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Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

Neural Regeneration Research 2025年第4期20卷 1135-1152页

作者： Yisheng Chen Zhongcheng Fan Zhiwen Luo Xueran Kang Renwen Wan Fangqi Li Weiwei Lin Zhihua Han Beijie Qi Jinrong Lin Yaying Sun Jiebin Huang Yuzhen Xu Shiyi Chen Department of Sport medicine Huashan HospitalFudan UniversityShanghaiChina Department of Orthopedic Surgery Hainan Province Clinical Medical CenterHaikou Affiliated Hospital of Central South University Xiangya School of MedicineHaikouHainan ProvinceChina Department of Basic medicine Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Neurosurgery Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina Department of Orthopedics Shanghai General HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural *** role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of *** used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other *** demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by *** underscores the intricate relationship between natural compounds such as nutlin-3 and immune *** comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma *** also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic ***-3a inhibited glioma cell proliferation and activated the p53 *** efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or *** using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway ***,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing *** results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma *** research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

关键词： exercise and SUMO-related gene signatures(ESLRS) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise

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Analgesic effect of AG490, a Janus kinase inhibitor, on oxaliplatin-induced acute neuropathic pain

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Neural Regeneration Research 2018年第8期13卷 1471-1476页

作者： Shuang-Feng Li Bi-Shan Ouyang Xin Zhao Ya-Ping Wang Department of Anesthesiology The Second Xiangya Hospital Xiangya School of Medicine Central South University Department of Anesthesiology Hainan General Hospital Department of Neurology Xiangya Hospital Xiangya School of Medicine Central South University

Neuropathic pain often occurs during chemotherapy with oxaliplatin. AG490 has been shown to exert an antagonistic effect on inflammatory pain, but its effect on oxaliplatin-induced neuropathic pain remains poorly understood. This study sought to observe the analgesic effect of AG490 on acute neuropathic pain induced by a single oxaliplatin treatment and to address the possible mechanism. In this study, we estab- lished a model of oxaliplatin-induced acute neuropathic pain by intraperitoneal injection of 6 mg/kg oxaliplatin. On day 2 after injection, models were intraperitoneally injected with i, 5, or 10 mg/kg AG490. Paw withdrawal threshold to mechanical stimuli and tail withdrawal latency to cold stimuli were determined. Western blot assay was performed to detect the expression of spinal phosphorylated signal transducer and activator of transcription 3 （p-STAT3）. Immunohistochemistry was used to determine the immunoreactivity of p-STAT3 and inter- leukin-6. Results demonstrated that paw withdrawal threshold and tail withdrawal latency were significantly increased by the treatment of AG490 in rats. There was no significant difference in the effect among the different doses of AG490. AG490 10 mg/kg decreased the expression of p-STAT3, the immunoreactivity of p-STAT3 and interleukin-6 in spinal cord of acute neuropathic pain rats. These findings confirm that AG490 can attenuate oxaliplatin-induced acute neuropathic pain and is associated with the inhibition in the JAK/STAT3 signaling pathway.

关键词： nerve regeneration A G490 analgesia oxaliplatin cancer chemotherapy neuropathic pain phosphorylated STA T3 JAK/STA Tsignaling pathway interleukin-6 neural regeneration

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Persistent alterations in gray matter in COVID-19 patients experiencing sleep disturbances:a 3-month longitudinal study

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Neural Regeneration Research 2025年第10期20卷 3013-3024页

作者： Kaixuan Zhou Gaoxiong Duan Ying Liu Bei Peng Xiaoyan Zhou Lixia Qin Lingyan Liang Yichen Wei Qingping Zhang Xiaocheng Li Haixia Qin Yinqi Lai Yian Lu Yan Zhang Jiazhu Huang Jinli Huang Yinfei Ouyang Bolin Bin Mingming Zhao Jun Liu Jianrong Yang Demao Deng Guangxi Key Laboratory of Special Biomedicine School of MedicineGuangxi UniversityNanningGuangxi Zhuang Autonomous RegionChina Department of Radiology the People’s Hospital of Guangxi Zhuang Autonomous RegionGuangxi Academy of Medical SciencesNanningGuangxi Zhuang Autonomous RegionChina Department of Sleep medicine the People’s Hospital of Guangxi Zhuang Autonomous RegionNanningGuangxi Zhuang Autonomous RegionChina Department of Radiology The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Guangxi Clinical Research Center for Sleep medicine the People’s Hospital of Guangxi Zhuang Autonomous RegionNanningGuangxi Zhuang Autonomous RegionChina

Sleep disturbances are among the most prevalent neuropsychiatric symptoms in individuals who have recovered from severe acute respiratory syndrome coronavirus 2 *** studies have demonstrated abnormal brain structures in patients with sleep disturbances who have recovered from coronavirus disease 2019(COVID-19).However,neuroimaging studies on sleep disturbances caused by COVID-19 are scarce,and existing studies have primarily focused on the long-term effects of the virus,with minimal acute phase *** a result,little is known about the pathophysiology of sleep disturbances in the acute phase of *** address this issue,we designed a longitudinal study to investigate whether alterations in brain structure occur during the acute phase of infection,and verified the results using 3-month follow-up data.A total of 26 COVID-19 patients with sleep disturbances(aged 51.5±13.57 years,8 women and 18 men),27 COVID-19 patients without sleep disturbances(aged 47.33±15.98 years,9 women and 18 men),and 31 age-and gender-matched healthy controls(aged 49.19±17.51 years,9 women and 22 men)were included in this *** COVID-19 patients with sleep disturbances were included in a longitudinal *** found that COVID-19 patients with sleep disturbances exhibited brain structural changes in almost all brain *** cortical thicknesses of the left pars opercularis and left precuneus were significantly negatively correlated with Pittsburgh Sleep Quality Index ***,we observed changes in the volume of the hippocampus and its subfield regions in COVID-19 patients compared with the healthy *** 3-month follow-up data revealed indices of altered cerebral structure(cortical thickness,cortical grey matter volume,and cortical surface area)in the frontal-parietal cortex compared with the baseline in COVID-19 patients with sleep *** findings indicate that the sleep disturbances patients had altered morphology in the cortical an

关键词： brain structure cortical gray matter volume cortical surface area cortical thickness hippocampus magnetic resonance imaging Pittsburgh Sleep Quality Index severe acute respiratory syndrome coronavirus 2 infections sleep disturbances sub-cortical volume

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Cells in G2/M phase increased in human nasopharyngeal carcinoma cell line by EBV-LMP1 through activation of NF-кB and AP-1

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Cell Research 2003年第3期13卷 187-194页

作者： LIN DENG,JING YANG,XIAO RONG ZHAO,XI YUN DENG,LIANG ZENG,HUAN HUA GU,MIN TANG,YA CAOCancer Research Institute,xiangya school of medicine,Central South University,xiangya Road 88,Chang-sha,Hunan 410078,China 1Cancer Research Institute Xiangya School of Medicine Central South University Xiangya Road 88 Changsha Hunan 410078 China 1Cancer Research Institute Xiangya School of Medicine Central South University Xiangya Road 88 Changsha Hunan 410078 China 1Cancer Research Institute Xiangya School of Medicine Central South University Xiangya Road 88 Changsha Hunan 410078 China 1Cancer Research Institute Xiangya School of Medicine Central South University Xiangya Road 88 Changsha Hunan 410078 China 1Cancer Research Institute Xiangya School of Medicine Central South University Xiangya Road 88 Changsha Hunan 410078 China 1Cancer Research Institute Xiangya School of Medicine Central South University Xiangya Road 88 Changsha Hunan 410078 China 1Cancer Research Institute Xiangya School of Medicine Central South University Xiangya Road 88 Changsha Hunan 410078 China 1Cancer Research Institute Xiangya School of Medicine Central South University Xiangya Road 88 Changsha Hunan 410078 China

Although previous studies showed that the principal oncoprotein encoded by Epstein-Barr virus, latentmembrane protein 1 （LMP1） 5 could induce the nasopharyngeal carcinoma cells in G2/M phase increased, littleis known about the target molecules and mechanisms. The present study demonstrated that LMP1 couldinduce the accumulation of p53 protein and upregulate its transactivity in a dose dependent manner, whichresulted in the decrease of the kinase activity of cdc2/cyclin B complex and inducing arrest at G2/M phasethrough the activation of NF-κB and AP-1 signaling pathways, and the effect of NF-κB was more obviousthan that of AP-1. This study provided some significant evidence for further elucidating the molecularmechanisms that LMP1 had effects on the surveillance mechanism of cell cycle and promoting the survivalof transformed cells and tumorigenesis.

关键词： LMP1 nasopharyngeal carcinoma p53 G2/M

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Effect of vasoactive intestinal peptide on pulmonary surfactants phospholipid synthesis in lung explants

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Acta Pharmacologica Sinica 2004年第12期25卷 86-92页

作者： Lian LI, Zi-qiang LUO2, Fu-wen ZHOU, Dan-dan FENG, Cha-xiang GUAN, Chang-qing ZHANG, Xiu-hong SUN Department of Physiology, xiangya schoolof medicine, CentralSouth University, Changsha 410078, China Department of Physiology Xiangya School of Medicine Central South University Changsha 410078 China

AIM: To investigate the effect of vasoactive intestinal peptide (VIP) on pulmonary surfactants (PS) phospholipid synthesis in cultured lung explants. METHODS: Lung explants were cultured with serum-free medium, [methyl- 3H]choline incorporation, total phospholipid, phosphatidylcholine, activity of choline-phosphate cytidylyltransferase (CCT) and CCTα mRNA level in lung explants were determined. RESULTS: (1) VIP (10-10-10-7mol/L) for 16 h promoted [methyl-3H]choline incorporation in dose dependence and VIP (10-8mol/L) for 2 h-16 h promoted [methyl- 3H]choline incorporation in time dependence. (2) VIP (10-8 mol/L) enhanced the contents of total phospholipids and phosphatidylcholine in lung explants. (3) VIP (10-10-10-7mol/L) elevated microsomal CCT activity of lung explants in dose dependence. (4) VIP (10-8 mol/L) increased expression of CCTα mRNA in lung explants and alveolar type II cells (ATII). (5) [D-P-Cl-Phe(6)-Leu(17)]-VIP (10-6 mol/L), a VIP receptors antagonist, abolished the increase of [3H]choline incorporation, microsomal CCT activity and CCTα mRNA level induced by VIP (10-8 mol/L) in lung explants. CONCLUSION: VIP could enhance synthesis of phosphatidylcholine, the major compo- nent of pulmonary surfactants by enhancing microsomal CCT activity and CCTα mRNA level via VIP receptor- mediated pathway.

关键词： vasoactive intestinal peptide pulmonary surfactants choline-phosphate cytidylyltransferase

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Schistosoma japonicum: Isolation and Identification of Peptides Mimicking Ferritin Epitopes from Phage Display Library

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Acta Biochimica et Biophysica Sinica 2004年第3期36卷 206-210页

作者： Lian-Fei TANG, Xin-Yuan YI*, Xian-Fang ZENG, Lin-Qian WANG, and Shun-Ke ZHANG Department of Parasitology, Central South University xiangya school of medicine, Changsha 410078, China Department of Parasitology Central South University Xiangya School of Medicine Changsha 410078 China

In an attempt to isolate and identify the antigenic epitopes on ferritin of Schistosoma japonicum (SjFer) and to test their protective potentiality against Schistosoma japonicum (S.j), polyclonal antisera against SjFer was prepared to screen a 12-mer random peptide library. Three rounds of biopan- ning were performed and resulted in an enrichment. Six peptides selected randomly from the third elute were all found to be positive by evaluating the binding to anti-SjFer sera by ELISA and Western blot- ting. Three amino acid sequences were deduced from the six phage clones by sequencing. When they were used to vaccinate mice, the three peptides could induce significant reduction in adult worms (26.7%, 20.4%, and 25.9%) as well as in liver eggs per gram (LEPG) (40.0%, 38.2%, and 40.8%). This result showed that three mimotopes on SjFer were obtained and they could induce significant protective efficacy against S.j.

关键词： phage displayed peptide library epitope Schistosoma japonicum ferritin

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A Bridge between the Innate Immunity System and Amyloid-β Production in Alzheimer’s Disease

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Neuroscience Bulletin 2021年第6期37卷 898-901页

作者： Xiying Wang xiangya school of medicine Central South UniversityChangsha 410078China

Extracellular deposition of amyloid-β(Aβ)is one of the pathological hallmarks of Alzheimer’s disease(AD)[1].It has emerged that innate immune activation plays an important role in AD and other neurodegenerative diseases[2].On the understanding of the interactions between Aβ and the innate immune system in the brain,it is well know that both fibrillary and oligomeric Aβ can activate the main innate immune cells,microglia,through multiple microglial receptors[2,3].

关键词： Alzheimer Aβ diseases

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Research Progress on the Association between Schizophrenia and Toxoplasma gondii Infection

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Biomedical and Environmental Sciences 2024年第6期37卷 647-660页

作者： Yiting Zhu Xiaohui Yang Miaoru Chen Yu Hu Yunfeng Chang Xiang Wu Department of Forensic medicine Science Xiangya School of Basic MedicineCentral South UniversityChangsha 410013HunanChina Nursing Department The Third Xiangya Hospital of Central South UniversityChangsha 410013HunanChina Department of Basic medicine Science Xiangya School of Basic MedicineCentral South UniversityChangsha 410013HunanChina Department of Parasitology Xiangya School of Basic MedicineCentral South UniversityChangsha 410013HunanChina

Toxoplasma gondii(*** or Tg),is an obligatory intracellular parasite with humans as its intermediate *** recent years,significant correlations between *** infection and schizophrenia have been reported,including the possible mediating ***,mechanisms and hypotheses focus on central neurotransmitters,immunity,neuroinflammation,and epigenetics;however,the exact underlying mechanisms remain *** this article,we review the studies related to *** infection and schizophrenia,particularly the latest research *** on dopamine(DA)and other neurotransmitters,the blood-brain barrier,inflammatory factors,disease heterogeneity,and other confounders is also *** addition,we also summarized the results of some new epidemiological investigations.

关键词： Toxoplasma gondii Schizophrenia Neurotransmitters Neuroinflammation Immunity Epigenetics

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Can patients with mild non-neoplastic lesions diagnosed at baseline screening be safely exempt from surveillance: evidence from multicenter community-based cohorts

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Science China Life Sciences 2025年第1期 263-271页

作者： Siyi He Zhiyi Zhang Guohui Song Zhenhai Wang Chunyun Dai Shipeng Yan Kun Jiang Bingbing Song He Li Maomao Cao Dianqin Sun Fan Yang Xinxin Yan Shaoli Zhang Yi Teng Qianru Li Changfa Xia Wanqing Chen Office of Cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Department of Gastroenterology Gansu Wuwei Tumor Hospital Cixian Cancer Institute Linzhou Cancer Hospital Center for Disease Control and Prevention of Sheyang County Department of Cancer Prevention and Control Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University Luoshan Center for Disease Control and Prevention Office for Cancer Control and Research Affiliated Cancer Hospital of Harbin Medical University

Surveillance recommendations for gastric cancer（GC） in current guidelines focused on advanced precancerous lesions and were based on precise diagnosis of severity/extent of baseline lesions. We aimed to develop a less endoscopy-related equipment-dependent risk-stratification tool, and assessed whether mild-precursor-lesion patients can be safely exempt from surveillance. In the multicenter communitybased cohort, 75,051 participants receiving baseline endoscopy were enrolled during 2015–2017 and followed-up until 2021. Cumulative incidence rates（CIRs） of GC for precancerous-conditions were calculated by Kaplan-Meier method and compared by Log-rank tests. Mixedeffects Cox regression models were used to detect potential factors for progression towards GC. A risk score was calculated as counts of selected factors. An independent cohort, including 26,586 participants was used for external validation. During a median follow-up of 6.25 years, CIRs of GC were 0.302%, 0.436%, and 4.756% for normal group, non-neoplastic（atrophic gastritis/intestinal metaplasia） and neoplastic lesions（low-grade/high-grade dysplasia）, respectively(Ptrend<0.001). Four predictors, including male, ≥60 years, smoking, and limited vegetable consumption, were selected for risk-stratification. High-risk patients（≥3 risk factors） with non-neoplastic lesions showed higher GC risks（adjusted HR=7.73, 95%CI: 4.29–13.92）, and their four-year CIR reached the one-year CIR of neoplastic lesions. Further categorizing non-neoplastic lesions by histological grade, both patients with moderate-to-severe lesions（aHR=3.07, 95%CI: 1.67–5.64） and high-risk patients with mild lesions（aHR=7.29, 95%CI: 3.58–14.86） showed higher risks. Consistent trends were observed in validation cohort. High-risk mild-precursor-lesion patients should receive surveillance within 3–5 years after baseline screening. Our study provides evidence on supplementing current guideline recommendations.

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GLP-1 receptor agonists and myocardial metabolism in atrial fibrillation

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Journal of Pharmaceutical Analysis 2024年第5期14卷 653-665页

作者： Jiani Zhong Hang Chen Qiming Liu Shenghua Zhou Zhenguo Liu Yichao Xiao Department of Cardiovascular medicine Second Xiangya HospitalCentral South UniversityChangsha410011China xiangya school of medicine Central South UniversityChangsha410008China Center for Precision medicine and Division of Cardiovascular medicine Department of MedicineSchool of MedicineUniversity of MissouriColumbiaMO65211USA

Atrial fibrillation(AF)is the most common cardiac *** medical conditions,including hypertension,diabetes,obesity,sleep apnea,and heart failure(HF),increase the risk for *** have unique metabolic characteristics to maintain adenosine triphosphate *** changes occur in myocardial metabolism in ***-like peptide-1 receptor agonists(GLP-1RAs)have been used to control blood glucose fluctuations and weight in the treatment of type 2 diabetes mellitus(T2DM)and ***-1RAs have also been shown to reduce oxidative stress,inflammation,autonomic nervous system modulation,and mitochondrial *** article reviews the changes in metabolic characteristics in cardiomyocytes in *** the clinical trial outcomes are unsatisfactory,the findings demonstrate that GLP-1 RAs can improve myocardial metabolism in the presence of various risk factors,lowering the incidence of AF.

关键词： Atrial fibrillation Glucagon-like peptide-1 receptor agonists Metabolism

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