With the wide application of Chinese herbal medicine, herb-drug interaction (HDI) has become increasingly prominent. Metabolic enzymes and transporters are the main targets of HDI, because the changes in expression and function of enzymes and transporters can influence the disposition of drugs. Metabolic enzymes are responsible for the metabolic clearance of drugs, including cytochrome P450 (CYP), UDP-glucuronyl transferase (UGT) and sulfotransferases (SULT); transporters widely expressed in the intestine, kidney, liver and brain are involved in the oral absorption, distribution and excretion of drugs. Pueraria, ginkgo, ginseng, St. John's wort and other Chinese herbal medicine often induce a HDI because those herbal medicines combined with chemical medicine are widely used in clinic. The components of herb medicines mentioned above are prone to interact with enzymes and transporters, which often induce a HDI. This paper reviews the advances in the study of enzymes and transporters-mediated pharmacokinetic mechanism of HDI.
Biological Products ; Biological Transport ; Cytochrome P-450 Enzyme System ; physiology ; Drugs, Chinese Herbal ; Ginkgo biloba ; Glucuronosyltransferase ; physiology ; Herb-Drug Interactions ; Humans ; Membrane Transport Proteins ; physiology ; Oxidation-Reduction ; Panax ; Plants, Medicinal ; Pueraria

Drug transporters are functional membrane proteins located in various tissues, which play vital roles in absorption, distribution and excretion of drugs, especially those located in intestine, liver and kidney. The expression and function of transporters will alter in diseases state, which affects the therapeutic effects of drugs by altering their pharmacokinetics. In this review, we focus on the alterations in related transporters and the effect on the drug therapy in common intestinal diseases, liver diseases, kidney diseases and diabetes mellitus.
Biological Transport ; Diabetes Mellitus ; pathology ; Humans ; Intestinal Diseases ; pathology ; Intestines ; Kidney ; Kidney Diseases ; pathology ; Liver ; Liver Diseases ; pathology ; Membrane Transport Proteins

Multidrug regimens and corresponding drug interactions cause many adverse reactions and treatment failures. Drug efflux transporters: P-glycoprotein (P-gp), multidrug resistance associated protein (MRP) and breast cancer resistance protein (BCRP) in conjunction with metabolizing enzymes (cytochrome P450, CYP450) are major factors in such interaction. In recent years, a large number of studies have shown that P-gp plays a role in the oxidative metabolism of its substrates that are also substrates of CYP3A4. Combined actions of P-gp and CYP3A could account in some part for the low oral bioavailability determined for many of these dual substrates. P-gp along with efflux transporters (MRP and BCRP) having overlapping substrate specificity plays critical role in drug disposition. The relationship between MRP or BCRP and CYP3A is similar to that between P-gp and CYP3A. In this paper, we summarize the classification of efflux transporters, the main metabolizing enzymes CYP3A, clinical significance interactions mediated by efflux transporters and CYP450 enzymes and in vitro studies.
ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; metabolism ; ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Biological Availability ; Cytochrome P-450 CYP3A ; metabolism ; Cytochrome P-450 Enzyme System ; metabolism ; Drug Interactions ; Humans ; Multidrug Resistance-Associated Proteins ; metabolism ; Neoplasm Proteins ; metabolism ; Substrate Specificity

Objective To explore diagnosis and prognosis of heart failure in children by measuring brain natriurettic peptide(BNP) and cardiac troponin I(CTnI).Methods Forty-one children subjects with heart failure were chosen,and then they were divided into three stages,early stage of heart failure,stage of heart failure and stage of recovery according to the ROSS cardiac function score method.In contrast with the former group,41 healthy children were chosen as control group.BNP and CTnI levels of blood plasma were analyzed by radioimmunoassay(RIA) and chemiluminescent immunoassay(CLIA) respectively,the relationship between the BNP level of blood plasma and prognosis of CHF group was analyzed.Results At early stage of heart failure,BNP and CTnI levels began to rise.They amount to highest peaks at stage of heart failure and went down at stage of recovery.But they were still higher than those of control group(P

Metformin is the most commonly prescibed drug for type 2 diabetes mellitus as it is inexpensive, safe, and efficient in ameliorating hyperglycemia and hyperinsulinemia. Numerous epidemiological studies indicate that diabetic population is not only at increased risk of cardiovascular complications, but also at substantially higher risk of many forms of malignancies. Meanwhile, epidemiological and clinical observation studies have shown that metformin use reduces risk of cancer in patients with type 2 diabetes mellitus and improves prognosis and survival rate of the cancer patients. Furthermore, metformin has been used for cancer therapy in clinical trials. Thus, metformin is emerging as a new cancer therapy or adjuvant anticancer drugs. This review summarizes recent progress in studies of metformin use and its molecular mechanism.
Antineoplastic Agents ; therapeutic use ; Diabetes Mellitus, Type 2 ; Humans ; Hyperglycemia ; Metformin ; therapeutic use ; Neoplasms ; drug therapy

Objective To evaluate the effects of Achilles tendon lengthening on talipes equinus in children with spastic cerebral palsy. Methods From December, 2013 to June, 2014, seventeen spastic cerebral palsy children with talipes equinus (34 feet) received Achilles ten-don lengthening. Ankle dorsiflexion range of motion (ROM) and surface electromyography from tibialis anterior and medial head of gastroc-nemius were measured before and 8 to 12 months after operation, respectively. ROM of passive and active dorsiflexion, root mean square (RMS) of tibia muscle group and co-contraction ratio (CR) when standing were compared. Results The ROM of ankle passive and active dorsiflexion increased (Z>4.867, P<0.001), while the RMS of gastrocnemius muscle decreased when ankle passively dorsiflex (t=4.31, P<0.001). RMS of tibialis anterior and gastrocnemius muscle changed little when standing (Z<1.291, P>0.05), while CR reduced (t=2.38, P<0.05). Conclusion Achilles tendon lengthening can improve the coordination of tibia muscle group to increase the ROM of ankle for chil-dren with talipes equinus after spastic cerebral palsy.

Objective To assess the diagnostic yields of clinical chromosomal microarray ( CMA) testing for patients with neurodevelopmetal disorders ( NDD) , and to characterize the spectrum of pathogenic copy number variation(CNV) in NDD.Methods The study was a cross-sectional study.NDD patients from Shanghai Children′s Medical Center ( SCMC ) from April 2014 to April 2015 were recruited.DNA samples from SCMC cohort were tested on Affymetrix Cytoscan Dx microarray platform.The diagnostic yields of CMA testing were further assessed for the whole NDD cohort and each subgroup.Results A genome-wide genotype-phenotype analysis on a total of 107 NDD cases with CMA testing was conducted.Based on the SCMC clinical cohort, the overall diagnostic yield of CMA testing for NDD patients was 20.6%(22/107). Excluding one case with chromosomal aneuploid, the frequency of non-polymorphic CNVs of the rest NDD cases were 25.5%(27/106).The diagnostic yield for developmental delay/intellectual disorder(DD/ID) and autism spectrum disorder(ASD)were 26.3% (15/57) and 10.2%(4/39) respectively.DD/ID was more likely to be associated with CNV than ASD and attention-deficit/hyperactivity disorder(ADHD).Five recurrent genomic loci were significantly enriched in patients including 1q21.1-q21.2, 15q11.2-q13.1, 22q11.2, 7q11.23 and 17q11.2.Conclusion CNV is an important pathogenesis in NDD.

Adult ; Enzyme-Linked Immunosorbent Assay ; Female ; HSP70 Heat-Shock Proteins ; blood ; Humans ; Lead ; toxicity ; Male ; Occupational Exposure

(3S)-Linalool synthase (LIS) is a key enzyme involved in the monoterpene biosynthetic pathway. Based on our previous transcriptome study, the expression level of LIS gene was exceedingly related to glycyrrhizic acid (GA) biosynthesis. Therefore, we used hairy root culturing to further investigate the effect of LIS on the GA biosynthesis. A LIS gene (GenBank accession number: MZ169552) was cloned from Glycyrrhiza uralensis. The plant binary overexpression vector pCA-LIS was constructed by gene fusion. G. uralensis hairy roots overexpressing LIS were induced by the Agrobacterium rhizogenes ATCC15834. The expression levels of LIS were analyzed by real-time quantitative PCR (RT-qPCR) and the contents of GA in hairy root lines were determined by UPLC. It was found that in the hairy root lines overexpressing LIS, the expression levels of LIS were significantly higher than that in the wild type, while the contents of GA were remarkably lower than those in the wild type and negative control. These findings indicate that the expression level of LIS is negatively correlated with the accumulation of GA. In this study, LIS was cloned from G. uralensis for the first time and the negative regulatory effect of LIS on GA biosynthesis was confirmed by reverse genetics. This work provides support for further improvement of the molecular regulatory network of GA biosynthesis in G. uralensis.