore, we chose immunocompromised mice (AG129 mice) deficient in IFN-α/β and IFN-γ receptors, which can abolish the innate immune system that prevents Zika virus infection early. AG129 mice were infected with the Zika virus, and this mouse model exhibited replication dynamics, tissue tropism, pathological lesion and immune activation of the Zika virus. Our results suggest that the inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in AG129 mice. By testing the potential antiviral drug favipiravir, several critical indicators, including replication dynamics and survival rates, were identified in AG129 mice after Zika virus infection. It is suggested that the model is reliable for drug evaluation. In brief, this model provides a potential platform for studies of the infectivity, virulence, and pathogenesis of the Zika virus. Moreover, the development of an accessible mouse model of Zika virus infection will expedite the research and deployment of therapeutics and vaccines.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"30"},"PeriodicalIF":6.3,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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