Ginsenoside Rg1 attenuates cerebral ischemia-reperfusion injury through inhibiting the inflammatory activation of microglia.

It is recognized that the cerebral ischemia/reperfusion (I/R) injury triggers inflammatory activation of microglia and supports microglia-driven neuronal damage. Our previous studies have shown that ginsenoside Rg1 had a significant protective effect on focal cerebral I/R injury in middle cerebral artery occlusion (MCAO) rats. However, the mechanism still needs further clarification. Here, we firstly reported that ginsenoside Rg1 effectively suppressed the inflammatory activation of brain microglia cells under I/R conditions depending on the inhibition of Toll-likereceptor4 (TLR4) proteins. In vivo experiments showed that the ginsenoside Rg1 administration could significantly improve the cognitive function of MCAO rats, and in vitro experimental data showed that ginsenoside Rg1 significantly alleviated neuronal damage via inhibiting the inflammatory response in microglia cells co-cultured under oxygen and glucose deprivation/reoxygenation (OGD/R) condition in gradient dependent. The mechanism study showed that the effect of ginsenoside Rg1 depends on the suppression of TLR4/MyD88/NF-κB and TLR4/TRIF/IRF-3 pathways in microglia cells. In a word, our research shows that ginsenoside Rg1 has great application potential in attenuating the cerebral I/R injury by targeting TLR4 protein in the microglia cells.

Suppression of phosphatase and tensin homolog protects insulin-resistant cells from apoptosis.

In the present study, a glucosamine-induced model of insulin-resistant skeletal muscle cells was established in order to investigate the effect of inhibition of phosphatase and tensin homolog (PTEN)/5'-adenosine monophosphate-activated protein kinase (AMPK) on these cells. The glucosamine-induced insulin-resistant skeletal muscle cells were produced and the rate of glucose uptake was measured using the glucose oxidase-peroxidase method. The expression levels of PTEN and phosphorylated PTEN (p-PTEN) were assessed using western blotting. Glucose transporter 4 (GLUT4) translocation was detected by immunofluorescence. Cell apoptosis was evaluated using flow cytometry. Following insulin stimulation, the rate of glucose uptake was significantly reduced in the cells with glucosamine-induced insulin-resistance in comparison with those in the control group. The expression and translocation of GLUT4 were reduced in the insulin-resistant muscle cells. By contrast, the expression of PTEN and p-PTEN as well as apoptosis were significantly increased. Following treatment with bisperoxopicolinatooxovanadate (BPV) or metformin in the insulin-resistant skeletal muscle cells, there was an increase in the rate of glucose uptake, an increase in GLUT4 expression and its translocation, a reduction in the expression of PTEN and p-PTEN, and a decrease in cell apoptosis compared with untreated insulin-resistant cells. Glucosamine may be used to produce an effective model of insulin-resistant skeletal muscle cells. Cells with glucosamine-induced insulin-resistance exhibited a reduced expression of GLUT4 and dysfunction in GLUT4 translocation, as well as increased activation of PTEN and increased cell apoptosis. Inhibition of PTEN or its upstream regulator, AMPK, protects glucosamine-induced insulin-resistant skeletal muscle cells from apoptosis.

Effect of propofol and ketamine anesthesia on cognitive function and immune function in young rats.

OBJECTIVE: To investigate the effects of propofol and ketamine on the cognitive function and immune function in young rats. METHOD: A total of 80 young rats were randomly divided into four groups: Control group, ketamine group (experimental group A), propofol group (experimental group B), ketamine and propofol group (experimental group C). All rats had continuous injection for three times, serum IL-2, IL-4 and IL-10 and whole brain IL-1ß level, hippocampal neuronal apoptosis level were measured. The cognitive ability in rats was tested by water maze. RESULTS: Water maze test showed on the 1st d, the maze test latency of the control group, the experimental group B and the experimental group C water were decreased gradually; Compared with the control group after 3 days, the latency of the experimental group A, experimental group B and experimental group C were all decreased, the crossing circle times were also reduced. Hippocampal neuron apoptosis were (2.3 ± 1.7)%, (14.7 ± 6.9)%, (4.2 ± 3.3)%, (10.2 ± 4.8)% in control group, experimental group A, experimental group B and experimental group C, respectively. The neurons apoptosis of experimental group A was significantly increased. The serum IL-4 and IL-10 of the experimental group A, experimental group B and experimental group C after anesthesia were significantly higher than the control group. The whole brain IL-1ß of the experimental group A, experimental group B and experimental group C were significantly lower than the control group. CONCLUSIONS: Propofol can reduce anesthesia effect of ketamine on the cognitive function and immune function in the young rats.

[Retrospective analysis of clinical and epidemiological characteristics of hand-foot-and-mouth disease deceased cases in Zhejiang Province].

OBJECTIVE: To understand the clinical and epidemiological characteristics of hand-foot-and-mouth disease (HFMD) deceased cases. METHOD: Information of demographics, diagnosis and treatment, clinical symptoms and signs, laboratory test results, and epidemiological contact history of 72 HFMD cases who died between May 2008 and September 2011, in Zhejiang Province, were collected and analyzed. RESULT: The average age of the 72 cases was 1.8 years, 45 were males, accounting for 62.5%, 63 (87.5%) of the cases were scattered children. Eighteen counties reported 2 or more deaths, accounting for 46.1% (18/39) among the counties where the deaths were reported. The deaths occurred mainly in April to August, the peak occurred in May and June. Fever (98.4%, 63/64) and rash (95.1%, 58/61) were the most common symptoms, but the rash was not obvious at the first diagnosis. Fever occurred before the rash (79.0%, 49/62), persisted for 4 days in average. Vomiting (71.9%, 46/64), dyspnea (65.6%, 42/64), cyanosis (53.1%, 34/64) and impaired consciousness (51.6%, 33/64) were often seen among the cases; 53.1% (34/64) cases went to see the doctor on the first day, but 82.5%(52/63)cases were misdiagnosed. Time to diagnosis of HFMD was in average 3 days. About 3 to 4 days after the onset, the disease deteriorated sharply, deaths occurred within 1 day after admission in 78.9%(45/57)of the deceased cases; 85.0% (34/40) cases had high white blood cells level, mainly neutrophils increased, the ratio of neutrophil was more than 70% in 55.6% (15/27) of cases. Enterovirus 71 (EV71) infection was found in 93.3% (56/60) cases, the deceased cases often died of pulmonary hemorrhage (42.9%, 21/49) and encephalitis (34.7%, 17/49). The sanitary conditions of the cases' family were poor (65.5%, 36/55), but 73.3% (33/45) cases had no exposure history. CONCLUSION: The HFMD deceased cases were mostly younger aged boys, scattered children, nonlocal-residents, and had poor sanitation. They were often infected with EV71, had high fever but had no typical rash, no clear exposure history, they had increased leukocyte, and were often misdiagnosed. Three or 4 days after onset, the disease deteriorated abruptly, most cases died within 1 week after onset. To decrease the HFMD mortality, early detection of severe cases should be stressed, and relative measures should be taken. The guardian should be aware of having good sanitary situation and healthy habits.

Crystallization and preliminary X-ray analysis of argininosuccinate lyase from Streptococcus mutans.

Argininosuccinate lyase (ASL) is an important enzyme in arginine synthesis and the urea cycle, which are highly conserved from bacteria to eukaryotes. The gene encoding Streptococcus mutans ASL (smASL) was amplified and cloned into expression vector pET28a. The recombinant smASL protein was expressed in a soluble form in Escherichia coli strain BL21 (DE3) and purified to homogeneity by two-step column chromatography. Crystals suitable for X-ray analysis were obtained and X-ray diffraction data were collected to a resolution of 2.5 Å. The crystals belonged to space group R3, with unit-cell parameters a = b = 254.5, c = 78.3 Å.

[Evidence-based quality assessment of 10-year orthodontic clinical trials in 4 major dental journals].

OBJECTIVE: To assess the quality of orthodontic clinical trials published in 4 major dental journals in the past 10 years and establish the reference standard for orthodontic clinical trials and quality control of dental journals. METHODS: All the clinical trials published in Chinese Journal of Stomatology, West China Journal of Stomatology, Journal of Practice Stomatology and Chinese Journal of Orthodontics from 1999 to 2008 were searched. The demographic information of the papers was extracted and the quality of the clinical trials according to the consolidated standards of reporting trials (CONSORT) was assessed. RESULTS: Four hundred and ninety-four clinical trials were retrieved, and 21.3% (105/494) of them were supported by grants. For the study design, only 26.1% (129/494) were prospective studies, and 3.8% (19/494) were randomized clinical trials. It was hard to evaluate precisely due to the lack of information about the details of the study designs. For the randomized clinical trials, the lack of details for randomization, allocation concealment, blinding and intention to treat compromised the quality. CONCLUSIONS: The general quality of clinical trials in orthodontics is poor. It needs to be improved both in the clinical study design and the paper writing.

Inhibitory effect of ghrelin on nicotine-induced VCAM-1 expression in human umbilical vein endothelial cells.

Endothelial dysfunction is thought to be a major cause of vascular injury in smokers. Ghrelin is a recently discovered peptide that plays a modulatory role in atherosclerosis. However, it is unknown how ghrelin regulates nicotine-induced vascular cell adhesion molecule-1 (VCAM-1) expression. We examined nicotine-induced VCAM-1 expression in human umbilical vein endothelial cells pretreated with ghrelin and detected the activity of protein kinase C (PKC), p38 mitogen-activated protein kinase (p38 MAPK), and nuclear factor (NF)-kappaB. Our study showed that ghrelin inhibited nicotine-induced VCAM-1 expression in human umbilical vein endothelial cells in a concentration-dependent and time-dependent way. We also found that ghrelin inhibited nicotine-induced PKC, p38 MAPK, and NF-kappaB activation. The results suggest that ghrelin inhibits nicotine-induced VCAM-1 expression, and PKC, p38 MAPK, and NF-kappaB play active roles in that process. Exogenous ghrelin may provide a possible approach for preventing or reversing atherosclerosis in smokers.

Expression of TNF-alpha protein in omental and subcutaneous adipose tissue in obesity.

BACKGROUND: During the last several years the role of adipose tissue in contributing to obesity-associated cardiovascular and metabolic risk has gained much attention. AIM: To examine the expression of TNF-alpha protein in omental and subcutaneous adipose tissue in correlation with plasma PAI-1 and other clinical parameters in obesity subjects. MATERIAL AND METHODS: Paired biopsies of omental and subcutaneous fat were collected during surgery in 32 obesity subjects. The expression of TNF-alpha protein in omental and subcutaneous fat was quantified by using Western blot method, and correlations with plasma PAI-1, homeostasis model assessment insulin resistance (HOMA-IR) and lipid were investigated. RESULTS: TNF-alpha protein expression was higher in omental than in subcutaneous adipose tissue (P<0.01). Significant positive linear correlations were found between TNF-alpha protein in omental adipose tissue and plasma PAI-1 in obesity subjects. TNF-alpha protein in omental fat was positively associated with HOMA-IR, triglycerides and negatively with HDL-cholesterol. CONCLUSION: TNF-alpha expression in omental adipose tissue could play a key role in contributing to cardiovascular risk in central obesity subjects.

Correlation between omental TNF-alpha protein and plasma PAI-1 in obesity subjects.

BACKGROUND: The role of TNF-alpha in contributing to obesity-associated cardiovascular and metabolic risk has gained much attention. MATERIALS AND METHODS: Paired biopsies of omental and subcutaneous fat were collected from 16 lean subjects and 32 central obesity subjects. The expression of TNF-alpha in omental and subcutaneous fat was quantified by western blotting method, and correlations with plasma PAI-1, homeostasis model assessment insulin resistance (HOMA-IR), and lipid were investigated. RESULTS: In obese female, TNF-alpha expression was higher in the omental than in the subcutaneous fat tissue. There was no significant difference in the levels of TNF-alpha between subcutaneous and visceral fat in obese male. Significant positive correlations were found between omental TNF-alpha protein and plasma PAI-1 levels in obesity. In obese female subjects, omental TNF-alpha protein levels showed a close association with most of the parameters studied: fasting glucose (r=0.541, P<0.05); fasting insulin (r=0.599, P<0.01); HOMA-IR (r=0.546, P<0.05); triglycerides (r=0.469, P<0.05); HDL-cholesterol (r=-0.759, P<0.01). In obese male population, correlations between omental TNF-alpha protein levels and fasting glucose (r=0.762, P<0.01); fasting insulin (r=0.622, P<0.05); triglycerides (r=0.650, P<0.05); HDL-cholesterol (r=-0.880, P<0.01) were found. CONCLUSION: Omental TNF-alpha may play a key role in contributing to cardiovascular risk in central obesity subjects.