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Liu S.,Soochow University of China | Cheng X.-Y.,Soochow University of China | Wang F.,Soochow University of China | Liu C.-F.,Soochow University of China | Liu C.-F.,Beijing Key Laboratory for Parkinsons Disease
Translational Neurodegeneration | Year: 2015

Maintaining the physiological pH of interstitial fluid is crucial for normal cellular functions. In disease states, tissue acidosis is a common pathologic change causing abnormal activation of acid-sensing ion channels (ASICs), which according to cumulative evidence, significantly contributes to inflammation, mitochondrial dysfunction, and other pathologic mechanisms (i.e., pain, stroke, and psychiatric conditions). Thus, it has become increasingly clear that ASICs are critical in the progression of neurologic diseases. This review is focused on the importance of ASICs as potential therapeutic targets in combating neurologic diseases. © 2015 Liu et al.; licensee BioMed Central.

Du H.-P.,Soochow University of China | Li J.,Soochow University of China | You S.-J.,Soochow University of China | Wang Y.-L.,Soochow University of China | And 5 more authors.
Biochemical and Biophysical Research Communications | Year: 2016

Recent studies suggest that epigenetic alterations such as DNA methylation control many aspects of monocytes/macrophages and participate in the pathogenesis of atherosclerosis, a lipid-driven inflammatory disorder. Our and other groups demonstrated that dysregulation of cystathionine γ-lyase (CSE) -hydrogen sulfide (H2S) pathway was involved in monocyte/macrophages-mediated inflammation and atherosclerosis. However, it remains unknown whether altered cse methylation in macrophages may play a role in linking CSE-H2S dysregulation and atherosclerosis. In the present study, we showed that plasma H2S and H2S production in the peritoneal macrophages of apolipoprotein knockout (apoE-/-) mice gradually decreased with ages, and were also lower than that in control mice at 12 weeks older. Moreover, CSE mRNA expressions decreased while DNA methyltransferase (DNMT) expressions increased in the peritoneal macrophages isolated from apoE-/- mice, compared to age-matched wildtype mice. Similar observations were obtained in an in vitro study. In oxidized low-density lipoprotein (ox-LDL)-treated raw264.7 macrophages, cse transcription was down-regulated while the expression and activity of DNMT was up-regulated, associated with enhanced DNA methylation in cse promoter. Suppression of DNMT with its inhibitor or siRNA reversed the decrease of CSE mRNA. Therefore, our data suggest that DNA hypermethylation of CpG rich region in cse promoter might contribute to the decrease of cse transcription and H2S production in macrophages, and thus contribute to atherosclerosis development. © 2015 Elsevier Inc. All rights reserved.

Wang Y.,Soochow University of China | Li S.,Soochow University of China | Liu W.,Soochow University of China | Wang F.,Soochow University of China | And 5 more authors.
Biochemical and Biophysical Research Communications | Year: 2016

Vesicular monoamine transporter 2 (Vmat2) is widely distributed in the central nervous system, and responsible for uptaking transmitters into the vesicles. However, whether Vmat2-deficiency is related to the anxiety is rarely investigated, especially in zebrafish. Here, we reported Vmat2 heterzygous mutant zebrafish displayed anxiety-like behavior. The mutants spent less time in the top area and took longer latency to the top in the novel tank test. Consistently, they showed dark avoidance in the light/dark box test, with longer duration in the light zone and increased number of crossing between the two zones. Monoamine concentration analysis showed that the levels of monoamine neurotransmitters including dopamine (DA), 5-hydroxy tryptamine (5-HT) and norepinephrine (NE), as well as their metabolites were decreased in VMAT mutants. Taken together, these findings suggest that Vmat2 heterzygous mutant zebrafish may serve as a new model of anxiety, which may be related with the low level of DA, 5-HT and NE. © 2016 Elsevier Inc. All rights reserved.

Li J.,Soochow University of China | Zhang Y.-L.,Soochow University of China | Chen R.,Soochow University of China | Wang Y.,Soochow University of China | And 5 more authors.
Chinese Medical Journal | Year: 2015

Background: Obstructive sleep apnea-hypopnea syndrome (OSAS) is associated with elevated liver enzymes and fatty liver. The purpose of this study was to measure serum liver enzyme levels in patients evaluated by polysomnography (PSG) and the factors associated with liver injury in OSAS patients. Methods: All patients referred to PSG for evaluation of sleep apnea symptoms between June 2011 and November 2014 were included in this study. Demographic data and PSG parameters were recorded. Serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase levels were systematically measured. OSAS patients were divided into mild, moderate, and severe groups according to the apnea-hypopnea index (AHI) values of 5-14 events/h, 15-29 events/h, and ≥30 events/h. Results: A total of 540 patients were enrolled in this study; among these patients, 386 were male. Elevated liver enzymes were present in 42.3% of OSAS patients (32.4% in mild/moderate group; 51.0% in severe group) and 28.1% patients without OSAS. Patients with OSAS had higher body mass index (BMI) (P < 0.01). In the bivariate correlation, the liver enzymes level was negatively correlated with age and the lowest arterial oxygen saturation (SaO 2), and was positively correlated with BMI, oxygen desaturation index, percent of total time with oxygen saturation level <90% (TS90%), AHI, total cholesterol (TC), and triglyceride (TG). In logistic regression analysis, Age, BMI, TS90%, TC, and TG were included in the regression equation. Conclusions: Our data suggest that OSAS is a risk factor for elevated liver enzymes. The severity of OSAS is correlated with liver enzyme levels; we hypothesize that hypoxia is one of main causes of liver damage in patients with OSAS. © 2015 Chinese Medical Journal.

Zhang J.-R.,Soochow University of China | Chen J.,Soochow University of China | Yang Z.-J.,Soochow University of China | Zhang H.-J.,Soochow University of China | And 6 more authors.
Chinese Medical Journal | Year: 2016

Background: Rapid eye movement (REM) sleep behavior disorder (RBD) may be a risk factor for cognitive impairment in patients with Parkinson’s disease (PD). However, little is known regarding the relation between the severity of RBD and the different domains of cognitive impairment. The aim of this study was: (1) to investigate the domains of cognitive impairment in patients with PD and RBD, and (2) to explore risk factors for PD‑mild cognitive impairment (PD‑MCI) and the relationship between RBD severity and impairment in different cognitive domains in PD. Methods: The participants were grouped as follows: PD without RBD (PD‑RBD; n = 42), PD with RBD (PD + RBD; n = 32), idiopathic RBD (iRBD; n = 15), and healthy controls (HCs; n = 36). All participants completed a battery of neuropsychological assessment of attention and working memory, executive function, language, memory, and visuospatial function. The information of basic demographics, diseases and medication history, and motor and nonmotor manifestations was obtained and compared between PD‑RBD and PD + RBD groups. Particular attention was paid to the severity of RBD assessed by the RBD Questionnaire‑Hong Kong (RBDQ‑HK) and the RBD Screening Questionnaire (RBDSQ), then we further examined associations between the severity of RBD symptoms and cognitive levels via correlation analysis. Results: Compared to PD‑RBD subjects, PD + RBD patients were more likely to have olfactory dysfunction and their Epworth Sleepiness Scale scores were higher (P < 0.05). During neuropsychological testing, PD + RBD patients performed worse than PD‑RBD patients, including delayed memory function, especially. The MCI rates were 33%, 63%, 33%, and 8% for PD‑RBD, PD + RBD, iRBD, and HC groups, respectively. RBD was an important factor for the PD‑MCI variance (odds ratio = 5.204, P = 0.018). During correlation analysis, higher RBDSQ and RBDQ‑HK scores were significantly associated with poorer performance on the Trail Making Test‑B (errors) and Auditory Verbal Learning Test (delayed recall) and higher RBD‑HK scores were also associated with Rey–Osterrieth complex figure (copy) results. Conclusions: When PD‑RBD and PD + RBD patients have equivalent motor symptoms, PD + RBD patients still have more olfactory dysfunction and worse daytime somnolence. RBD is an important risk factor for MCI, including delayed memory. Deficits in executive function, verbal delayed memory, and visuospatial function were consistently associated with more severe RBD symptoms. © 2016 Chinese Medical Journal.

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