1.Improved immune response and anti-tumor effect of WT1 peptide emulsion adjuvant vaccine for acute myeloid leukemia
Yan YE ; Zelong ZHANG ; Baohang ZHU ; Shulin LIU ; Zhen SONG ; Qingpeng YUAN ; Yun YANG ; Haibo LI ; Quanmin ZOU ; Hao ZENG ; Hongwu SUN
Journal of Army Medical University 2024;46(9):1024-1033
Objective To evaluate the stability,safety and immune enhancement and anti-tumor effects of Wilms'tumor gene 1(WT1)peptide combined with AddaVaxTM emulsion vaccine for acute myeloid leukemia.Methods The stability of WT1 peptide in the adjuvant vaccine was evaluated using MALDI-TOF-MS time-of-flight mass spectrometry.Female C57BL/6 mice were randomly divided into PBS group,WT1 peptide group,and WT1 peptide+AddaVaxTMemulsion adjuvant vaccine group.The immunization was performed at a dose of 50 μg/mouse for antigen and 50 μg/mouse for adjuvant,with intramuscular injection on days 0,14,and 28.HE staining was used to assess the toxicity of intramuscular vaccination on mouse organ tissues.Cytokine levels were detected by ELISA,and the number of IFN-γ-secreting splenocytes was measured by ELISpot.Flow cytometry was employed to detect the maturation of bone marrow-derived dendritic cells(BMDCs)promoted by the vaccine in vitro and the promotion for lymphocyte activation,and H-2Db WT1 tetramer was utilized to detect the proportion of specific CD8+T cells.After establishing a mouse leukemia tumor model using the C1498-mWT1 stable cell line,the anti-tumor effects of the vaccine for prevention and treatment were evaluated.Results The WT1 peptide stably existed in the vaccine without causing significant organ tissue changes in mice after intramuscular injection.Compared to the mice immunized with WT1 aqueous solution,the mice after intramuscular injection of the WT1 peptide emulsion adjuvant vaccine showed stronger immune responses of Th1 cells,including IFN-γ and TNF-α,as well as Th17 cells of IL-17A(P<0.05),and the mice had not only promoted number of IFN-γ secreting splenocytes(P<0.01)but also enhanced maturation of BMDCs,as indicated by an increase in the proportions of CD40+/CD11c+and CD86+CD80+/CD11c+ cells(P<0.05).Additionally,there were increases in both the proportion of CD4+/CD3+T and CD69+/CD8+T cells(P<0.05)and the proportion of specific CD8+T cells(P<0.05).In the anti-tumor effect study using the C1498-mWT1 mouse model,the median survival time of the WT1+AddaVaxTM group was extended by 6 d compared to the WT1 aqueous solution group.At day 50,the survival rate of mice in the WT1+AddaVaxTM group was still 28.5%,while all mice in the other groups had died(P<0.05).Conclusion The vaccine with the WT1 peptide and AddaVaxTM emulsion adjuvant exhibits good immunological and anti-tumor effects.
2.Anti-bacterial effect and its mechanism of lavender essential oil against multi-drug resistant Acinetobacter baumannii
Man ZHAO ; Zijing WU ; Cun SUN ; Yan YE ; Ting CHEN ; Shulin LIU ; Baohang ZHU ; Anni ZHAO ; Zhen SONG ; Yun YANG ; Hongwu SUN ; Hao ZENG
Journal of Army Medical University 2024;46(18):2046-2056
Objective To investigate the antibacterial effect and its preliminary mechanism of lavender essential oil on multi-drug resistant Acinetobacter baumannii.Methods Micro-dilution method was used to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)of lavender essential oil against multi-drug resistant Acinetobacter baumannii,and bactericidal kinetic study was employed to determine the onset and maintenance time of lavender essential oil.Meanwhile,the promoting and therapeutic effects of lavender essential oil on wound healing were observed in a mouse model of infection.Subsequently,crystal violet staining was used to determine the inhibition and clearance of multi-drug resistant Acinetobacter baumannii biofilm by lavender essential oil,and laser confocal microscopy was utilized to observe the survival of bacteria in biofilms.NanoDrop instrument was utilized to quantify the leakage of bacterial DNA nucleic acid and protein after intervention with 3 and 6 mg/mL lavender essential oil,and the leakage of bacterial potassium ion was measured by potassium ion test kit.Proteomics technology combined with bio-informatics were applied to explore the action mechanism of lavender essential oil against multi-drug resistant Acinetobacter baumannii.Results The MIC and MBC of lavender essential oil were both 6 mg/mL,which could kill almost all multi-drug resistant Acinetobacter baumannii at the time point of 120 min,and showed an obvious dose-and time-dependent manner.The overall animal model evaluation showed that both 3 and 6 mg/mL lavender essential oil could promote wound healing,and the curative effect was obvious.Further studies confirmed that 3 mg/mL lavender essential oil had a certain biofilm inhibitory effect on multi-drug resistant Acinetobacter baumannii,and 6 mg/mL also had a certain biofilm clearance effect under the same conditions.Meanwhile,when incubated at 37℃ for 1 h,the dose of 3 mg/mL could increase the leakage of DNA nucleic acid and protein,and significantly promote the efflux of potassium ions.Proteomic analysis suggested that the antibacterial effect of lavender essential oil may be related to affecting the oxidorereductase activity and cell metabolic process of multi-drug resistant Acinetobacter baumannii,and interfering with the biosynthesis of cell wall/membrane/envelope and other structures.Conclusion Lavender essential oil at 3 mg/mL can play an antibacterial effect against multi-drug resistant Acinetobacter baumannii,and its mechanism may be related to the destruction of bacterial biofilm and interference with bacterial metabolism.
3.Clinic information,pathological,and imaging characteristics in 2 058 surgical patients with lung cancer from a single center
Bingqing LONG ; Zeng XIONG ; Shulin LIU ; Yuanda CHENG ; Min LI ; Weihua LIAO
Journal of Central South University(Medical Sciences) 2024;49(2):247-255
Objective:Lung cancer is characterized by its high incidence and case fatality rate.Factors related to population composition and cancer prevention programme policy have an effect on the incidence and diagnosis of lung cancer.This study aims to provide scientific support for early diagnosis and treatment of lung cancer by investigating the clinic information,pathological,and imaging characteristics of surgical patients with lung cancer. Methods:The data of 2 058 patients,who underwent surgery for lung cancer in the Department of Thoracic Surgery of Xiangya Hospital of Central South University from 2016 to 2019,were retrospectively collected to analyze changes in clinic information,pathological,and imaging characteristics. Results:From 2016 to 2019,the number of patients per year was 280,376,524,and 878,respectively.Adenocarcinoma(68.1%)was the most common pathological type of surgical patients with lung cancer.From 2016 to 2019,the proportion of adenocarcinoma was increased from 55.5%to 74.1%.The proportion lung cancer patients in stage IA was increased from 38.9%to 62.3%,and the proportion of patients who underwent sublobar resection was increased from 1.8%to 8.6%.The proportion of lymph node sampling was increased in 2019.Compared with the rate in 2016,the detection rate of nodules with diameter≤1 cm detected by CT before surgery in 2019 was significantly improved(2.0%vs 18.2%),and the detection rate of nodules with diameter>3 cm was decreased(34.7%vs 18.3%).From 2016 to 2019,the proportion of lesions with pure ground-glass density and partial solid density detected by CT was increased from 2.0%and 16.6%to 20.0%and 37.3%,respectively.The proportion of solid density was decreased from 81.4%to 42.7%. Conclusion:The number of lung cancer surgery patients is rapidly increasing year by year,the proportion of CT-detected purely ground-glass density and partially solid density lesions are increasing,the proportion of patients with adenocarcinoma is rising,the proportion of early-stage lung cancer is increasing,smaller lung cancers are detected in earlier clinical stage leading to a more minimally invasive approach to the surgical methods.
4.Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases
Jiuping ZENG ; Mingxing LI ; Qianyun ZHAO ; Meijuan CHEN ; Long ZHAO ; Shulin WEI ; Huan YANG ; Yueshui ZHAO ; Anqi WANG ; Jing SHEN ; Fukuan DU ; Yu CHEN ; Shuai DENG ; Fang WANG ; Zhuo ZHANG ; Zhi LI ; Tiangang WANG ; Shengpeng WANG ; Zhangang XIAO ; Xu WU
Journal of Pharmaceutical Analysis 2023;13(6):545-562
As a ligand-dependent transcription factor,retinoid-associated orphan receptor γt(RORyt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the pro-gression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORyt to decrease Th17 cell development and IL-17 production.Several RORyt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORyt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORyt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORyt inhibitors were summarized,with an emphasis on their optimization from lead compounds,ef-ficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.
5.Role of active screening in the diagnosis and treatment of early lung cancer and suggestions for health management
Zeng XIONG ; Bingqing LONG ; Shaohui LIU ; Shulin LIU ; Yuanda CHENG ; Bihan OUYANG ; Baoxiang WANG ; Xuewei ZHANG ; Weihua LIAO
Chinese Journal of Health Management 2023;17(3):188-193
Objective:To explore the role of active screening in the diagnosis and treatment of early lung cancer, and give health management recommendations.Methods:A retrospective study was conducted to collect lung cancer patients who had complete population sociology, clinical information, pathology and imaging characteristics in the Thoracic Surgery in Xiangya Hospital of Central South University from 2016 to 2019. According to different diagnostic modes, they were divided into an active screening group (1082 cases) and a passive case finding group (974 cases), to analyze their differences in demographic sociological, clinical information, pathology and imaging characteristics, and to discuss the key points of population management in the active screening group.Results:From 2016 to 2019, the proportion of lung cancer patients in the active screening group increased from 36.1% to 54.2%, and the proportion of patients found to have lung cancer by CT examination in the active screening group increased from 82.2% to 96.8%. Compared with the passive case finding group, the active screening group had a higher proportion of women, non-smokers, patients with precursor glandular lesions and adenocarcinoma, patients in stage 0 and stage I, patients with lesion diameter (d)≤1 cm and 1
6.Chinese herbal medicines for treating ulcerative colitis via regulating gut microbiota-intestinal immunity axis.
Yifei YANG ; Yi WANG ; Long ZHAO ; Fang WANG ; Mingxing LI ; Qin WANG ; Haoming LUO ; Qianyun ZHAO ; Jiuping ZENG ; Yueshui ZHAO ; Fukuan DU ; Yu CHEN ; Jing SHEN ; Shulin WEI ; Zhangang XIAO ; Xu WU
Chinese Herbal Medicines 2023;15(2):181-200
Ulcerative colitis (UC) is one of types of inflammatory bowel disease with high recurrence. Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a series of inflammatory responses in the UC. Modulating the gut microbiota-intestinal immunity loop has been suggested as one of key strategies for relieving UC. Many Chinese herbal medicines including some of single herb, herbal formulas and the derived constituents have been reported with protective effect against UC through modulating gut microbiome and intestinal immunity. Some clinical trials have shown promising results. This review thus focused on the current knowledge on using Chinese herbal medicines for treating UC from the mechanism aspects of regulating intestinal homeostasis involving microbiota and gut immunity. The existing clinical trials are also summarized.
7.The value of clinical application of 3 indexes in coronary heart disease
Chun XIA ; Xianyun CHEN ; Shulin ZENG
International Journal of Laboratory Medicine 2017;38(2):219-220,223
Objective To observe the level of homocysteine(Hcy),high sensitive C-reactive protein(hs-CRP)and D-Dimer(D-D) in peripheral blood of patients with coronary heart disease,and to explore their values in clinical diagnosis of the coronary heart dis-ease(CHD).Methods Total of 95 patients with coronary heart disease were selected including 27 patients with AMI,42 patients with UAP and 26 patients with SAP.50 health examination volunteers were served as contro1.The levels of Hcy,hs-CRP and D-D were measured.Results The levels of Hcy in AMI group,UAP group and SAP group were significantly higher than those in con-trol group(P <0.05).The levels of hs-CRP and D-D in AMI group and UAP group were significant higher than control group and SAP group(P <0.05).The level of hs-CRP in SAP group was much higher than the control group(P <0.05),whereas the level of D-D in SAP group was not significantly different from control group(P <0.05).Conclusion The changes of serum levels of Hcy, hs-CRP and D-D are related with the occurrence and development of CHD.The joint detection of Hcy,hs-CRP and D-D can better reflect the severe degree of CHD,and could be helpful for early diagnosis,therapy and prognosis of CHD.
8.Overexpression of Chk1/2 gene affects G2/M arrest in MGC803 cells induced by diallyl disulfide
Hong XIA ; Shulin XIANG ; Ying ZENG ; Lifeng LU ; Fang LIU ; Hui LING ; Bo SU ; Qi SU
Chinese Pharmacological Bulletin 2016;(2):199-203,204
Aim To investigate the effects of diallyl di-sulfide( DADS) on G2/M arrest in Chk1/MGC803 and Chk2/MGC803 cells so as to establish stable human gastric cancer MGC803 cells with overexpression of Chk1/2 gene. Methods The colony formation, flow cytometry, RT-PCR and Western blot were used to de-tect the proliferation, cell cycle, and expression of Chk1/2 mRNA and protein, p-Chk1/2, CDC25C and cyclinB1, respectively. Results The colony formation showed that the colony forming efficiency in Chk1/MGC803 and Chk2/MGC803 cells treated by 30 mg· L-1 DADS was lower than in control group and vector group ( P <0. 05 ) . Flow cytometry demonstrated that 41. 3%, 57. 4%, 68. 9% and 42. 9% of G2/M cells in Chk1/MGC803 were increased than in MGC803 and Chk2/MGC803 , respectively after treated by DADS in 12,24, 36 and 48 h(P <0. 05). At the same time, RT-PCR disclosed that expression of Chk1 and Chk2 mRNA had no marked change. Western blot showed that total proteins of Chk1 and Chk2 and p-Chk2 had invisible change, but expression of p-Chk1 was up-reg-ulated, and CDC25C and cyclinB1 were down-regula-ted time-dependently in Chk1/MGC803 cells ( P <0. 05 ) . Conclusion DADS arrests MGC803 cells at G2/M by increasing p-Chk1 expression to cause down-regulation of CDC25C and cyclinB1 simultaneously.
9.The roles of different signaling pathways and their related genes in the occurrence and development of colorectal cancer
Yao LI ; Qingxuan ZENG ; Yu QIAN ; Feifeng LI ; Shulin LIU
Cancer Research and Clinic 2015;(9):635-640
Colorectal cancer is a kind of malignancies with high incidence in the worldwide, that is seriously harmed human health. So far the pathogenesis of the disease is not fully understood, this causing many difficulties to the diagnosis and treatment of the disease, and resulting in the cure rates of disease is not ideal. With the development of molecular genetics and molecular biology, many oncogenes and tumor suppressor genes have been found to be associated with the disease, and this made it is possible to reveal the pathogenesis of colorectal cancer at the molecular level. However, it is a complex and multi-step process from normal colorectal epithelial cells transformed to colorectal cancer cells, and it is the results of polygenic and multifactorial interactions. Now it is thought that the Wnt, TGF-beta, PI3K/Akt, MAPK and p53 signaling pathways are closely associated with pathogenesis of colorectal cancer. Based on the five kinds of signaling pathways as the main line, this article reviewed the roles of different signaling pathways and their related genes in the pathogenesis of colorectal cancer.
10.Effect of killer cell immunoglobulin-like receptor gene in immune killing of hepatoma cells
Mian HE ; Xiaohui QIU ; Wenfeng ZHANG ; Han SHEN ; Hui WANG ; Huaben BO ; Shulin HUANG ; Xiancheng ZENG ; Hongwei SHAO
Chinese Journal of Hepatic Surgery(Electronic Edition) 2015;(5):318-322
ObjectiveTo investigate the effect of killer cell immunoglobulin-like receptor (KIR) gene in immune killing of hepatoma cells.MethodsPeripheral blood mononuclear cell (PBMC) and hepatoma cells were co-cultured with different effector-target ratios. The expression of KIR gene family in PBMC, the content to interferon-γ (IFN-γ), the morphological change of hepatoma cell and the cytotoxicity to hepatoma cell by PBMC were observed after the co-incubation with different effector-target ratios. The comparison on cytotoxicity rates was conducted using one-way analysis of variance and LSD-t test.ResultsThe expression of activating KIR gene increased after 12 h of co-culture, but decreased after 24 h of co-culture. The expression of inhibitory KIR gene decreased after 12 h of co-culture. DAP12 maintained high expression all the time. The content of IFN-γ in PBMC decreased with the increase of effector-target ratio and reached the peak at 12 h of co-culture. Hepatoma cells co-cultured with different effector-target ratios were observed with increased chromatin condensation, rising proportion of cells with hemispherical or half moon shape and marginalized nucleus, and stagnant of active cell division. The cytotoxicity rate of effector-target ratio 1∶1, 10∶1 and 50∶1 was (8±3) %, (14±4) % and (32±6) %, respectively, with 50∶1 group significantly higher than 11∶1 and 10∶1 group (LSD-t=5.97, 4.61;P<0.05).ConclusionThe activating KIR gene plays an important role in immune killing of hepatoma cells.

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