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.

Objective To examine the interfractional dosimetric variations among inverse three-dimensional (3D) plan, forward 3D plan, and two-dimensional (2D) plan of intracavitary brachytherapy for cervical cancer, and to discuss the risk of implementing the interval plan on different implantation applicators at short time intervals.Methods Twenty-five groups of CT-guided intracavitary brachytherapy (two consecutive radiations at ≤4 d apart) plans from 11 cervical cancer patients who received radical radiation therapy in our hospital were reviewed and compared.The dwelling location and time of the first intracavitary brachytherapy plan (Plan-1) were simulated on the CT image of the second intracavitary brachytherapy to form Plan-1-S.The target coverage indices and D 2 cc of organs at risk (OARs) of Plan-1-S and Plan 2(actual plan of the second intracavitary brachytherapy) under the three planning modes were recorded and compared using the paired t-test, Wilcoxon signed rank test, and ANOVA.Results The D90, D100, and V100 of high-risk CTV were significantly lower in Plan-1-S created under the inverse mode in the actual plan (-9.11±13.46%,-13.16±18.79%, and-7.80±13.34%, P=0.002, 0.002, and 0.005, respectively).D90, D100, and V100 of the interval plan had the greatest reduction under the inverse mode (76%, 80%, and 76%, respectively).The maximum reductions in D90, D100, and V100 were 332.14 cGy (2D), 244.12 cGy (forward), and 41.76%(inverse).OAR overdose occurred most frequently under the forward mode;the rates of D90, D100, and V100 reductions accompanied by one OAR overdose were 29.41%, 37.50%, and 25.00%, and the rates of D90, D100, and V100 reductions by two OAR overdoses were 5.88%, 12.50%, and 6.25%,respectively.Overdose occurred most frequently in the small intestine (36%).Comparison of the three planning modes showed that the inverse plan had a greater reduction in each target coverage index than the 2D plan.Conclusions The simulated interval plan can significantly reduce target coverage and increase the risk of OAR overdose regardless of the planning mode and the short time intervals, and is therefore not recommended for clinical application.

Aims To study the role of NGF/Trk A sig-naling pathway in Memantine ( MEM) improving APP/PS1 transgenic mice cognitive deficits and to explore its possible mechanisms. Methods Cognitive perform-ance was assessed by Morris water maze( MWM) , pas-sive avoidance test( PAT) and locomotivity test. Aβ1-42 protein levels were determined by immunohistochemis-try. The activities of AChE and ChAT were also exam-ined by ELISA and colorimetry. Western blot was used to detect the expression levels of NGF and its receptor TrkA and the downstream ERK pathway. Results MEM treatment significantly ameliorated the cognitive deficits, dramatically reduced the Aβ1-42 overexpres-sion. MEM increased the activity of choline acetyl-transferase( ChAT) , while decreased that of acetylcho-line esterase( AChE) . Moreover, MEM activiated NGF signaling by increasing the phosphorylation of TrkA fol-lowing the increased phosphorylation of c-Raf, ERK1/2 and downstream effector CREB after MEM treatment. Conclusion MEM treatment may activate the NGF/TrkA signaling in APP/PS1 mice to reduce amyloidosis and cognitive deficits.