Generation and characterization of a high-affinity chimeric anti-OX40 antibody with potent antitumor activity.

OX40 is a costimulatory molecule that belongs to the tumor necrosis factor receptor (TNFR) superfamily. OX40 agonist-based combinations are emerging as promising candidates for novel cancer immunotherapy. Clinical trials have shown that OX40 agonist antibodies could lead to better results in cancer patients.

Hepatic Induction of Fatty Acid Binding Protein 4 Plays a Pathogenic Role in Sepsis in Mice.

Sepsis is defined as the host's deleterious systemic inflammatory response to microbial infections. Herein, we report an essential role of the fatty acid binding protein 4 (FABP4; alias adipocyte protein 2 or aP2), a lipid-binding chaperone, in sepsis response. Bioinformatic analysis of the Gene Expression Omnibus data sets showed the level of FABP4 was higher in the nonsurvival sepsis patients' whole blood compared to the survival cohorts.

Oestrogen sulfotransferase ablation sensitizes mice to sepsis.

Sepsis is the host's deleterious systemic inflammatory response to microbial infections. Here we report an essential role for the oestrogen sulfotransferase (EST or SULT1E1), a conjugating enzyme that sulfonates and deactivates estrogens, in sepsis response. Both the caecal ligation and puncture (CLP) and lipopolysaccharide models of sepsis induce the expression of EST and compromise the activity of oestrogen, an anti-inflammatory hormone.

Serine 350 of human pregnane X receptor is crucial for its heterodimerization with retinoid X receptor alpha and transactivation of target genes in vitro and in vivo.

The human pregnane X receptor (hPXR), a member of the nuclear receptor superfamily, senses xenobiotics and controls the transcription of genes encoding drug-metabolizing enzymes and transporters. The regulation of hPXR's transcriptional activation of its target genes is important for xenobiotic detoxification and endobiotic metabolism, and hPXR dysregulation can cause various adverse drug effects. Studies have implicated the putative phosphorylation site serine 350 (Ser(350)) in regulating hPXR transcriptional activity, but the mechanism of regulation remains elusive.

[Expression of human glutathione S-transferase A1, P1 and T1 in Escherichia coli].

Objective: To construct the vectors of human glutathione S-transferase A1 (GSTA1), P1 (GSTP1), T1(GSTT1) genes and express in Escherichia coli (E. coli).

Methods: Human GSTA1, GSTP1 and GSTT1 gene whole length cDNAs were amplified by RT-PCR and then subcloned into pET-28a(+) vectors.

Nuclear receptors PXR and CAR: implications for drug metabolism regulation, pharmacogenomics and beyond.

Introduction: 'Orphan' nuclear receptors belong to the nuclear receptor (NR) superfamily of transcriptional factors. Binding of ligands to these receptors results in the recruitment of the co-activators, thereby regulating the expression of cognate target genes.

Areas Covered: This review discusses the transcriptional regulation of P450 genes by two major xenobiotic nuclear receptors, pregnane X receptor (PXR) and constitutive androstane receptor (CAR).

Estrogen sulfotransferase inhibits adipocyte differentiation.

The estrogen sulfotransferase (EST) is a phase II drug-metabolizing enzyme known to catalyze the sulfoconjugation of estrogens. EST is highly expressed in the white adipose tissue of male mice, but the role of EST in the development and function of adipocytes remains largely unknown. In this report, we showed that EST played an important role in adipocyte differentiation.

Identification of novel pregnane X receptor activators from traditional Chinese medicines.

Aim Of The Study: To investigate the ability of traditional Chinese medicines (TCMs) and their bioactive compounds to activate pregnane X receptor (PXR) signalling pathway.

Materials And Methods: We screened ethanol extracts of 28 commonly used TCMs for their capability to induce cytochrome P450 3A4 (CYP3A4) via PXR signalling pathway using a cell-based reporter gene assay combined with RT-PCR analysis. In addition, 34 bioactive components from these TCMs were examined for their potential to activate PXR.

Metabolism of ebracteolata compound B studied in vitro with human liver microsomes, HepG2 cells, and recombinant human enzymes.

Ebracteolata compound B (ECB) is one major active component of both Euphorbia ebracteolata and Euphorbia fischeriana, which have been extensively used as a tuberculocide in the Asian countries. The aim of our present study was to characterize ECB metabolism in human liver microsomes, HepG2 cells, and recombinant human enzymes. One monohydroxylation metabolite, determined by mass spectrometry to be 1-(2,4-dihydroxy-6-methoxy-3-methylphenyl)-2-hydroxyethanone, and one monoglucuronide, isolated and determined by hydrolysis with β-glucuronidase, mass spectrometry, and (1)H NMR to be 2-hydroxy-6-methoxy-3-methyl-acetophenone-4-O-β-glucuronide, were observed in human liver microsomal incubates in the presence of NADPH or UDP-glucuronic acid (UDPGA), respectively.

Development of enantioselective polyclonal antibodies to detect styrene oxide protein adducts.

Styrene has been reported to be pneumotoxic and hepatotoxic in humans and animals. Styrene oxide, a major reactive metabolite of styrene, has been found to form covalent binding with proteins, such as albumin and hemoglobin. Styrene oxide has two optical isomers and it was reported that the (R)-enantiomer was more toxic than the (S)-enantiomer.