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OBJECTIVE: Diabetic patients are often comorbid with dyslipidemia, however, the relationship between high-density lipoprotein cholesterol(HDL-C) and diabetic retinopathy (DR) in the adult diabetic population remains to be fully elucidated.The aim of this study is to evaluate the associations between HDL-C and DR in the United States adults with diabetes. METHODS: A total of 1708 participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2008 were enrolled in the present study. Fundus images of all study subjects were captured and evaluated using a digital camera and an ophthalmic digital imaging system, and the diagnosis of DR was made by the severity scale of the Early Treatment Diabetic Retinopathy Study (ETDRS).Roche Diagnostics were used to measure serum HDL-C concentration. The relationship of DR with HDL-C was investigated using multivariable logistic regression. The potential non-line correlation was explored with smooth curve fitting approach. RESULTS: The fully-adjusted model showed that HDL-C positively correlated with DR(OR:1.69, 95%CI: 1.25-2.31).However, an inverted U-shaped association between them was observed by applying the smooth curve fitted method. The inflection point of HDL-C(1.99mmol/l) was calculated by utilizing the two-piecewise logistic regression model. In the subgroup analysis, the inverted U-shaped nonlinear correlation between HDL-C and DR was also found in female, Non-Hispanic White, and lower age groups. CONCLUSION: Our study revealed an inverted U-shaped positive relationship between HDL-C and DR.The findings may provide us with a more comprehensive understanding of the association between HDL-C and DR.

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PURPOSE: Nutrition intake is one of the modifiable risk factors for cognitive decline. Whether energy and protein intakes alter the association between pulmonary function (PF) and cognition has not been studied. METHODS: We made use of information from the U.S. National Health and Nutrition Examination Survey (NHANES) 2011-2012. PF measures, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF), were calculated, whereas cognitive function was assessed through four tests: the Immediate Recall test (IRT), the Delayed Recall test (DRT), the Animal Fluency test (AFT) and the Digit Symbol Substitution test (DSST). Energy and protein intakes were measured using the 24-h dietary recall method. Weighted generalized linear regression was performed upon adjustment for covariates. Further interaction analyses were conducted to investigate the effect of energy and protein intakes on the association between PF and cognition. RESULTS: We finally included 803 participants aged ≥ 60 years (54.4% female, weighted value). After adjusting for covariates, multiple measures (including FEV1, FVC, PEF, and composite PF) were all positively associated with better global cognition and the DSST score (P < 0.05). A stronger positive association between the DSST score and FEV1 (P for interaction = 0.001), FVC (P for interaction = 0.004), PEF (P for interaction = 0.003), and composite PF (P for interaction = 0.001) in lower energy intake. Similar results were observed in lower protein intake (all P for interaction < 0.05). CONCLUSION: Higher PF was independently associated with improved specific components of cognitive function (i.e., the DSST score). The positive association between PF and the DSST score was stronger in individuals with lower energy and protein intakes.

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Background: Neuroinflammation is related with the inflammatory stress of brain tissue induced by the activation of microglial in the central nervous system (CNS), which is still an intractable disease for modern clinical system. Chlorogenic acid has multiple biological activities such as antivirus and anti-inflammation, while few researches have revealed its therapeutic functions in neuroinflammation. Methods: BV2 cells were treated with lipopolysaccharide (LPS) to establish neuroinflammation cell models, and the effects and mechanism of chlorogenic acid in improving the inflammatory progression were investigated. In brief, the toxicity of chlorogenic acid on BV2 cells was detected with MTT assay. The levels of the inflammatory factors including TNF-α, IL-6, IL-1ß, and IFN-α were measured with ELISA, and the abundances of TLR4, MyD88, TRIF, and NF-κB were observed by qRT-PCR and western blot. Results: Chlorogenic acid did not exhibit obvious toxic and side effects on BV2 cells. The levels of TNF-α, IL-6, IL-1ß, and IFN-α were observably upregulated in BV2 cells after treating with LPS. Chlorogenic acid significantly reduced the levels of TNF-α, IL-6, IL-1ß, and IFN-α. Moreover, the abundances of TLR4, MyD88, TRIF, and NF-κB were increased in LPS-induced BV2 cells, while chlorogenic acid could obviously reduce their expressions. Conclusion: This study suggests that chlorogenic acid can improve the inflammatory stress of LPS-induced BV2 cell via interacting with the TLR4-mediated downstream pathway, which is a potential drug for neuroinflammation treatment.

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Nonalcoholic fatty liver disease (NAFLD), which has a wide global distribution, includes different stages ranging from simple steatosis to nonalcoholic steatohepatitis, advanced fibrosis, and liver cirrhosis according to the degree of severity. Chronic low-grade inflammation, insulin resistance, and lipid accumulation are the leading causes of NAFLD. To date, no effective medicine for NAFLD has been approved by governmental agencies. Our study demonstrated that the expression of dual-specificity phosphatase 26 (Dusp26), a member of the Dusp protein family, was decreased in the liver tissue of mice with hepatic steatosis and genetically obese (ob/ob) mice. In our study, hepatic steatosis, inflammatory responses, and insulin resistance were exacerbated in liver-specific Dusp26-knockout (KO) mice but ameliorated in liver-specific Dusp26-transgenic mice induced by a high-fat diet. In addition, the degree of liver fibrosis was aggravated in high-fat high-cholesterol diet-induced Dusp26-KO mice. We further found that the binding of Dusp26 to transforming growth factor beta-activated kinase 1 (TAK1) to block the phosphorylation of TAK1 regulated the TAK1-p38/c-Jun NH2-terminal kinase signaling axis to alleviate hepatic steatosis and metabolic disturbance. Conclusion: These findings suggest that Dusp26 is a good TAK1-dependent therapeutic target for NAFLD.

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The objective of this study was to explore the efficacy of glial fibrillary acidic protein (GFAP) in differentiating intracerebral hemorrhage (ICH) from ischemic stroke (IS). Suspicious patients of acute stroke were screened and finally diagnosed by computed tomography and magnetic resonance imaging. Blood samples were collected within 2-6 h after onset of symptoms, and serum GFAP level was determined by ELISA assay. The functional outcome for the patients was determined by modified Rankin Scale (mRS) 90 days after onset of symptoms. 43 ICH patients and 65 IS patients were enrolled. GFAP concentration in ICH group was significantly higher than in IS group (p < 0.001). Significant correlation was found when comparing GFAP with National Institutes of Health Stroke Scale (NIHSS) (r = 0.418, p = 0.005) and hemorrhage volume (r = 0.840, p < 0.001) in ICH group, while such correlation was not observed in IS group. ROC analysis indicated that GFAP level at the cut-point of 0.7 ng/ml yielded an AUC of 0.901 (95 % CI 0.828-0.950) with high sensitivity (86.0 %) and specificity (76.9 %) to differentiate ICH from IS. Patients with higher serum GFAP concentration in ICH group experienced poorer functional disability (r = 0.755, p < 0.001), while this phenomenon was not observed in IS group (r = -0.114, p = 0.368). ROC curve analysis found that GFAP level at the cut-point of 1.04 ng/ml yielded an AUC of 0.936 (95 % CI 0.817-0.988) in identifying patients with poor functional outcome, at the sensitivity and specificity of 95.7 and 80.0 %, respectively. GFAP test is a promising technique for diagnosis of ICH from IS and prediction of short-term functional outcomes.

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BACKGROUND: Cerebral stroke is a disease with a high disability rate and a high fatality rate. This study was undertaken to assess the risk of stroke associated pneumonia (SAP) in patients with ischemic stroke using A2DS2 score. METHODS: Altogether 1 279 patients with ischemic stroke who were treated in our department from 2009 to 2011 were retrospectively analyzed with A2DS2 score. A2DS2 score was calculated as follows: age ≥75 years=1, atrial fibrillation=1, dysphagia=2, male sex=1; stroke severity: NIHSS score 0-4=0, 5-15=3, ≥16=5. The patients were divided into three groups according to A2DS2 score: 620 in score 0 group, 383 in score 1-9 group, and 276 in score ≥10 group. The three groups were comparatively analyzed. The diagnostic criteria for SAP were as follows: newly emerging lesions or progressively infiltrating lesions on post-stroke chest images combined with more than two of the following clinical symptoms of infection: (1) fever ≥38 °C; (2) newly occurred cough, productive cough or exacerbation of preexisting respiratory tract symptoms with or without chest pain; (3) signs of pulmonary consolidation and/or wet rales; (4) peripheral white blood cell count ≥10×10(9)/L or ≤4×10(9)/L with or without nuclear shift to left, while excluding some diseases with clinical manifestations similar to pneumonia, such as tuberculosis, pulmonary tumors, non-infectious interstitial lung disease, pulmonary edema, pulmonary embolism and atelectasis. The incidence and mortality of SAP as well as the correlation with ischemic stroke site were analyzed in the three groups respectively. Mean± standard deviation was used to represent measurement data with normal distribution and Student's t test was used. The chi-square test was used to calculate the percentage for enumeration data. RESULTS: The incidence of SAP was significantly higher in the A2DS2 score≥10 group than that in the score 1-9 and score 0 groups (71.7% vs. 22.7%, 71.7% vs. 3.7%, respectively), whereas the mortality in the score≥10 group was significantly higher than that in the score 1-9 and score 0 groups (16.7% vs. 4.96%, 16.7% vs. 0.3%, respectively). The incidences of cerebral infarction in posterior circulation and cross-MCA, ACA distribution areas were significantly higher than those in the SAP group and in the non-SAP group (35.1% vs.10.1%, 11.4% vs. 7.5%, respectively). The incidence of non-fermentative bacteria infection was significantly increased in the score≥10 group. CONCLUSIONS: A2DS2 score provides a basis for risk stratification of SAP. The prevention of SAP needs to be strengthened in acute ischemic stroke patients with a A2DS2 score≥10.

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The calcium/calmodulin-dependent protein kinase kinase 2, adenosine monophosphate-activated protein kinase (CAMKK2-AMPK) pathway mediated amyloid ß42 (Aß42)-induced synaptotoxicity and blockage of CAMKK2-protected neurons against the effect of Aß42. Numerous microRNAs (miRNAs) were downregulated in response to Aß42, including miR-9, a synapse-enriched miRNA that is decreased in Alzheimer's disease. In the present study the effect of miR-9 on Aß42­triggered CAMKK2-AMPK activation and the synaptotoxic impairment was investigated. Aß42 oligomers were identified to be capable of inducing CAMKK2-AMPK pathway activation, which was attenuated by miR-9 overexpression. CAMKK2 was predicted to be a target of miR-9 using Pictar and Targetscan 6.2 Bioinformatics' algorithms. A luciferase activity assay and western blot analysis confirmed that miR-9 significantly inhibited CAMKK2 expression. Additionally, overexpression of miR-9 was sufficient to restore Aß42-induced dendritic spine loss and rescued Aß42-induced τ phosphorylation at Ser-262 mediated by the CAMKK2-AMPK pathway. The results of the present study demonstrated that miR-9 attenuated Aß-induced synaptotoxicity by targeting CAMKK2.

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Neuroprotection has been the focus of several current efforts to develop a strategy for the treatment of Parkinson's disease (PD). The B-type monoamine oxidase (MAO-B) inhibitor deprenyl (selegiline) is used clinically as a PD therapeutic agent, however, its cytoprotective mechanism has not yet been fully elucidated. In this study, we show that deprenyl upregulates the expression and activity of NAD(P)H: quinone oxidoreductase 1 (NQO1), attenuates the increase in the quinoprotein levels in 1-methyl-4-phenylpyridinium (MPP(+))-treated PC12 cells, and protects PC12 cells from oxidative damage. Deprenyl triggers the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway by increasing the nuclear translocation and DNA-binding activity of Nrf2. Both the antioxidant activity of deprenyl and its effect on NQO1 upregulation were greatly attenuated in Nrf2 siRNA transfected cells. The phosphorylation of extracellular regulating protein kinase (Erk) and Akt can be induced by the administration of 50µM deprenyl in PC12 cells, and the ability of deprenyl to enhance NQO1 expression and Nrf2 nuclear translocation is partly attenuated by the mitogen-activated protein kinase kinase (MEK) inhibitor PD98059 and is almost completely attenuated by the phosphatidyl-inositol 3 kinase (PI3K) inhibitor LY294002. The activation of Nrf2/ARE signaling by deprenyl in PC12 cells is independent of MAO-B inhibition. Altogether, our findings indicate that deprenyl protects PC12 cells exposed to MPP(+) resulting from oxidative stress via the Nrf2-mediated upregulation of NQO1 involving both the PI3K/Akt and Erk pathways.

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