Role of histone deacetylases and their inhibitors in neurological diseases.

Histone deacetylases (HDACs) are zinc-dependent deacetylases that remove acetyl groups from lysine residues of histones or form protein complexes with other proteins for transcriptional repression, changing chromatin structure tightness, and inhibiting gene expression. Recent in vivo and in vitro studies have amply demonstrated the critical role of HDACs in the cell biology of the nervous system during both physiological and pathological processes and have provided new insights into the conduct of research on neurological disease targets. In addition, in vitro and in vivo studies on HDAC inhibitors show promise for the treatment of various diseases. This review summarizes the regulatory mechanisms of HDAC and the important role of its downstream targets in nervous system diseases, and summarizes the therapeutic mechanisms and efficacy of HDAC inhibitors in various nervous system diseases. Additionally, the current pharmacological situation, problems, and developmental prospects of HDAC inhibitors are described. A better understanding of the pathogenic mechanisms of HDACs in the nervous system may reveal new targets for therapeutic interventions in diseases and help to relieve healthcare pressure through preventive measures.

Histone deacetylases and their inhibitors in inflammatory diseases.

Despite considerable research efforts, inflammatory diseases remain a heavy burden on human health, causing significant economic losses annually. Histone deacetylases (HDACs) play a significant role in regulating inflammation (via histone and non-histone protein deacetylation) and chromatin structure and gene expression regulation. Herein, we present a detailed description of the different HDACs and their functions and analyze the role of HDACs in inflammatory diseases, including pro-inflammatory cytokine production reduction, immune cell function modulation, and anti-inflammatory cell activity enhancement. Although HDAC inhibitors have shown broad inflammatory disease treatment potentials, their clinical applicability remains limited because of their non-specific effects, adverse effects, and drug resistance. With further research and insight, these inhibitors are expected to become important tools for the treatment of a wide range of inflammatory diseases. This review aims to explore the mechanisms and application prospects of HDACs and their inhibitors in multiple inflammatory diseases.

miRNA-143 as a potential biomarker in the detection of bladder cancer: a meta-analysis.

Aim: This study aimed to systematically evaluate the value of miRNA-143 in the early detection of bladder cancer (BCa). Methods: CNKI, WanFang, PubMed and Wiley Online Library databases were explored according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. A random-effects model was used to obtain pooled sensitivity, specificity and other related indicates. Results: Six studies were included for analysis. The overall pooled sensitivity and specificity were 0.80 (95% CI: 0.74-0.85) and 0.85 (95% CI: 0.78-0.91), and the area under the curve was 0.88 (95% CI: 0.85-0.91). Coupled with miR-100, it showed better diagnostic power (area under the curve: 0.95). Conclusion: miRNA-143 may serve as a promising noninvasive tool for the early detection of BCa.

Bladder cancer (BCa) is a common and deadly malignant tumor worldwide; however, noninvasive diagnosis can significantly improve the prognosis of patients. Recently, miRNAs have emerged as potential diagnostic biomarkers for BCa. Among them, miRNA-143 has shown promising results in several studies. This meta-analysis aimed to evaluate the overall diagnostic accuracy of miRNA-143 for BCa through a systematic review and meta-analysis of six published articles. Excitingly, the results of this meta-analysis suggest that miRNA-143 has potential diagnostic value in BCa. Particularly, miRNA-143 combined with miRNA-100 maintained better competence. Besides, miRNA-143 in plasma exhibited better diagnostic strength than that in urine. The authors believe that their study provides valuable insights into the use of miRNA-143 as a diagnostic biomarker for BCa.

Identification of m6A regulator-mediated RNA methylation modification patterns and key immune-related genes involved in atrial fibrillation.

The role of m6A in the regulation of the immune microenvironment in atrial fibrillation (AF) remains unclear. This study systematically evaluated the RNA modification patterns mediated by differential m6A regulators in 62 AF samples, identified the pattern of immune cell infiltration in AF and identified several immune-related genes associated with AF. A total of six key differential m6A regulators between healthy subjects and AF patients were identified by the random forest classifier. Three distinct RNA modification patterns (m6A cluster-A, -B and -C) among AF samples were identified based on the expression of 6 key m6A regulators. Differential infiltrating immune cells and HALLMARKS signaling pathways between normal and AF samples as well as among samples with three distinct m6A modification patterns were identified. A total of 16 overlapping key genes were identified by weighted gene coexpression network analysis (WGCNA) combined with two machine learning methods. The expression levels of the NCF2 and HCST genes were different between controls and AF patient samples as well as among samples with the distinct m6A modification patterns. RT-qPCR also proved that the expression of NCF2 and HCST was significantly increased in AF patients compared with control participants. These results suggested that m6A modification plays a key role in the complexity and diversity of the immune microenvironment of AF. Immunotyping of patients with AF will help to develop more accurate immunotherapy strategies for those with a significant immune response. The NCF2 and HCST genes may be novel biomarkers for the accurate diagnosis and immunotherapy of AF.

Effects of a Macroporous Resin Extract of Dendrobium officinale Leaves in Rats with Hyperuricemia Induced by Anthropomorphic Unhealthy Lifestyle.

Aim: Hyperuricemia (HUA) has received increased attention in the last few decades due to its global prevalence. Our previous study found that administration of a macroporous resin extract of Dendrobium officinale leaves (DoMRE) to rats with HUA that was induced by exposure to potassium oxazine combined with fructose and a high-purine diet led to a significant reduction in serum uric acid (SUA) levels. The aim of this study was to explore the effects of DoMRE on hyperuricemia induced by anthropomorphic unhealthy lifestyle and to elucidate its possible mechanisms of action. Methods: Dosages (5.0 and 10.0 g/kg/day) of DoMRE were administered to rats daily after induction of HUA by anthropomorphic unhealthy lifestyle for 12 weeks. The levels of UA in the serum, urine, and feces; the levels of creatinine (Cr) in the serum and urine; and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were all measured using an automatic biochemical analyzer. The activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the serum, liver, and intestine tissue supernatant were measured using appropriate kits for each biological target. The expressions levels of UA transporters (ABCG2 and GLUT9), tight junction (TJ) proteins (ZO-1 and occludin), and inflammatory factors (IL-6, IL-8, and TNF-α) in the intestine were assayed by immunohistochemical (IHC) staining. Hematoxylin and eosin (H&E) staining was used to assess histological changes in the renal and intestinal tissues. Results: DoMRE treatment significantly reduced SUA levels and concomitantly increased fecal UA (FUA) levels and the fractional excretion of UA (FEUA) in HUA rats. Furthermore, DoMRE significantly reduced both the XOD activity in the serum, liver, and intestine and the ADA activity in the liver and intestine. DoMRE also effectively regulated the expression of GLUT9 and ABCG2 in the intestine, and it significantly upregulated the expression of the intestinal TJ proteins ZO-1 and occludin. Therefore, DoMRE reduced the damage to the intestinal barrier function caused by the increased production of inflammatory factors due to HUA to ensure normal intestinal UA excretion. Conclusion: DoMRE demonstrated anti-HUA effects in the HUA rat model induced by an anthropomorphic unhealthy lifestyle, and the molecular mechanism appeared to involve the regulation of urate transport-related transporters (ABCG2 and GLUT9) in the intestine, protection of the intestinal barrier function to promote UA excretion, and inhibition of XOD and ADA activity in the liver and intestine to inhibit UA production in the HUA-induced rats.

Effects of Dendrobium officinale ultrafine powder on sub-health mice induced by unhealthy lifestyle based on neuroendocrine immune system.

Sub-health status, in which a person's mind and body exist in a low-quality state of being between disease and health, has become an urgent public health problem that cannot be ignored globally. One of the most apparent sub-health symptoms is fatigue, and it also shows a significant decrease in mental vitality and adaptability caused by disruption of the neuroendocrine-immune system. Dendrobium officinale (DOF) has a long history of use in China as a medicinal food with immune-regulating, anti-fatigue, anti-oxidant, and hypoglycemic effects. The ameliorative effects of Dendrobium officinale on sub-health mice are investigated in this present study, as well as its underlying mechanisms via neuroendocrine-immune (NEI) modulation. Forty male KM mice were divided into normal control group (NC), model control group (MC), and two doses of ultrafine DOF powder (DOFP) intervention groups: DOFP-L (0.1 g kg-1), DOFP-H (0.2 g kg-1) groups. Sub-health mice were induced by mimicking unhealthy human lifestyles, including cold water swimming, limbs restriction, an unhealthy diet, and sleep deprivation for seven weeks. The findings revealed that DOFP intervened sub-health mice have less bodyweight loss, normal fecal morphology, as well as lower face temperature and blood flow, which is similar to the normal mice. Moreover, sub-health mice treated with DOFP showed improved forelimb grip strength and exercise endurance in weight-loaded exhaustion swimming and cold water exhaustion swimming, combined with reduced content of lactic acid (LD), lactate dehydrogenase (LDH), blood urea nitrogen (BUN) in the plasma, increased storage of liver glycogen (LG), and muscle glycogen (MG), as well as increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), reduced malondialdehyde (MDA) levels in the liver. Additionally, DOFP could increase the counts of autonomous movements of sub-health mice, minimize tail suspension time, and perform well in the elevated plus maze and open field tests, all of which are associated with anti-depression and anti-anxiety. Moreover, mechanistic investigations revealed that DOFP could alleviate plasma corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol (CORT) related hormones in the HPA axis, increase the level of hypothalamic norepinephrine (NE) and plasma ß-endorphin (ß-EP) of sub-health mice, while downregulating the content of 5-hydroxytryptamine (5-HT), dopamine (DA), and the relative mRNA expression of 5-HT1A and CRH in hypothalamus, and increase immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), and CD4+/CD8+ T cell ratio levels. In conclusion, DOFP can relieve symptoms such as fatigue and depression in sub-health mice by regulating the disorder of the neuroendocrine-immune network.

Genome-Wide Profiling of Human Papillomavirus DNA Integration into Human Genome and Its Influence on PD-L1 Expression in Chinese Uygur Cervical Cancer Women.

BACKGROUND: The Uygur is the fifth most populous ethnic group in China. Compared to other Chinese population, cervical cancer in them had high incidence, and HPV infection also was particular. Their HPV integration situation has never been reported. We aimed to investigate the integration situation of 20 subtypes of HPV gene into host cell genome in Chinese Uygur cervical cancer patients; meanwhile, we explored the influence of gene integration on PD-L1 expression. METHODS: 40 frozen Chinese Uygur cervical cancer specimens with positive HPV infection were obtained from the cancer prevention and treatment institute of Tumor Hospital Affiliated to Xinjiang Medical University. The integration situation of HPV gene into host cell genome was detected by Agilent SureSelect™ Target Enrichment Chip and Next-Generation Sequencing. The related genes were analyzed by GO functional annotation and KEGG pathway enrichment. The expression levels of PD-L1 in cancer cells were tested by immunohistochemical assay (IHC). Meanwhile, the relationship between PD-L1 levels in cancer cells and gene integration were analyzed. RESULTS: The HPV multiple infection rate by HIVID was as high as 92.5%, much higher than 35.0% by the commercial kit (P < 0.05). There were 13423 integration events in 40 specimens, involving 6867 human genes. These integration events were distributed on all human chromosomes, and chromosome 19 had the excessive concentration phenomenon of integration events. There were some integration hotspots in human genome such as PPP1R37, HECW2, EMBP1, ANKRD50, SPTBN4, LINC00895, LYRM4-AS1, LINC00374, RBFOX1, CSMD1, CDH13, and KLHL4. Insertion breakpoints can be found in all gene regions of the HPV genome. The actual observation of the integration times of E1 and E6 was much higher than the expected value, while the actual observation times of E5 were much lower than the expected value. The result of GO functional analysis showed that binding molecular function and cellular process biological process were the main ways to influence the cell biological behavior of HPV gene integration. The enrichment pathway analysis of KEGG showed that pathways in cancer were the most important enrichment pathways involved in the genomic integration of HPV. The positive PD-L1 rate was 62.5%. Logistic regression analysis showed that 9p24.1 existing integration sites and the number of all gene integration were risk factors for PD-L1 expression (odds ratio 17.313 and 1.012; 95% confidence interval 1.691-177.213 and 1.001-1.023). Conclusions and Relevance. Most high-frequency sites of HPV integration in Chinese Uygur cervical cancer are related to cancer progression, and the gene integration hotspots may be potential HPV carcinogenic targets. The problem of multiple HPV infection in Chinese Uygur cervical cancer patients should be paid attention. L1 and E6 genes are inapposite as the target gene of commercial HPV type detection kit, because of high-frequency breakpoints in these genes. The gene integration especially the integration existing on 9p24.1 could affect the expression level of PD-L1.

DNA barcodes of Plecoptera from China: The preliminary dataset and its performance in species delimitation.

The DNA barcodes of Chinese Plecoptera project has a goal to promote species identification, life stage association, systematic, conservation, biodiversity, and population genetic studies for stoneflies of China. In this study, we sequenced and analyzed 19 DNA barcode sequences belonging to 19 stonefly species, increasing the Chinese barcoded stonefly species number to 53. Genetic distances were calculated and the gene trees constructed, suggesting the efficiency of delimiting Chinese stonefly species using DNA barcodes.

The Prognostic Roles of Pretreatment Circulating Tumor Cells, Circulating Cancer Stem-Like Cells, and Programmed Cell Death-1 Expression on Peripheral Lymphocytes in Patients with Initially Unresectable, Recurrent or Metastatic Head and Neck Cancer: An Exploratory Study of Three Biomarkers in One-time Blood Drawing.

Circulating tumor cells (CTCs) and immune status are strongly related to cancer prognosis, although few studies have examined both factors. This prospective observational study (ClinicalTrials.gov: NCT02420600) evaluated whether CTCs, circulating cancer stem-like cells (cCSCs), and peripheral lymphocytes with/without Programmed cell death protein 1 (PD-1) expression were associated with prognosis among patients receiving palliative chemotherapy for initially unresectable, recurrent/metastatic head and neck squamous cell carcinoma (rmHNSCC). Thirty-four patients were enrolled between January 2015 and June 2016. Overall survival (OS) was associated with a higher CTC number (hazard ratio [HR]: 1.01, p = 0.0004) and cCSC ratio (HR: 29.903, p < 0.0001). Progression-free survival (PFS) was also associated with CTC number (HR: 1.013, p = 0.002) and cCSC ratio (HR: 10.92, p = 0.003). A CD8⁺ proportion of ≥ 17% was associated with improved OS (HR: 0.242, p = 0.004). A CD4: CD8 ratio of >1.2 was associated with poorer trend of PFS (HR: 2.12, p = 0.064). PD-1 expression was not associated with survival outcomes. Baseline CTCs, cCSC ratio, and CD8⁺ ratio may predict prognosis in rmHNSCC.

Isolation of two bis(silyl)nickel complexes with Si-Si bond formation in a single-crystal-to-single-crystal fashion.

A unique penta-coordinate nickel complex [{1,2-C6H4(SiMe2)(SiH)}2Ni(PEt3)(depe)] (6) that generates two new Si-Si single bonds has been prepared exclusively by the reaction of a chelating silyl hydride 1-(dimethylsilyl)-2-silylbenzene (4) and Ni(depe)(PEt3)2 (depe = Et2PCH2CH2PEt2) in a 2 : 1 ratio. Complex 6 is the first example of mononuclear silyl nickel complexes containing a Si-Si single bond formed in situ. Interestingly, framework 6 exhibits reversible single-crystal-to-single-crystal transformations upon the removal and rebinding of the coordinating PEt3 molecule, which give rise to a PEt3-free complex [{1,2-C6H4(SiMe2)(SiH)}2Ni(depe)] (6'), concomitant with the alteration of the coordination geometry of central metal atoms.

Assessment of the relationship between red blood cell distribution width and preganecy hypertension disease.

AIMS: The aim of this study was to explore the correlation between red blood cell distribution width (RDW) and Preganecy Heypertion Disease (PHD) . METHODS: A retrospective study was carried out involving 149 pregnancies with PHD(67 gestational hypertension, 39 Mild preeclampsia, 24 severe preeclampsia and 19 eclampsia) and 70 health pregnant women as controls. The data of RDW were reviewed from antenatal and delivery records. Explored the correlation between RDW and PDH through Logistic Regression analysis, analyzed the clinical value of RDW to predict PHD by receiver operating characteristic (ROC) curve analysis. RESULTS: RDW in different gestational time(20th week, 24th week, 28th week) of different pregnant women groups had differences (P < 0.05), but pregnant women in the same group had no difference from 20th week to 28th week(P > 0.05). Logistic regression analysis showed that RDW was a risk factor for PHD (odds ratio 2.683; 95 % confidence interval 1.472-6.096), the optimal RDW-CV threshold was 14.1 % to predict PHD by the ROC curve, the sensitivity and speciality were 72.5 % and 77.9 %. CONCLUSIONS: RDW as a new chronic inflammation mediator, which was a high-risk factor of PHD, also had certain clinical value to predict the occurrence of PHD.

Predicting safety culture: the roles of employer, operations manager and safety professional.

INTRODUCTION: This study explores predictive factors in safety culture. METHOD: In 2008, a sample 939 employees was drawn from 22 departments of a telecoms firm in five regions in central Taiwan. The sample completed a questionnaire containing four scales: the employer safety leadership scale, the operations manager safety leadership scale, the safety professional safety leadership scale, and the safety culture scale. The sample was then randomly split into two subsamples. One subsample was used for measures development, one for the empirical study. RESULTS: A stepwise regression analysis found four factors with a significant impact on safety culture (R²=0.337): safety informing by operations managers; safety caring by employers; and safety coordination and safety regulation by safety professionals. Safety informing by operations managers (ß=0.213) was by far the most significant predictive factor. IMPACT ON INDUSTRY: The findings of this study provide a framework for promoting a positive safety culture at the group level.