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Effect of DPC4 Gene on Invasion and Metastasis of Colorectal Carcinoma Cells

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Acta Biochimica et Biophysica Sinica 2006年第12期38卷 883-892页

作者： De-Sheng XIAO Ji-Fang WEN* Jing-He LI Kuan-Song WANG Zhong-Liang HU Jian-Hua ZHOU Zheng-Hao DENG Ying LIU Department of Pathology,xiangya school of medicine,Central South University,Changsha 410078,China Department of Pathology Xiangya School of Medicine Central South UniversityChangsha 410078 China

To investigate the effect of DPC4 gene on invasion and metastasis of colorectal carcinomacells,the expression of DPC4 was detected in sixty-three samples of colorectal tumors and seven cases ofcolorectal mucosa.The biological behavior of tumors expressing DPC4 was evaluated (including tumorstaging,differentiation degree and metastasis).pcDNA3.1-DPC4 plasmid was constructed and transferredinto HCT116 cells not expressing DPC4.The cell models (DPC4~+-HCT116) steadily expressing DPC4 wereobtained.Compared with HCT116 and pcDNA3.1-HCT116 cells,the doubling time of DPC4~+-HCT116 cellswas lengthened obviously (P<0.01),the apoptosis rate of DPC4~+-HCT 116 cells was significantly increased(P<0.01),the cloning efficiency,cell adherency,migration and invasion ability of DPC4~+-HCT116 cells weredropped obviously (P<0.01).The number of cancer nodules was decreased significantly in abdominal cavityand liver of the nude mice inoculated with DPC4~+-HCT116 cells.The activity of MMP-9 and MMP-2 wasdetected by gelatin zymography.In comparison with HCT116 and pcDNA3.1-HCT116 cells,the activity ofMMP-9 was decreased in DPC4~+-HCT116 cells.Therefore,the down-regulation of DPC4 expression may beassociated with the carcinogenesis of colorectal carcinoma.DPC4 may inhibit the proliferation of coloncancer cell by restraining growth and inducing apoptosis,and the invasion and metastasis of colorectalcarcinoma cells.MMP-9 may be one of the downstream target genes regulated by DPC4.

关键词： DPC4 colorectal carcinoma invasion metastasis MMP9

Glymphatic system:a gateway for neuroinflammation

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Neural Regeneration Research 2024年第12期19卷 2661-2672页

作者： Kailu Zou Qingwei Deng Hong Zhang Changsheng Huang Department of Anesthesiology Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina xiangya school of medicine Central South UniversityChangshaHunan ProvinceChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

The glymphatic system is a relatively recently identified fluid exchange and transpo rt system in the brain.Accumulating evidence indicates thatglymphatic function is impaired not only in central nervous system disorders but also in systemic diseases.Systemic diseases can trigger the inflammatory responses in the central nervous system,occasionally leading to sustained inflammation and functional disturbance of the central nervous system.This review summarizes the current knowledge on the association between glymphatic dysfunction and central nervous system inflammation.In addition,we discuss the hypothesis that disease conditions initially associated with peripheral inflammation ove rwhelm the performance of the glymphatic system,thereby triggering central nervous system dysfun ction,chronic neuroinflammation,and neurodegeneration.Future research investigating the role of the glymphatic system in neuroinflammation may offer innovative therapeutic approaches for central nervous system disorders.

关键词： aquaporin-4 central nervous system disease cerebrospinal fluid chronic neuroinflammation glymphatic dysfunction neurodegeneration peripheral nerve injury perivascular space systemic disease vicious cycle

Identification of Genes Related to Nasopharyngeal Carcinoma with the Help of Pathway-based Networks

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Acta Biochimica et Biophysica Sinica 2006年第12期38卷 900-910页

作者： Hui LI~1 Cai-Ping REN~1* Xiao-Jun TAN~2 Xu-Yu YANG~1 Hong-Bo ZHANG~1 Wen ZHOU~1 Kai-Tai YAO~11 Cancer Research Institute,xiangya school of medicine,Central South University,Changsha 410078,China 2 Reproductive and Stem Cell Engineering Institute,xiangya school of medicine,Central South University,Changsha 410078,China Cancer Research Institute Xiangya School of Medicine Central South UniversityChangsha 410078 China Reproductive and Stem Cell Engineering Institute Xiangya School of Medicine Central South UniversityChangsha 410078 China

cDNA microarray is a powerful tool to analyze simultaneously the expression levels of tens ofthousands of genes.Compared with normal nasopharynx （NP） tissues,2210 genes were highly differentiallyexpressed in nasopharyngeal carcinoma （NPC） tissues detected by cDNA microarray.Since signal pathwayis widely used to describe the complex relationship between genes,a pathway-based network was con-structed to visualize the connection between the genes obtained from microarray data in this report.Weanalyzed the targeted genes that may have more important influence on this gene network with statisticalmethods and found that some genes might have significant influence on this network,especially Ras-relatednuclear protein （RAN）,carboxyl ester lipase （CEL）,v-rel reticuloendotheliosis viral oncogene homolog A（RELA） genes.To verify the results from pathway-based selection,reverse transcription-polymerase chainreaction （RT-PCR） and real-time RT-PCR were performed to detect the expression levels of RAN,CEL andRELA genes and it was found that the RAN and CEL genes were significantly up-regulated in more than 80%of NPC tissues.To further elucidate the function of the RAN gene,RAN expression was specifically sup-pressed in a 5-8F NPC cell line by RNA interference （RNAi）.As expected,the depletion of RAN couldeffectively block the proliferation of tumor cells.Therefore,our study may open up a new way to analyze thevast microarray data.

关键词： nasopharyngeal carcinoma microarray real-time PCR RNA interference Ras-related nuclear protein (RAN)

Genetic and Epigenetic Alterations of DLC-1,a Candidate Tumor Suppressor Gene,in Nasopharyngeal Carcinoma

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Acta Biochimica et Biophysica Sinica 2006年第5期38卷 349-355页

作者： Dan PENG Cai-Ping REN Hong-Mei YI Liang ZHOU Xu-Yu YANG Hui LI Kai-Tai YAO Cancer Research Institute,xiangya school of medicine,Central South University,Changsha 410078,China Cancer Research Institute Xiangya School of Medicine Central South UniversityChangsha 410078 China

The DLC-1 gene,located at the human chromosome region 8p22,behaves like a tumorsuppressor gene and is frequently deleted in diverse tumors.The deletion of 8p22 is not an uncommon eventin nasopharyngeal carcinoma(NPC),therefore we explored the expression levels of the DLC-1 gene in NPCsand NPC cell lines by reverse transcription-polymerase chain reaction.The results showed the mRNA levelof DLC-1 was downregulated.To identify the mechanism of DLC-1 downregulation in NPC,we investigatedthe methylation status of the DLC-1 gene using methylation-specific PCR,and found that 79%(31 of 39)ofthe NPC tissues and two DLC-1 nonexpressing NPC cell lines,6-10B and 5-8F,were methylated in theDLC-1 CpG island.Microsatellite PCR was also carried out,and loss of heterozygosity was found at fourmicrosatellite sites(D8S552,D8S 1754,D8S 1790 and D8S549)covering the whole DLC-1 gene with ratiosof 33%(4 of 12 informative cases),18%(2 of 11),5%(1 of 18),and 25%(3 of 12),respectively.Takentogether,our results suggest that DLC-1 might be an NPC-related tumor suppressor gene affected by aberrantpromoter methylation and gene deletion.

关键词： DLC-I nasopharyngeal carcinoma hypermethylation loss of heterozygosity

Vaccination against Schistosoma japonicum Infection by DNA Vaccine Encoding Sj22.7 Antigen

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Acta Biochimica et Biophysica Sinica 2007年第1期39卷 27-36页

作者： Gan DAI Shiping WANG Junlong YU Shaorui XU Xianchu PENG Zhuo HE Xueqin LIU Songhua ZHOU and Fen LIU Institute of Schistosomiasis Research.xiangya school of medicine,Central South University,Changsha 410078 China Institute of Schistosomiasis Research Xiangya School of Medicine Central South UniversityChangsha 410078 China

To observe the in vitro expression of DNA vaccine pcDNA3-Sj22.7 and its immunologicaleffect in mice,the recombinant plasmid pcDNA3-Sj22.7 was used to transfect HeLa cells with liposome-mediated method and the expression of Sj22.7 mRNA and protein was examined using reversetranscription-polymerase chain reaction, sodium dodecylsulfate-polyacrylamide gel electrophoresis andWestern blot.Then,the ability of pcDNA3-Sj22.7 to protect against Schistosoma japonicum challengeinfections was analyzed according to worm reduction rate and egg reduction rate after vaccination of mice.The serum levels of specific IgG antibody and T lymphocyte proliferation response were also determined.After the challenge infection,Sj22.7-driven interferon (IFN)-γand interleukin (IL)-4 was also quantified.Results showed that pcDNA3-Sj22.7 could express Sj22.7 mRNA and protein in vitro.Immunizationresulted in a worm reduction rate of 29.70%,egg reduction rate of 47.25% (liver) and 51.73% (intestine),and egg reduction rate of 25.90% (eggs per female),suggesting induction of significant anti-fecundityin the pcDNA3-Sj22.7 group. Enzyme-linked immunosorbent assay and Western blot analysis indicatedthat immunized mice generated specific IgG against Sj22.7.T lymphocytes from mice immunized withpcDNA3-Sj22.7 showed a significant proliferation response to rSj22.7.The culture of spleen cells showedthat secretion of IFN-γ increased but IL-4 decreased. The results indicate that DNA vaccination bypcDNA3-Sj22.7 is sufficient to elicit significant levels of protective immunity against S.japonicum infection.The DNA vaccine could induce significant cellular and humoral immune response,and display predominantT helper cell type 1 type immune responses,which contribute to the protective immunity against challengeinfection in mice.

关键词： response Schistosoma japonicum DNA vaccine Sj22.7 gene expression immune protection immune

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

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

关键词： Toxoplasma gondii Schizophrenia Neurotransmitters Neuroinflammation Immunity Epigenetics

Klebsiella pneumoniae infections after liver transplantation:Drug resistance and distribution of pathogens,risk factors,and influence on outcomes

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World Journal of Hepatology 2024年第4期16卷 612-624页

作者： Long Guo Peng Peng Wei-Ting Peng Jie Zhao Qi-Quan Wan Department of Respiratory and Critical Care medicine The Third Xiangya Hospital of Central South UniversityChangsha 410013Hunan ProvinceChina Clinical Laboratory medicine Center Zhuzhou Hospital Affiliated to Xiangya School of MedicineCentral South UniversityZhuzhou 421007Hunan ProvinceChina The Second Affiliated Hospital Class Xiangya School of MedicineCentral South UniversityChangsha 410013Hunan ProvinceChina Department of Liver Surgery Renji HospitalShanghai Jiaotong University School of MedicineShanghai 200127China Department of Transplant Surgery The Third Xiangya Hospital of Central South UniversityChangsha 410013Hunan ProvinceChina Engineering and Technology Research Center for Transplantation medicine of National Health Commission The Third Xiangya Hospital of Central South UniversityChangsha 410013Hunan ProvinceChina

BACKGROUND Liver transplantation(LT)is the only curative treatment for end-stage liver disease.However,LT recipients are susceptible to infection,which is the leading cause of early mortality after LT.Klebsiella pneumoniae infections(KPIs)in the bloodstream are common in LT recipients.We hypothesized that KPIs and carbapenemresistant Klebsiella pneumoniae(CRKP)infections may affect the outcomes of LT recipients.AIM To assess KPI incidence,timing,distribution,drug resistance,and risk factors following LT and its association with outcomes.METHODS This retrospective study included 406 patients undergoing LT at The Third xiangya Hospital of Central South University,a tertiary hospital,from January 2015 to January 2023.We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis.RESULTS KPI incidence was 7.9%(n=32),with lung/thoracic cavity the most frequent site of infection;the median time from LT to KPI onset was 7.5 d.Of 44 Klebsiella pneumoniae isolates,43(97.7%)and 34(77.3%)were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline,respectively;>70%were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin.Female sex[odds ratio(OR)=2.827,95%confidence interval(CI):1.256-6.364;P=0.012],pre-LT diabetes(OR=2.794,95%CI:1.070-7.294;P=0.036),day 1 post-LT alanine aminotransferase(ALT)levels≥1500 U/L(OR=3.645,95%CI:1.671-7.950;P=0.001),and post-LT urethral catheter duration over 4 d(OR=2.266,95%CI:1.016-5.054;P=0.046)were risk factors for KPI.CRKP infections,but not KPIs,were risk factors for 6-month all-cause mortality post-LT.CONCLUSION KPIs occur frequently and rapidly after LT.Risk factors include female sex,pre-LT diabetes,increased post-LT ALT levels,and urethral catheter duration.CRKP infections,and not KPIs,affect mortality.

关键词： Liver transplantation Klebsiella pneumoniae infections Carbapenem-resistant Klebsiella pneumoniae Risk factors Outcomes

Role of adhesion molecules in cancer and targeted therapy

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Science China(Life Sciences) 2024年第5期67卷 940-957页

作者： Chunmei Fan Fang Xiong Shanshan Zhang Zhaojian Gong Qianjin Liao Guiyuan Li Can Guo Wei Xiong He Huang Zhaoyang Zeng NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410000China Department of Histology and Embryology Xiangya School of MedicineCentral South UniversityChangsha410013China Department of Stomatology Xiangya HospitalCentral South UniversityChangsha 410078China Department of Oral and Maxillofacial Surgery The Second Xiangya HospitalCentral South UniversityChangsha 410011China Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education Cancer Research InstituteCentral South UniversityChangsha 410078China

Adhesion molecules mediate cell-to-cell and cell-to-extracellular matrix interactions and transmit mechanical and chemical signals among them.Various mechanisms deregulate adhesion molecules in cancer,enabling tumor cells to proliferate without restraint,invade through tissue boundaries,escape from immune surveillance,and survive in the tumor microenvironment.Recent studies have revealed that adhesion molecules also drive angiogenesis,reshape metabolism,and are involved in stem cell self-renewal.In this review,we summarize the functions and mechanisms of adhesion molecules in cancer and the tumor microenvironment,as well as the therapeutic strategies targeting adhesion molecules.These studies have implications for furthering our understanding of adhesion molecules in cancer and providing a paradigm for exploring novel therapeutic approaches.

关键词： adhesion molecules tumor microenvironment invasion and metastasis reshaping metabolism angiogenesis immune evasion tumor stemness therapeutic strategy