{"title":"A Novel Signature Combing Cuproptosis- and Ferroptosis-Related Genes in Nonalcoholic Fatty Liver Disease.","authors":"Rou-Rou Fang, Qi-Fan Yang, Jing Zhao, Shou-Zhu Xu","doi":"10.24920/004403","DOIUrl":"https://doi.org/10.24920/004403","url":null,"abstract":"<p><strong>Objectives: </strong>To identify cuproptosis- and ferroptosis-related genes involved in nonalcoholic fatty liver disease and to determine the diagnostic value of hub genes.</p><p><strong>Methods: </strong>The gene expression dataset GSE89632 was retrieved from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) between the non-alcoholic steatohepatitis (NASH) group and the healthy group using the 'limma' package in R software and weighted gene co-expression network analysis. Gene ontology, kyoto encyclopedia of genes and genomes pathway, and single-sample gene set enrichment analyses were performed to identify functional enrichment of DEGs. Ferroptosis- and cuproptosis-related genes were obtained from the FerrDb V2 database and available literatures, respectively. A combined signature for cuproptosis- and ferroptosis-related genes, called CRF, was constructed using the STRING database. Hub genes were identified by overlapping DEGs, WGCNA-derived key genes, and combined signature CRF genes, and validated using the GSE109836 and GSE227714 datasets and real-time quantitative polymerase chain reaction. A nomogram of NASH diagnostic model was established utilizing the 'rms' package in R software based on the hub genes, and the diagnostic value of hub genes was assessed using receiver operating characteristic curve analysis. In addition, immune cell infiltration in NASH <i>versus</i> healthy controls was examined using the CIBERSORT algorithm. The relationships among various infiltrated immune cells were explored with Spearman's correlation analysis.</p><p><strong>Results: </strong>Analysis of GSE89632 identified 236 DEGs between the NASH group and the healthy group. WGCNA highlighted 8 significant modules and 11,095 pivotal genes, of which 330 genes constituted CRF. Intersection analysis identified <i>IL</i>6, <i>IL</i>1<i>B</i>, <i>JUN</i>, <i>NR</i>4<i>A</i>1, and <i>PTGS</i>2 as hub genes. The hub genes were all downregulated in the NASH group, and this result was further verified by the NASH validation dataset and real-time quantitative polymerase chain reaction. Receiver operating characteristic curve analysis confirmed the diagnostic efficacy of these hub genes with areas under the curve of 0.985, 0.941, 1.000, 0.967, and 0.985, respectively. Immune infiltration assessment revealed that gamma delta T cells, M1 macrophages, M2 macrophages, and resting mast cells were predominantly implicated.</p><p><strong>Conclusions: </strong>Our investigation underscores the significant association of cuproptosis- and ferroptosis-related genes, specifically <i>IL</i>6, <i>IL</i>1<i>B</i>, <i>JUN</i>, <i>NR</i>4<i>A</i>1, and <i>PTGS</i>2, with NASH. These findings offer novel insights into the pathogenesis of NASH, potentially guiding future diagnostic and therapeutic strategies.</p>","PeriodicalId":35615,"journal":{"name":"Chinese Medical Sciences Journal","volume":"39 4","pages":"261-272"},"PeriodicalIF":0.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956123","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}
Shu-Xia Liu, Yan Wang, Shuang Yang, Ya-Qing Wang, Mei-Mei Xu
{"title":"Current Status and Future Suggestions for Innovative Drug Research and Development in China.","authors":"Shu-Xia Liu, Yan Wang, Shuang Yang, Ya-Qing Wang, Mei-Mei Xu","doi":"10.24920/004363","DOIUrl":"10.24920/004363","url":null,"abstract":"<p><p>In recent years, with the policy reform of new drug review and approval, China has ushered in a surge of innovative drug development. Based on the Pharnexcloud database and the Pharmcube database, we analyzed the innovative drugs approved for marketing and entered clinical trials in China, sorted out the major research and development (R&D) institutions and enterprises, the distribution of innovative drug target types, and the primary therapeutic areas of the approved innovative drugs, and compared with the global innovative drug R&D landscape. Since 2020, China's innovative drug development has shown a rapid growth trend, with intense competition among biopharmaceutical companies, and the emergence of a number of leading biopharmaceutical enterprises. Popular targets for clinical-stage and approved drugs include protein tyrosine kinase, epidermal growth factor receptor, vascular endothelial growth factor receptor, and others. Oncological diseases are the most active domain for new drug R&D in China, followed by infectious diseases and neurological diseases. Suggestions for future development are proposed to increase policy support, enhance R&D innovation investment, optimize pipeline layout, strengthen international cooperation, and focus on innovative targets. This review provides a reference for pharmaceutical R&D enterprises, scientific researchers, and government administrators.</p>","PeriodicalId":35615,"journal":{"name":"Chinese Medical Sciences Journal","volume":"39 4","pages":"288-296"},"PeriodicalIF":0.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956124","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":"Predictive Value of Systemic Immune Inflammation Index, Aggregate Index of Systemic Inflammation, and Systemic Inflammation Response Index in Lower Extremity Deep Venous Thrombosis Following Severe Trauma.","authors":"Peng-Fei Li, Xin Lu, Yu-Qian Zhou, Ke Wang, Peng Yang, Xiong-Hui Chen, Feng Xu","doi":"10.24920/004411","DOIUrl":"https://doi.org/10.24920/004411","url":null,"abstract":"<p><strong>Objectives: </strong>Venous thromboembolism is a highly prevalent condition after polytrauma, and recognized as an important factor contributing to poor prognosis. The aim of this study was to investigate the risk factors for lower extremity deep venous thrombosis (LEDVT) in a severely traumatized population and to evaluate their predictive value for LEDVT.</p><p><strong>Methods: </strong>This was a retrospective, single-center observational study. All subjects were severely traumatized patients who were admitted to the Traumatic Intensive Care Unit from January 2021 to May 2024. Based on Doppler ultrasound findings of both lower extremities from the time of injury to 30 days post-injury, patients who developed LEDVT were enrolled in the LEDVT group, and those who did not develop LEDVT were enrolled in the NLEDVT group. Demographic, clinical, and laboratory data were collected upon admission. Multivariable logistic regression analysis was performed to identify risk factors for LEDVT. Receiver operating characteristic (ROC) curve was used to evaluate the overall fit of the final model.</p><p><strong>Results: </strong>There were 56 patients enrolled in the LEDVT group and 81 patients in the NLEDVT group.Age, Aggregate Index of Systemic Inflammation (AISI), Systemic Inflammation Response Index (SIRI), ICU length of stay, and albumin were identified as independent risk factors for LEDVT (all <i>P</i> < 0.05). The area under their ROC curves were 0.604, 0.657, 0.694, 0.668, and 0.405, respectively. Combined model for early clinical prediction of LEDVT in severely traumatized patients by age, SIRI, AISI, and albumin resulted in an area under the ROC curve of 0.805 (95%<i>CI</i>: 0.73-0.88, <i>SE</i> = 0.037).</p><p><strong>Conclusions: </strong>The combination of age, SIRI, AISI, and albumin has a predictive value for LEDVT in severely traumatized patients.</p>","PeriodicalId":35615,"journal":{"name":"Chinese Medical Sciences Journal","volume":"39 4","pages":"241-248"},"PeriodicalIF":0.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956128","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}
Di Xia, Ya-Hong Gong, Xia Ruan, Li Xu, Li-Jian Pei, Xu Li, Rui-Ying Wang
{"title":"Video Feedback Improves Anesthesia Residents' Communication Skill and Performance on Showing Empathy During Preoperative Interviews.","authors":"Di Xia, Ya-Hong Gong, Xia Ruan, Li Xu, Li-Jian Pei, Xu Li, Rui-Ying Wang","doi":"10.24920/004379","DOIUrl":"https://doi.org/10.24920/004379","url":null,"abstract":"<p><strong>Objectives: </strong>To determine the impact of scenario-based lecture and personalized video feedback on anesthesia residents' communication skills during preoperative visits.</p><p><strong>Methods: </strong>A total of 24 anesthesia residents were randomly divided into a video group and a control group. Residents in both groups took part in a simulated interview and received a scenario-based lecture on how to communicate with patients during preoperative visits. Afterwards, residents in the video group received personalized video feedback recorded during the simulated interview. One week later all the residents undertook another simulated interview. The communication skills of all the residents were assessed using the Consultation and Relational Empathy measure (CARE) scale by two examiners and one standardized patient (SP), both of whom were blinded to the group allocation.</p><p><strong>Results: </strong>CARE scores were comparable between the two groups before training, and significantly improved after training in both groups (all <i>P</i> < 0.05). The video group showed significantly greater increase in CARE score after the training than the control group, especially assessed by the SP (<i>t</i> = 6.980, <i>P</i> <0.001). There were significant correlations between the examiner-assessed scores and SP-assessed scores (both <i>P</i> = 0.001).</p><p><strong>Conclusions: </strong>Scenario-based lectures with simulated interviews provide a good method for training communication skills of anesthesia residents, and personalized video feedback can enhance their performance on showing empathy during preoperative interview.</p>","PeriodicalId":35615,"journal":{"name":"Chinese Medical Sciences Journal","volume":"39 4","pages":"282-287"},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956130","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":"Duration of Hypothermia is Associated with Postoperative Complications in Patients Undergoing Gynecological Surgery: A Prospective Cohort Study.","authors":"Su-Mei Wang, Li-Jian Pei, Yue-Lun Zhang, Jie Yi","doi":"10.24920/004419","DOIUrl":"https://doi.org/10.24920/004419","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the relationship between hypothermia duration and postoperative complications in patients undergoing gynecological surgery.</p><p><strong>Methods: </strong>Patients who underwent elective gynecological surgery at our hospital were consecutively enrolled between October 2020 and January 2022. Core temperature was continuously monitored intraoperatively, and early postoperative complications were collected. By adjusting the logistic regression model for potential confounding factors, the association of postoperative complications with the duration of hypothermia, the lowest body temperature below 36°C, and the hypothermia upon admission to postanesthesia care unit (PACU) or intensive care unit (ICU) were analyzed. Additionally, the potential inflection point in the relationship between the duration of hypothermia and the risk of postoperative complications was explored by using cumulative probability scatter plots and moving average sequences.</p><p><strong>Results: </strong>The study included 370 patients, with 193 (52.2%) experiencing hypothermia and 177 (47.8%) not. Among them, 92 (24.9%) developed complications. The duration of hypothermia (adjusted odds ratio [<i>OR</i>] for each one-minute increase: 1.003; 95% confidence interval [<i>CI</i>]: 1.000-1.006, <i>P</i>=0.047) and hypothermia upon admission to PACU or ICU (adjusted <i>OR</i>: 1.980; 95% <i>CI</i>: 1.135-3.454, <i>P</i>=0.016) were associated with early postoperative complications. Notably, the cumulative incidence of postoperative complications tended to rise as the duration of hypothermia increased, with a potential inflection point observed at 120 minutes.</p><p><strong>Conclusions: </strong>In gynecological surgery, the duration of hypothermia as well as hypothermia upon admission to PACU or ICU are associated with postoperative complications. Minimizing the duration of hypothermia may be clinically beneficial.</p>","PeriodicalId":35615,"journal":{"name":"Chinese Medical Sciences Journal","volume":"39 4","pages":"233-240"},"PeriodicalIF":0.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956125","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":"Medication Rules of Hub Herb Pairs for Insomnia and Mechanism of Action: Results of Data Mining, Network Pharmacology, and Molecular Docking.","authors":"Wen-Long Guo, Hui-Juan Jiang, Yan-Rong Li, Jin-Long Yang, Yu-Chan Chen","doi":"10.24920/004384","DOIUrl":"https://doi.org/10.24920/004384","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the medication rules of traditional Chinese medicine (TCM) and mechanism of action of hub herb pairs for treating insomnia.</p><p><strong>Methods: </strong>Totally 104 prescriptions were statistically analyzed. The association rule algorithm was applied to mine the hub herb pairs. Network pharmacology was utilized to analyze the mechanism of the hub herb pairs, while molecular docking was applied to simulate the interaction between receptors and herb molecules, thereby predicting their binding affinities.</p><p><strong>Results: </strong>The most frequently used herbs in TCM prescriptions for treating insomnia included <i>Semen Ziziphi Spinosae</i>, <i>Radix Glycyrrhizae</i>, <i>Radix et Rhizoma Ginseng</i>, and <i>Poria cum Radix Pini</i>. Among them, the most commonly used were the supplementing herbs, followed by heat-clearing, mind-calming, and exterior-releasing ones, with their properties of warm and cold, flavors of sweet, Pungent, and bitter, and meridian tropisms of liver, lungs, spleen, kidneys, heart, and stomach. The hub herb pairs based on the association rules included <i>Radix Astragali</i>-<i>Radix et Rhizoma Ginseng</i>, <i>Rhizoma Chuanxiong</i>-<i>Radix Glycyrrhizae</i>, <i>Seman Platycladi</i>-<i>Semen Ziziphi Spinosae</i>, <i>Pericarpium Citri Reticulatae</i>-<i>Radix Glycyrrhizae</i>, <i>Radix Polygalae</i>-<i>Semen Ziziphi Spinosae</i>, and <i>Radix Astragali</i>-<i>Semen Ziziphi Spinosae</i>. Network pharmacology revealed that the cAMP signaling pathway might play a key role in treating insomnia synergistically with HIF-1 signaling pathway, prolactin signaling pathway, chemical carcinogenesis receptor activation, and PI3K-Akt signaling pathway. Molecular docking indicated that there was good binding between the active ingredients of the hub herb pairs and the hub targets.</p><p><strong>Conclusions: </strong>This study identified six hub herb pairs for treating insomnia in TCM. These hub herb pairs may synergistically treat insomnia with HIF-1 signaling pathway, prolactin signaling pathway, chemical carcinogenesis receptor activation, and PI3K-Akt signaling pathway through the cAMP signaling pathway.</p>","PeriodicalId":35615,"journal":{"name":"Chinese Medical Sciences Journal","volume":"39 4","pages":"249-260"},"PeriodicalIF":0.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956127","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}
Wei Yang, Jian-Xia Yang, Jing-Yuan Guan, Wu-Yun Bao, Mei Zhang
{"title":"Value of Myocardial Strain in Monitoring Fluorouracil-Based Chemotherapy-Related Cardiac Dysfunction in Gastrointestinal Cancer Patients.","authors":"Wei Yang, Jian-Xia Yang, Jing-Yuan Guan, Wu-Yun Bao, Mei Zhang","doi":"10.24920/004387","DOIUrl":"https://doi.org/10.24920/004387","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the predictive value of myocardial strain for cardiotoxicity associated with fluorouracil-based chemotherapies in gastrointestinal cancer patients.</p><p><strong>Methods: </strong>Patients with diagnosis of gastrointestinal cancers, who were hospitalized for chemotherapy involving antimetabolic drugs, were eligible in this prospective study. Echocardiography was performed before and after each chemotherapy cycle during hospitalization until the completion of chemotherapy. Cancer therapy-related cardiac dysfunction (CTRCD) was identified if there was a decrease in left ventricular ejection fraction (LVEF) by at least 5% to an absolute value of < 53% from the baseline, accompanied by symptoms or signs of heart failure; or a decrease in LVEF of at least 10% to an absolute value of < 53% from the baseline, without symptoms or signs of heart failure. Subclinical cardiac impairment is defined as a decrease in the left ventricular global longitudinal strain (GLS) of at least 15% from baseline.Clinical data and myocardial strain variables were collected. Changes of echocardiographic indexes after chemotherapy at each cycle were observed and compared to those of pre-chemotherapy. Cox regression analysis was used to determine the associated indexes to CTRCD, and receiver operating characteristic (ROC) curves were plotted for evaluation of their predicting efficacy.</p><p><strong>Results: </strong>Fifty-one patients completed 4 cycles of chemotherapy and were enrolled in the study analysis. LVEF, GLS, GLS epicardium (GLS-epi), and GLS endocardium (GLS-endo) were decreased after the 4 cycles of chemotherapy. Throughout the chemotherapy period, 6 patients (11.8%) progressed to CTRCD. The Cox regression analysis revealed that the change in left atrial ejection fraction (LAEF) and LAS during the reservoir (LASr) phase after the first cycle of chemotherapy (C1v-LAEF and C1v-LASr, respectively) were significantly associated with the development of CTRCD [C1v-LAEF (<i>HR</i>=1.040; 95%<i>CI</i>: 1.000-1.082; <i>P</i>=0.047); C1v-LASr (<i>HR</i>=1.024; 95%<i>CI</i>: 1.000-1.048; <i>P</i>=0.048)]. The sensitivity and specificity were 50.0% and 93.3%, respectively, for C1v-LAEF predicting CTRCD when C1v-LAEF > 19.68% was used as the cut-off value, and were 66.7% and 75.6%, respectively, for C1v-LASr predicting CTRCD when C1v-LASr > 14.73% was used as the cut-off value. The areas under the ROC curve (AUC) for C1v-LAEF and C1v-LASr predicting CTRCD were 0.694 and 0.707, respectively.</p><p><strong>Conclusions: </strong>GLS changes among patients with subclinical impairment of cardiac function who were treated with fluorouracil-based chemotherapies, and C1v-LAEF and C1v-LASr of the left atrium are early predictors of cardiac function deterioration.</p>","PeriodicalId":35615,"journal":{"name":"Chinese Medical Sciences Journal","volume":"39 4","pages":"273-281"},"PeriodicalIF":0.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956129","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}
Zhi-Yuan Xiao, Yan-Xia Sun, Dong-Rui Xu, Xiao-Hong Ning, Yu Wang, Yi Zhang, Wen-Bin Ma
{"title":"End-of-Life Inpatient Palliative Care for Glioblastoma Multiforme: Lessons Learned from One Case.","authors":"Zhi-Yuan Xiao, Yan-Xia Sun, Dong-Rui Xu, Xiao-Hong Ning, Yu Wang, Yi Zhang, Wen-Bin Ma","doi":"10.24920/004394","DOIUrl":"https://doi.org/10.24920/004394","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor with a poor prognosis and limited survival. Patients with GBM have a high demand for palliative care. In our present case, a 21-year-old female GBM patient received inpatient palliative care services including symptom management, mental and psychological support for the patient, psychosocial and clinical decision support for her family members, and pre- and post-death bereavement management for the family. Furthermore, we provided the family members with comprehensive psychological preparation for the patient's demise and assisted the patient's family throughout the mourning period.The aim of this study is to provide a reference and insights for the clinical implementation of palliative care for patients with malignant brain tumors.</p>","PeriodicalId":35615,"journal":{"name":"Chinese Medical Sciences Journal","volume":"39 4","pages":"297-302"},"PeriodicalIF":0.0,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956126","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":"BILL Strategy: Points to Consider During the Performance and Interpretation of Critical Care Echocardiography","authors":"Hong-Min Zhang , Hui Lian , Xiao-Ting Wang","doi":"10.24920/004357","DOIUrl":"10.24920/004357","url":null,"abstract":"<div><div>The growing utilization of critical care echocardiography (CCE) by clinicians necessitates a meticulous review of clinical conditions in critically ill patients, both before and during the examination. The reviewing process of clinical conditions minimizes the risk of overlooking or misinterpreting crucial findings. This article proposes a comprehensive strategy, namely BILL strategy, to integrate into the CCE protocol, where “B” represents baseline respiratory and hemodynamic support, “I” signifies information gleaned from invasive monitoring, including central venous pressure and thermodilution-derived cardiac output, the first “L” denotes laboratory results such as central venous oxygen saturation, troponin, and brain natriuretic peptide, and the second “L” refers to lung ultrasound data. Combining the BILL strategy with CCE can enhance comprehensive understanding of critical conditions, potentially leading to improved diagnostic accuracy and patient outcomes.</div></div>","PeriodicalId":35615,"journal":{"name":"Chinese Medical Sciences Journal","volume":"39 3","pages":"Pages 226-232"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297224","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}
Moliduer Hamiti , Xin-Tian Zhang , Rui-Min Zhu , Yun-Peng Liu , Bin Yin , Peng-Cheng Shu , Xiao-Zhong Peng
{"title":"Polypyrimidine Tract-Binding Protein Enhances Zika Virus Translation by Binding to the 5’UTR of Internal Ribosomal Entry Site","authors":"Moliduer Hamiti , Xin-Tian Zhang , Rui-Min Zhu , Yun-Peng Liu , Bin Yin , Peng-Cheng Shu , Xiao-Zhong Peng","doi":"10.24920/004393","DOIUrl":"10.24920/004393","url":null,"abstract":"<div><h3>Objectives</h3><div>To identify the 5’ untranslated region of Zika virus (ZIKV 5’UTR) RNA-binding proteins and to investigate the impact of the binding protein on the activity of internal ribosomal entry site (IRES) located in ZIKV 5’UTR and virus production.</div></div><div><h3>Methods</h3><div>Interacting proteins in U251 cells were captured using tRSA-tagged ZIKV 5’UTR RNA and tRSA-ZIKV 5’UTR RNA-binding proteins were visualized by SDS-PAGE silver staining. Subsequently, liquid chromatographytandem mass spectrometry (LC-MS/MS), bioinformatics analysis, and Western blot were used to identify the candidate proteins binding to ZIKV 5’UTR. Dicistronic expression assay and plaque forming assay were performed to analyze the effect of the binding protein on ZIKV IRES activity and ZIKV production, respecitvely.</div></div><div><h3>Results</h3><div>tRSA RNA pull-down assay, LC-MS/MS, and Western blot analysis showed that polypyrimidine tract-binding protein (PTB) bound to the ZIKV 5’UTR. Furthermore, dual luciferase reporter assay revealed that overexpression of PTB significantly enhanced the IRES activity of ZIKV (<em>t</em> = 10.220, <em>P</em> < 0.001), while PTB knockdown had the opposite effect (<em>t</em> = 4.897, <em>P</em> < 0.01). Additionally, virus plaque forming assay demonstrated that up-regulation of PTB expression significantly enhanced viral titer (<em>t</em> = 6.400, <em>P</em> < 0.01), whereas reducing PTB expression level weakened virus infectivity (<em>t</em> = 5.055, <em>P</em> < 0.01).</div></div><div><h3>Conclusion</h3><div>PTB positively interacts with the ZIKV 5’UTR and enhances IRES activity and virus production.</div></div>","PeriodicalId":35615,"journal":{"name":"Chinese Medical Sciences Journal","volume":"39 3","pages":"Pages 162-170"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355605","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}