Investigation on the mechanism of anti-drug-induced liver injury and related effector substances of traditional Chinese medicine from the perspective of metabolism / 药学学报

Drug-induced liver injury (DILI) is one of the common clinical adverse drug reactions and remains a major cause of drug restriction, development termination and withdrawal from the pharmaceutical market today. In recent years, a variety of chemical components and metabolites of traditional Chinese medicine (TCM), as well as the endogenous effector substances influenced by metabolism of both, have attracted much attention for their significant hepatoprotective activities. However, the mechanism of TCM against DILI is complex, the related effector substances are still unclear, and its metabolism-related studies are still relatively weak. Therefore, this review summarized the mechanisms of DILI and its treatment by TCM from the perspective of metabolism, and for the first time, innovatively classified the Chinese medicine effector substances into two categories: exogenous (active components and metabolites of TCM) and endogenous (intestinal probiotics and endogenous metabolites), in order to reduce the occurrence of DILI, explore and develop effective anti-drug-induced liver injury effector substances of TCM, and further develop clinical drugs with hepatoprotective effects.

Effects of puerarin on blood pressure and aortic endothelial function in obese mice / 中国药理学通报

Aim To explore the effeet of puerarin (Pue) on aortic function and blood pressure in hyper-tensive mice induced by high-fat diet.Methods Thirty male mice were divided into five groups named as normal diet group ( Con ) , high-fat diet group (1)10), high-fat diet + low-dose puerarin group (20 mg 'kg-1 •(!"'), high-fat diet + medium-dose puera¬rin (40 mg • kg"1 • d ~1 ) group and high-fat diet + high-dose puerarin group (80 mg 'kg-1 • d~l).Hie mice were injected intraperitoneally with Pue for eight weeks.Body weight, blood pressure and blood glucose were measured.Serum was collected to detect blood lipid.Aortas were separated from aortic endothelial cells to test the vasodilative function.Aortic endotheli¬al cells from 1)10 mice were isolated to perform Iran-swell and cell proliferation experiments.Results I High-rlose puerarin treatment could reduce the body weight, body fat, blood glucose and blood pressure in obese mice ( P < 0.01 ) ; 2 High dose of puerarin could improve the vasodilative function of aortas com¬pared with those from 1)10 mice (P <0.01 ) ; (3) The migration ability of primary endothelial cells from 1)10 + Pue group was improved compared with that from 1)10 group (P <0.01 ).Conclusions Puerarin can significantly reduce blood pressure in obese mice in¬duced by high fat diet by improving the aortic diastolic function and endothelial cell proliferation and migra-tion.

development and application of dna extraction methods, pcr parameter optimization and rapid detection reagent for fetus cervi / 中国药学杂志

OBJECTIVE: To optimize DNA extraction methods and PCR reaction parameters, and develop an excellent and accurate rapid detection reagent for Fetus Cervi. METHODS: The DNA of Fetus Cervi was extracted by the modified salting method, modified SDS method A and modified SDS method B. Four DNA polymerase were chosen from the market and compared with each other. The annealing temperature and annealing time were optimized by classical control variable method and intersected experiment. A rapid detection reagent of Fetus Cervi was developed and then evaluated. RESULTS: The A260 /A280 ratio of the DNA extracted by modified SDS method B was (1.74 ± 0.05), and the mass concentration was (0.250 ± 0.005) μg•L -1. With high fidelity Taq DNA polymerase, the PCR product concentration could reach (0.185 ± 0.005) μg•L-1. Through these experiments, the annealing temperature was set at 58 ℃ and the annealing time was 30 s. The rapid detection reagent course was established to quickly and accurately identify Fetus Cervi and their artefacts, with one clear and bright band at 563 bp. CONCLUSION: The rapid detection reagent of Fetus Cervi combines the optimal DNA extraction method and the optimal PCR reaction parameters, and can accomplish the identification of Fetus Cervi and its pseudo-products with high accuracy and specificity.

Factors affecting the stability of carotid atherosclerotic plaque by left ventricular function / 医学研究生学报

Objective At present, there are few reports on the stability of carotid plaque and left ventricular function at home and abroad. The article investigated the factors influencing the stability of left ventricular function on carotid atherosclerotic plaque. Methods 90 patients with carotid atherosclerosis (carotid intima-media thickness >0.2 cm) admitted in the Department of Neurology, Jiangsu Provincial Hospital of Traditional Chinese Medicine from June 10, 2017 to January 8, 2019 were selected and their stability of plaques was graded by contrast-enhanced ultrasound (CEUS). The patients were divided into two groups according to the stability of plaque. The differences of general clinical data, related biochemical indexes and left ventricular function indexes between the two groups were compared. The effects of left ventricular structural function on plaque stability were examined by logistic multivariate regression analysis. Results Univariate analysis showed that E peak (χ2=2.170, P=0.034), ventricular septal thickness (χ2=-1.972, P=0.049), diabetes history (χ2=10.102, P=0.001) were the risk factors of plaque stability and the differences were statistically significant (P < 0.05). Multivariate analysis showed that E peak (OR=0.022, P=0.014) and diabetes history (OR=0.185, P=0.002) were independent influencing factors of plaque stability. Conclusion There is an independent correlation between left ventricular function and plaque stability, and plaque stability can predict changes in ventricular structural function.

Chromosome polymorphisms and their influence on semen quality and sperm DNA integrity in males undergoing IVF/ICSI / 中华男科学杂志

Objective@#To investigate the incidence of chromosome polymorphisms and their influence on semen quality and sperm DNA integrity in male patients receiving in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI).@*METHODS@#We retrospectively analyzed the chromosomal karyotypes and the types and incidence rate of chromosome polymorphisms in 2 370 male patients undergoing IVF/ICSI between June 2016 and June 2018. We classified the patients into groups A (with variation in the secondary constriction region in the autosomal long arm), B (with variation in the short arm of the D/G group chromosomes), C (with interbrachial inversion of chromosome 9) and D (with Y chromosome polymorphisms), and compared the semen parameters and sperm DNA fragmentation indexes (DFI) between the patients with chromosome polymorphisms and those with normal chromosomes.@*RESULTS@#Totally, 154 (6.50%) of the patients undergoing IVF/ICSI were found with chromosome polymorphisms, including 34 cases of secondary constriction variation in the long arm of the autosome (1.43% ［34/2 370］, 22.08% ［34/154］), 82 cases of short arm polymorphisms of the D/G group chromosomes (3.46% ［82/2 370］, 53.25% ［82/154］), 26 cases of interbrachial inversion of chromosome 9 (1.10% ［26/2 370］, 16.88% ［26/154］), 10 cases of Y chromosome polymorphisms (0.42% ［10/2 370］, 6.50% ［10/154］), and 2 cases of mixed chromosome polymorphisms (0.08% ［2/2 370］, 1.42% ［2/154］). The total sperm count was lower in group D than in the other polymorphism groups and the normal chromosome group, but with no statistically significant difference among the five groups (P > 0.05). The sperm progressive motility was also lower in group D than in the other five groups, with statistically significant difference from group B (27.5 ± 13.5 vs. 41.5 ± 21.1, P = 0.027), but not from the other groups (P > 0.05). No statistically significant difference was observed in the sperm DFI between the polymorphism groups and the normal chromosome group (P > 0.05), or among the polymorphism groups (P > 0.05). The proportion of normal semen was lower in group D than in the other four groups, but with no statistically significant difference among the five groups (P > 0.05). The incidence rate of asthenospermia was higher in group D than in the other four groups, but with no statistically significant difference among the five groups (P > 0.05), and so was that of oligoasthenospermia, with statistically significant difference from the normal chromosome group (30.0% vs 8.0%, P = 0.041), but not from the other polymorphism groups (P > 0.05).@*CONCLUSIONS@#Short arm polymorphisms of the D/G group chromosomes are the most common type of chromosome polymorphisms in male patients undergoing IVF/ICSI. Polymorphisms of the Y chromosome have a negative effect on semen quality, while those of the other chromosomes do not significantly affect semen quality and sperm DNA integrity.

Advances in biomarkers and stem cell-targeted therapy for hepatocellular carcinoma / 药学学报

Primary hepatocellular carcinoma as the main pathological type of liver cancer is one of the common malignant tumors in our country. Liver cancer stem cells (LCSCs) have the characteristics of multidrug resistance, anti-radiotherapy and high tumorigenicity in addition to the characteristics of stem cells, namely, self-renewal, multi-directional differentiation and unlimited proliferation. Based on the above features, relapse and metastasis often occur after the patients being treated with conventional methods, which results in poor prognosis. Effective treatment targeting LCSCs has the potential to cure hepatocellular carcinoma (HCC) completely. This article reviews the common biomarkers used in identification of LCSCs and development of stem cell-targeted therapy for HCC.

Influence of targeted gene VEGF silencing of bladder cancer cell line T24 on differentiation , maturation and function of dendritic cells / 基础医学与临床

Objective To observe the influence of targeted gene VEGF silencing of bladder cancer cell line T 24 on differentiation, maturation and function of dendritic cells .Methods A lentiviral vector named LV-VEGFA-RNAi ( experimental group ) for gene silencing targeting VEGF and a lentiviral vector named LV-CON ( negative control group ) without any valid sequences were constructed .The blank control group accepted no intervention measures . The expression of VEGF's mRNA and protein of T24 cells from each group were detected by RT-PCR and ELISA respectively .Then the immature DCs were co-cultured respectively with the supernatant of all the groups as men-tioned above.CD1a, CD83 as the maturation marker and CD86 as the immunity marker of the DCs were detected by flow cytometry.Results The expression of VEGF's mRNA and protein of T24 cells in the experimental group were obviously inhibited ( P<0.05 ) as compared with that in the negative control group and the blank control group.DCs of the experimental group had an obviously increased ( P<0.05 ) expression of CD1a, CD83 and CD86 compared with the negative control group and the blank control group .Conclusions Targeted gene VEGF silencing by RNAi has advantages to the growth and immunity of DCs , which may strengthen the anti-tumor ca-pacity of the DCs by repairing their damaged immune monitoring function .

Development and evaluation of Fritillaria cirrhosa D. Don DNA detection kit / 中国药学杂志

OBJECTIVE: To develop a kit for detection of DNA of Fritillaria cirrhosa D. Don and optimize its components as well as process protocols, in order to set up a simple, rapid molecular biology method for identification of Fritillaria cirrhosa D. Don. METHODS: All genomic DNA of Fritillaria cirrhosa D. Don was extracted by kit assay and pharmacopoeia method recorded in the expanded supplement of China Pharmacopoeia 2010, respectively; ultraviolet spectrophotometer was used to measure the quantity of extracted DNA; PCR amplification and restriction fragment length polymorphism analysis (RFLP) were carried out to identify the authentication of Fritillaria cirrhosa D. Don. RESULTS: The maximum value of genomic DNA extracted by pharmacopoeia method was (1.57±0.05) (OD260/OD280) and (1.73±0.10) by kit assay. The PCR amplification showed a single band over 300 bp, while the RFLP showed two distinct bands between 100 and 250 bp in agarose electrophoresis. CONCLUSION: The data demonstrated that the kit assay was better than the pharmacopoeia method, especially in the extraction quantity and DNA purity of Fritillaria cirrhosa D. Don nicleic acid; the PCR and RFLP results showed that the kit assay was consistent with pharmacopoeia method. The detection kit has good specificity, high sensitivity and good stability, so it is suitable for the rapid detection of Fritillaria cirrhosa D. Don.

Network systems biology for targeted cancer therapies / 癌症

The era of targeted cancer therapies has arrived. However, due to the complexity of biological systems, the current progress is far from enough. From biological network modeling to structural/dynamic network analysis, network systems biology provides unique insight into the potential mechanisms underlying the growth and progression of cancer cells. It has also introduced great changes into the research paradigm of cancer-associated drug discovery and drug resistance.

Influence of fluoride on the expression TM9SF1 mRNA and Ras mRNA of human osteoblasts / 中国地方病学杂志

Objective To detect the influence of fluoride on the expression TM9SF1 mRNA and Ras mRNA of osteoblasts. Methods The third generation of primary cultured osteoblasts were exposed to a series concentrations of 0,2.5,5.0, 10.0,20.0 mg/L fluoride for 10 days. The influence of different doses of fluorine on the expression of TM9SF1 mRNA and Ras mRNA of osteoblasts cultured in vitro was investigated by SYBR Green I methods. Results The osteoblasts of the control group and the 2.5 mg/L group were in the shape of long spindle, triangle or irregular polygon and had processes, and the cytoplasm was translucent, adjacent cells affixed to each other under light microscope. Those of the 20.0 mg/L group shaped as long spindle or irregular polygon, and some vacuolization and granular materials appeared in cytoplasm. The number of the cells decreased and the volume increased significantly. After exposed to fluoride for 10 days, osteoblasts of 2.5 mg/L group morphologically proliferated. There were statistical siguificances between each groups of TM9SF1 mRNA in human osteoblasts(F = 322.82, P < 0.01). The highest in the 2.5 mg/L group(9326.0 ± 115.97), the expression of TM9SF1 mRNA decreased along with the increasing dose of fluorine. There were statistical significances between 5.0, 10.0,20.0 mg/L groups(6495.0 ± 323.9, 4387.5 ± 545.2, 5962.5 ± 536.7) and control group(9221.0 ± 107.5, all P< 0.01). There was a statistical significance between each groups of Ras mRNA in human osteoblasts(F = 703.28, P < 0.01). The highest in the control group, the expression of Ras mRNA decreased along with the increasing of dose of fluorine. There were statistical significance between 2.5, 5.0, 10.0, 20.0 mg/L groups(6144.5 ± 270.82,5603.5 ± 88.39,3181.0 ± 159.81,4067.5 ± 37.4) and control group(6571.0 ± 196.58). Conclusion The influence on TM9SFI mRNA and Ras mRNA expression in osteoblasts correlates with the dose of fluorine.