5. Establishment and biological characterization of drug-resistant cells and identification of multidrug resistance in small-cell lung cancer
Yong-Qing HAN ; Zheng-Yuan WANG ; Xiu-Fen DAI ; Zi-Ran WANG ; Jing LI ; Xin QI ; Jing LI
Chinese Pharmacological Bulletin 2024;40(2):279-284
Aim To establish NCI-H446/EP for small cell lung cancer resistant cells resistant to cisplatin and etoposide, and to evaluate their biological characteristics and multidrug resistance. Methods Nude mice were subcutaneously inoculated with NCI-H446 cells of SCLC to construct an in vivo model of xenograft tumor, and were given first-line EP regimen treatment for SCLC, inducing drug resistance in vivo, and stripping tumor tissue in vitro culture to obtain drug-resistant cells. The resistance coefficient, cell doubling time, cell cycle distribution, expression of multidrug resistance gene (MDR1), and drug resistance-related protein were detected in vitro, and the drug resistance to cisplatin and etoposide in vivo were verified. Results Mice with NCI-H446 tumors acquired resistance after eight weeks' EP regimen treatment, and the drug-resistant cell line NCI-H446/EP was obtained by isolation and culture in vitro. The resistance factors of this cell line to cisplatin, etoposide, SN38 and doxorubicin were 12.01, 18.36, 65.4 and 10.12, respectively. Compared with parental cells, the proportion of NCIH446/EP cells in Q
6. Ligustilide delays senescence of auditory cortex in mice by inhibiting ferritinophagy
Ying-Dong ZHOU ; Meng-Xian ZHANG ; Qing-Ling WANG ; Hao-Ran KANG ; Zhi-Cheng ZHANG ; Xiang-Dong GUO ; Qing-Lin WANG ; Ya-Min LIU
Chinese Pharmacological Bulletin 2024;40(3):455-461
Aim To investigate the mechanism of ligu aged 2 months of the same strain were used as the constilide (LIG) in delaying the senescence of auditory trol (Ctrl) group. Auditory brainstem response test was cortex and treating central presbycusis. Methods used to detect the auditory threshold of mice before and Forty C57BL/6J mice aged 13 months were randomly di after treatment. Levels of serum MDA and activity of vided into ligustilide low-dose(L-LIG) group, ligustil serum SOD were detected to display the level of oxidative ide medium-dose (M-LIG) group, ligustilide high-dose stress. The pathological changes of auditory cortex were (H-LIG) group and aging (Age) group, and 10 mice observed by HE staining. Ferroptosis was observed by
7.Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics
Yu-long CHEN ; You ZHAI ; Xiao-yan WANG ; Wei-xia LI ; Hui ZHANG ; Ya-li WU ; Liu-qing YANG ; Xiao-fei CHEN ; Shu-qi ZHANG ; Lu NIU ; Ke-ran FENG ; Kun LI ; Jin-fa TANG ; Ming-liang ZHANG
Acta Pharmaceutica Sinica 2024;59(2):382-394
Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and
8.Novel antibacterial drug target against Gram-negative bacteria: lipopolysaccharide transport protein LptDE and its inhibitors
Yue LI ; Guo-qing LI ; Yuan-yuan TIAN ; Cong-ran LI ; Xin-yi YANG ; Kai-hu YAO ; Xue-fu YOU
Acta Pharmaceutica Sinica 2024;59(2):279-288
The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non
9.Epidemiological Investigation of Dampness Syndrome Manifestations in the Population at Risk of Cerebrovascular Disease
Xiao-Jia NI ; Hai-Yan HUANG ; Qing SU ; Yao XU ; Ling-Ling LIU ; Zhuo-Ran KUANG ; Yi-Hang LI ; Yi-Kai ZHANG ; Miao-Miao MENG ; Yi-Xin GUO ; Xiao-Bo YANG ; Ye-Feng CAI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):531-539
Objective To make an epidemiological investigation on traditional Chinese medicine(TCM)dampness syndrome manifestations in the population at risk of cerebrovascular diseases in Guangdong area.Methods A cross-sectional study was conducted to analyze the clinical data related to the risk of cerebrovascular diseases in 330 Guangdong permanent residents.The diagnosis of dampness syndrome,quantitative scoring of dampness syndrome and rating of the risk of stroke were performed for the investigation of the distribution pattern of dampness syndrome and its influencing factors.Results(1)A total of 306(92.73%)study subjects were diagnosed as dampness syndrome.The percentage of dampness syndrome in the risk group was 93.82%(258/275),which was slightly higher than that of the healthy group(48/55,87.27%),but the difference was not statistically significant(χ2 = 2.91,P = 0.112).The quantitative score of dampness syndrome in the risk group was higher than that of the healthy group,and the difference was statistically significance(Z =-2.24,P = 0.025).(2)Among the study subjects at risk of cerebrovascular disease,evaluation time(χ2 = 26.11,P = 0.001),stroke risk grading(χ2= 8.85,P = 0.031),and history of stroke or transient ischemic attack(TIA)(χ2 = 9.28,P = 0.015)were the factors influencing the grading of dampness syndrome in the population at risk of cerebrovascular disease.Conclusion Dampness syndrome is the common TCM syndrome in the population of Guangdong area.The manifestations of dampness syndrome are more obvious in the population with risk factors of cerebrovascular disease,especially in the population at high risk of stroke,and in the population with a history of stroke or TIA.The assessment and intervention of dampness syndrome should be taken into account for future project of stroke prevention in Guangdong.
10.The Effects of Bronchoalveolar Lavage Combined with Microbiological Rapid on-site Evaluation in the Maintenance of Potential Donor Lung
Liming GONG ; Jianghua RAN ; Yinjia WANG ; Zhiwei LI ; Qian YANG ; Qing WANG ; Dongkun WANG ; Zhengneng TANG
Journal of Kunming Medical University 2024;45(1):107-115
Objective To explore the effects of bronchoalveolar lavage combined with microbiological rapid on-site evaluation in potential donor lung maintenance.Methods Brain death patients who met the inclusion criteria and were admitted to the Intensive Care Unit(ICU)of Calmette Hospital Affiliated to Kunming Medical University from September 2020 to December 2022 were selected for bronchoalveolar lavage(BAL)and(BAL)and the lavage fluid were collected for M-ROSE to compare the pathogen detection rate and initial diagnosis time.According to the positive results of the microbiological rapid on-site evaluation,patients with the brain death were treated with empirical anti-infective therapy,and the oxygenation index,chest X-ray score,and the infection index(WBC,CRP,PCT)of anti-infective treatment 48 hours were evaluated.Results 1.Comparison of the detection rate of pathogenic microorganisms:The results of M-ROSE were highly consistent with a routine microbiological smear(Kappa = 0.921,P<0.001).2.Comparison of diagnostic time:The initial diagnosis time of M-ROSE was significantly lower than routine microbiological smear time and microbial culture time(P<0.001).3.Comparison of therapeutic effects of anti-infective therapy for 48 hours:There was no significant difference in oxygenation index,white blood cells and hypersensitive C-reactive protein before and after the anti-infective treatment(P>0.05).There were significant differences in procalcitonin and chest X-ray before and after the anti-infective treatment(P<0.05).Conclusion Bronchoalveolar lavage combined with microbiological rapid on-site evaluation has the high timeliness in the diagnosis of potential donor pulmonary infection,which can provide a preliminary basis for the early anti-infective therapy of donor lung maintenance.

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