1.SUICIDAL INTOXICATION WITH SEDATIVE SOPORIFIC DRUGS—AN ANALYSIS OF 6 CASES
Meiyu SHEN ; Ziqin ZHAO ; Xianglin KONG ; Qiying ZHANG ;
Chinese Journal of Forensic Medicine 1987;0(03):-
Six cases of suicidal sedative-soporific drug poisoning is reported.The main clinical features were coma,respiratory depression,hypotension,disappearance of reflexes and peripherel circulatory failure.Thepathological fingdings were as follows:pulmonary congestion and edema;fatty degeneration of the liver;degeneration of the epithalial cells of the proximal convoluted tubules and cerebral edema.The severityof the pathological changes depend upon the duration between the drug administration and the time of deathThe longer the course,the more prominent the changes.The fatality rate related with the dose of drugadministration,the underlying deseases and the complications.
2.Development and validation of an in vitro model of mycobacterial granuloma
Weiwei TIAN ; Xiaodong ZHANG ; Qiuling WANG ; Meiyu TANG ; Jianping SHEN ; Hongsheng WANG ; Qianqiu WANG
Chinese Journal of Dermatology 2014;47(3):186-191
Objective To establish an in vitro model of mycobacterial granuloma.Methods Mononuclear cells were isolated from peripheral blood of healthy human subjects,and stimulated to differentiate into macrophages,which were then classified into four groups to be cocultured with Mycobacterium marinum,Mycobacterium tuberculosis,Bacillus Calmette-Guérin,and Mycobacterium leprae,respectively,for five days followed by incubation with peripheral blood mononuclear cells (PBMCs) from the corresponding donors to establish an in vitro model of mycobacterial granuloma.The macrophages cocultured with PBMCs or mycobacteria alone served as the control.Microscopy was performed to dynamically visualize the formation of granuloma in vitro,flow cytometry to detect the expressions of cell surface antigens at different stages,real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA) to determine the mRNA expressions of important cytokines and their protein levels in the supernatant of macrophages,respectively.Results After 7-9 days of coculture with mycobacteria and PBMCs,the macrophages aggregated to form granuloma-like clumps,and some cells fused to form multinuclear giant cells,along with the expressions of some surface antigens such as CD14,CD68 and CD86 on these macrophages.The mRNA expressions of some important cytokines,including tumor necrosis factor-a,interferon-γ interleukin (IL)-1 β and IL-10,were detectable in the macrophages cocultured with mycobacteria and PBMCs,and the secretion of these cytokines was confirmed by ELISA in the supernatant of these cells.Conclusions An in vitro model of mycobacterial granuloma is basically established,which may facilitate the investigation into the formation of granuloma caused by and immune response to mycobacterial infection.
3.Correlation analysis of infrared radiant intensity between hyperplastic breast tissue and tongue surface in patients with hyperplasia of mammary glands
Zhifeng ZHANG ; Ziyan WANG ; Jian YING ; Jiatuo XU ; Xueyong SHEN ; Changle ZHOU ; Huayuan YANG ; Meiyu SHI ; Yun WU ; Zhujuan YAN
Journal of Integrative Medicine 2007;5(6):625-9
OBJECTIVE: To establish a supplementary diagnostic indicator (infrared radiant intensity) in tongue diagnosis of traditional Chinese medicine (TCM) in patients with hyperplasia of mammary glands through correlation analysis of infrared radiant intensity between hyperplastic breast tissue and tongue surface. METHODS: Infrared radiant intensity of the hyperplastic breast tissue and different points on tongue surface in 20 cases of hyperplasia of mammary glands with liver-energy stagnation and phlegm retention syndrome and 16 cases of hyperplasia of mammary glands with irregular thoroughfare and conception vessels syndrome were measured with external infrared spectrometer PHE-201 made by Shanghai Institute of Technical Physics. Correlation of infrared radiant intensity between the hyperplastic breast tissue and the different points on tongue surface was assessed by using bivariate correlation analysis. RESULTS: The results showed that the numbers of positive correlated wave bands of infrared radiant intensity between the hyperplastic breast tissue and different detected points on tongue surface in the patients with liver-energy stagnation and phlegm retention syndrome and irregular thoroughfare and conception vessels syndrome were 127 (83.55%) and 71 (46.71%), respectively. Infrared radiant intensity between the hyperplastic breast tissue and the tongue surface had a positive correlation. CONCLUSION: Infrared radiant intensity can be used as one of supplementary diagnostic indicators in TCM tongue diagnosis of hyperplasia of mammary glands.
4.Progress in mechanism of tumor-derived exosomes on myeloid-derived suppressor cells
Mengyu ZHANG ; Jie SHEN ; Meiyu PENG
Chinese Journal of Microbiology and Immunology 2022;42(11):912-916
Myeloid-derived suppressor cells (MDSCs) play an important immunosuppressive role in the tumor microenvironment. Tumor cells can regulate the immunosuppressive function of MDSCs in the tumor microenvironment through exosomes, thereby affecting the development of tumors. Tumor-derived exosomes (TEXs) promote the development of MDSCs and improve their immunosuppressive function in the tumor microenvironment mainly by participating in the processes such as intercellular information exchange and information transmission. Moreover, the miRNAs in TEXs will also be transferred to recipient cells to inhibit the immunosuppressive function of MDSCs by inducing the negative regulation of target genes. This review summarized the progress in the mechanism of TEXs on MDSCs.
5.Predictive value of in vitro methyl thiazolyl tetrazolium assay chemosensitivity test of cytotoxic drug activity in breast cancer
Meiyu XU ; Ye SHEN ; Yeping JIANG ; Yuanzhou SHAN ; Tao WU
Clinical Medicine of China 2019;35(1):5-10
Objective To investigate the value of methyl thiazolyl tetrazolium assay ( MTT) in predicting drug sensitivity of breast cancer cells in vitro. Methods From January 2010 to July 2016,one hundred and ninety-two patients with breast cancer who underwent modified radical mastectomy or breast conserving surgery (no preoperative radiotherapy or chemotherapy) in the Shanghai Fengxian District Central Hospital were selected. MTT method was used to determine the inhibitory level and sensitivity of 12 drugs and 3 chemotherapy regimens to primary cultured cancer cells of 192 patients with breast cancer. Results (1) The sensitivity of breast cancer cells to 12 drugs were in sequence from high to low as follows: Paclitaxel (PTX)> Epirubicin ( EPI )> Cisplatin ( DDP )> 5-Fluorouracil ( 5-FU )> Mitoxantrone ( MIT )>Vincristine ( VCR )> Pirarubicin ( THP )> Isosophosphamide ( IFO )> Carboplatin ( CBP )>Cyclophosphamide ( CTX)> Methotrexate ( MTX)> Changchun Rui bin ( NVB) . The sensitivity of chemotherapy regimens in the three groups from high to low was docetaxel/doxorubicin/cyclophosphamide (TAC )>cyclophosphamide/epirubicin/fluorouracil ( CEF )>cyclophosphamide/methotrexate/fluorouracil (CMF). The sensitivity rates of PTX,EPI and DDP were 54%(104/192),42%(81/192) and 37%(71/192) respectively. (2) The average inhibitory rates of DDP,CBP and MIT in stage III breast cancer was higher than those in stage I and II breast cancer,and the differences were statistically significant ( F=11. 14,4. 303,3. 182,P<0. 05). (3) HR-breast cancer is more sensitive than HR+breast cancer,PTX, EPI,THP,MIT in HER-2(+) breast cancer is more sensitive than in HER-2(-) breast cancer. Conclusion As a widely used drug sensitivity test method, MTT assay has a certain reference value for screening sensitive drugs and selecting clinical chemotherapy regimens in neoadjuvant chemotherapy of breast cancer. PTX,EPI and DDP are more sensitive to other breast cancer cells than other drugs. Chemotherapy based on in vitro susceptibility results improves the efficiency of chemotherapy and decreases the proportion of changes in chemotherapy schemes due to inefficiency.
6.Design and practice of phenobarbital comprehensive experiment
Meiyu LIN ; Yue GAO ; Xiaoyan WANG ; Songzhang SHEN ; Tingfang WANG ; Juan SU
Chinese Journal of Medical Education Research 2018;17(2):180-183
A set of comprehensive chemical experiments was designed for the second-year undergraduate majoring in pharmacy which contained synthesis,refinement,structural identification and appraisal analysis and assaying in phenobarbital.The purpose of the experiment was to improve the comprehensive strength,the ability of investigation and operation.The paper mainly discusses the design and application of the comprehensive experiment in the phenobarbital for pharmacy and Chinese medicine majors from the following aspects including design idea,teaching plan,effectiveness and popularization.
7.Catalpol Inhibits Tregs-to-Th17 Cell Transdifferentiation by Up-Regulating Let-7g-5p to Reduce STAT3 Protein Levels
Yuxi DI ; Mingfei ZHANG ; Yichang CHEN ; Ruonan SUN ; Meiyu SHEN ; Fengxiang TIAN ; Pei YANG ; Feiya QIAN ; Lingling ZHOU
Yonsei Medical Journal 2022;63(1):56-65
Purpose:
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease, and Th17 cells are key factors in the pathogenesis of human inflammatory conditions, such as RA. Catalpol (CAT), a component in Rehmanniae Radix (RR), has been found to regulate human immunity. However, the effects of CAT on Th17 cell differentiation and improvement of RA are not clear.
Materials and Methods:
Collagen-induced arthritis (CIA) mice were constructed to detect the effects of CAT on arthritis and Th17 cells. The effect of CAT on Th17 differentiation was evaluated with let-7g-5p transfection experiments. Flow cytometry was used to detect the proportion of Th17 cells after CAT treatment. Levels of interleukin-17 and RORγt were assessed by qRT-PCR and enzyme-linked immunosorbent assay. The expression of signal transducer and activator of transcription 3 (STAT3) was determined by qRT-PCR and Western blot.
Results:
We found that the proportion of Th17 cells was negatively associated with let-7g-5p expression in CIA mice. In in vitro experiments, CAT suppressed traditional differentiation of Th17 cells. Simultaneously, CAT significantly decreased Tregs-to-Th17 cells transdifferentiation. Our results demonstrated that CAT inhibited Tregs-to-Th17 cells transdifferentiation by up-regulating let-7g-5p and that the suppressive effect of CAT on traditional differentiation of Th17 cells is not related with let-7-5p.
Conclusion
Our data indicate that CAT may be a potential modulator of Tregs-to-Th17 cells transdifferentiation by up-regulating let-7g-5p to reduce the expression of STAT3. These results provide new directions for research into RA treatment.
8.Chromopeptide A, a highly cytotoxic depsipeptide from the marine sediment-derived bacterium Chromobacterium sp. HS-13-94.
Zhenfang ZHOU ; Xin WANG ; Hui ZHANG ; Jingya SUN ; Linghui ZHENG ; Hongchun LIU ; Jidong WANG ; Aijun SHEN ; Meiyu GENG ; Yuewei GUO
Acta Pharmaceutica Sinica B 2015;5(1):62-66
A bicyclic depsipeptide, chromopeptide A (1), was isolated from a deep-sea-derived bacterium Chromobacterium sp. HS-13-94. Its structure was determined by extensive spectroscopic analysis and by comparison with a related known compound. The absolute configuration of chromopeptide A was established by X-ray diffraction analysis employing graphite monochromated Mo K α radiation (λ=0.71073 Å) with small Flack parameter 0.03. Chromopeptide A suppressed the proliferation of HL-60, K-562, and Ramos cells with average IC50 values of 7.7, 7.0, and 16.5 nmol/L, respectively.
9.Tetrahydroisoquinolines as novel histone deacetylase inhibitors for treatment of cancer.
Danqi CHEN ; Aijun SHEN ; Guanghua FANG ; Hongchun LIU ; Minmin ZHANG ; Shuai TANG ; Bing XIONG ; Lanping MA ; Meiyu GENG ; Jingkang SHEN
Acta Pharmaceutica Sinica B 2016;6(1):93-99
Histone acetylation is a critical process in the regulation of chromatin structure and gene expression. Histone deacetylases (HDACs) remove the acetyl group, leading to chromatin condensation and transcriptional repression. HDAC inhibitors are considered a new class of anticancer agents and have been shown to alter gene transcription and exert antitumor effects. This paper describes our work on the structural determination and structure-activity relationship (SAR) optimization of tetrahydroisoquinoline compounds as HDAC inhibitors. These compounds were tested for their ability to inhibit HDAC 1, 3, 6 and for their ability to inhibit the proliferation of a panel of cancer cell lines. Among these, compound 82 showed the greatest inhibitory activity toward HDAC 1, 3, 6 and strongly inhibited growth of the cancer cell lines, with results clearly superior to those of the reference compound, vorinostat (SAHA). Compound 82 increased the acetylation of histones H3, H4 and tubulin in a concentration-dependent manner, suggesting that it is a broad inhibitor of HDACs.
10.Discovery of a series of dimethoxybenzene FGFR inhibitors with 5pyrrolo2,3-pyrazine scaffold: structure-activity relationship, crystal structural characterization and study.
Peng WEI ; Bo LIU ; Ruifeng WANG ; Yinglei GAO ; Lanlan LI ; Yuchi MA ; Zhiwei QIAN ; Yuelei CHEN ; Maosheng CHENG ; Meiyu GENG ; Jingkang SHEN ; Dongmei ZHAO ; Jing AI ; Bing XIONG
Acta Pharmaceutica Sinica B 2019;9(2):351-368
Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors (FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structure-activity relationship was elaborated. Together with metabolic stability tests and pharmacokinetic profiling, a representative compound () was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor was effective against tumors with FGFR genetic alterations, exhibiting potential for further development.