Tissue-derived extracellular vesicles: Research progress from isolation to application.

Extracellular vesicles (EVs) are the structures that all cells release into the environment. They are separated by a lipid bilayer and contain the cellular components that release them. To date, most studies have been performed on EVs derived from cell supernatants or different body fluids, while the number of studies on EV isolation directly from tissues is still limited.

Discovery of pyrazolones as novel carboxylesterase 2 inhibitors that potently inhibit the adipogenesis in cells.

Carboxylesterase 2 (CES2) is one of the most important Phase I drug metabolizing enzymes in the carboxylesterase family. It plays crucial roles in the bioavailability of oral ester prodrugs and the therapeutic effect of some anticancer drugs such as irinotecan (CPT11) and capecitabine. In addition to the well-known roles of CES2 in xenobiotic metabolism, the enzyme also participates in endogenous metabolism and the production of lipids.

Clinical value of preoperative methylated septin 9 in Chinese colorectal cancer patients.

Background: The methylated septin 9 (mSEPT9) assay was the first blood-based test approved by the United States Food and Drug Administration as a colorectal screening test. However, the diagnostic and prognostic role of preoperative mSEPT9 for colorectal cancer (CRC) in Chinese patients is still unknown.

Aim: To improve the understanding of diagnostic and prognostic factors, serum mSEPT9 was detected in Chinese CRC patients.

[Inhibitory effect of flavonoids from Scutellariae Radix on human cytochrome P450 1A].

This study investigated the inhibitory effect of eight natural flavonoids in Chinese herb Scutellariae Radix on huamn cytochrome P450 1 A(CYP1 A), a key cancer chemo-preventive target. In this study, phenacetin was used as a probe substrate for CYP1 A, while human liver microsomes and recombinant human CYP1 A enzymes were used as enzyme sources. Liquid chromatography-tandem mass spectrometry was used to monitor the formation rates of acetaminophen, the O-deethylated metabolite of phenacetin.

Cytochrome P450 3A Enzymes Are Key Contributors for Hepatic Metabolism of Bufotalin, a Natural Constitute in Chinese Medicine Chansu.

Bufotalin (BFT), one of the naturally occurring bufodienolides, has multiple pharmacological and toxicological effects including antitumor activity and cardiotoxicity. This study aimed to character the metabolic pathway(s) of BFT and to identify the key drug metabolizing enzyme(s) responsible for hepatic metabolism of BFT in human, as well as to explore the related molecular mechanism of enzymatic selectivity. The major metabolite of BFT in human liver microsomes (HLMs) was fully identified as 5β-hydroxylbufotalin by LC-MS/MS and NMR techniques.

Comparative metabolism of DDAO benzoate in liver microsomes from various species.

DDAB (6,8-dichloro-9,9-dimethyl-7-oxo-7,9-dihydroacridin-2-yl benzoate) is a newly developed near-infrared fluorescent probe for human carboxylesterase 2 (hCE2), exhibiting high specificity and good reactivity for real-time monitoring the enzymatic activities of hCE2 in complex biological systems. In order to explore the applicability of DDAB in commonly used animal species, the interspecies difference in DDAB hydrolysis was carefully investigated by using liver microsomes from human and five experimental animals including mouse, rat, dog, minipig and monkey. Metabolite profiling demonstrated that DDAB hydrolysis could be catalyzed by all tested liver microsomes from different animals but displayed significant difference in the reaction rate.

The relationship between the variants in the 5'-untranslated regions of equine chorionic gonadotropin genes and serum equine chorionic gonadotropin levels.

Objective: An experiment was conducted to study the association between the single nucleotide polymorphisms (SNPs) in 5'-untranslated regions (5'-UTR) of equine chorionic gonadotropin (eCG) genes and the serum eCG levels.

Methods: SNPs in 5'-UTR of eCG genes were screened across 10 horse breeds, including 7 Chinese indigenous breeds and 3 imported breeds using iPLEX chemistry, and the association between the serum eCG levels of 174 pregnant Da'an mares and their serum eCG levels (determined with ELISA) was analyzed.

Results: Four SNPs were identified in the 5'-UTR of the eCGα gene, and one of them was unique in the indigenous breeds.

Association of CYP2C9, CYP2A6, ACSM2A, and CPT1A gene polymorphisms with adverse effects of valproic acid in Chinese patients with epilepsy.

Objective: To explore the influence of CYP2C9, CYP2A6, ACSM2A, CPT1A gene polymorphisms on valproic acid (VPA) and its role in metabolism-related liver dysfunction in order to guide the clinical safety and rational use of VPA.

Methods: One hundred two patients taking sodium valproate oral solution were genotyped. To assess the genotypes of relevant genes, the CYP2C9 gene was directly sequenced; for polymorphism classification, multiple Long-PCR electrophoresis was conducted for CYP2A6; and imLDR method was used for ACSM2A and CPT1A.

Effects of CYP3A4/5 and ABCB1 genetic polymorphisms on carbamazepine metabolism and transport in Chinese patients with epilepsy treated with carbamazepine in monotherapy and bitherapy.

Objective: To examine the effects of cytochrome P450 3A4 (CYP3A4), cytochrome P450 3A5 (CYP3A5) and ATP-binding cassette sub-family B member 1 (ABCB1) genetic polymorphisms on carbamazepine (CBZ) plasma concentrations in Chinese patients with epilepsy using CBZ as monotherapy and bitherapy with phenytoin (PHT), phenobarbital (PB), or valproic acid (VPA).

Methods: Eighty-eight Chinese patients with epilepsy were recruited from Xiangya Hospital Central South University, of whom 66 patients were placed in the CBZ monotherapy group, 10 patients were placed in the CBZ bitherapy group combined with one enzyme-inducing anti-seizure medications (PHT or PB), and 12 patients were placed in the CBZ bitherapy group combined with VPA. Carbamazepine and carbamazepine-10,11-epoxide (CBZ-E) plasma concentration of these patients were measured.

Mining chemodiversity from biodiversity: pharmacophylogeny of medicinal plants of Ranunculaceae.

This paper reports a pharmacophylogenetic study of a medicinal plant family, Ranunculaceae, investigating the correlations between their phylogeny, chemical constituents, and pharmaceutical properties. Phytochemical, ethnopharmacological, and pharmacological data were integrated in the context of the systematics and molecular phylogeny of the Ranunculaceae. The chemical components of this family included several representative metabolic groups: benzylisoquinoline alkaloids, ranunculin, triterpenoid saponin, and diterpene alkaloids, among others.

Novel pH-sensitive nanoformulated docetaxel as a potential therapeutic strategy for the treatment of cholangiocarcinoma.

Background: Cholangiocarcinoma (CC) is one of the fatal malignant neoplasms with poor prognosis. The traditional chemotherapy has been resistant to CC and does not improve the quality of life. The aim of the present study is to investigate the potential of chondroitin sulphate (CS)-histamine (HS) block copolymer micelles to improve the chemotherapeutic efficacy of docetaxel (DTX).

Macrolide therapy in cryptogenic organizing pneumonia: A case report and literature review.

Cryptogenic organizing pneumonia (COP) is a pulmonary disorder associated with nonspecific clinical presentations. The macrolide class of antimicrobial agents is widely used to treat infectious and inflammatory respiratory diseases in humans. The present study reports a case of COP that was effectively treated with azithromycin in combination with glucocorticoid.

C-reactive protein as a prognostic marker in chronic obstructive pulmonary disease.

The present study aimed to evaluate whether circulating C-reactive protein (CRP) levels are a biomarker of systemic inflammation and a significant predictor of future chronic obstructive pulmonary disease (COPD) outcome. During the study, 116 patients with stable COPD and 35 age- and gender-matched healthy subjects with normal pulmonary function were observed. Patient follow-up was also performed to evaluate the strength of the associations between CRP levels and future outcomes.

[Efficacy of lamivudine and adefovir de novo combination therapy or after mono-therapy in chronic hepatitis B patients].

To investigate the efficacy of 104 weeks of lamivudine (LAM) and adefovir (ADV) de novo combination therapy, as compared to optimized combination therapy administered after 48 weeks of treatment with lamivudine or adefovir mono-therapy, in chronic hepatitis B (CHB) patients. A total of 174 patients with CHB were equally divided among three treatment groups: LAM mono-therapy; ADV mono-therapy; and LAM + ADV combination therapy. The patients in the LAM + ADV group were treated with LAM plus ADV for 104 consecutive weeks.

Excision repair cross complementation group 1 polymorphisms and lung cancer risk: a meta-analysis.

Background: Several studies have evaluated the association between polymorphisms of encoding excision repair cross complementation group 1 (ERCC1) enzyme and lung cancer risk in diverse populations but with conflicting results. By pooling the relatively small samples in each study, it is possible to perform a meta-analysis of the evidence by rigorous methods.

Methods: Embase, Ovid, Medline and Chinese National Knowledge Infrastructure were searched.

Polymorphism of vascular endothelial growth factor -2578C/A with cancer risk: evidence from 11263 subjects.

Published data on the association between vascular endothelial growth factor (VEGF) -2578C/A polymorphism and cancer risk is inconclusive. To derive a more precise estimation of association between VEGF -2578C/A polymorphism and the risk of cancer, we performed a meta-analysis of 5415 cancer cases and 5848 controls from 16 published case-control studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association.