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Inflammatory Factor IL1αInduces Aberrant Astrocyte Proliferation in Spinal Cord Injury Through the Grin2c/Ca^(2+)/CaMK2b Pathway

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Neuroscience Bulletin 2024年第4期40卷 421-438页

作者： Yu Xia Lu Ding Changlin Zhang Qi Xu Ming Shi Tianshun Gao Feng-Quan Zhou David Y.B.Deng Scientific Research Center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Department of Gynecology The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Pelvic Floor Disorders Center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Big Data Center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Sir Run Run Shaw hospital Zhejiang University School of MedicineHangzhou310016China Orthopaedic and Neurological Repair Center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

Spinal cord injury(SCI)is one of the most devastating traumas,and the aberrant proliferation of astrocytes usually causes neurological ***,the mechanism underlying astrocyte over-proliferation after SCI is ***2c(glutamate ionotropic receptor type 2c)plays an essential role in cell *** bioinformatic analysis indicated that Grin2c and Ca^(2+)transport functions were inhibited in astrocytes after *** of Grin2c stimulated astrocyte proliferation by inhibiting the Ca^(2+)/calmodulin-dependent protein kinase 2b(CaMK2b)pathway in *** screening different inflammatory factors,interleukin 1α(IL1α)was further found to inhibit Grin2c/Ca^(2+)/CaMK2b and enhance astrocyte proliferation in an oxidative damage *** of IL1αusing neutralizing antibody resulted in increased Grin2c expression and the inhibition of astrocyte proliferation ***,this study suggests that IL1αpromotes astrocyte proliferation by suppressing the Grin2c/Ca^(2+)/CaMK2b pathway after SCI,revealing a novel pathological mechanism of astrocyte proliferation,and may provide potential targets for SCI repair.

关键词： IL1α Grin2c Astrocyte Spinal cord injury

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RP11-789C1.1 inhibits gastric cancer cell proliferation and accelerates apoptosis via the ATR/CHK1 signaling pathway

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中华医学杂志(英文版) 2024年第15期137卷 1835-1843页

作者： Liu Wenwei Feng Wei Zhang Yongxin Lei Tianxiang Wang Xiaofeng Qiao Tang Chen Zehong Song Wu Digestive Diseases Center The Seventh Affiliated Hospital of Sun Yat-sen University Shenzhen Guangdong China Department of Gastrointestinal Surgery The First Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong China Laboratory of General Surgery The First Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong China Department of Gastrointestinal Surgery The Third Affiliated Hospital of Sun Yat-sen University Guangzhou Guangdong China

Background: Long non-coding RNAs (lncRNAs) plays an important role in the progression of gastric cancer (GC). Their involvement ranges from genetic regulation to cancer progression. However, the mechanistic roles of RP11-789C1.1 in GC are not fully ***: We identified the expression of lncRNA RP11-789C1.1 in GC tissues and cell lines by real-time fluorescent quantitative polymerase chain reaction. A series of functional experiments revealed the effect of RP11-789C1.1 on the proliferation of GC *** vivo experiments verified the effect of RP11-789C1.1 on the biological behavior of a GC cell line. RNA pull-down unveiled RP11-789C1.1 interacting proteins. Western blot analysis indicated the downstream pathway changes of RP11-789C1.1, and an oxaliplatin dosing experiment disclosed the influence of RP11-789C1.1 on the drug sensitivity of ***: Our results demonstrated that RP11-789C1.1 inhibited the proliferation of GC cells and promoted the apoptosis of GC cells. Mechanistically, RP11-789C1.1 inhibited checkpoint kinase 1 (CHK1) phosphorylation by binding ataxiatelangiectasia mutated and Rad3 related (ATR), a serine/threonine-specific protein kinase, promoted GC apoptosis, and mediated oxaliplatin ***: In general, we discovered a tumor suppressor molecule RP11-789C1.1 and confirmed its mechanism of action, providing a theoretical basis for targeted GC therapy.

关键词： Long non-coding RNA RP11-789C1.1 Stomach neoplasms ATR CHK1 Oxaliplatin

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Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of B-cell hematologic malignancies in vivo

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Oncology Research 2024年第6期32卷 1109-1118页

作者： ZHIGANG XIA MENGYAO TIAN YUCAI CHENG WENFANG YI ZEFAN DU TIANWEN LI YUCHEN WEN LINDI LI YONG LIU CHUN CHEN Pediatric Hematology Laboratory Division of Hematology/OncologyDepartment of PediatricsThe Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Scientific Research Center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological ***,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion *** and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell ***,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment ***:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological ***,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.

关键词： CD19 CAR-T B-cell hematologic malignancies Metabolism In vivo

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Epigenetic and transcriptional landscapes during cerebral cortex development in a microcephaly mouse model

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Journal of Genetics and Genomics 2024年第4期51卷 419-432页

作者： Qing Yang Qiang Cao Yue Yu Xianxin Lai Jiahao Feng Xinjie Li Yinan Jiang Yazhou sun Zhong-Wei Zhou Xin Li School of Medicine Shenzhen Campus of Sun Yat-sen UniversityShenzhenGuangdong 518107China Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjin 300072China Scientific Research Center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhenGuangdong 518107China Guangdong Provincial Key Laboratory of Digestive Cancer Research The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhenGuangdong 518107China

The cerebral cortex is a pivotal structure integral to advanced brain functions within the mammalian central nervous *** methylation and hydroxymethylation play important roles in regulating cerebral cortex ***,it remains unclear whether abnormal cerebral cortex development,such as microcephaly,could rescale the epigenetic landscape,potentially contributing to dysregulated gene expression during brain *** this study,we characterize and compare the DNA methylome/hydroxymethylome and transcriptome profiles of the cerebral cortex across several developmental stages in wild-type(WT)mice and Mcph1 knockout(Mcph1-del)mice with severe ***,we discover a global reduction of 5′-hydroxymethylcytosine(5hmC)level,primarily in TET1-binding regions,in Mcph1-del mice compared to WT mice during juvenile and adult ***,genes exhibiting diminished 5hmC levels and concurrently decreased expression are essential for neurodevelopment and brain ***,genes displaying a delayed accumulation of 5hmC in Mcph1-del mice are significantly associated with the establishment and maintenance of the nervous system during the adult *** findings reveal that aberrant cerebral cortex development in the early stages profoundly alters the epigenetic regulation program,which provides unique insights into the molecular mechanisms underpinning diseases related to cerebral cortex development.

关键词： Microcephaly Epigeneticmodification Tet1 Cerebral cortexdevelopment DNA hydroxymethylome Transcriptome

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An intelligent prediction model of epidemic characters based on multi-feature

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CAAI Transactions on Intelligence Technology 2024年第3期9卷 595-607页

作者： Xiaoying Wang Chunmei Li Yilei Wang Lin Yin Qilin Zhou Rui Zheng Qingwu Wu Yuqi Zhou Min Dai Information Center Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina School of Computer Science Qufu Normal UniversityRizhaoChina Department of Allergy Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhou China 4Department of Otorhinolaryngology‐Head and Neck Surgery Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina Department of Pulmonary and Critical Care Medicine Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina Department of Traditional Chinese Medicine Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina

The epidemic characters of Omicron(***-scale transmission)are significantly different from the initial variants of *** data generated by large-scale transmission is important to predict the trend of epidemic ***,the re-sults of current prediction models are inaccurate since they are not closely combined with the actual situation of Omicron *** consequence,these inaccurate results have negative impacts on the process of the manufacturing and the service industry,for example,the production of masks and the recovery of the tourism *** authors have studied the epidemic characters in two ways,that is,investigation and ***,a large amount of data is collected by utilising the Baidu index and conduct questionnaire survey concerning epidemic ***,theβ-SEIDR model is established,where the population is classified as Susceptible,Exposed,Infected,Dead andβ-Recovered persons,to intelligently predict the epidemic characters of *** thatβ-Recovered persons denote that the Recovered persons may become Sus-ceptible persons with probabilityβ.The simulation results show that the model can accurately predict the epidemic characters.

关键词： artificial intelligence big data data analysis evaluation feature extraction intelligent information processing medical applications

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High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke

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Neural Regeneration Research 2024年第8期19卷 1772-1780页

作者： Jing Luo Yuan Feng Zhongqiu Hong Mingyu Yin Haiqing Zheng Liying Zhang Xiquan Hu Department of Rehabilitation Medicine The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Hepatobiliary Surgery The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction *** magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem ***,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic ***-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ***,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and *** effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem ***,we validated the effect of repetitive TMS on AKT *** found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin *** findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling *** study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro *** results provide a stro ng scientific foundation for the clinical application of repetitive ***,repetitive TMS treatment may not only be an efficient an

关键词： AKT/β-catenin signaling brain stimulation Ca2+influx cell proliferation ischemic stroke middle cerebral artery occlusion neural stem cells neurological rehabilitation repetitive transcranial magnetic stimulation

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Bronchoalveolar lavage fluid metagenomic next-generation sequencing assay for identifying pathogens in lung cancer patients

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BIOCELL 2024年第4期48卷 623-637页

作者： JIYU WANG HUIXIA LI DEYUAN ZHOU LIHONG BAI KEJING TANG Division of Pulmonary and Critical Care Medicine The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Institute of Pulmonary Diseases Sun Yat-sen UniversityGuangzhouChina Department of Pharmacy The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina

Background:For patients with lung cancer,timely identiﬁcation of new lung lesions as infectious or non-infectious,and accurate identiﬁcation of pathogens is very important in improving OS of *** a new auxiliary examination,metagenomic next-generation sequencing(mNGS)is believed to be more accurate in diagnosing infectious diseases in patients without underlying diseases,compared with conventional microbial tests(CMTs).We designed this study toﬁnd out whether mNGS has better performance in distinguishing infectious and non-infectious diseases in lung cancer patients using bronchoalveolar lavageﬂuid(BALF).Materials and Methods:This study was a real-world retrospective review based on electronic medical records of lung cancer patients with bronchoalveolar lavage(BAL)and BALF commercial mNGS testing as part of clinical care from 1 April 2019 through 30 April 2022 at The First Afﬁliated hospital of sun yat-sen university.164 patients were included in this *** were categorized into the pulmonary non-infectious disease(PNID)group(n=64)and the pulmonary infectious disease(PID)group(n=100)groups based onﬁnal ***:BALF mNGS increased the sensitivity rate by 60%compared to CMTs(81%vs.21%,p0.1).Among the patients with PID,bacteria were the most common cause of *** infections occurred in 32%of patients,and Pneumocystis Yersini was most *** with Tyrosine kinase inhibitors(TKIs)therapy possess longer overall survival(OS)than other anti-cancer agents,the difference between TKIs and immuno-checkpoint inhibitors(ICIs)was insigniﬁcant(median OS TKIs *** ***-angiogenic *** ***=76 vs.84 vs.61 vs.58 vs.60).Conclusions:our study indicates that BALF mNGS can add value by improving overall sensitivity in lung cancer patients with potential pulmonary infection,and was outstanding in identifying Pneumocystis *** could be able

关键词： Lung cancer Bronchoalveolar lavage fluid Metagenomic next-generation sequencing Infectious diseases

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癫痫学报（英文） 2024年第2期7卷 119-129页

作者： Man Yang Yinchao Li Xianyue Liu Shangnan Zou Lei Lei Qihang Zou Yaqian Zhang Yubao Fang Shuda Chen Liemin Zhou Department of Neurology The Seventh Affiliated HospitalSun Yat-Sen UniversityShenzhen 518107Guangdong ProvinceChina

Background Autophagy plays essential roles in the development and pathogenesis of mesial temporal lobe epilepsy(mTLE).In this research,we aim to identify and validate the autophagy-related genes associated with mTLE through bioinformatics analysis and experimental validations.Methods We obtained the dataset GSE143272 and high-throughput sequencing results of mTLE from public *** differentially expressed autophagy-related genes related to mTLE were identified using R ***,genomes pathway enrichment analysis,protein-protein interactions(PPIs),and the gene ontology(GO)enrichment were performed for the selected autophagy-related *** mRNA expression profiles of hub genes were then used to establish a least absolute shrinkage and selection operator(LASSO)***,seven hub candidate autophagy-related genes were confirmed in hippocampus using the lithium-pilocarpine chronic epilepsy model.Results A total of 40 differential expression genes(DEGs)among the core autophagy-related genes were *** analysis results of PPI revealed that interactions among these *** pathway and GO analysis of selected candidate autophagy-related genes indicated that those enriched terms mainly focused on macroautophagy,regula-tion of autophagy,cellular response to extracellular stimulus and mitochondrion *** results suggested that SQSTM 1,VEGFA,BNIP and WIPI2 were consistent with the bioinformatics *** expression levels of SQSTM1 and VEGFA in epilepsy model samples were significantly higher than those in normal control,while BNIP and WIPI2 expression levels were notably *** final hub gene-based LASSO regression model accurately predicted the occurrence of epilepsy(AUC=0.88).Conclusions Through bioinformatics analysis of public data,we identified 40 candidate autophagy-related genes associated with ***1,VEGFA,BNIP and WIPI2 may play significant roles in autophagy,influencing the onset and develo

关键词： Autophagy Mesial temporal lobe epilepsy Bioinformatics analysis Biomarkers

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Glucagon-like peptide-1 receptor agonists rescued diabetic vascular endothelial damage through suppression of aberrant STING signaling

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2613-2630页

作者： Xuemin He Siying Wen Xixiang Tang Zheyao Wen Rui Zhang Shasha Li Rong Gao Jin Wang Yanhua Zhu Dong Fang Ting Li Ruiping Peng Zhaotian Zhang Shiyi Wen Li Zhou Heying Ai Yan Lu Shaochong Zhang Guojun Shi Yanming Chen Department of Endocrinology and Metabolic Diseases the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Guangdong Provincial Key Laboratory of Diabetology&Guangzhou Municipal Key Laboratory of Mechanistic and Translational Obesity Research the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China VIP Medical Service Center the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Clinical Immunology the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Ophthalmology the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China Department of Fundus Shenzhen Eye Hospital of Jinan UniversityShenzhen 518048China

Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)protect against diabetic cardiovascular diseases and ***,their activity in diabetic retinopathy(DR)remains *** retrospective cohort study involving 1626 T2DM patients revealed superior efficacy of GLP-1 RAs in controlling DR compared to other glucose-lowering medications,suggesting their advantage in DR *** single-cell RNA-sequencing analysis and immunostaining,we observed a high expression of GLP-1R in retinal endothelial cells,which was down-regulated under diabetic *** of GLP-1 RAs significantly restored the receptor expression,resulting in an improvement in retinal degeneration,vascular tortuosity,avascular vessels,and vascular integrity in diabetic *** and GSEA analyses further implicated enhanced mitochondrial gene translation and mitochondrial functions by GLP-1 ***,the treatment attenuated STING signaling activation in retinal endothelial cells,which is typically activated by leaked mitochondrial *** of STING mRNA was positively correlated to the levels of angiogenic and inflammatory factors in the endothelial cells of human fibrovascular *** investigation revealed that the cAMP-responsive element binding protein played a role in the GLP-1R signaling pathway on suppression of STING *** study demonstrates a novel role of GLP-1 RAs in the protection of diabetic retinal vasculature by inhibiting STING-elicited inflammatory signals.

关键词： GLP-1 RAs STING signaling Retinal endothelial cells Mitochondrial leakage Retinal vascular dysfunction Diabetic retinopathy CREB Inflammation

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Pharmacokinetic enhancement of oncolytic virus M1 by inhibiting JAK-STAT pathway

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2554-2566页

作者： Jingyi Tan Jiayu Zhang Cheng Hu Gongwei Wang Qianyao Ren Chaoqun Wang Jia Dan Zexin Zeng Jun Hu Wenbo Zhu Jiankai Liang Jing Cai Ying Liu Guangmei Yan Yuan Lin Department of Pharmacology Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China The Sixth affiliated hospital Sun Yat-sen UniversityGuangzhou 510655China Department of Urology the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Advanced Medical Technology Center the First Affiliated Hospital-Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China Key Laboratory of Human Microbiome and Elderly Chronic Diseases Ministry of EducationGuangzhou 510655China Department of Infectious Diseases the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China

Oncolytic viruses(OVs),a group of replication-competent viruses that can selectively infect and kill cancer cells while leaving healthy cells intact,are emerging as promising living anticancer *** traditional drugs composed of non-replicating compounds or biomolecules,the replicative nature of viruses confer unique pharmacokinetic properties that require further *** some pharmacokinetics studies of OVs,mechanistic insights into the connection between OV pharmacokinetics and antitumor efficacy remain ***,we characterized the pharmacokinetic profile of oncolytic virus M1(OVM)in immunocompetent mouse tumor models and identified the JAK-STAT pathway as a key modulator of OVM *** suppressing the JAK-STAT pathway,early OVM pharmacokinetics are ameliorated,leading to enhanced tumor-specific viral accumulation,increased AUC and Cmax,and improved antitumor *** than compromising antitumor immunity after JAK-STAT inhibition,the improved pharmacokinetics of OVM promotes T cell recruitment and activation in the tumor microenvironment,providing an optimal opportunity for the therapeutic outcome of immune checkpoint blockade,such as *** together,this study advances our understanding of the pharmacokinetic-pharmacodynamic relationship in OV therapy.

关键词： Pharmacokinetics Oncolytic virus JAK-STAT Anticancer

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