Inhibition of Human Sulfotransferases by Phthalate Monoesters.

Objective: This study aimed to investigate the inhibition of human important phase II metabolic enzyme sulfotransferases (SULTs) by phthalate monoesters, which are important metabolites of phthalate esters (PAEs). Method: Recombinant SULT-catalyzed metabolism of p-nitrophenol (PNP) was employed as the probe reactions of SULTs to investigate the inhibition of 8 kinds of phthalate monoesters towards SULT isoforms. An in vitro incubation system was utilized for preliminary screening, and 100 µM of phthalate monoesters was used. Inhibition kinetics were carried out to determine the inhibition of SULTs by phthalate monoesters. Result: Multiple phthalate monoesters have been demonstrated to exert strong inhibition potential towards SULT1A1, SULT1B1, and SULT1E1, and no significant inhibition of phthalate monoesters towards SULT1A3 was found. The activity of SULT1A1 was strongly inhibited by mono-hexyl phthalate (MHP), mono-octyl phthalate (MOP), mono-benzyl phthalate (MBZP), and mono-ethylhexyl phthalate (MEHP). Monobutyl phthalate (MBP), MHP, MOP, mono-cyclohexyl phthalate (MCHP), and MEHP significantly inhibited the activity of SULT1B1. MHP, MOP, and MEHP significantly inhibited the activity of SULT1E1. MOP was chosen as the representative phthalate monoester to determine the inhibition kinetic parameters (Ki) towards SULT1B1 and SULT1E1. The inhibition kinetic parameters (Ki) were calculated to be 2.23 µM for MOP-SULT1B1 and 5.54 µM for MOP-SULT1E1. In silico docking method was utilized to understand the inhibition mechanism of SULT1B1 by phthalate monoesters. Conclusions: All these information will be beneficial for understanding the risk of phthalate monoester exposure from a new perspective.

Hydroxylated polychlorinated biphenyls (OH-PCBs) exert strong inhibitory effects towards human carboxylesterases (CESs).

Polychlorinated biphenyls (PCBs) have been reported to pose a severe risk towards human health, and hydroxylated polychlorinated biphenyls (OH-PCBs) were potential substances basis for PCBs' toxicity. This study aims to determine the inhibition of OH-PCBs towards human carboxylesterases (CESs), including CES1 and CES2. For phenotypic analysis of CES1 and CES2 activity, we used the hydrolysis metabolism of 2-(2-benzoyl3-methoxyphenyl) benzothiazole (BMBT) and fluorescein diacetate (FD) catalyzed by human liver microsomes (HLMs) as the probe reactions. Preliminary inhibition screening showed that the inhibition potential of OH-PCBs towards CES1 and CES2 increased with the increased numbers of chlorine atoms in OH-PCBs. Both 2'-OH-PCB61 and 2'-OH-PCB65 showed concentration-dependent inhibition towards both CES1 and CES2. Lineweaver-Burk plots showed that 2'-OH-PCB61 and 2'-OH-PCB65 exerted non-competitive inhibition towards CES1 and competitive inhibition towards CES2. The inhibition kinetics parameters (Ki) were 6.8 µM and 7.0 µM for 2'-OH-PCB61 and 2'-OH-PCB65 towards CES1, respectively. The inhibition kinetics parameters (Ki) were 1.4 µM and 1.0 µM for 2'-OH-PCB61 and 2'-OH-PCB65 towards CES2, respectively. In silico docking methods elucidate the contribution of hydrogen bonds and hydrophobic contacts towards the binding of 2'-OH-PCB61 and 2'-OH-PCB65 with CES1 and CES2. All these results will provide a new perspective for elucidation of toxicity mechanism of PCBs and OH-PCBs.

Meta-analysis of randomized trials comparing the effectiveness of on-pump and off-pump coronary artery bypass.

BACKGROUND: The growing enthusiasm for coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) is emerging, but the role of off-pump coronary artery bypass (OPCAB) in clinical practice remains controversial. The purpose of this study was to assess differences in the incidences of stroke, atrial fibrillation (AF), and myocardial infarction (MI) between OPCAB and conventional coronary artery bypass grafting (CCABG) by meta-analyses of randomized clinical trials. METHODS: A literature search for the period before March 2010 supplemented with manual bibliographic review was performed for all Chinese or English publications in Medline, the Science Citation Index Expanded, the Cochrane Central Register of Controlled Trials (CENTRAL) and CBMdisc. A systematic overview (meta-analyses) of randomized clinical trials was conducted to evaluate the differences between OPCAB and CCABG in the incidences of stroke, AF, and MI. The meta-analysis was performed using RevMan 5 software. RESULTS: Forty-three randomized clinical trials were selected for meta-analysis after screening a total of 356 references, with 8104 patients in the OPCAB group and 8724 cases in the CCABG group. The meta-analyses of these trials showed no significant difference between OPCAB and CCABG in the incidences of stroke (odds ratio (OR) = 0.80, 95% confidence interval (CI) = 0.52 - 1.22, P = 0.30) and MI (OR = 0.73, 95%CI = 0.52 - 1.02, P = 0.06). However, we found a significantly reduced risk of AF (OR = 0.65, 95%CI = 0.52 - 0.82, P = 0.0002) in off-pump patients. CONCLUSIONS: Our meta-analyses suggest that OPCAB reduces the risk of postoperative AF compared with CCABG, but there is no significant difference in the incidences of stroke and MI between OPCAB and CCABG.

Comparison of compensatory sweating and quality of life following thoracic sympathetic block for palmar hyperhidrosis: electrocautery hook versus titanium clip.

BACKGROUND: Video-assisted thoracic sympathetic block is an effective, safe, and minimally invasive method for treatment of primary hyperhidrosis. The purpose of this study was to decide which one of using electrocautery hook and titanium clip is the appropriate procedure for primary palmar hyperhidrosis by assessing the compensatory sweating (CS) and quality of life (QOL) of patients after sympathetic block. METHODS: Between October 2007 to August 2010, 120 patients with primary palmar hyperhidrosis were randomly divided into two groups, electrocautery hook group (60 patients) and titanium clip group (60 patients). All patients were treated by sympathetic block at T4 level. The CS was graded based on severity and location; the QOL was classified to 5 different levels based upon the summed total scores (range from 20 to 100) before and after surgery. The variables were compared. RESULTS: The postoperative follow-up period was 2 months. All patients were cured. Three patients in electrocautery hook group and 1 patient in titanium clip group had a unilateral pneumothorax on chest X-ray, but none of them was necessary to have chest drainage. Neither perioperative mortality nor serious complications such as cardiac arrhythmia or arrest were observed during the operation. No bradycardia or Horner's syndrome occured. CS was not more common in patients in titanium clip group than in those in electrocautery hook group (P = 0.001). Moderate and severe CS was few in all patients, and there was no significant difference between two groups (P = 0.193). Most of the patients feel a notable improvement of the the QOL; nevertheless, there was no significant difference between the groups (P = 0.588). CONCLUSIONS: Both electrocautery hook and titanium clip used for sympathetic block at the T4 level are effective, safe, and minimally invasive for palmar hyperhidrosis. Because of the lower severity of CS and the similar improvements in the QOL after operation, we prefer to use of titanium clip for treating palmar hyperhidrosis.

XAF1 as a prognostic biomarker and therapeutic target in squamous cell lung cancer.

BACKGROUND: X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is a new tumor suppressor. Low expression of XAF1 is associated with poor prognosis of human cancers. However, the effect of XAF1 on lung cancer remains unknown. In this study, we investigated the expression of XAF1 and its role in squamous cell lung cancer. METHODS: Cancer tissues, cancer adjacent tissues and normal lung tissues were collected from 51 cases of squamous cell lung cancer. The expression of XAF1 mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR). The expression of XAF1 protein was determined by Western blotting and immunohistochemical staining. Ad5/F35-XAF1 virus was generated. Cell proliferation and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and flow cytometry (FACS), respectively. RESULTS: The levels of XAF1 protein and mRNA in cancer tissues were significantly lower than those in cancer adjacent and normal lung tissues (P < 0.05). The low expression of XAF1 was associated with tumor grade, disease stage, differentiation status and lymph node metastasis in squamous cell lung cancer patients. The restoration of XAF1 expression mediated by Ad5/F35-XAF1 virus significantly inhibited cell proliferation and induced apoptosis in a dose- and time-dependent manner. CONCLUSION: XAF1 is a valuable prognostic marker in squamous cell lung cancer and may be a potential candidate gene for lung cancer therapy.