Mammalian Metallothionein-2A and Oxidative Stress.

Mammalian metallothionein-2A (MT2A) has received considerable attention in recent years due to its crucial pathophysiological role in anti-oxidant, anti-apoptosis, detoxification and anti-inflammation. For many years, most studies evaluating the effects of MT2A have focused on reactive oxygen species (ROS), as second messengers that lead to oxidative stress injury of cells and tissues. Recent studies have highlighted that oxidative stress could activate mitogen-activated protein kinases (MAPKs), and MT2A, as a mediator of MAPKs, to regulate the pathogenesis of various diseases. However, the molecule mechanism of MT2A remains elusive. A deeper understanding of the functional, biochemical and molecular characteristics of MT2A would be identified, in order to bring new opportunities for oxidative stress therapy.

Effects of high glucose on expression of OPG and RANKL in rat aortic vascular smooth muscle cells.

OBJECTIVE: To explore effect of high glucose on expression of osteoprotegerin (OPG) and receptor activator of NF- κ B ligand (RANKE) in rat aortic vascular smooth muscle cells. METHODS: SD rats were intraperitoneally injected with streptozotocin, OPG and RANKL expression in rat thoracic aortas were detected by immunohistochemical staining. In cultured vascular smooth muscle cells (VSMCs) (A7r5), qRT-PCR and Western blot analysis were used to examine the mRNA and protein levels of OPG and RANKL. RESULTS: Our results demonstrated that OPG expression was increased in hyperglycemic rat aortic VSMCs, while RANKL expression was decreased. Besides, in vitro experiments high glucose induced OPG expression, but depressed RANKL expression by dose- and time-dependent manner in cultured A7r5. CONCLUSIONS: Our findings suggested that high glucose could promote the expression of OPG, and inhibit the expression of RANKL in VSMCs, which may be partly be the molecular mechanism of diabetic vascular calcification.

Interposed abdominal compression-cardiopulmonary resuscitation after cardiac surgery.

OBJECTIVES: The management of cardiac arrest after cardiac surgery differs from the management of cardiac arrest under other circumstances. In other studies, interposed abdominal compression-cardiopulmonary resuscitation (IAC-CPR) resulted in a better outcome compared with conventional CPR. The aim of the present study was to determine the feasibility, safety and efficacy of IAC-CPR compared with conventional CPR in patients with cardiac arrest after cardiac surgery. METHODS: Data on all cardiac surgical patients who suffered a sudden cardiac arrest during the first 24 h after surgery were collected prospectively. Cardiac arrest was defined as the cessation of cardiac mechanical activity with the absence of a palpable central pulse, apnoea and unresponsiveness, including ventricular fibrillation, asystole and pulseless electrical activity. Forty patients were randomized to either conventional CPR (n = 21) or IAC-CPR (n = 19). IAC-CPR was initially performed by compressing the abdomen midway between the xiphoid and the umbilicus during the relaxation phase of chest compression. If spontaneous circulation was not restored after 10-15 min, the surgical team would immediately proceed to resternotomy. The endpoints of the study were safety, return of spontaneous circulation (ROSC) >5 min, survival to hospital discharge and survival for 6 months. RESULTS: With IAC-CPR, there were more patients in terms of ROSC, survival to hospital discharge, survival for 6 months and fewer CPR-related injuries compared with patients who underwent conventional CPR. CONCLUSIONS: IAC-CPR is feasible and safe and may be advantageous in cases of cardiac arrest after cardiac surgery.

p42/p44 mitogen-activated protein kinases inhibit atrial natriuretic peptide mRNA transcription in gp130-mediated hypertrophic ventricular myocytes.

OBJECTIVE: To understand the role of ANP mRNA transcription regulation in gp130-mediated cardiomyocyte hypertrophy, and the involved mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK, also called p42/p44 MAPK) signaling pathway. METHODS: Isolated neonatal ventricular myocytes were treated with different concentrations of CT-1 (10(-9), 10(-8)and 10(-7)mol/L). MTT was used to analyze the viability and RT-PCR was used to detect ANP mRNA levels in cardiomyocyte. To inhibit p42/p44 MAPK activity in hypertrophic cardiomyocytes, the cells were pretreated with a specific MEK1 inhibitor. RESULTS: CT-1 significantly induced ANP mRNA expression and the viability of cardiomyocytes in a dose- and time-dependent manner. Furthermore, blocking p42/p44 MAPK activity by the special MEK1 inhibitor upregulated the ANP mRNA. CONCLUSIONS: p42/p44 MAPK have an important role in suppressing ANP mRNA transcription and cell activity in gp130-mediated hypertrophic ventricular myocytes.

Toxicarioside A inhibits SGC-7901 proliferation, migration and invasion via NF-κB/bFGF signaling.

AIM: To investigate the inhibitory role of toxicarioside A on the gastric cancer cell line human gastric cancer cell line (SGC-7901) and determine the underlying molecular mechanism. METHODS: After SGC-7901 cells were treated with toxicarioside A at various concentrations (0.5, 1.5, 4.5, 9.0 µg/mL) for 24 h or 48 h, cell viability was determined by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, and the motility and invasion of tumor cells were assessed by the Transwell chamber assay. Immunofluorescence staining, reverse transcription polymerase chain reaction and Western blotting were performed to detect the expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR1), and nuclear factor-kappa B (NF-κB) activation was examined by electrophoretic mobility shift assay. RESULTS: The results showed that toxicarioside A was capable of reducing cell viability, inhibiting cell growth, and suppressing cell migration and invasion activities in a time- and dose-dependent manner in SGC-7901 cells. Further analysis revealed that not only the expression of bFGF and its high-affinity receptor FGFR1 but also the NF-κB-DNA binding activity were effectively blocked by toxicarioside A in a dose-dependent manner compared with the control group (P < 0.05 or P < 0.01). Interestingly, application of the NF-κB specific inhibitor, pyrrolidinedithiocarbamate (PDTC), to SGC-7901 cells significantly potentized the toxicarioside A-induced down-regulation of bFGF compared with the control group (P < 0.05). CONCLUSION: These findings suggest that toxicarioside A has an anti-gastric cancer activity and this effect may be achieved partly through down-regulation of NF-κB and bFGF/FGFR1 signaling.

[Analysis on therapeutic effect of bird-pecking moxibustion combined with western medicine for treatment of infantile hand, foot and mouth disease].

OBJECTIVE: To observe therapeutic effects of bird-pecking moxibustion in children of hand, foot and mouth disease, and to analyze the mechanism. METHODS: Seventy-five children of hand, foot and mouth disease were randomly divided into 3 groups, a combined moxibustion and medicine group (n = 22), a Chinese medicine group (n = 29), and a western medicine group (n = 24). The combined moxibustion and medicine group was treated with bird-pecking moxibustion combined with routine western medicine, the Chinese medicine group with oral administration of Chinese medicine and routine western medical therapy, and the western medicine group with routine western medicine. After treatment of 7 days, the therapeutic effects on skin rash, oral herpes, constipation or loose stool, dyspepsia and anorexia, etc. were comprehensively assessed, and their therapeutic effects were compared. RESULTS: The total effective rate was 95.5% in the combined moxibustion and medicine group, 86.2% in the Chinese medicine group, and 83.3% in the western medicine group, the former being significantly better than those of the other two groups (both P < 0.05). The combined moxibustion and medicine group was significantly better than the other two groups in the relieving time of skin rash, oral herpes, constipation or loose stool, dyspepsia and anorexia, etc. (all P < 0.05) CONCLUSION: The combined moxibustion and medication can effectively improve symptoms of the digestive tract, shorten duration of disease, reduce pain in the patient with hand, foot and mouth disease.