A mind in motion: Exercise improves cognitive flexibility, impulsivity and alters dopamine receptor gene expression in a Parkinsonian rat model.

Cognitive impairment, particularly deficits in executive function (EF) is common in Parkinson's disease (PD) and may lead to dementia. There are currently no effective treatments for cognitive impairment. Work from our lab and others has shown that physical exercise may improve motor performance in PD but its role in cognitive function remains poorly eludicated. In this study in a rodent model of PD, we sought to examine whether exercise improves cognitive processing and flexibility, important features of EF. Rats received 6-hydroxydopamine lesions of the bilateral striatum (caudate-putamen, CPu), specifically the dorsomedial CPu, a brain region central to EF. Rats were exercised on motorized running wheels or horizontal treadmills for 6-12 weeks. EF-related behaviors including attention and processing, as well as flexibility (inhibition) were evaluated using either an operant 3-choice serial reaction time task (3-CSRT) with rule reversal (3-CSRT-R), or a T-maze task with reversal. Changes in striatal transcript expression of dopamine receptors (Drd1-4) and synaptic proteins (Synaptophysin, PSD-95) were separately examined following 4 weeks of exercise in a subset of rats. Exercise/Lesion rats showed a modest, yet significant improvement in processing-related response accuracy in the 3-CSRT-R and T-maze, as well as a significant improvement in cognitive flexibility as assessed by inhibitory aptitude in the 3-CSRT-R. By four weeks, exercise also elicited increased expression of Drd1, Drd3, Drd4, synaptophysin, and PSD-95 in the dorsomedial and dorsolateral CPu. Our results underscore the observation that exercise, in addition to improving motor function may benefit cognitive performance, specifically EF, and that early changes (by 4 weeks) in CPu dopamine modulation and synaptic connectivity may underlie these benefits.

LncRNA Gaplinc promotes the pyroptosis of vascular endothelial cells through SP1 binding to enhance NLRP3 transcription in atherosclerosis.

Pyroptosis, characterized by activation of the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and its downstream effector inflammatory factors, has been shown to play a crucial role in atherosclerosis development. Long noncoding RNAs (lncRNAs) are involved in the progression of pyroptosis. However, the role and mechanism of the novel lncRNA gastric adenocarcinoma associated, positive CD44 regulator (Gaplinc), in endothelial cell pyroptosis during atherosclerosis development remain unexplored. Bioinformatics was performed to evaluate dysregulated lncRNAs in atherosclerotic mice fed a high-fat diet. The effect of Gaplinc on atherosclerosis progression in vivo was assessed via Oil Red O staining and fluorescence in situ hybridization. Its function in oxidized low-density lipoprotein (ox-LDL)-induced pyroptosis of endothelial cells was determined through ectopic expression. Additionally, RNA pull-down and immunoprecipitation (RIP) assays were performed to determine Gaplinc and transcription factor SP1 interactions. Then the pyroptosis pathway proteins were analyzed via immunofluorescence and western blotting. We found that lncRNA Gaplinc was highly expressed in ox-LDL-induced endothelial cells as well as in the plaque and plasma of high-fat diet-treated ApoE-/- mice. Gaplinc silencing significantly inhibited endothelial cell pyroptosis and atherosclerotic plaque formation. Mechanistically, Gaplinc could interact with SP1 to bind to the NLRP3 promoter and upregulate the target gene expression of NLRP3, facilitating endothelial cell pyroptosis and atherosclerotic plaque enlargement in high- fat diet-fed mice. In conclusion, our results revealed the underlying mechanism of the lncRNA Gaplinc /SP1/NLRP3 axis in endothelial cell pyroptosis, which may provide new potential targets for the treatment of atherosclerosis.

Upregulation of microRNA-34a enhances myocardial ischemia-reperfusion injury via the mitochondrial apoptotic pathway.

Mitochondrial oxidative injury can result in many cardiovascular diseases including cardiac ischemia-reperfusion (I/R) injury. This study was designed to investigate whether microRNA-34a (miR-34a) influences cardiac I/R or hypoxia/reoxygenation (H/R) injury by regulating the mitochondrial apoptotic pathway from oxidative injury.In vivo, myocardial infarction size was examined by Evan blue/TTC staining. Apoptosis was assessed by TUNEL assay. Heart function was measured by echocardiography. Lactate dehydrogenase (LDH) and creatine kinase (CK) were evaluated. In vitro, H9c2 cardiomyocytes were exposed to H/R stimulation. Cell viability was assessed by the CCK-8 assay and apoptosis was detected by Annexin V/PI staining. Mitochondrial superoxide, mitochondrial membrane potential (MMP) and ATP production was evaluated by detection kits, and related proteins were detected by western blotting analysis. We observed that the level of miR-34a was significantly upregulated in I/R rats compared to the sham group. Injection of adenovirus inhibiting miR-34a into the left ventricular anterior wall improved heart function and decreased I/R injury. H9c2 cardiomyocytes exposed to H/R stimulation displayed an obvious increase in miR-34a expression. In addition, miR-34a inhibitor alleviated, whereas miR-34a mimic aggravated H/R-induced mitochondrial injury. Bcl-2 was identified as a target gene of miR-34a by dual-luciferase reporter gene detection. Knockdown of Bcl-2 abolished the cardioprotection of the miR-34a inhibitor in H9c2 cells. In summary,our study demonstrates that inhibition of miR-34a exhibits therapeutic potential in treatment of myocardial I/R injury by restraining mitochondrial apoptosis.

[Protective effect of ginsenoside Rg_1 on hypoxia/reoxygenation injury and its mechanism].

This project aimed to explore the protective effect of ginsenoside Rg_1 on hypoxia/reoxygenation(H/R)-induced H9 c2 cardiomyocyte injury and its underlying signaling pathway. The H/R model of H9 c2 cardiomyocytes was established and then the cells were divided into different treatment groups. CCK-8(cell counting kit-8) was used to detect the activity of cardiomyocytes; Brdu assay was used to detect the proliferation of H9 c2 cells; the caspase-3 activity was tested, and then the protein expression was assessed by Western blot. Flow cytometry was used to evaluate the apoptosis level of cardiomyocytes. Ginsenoside Rg_1 inhibited H/R-induced cardiomyocyte apoptosis and caspase-3 activity, promoted nuclear transcription of nuclear factor erythroid-2 related factor 2(Nrf2), and enhanced the expression of the downstream heme oxygenase-1(HO-1). Ginsenoside Rg_1 could increase Nrf2 nuclear transcription and HO-1 expression with the increase of concentration(10, 20, 40, 60 µmol·L~(-1)). However, the protective effect of ginsenoside Rg_1 on cardiomyocytes was significantly weakened after the transfection of Nrf2-siRNA. Ginsenoside Rg_1 could protect cardiomyocytes by activating the Nrf2/HO-1 pathway.

Advances in single-cell whole genome sequencing technology and its application in biomedicine.

The advent and development of single-cell whole-genome sequencing (scWGS) technology has shed lights on the genomic heterogeneities within biosamples at the single-cell resolution. The technology is particularly well-established in the recent decade and witnesses a variety of clinical applications, such as circulating tumor cell (CTC) detection and preimplantation genetic diagnosis/screening (PGD/PGS). In this review, we summarize the latest practical breakthroughs of scWGS in the field of biomedicine, with the hope of providing a guideline to apply single-cell genomic sequencing in clinical researches.

Visible-Light-Promoted C2 Selective Arylation of Quinoline and Pyridine N-Oxides with Diaryliodonium Tetrafluoroborate.

A protocol of visible-light-promoted C2 selective arylation of quinoline and pyridine N-oxides, with diaryliodonium tetrafluoroborate as an arylation reagent, using eosin Y as a photocatalyst for the construction of N-heterobiaryls was presented. This methodology provided an efficient way for the synthesis of 2-aryl-substituted quinoline and pyridine N-oxides. This strategy has the following advantages: specific regioselectivity, simple operation, good functional group tolerance, and high to moderate yields under mild conditions.

Effects of atorvastatin on chronic subdural hematoma: A systematic review.

BACKGROUND: The high recurrent rate of chronic subdural hematoma (CSDH) has consistently confused the neurosurgeons, and the role of atorvastatin in the management of CSDH has remained unclear over past decade, and atorvastatin seems to be a safe and cost-effective treatment to CSDH. Therefore, it is necessary to conduct a systematic review to discuss the effect of atorvastatin in CSDH. METHOD: We searched the PubMed, EMBASE, Cochrane Library, and the China Biology Medicine disc, up to March 2017, for published studies on the effects of atorvastatin in the management of CSDH, and reviewers performed a brief qualitative descriptive analysis of atorvastatin's efficacy in the management of CSDH. RESULTS: Three eligible studies were included in this systematic review. Results indicated that atorvastatin accelerated hematoma absorption, decreased recurrence risk, and surgical requirement. CONCLUSION: Limited evidence suggests that oral atorvastatin may be beneficial in the management of CSDH. Further high-quality studies focused on dosage, duration, hematoma size are needed to further elucidate the role of atorvastatin in the management of CSDH.

A genetic variant in long non-coding RNA MALAT1 associated with survival outcome among patients with advanced lung adenocarcinoma: a survival cohort analysis.

BACKGROUND: Recently studies have demonstrated that the long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) may participate in the development and progression of lung cancer. In this study, we hypothesized that genetic variant of this lncRNA may affect the prognosis of lung cancer patients. METHODS: We conducted a follow-up study for 538 patients with non-small cell lung carcinoma (NSCLC), including 140 early-staged (stage I and II) and 398 advanced staged (stage III and IV) patients. The genetic variant rs3200401 in MALAT1 was then genotyped among this population by using TaqMan assay. The association of this variant with overall survival of these patients was further analyzed. RESULTS: It was shown that among the advanced lung adenoma patients, subjects carrying rs3200401 CT and CT + TT genotypes had significantly longer median survival time (MST = 29.9, 28.9 vs. 19.3 month, Long-rank P = 0.019 and 0.024, respectively) and decreased death risks [crude HR (95% CI) = 0.65 (0.43-0.98) and 0.64 (0.44-0.95), P = 0.040 and 0.025, respectively], when compared to subjects wtih the MALAT1 rs3200401 CC genotype. However, the beneficial effect of rs3200401 was not seen among early NSCLC and advanced lung squamous cell carcinoma patients. We further tested the TCGA data, and found that a higher expression of MALAT1 was associated with metastatic of advanced lung adenocarcinoma but not with lung squamous cell carcinoma. CONCLUSIONS: The rs3200401 T allele located on the lncRNA MALAT1 was associated with a better survival for advanced lung adenocarcinoma patients, which may offer a novel prognostic biomarker for this patient subgroup. However, these results need to be validated in larger populations of lung cancer and the biological function of this variant still warrants further investigation.

Resting-state EEG network change in alpha and beta bands after upper limb amputation.

To investigate the reorganization of functional brain network following amputation, twenty-two right-hand amputees and twenty-four age- and education-matched controls participated in a resting-state EEG study. EEG networks in alpha and beta bands were constructed using phase synchronization. Both global and local network parameters were compared between amputees and healthy controls. In the aspect of global connectivity, amputees showed increased clustering coefficient (C), decreased characteristic path length (L) and increased small worldness (S) in alpha band, and an increase of L in beta band. Meanwhile, in comparison with the controls, the right-hand amputees have lower nodal degree (k) in the sensorimotor cortex but higher k in the parietal area in the right hemisphere in alpha band. These alterations of network following amputation implied a decreased inhibition from the intact sensorimotor area and increased connections in the right parietal area, which supported the unmasking theory. Such connectivity changes might also relate to the phantom limb phenomenon.

A Simple Protein Precipitation-based Simultaneous Quantification of Lovastatin and Its Active Metabolite Lovastatin Acid in Human Plasma by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry using Polarity Switching.

Lovastatin is an anti-cholesterol lactone drug indicated for the treatment of hyperlipidemia and to reduce the risk of coronary heart disease. It is converted to the ß-hydroxy acid form (lovastatin acid) in vivo, which is the major pharmacologically active metabolite. Here, we describe the development and validation of an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based method utilizing polarity switching for the simultaneous quantification of lovastatin and lovastatin acid in human plasma. Simple protein precipitation extraction and direct injection of the extracted samples without drying/reconstitution showed good recoveries of both analytes (~70%). The developed method exhibited satisfactory intra-day and inter-day accuracy and precision. The interconversion between lovastatin and lovastatin acid during sample preparation and storage was minimal (< 1.9%). The lower limits of quantification were 0.5 and 0.2 nM (or 0.2 and 0.084 ng/mL) for lovastatin and lovastatin acid, respectively, using only 50 µL of plasma during extraction. The validated method was successfully applied to analyze plasma samples obtained from a healthy human subject who enrolled in a clinical drug interaction study involving lovastatin.

[Investigation on the current status of oral health care in the disease controls system in Sichuan Province].

OBJECTIVE: To analyze the status and characteristics of dental manpower in the center for disease controls (CDC) in Sichuan Province and to provide more evidence for strengthening the oral healthcare workforce in the CDC system. METHODS: A mass survey on dental manpower was made in CDCs in Sichuan Province through questionnaire investigation. Data were collected and entered with the Epidemiological Dynamic Data Collection (EDDC) platform and analyzed with SPSS 13.0 software. RESULTS: Sichuan Province had 0.15 hospitals providing oral health services and 0.38 dentists on average per 10,000 people. About 65.53% (135/206) of the CDCs had one department responsible for the oral health service. However, oral health care personnel comprised only 2.23% (237/10,624) of the personnel of the whole CDC system. About 64.67% (119/184) of county CDCs and 47.62% (10/21) of city CDCs knew well the dental health status of local residents. Less than 5% of the CDCs used the data and assisted in the policy making of public health administrators. CONCLUSION: The dental care personal deficit exists in the CDC system in Sichuan Province. The distribution and composition of dental manpower are not reasonable. The oral health service ability of CDCs in Sichuan Province should be strengthened and improved.

The tumor necrosis factor-alpha promoter -1031C polymorphism is associated with decreased risk of endometriosis in a Japanese population.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional proinflammatory cytokine, associated with various inflammatory and autoimmune diseases. Elevated TNF-alpha levels in peritoneal fluid have been reported in women with endometriosis, suggesting that TNF-alpha may be involved in the development of endometriosis. In this study, we investigated the possible association between endometriosis and the TNF-alpha gene promoter polymorphisms -238G/A, -308G/A, -857C/T, -863C/A and -1031T/C in a Japanese population. METHODS: We compared the distribution of the -238G/A, -308G/A, -857C/T, -863C/A and -1031T/C polymorphisms in the promoter region of TNF-alpha in 130 endometriosis cases and 185 controls using PCR-RFLP analysis. RESULTS: The allele frequencies of -238A, -308A, -857T, -863A and -1031C in controls were 2.0%, 1.3%, 19.4%, 17.0% and 18.6%, and in the cases 1.1%, 0.3%, 19.6%, 18.6% and 13.6%, respectively. No significant differences in frequencies were found between the crude endometriosis cases and controls. However, when the endometriosis group was divided into a subgroup of women with stage IV disease only, the frequency of the -1031C allele was significantly lower in this subgroup than controls. CONCLUSIONS: The variability of the -1031T/C polymorphism of the TNF-alpha gene may be associated with susceptibility to (AUTHOR: as meant?) endometriosis.