[Intestinal absorption and renal excretion mediated by transporters and the relationship with drug-drug interaction].

Drug-drug interaction (DDI) is referred as the changes of physical and chemical properties, as well as the pharmacokinetics or pharmacodynamics of drugs administered simultaneously or consecutively. The clinical results for drug-drug interaction could be divided into good clinical efficacy and adverse interaction. With the kinds of drugs increasing every year, new drug resistances spring up frequently.

Effects of JBP485 on the expression and function of PEPT1 in indomethacin-induced intestinal injury in rats and damage in Caco-2 cells.

To investigate the effect of JBP485 (an anti-inflammatory dipeptide) on PEPT1 in indomethacin-induced intestinal injury in rats and damage in Caco-2 cells, the activity and expression of PEPT1 were examined. The effects of treatment with indomethacin and co-treatment with JBP485 were examined in terms of intestinal histological changes, MDA and MPO levels in rats; as well as LDH-release and oxidative stress in Caco-2 cells. Uptake of glycylsarcosine (Gly-Sar) by PEPT1 was determined by in vivo, in vitro and in situ studies.

Uptake, transport and regulation of JBP485 by PEPT1 in vitro and in vivo.

Cyclo-trans-4-L-hydroxyprolyl-L-serine (JBP485) is a dipeptide with anti-hepatitis activity that has been chemically synthesized. Previous experiments in rats showed that JBP485 was well absorbed by the intestine after oral administration. The human peptide transporter (PEPT1) is expressed in the intestine and recognizes compounds such as dipeptides and tripeptides.

Amelioration effects of berberine on diabetic microendothelial injury model by the combination of high glucose and advanced glycation end products in vitro.

Microvascular complications are much earlier and common in diabetes. Advanced glycation end products (AGEs), together with high glucose, play a key role in the endothelial dysfunction of diabetic vascular complications. So it is of more significance to expedite the therapies to block the formation and/or the effects of AGEs.

Inhibition of Rho kinase by fasudil hydrochloride attenuates lung injury induced by intestinal ischemia and reperfusion.

Aim: The aim of this study is to evaluate the role of Rho-kinase in the pathogenesis of lung injury induced by intestinal ischemia/reperfusion (I/R) and the preconditioning effects of fasudil hydrochloride. The novel therapeutic approach of using Rho-kinase inhibitors in the treatment of intestinal I/R is introduced.

Methods: Sprague-Dawley (SD) rats were divided into 4 groups: intestinal I/R group, two fasudil pretreatment groups (7.

Pharmacokinetics and mechanism of intestinal absorption of JBP485 in rats.

To investigate the pharmacokinetics and mechanism of intestinal absorption of JBP485 in rats, the pharmacokinetics of JBP485 were investigated in vivo both intravenously and orally. The effects of glycylsarcosine (Gly-Sar) on the uptake and transepithelial transport of JBP485 were examined in everted intestinal sacs, in situ jejunal perfusion, Caco-2 cells and PEPT1 transfected Hela cells. The gastrointestinal absorption of JBP485 was rapid.

Molecular mechanisms of biliary excretion of cefditoren and the effects of cefditoren on the expression levels of hepatic transporters.

Cefditoren, a third generation cephalosporin antibiotics, has been used in clinics extensively. Previous results have indicated that cefditoren is excreted into bile as unchanged form. To investigate whether canalicular membrane transporters of hepatocytes were involved in the biliary excretion of cefditoren, we examined the hepatobiliary disposition of cefditoren using probenecid, novobiocin and verapamil as inhibitors of Mrp2, Bcrp and P-gp respectively in perfused rat livers.

Protective effect of carnosol on lung injury induced by intestinal ischemia/reperfusion.

Purpose: Carnosol is a phenolic diterpene that has potent antioxidant and anti-inflammatory activities. The purpose of this study was to investigate the preconditioning effects of carnosol on lung injury induced by intestinal ischemia/reperfusion (II/R).

Methods: Rats were divided into control, II/R, and carnosol groups.

Cytotoxicity of berberine on human cervical carcinoma HeLa cells through mitochondria, death receptor and MAPK pathways, and in-silico drug-target prediction.

Berberine, a natural product, has been widely used to treat hyperlipoidemia and intestinal diseases. In the present paper, berberine showed a significant anti-proliferative effect to human cervical carcinoma HeLa cells confirmed by 3-(4,5)-dimethyl-thiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT), flow cytometry analysis (FCM) and so on. The methods including western blotting, radioimmunity assay (RIA), reverse transcription-polymerase chain reaction (RT-PCR) were used to investigate protein and mRNA expressions.

[Composition and seasonal variations of carbon isotopes in aerosols of Lhasa, Tibet].

A total of 30 samples of total suspended particles were collected at an urban site in western of Lhasa city, Tibet from August 2006 to July 2007 for investigating carbonaceous aerosol features. 14C was taken as a reference to quantitatively distinguish the fossil and biogenic-derived origins along with the characteristics of seasonal variations of all carbonaceous materials in Lhasa are discussed. The results showed that the f(c) values in Lhasa ranged from 0.

Nanoparticles of Poly(Lactide-Co-Glycolide)-d-a-Tocopheryl Polyethylene Glycol 1000 Succinate Random Copolymer for Cancer Treatment.

Cancer is the leading cause of death worldwide. Nanomaterials and nanotechnologies could provide potential solutions. In this research, a novel biodegradable poly(lactide-co-glycolide)-d-a-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) random copolymer was synthesized from lactide, glycolide and d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS) by ring-opening polymerization using stannous octoate as catalyst.

Efficient isolation and purification of five products from microbial biotransformation of cinobufagin by high-speed counter-current chromatography.

An efficient separation method of using high-speed counter-current chromatography was successfully established to directly purify cytotoxic transformed products of cinobufagin by Cordyceps militaris. The two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (4:6:3:4, v/v) was used in high-speed counter-current chromatography. A total of 9 mg of 4beta,12alpha-dihydroxyl-cinobufagin (1), 15 mg of 12beta-hydroxyl-cinobufagin (2), 8 mg of 5beta-hydroxyl-cinobufagin (3), 12 mg of deacetylcinobufagin (4) and 6 mg of 3-keto-cinobufagin (5) were obtained in a one-step separation from 400 mg of the crude extract with purity of 98.

Pharmacokinetic interaction between JBP485 and cephalexin in rats.

The purpose of this study was to investigate the pharmacokinetic mechanism of interaction between JBP485 (cyclo-trans-4-L-hydroxyprolyl-L-serine, a dipeptide) and cephalexin when they were coadministered in rats. The plasma concentrations of JBP485 and cephalexin were both decreased significantly after oral combination, but little difference was observed after simultaneous intravenous administration of the two agents, suggesting that the interaction target localized in the intestine during the absorption process. The uptake in everted intestinal sacs and absorption in jejunal perfusions of JBP485 and cephalexin were dramatically reduced after drug combination.

A novel mifepristone-loaded implant for long-term treatment of endometriosis: in vitro and in vivo studies.

The objective of this study was to prepare a novel mifepristone-loaded PCL/Pluronic F68 implant to achieve long-term treatment of endometriosis. PCL/Pluronic F68 compound (90/10, w/w) with viscosity average molecular weight of 65,000 was successfully synthesized. The end-capped Pluronic F68 was incorporated in PCL matrixes as molecular dispersion without forming a copolymer.

A novel paclitaxel-loaded poly(epsilon-caprolactone)/Poloxamer 188 blend nanoparticle overcoming multidrug resistance for cancer treatment.

Multidrug resistance (MDR) of tumor cells is a major obstacle to the success of cancer chemotherapy. Poloxamers have been used in cancer therapy to overcome MDR. The objective of this research is to test the feasibility of paclitaxel-loaded poly(epsilon-caprolactone)/Poloxamer 188 (PCL/Poloxamer 188) nanoparticles to overcome MDR in a paclitaxel-resistant human breast cancer cell line.

Prophylaxis with carnosol attenuates liver injury induced by intestinal ischemia/reperfusion.

Aim: To investigate the possible protective effects of carnosol on liver injury induced by intestinal ischemia reperfusion (I/R).

Methods: Rats were divided randomly into three experimental groups: sham, intestinal I/R and carnosol treatment (n = 18 each). The intestinal I/R model was established by clamping the superior mesenteric artery for 1 h.

Protective effect of JBP485 on concanavalin A-induced liver injury in mice.

Objectives: Cyclo-trans-4-l-hydroxyprolyl-l-serine (JBP485) was first isolated from Laennec (hydrolysate of human placenta). We thought it valuable to clarify the anti-hepatitis molecular mechanism of JBP485 to develop a new oral anti-hepatitis drug.

Methods: We investigated the hepatoprotective effect of JBP485 on immune-mediated, concanavalin A (Con A)-induced liver injury in mice.

Radiocarbon dating of charcoal and bone collagen associated with early pottery at Yuchanyan Cave, Hunan Province, China.

Yuchanyan Cave in Daoxian County, Hunan Province (People's Republic of China), yielded fragmentary remains of 2 or more ceramic vessels, in addition to large amounts of ash, a rich animal bone assemblage, cobble and flake artifacts, bone tools, and shell tools. The artifacts indicate that the cave was a Late Paleolithic foragers' camp. Here we report on the radiocarbon ages of the sediments based on analyses of charcoal and bone collagen.

PEPT1 involved in the uptake and transepithelial transport of cefditoren in vivo and in vitro.

Cefditoren is a third-generation cephalosporin developed by Meiji Seika Kaisha Ltd. Many beta-lactam antibiotics are transported by the H+/peptide symporters PEPT1 and PEPT2 that are preferentially expressed in the luminal membrane of the intestine and kidney, respectively. In this study, we employed everted small intestinal preparations, in situ jejunal perfusion, and Caco-2 cells as models to determine the effects of glycylsarcosine (Gly-Sar) and clonidine on uptake and transport of cefditoren.

Protective effect of tea polyphenols against paracetamol-induced hepatotoxicity in mice is significantly correlated with cytochrome P450 suppression.

Aim: To investigate the hepatoprotective activity of tea polyphenols (TP) and its relation with cytochrome P450 (CYP450) expression in mice.

Methods: Hepatic CYP450 and CYPb(5) levels were measured by UV-spectrophotometry in mice 2 d after intraperitoneal TP (25, 50 and 100 mg/kg per day). Then the mice were intragastricly pre-treated with TP (100, 200 and 400 mg/kg per day) for six days before paracetamol (1000 mg/kg) was given.

In vivo inhibition of S180 tumors by the synergistic effect of the Chinese medicinal herbs Coptis chinensis and Evodia rutaecarpa.

The aim of the present paper was to investigate the synergistic effect and mechanism of anticancer activity of Zuojinwan ( ZJW) comprising Coptis chinensis Franch ( HL) and Evodia rutaecarpa (Juss.) Benth ( WZY) at a ratio of 6 : 1 (w/w). In vivo anticancer activity testing was carried out by inhibiting the growth of S180 tumor.

Microbial transformation of bufotalin by Alternaria alternata AS 3.4578.

The microbial transformation of a cytotoxic bufadienolide, bufotalin (1), was carried out. Three transformed products from 1 by Alternaria alternata were isolated. Their structures were characterized as 3-keto-bufotalin (2), 12 beta-hydroxyl-bufotalin (3), and 3-keto-12 beta-hydroxyl-bufotalin (4) based on the extensive NMR studies.

Characterization of the enhancing effect of protamine on the proliferative activity of hepatocyte growth factor in rat hepatocytes.

Purpose: The aim of the present study was to characterize the mechanism of the stimulatory effect of protamine on HGF activity.

Methods: The enhancing effects of protamine on the proliferative activity of HGF were investigated in vivo, in primary cultured rat hepatocytes, and in perfused rat liver.

Results: In alpha-naphthylisothiocyanate-intoxicated rats, pretreatment with protamine increased HGF-induced autophosphorylation of the HGF receptor in liver.

(E)-N'-(5-Chloro-2-hydroxy-benzyl-idene)-3,5-dihydroxy-benzohydrazide mono-hydrate.

In the title compound, C(14)H(11)ClN(2)O(4)·H(2)O, the dihedral angle between the two benzene rings is 8.5 (2)° and an intra-molecular O-H⋯N hydrogen bond is observed in the Schiff base mol-ecule. In the crystal structure, the water mol-ecule accepts an N-H⋯O hydrogen bond and makes O-H⋯O hydrogen bonds to two further Schiff base mol-ecules.

A Novel Docetaxel-Loaded Poly (ε-Caprolactone)/Pluronic F68 Nanoparticle Overcoming Multidrug Resistance for Breast Cancer Treatment.

Multidrug resistance (MDR) in tumor cells is a significant obstacle to the success of chemotherapy in many cancers. The purpose of this research is to test the possibility of docetaxel-loaded poly (ε-caprolactone)/Pluronic F68 (PCL/Pluronic F68) nanoparticles to overcome MDR in docetaxel-resistance human breast cancer cell line. Docetaxel-loaded nanoparticles were prepared by modified solvent displacement method using commercial PCL and self-synthesized PCL/Pluronic F68, respectively.