Retracted: Obestatin Plays Beneficial Role in Cardiomyocyte Injury Induced by Ischemia-Reperfusion In Vivo and In Vitro.

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Qin Zhang, Xin-wei Dong, Jia-ying Xia, Ke-ying Xu, Zhe-rong Xu. Obestatin Plays Beneficial Role in Cardiomyocyte Injury Induced by Ischemia-Reperfusion In Vivo and In Vitro. Med Sci Monit, 2017; 23: 2127-2136. DOI: 10.12659/MSM.901361.

Characteristics of hyperuricemia in older adults in China and possible associations with sarcopenia.

OBJECTIVE: This cross-sectional study aimed to investigate the characteristics and epidemiology of hyperuricemia in older adults in China and evaluate possible associations between hyperuricemia and sarcopenia. METHODS: Three hundred and eighty-eight study subjects (>60 years old) meeting the inclusion criteria received blood tests and standardized examinations for bone mineral density, muscle mass, muscle strength, and physical performance. Data including demographic and clinical characteristic and comorbidity were also collected. All data were analyzed retrospectively. RESULTS: In the study population, higher uric acid levels were significantly correlated with higher muscle mass, grip strength, and bone density, but were unrelated to physical performance. When uric acid levels were separated into quartiles and the population was divided by sex, the correlation of uric acid to muscle mass was retained in some quartiles for both men and women, and the correlation to handgrip was only retained for one quartile for men. The correlation to bone density was retained in women in all analyses. CONCLUSION: In the population as a whole, higher uric acid levels were significantly correlated with higher muscle mass, grip strength, and bone density, but had no relationship to physical performance. Differences between men and women in these relationships need to be studied further.

Obestatin Plays Beneficial Role in Cardiomyocyte Injury Induced by Ischemia-Reperfusion In Vivo and In Vitro.

BACKGROUND Obestatin, primarily recognized as a peptide within the gastrointestinal system, has been shown to benefit the cardiovascular system. We designed this experiment to study the protective role and underlying mechanism of obestatin against ischemia-reperfusion(I/R) injury in myocardial cells. MATERIAL AND METHODS In an In vivo experiment, LAD was ligated for 0.5 h and then opened for reperfusion with obestatin for 24 h. Then, the infarction area was shown with TTC staining, and inflammation factors in serum were analyzed by qRT-PCR. In primary cultured cardiomyocytes, we measured the level of LDH, MDA, GSH, and SOD. Finally, we assessed cells apoptosis using flow cytometry and detected the concentrations of caspase-3, Bax, and Bcl-2 using Western blot analysis. RESULTS TTC staining showed that in the 3 obestatin groups, the infarct area became smaller with the increase of obestatin concentration. Obestatin also inhibited LDH expression in rat serum and decreased mRNA levels of TNF-α, IL-6, ICAM-1, and iNOS in rat cardiomyocytes after reperfusion. In primary cultured cardiomyocytes, obestatin decreased LDH content and increased GSH level after I/R injury. Obestatin was also found to antagonize the apoptosis of cardiomyocytes in a dose-dependent manner. Western blot analysis showed that obestatin downregulated the expression of caspase-3 and Bax and upregulated the expression of Bcl-2. CONCLUSIONS Obestatin can protect cardiomyocyte from I/R-induced injury in vitro and in vivo. This beneficial effect is closely related with its properties of anti-inflammation, anti-cytotoxicity, and anti-apoptosis. The protective effect of obestatin might be associated with activation of Bcl-2 and inhibition of caspase-3 and Bax.

Clinical Outcomes of Coronary Artery Bypass Grafting vs Percutaneous Coronary Intervention in Octogenarians With Coronary Artery Disease.

BACKGROUND: The number of elderly people receiving treatment for coronary artery disease (CAD) is increasing, and there are few studies that compared the outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in the elderly. The objective of this study was to compare outcomes of CABG and PCI in octogenarians with CAD. METHODS: We conducted a search to identify articles that reported the results of 2-arm studies that compared CABG with PCI in octogenarians. The primary outcomes were short-term mortality and overall survival, and secondary outcomes included length of hospital stay and cerebrovascular accident (CVA) and myocardial infarction (MI) rates. RESULTS: Seven studies that enrolled 1879 patients who received CABG and 1432 treated with PCI were included. Short-term mortality was significantly less for patients in the PCI arms (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.05-2.06; P = 0.02), as was duration of hospital stay (difference in means, 6.07; 95% CI, 2.81-9.34; P < 0.001). Patients in the CABG arms had longer overall survival (hazard ratio, 0.81; 95% CI, 0.73-0.89; P < 0.001). CVA and MI rates were similar (CVA: OR, 1.06; 95% CI, 0.57-1.95; P = 0.86; MI: OR, 0.70; 95% CI, 0.42-1.17; P = 0.17). CONCLUSIONS: The results suggest that physicians should consider not only the clinical features of CAD, but also the elderly patients future health outlook when choosing a revascularization procedure.

The Efficacy of Ginseng-Related Therapies in Type 2 Diabetes Mellitus: An Updated Systematic Review and Meta-analysis.

Few randomized clinical trials have evaluated the efficacy of ginseng in patients with type 2 diabetes mellitus (T2DM). The current meta-analysis evaluated the ginseng-induced improvement in glucose control and insulin sensitivity in patients with type-2 diabetes or impaired glucose tolerance.Randomized clinical trials comparing ginseng supplementation versus control, in patients with T2DM or impaired glucose tolerance, were hand-searched from Medline, Cochrane, and Google Scholar databases by 2 independent reviewers using the terms "type 2 diabetes/diabetes/diabetic, impaired glucose tolerance, and ginseng/ginsenoside(s)." The primary outcome analyzed was the change in HbA1c, whereas the secondary outcomes included fasting glucose, postprandial glucose, fasting insulin, postprandial insulin, insulin resistance Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), triglycerides, total cholesterol, low density lipoprotein (LDL), and high density lipoprotein (HDL).Of the 141 studies identified, 8 studies were chosen for the current meta-analysis. The average number of patients, age, and sex distribution among the groups were comparable. Results reveal no significant difference in HbA1c levels between the ginseng supplementation and the control groups (pooled standardized difference in means = -0.148, 95% CI: -0.637 to 0.228, P = 0.355). Ginseng supplementation improved fasting glucose, postprandial insulin, and HOMA-IR levels, though no difference in postprandial glucose or fasting insulin was observed among the groups. Similarly, triglycerides, total cholesterol, and LDL levels showed significant difference between the treatment groups, while no difference in HDL was seen. In addition, ginseng-related therapy was ineffective in decreasing the fasting glucose levels in patients treated with oral hypoglycemic agents or insulin.The present results establish the benefit of ginseng supplementation in improving glucose control and insulin sensitivity in patients with T2DM or impaired glucose intolerance.

Effects of comprehensive intensive therapies on the change of intima-media thickness of carotid arteries in type 2 diabetic patients: A report of 4-year follow-up with a literature review.

BACKGROUND: The aim was to evaluate the effect of comprehensive intensive therapy on the carotid and femoral arteries of intima-media thickness in patients with type 2 diabetes mellitus after 4-year follow-up. METHODS: In this prospective 4-year study, patients (N = 210) with newly diagnosed type 2 diabetes received either comprehensive intensive therapy (n = 110) or conventional therapy (n = 100). Blood pressure, blood glucose and lipid levels were monitored every 3-6 months, and carotid and femoral arteries of intima-media thickness were monitored with ultrasonography. For the literature review, various databases were searched until 20 December 2014 for studies that evaluated effects of intensive multi-factorial therapies on comprehensive intensive therapy in type 2 diabetes mellitus patients. RESULTS: The comprehensive intensive therapy group had a smaller rate of carotid intima-media thickness increase than the conventional therapy (control) group (p < 0.05). The carotid intima-media thickness in comprehensive intensive therapy group remained stable while the adjusted rate of carotid intima-media thickness increase was 12.55% in the control group. The femoral intima-media thickness change was also smaller in comprehensive intensive therapy group but the difference over time did not reach significance. CONCLUSION: The carotid intima-media thickness remained stable in type 2 diabetes mellitus patients who received comprehensive intensive therapy, suggesting that multi-factorial intensive therapies might have potential in reducing macro-vascular events in these patients.

Efficacy and Safety of Denosumab in Postmenopausal Women With Osteoporosis: A Meta-Analysis.

The purpose of this study was to perform a meta-analysis to examine the efficacy and safety of denosumab in postmenopausal women with osteoporosis.Medline, Cochrane Library, EMBASE, and Google Scholar databases were searched until October 30, 2014 using combinations of the following search terms: osteoporosis, postmenopause, postmenopausal, women, denosumab. The primary outcome was bone mineral density (BMD) change, and secondary outcomes were change in the bone turnover markers ß-isomerized carboxy-terminal cross-linking telopeptide of type I collagen (CTX) and serum procollagen type I amino-terminal propeptide (P1NP), and adverse events.Patients treated with denosumab had significantly increased BMD of the lumbar spine (7.58%), total hip (4.86%), and distal third of the radius (2.92%) than those treated with placebo (all, P < 0.001). Patients treated with denosumab had a significant decrease of CTX (-66.16%) and P1NP (-64.65%) as compared with those treated with placebo (both, P < 0.001). Adverse events were similar between the 2 groups (pooled odds ratio = 1.04, P = 0.625).Denosumab increases BMD and decreases markers of bone turnover in postmenopausal women with osteoporosis, and is not associated with significant side-effects.

Apple Polyphenols Decrease Atherosclerosis and Hepatic Steatosis in ApoE-/- Mice through the ROS/MAPK/NF-κB Pathway.

In this study, we examined the effects of apple polyphenols (APs) on hyperlipidemia, atherosclerosis, hepatic steatosis and endothelial function and investigated the potential mechanisms. ApoE(-/-) mice were fed a western-type diet and orally treated with APs (100 mg/kg) or atorvastatin (10 mg/kg) for 12 weeks. Hyperlipidemia and atherosclerosis in the aortic sinuses and, and hepatic lipidosis were measured. The treatment with APs or atorvastatin induced a remarkable reduction in the atherosclerotic lesions and hepatic steatosis and decreased the levels of low-density lipoprotein, triglyceride, CCL-2 and VCAM-1 levels in the plasma. Conversely, the APs significantly increased the plasma levels of high-density lipoprotein (HDL) cholesterol and markedly up-regulated the glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) levels in liver tissues. Moreover, the APs treatment modulated lipid metabolism by up-regulating the transcription of associated hepatic genes including PPARα, while down-regulating the transcription of SCAP and its downstream genes associated with lipid synthesis in the liver. Histological assessment showed that the APs treatment also reduced the macrophage infiltration in the aortic root plaque and the inflammatory cells infiltrations to the liver tissues. Moreover, we confirmed that the APs treatment greatly reduced the ox-LDL-induced endothelial dysfunction and monocyte adhesion to rat aortic endothelial cells (RAECs). Mechanistically, the APs treatment suppressed the ROS/MAPK/NF-κB signaling pathway, and consequently, reduced CCL-2, ICAM-1 and VCAM-1 expression. Our results suggest that the APs are a beneficial nutritional supplement for the attenuation of atherosclerosis.

The effectiveness of leucine on muscle protein synthesis, lean body mass and leg lean mass accretion in older people: a systematic review and meta-analysis.

In the present study, we performed a meta-analysis to assess the ability of leucine supplementation to increase the muscle protein fraction synthetic rate and to augment lean body mass or leg lean mass in elderly patients. A literature search was conducted on Medline, Cochrane, EMBASE and Google Scholar databases up to 31 December 2013 for clinical trials that investigated the administration of leucine as a nutrient that affects muscle protein metabolism and muscle mass in elderly subjects. The included studies were randomised controlled trials. The primary outcome for the meta-analysis was the protein fractional synthetic rate. Secondary outcomes included lean body mass and leg lean mass. A total of nine studies were included in the meta-analysis. The results showed that the muscle protein fractional synthetic rate after intervention significantly increased in the leucine group compared with the control group (pooled standardised difference in mean changes 1·08, 95% CI 0·50, 1·67; P< 0·001). No difference was found between the groups in relation to lean body mass (pooled standardised difference in mean changes 0·18, 95% CI - 0·18, 0·54; P= 0·318) or leg lean mass (pooled standardised difference in mean changes 0·006, 95% CI - 0·32, 0·44; P= 0·756). These findings suggest that leucine supplementation is useful to address the age-related decline in muscle mass in elderly individuals, as it increases the muscle protein fractional synthetic rate.

Clinical effectiveness of protein and amino acid supplementation on building muscle mass in elderly people: a meta-analysis.

OBJECTIVE: A major reason for the loss of mobility in elderly people is the gradual loss of lean body mass known as sarcopenia. Sarcopenia is associated with a lower quality of life and higher healthcare costs. The benefit of strategies that include nutritional intervention, timing of intervention, and physical exercise to improve muscle loss unclear as finding from studies investigating this issue have been inconsistent. We have performed a systematic review and meta-analysis to assess the ability of protein or amino acid supplementation to augment lean body mass or strength of leg muscles in elderly patients. METHODS: Nine studies met the inclusion criteria of being a prospective comparative study or randomized controlled trial (RCT) that compared the efficacy of an amino acid or protein supplement intervention with that of a placebo in elderly people (≥ 65 years) for the improvement of lean body mass (LBM), leg muscle strength or reduction associated with sarcopenia. RESULTS: The overall difference in mean change from baseline to the end of study in LBM between the treatment and placebo groups was 0.34 kg which was not significant (P = 0.386). The overall differences in mean change from baseline in double leg press and leg extension were 2.14 kg (P = 0.748) and 2.28 kg (P = 0.265), respectively, between the treatment group and the placebo group. CONCLUSIONS: These results indicate that amino acid/protein supplements did not increase lean body mass gain and muscle strength significantly more than placebo in a diverse elderly population.

Efficacy of topical recombinant human platelet-derived growth factor for treatment of diabetic lower-extremity ulcers: Systematic review and meta-analysis.

OBJECTIVE: Recombinant human platelet-derived growth factor (rhPDGF) is used topically in the treatment of diabetic lower-extremity ulcers. There have been few meta-analyses of the efficacy of rhPDGF in this treatment context. The aim of this study was to perform an updated systematic review and meta-analysis to assess the clinical efficacy of rhPDGF in the treatment of diabetic lower-extremity ulcers. METHODS: We searched the MEDLINE, Cochrane Library, EMBASE and Web of Knowledge databases up to April 30, 2014. Studies were identified and selected, and data were extracted by two independent reviewers. The primary efficacy outcome was complete healing rate. Adverse events were also assessed. The studies were evaluated for quality and publication bias. RESULTS: A total of 6 randomized controlled trials including 992 patients were selected from 173 identified studies. The studies compared rhPDGF treatment in the context of standard of care (SOC) to placebo or SOC alone. In the absence of study heterogeneity, a fixed-effects model was performed, and the combined odds ratio (OR) indicated a significantly greater complete healing rate in patients treated with rhPDGF compared to placebo or SOC alone. The ORs ranged from 0.58 to 2.77, with a combined OR of 1.53 (95% CI = 1.14 to 2.04, p = 0.004). A sensitivity analysis (leave-one-out method) indicated good study reliability, and a funnel plot with Egger test showed no publication bias. CONCLUSION: These results indicate that rhPDGF is efficacious in the treatment of diabetic lower-extremity ulcers.

[Atorvastatin inhibits the H2O2-induced apoptosis of human vascular endothelial cells through a down-regulation of cleaved caspase-9/caspase-3].

OBJECTIVE: To investigate the effect and potential mechanism of atorvastatin against H2O2-induced apoptosis of human umbilical vein endothelial cells (ECV-304). METHODS: ECV-304 cells were pretreated with different concentrations of atorvastatin (0.1, 1 and 10 µmol/L) for 2 h, followed by an exposure to 100 µmol/L H2O2 for 18 h. Cellular morphology was observed under fluorescence microscope. Cellular viability and apoptosis were evaluated by methyl thiazolyl tetrazolium (MTT) and flow cytometry. Finally the expressions of cleaved caspase-3 and caspase-9 were measured by Western blot. RESULTS: H2O2 treatment caused an obvious apoptosis of ECV-304 cells and significantly decreased the cellular viability as characterized by a high percentage (50.71%) of apoptotic cells. Atorvastatin pretreatment inhibit cellular apoptosis induced by H2O2 (39.45%, 20.53% and 7.83%). Western blot assay showed that H2O2 treatment caused a high expression of cleaved caspase-3 and caspase-9 while atorvastatin pretreatment obviously inhibited the expression in a dose-dependent manner. CONCLUSIONS: Atorvastatin inhibits the H2O2-induced apoptosis of ECV-304 cells in a dose-dependent manner. This effect may be associated with the down-regulation of cleaved caspase-9/caspase-3.

Effect of intensive multifactorial treatment on the intima-media thickness of large arteries in patients with new-onset type 2 diabetes mellitus.

OBJECTIVE: To quantify the changes in blood glucose, blood lipids, blood pressure, and the intima-media thickness (IMT) of large arteries in patients with new-onset type 2 diabetes mellitus who received either intensive multifactorial treatment or conventional treatment. METHODS: Two-hundred and ten patients with new-onset type 2 diabetes mellitus were randomly assigned to two groups: an intensive treatment group (n=110) and a conventional treatment group (n=100). Fasting blood glucose (FBG), glycosylated hemoglobin A1c (HbA1c), blood pressure, blood lipids [total cholesterol (TC), triglyceride (TG), low-density lipoprotein C (LDL-C), and high-density lipoprotein C (HDL-C)], and IMTs of large arteries (carotid, iliac, and femoral arteries) were determined before and at one and two years after starting treatment. The patients in the conventional treatment group received routine diabetes management in our outpatient department. Targets were established for patients in the intensive treatment group. Their blood glucose, blood lipids, and blood pressure levels were regularly monitored and therapeutic regimens were adjusted for those whose measurements did not meet the target values until all the parameters met the established targets. Within-group and between-group differences were evaluated. RESULTS: A significantly greater percentage of patients in the intensive treatment group had LDL-C levels that reached the target value one year after starting treatment than those in the conventional treatment group (52.04% vs. 33.33%, P<0.05). No significant differences were found between groups for FBG, HbA1c, blood pressure, TG, TC, or HDL-C. The percentages of patients with TG (51.02% vs. 34.48%), TC (52.04% vs. 33.33%), and LDL-C (61.22% vs. 43.67%) who met the respective target values in the intensive treatment group were all significantly higher than the corresponding percentages in the conventional treatment group two years after starting treatment (P<0.05). There were no significant differences in the percentages of patients with FBG, HbA1c, and blood pressure values meeting the respective targets between the groups at the two-year follow-up. One year after starting treatment, the LDL-C level, diastolic blood pressure (DBP), and the IMTs of the femoral and iliac arteries of the intensive treatment group were significantly lower compared to those of the conventional treatment group (P<0.05), although there was no significant difference in other metabolic parameters. Two years after starting treatment, the TC, LDL-C, blood pressure [systolic blood pressure (SBP) and DBP], and the IMTs of the carotid and femoral arteries of the intensive treatment group were significantly lower than those of the conventional treatment group (P<0.05). No significant differences in other metabolic parameters existed between the two groups two years after starting treatment. CONCLUSIONS: Early comprehensive and intensive treatment of type 2 diabetes mellitus can delay or even reverse the increase in IMT of large arteries. Lowering blood pressure and blood lipid regulation in patients with type 2 diabetes mellitus have great significance in decreasing the risk of diabetes-related macrovascular lesions.

[Plasma gamma-glutamyl transpeptidase level as a cardiovascular risk factor in elderly patients with hypertension or hypertension with diabetes mellitus].

OBJECTIVE: To investigate plasma gamma-glutamyl transpeptidase (γ-GGT) level as a cardiovascular risk factor in elderly patients with hypertension or hypertension with diabetes mellitus. METHODS: Forty-nine elderly patients of hypertension and 42 elderly patients of hypertension with diabetes mellitus and 39 healthy elderly subjects were enrolled in the study. The height, weight and blood pressure of patients were measured, serum C reactive protein and other biochemical indicators were detected. The relation between plasma γ-GGT and cardiovascular risk factors in three groups were analyzed. RESULTS: There was no significant difference in plasma γ-GGT levels among three groups. There was a positive correlation of plasma γ-GGT levels with systolic pressure, pulse pressure, hemoglobin A1c and CRP in control group. While in hypertension with diabetes mellitus group, plasma γ-GGT levels were correlated with systolic pressure, mean arterial pressure, fasting blood sugar and cystatin. CONCLUSION: Plasma γ-GGT might be a risk factor for cardiovascular diseases, and may be used as a predictive indicator for kidney injury in early patients with hypertension with diabetes mellitus.

Simvastatin protects human osteosarcoma cells from oxidative stress-induced apoptosis through mitochondrial-mediated signaling.

Apoptosis of osteoblasts has been proposed as the common basis of osteoporosis, with oxidative stress as the major cause. This study was performed to investigate the protective effect of simvastatin (0.001-0.1 µM) on 100 µM hydrogen peroxide (H2O2)-mediated oxidative stress-induced apoptosis in human osteosarcoma (MG63) cells and the molecular mechanisms involved. Cell apoptosis was evaluated by observation of morphological changes and Annexin V-propidium iodide double staining followed by flow cytometric analysis. MTS assays were used to evaluate cell viability. To investigate the underlying molecular mechanisms, the expression of caspase-3, caspase-9 and Bcl-2 were analyzed by Western blotting. Following stimulation with H2O2 for 24 h, a high proportion of MG63 cells underwent apoptosis, while a dose-dependent inhibition of apoptosis was observed in the presence of simvastatin. A significant, dose-dependent reduction in the expression of caspase-3 and caspase-9 protein induced by H2O2 in MG63 cells was observed in response to simvastatin and the Bcl-2 levels were increased. In conclusion, simvastatin protects MG63 cells from oxidative stress-induced apoptosis through downregulation of caspase-3 and caspase-9 activation and upregulation of Bcl-2 expression, suggesting a protective effect in osteoporosis.

Chewing substances with or without tobacco and risk of cardiovascular disease in Asia: a meta-analysis.

OBJECTIVE: To assess whether people who ever use any form of chewing substance in Asia are at increased risk of cardiovascular disease (CVD). METHODS: PubMed and ISI Web of Science were searched for relevant studies, with no limitation on language or study year. Studies were included if they provided quantitative estimate of the association between ever use of chewing substance and the occurrence of CVD. Two authors independently implemented inclusion criteria, abstracted study characteristics, and performed meta-analysis. Summary relative risks were estimated on the basis of a random effect model. We used Q statistic and Egger's test to examine heterogeneity across studies and potential publication bias, respectively. RESULTS: Eight eligible studies were included. The relative risk of CVD for ever using chewing substances with or without tobacco was 1.26 (95% confidence interval (CI) 1.12-1.40), which was unchanged when restricted to cohort studies [1.25 (1.08-1.42)] or cohort studies in Taiwan [1.31 (1.12-1.51)]. The summary relative risk for ischemic heart disease was 1.27 (1.02-1.52), and was lowered to 1.26 (0.85-1.67) after exclusion of a cross-sectional study. The overall relative risk for cerebrovascular disease was 1.32 (1.08-1.56). On the basis of the Taiwan data, the summary relative risk of CVD for betel (Areca catechu) chewing was 1.30 (1.17-1.44). Data on dose-response were limited to betel chewing in Taiwan, suggesting a relationship between risk of CVD and cumulative exposure. Two large cohorts in Taiwan reported a greater risk of CVD with betel chewing than with smoking. CONCLUSIONS: An association was detected between betel chewing with or without tobacco and the risk of CVD. Betel chewing may impose a greater CVD risk than smoking. More effort is needed in developing betel chewing cessation programmes. The relationship between betel chewing and subgroups of CVD requires further investigation.

Dihydrotestosterone protects human vascular endothelial cells from H(2)O(2)-induced apoptosis through inhibition of caspase-3, caspase-9 and p38 MAPK.

Oxidative stress is proved to be harmful to the vascular endothelial cells which are important in preventing the formation and progression of atheromatous plaque. This study was designed to investigate the protective effect and potential mechanisms of dihydrotestosterone (DHT) against H(2)O(2)-induced apoptosis of human umbilical vein endothelial cells (ECV-304). ECV-304 cells were pretreated with different concentrations of DHT (0.01, 0.1 and 1 microM) for 2h, followed by exposure to 100 microM H(2)O(2) for 18h. 3-(4,5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to evaluate cell viability. To detect apoptosis, the cells were assessed by morphologic examination and Annexin V-propidium iodide double staining with flow cytometry. Finally, the expression of caspase-3, caspase-9 and phospho p38 MAPK was assayed by Western blot to investigate the possible molecular mechanisms. We found that H(2)O(2) treatment for 18h significantly decrease the viability of ECV-304 cells characterized by a high percentage of apoptotic cells. DHT could antagonize the apoptosis inducing effect of H(2)O(2) in a dose-dependent manner. Consistently, DHT also significantly inhibit the expression of caspase-3, caspase-9 and phospho p38 MAPK induced by H(2)O(2). In summary, pretreatment with DHT can inhibit apoptosis of ECV-304 cells induced by H(2)O(2). The protective effect of DHT was associated with the inhibition of caspase-3, caspase-9 and phospho p38 MAPK expression.

[Changes of blood pressure, blood glucose and blood lipids levels after intensive treatment in incipient diabetes II patients].

OBJECTIVE: To evaluate the effect of intensive treatment on the blood sugar, blood lipids and blood pressure levels in incipient diabetes II patients. METHODS: One hundred and sixty incipient diabetes patients were allocated into two groups according to chronological order: 80 cases received routine treatment and 80 cases received intensive treatment. Fasting blood-glucose (FBG), glycosylated hemoglobin (HbA1C), blood pressure, blood cholesterol (TC), triglyceride (TG), LDL cholesterol-C (LDL-C), alanine aminotransferase (ALT) and aspertate aminotransferase (AST) were tested before treatment. For intensive treatment group blood pressure, blood sugar and blood lipids were regularly tested, and the therapeutic protocols were adjusted according to the test results until the therapeutic target reached. After six months, HbA1C, blood pressure, TC, LDL-C, ALT and AST were tested again and comparison was made between the two groups. RESULTS: There was a significant decrease in TC and LDL-C in the intensive treatment group compared with those in the routine treatment group (P <0.05). CONCLUSION: The intensive treatment on the incipient diabetes II patients facilitate the control of the blood lipids and blood sugar.

Construction of a recombinant adenovirus vector expressing IL-18BP/IL-4 fusion gene and the anti-inflammatory effect induced by this gene on lipopolysaccharide-stimulated synovial fibroblasts.

OBJECTIVE: To construct a recombinant adenovirus vector for expressing the IL-18 binding protein (IL-18BP)/IL-4 fusion gene and confirm the anti-inflammatory effect of this gene. MATERIALS AND METHODS: The recombinant virus expressing IL-18BP/IL-4 fusion protein (AD-IL-18BP/IL-4) was constructed. AD-IL-18BP/IL-4 was used to infect synovial fibroblasts (SF). ELISA and Western blot analysis were used to determine the expressions of the proteins IL-4 and IL-18BP. To investigate the protective effects of this vector on rheumatoid arthritis, SF were infected with AD-IL-18BP/IL-4 and stimulated by LPS (1 microg/ml) 4 h later. The expression levels of TNF-alpha, IL-6, IL-8, and IL-18 in the culture supernatant were detected by ELISA and production of PGE2 and NO was estimated. The protein expression of COX-2, iNOS, and NF-kappaB p50 in treated SF was analyzed by Western blot. RESULTS: AD-IL-18BP/IL-4 can effectively express the IL-18BP/IL-4 fusion protein. The expressions of TNF-alpha, IL-6, IL-8, and IL-18 were significantly inhibited in LPS-stimulated SF after treatment with AD-IL-18BP/IL-4. The production of PGE2 and NO was significantly decreased. Moreover, NF-kappaB p50, COX-2, and iNOS levels in SF were markedly suppressed by AD-IL-18BP/IL-4. CONCLUSION: AD-IL-18BP/IL-4 can suppress the production and expression of inflammatory cytokines such as COX-2, iNOS, and NF-kappaB in LPS-stimulated SF.