BRM promoter insertion polymorphisms increase the risk of cancer: A meta-analysis.

INTRODUCTION: Many studies have suggested that the BRM promoter insertion polymorphisms might be associated with susceptibility to many different types of cancer. However, previous studies reported contradictory results. This current meta-analysis was performed to address this issue. EVIDENCE ACQUISITION: A comprehensive search was conducted in multiple databases, including PubMed, Embase and China National Knowledge Infrastructure (CNKI). We collected relevant articles to explore the association between the BRM insertion polymorphisms and susceptibility of cancers. EVIDENCE SYNTHESIS: For the BRM-741 polymorphism, a total of 2901 cases and 3667 controls from 6 studies were included. For the BRM-1321 polymorphism, a total of 2899 cases and 3769 controls from 6 studies were included. Overall, a significant difference was observed in BRM-741 (OR 0.81; 95%CI 0.68, 0.96; P=0.02) and BRM-1321 (OR 0.76; 95%CI 0.66, 0.88; P<0.01) for allele frequency (D versus I). In the subgroup analysis, for the BRM-741, a significant difference was observed in Asian (OR 0.88; 95%CI 0.78, 0.99; P=0.03) for D versus I. Similarly, for the BRM-1321, a significant difference was observed in Asian (OR 0.43; 95%CI 0.32, 0.58; P<0.001) and Caucasian (OR 0.74; 95%CI 0.62, 0.88; P<0.001) for DD versus II. CONCLUSIONS: BRM-741 and BRM-1321 insertion polymorphisms are associated with susceptibility to cancer. Further studies are warranted to verify the clinical utility of BRM promoter insertion polymorphisms in human tumors.

Periprostatic implantation of neural differentiated mesenchymal stem cells restores cavernous nerve injury-mediated erectile dysfunction.

Mesenchymal stem cells (MSCs) have been utilized to restore erectile function in animal models of cavernous nerve injury (CNI). However, transplantation of primary MSCs may lead to unpredictable therapeutic outcomes. In this study, we investigated the efficiency of neural differentiated MSCs (d-MSCs) on the restoration of erectile function in CNI rats. Rat bone marrow MSCs (r-BM-MSCs) were treated with all-trans retinoic acid to induce neural differentiation. Rats were divided into five groups: a sham operation group; a bilateral CNI group that received an intracavernous injection of r-BM-MSCs (IC group); and three groups that received periprostatic implantation of either r-BM-MSCs (IP group), d-MSCs (IP-d group), or PBS (PBS group). The data revealed that IP injection of d-MSCs ameliorated erectile function in a similar manner to an IC injection of MSCs and enhanced erectile function compared to an IP injection of MSCs. An in vivo time course of d-MSCs survival revealed that PKH26-labled d-MSCs were detectable either within or surrounding the cavernous nerve tissue. In addition, the expression of caspase-3 significantly increased in the PBS group and decreased after treatment with MSCs, especially in the IC and IP-d groups. Furthermore, the expression levels of neurotrophic factors increased significantly in d-MSCs. This study demonstrated that periprostatic implantation of d-MSCs effectively restored erectile function in CNI rats. The mechanism might be ascribed to decreases in the frequency of apoptotic cells, as well as paracrine signaling by factors derived from d-MSCs.

Mechanism of acute lung injury due to phosgene exposition and its protection by cafeic acid phenethyl ester in the rat.

The mechanism of phosgene-induced acute lung injury (ALI) remains unclear and it is still lack of effective treatments. Previous study indicated that oxidative stress was involved in phosgene-induced ALI. Caffeic acid phenethyl ester (CAPE) has been proved to be an anti-inflammatory agent and a potent free radical scavenger. The purpose of this study was to investigate the protective effects of CAPE on phosgene-induced ALI and identify the mechanism, in which oxidative stress and inflammation were involved. The phosgene was used to induce ALI in rats. The results showed that after phosgene exposure, total protein content in BALF was not significantly changed. The increase of MDA level and SOD activity induced by phosgene was significantly reduced by CAPE administration, and the decrease of GSH level in BALF and lung were significantly reversed by CAPE. CAPE also partially blocked the translocation of NF-κB p65 to the nucleus, but it had little effect on the phosphorylation of p38 MAPK. In conclusion, CAPE showed protective effects on lung against phosgene-induced ALI, which may be related with a combination of the antioxidant and anti-inflammatory functions of CAPE.

Resveratrol attenuates renal hypertrophy in early-stage diabetes by activating AMPK.

BACKGROUND: Recent studies suggest the involvement of the adenosine monophosphate-activated serine/threonine protein kinase (AMPK) pathway in the pathogenesis of diabetic nephropathy (DN). Resveratrol, an agent that activates AMPK, may have the potential to protect against the development of DN. This study was designed to investigate the therapeutic effects of resveratrol on renal hypertrophy in early-stage diabetes and the underlying mechanisms. METHOD: Molecular and structural changes involved in the pathogenesis of DN were tested in a rat model of early-stage diabetes. Renal mesangial cells (RMCs) were cultured in media containing different concentrations of glucose with or without resveratrol. Cellular DNA synthesis was assayed by measuring (3)H-thymidine incorporation. The phosphorylation status of AMPK, eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), and phospho- ribosomal protein S6 (S6) was analyzed by Western blot. RESULTS: Resveratrol reduced plasma creatinine and urinary albumin excretion and attenuated renal hypertrophy without affecting blood glucose levels. Moreover, resveratrol activated AMPK and inhibited phosphorylation of 4E-BP1 and S6 in diabetic rat kidneys. In vitro, resveratrol blocked high glucose-induced dephosphorylation of AMPK and phosphorylation of 4E-BP1 and S6 and strongly inhibited both the DNA synthesis and proliferation of RMCs. CONCLUSION: These findings suggest the possibility that resveratrol exerts antiproliferative, antihypertrophic effects by activating AMPK and reducing 4E-BP1 and S6 phosphorylation, thus suppressing the development and progression of DN.

Antioxidant activities of oleanolic acid in vitro: possible role of Nrf2 and MAP kinases.

Oleanolic acid (OA) is a natural triterpenoid, which has been used in Chinese medicine for the treatment of liver disorders for many years. Its pharmacological activities have been the focus of intense research in recent years. However, there is little research on the antioxidant activities of OA. In the present study, we aim to investigate whether OA produces its protective effects mainly through antioxidant mechanisms and whether OA plays as an antioxidant through quenching reactive oxygen species (ROS), inhibiting lipid peroxidation or stimulating cellular antioxidant defenses. In the in vitro antioxidant activity-assessing models, OA acted as not only a free radical-scavenger through direct chemical reactions but also a biological molecule, which may enhance the antioxidant defenses. tert-Butyl hydroperoxide (tBHP) induced ROS generation, damaged plasma membrane and decreased cell viability and the expression of key antioxidant enzymes and MAP kinases in QZG cells. OA ameliorated the oxidative injury induced by tBHP through increasing the generation of antioxidant (glutathione) and the expression of key antioxidant enzymes mediated by nuclear factorerythroid 2 p45-related factor 2 (Nrf2), in which process, activation of JNK and ERK, but not p38, was involved. The present study, for the first time, investigated the antioxidant activities of OA systematically. OA probably functions mainly through indirect biological effect and protects QZG cells against cytotoxicity induced by tBHP through increasing the generation of antioxidant and the expression of oxidative stress sensitive transcription factor-Nrf2, and MAP kinases, mainly JNK and ERK. These findings may significantly better the understanding of OA and advance therapeutic approaches to the diseases which are associated with oxidative stress.

Activation of cloned BK(Ca) channels in nitric oxide-induced apoptosis of HEK293 cells.

The large conductance Ca(2+)-activated K(+) (BK(Ca)) channels are highly expressed in vascular smooth muscle cells (VSMCs) and play an essential role in the regulation of various physiological functions. Besides its electrophysiological function in vascular relaxation, BK(Ca) has also been reported to be implicated in nitric oxide (NO)-induced apoptosis of VSMCs. However, the molecular mechanism is not clear and has not been determined on cloned channels. The present study was designed to clarify whether activation of cloned BK(Ca) channel was involved in NO-induced apoptosis in human embryonic kidney 293 (HEK293) cell. The cDNA encoding the alpha-subunit of BK(Ca) channel, hSloalpha, was transiently transfected into HEK293 cells. The apoptotic death in HEK-hSloalpha cells was detected using immunocytochemistry, analysis of fragmented DNA by agarose gel electrophoresis, MTT test, and flow cytometry assays. Whole-cell and single-channel characteristics of HEK-hSloalpha cells exhibited functional features similar to native BK(Ca) channel in VSMCs. Exposuring of HEK- hSloalpha cells to S-nitroso-N-acetyl-penicillamine increased the hSloalpha channel activities of whole-cell and single-channel, and then increased percentage of cells undergoing apoptosis. However, blocking hSloalpha channels with 1 mM tetraethylammonia or 100 nM iberiotoxin significantly decreased the NO-induced apoptosis, whereas 30 microM NS1619, the specific agonist of BK(Ca), independently increased hSloalpha currents and induced apoptosis. These results indicated that activation of cloned BK(Ca) channel was involved in NO-induced apoptosis of HEK293 cells.