Exploring Long Non-Coding RNAs Associated with IP3/DAG Signaling Pathway as Potential Biomarkers Involved in Mast Cell Degranulation in Chronic Spontaneous Urticaria with 2-Year Follow-Up.

PURPOSE: Chronic spontaneous urticaria (CSU) pathogenesis involves mast cell degranulation induced by the inositol 1,4,5-trisphosphate/diacylglycerol (IP3/DAG) pathway, but the condition lacks specific biomarkers. This study was performed to investigate long non-coding RNA (lncRNA) expression profiles, identify those associated with IP3/DAG pathway, and assess their diagnostic and prognostic value for CSU. METHODS: Ten samples were selected from CSU and control groups, and microarray was performed to screen differentially expressed (DE) lncRNAs and mRNAs. Bioinformatic and co-expression network analyses were used to identify lncRNAs associated with IP3/DAG pathway. Quantitative real-time polymerase chain reaction was used to validate lncRNA expression levels. Combined with disease characteristics and serum indices detected with enzyme-linked immunosorbent assays, Spearman analysis and logistic regression were applied to analyze lncRNA-associated disease risk. Receiver operating characteristic (ROC) curves and 2-year follow-up data were applied to evaluate lncRNA diagnostic and prognostic value. RESULTS: A total of 678 up- and 573 downregulated DE lncRNAs and 609 up- and 176 downregulated DE mRNAs were identified. Seven lncRNAs (upregulated T264761, T280622, ENST00000587970, T224062, ENST00000562459, and his-1_RNA_dna; downregulated ENST00000417930) were associated with the IP3/DAG pathway. D-dimer and histamine levels were significantly different between the two groups. Correlation analysis showed that his-1_RNA_dna positively correlated with the frequency of symptom appearance, while his-1_RNA_dna, ENST00000417930, T264761, and T280622 negatively correlated with the maximum wheal diameter. Regression analysis showed T264761 was associated with CSU risk. ROC analysis showed that the specificity of T264761 was 90%, with an area under the curve of 0.666. In follow-up, the rate of well-controlled disease in the low T264761 expression group was 82.61%. CONCLUSION: This study established lncRNA and mRNA expression profiles in CSU and identified lncRNAs associated with IP3/DAG pathway, which is mechanistically involved in this disease. T264761 may be a novel biomarker for CSU, but further study is needed to confirm its specific mechanism.

Xiaoyaosan Improves Antibiotic-Induced Depressive-Like and Anxiety-Like Behavior in Mice Through Modulating the Gut Microbiota and Regulating the NLRP3 Inflammasome in the Colon.

Disturbance of the gut microbiota plays an essential role in mental disorders such as depression and anxiety. Xiaoyaosan, a traditional Chinese medicine formula, has a wide therapeutic spectrum and is used especially in the management of depression and anxiety. In this study, we used an antibiotic-induced microbiome-depleted (AIMD) mouse model to determine the possible relationship between imbalance of the intestinal flora and behavioral abnormalities in rodents. We explored the regulatory effect of Xiaoyaosan on the intestinal flora and attempted to elucidate the potential mechanism of behavioral improvement. We screened NLRP3, ASC, and CASPASE-1 as target genes based on the changes in gut microbiota and explored the effect of Xiaoyaosan on the colonic NLRP3 pathway. After Xiaoyaosan intervention, AIMD mice showed a change in body weight and an improvement in depressive and anxious behaviors. Moreover, the gut flora diversity was significantly improved. Xiaoyaosan increased the abundance of Lachnospiraceae in AIMD mice and decreased that of Bacteroidaceae, the main lipopolysaccharide (LPS)-producing bacteria, resulting in decreased levels of LPS in feces, blood, and colon tissue. Moreover, serum levels of the inflammatory factor, IL-1ß, and the levels of NLRP3, ASC, and CASPASE-1 mRNA and DNA in the colon were significantly reduced. Therefore, Xiaoyaosan may alleviate anxiety and depression by modulating the gut microbiota, correcting excessive LPS release, and inhibiting the immoderate activation of the NLRP3 inflammasome in the colon.

Xiaoyaosan Exerts Therapeutic Effects on the Colon of Chronic Restraint Stress Model Rats via the Regulation of Immunoinflammatory Activation Induced by the TLR4/NLRP3 Inflammasome Signaling Pathway.

Depression is the neurological manifestation most commonly associated with gastrointestinal diseases. The release of inflammatory cytokines mediated by TLR4/NLRP3 inflammasome signaling-induced immunoinflammatory activation may represent a common pathogenic process underlying the development of gastrointestinal diseases and depression. Clinical studies have indicated that Xiaoyaosan (XYS) can relieve depressive behavior by improving gastrointestinal symptoms. We previously demonstrated that XYS can reduce colonic inflammation in a rat model of chronic unpredictable mild stress; however, the precise anti-inflammatory mechanisms involved remain unclear. Here, we investigated whether XYS can ameliorate depressive behavior through regulating the TLR4/NLRP3 inflammasome signaling pathway, thereby inhibiting immunoinflammatory activation and reducing colonic proinflammatory cytokine levels. Fifty-two healthy male Sprague-Dawley rats were randomly divided into four groups (control, model, XYS, and fluoxetine). The latter three groups were subjected to 21 days of chronic restraint stress to generate a model of stress-induced depression. XYS and fluoxetine were administered intragastrically. Behavioral changes in the rats were assessed after 21 days. Serum and colon samples were collected, and the relative levels of the inflammation indicators IL-6, IL-1ß, and TNF-α were determined by ELISA. Pathological changes in colon tissue were assessed by hematoxylin and eosin staining. The levels of TLR4, MyD88, NF-κB-p65, TAK1, IRAK1, and TRAF6 were detected by immunohistochemistry, while the gene and protein expression levels of TLR4, MyD88, NF-κB-p65, TAK1, IRAK1, TRAF6, NLRP3, ASC, and caspase-1 were detected by quantitative polymerase chain reaction (qPCR) and Western blotting. The results indicated that XYS could improve the depressive-like behavior and the weight loss of rats with stress-induced depression. Furthermore, depressed rats treated with XYS exhibited decreased expression levels of TLR4, MyD88, NF-κB-p65, TAK1, IRAK1, TRAF6, NLRP3, ASC, and caspase-1 in colonic tissue; reduced colon and serum concentrations of the inflammatory factors IL-6, IL-1ß, and TNF-α; and lowered levels of colonic inflammation.

Xiaoyaosan improves depressive-like behavior in rats with chronic immobilization stress through modulation of the gut microbiota.

Depression has become the leading cause of disability worldwide and a growing public health problem in China. In addition, intestinal flora may be associated with depression. This study investigated the effect of the decoction Xiaoyaosan (XYS) against depressive behavior through the regulation of intestinal flora. Fifty-two healthy male Sprague-Dawley rats were randomly divided into four groups (i.e., control, model, XYS, and fluoxetine). The latter three groups were subjected to 21 days of chronic restraint stress to produce the stress depression model. Rats in the XYS and fluoxetine groups received intragastric administration of XYS and fluoxetine, respectively. The behavioral changes of the rats were observed after 21 days. Stool specimens were sequenced using the 16S rDNA high-throughput method to detect the structure and changes in intestinal flora. There was no difference observed in alpha diversity among the groups. At the phylum level, XYS regulated the abundance of Bacteroidetes, Proteobacteria, Firmicutes, Chloroflexi, and Planctomycetes. At the genus level, XYS reduced the abundance of the Prevotellaceae_Ga6A1_group, Prevotellaceae_UCG-001, and Desulfovibrio. On the contrary, it increased the abundance of the Ruminococcaceae family to improve depression-like behavior. The mechanism involved in this process may be related to short-chain fatty acids, lipopolysaccharides, and intestinal inflammation.

Study of acupuncture for low back pain in recent 20 years: a bibliometric analysis via CiteSpace.

BACKGROUND: Acupuncture has been applied to relieve low back pain (LBP) in many countries. However, a bibliometric analysis of the global use of acupuncture for LBP is rare. OBJECTIVE: The aim of this study was to demonstrate the state of the art and trends concerning the global use of acupuncture for LBP in recent 20 years. METHODS: Literature relating to acupuncture for LBP from 1997 to 2016 was retrieved from Web of Science. CiteSpace was used to analyze country/institution, cited journals, authors/cited authors, cited references, and keywords. An analysis of counts and centrality was used to reveal publication outputs, countries/institutions, core journals, active authors, foundation references, hot topics, and frontiers. RESULTS: A total of 958 references were obtained, and the total number of publications continually increased over the investigated period. Journal articles (662) were the most frequently occurring document type. The most productive country and institution in this field was the USA (342) and Harvard University (47), respectively. The J Altern Complem Med (69) was the most productive journal, and Pain (636) was the most cocited journal, which reflected the nature of the research. The Haake's (2007) article (cocitation counts: 130) and the Cherkin's (2001) article (centrality: 0.59) were the most representative and symbolic references, with the highest cocitation number and centrality, respectively. Cherkin was the most influential author, with the highest number of publications of 25 and a cocitation number of 226. The four hot topics in acupuncture for LBP were research method, evaluation, economy, and comprehensive therapy. The three frontier topics were intervention, test reliability, and prevalence. CONCLUSION: This study provides an insight into acupuncture for LBP and valuable information for acupuncture researchers to identify new perspectives on potential collaborators and cooperative institutions, hot topics, and research frontiers.

Relation of N-terminal pro-brain natriuretic peptide and new-onset atrial fibrillation in patients with acute coronary syndrome: a systematic review and meta-analysis.

BACKGROUND: Several observational studies evaluated the associations of baseline N-terminal pro-brain natriuretic peptide (NT-proBNP) and new-onset atrial fibrillation (AF) in patients with acute coronary syndrome (ACS), but the results were contradictory. METHODS: Electronic bibliographic databases were searched from inception to May 2015, and the results reviewed by two independent reviewers. Pooled standardized mean difference (SMD) and 95% confidence interval (CI) were calculated to assess associations between NT-proBNP levels and new-onset AF in patients with ACS. We performed sensitivity analyses to explore the potential sources of heterogeneity and estimated publication biases. RESULTS: Six papers, including 5861 patients (438 with AF and 5423 without AF) with ACS were analyzed. Overall, the NT-proBNP levels were higher in patients with new-onset AF than controls without AF. The SMD of the NT-proBNP levels between the patients with and those without AF was 0.53 units (95% CI 0.37-0.70), test for overall effect z-score =6.30 (p < 0.00001). The heterogeneity test showed that there were moderate differences between individual studies (p = 0.02; I(2) =( )62%). Further analysis revealed that differences of ethnic groups and the sample size of studies possibly account for this heterogeneity. CONCLUSIONS: In spite of moderate heterogeneity across the enrolled studies, our meta-analysis suggests that increased NT-proBNP levels are associated with greater risk of new-onset AF with ACS, which indicates that NT-proBNP levels may be a useful biomarker in predicting new-onset AF in patients with ACS.

An antitumor agent of beta-cyclodextrin-modified titanocene complex: synthesis and characterization.

The complex of a derivative of beta-cyclodextrin, that is mono[6-deoxy-6-(2-butenedinitrile-2,3-dimercapto sodium salt)]-beta-cyclodextrin (6-mnt-beta-CD), with titanocene (titanocene di[mono[6-deoxy-6-(2-butenedinitrile-2,3-dimercapto)]-beta-cyclodextrin], Cp2Ti[6-mnt-beta-CD]2) has been synthesized and characterized by IR spectroscopy, UV spectroscopy, elemental analysis, thermogravimetry, 1H- and 13C-NMR spectroscopy. The stoichiometry of the target molecule was determined by 1H-NMR spectroscopy and elemental analysis.