Tetramethylpyrazine protects neural stem cells against sevoflurane-induced toxicity through Akt/GSK-3ß pathway.

Sevoflurane, a commonly used anesthetic, has been found to cause neural stem cell (NSC) injury, thereby contributing to neurocognitive impairment following general anesthesia. Tetramethylpyrazine (TMP), one of the most widely used medicinal compounds isolated from a traditional Chinese herb, possess neuroprotective activity. However, its effect on sevoflurane-induced NSC injury remains unclear. NSCs were pretreated with indicated concentrations of TMP for 2 h and then exposed to sevoflurane for 6 h. Cell injury was measured using lactate dehydrogenase (LDH) release assay. Cell viability and proliferation were detected by cell counting kit-8 (CCK-8) assay and 5-bromo-2'-deoxyuridine (BrdU) labeling, respectively. Apoptotic cells were detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The levels of cleaved caspase-3, phosphorylated protein kinase B (Akt) and phosphorylated glycogen synthase kinase-3ß (GSK-3ß) were detected by western blotting. Our results showed exposure to sevoflurane decreased the viability and proliferation of NSCs, while TMP preserved NSC viability and proliferation after sevoflurane exposure. In addition, the expression of cleaved caspase-3 and TUNEL positive cells were markedly decreased in TMP-treated NSCs compared with the control. Furthermore, pretreatment with TMP significantly increased the levels of phosphorylated Akt and GSK-3ß in sevoflurane-injured NSCs. However, an upstream inhibitor of Akt, LY294002 abolished the protective of TMP on the cell viability of NSCs. In conclusion, these findings indicate that TMP protects NSCs from sevoflurane-induced toxicity through Akt/GSK-3ß pathway.

Contribution of WNT2B Genetic Variants to Ischemic Stroke Occurrence in a Chinese Han Population.

ABSTRACT: Wnt signaling pathway-related WNT2B gene was upregulated in ischemic brain damage. We aimed to assess the contribution of WNT2B genetic variant to ischemic stroke (IS) susceptibility in the Chinese Han population. Five polymorphisms including rs3790606, rs351364, rs3790608, rs12037987, and rs10776752 in WNT2B were genotyped using Agena MassARRAY platform in 476 healthy controls and 501 patients with IS. Odds ratio (OR) and 95% confidence interval (CI) adjusted for age and gender were estimated by logistic regression analysis. Analysis of variance was used to evaluate the association between genotypes of WNT2B variants and blood lipid parameters. Rs12037987 (OR = 1.82, 95% CI: 1.18-2.82, P = 0.007) and rs10776752 (OR = 1.74, 95% CI: 1.13-2.68, P = 0.012) were related to the increased IS susceptibility. Interestingly, rs12037987 (OR = 2.01, P = 0.028) and rs10776752 (OR = 2.02, P = 0.028) had the higher IS risk in the subjects younger than or equal to 65 years. Rs12037987 (OR = 2.70, P = 0.013), rs10776752 (OR = 2.71, P = 0.012), and rs3790606 (OR = 1.89, P = 0.036) manifested an increasing-risk association with IS occurrence in women. Moreover, rs3790606 genotype was related to serum levels of triglyceride (P = 0.008) and total cholesterol (P = 0.001). Our study reported that rs12037987 and rs10776752 were associated with the increased risk for IS in the Chinese Han population. Our findings may be useful for insight into the contribution of WNT2B variants to the complex pathogenesis of IS.

Role of PVT1 polymorphisms in the glioma susceptibility and prognosis.

BACKGROUND: Genetic factors play a crucial role in the glioma risk and prognosis of glioma patients. To explore the role of plasmacytoma variant translocation 1 (PVT1) polymorphism in the susceptibility and survival of glioma in the Chinese Han population, we conducted a case-control study. METHODS: The three single-nucleotide polymorphisms (SNPs) in PVT1 were genotyped using Agena MassARRAY from 575 patients with glioma and 500 healthy controls. We used the χ2 test to analyze the differences in distribution of allele and genotype between the cases and controls. Odds ratio and 95% confidence interval (CI) were calculated by logistic regression analysis to evaluate the association SNPs with glioma risk. The effects of polymorphisms and clinical features on survival of glioma patients were evaluated using the log-rank test, Kaplan-Meier and Cox regression analysis. RESULTS: We found that rs13255292 was associated with a decreased risk of glioma in the recessive model in overall or male; and rs4410871 was significantly associated with an increased the risk of glioma in age ≤40 years old or female. Moreover, the extent of resection and chemotherapy were found to be key prognostic factors in survival of glioma patients. However, the gender, age, tumor grade, radiotherapy and PVT1 polymorphisms have no effect on prognosis of glioma patients. CONCLUSIONS: Our results indicated that PVT1 polymorphisms (rs13255292 and rs4410871) were associated with glioma susceptibility, but have no effect on prognosis of glioma patients. Further studies with large samples are required to confirm the results.

Genetic variants of the MIR31HG gene are related to a risk of IgA nephropathy.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Previous studies reveal that genetic factors play a crucial role in IgAN progression. This study was conducted to investigate the association between MIR31HG variants and IgAN risk. A total of 836 subjects were recruited to detect the relationship of MIR31HG variants with IgAN susceptibility. Odds ratios (OR) and 95% confidence intervals (CI) were computed to evaluate the associations. Multifactor dimensionality reduction was performed to analyze the SNP-SNP interaction with IgAN risk. Our study showed that rs1332184 and rs55683539 significantly related to an increased risk of IgAN (OR 1.34, p = 0.041; OR 1.39, p = 0.025). Stratified analyses indicated rs72703442, rs55683539, and rs10965064 exhibited strongly enhanced risk of IgAN in age ≤ 35 years (OR 1.55, p = 0.023; OR 1.60, p = 0.012; OR 1.46, p = 0.037). Besides, we found rs1332184, rs55683539 and rs2181559 significantly increased the susceptibility of IgAN in males (OR 1.71, p = 0.003; OR 1.44, p = 0.042; OR 1.60, p = 0.010). We also observed that rs1332184 could enhance IgAN risk for Lee's grade ≥ III (OR 1.39, p = 0.045). Rs55683539 significantly increased a risk of IgAN (OR 1.58, p = 0.027), while rs2025327 had a lower risk of IgAN in Lee's grade < III (OR 0.46, p = 0.007). Interestingly, we found rs72703442 polymorphism was related to hemoglobin (p = 0.043), and rs10965064 was associated with Urine red blood cell (p = 0.040). Our study proposed that MIR31HG polymorphisms associate with susceptibility to IgAN in Chinese population.

The Impact of PPARD and PPARG Polymorphisms on Glioma Risk and Prognosis.

Recent studies showed that peroxisome proliferator-activated receptors (PPARs) had effects on the progression of multiple tumors, but the role of PPARD and PPARG in glioma remains poorly understand. We conducted a case-control study to investigate the association of polymorphisms in PPARD and PPARG with glioma risk and prognosis in the Chinese Han population. Seven polymorphisms (PPARD: rs2016520, rs67056409, rs1053049 and rs2206030; PPARG: rs2920503, rs4073770 and rs1151988) were genotyped using the Agena MassARRAY system in 568 glioma patients and 509 healthy controls. The odd ratios (OR) and 95% confidence interval (CI) were calculated to assess the association of PPARD and PPARG polymorphisms with glioma risk. The Multifactor dimensionality reduction (MDR) method was used to analysis interactions of genetic polymorphisms on glioma risk. Then, we conducted log-rank test, Kaplan-Meier analysis and Cox regression model to evaluate the relationship of PPARD and PPARG polymorphisms with glioma prognosis. We found PPARD polymorphisms (rs2016520, rs67056409, rs1053049) were significantly associated with glioma risk in multiple models (P < 0.05). Stratified analysis showed rs2016520, rs67056409, rs1053049 of PPARD significantly decreased risk of glioma in the subgroup of age > 40 and astrocytoma (P < 0.05). For male, PPARD rs1053049 had a strong relationship with glioma risk in allele (P = 0.041), dominant (P = 0.040) and additive (P = 0.040) models. The effect of PPARG rs2920503 on glioma risk was related to glioma grade (P < 0.05). MDR showed that a seven-locus model was the best polymorphisms interaction pattern. Moreover, surgery and chemotherapy had strongly impact on overall survival and progression free survival of glioma patients. Our findings suggested that PPARD and PPARG polymorphisms were associated with glioma risk and prognosis in the Chinese Han population, and further studies are need to confirm our results.

Efficacy of infection control pathway in reducing postoperative infections in patients undergoing neurosurgery.

INTRODUCTION: The environment of the operating room (OR) is closely related to the postoperative complications of patients, and it is necessary to study, to what extent, the stringent management of the OR can reduce postoperative complications. METHODOLOGY: 426 patients who underwent surgery between January 2016 and December 2017 were selected from two class-100 laminar flow ORs of equivalent area, and were divided into an experimental group and a control group. RESULTS: The experimental group had significantly lower total air-borne bacterial count in the OR than the control group 10 minutes before surgery (6.21 ± 4.14 vs. 11.58 ± 5.36 CFU/cm3), 10 minutes (15.67 ± 6.21 vs. 20.83 ± 5.78 CFU/cm3), 30 minutes (27.34 ± 8.18 vs. 39.56 ± 7.86 CFU/cm3) and 60 minutes (43.62 ± 7.66 vs. 51.63 ± 8.43 CFU/cm3) into surgery, and at the end of surgery (57.34 ± 7.67 vs. 69.33 ± 9.41 CFU/cm3) (all p < 0.05). The incidence rates of increased body temperature and leukocyte count 3 days post-surgery, and the duration of antibiotic therapy and hospital stay were significantly reduced in the experimental group compared to the control group (all p < 0.05). Furthermore, the total number of pathogens in the incision at 2 hours into surgery was also significantly lower in the experimental group than in the control group (p < 0.05). CONCLUSION: Stringent application of the infection control pathway is an efficacious measure for improving the air cleanliness of the neurosurgery OR, decreasing the incidence rates of postoperative complications and infection, as well as controlling pathogen transmission.

The Association of Peroxisome Proliferator-Activated Receptor δ and Additional Gene-Gene Interaction with C-Reactive Protein in Chinese Population.

Aims. To examine the association between 4 single nucleotide polymorphisms (SNPs) of peroxisome proliferator-activated receptors δ (PPARδ) polymorphisms and C-reactive protein (CRP) level and additional gene-gene interaction. Methods. Line regression analysis was performed to verify polymorphism association between SNP and CRP levels. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the interaction. Results. A total of 1028 subjects (538 men, 490 women) were selected. The carriers of the C allele (TC or CC) of rs2016520 were associated with a significant decreased level of CRP, regression coefficients was -0.338, and standard error was 0.104 (p = 0.001). The carriers of the G allele (CG or GG) of rs9794 were also significantly associated with decreased level of CRP, regression coefficients was -0.219, and standard error was 0.114 (p = 0.012). We also found a potential gene-gene interaction between rs2016520 and rs9794. Subjects with rs2016520-TC or CC, rs9794-CG or GG genotypes have lowest CRP level, difference (95% CI) = -0.50 (-0.69 to -0.21) (p < 0.001), compared to subjects with rs2016520-TT and rs9794-CC genotypes. Conclusions. rs2016520 and rs9794 minor allele of PPARδ and combined effect between the two SNP were associated with decreased CRP level.

Uremia-caused changes of ghrelin system in hippocampus may be associated with impaired cognitive function of hippocampus.

PURPOSE: Hippocampus plays an important role in spatial learning and memory. Ghrelin, a brain-gut peptide, participates in the mnestic functions of hippocampus through its receptor growth hormone secretagogue receptor (GHS-R) distributed in hippocampus. This study was to investigate whether there was a correlation between the changes of ghrelin system in hippocampus and the spatial cognitive impairment caused by chronic renal failure (CRF). METHODS: Sprague-Dawley rats (male, 180 ± 10 g, 7-8 weeks old) were randomly classified into CRF group and control group (n = 18 per group). The CRF model was constructed by 5/6 nephrectomy and the controls treated with sham operation. By the 8th week after the surgery, the spatial cognitive function of rats was assessed by Morris water-maze test (MWM), the protein expression of ghrelin and GHS-R in the hippocampus by immunohistochemistry, and the mRNA expression by real-time PCR. Statistical analysis was performed using ANOVA, Student-Newman-Keuls-q test and Pearson correlation analysis, and P < 0.05 was considered significant. RESULTS: Compared with the controls, the time spent in "platform" quadrant (TSPQ) of rats with CRF was decreased, but the escape latency (EL) was increased significantly in MWM, and meanwhile the protein and mRNA expression of ghrelin and GHS-R in hippocampus was also increased significantly (P < 0.05 or P < 0.01). Correlation analysis suggested that the TSPQ was negatively but the EL was positively correlated with the mRNA expression of ghrelin and GHS-R (P < 0.01). CONCLUSION: The CRF-caused changes of ghrelin system in hippocampus might be correlated with the CRF-caused cognitive function impairment.

Effects of chronic renal failure on gastrointestinal motility: a study on the changes of gastric emptying, small intestinal transit, interdigestive myoelectric complex, and fecal water content.

BACKGROUND: Gastrointestinal (GI) dysfunction may lead to malnutrition in patients with chronic renal failure (CRF). This study investigated the effects of CRF on GI motility. METHODS: Forty-eight Sprague Dawley rats (180 ± 20 g) were randomly classified into CRF group and sham-operated (Sham) group, and each group was further assigned for gastric emptying (GE), small intestinal transit (SIT), interdigestive myoelectric complex (IMC), and fecal water content (FWC) experiments (6 CRF and 6 Sham rats per experiment). The CRF model was established by 5/6 nephrectomy. The body weight (BT), GE, SIT, IMC, and FWC of the rats were observed. ANOVA and Student-Newman-Keuls q-test were utilized to do statistical analysis. RESULTS: The BT of the rats in the two groups had no statistical difference before surgery. But in the ninth week after surgery, the CRF rats (230 ± 20 g) weighed less than the Sham rats (260 ± 15 g) (p < 0.05). The GE rate and SIT rate in CRF rats were significantly lower than that of Sham rats (GE 33.08 ± 7.50 vs. 53.37 ± 9.78%; SIT 42.92 ± 8.96 vs. 58.67 ± 9.12%) (p < 0.05). Compared with the IMC of the Sham rats, the CRF rats showed obvious alterations in (a) IMC cycle; (b) phase II and phase III duration; and (c) phase III cycling frequency, amplitude, and percentage (p < 0.05). FWC of the CRF rats increased significantly (p < 0.05). CONCLUSION: The GI motility of the CRF rats is obviously impaired. This finding may indicate that the effects of CRF on GI motility might be relatively prevalent.

[Expression of ghrelin and its receptor GHS-R in the hypothalamus and gastrointestinal tract in rats with chronic renal failure].

OBJECTIVE: To investigate the expression of ghrelin and its receptor, growth hormone secretagogue receptor (GHS-R), in the hypothalamus and gastrointestinal tract in rats with chronic renal failure (CRF) and explore their relationship with the disorder of gastrointestinal tract motility. METHODS: SD rats were randomly divided into sham-operated group (n=8) and CRF group (n=16), and in the latter group, the rats were subjected to 5/6 nephrectomy to induce CRF. Real-time PCR and immunohistochemical staining were used to detect the distribution of mRNA and protein of ghrelin and GHS-R in the gastric fundus, duodenum, and hypothalamus. RESULTS: The rats in the CRF group showed a significantly higher expression of ghrelin mRNA and protein in the gastric fundus but a lower expression in the hypothalamus than those in the sham-operated group (P<0.01), but the expression in the duodenum was similar between the two groups (P>0.05). The expression of GHS-R mRNA and protein in the gastric fundus was significantly higher in the CRF group than in the sham-operated group (P<0.01), while in the hypothalamus and duodenum, the expression was significantly lower in the CRF group (P<0.01). CONCLUSION: The different distribution patterns of ghrelin and GHS-R in the tissues may be an important pathological basis of gastrointestinal motility disorder in CRF.