3D culture of the spinal cord with roots as an ex vivo model for comparative studies of motor and sensory nerve regeneration.

Motor and sensory nerves exhibit tissue-specific structural and functional features. However, in vitro models designed to reflect tissue-specific differences between motor and sensory nerve regeneration have rarely been reported. Here, by embedding the spinal cord with roots (SCWR) in a 3D hydrogel environment, we compared the nerve regeneration processes between the ventral and dorsal roots. The 3D hydrogel environment induced an outward migration of neurons in the gray matter of the spinal cord, which allowed the long-term survival of motor neurons. Tuj1 immunofluorescence labeling confirmed the regeneration of neurites from both the ventral and dorsal roots. Next, we detected asymmetric ventral and dorsal root regeneration in response to nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF), and we observed motor and sensory Schwann cell phenotypes in the regenerated ventral and dorsal roots, respectively. Moreover, based on the SCWR model, we identified a targeted effect of collagen VI on sensory nerve fasciculation and characterized the protein expression profiles correlating to motor/sensory-specific nerve regeneration. These results suggest that the SCWR model can serve as a valuable ex vivo model for comparative study of motor and sensory nerve regeneration and for pharmacodynamic evaluations.

Cardiovascular autonomic neuropathy in patients with type 2 diabetes.

AIMS/INTRODUCTION: Heart rate recovery (HRR) after exercise is considered to be a new index of autonomic dysfunction associated with cardiovascular disease and mortality. The present study aimed to investigate the risk factors of HRR and the effects of exercise on the abnormal HRR in type 2 diabetes. MATERIALS AND METHODS: A total of 123 type 2 diabetes patients were recruited, and the oral glucose tolerance test and exercise test were carried out to analyze the risk factors associated with abnormal HRR. Among these patients, 42 patients with abnormal HRR were further randomized to either the conventional therapy group (CT group; n = 20) or the intensive therapy group (IT group; n = 22). The CT group patients underwent metformin and diet control, whereas the IT group additionally underwent a combined moderate intensity aerobic and resistance training three times per week for 12 weeks. The results of blood sample analysis and HRR were recorded before and after the training. RESULTS: Abnormal HRR was related to fasting blood glucose, glycosylated hemoglobin, low-density lipoprotein cholesterol, and resting and maximum heart rates (P < 0.05 for both). After training, the IT group had significantly lower levels of fasting blood glucose, glycosylated hemoglobin and resting heart rate than the CT group (all P < 0.01 or P < 0.005). Significant improvement in HRR and metabolic equivalents was observed in the IT group compared with the CT group (P < 0.05). CONCLUSIONS: These data suggested that combined aerobic and resistance training improved cardiac autonomic dysfunction as measured by HRR in type 2 diabetes patients. This might be due to better improvement of glycemic control, resting heart rate and physical fitness.

Effects of combined aerobic and resistance training on the glycolipid metabolism and inflammation levels in type 2 diabetes mellitus.

[Purpose] To investigate the effects of combined aerobic and resistance training on glycolipid metabolism and inflammation levels in type 2 diabetes mellitus patients. [Subjects and Methods] Forty-two diabetes patients were randomized to the conventional therapy group (n = 20) or intensive therapy group (n = 22). The control group contained 20 healthy people. The conventional therapy group received routine drug therapy and diet control, while the intensive therapy group additionally underwent combined aerobic and resistance training for 12 weeks. The oral glucose tolerance test and cardiopulmonary exercise testing were performed. Toll-like receptor 4 and NF-κBp65 protein and mRNA expressions were determined by qPCR and western blotting. ELISA was used to determine the expression levels of interleukin-18, interleukin-33, pentraxin-related protein 3, and human cartilage glycoprotein 39. [Results] After exercise training, the intensive therapy group had significantly lower postprandial blood glucose, postprandial insulin, and glycated hemoglobin level and insulin resistance index than the conventional therapy group. The intensive therapy group had significantly lower toll-like receptor 4 and NF-κBp65 protein and mRNA expressions, and serum interleukin-18 levels but significantly higher serum interleukin-33 levels. [Conclusion] Combined aerobic and resistance training can improve glycolipid metabolism and reduce low-grade inflammation in patients with diabetes mellitus patients.

Histone deacetylase HDAC4 promotes gastric cancer SGC-7901 cells progression via p21 repression.

Gastric cancer (GC) is one of the leading causes of cancer death in the world. The role of histone deacetylase 4 (HDAC4) in specific cell and tissue types has been identified. However, its biological roles in the development of gastric cancer remain largely unexplored. Quantitative real time PCR (qRT-PCR) and western blot were used to analyze the expression of HDAC4 in the clinical samples. siRNA and overexpression of HDAC4 and siRNA p21 were used to study functional effects in a proliferation, a colony formation, a adenosine 5'-triphosphate (ATP) assay and reactive oxygen species(ROS) generation, cell cycle, cell apoptosis rates, and autophagy assays. HDAC4 was up-regulated in gastric cancer tissues and several gastric cancer cell lines. The proliferation, colony formation ability and ATP level were enhanced in HDAC4 overexpression SGC-7901 cells, but inhibited in HDAC4 knockdown SGC-7901 cells. HDAC4 knockdown led to G0/G1 phase cell arrest and caused apoptosis and ROS increase. Moreover, HDAC4 was found to inhibit p21 expression in gastric cancer SGC-7901 cells. p21 knockdown dramatically attenuated cell proliferation inhibition, cell cycle arrest, cell apoptosis promotion and autophagy up-regulation in HDAC4-siRNA SGC-7901 cells. We demonstrated that HDAC4 promotes gastric cancer cell progression mediated through the repression of p21. Our results provide an experimental basis for understanding the pro-tumor mechanism of HDAC4 as treatment for gastric cancer.

[Relationship between methylenetetrahydrofolate reductase gene C677T polymorphism and susceptibility of ischemic stroke: a meta-analysis].

OBJECTIVE: To evaluate the relationship between the methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and the susceptibility of ischemic stroke among different ethnic populations. METHODS: The databases of MEDLINE, EMBASE, Cochrane Library and others were searched. And a total of 17 studies published in English between 2000 and October 2010 on the association of MTHFR gene C677T polymorphism with ischemic stroke were selected. A comprehensive quantitative analysis was performed by meta-analysis. RESULTS: The results showed that the pooled OR values of ischemic stroke with TT and CC genotype were 1.30 (95%CI: 1.11 to 1.52) and 0.88 (95%CI: 0.79 to 0.98) respectively. And when sub-grouped by ethnic populations, the Caucasians were more likely than other populations to suffer ischemic stroke. There was a low probability of publication bias. CONCLUSION: The presence of MTHFR TT gene is associated with an elevated risk of developing ischemic stroke, especially in Caucasians.

[Meta-analysis on the association between subclinical hypothyroidism and the left ventricular functions under Doppler echocardiography].

OBJECTIVE: To explore the association between subclinical hypothyroidism and the left ventricular functions under conventional 2D Doppler echocardiography and to provide evidence for the protection of heart function. METHODS: Literatures regarding the association of subclinical hypothyroidism and the left ventricular functions were retrieved in large databases from home and abroad for the last 12 years. The left ventricular systolic function was assessed by left ventricular ejection fraction and the shortening of left ventricular fraction. The left ventricular diastolic function was assessed by left ventricular early diastolic filling flow velocity, late diastolic filling flow velocity, their ratios (E/A), and the left ventricular isovolumic relaxation time. The relationship between subclinical hypothyroidism and the left ventricular functions were assessed by Meta-analysis with Stata 11 software. The weighted mean difference (WMD) and 95% confidence interval (CI) were calculated, and the publication bias was assessed by Begg's test. RESULTS: 13 eligible papers were included. (1) Statistics on the combined data showed that in the evaluation of left ventricular diastolic function indicators. There were significant differences in left ventricular late diastolic filling flow velocity (WMD = 4.51, 95%CI: 2.41 to 6.61) and E/A (WMD = -0.22, 95%CI: -0.30 to -0.13), as well as the left ventricular isovolumic relaxation time (WMD = 6.13, 95%CI: 2.79 to 9.48) between patients with subclinical hypothyroidism and normal controls but, no significant difference was found in left ventricular early diastolic filling flow velocity. Looking at the left ventricular systolic function indicators. There were no significant differences in the left ventricular ejection fraction and left ventricular fractional shortening between patients with subclinical hypothyroidism and normal controls. (2) Data from the subgroup analysis showed that the differences of left ventricular late diastolic filling flow velocity, E/A and left ventricular isovolumic relaxation time were significantly different between patients with subclinical hypothyroidism and normal controls in the mean heart rate ≥ 72 bpm group. The difference of left ventricular isovolumic relaxation time was significantly different in the mean heart rate < 72 bpm group, and the difference of left ventricular late diastolic filling flow velocity was significant in the mean age < 60-year-old group. CONCLUSION: Subclinical hypothyroidism was associated with the left ventricular diastolic dysfunction, but not associated with the left ventricular systolic dysfunction. The results suggested that subclinical hypothyroidism might change the heart function which could be evaluated by Doppler echocardiography.

Remission induction and maintenance effect of probiotics on ulcerative colitis: a meta-analysis.

AIM: To evaluate the induction of remission and maintenance effects of probiotics for ulcerative colitis. METHODS: Information was retrieved from MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The induction of remission and promotion of maintenance were compared between probiotics treatment and non-probiotics treatment in ulcerative colitis. RESULTS: Thirteen randomized controlled studies met the selection criteria. Seven studies evaluated the remission rate, and eight studies estimated the recurrence rate; two studies evaluated both remission and recurrence rates. Compared with the non-probiotics group, the remission rate for ulcerative colitis patients who received probiotics was 1.35 (95% CI: 0.98-1.85). Compared with the placebo group, the remission rate of ulcerative colitis who received probiotics was 2.00 (95% CI: 1.35-2.96). During the course of treatment, in patients who received probiotics for less than 12 mo compared with the group treated by non-probiotics, the remission rate of ulcerative colitis was 1.36 (95% CI: 1.07-1.73). Compared with the non-probiotics group, the recurrence rate of ulcerative colitis patients who received probiotics was 0.69 (95% CI: 2.47-1.01). In the mild to moderate group who received probiotics, compared to the group who did not receive probiotics, the recurrence rate was 0.25 (95% CI: 0.12-0.51). The group who received Bifidobacterium bifidum treatment had a recurrence rate of 0.25 (95% CI: 0.12-0.50) compared with the non-probiotics group. CONCLUSION: Probiotic treatment was more effective than placebo in maintaining remission in ulcerative colitis.

[Effects of electroacupuncture on tumor growth and immune function in the Walker-256 model rat].

OBJECTIVE: To study the effect of acupuncture on tumor and its mechanism. METHODS: Liver cancer, gastric cancer and hypodermic tumor rat models were made by implantation of replicated Walker-256 cell strain. The 3 model rats were respectively divided into two groups at random, a model control group and an electroacupuncture group. The electroacupuncture groups were treated with electroacupuncture (EA) at "Zusanli" (ST 36), "Hegu" (LI 4) and "San-yinjiao" (SP 6), once each day, 15 min one session, for 15 days. The gross tumor volume and the tumor inhibitory rate, and the levels of humoral immunity index, including serum 1gG, IgM, IgA and C3, C4, and the levels of cellular immunity index, including CD4+, CD8+ and CD4+/CD8+ in the peripheral blood in each group were detected. RESULTS: The gross tumor volumes in the EA groups were significantly smaller than those in the model control group (P<0.01). The contents of IgG, IgM and C3 in the EA groups increased significantly compared with those in the model control group (P<0.05 or P<0.01). The contents of IgA and C4 in the EA groups did not significantly change (P>0.05). The content of CD4+ and CD4+/CD8+ in the EA groups are significantly higher than those in the model control group (P<0.05 or P<0.01). CONCLUSION: Acupuncture at "Zusanli" (ST 36), "Hegu" (LI 4) and "Sanyinjiao" (SP 6) can increase immune function and inhibit tumor growth in Walker-256 liver cancer, gastric cancer and hypodermic tumor rats.

[Preliminary analysis on the significance of the new edition of pharmacology of Chinese Materia Medica in guiding theoretical research and clinical practice of integrated Chinese and Western medicine].

The new edition of Pharmacology of Chinese Materia Medica has broken through the previous mode of the teaching materials, it classified traditional Chinese drugs distinctly into three categories--the drugs for radical cure depending on syndrome differentiation, the drugs for etiological treatment aimed at pathogenesis, and the drugs for symptomatic treatment, and introduced some new concepts about integrated Chinese and Western medicine, showing active significance in guiding the theoretical research and clinical practice of integrated traditional Chinese and Western medicine.