{"title":"Il34 rescues metronidazole-induced impairment of spinal cord regeneration in zebrafish central nervous system.","authors":"Ji-Xiang Liu, Si-Ting Lai, Jing Bai, Jin Xu","doi":"10.16288/j.yczz.24-083","DOIUrl":"10.16288/j.yczz.24-083","url":null,"abstract":"<p><p>Metronidazole (MTZ), a commonly used anti-infective drug in clinical practice, has also been employed as a prodrug in cell-targeted ablation systems in scientific research, exhibiting significant application value. However, it has been demonstrated that MTZ can induce neurotoxic symptoms to some extent during its use, and there is currently a lack of effective means to circumvent its toxicity in both clinical and research settings, which limits its application. Therefore, exploring the specific mechanisms underlying MTZ-induced neurotoxic symptoms and elucidating countermeasures will enhance the practical value of MTZ. In this study, using a zebrafish spinal cord injury regeneration model, we confirmed that MTZ neurotoxicity leads to impaired axon regeneration in the central nervous system. By overexpressing <i>il34</i> in the central nervous system of zebrafish, we eliminated the inhibitory effect of MTZ on axonal regeneration and demonstrated that the pro-regenerative effect against MTZ neurotoxicity is not caused by excessive macrophages/microglia chemoattracted by interleukin 34(Il34). Transcriptome sequencing analysis and GO enrichment analysis of differentially expressed genes between groups revealed that Il34 may counteract MTZ neurotoxicity and promote spinal cord injury repair through biological processes that enhance cellular adhesion and cell location. In summary, our work uncovers a possible cause of MTZ neurotoxicity and provides a new perspective for eliminating MTZ toxicity.</p>","PeriodicalId":35536,"journal":{"name":"Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Progress on the role of LIN28A/B in tumor development and progression.","authors":"Yi-Wen Zhang, Qin Huang, Yan-Yun Wu, Yue Sun, Yong-Long Wei","doi":"10.16288/j.yczz.24-056","DOIUrl":"10.16288/j.yczz.24-056","url":null,"abstract":"<p><p>LIN28A and its homolog LIN28B are highly conserved RNA-binding proteins that play important roles in early embryonic development, somatic cell reprogramming, metabolism and tumorigenesis. LIN28A/B are highly expressed in a variety of malignant tumors such as breast cancer. They play important roles in the initiation, maintenance, and metastasis of tumors and are associated with poor prognosis. Previous studies have shown that the main regulatory mechanisms of LIN28A/B include let-7s dependent ways and let-7s independent ways, such as directly targeting mRNA. In this review, we summarize the function and molecular regulatory mechanisms of LIN28A/B in malignant tumors such as liver cancer, breast cancer and colorectal cancer, in order to provide references for further exploring the function and mechanism of LIN28A/B and their possible roles in clinical applications.</p>","PeriodicalId":35536,"journal":{"name":"Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jian Yang, Guo-Juan Shi, Ang-Hui Peng, Qing-Bo Xu, Rui-Qi Wang, Lei Xue, Xin-Yang Yu, Yi-Hao Sun
{"title":"Tip60-FOXO regulates JNK signaling mediated apoptosis in <i>Drosophila</i>.","authors":"Jian Yang, Guo-Juan Shi, Ang-Hui Peng, Qing-Bo Xu, Rui-Qi Wang, Lei Xue, Xin-Yang Yu, Yi-Hao Sun","doi":"10.16288/j.yczz.24-105","DOIUrl":"10.16288/j.yczz.24-105","url":null,"abstract":"<p><p>The JNK signaling pathway plays crucial roles in various physiological processes, including cell proliferation, differentiation, migration, apoptosis, and stress response. Dysregulation of this pathway is closely linked to the onset and progression of numerous major diseases, such as developmental defects and tumors. Identifying and characterizing novel components of the JNK signaling pathway to enhance and refine its network hold significant scientific and clinical importance for the prevention and treatment of associated cancers. This study utilized the model organism <i>Drosophila</i> and employed multidisciplinary approaches encompassing genetics, developmental biology, biochemistry, and molecular biology to investigate the interplay between Tip60 and the JNK signaling pathway, and elucidated its regulatory mechanisms. Our findings suggest that loss of Tip60 acetyltransferase activity results in JNK signaling pathway activation and subsequent induction of JNK-dependent apoptosis. Genetic epistasis analysis reveals that Tip60 acts downstream of JNK, paralleling with the transcription factor FOXO. The biochemical results confirm that Tip60 can bind to FOXO and acetylate it. Introduction of human Tip60 into <i>Drosophila</i> effectively mitigates apoptosis induced by JNK signaling activation, underscoring conserved regulatory role of Tip60 in the JNK signaling pathway from <i>Drosophila</i> to humans. This study further enhances our understanding of the regulatory network of the JNK signaling pathway. By revealing the role and mechanism of Tip60 in JNK-dependent apoptosis, it unveils new insights and potential therapeutic avenues for preventing and treating associated cancers.</p>","PeriodicalId":35536,"journal":{"name":"Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bao-Xia Ma, Sen Yang, Ming Lyu, Yu-Ren Wang, Li-Ye Chang, Yi-Fan Han, Jian-Gang Wang, Yang Guo, Kun Xu
{"title":"Comparison and optimization of different CRISPR/Cas9 donor-adapting systems for gene editing.","authors":"Bao-Xia Ma, Sen Yang, Ming Lyu, Yu-Ren Wang, Li-Ye Chang, Yi-Fan Han, Jian-Gang Wang, Yang Guo, Kun Xu","doi":"10.16288/j.yczz.23-273","DOIUrl":"10.16288/j.yczz.23-273","url":null,"abstract":"<p><p>Gene knock-in in mammalian cells usually uses homology-directed repair (HDR) mechanism to integrate exogenous DNA template into the target genome site. However, HDR efficiency is often low, and the co-localization of exogenous DNA template and target genome site is one of the key limiting factors. To improve the efficiency of HDR mediated by CRISPR/Cas9 system, our team and previous studies fused different adaptor proteins with SpCas9 protein and expressed them. By using their characteristics of binding to specific DNA sequences, many different CRISPR/SpCas9 donor adapter gene editing systems were constructed. In this study, we used them to knock-in <i>eGFP</i> gene at the 3'-end of the terminal exon of <i>GAPDH</i> and <i>ACTB</i> genes in HEK293T cells to facilitate a comparison and optimization of these systems. We utilized an optimized donor DNA template design method, validated the knock-in accuracy via PCR and Sanger sequencing, and assessed the efficiency using flow cytometry. The results showed that the fusion of yGal4BD, hGal4BD, hLacI, hTHAP11 as well as N57 and other adaptor proteins with the C-terminus of SpCas9 protein had no significant effect on its activity. At the <i>GAPDH</i> site, the donor adapter systems of SpCas9 fused with yGal4BD, hGal4BD, hLacI and hTHAP11 significantly improved the knock-in efficiency. At the <i>ACTB</i> site, SpCas9 fused with yGal4BD and hGal4BD significantly improved the knock-in efficiency. Furthermore, increasing the number of BS in the donor DNA template was beneficial to enhance the knock-in efficiency mediated by SpCas9-hTHAP11 system. In conclusion, this study compares and optimizes multiple CRISPR/Cas9 donor adapter gene editing systems, providing valuable insights for future gene editing applications.</p>","PeriodicalId":35536,"journal":{"name":"Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}