Quantitative characterization of cell physiological state based on dynamical cell mechanics for drug efficacy indication / 药物分析学报

Cell mechanics is essential to cell development and function,and its dynamics evolution reflects the physiological state of cells.Here,we investigate the dynamical mechanical properties of single cells under various drug conditions,and present two mathematical approaches to quantitatively character-izing the cell physiological state.It is demonstrated that the cellular mechanical properties upon the drug action increase over time and tend to saturate,and can be mathematically characterized by a linear time-invariant dynamical model.It is shown that the transition matrices of dynamical cell systems signifi-cantly improve the classification accuracies of the cells under different drug actions.Furthermore,it is revealed that there exists a positive linear correlation between the cytoskeleton density and the cellular mechanical properties,and the physiological state of a cell in terms of its cytoskeleton density can be predicted from its mechanical properties by a linear regression model.This study builds a relationship between the cellular mechanical properties and the cellular physiological state,adding information for evaluating drug efficacy.

Application of metabonomics in breast cancer / 药学实践杂志

Breast cancer is a kind of malignant tumor discovered lately, with a high incidence and a poor prognosis. The shortage of relevant biological biomarkers lead to the unsatisfactory treatment efficacy and the early diagnosis in breast cancer. Metabolomics is a new discipline that uses high-throughput analysis techniques to study the dynamic changes of endogenous metabolites under the influence of different pathological physiological stimulation or gene mutations, which has provided a novel way for biomarker screening and disease diagnosis and treatment. The overview of metabolomics and its applications in breast cancer early diagnosis, drug efficacy evaluation, and disease prognosis were summarized in this review.

Genetic Diversity and Molecular Surveillance of Antimalarial Drug Resistance of Plasmodium falciparum among Hospitals Patients in Benue State Nigeria

Introduction: Malaria is a febrile illness caused by parasites of the genus Plasmodium and transmitted by female Anopheles mosquitoes. The genetic diversity and antimalarial drug resistance of Plasmodium falciparum are some of the major challenges of malaria control programme in Nigeria. Aim: This study was aimed at determining the genetic diversity, and molecular surveillance of antimalarial drug resistance among patients attending Government hospitals in Benue State, Nigeria. Methodology: Plasmodium falciparum deoxyribonucleic acid was extracted from dried blood spots of 60 positive malariacases among the patients. The diversity of Plasmodium falciparum was done by genotyping 3D7 and FC27 families of merozoite surface protein- 2 alleles. The Plasmodium falciparum multidrug resistance 1 and Plasmodium falciparum kelch13 genes of Plasmodium falciparum were also amplified and assessed by restriction fragment length polymorphism (RFLP) to survey molecular resistance to antimalarial drugs. Results: The results showed that the frequency of 3D7 allele 37(61.7%) was higher than FC27 allele 18(30.0%). The frequency of merozoite surface protein- 2 infections with both allelic types was 5(8.3%). There was a significant difference in the distribution of the merozoite surface protein two alleles (?2=25.9,df=2 P<.0.001). Both the Plasmodium falciparum multidrug resistance 1 Asparagine 86Tyrosine (N86Y) and Aspartic acid 1246Tyrosine (D1246Y), had 100 % mutant while the 100% while the Plasmodium falciparum kelch13 G449A had 100% wild type allele. Conclusion: The current study underscores the need for frequent monitoring of indicators of antimalaria drug resistance in Nigeria.

Pharmacogenomics: Current Actionable Variants

Pharmacogenomics (PGx), one of the several tools of precision medicine, has been slowly implemented in the clinic during the past decades. This process generally starts with direct and indirect genotype-phenotype associations of gene variants and drug efficacy, or adverse drug reactions, followed by replication and validation studies. Institutional efforts led by the PGx Research Network, The PGx Knowledge Base, and The Clinical Pharmacogenetics Implementation Consortium, mine all available data for further validation or research in additional populations. This data mining gives rise to a detailed classification of over 200 drug-gene pairs which, with enough documentation, may become part of a publishable guideline to aid clinicians in drug selection and dosing using genetics. The US Food and Drug Administration utilizes these guidelines to issue warnings and recommendations for specific drugs and their cautioning serves clinicians and pharmacists worldwide. Here, we aim to discuss the steps of this process and list existing actionable drug-gene pairs. Moreover, we describe the current status of PGx knowledge in populations from Mexico for actionable variants on the 19 genes listed by present PGx guidelines affecting 47 drugs. Our review collects current allele frequency information for these actionable variants, lists gaps of PGx information for relevant markers, and highlights the importance of continuing PGx research in Native and Mestizo populations. (REV INVEST CLIN. 2020;72(5):271-9)

Establishment of a database of in vitro combined drug efficacy against multi-drug resistant Gram-negative bacilli / 中华微生物学和免疫学杂志

Objective To study the synergistic and additive effects of commonly used antibiotics on multi-drug resistant Gram-negative bacilli and to establish a database of combined pharmacodynamics in vitro. Methods Seven antibiotics including fosfomycin (PHOS), levofloxacin (LEV), ceftazidime ( CAZ ) , compound sulfamethoxazole ( SMZ ) , piperacillin/tazobactam ( TZP ) , cefoperazone/sulbactam ( SCF) and imipenem ( IMP) were selected and grouped into 21 drug pairs. Based on the results of extended spectrum β-lactamases ( ESBLs) test and modified carbapenem inactivation method ( mCIM) , a total of 172 strains of multidrug-resistant Gram-negative bacilli were divided into four groups:20 strains of carbapenem-resistant Klebsiella pneumoniae ( group A) , 50 strains of pan-resistant Acinetobacter baumannii ( group B) , 62 strains of ESBLs-producing Enterobacter ( group C) and 40 strains of carbapenem-resistant Pseudomonas aeruginosa ( group D) . Chessboard dilution method was used to detect the in vitro combined efficacy of 21 drug pairs on drug-resistant bacteria from the four groups. Whonet 5. 6 was used for statistical analysis. Re-sults All 172 strains were single drug resistant to the seven antibiotics. Results of the combined drug effi-cacy test showed that no antagonism was found in the four groups. In group A, ten drug pairs, especially the combination of PHOS+LEV (30％, 6/20), had synergistic effects and 14 showed partial synergistic effects,but no additive effect was detected. Synergistic effects, partial synergistic effects and additive effects were respectively achieved by 12, ten and three drug pairs in group B. The LEV+SMZ combination had synergis-tic effects against 56％ (28/50) of the strains, which was the highest among all combinations. There were 14, 17 and 16 drug pairs showing synergistic effects, partial synergistic effects and additive effects in group C, respectively, and the strongest synergistic effects were achieved by the IMP+LEV combination (30. 6％, 19/62). There were 12, 14 and 13 drug pairs having synergistic effects, partial synergistic effects and addi-tive effects in group D, respectively, and the strongest synergistic effects were achieved by the IMP+LEV combination (20％, 8/40). Conclusions The combined use of quinolones, carbapenems, sulfonamides and PHOS could have good synergistic effects against multi-drug-resistant gram-negative bacilli. Monitoring the in vitro combined efficacy before treatment would improve the accuracy of antibiotic use and is of great clinical value.

Establishment of a database of in vitro combined drug efficacy against multi-drug resistant Gram-negative bacilli / 中华微生物学和免疫学杂志

Objective@#To study the synergistic and additive effects of commonly used antibiotics on multi-drug resistant Gram-negative bacilli and to establish a database of combined pharmacodynamics in vitro.@*Methods@#Seven antibiotics including fosfomycin (PHOS), levofloxacin (LEV), ceftazidime (CAZ), compound sulfamethoxazole (SMZ), piperacillin/tazobactam (TZP), cefoperazone/sulbactam (SCF) and imipenem (IMP) were selected and grouped into 21 drug pairs. Based on the results of extended spectrum β-lactamases (ESBLs) test and modified carbapenem inactivation method (mCIM), a total of 172 strains of multidrug-resistant Gram-negative bacilli were divided into four groups: 20 strains of carbapenem-resistant Klebsiella pneumoniae (group A), 50 strains of pan-resistant Acinetobacter baumannii (group B), 62 strains of ESBLs-producing Enterobacter (group C) and 40 strains of carbapenem-resistant Pseudomonas aeruginosa (group D). Chessboard dilution method was used to detect the in vitro combined efficacy of 21 drug pairs on drug-resistant bacteria from the four groups. Whonet 5.6 was used for statistical analysis.@*Results@#All 172 strains were single drug resistant to the seven antibiotics. Results of the combined drug efficacy test showed that no antagonism was found in the four groups. In group A, ten drug pairs, especially the combination of PHOS+ LEV (30%, 6/20), had synergistic effects and 14 showed partial synergistic effects, but no additive effect was detected. Synergistic effects, partial synergistic effects and additive effects were respectively achieved by 12, ten and three drug pairs in group B. The LEV+ SMZ combination had synergistic effects against 56% (28/50) of the strains, which was the highest among all combinations. There were 14, 17 and 16 drug pairs showing synergistic effects, partial synergistic effects and additive effects in group C, respectively, and the strongest synergistic effects were achieved by the IMP+ LEV combination (30.6%, 19/62). There were 12, 14 and 13 drug pairs having synergistic effects, partial synergistic effects and additive effects in group D, respectively, and the strongest synergistic effects were achieved by the IMP+ LEV combination (20%, 8/40).@*Conclusions@#The combined use of quinolones, carbapenems, sulfonamides and PHOS could have good synergistic effects against multi-drug-resistant gram-negative bacilli. Monitoring the in vitro combined efficacy before treatment would improve the accuracy of antibiotic use and is of great clinical value.

Difference of hypoglycemic and hypolipidemic effects of endangered species (Coptis deltoidea) and its processed products on T2DM rats / 中草药

Objective To investigate the difference of hypoglycemic and hypolipidemic effects of Coptis deltoidea (Coptis chinensis) and its processed products on T2DM rats. Methods Type 2 diabetes mellitus induced by high sugar, high fat diet and low dose of streptozotocin. C. deltoidea were processed with yellow wine, ginger, and evodia rutaecarpa, respectively. The effects of C. deltoidea on fasting blood glucose (FBG), fasting insulin (FINS), glycosylated serum protein (GSP), pancreatic pathology, serum triglyceride (TG), total cholesterol (TC) and lipoprotein (HDL-C or LDL-C) and key protein and gene expression of SCAP\SREBP-1c pathway in liver of model rats were investigated. Result C. deltoidea and its processed products reduced the FBG and GSP in T2DM rats. The wine products significantly reduced FBG and GSP in model rats (P < 0.01). The hypoglycemic range was better than raw and ginger products. At hypolipidemic aspect, C. deltoidea and its processed products decreased the content of TG, TC, and LDL-C (P < 0.05, 0.01), increased the content of HDL-C in serum (P < 0.05, 0.01), and down-regulated the protein and gene expression of SCAP/SREBP-1c in liver, the insulin target organ. However, wine and evodia products were better than crude drug or ginger products. Conclusion C. deltoidea processed by yellow wine, ginger and evodia rutaecarpa is traditional method to improve the disadvantages of C. deltoidea with bitter cold nature and not easy to take for a long time. However, different processing methods have different effects. Clinical medication should be combied withTCM syndrome differentiation and simple hypoglycemic effect of wine product is appropriate; while wine and evodia products were better in hypoglycemic and lipid regulation aspects.

Evaluation of Antiplasmodial Activity and Safety of Flower Extracts of Chrysanthemum cinerariaefolium, Singly and in Combination with Chloroquine, Lumefantrine and Piperaquine

Objective: To evaluate the antiplasmodial activity and safety of organic and aqueous flower extracts of Chrysanthemum cinerariaefolium from Kenya, singly and in combination with chloroquine, lumefantrine and piperaquine. Methodology: Antiplasmodial activity of organic and aqueous flower extracts of C. cinerariaefolium was assessed in vitro by serial micro-dilution assay technique against Plasmodium falciparum, and in vivo using the 4-day suppressive test as well as the established infection test against P. berghei ANKA in mice. To determine the safety of the extracts, cytotoxicity evaluation of extracts against Vero E6 cells and acute toxicity studies in mice were also done. Results: In vitro antiplasmodial assays showed that methanolic extract of C. cinerariaefolium flowers was active, petroleum ether extract was moderately active, while the aqueous extract was inactive. Methanolic extract combined with chloroquine (CQ) against CQ-sensitive (3D7) and CQ-resistant (W2) P. falciparum showed marked synergy. Both methanol and aqueous extracts (1000mg/kg) showed chemosuppression of >45% (P<0.05) in both 4-day suppression test and established infection test against P. berghei ANKA in mice. Lumefantrine (LU) or piperaquine (PQ) combined with either methanol or aqueous extracts showed chemosuppression of >63% (P<0.05) against LU-resistant and PQ-resistant P. berghei ANKA strains, indicating synergistic interactions. Methanolic and aqueous flower extracts of C. cinerariaefolium had no cytotoxic effect on Vero E6 cells and no overt signs of toxicity in mice. Conclusion: The findings showed that C. cinerariaefolium flower extracts are safe in mammalian systems, have antiplasmodial activity and have potentiation effect of conventional antimalarials. There is need therefore to further explore the plant’s bioactive molecules which may serve as template for development of novel, effective and affordable antimalarial agents for management of malaria.

Study on the efficacy evaluation of real-time fluorescence assay of RNA isothermal amplification in the treatment of patients with positive pulmonary tuberculosis / 天津医药

@#Objective To investigate the value of real-time fluorescence detection technique of RNA (SAT) constantamplification in monitoring the effect of chemotherapy on patients with sputum positive pulmonary tuberculosis. Methods Sixty-two patients were selected, who were clinically diagnosed as the first-time retreatment for sputum smear-positive pulmonary tuberculosis and were hospitalized in our department from June 2015 to December 2016. After two-month standard anti-tuberculosis treatment, sputum samples were detected by Peng’s vessel acid-fast staining, BACTEC MGIT- 960 culture and strain identification, SAT detection. The BACTEC MGIT-960 culture and strain identification were used as gold standards, the value of SAT during the monitoring the therapeutic effect of the anti-tuberculosis drugs was assessed. Results After the treatment, 49 cases out of 62 showed positive results in mycobacterium tuberculosis culture test, among them 42 patients were diagnosed as human type mycobacterium tuberculosis, 7 patients were diagnosed as nontuberculous mycobacteria infection, and 13 cases showed negative results in mycobacterium tuberculosis culture. Thirty-two cases showed positive results in sputum Peng’s vessel acid-fast staining test, and 30 cases showed negative results. Forty-one cases showed positive results in SAT test and 21 cases showed negative results in SAT. SAT results were well concordant with sputum culture results (Kappa value=0.964), and the sensitivity, the specificity, the positive predictive value and the negative predictive value of SAT were 97.62%, 100%, 100% and 95.24% respectively. Peng’s vessel acid-fast staining results were badly concordant with MGIT-960 culture results (Kappa value=0.086), and the sensitivity, the specificity, the positive predictive value and the negative predictive value of Peng’s vessel acid-fast staining were 54.76%, 55.00%, 71.88% and 36.67% respectively. Conclusion SAT results can be used as good indices during the monitoring therapeutic effects of drugs used for the first-time retreatment in patients with sputum smear-positive pulmonary tuberculosis, which is worth promoting.

Role of pulmonary function analysis in drug efficacy evaluation of radiation-induced lung injury / 军事医学

Objective To explore the role of pulmonary function analysis in drug efficacy evaluation of radiation-induced lung injury.Methods Totally 30 C57BL/6 mice were randomly divided into 3 groups:control group, radiation group and dexamethasone group.Mice in radiation group and dexamethasone group were irradiated with 20 Gy X-ray on the whole chest.Then mice in dexamethasone group was intraperitoneally injected with dexamethasone at the dose of 4.5 mg/( kg· d) for 2 weeks and then the dose was halved up to 1 month after radiation while control group and radiation group were intraperitoneally injected with 0.9%saline.One month after irradiation, pulmonary function of all the mice was tested with EMKA system.Then mice were sacrificed and pathological changes of pulmonary tissue were observed by HE staining. Furthermore, the area of alveolar cavity was measured with the Image-pro plus software.Results One month after irradiation, the pulmonary function parameters of mice in radiation and dexamethasone groups, such as mid-expiratory flow, minute volume,tidal volume,peak inspiratory flow,and peak expiratory flow,decreased obviously compared with the control group, but those parameters of the dexamethasone group decreased much less significantly than in the radiation group.The pathological changes of pulmonary tissues showed that the area of alveolar cavity of radiation group and dexamethasone group was smaller than that of the control group, but the extent of the loss of alveolar cavity area of the dexamethasone group was less than in the radiation group.Neutrophils infiltration could be found in the radiation group and dexamethasone group, but was less serious in the dexamethasone group.The result of pulmonary function analysis was coincident with pathological changes of the lung.Conclusion Dexamethasone can alleviate radiation induced pulmonary injury.Pulmonary function analysis combined with pathological observation of pulmonary tissues can effectively evaluate the efficacy of drugs in radiation induced lung injury.

Recognition of anxiolytic constituents from Juncus effusus based on constituents knock-out technique / 中草药

Objective: To clarify the main anxiolytic components from Juncus effusus. Methods: Silica gel column chromatography was used to extract the stem pith of J. effuses by 80% ethanol. The ethy lacetate extracts of J. effuses by ultraphonic extraction were separated to be phenanthrene constituents, such as dehydroeffusol, effusol, dehydrojuncusol, and juncusol. The phenanthrenes were knocked out and the target phenanthrene constituents and negative samples were prepared. The anxiolytic effects of the two separated fractions and the whole extract were evaluated by elevated plus-maze test in mice. Results: In the elevated plus-maze test, phenanthrene constituents and the whole ethylacetate extract could significantly improve the time and number of times of mice into the open arms, without difference in the intensity of action, but no anxiolytic activity was shown in the negative sample. Conclusion: Phenanthrene constituents are the main anxiolytic components in J. effusus. Other constituents in the ethylacetate extract of J. effusus do not influence the anxiolytic effect of phenanthrene constituents.

Pharmacometabolomics: Current Applications and Future Perspectives

Metabolomics, a novel "omics" platform, is a powerful tool for the discovery of clinically useful biomarkers and biochemical processes to improve diagnosis and therapy. Through the use of advanced analytical technologies, metabolomics enables the assessment of comprehensive metabolic profiles that are affected by both genotype and environmental factors. Recently, attention has been focused on the concept of pharmacometabolomics, an emerging field that is derived from metabolomics. Pharmacometabolomics is focused on the use of individual metabolic signatures for the prediction and evaluation of drug efficacy and safety, eventually accelerating clinical pharmacology toward personalized drug therapy.

Efficacy of Xiaoyao Pill in Regulating Menstruation / 中国药房

OBJECTIVE:To study the effect of Xiaoyao pill on animal uterus and to evaluate its efficacy in regulating menstruation to serve as theoretical basis for its clinical application.METHODS:The convulsion model of both ex vivo and in vivo uterus of rats was induced by oxytocin and the effects of Xiaoyao pill on the tension as well as the contraction frequency change of smooth muscle of uterus were observed.RESULTS:Xiaoyao pill could markedly inhibit the enhanced activities of either ex vivo or in vivo uterus of rats induced by oxytocin,inhibit the tension of smooth muscle and slow down the contraction frequency.CONCLUSION:Xiaoyao pill has satisfactory efficacy in regulating menstruation.

Jiangxi treatment is an effective way to increase clinical efficacy of drugs / 中华中医药杂志

The report expounds the importancr of 'jiangxi treatment' by discussing the meaning,the researches in the past dynasties and the collation of variety methods of 'jiangxi treatment'. It thinks that the 'jiangxi treatment'in TCM includes the right way to decoct drugs,the rational way to take drugs and the variety ways to 'jiangxi 'after taking drugs. Thus,it should be used selectively in clinical. And the report suggests that the 'jiangxi treatment' is a effective way to increase the clinical eff icacy of drugs.