Coronavirus disease 2019 (COVID-19) not only causes a range of respiratory symptoms but also has a great impact on individual mental health. With the global pandemic of SARS-CoV-2, the incidence of ...COVID-19 comorbid with depression has increased significantly. Curcumin, a natural polyphenol compound, has been shown to have antidepressant and anti-coronavirus activities.
This study aimed to explore the molecular targets and underlying biological mechanisms of curcumin in the treatment of COVID-19 with depression through an integrative pharmacology strategy, including target prediction, network analysis, PPI analysis, GO and KEGG enrichment analyses, and molecular docking.
After a comprehensive search and thorough analysis, 8 core targets (ALB, AKT1, CASP3, STAT3, EGFR, PTGS2, FOS, and SERPINE1) were identified. GO and KEGG enrichment analysis results revealed that the pathways related to viral infection, immune regulation, neuronal reorganization, apoptosis, and secretion of inflammatory cytokines were involved in the pathological process. Furthermore, molecular docking showed that curcumin could spontaneously bind to the SARS-CoV-2-related receptor proteins and the core targets with a strong binding force.
The potential pharmacological mechanisms of curcumin in COVID-19 comorbid depression were evaluated. Curcumin can be used as a therapeutic agent for COVID-19 comorbid depression. One of the potential mechanisms may be to reduce the inflammatory response and suppress the cytokine storm by regulating the JAK-STAT signaling pathway and MAPK signaling pathway. These findings may help to overcome the impact of the COVID-19 pandemic on psychological health.
In this paper, we are interested in a coupled Schrödinger system with Stein–Weiss type convolution part. Firstly we study the existence and nonexistence of the solutions by variational methods. ...Second, by changing the system into an equivalent integral form, we study the symmetry, regularity and asymptotic behaviors of the solutions by moving plane arguments.
Objective:
To objectively evaluate the effectiveness of Baduanjin exercise on cardiopulmonary function and quality of life in chronic obstructive pulmonary disease patients.
Data sources:
Articles ...published in PubMed, EMBASE, China National Knowledge Infrastructure Database, the Cochrane Library, Wanfang Database, and China Biological Medicine Database from inception to March 2020.
Review Method:
Articles on randomized controlled trials about Baduanjin exercise for the treatment of chronic obstructive pulmonary disease were identified. Cochrane handbook was applied to assess the quality of included trials. Stata (version 14.0) and Review Manager (version 5.3) were employed for data analysis. Mean difference with 95% confidence intervals were calculated for pulmonary function, 6-minute walking distance, and the quality of life.
Results:
Thirty-one randomized controlled trials including 3045 patients were included. The result of meta-analysis indicated that comparing with any other type of treatment alone, Baduanjin exercise combined other type of treatment revealed well efficacy in improving exercise capability on 6-minute walking distance (mean difference = 43.83, 95% confidence interval (29.47, 58.20), P < 0.00001), forced expiratory volume in 1 second (mean difference = 0.23, 95% confidence interval (0.15, 0.31), P < 0.00001), forced volume vital capacity (mean difference = 0.19, 95% confidence interval (0.08, 0.30), P = 0.0007), the ratio of forced expiratory volume in the first second to forced vital capacity (mean difference = 3.85, 95% confidence interval (2.19, 5.51), P < 0.00001), and the quality of life in chronic obstructive pulmonary disease patients regarding the St. George respiratory questionnaire (mean difference = –7.71, 95% confidence interval (–10.54, –4.89), P < 0.00001) and chronic obstructive pulmonary disease assessment test (mean difference = –2.56, 95% confidence interval (–4.13, –1.00), P = 0.001).
Conclusions:
Baduanjin exercise could improve exercise capacity, pulmonary function, and quality of life for patients with chronic obstructive pulmonary disease.
In this paper, we study the qualitative properties and classification of the solutions to the elliptic equations with Stein-Weiss type convolution part. Firstly, we study the qualitative properties, ...such as the symmetry, regularity and asymptotic behavior of the positive solutions. Secondly, we classify the non-positive solutions by proving some Liouville type theorems for the finite Morse index solutions and stable solutions to the nonlocal elliptic equations with double weights.
In this paper, we study the following weighted nonlocal system with critical exponents related to the Stein–Weiss inequality
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By using moving plane arguments in integral form, we obtain symmetry, regularity and asymptotic properties, as well as sufficient conditions for the nonexistence of solutions to the nonlocal Stein–Weiss system.
Numerous metabolomic studies have confirmed the pivotal role of metabolic abnormalities in the development of idiopathic pulmonary fibrosis (IPF). Nevertheless, there is a lack of evidence on the ...causal relationship between circulating metabolites and the risk of IPF.
The potential causality between 486 blood metabolites and IPF was determined through a bidirectional two-sample Mendelian randomization (TSMR) analysis. A genome-wide association study (GWAS) involving 7,824 participants was performed to analyze metabolite data, and a GWAS meta-analysis involving 6,257 IPF cases and 947,616 control European subjects was conducted to analyze IPF data. The TSMR analysis was performed primarily with the inverse variance weighted model, supplemented by weighted mode, MR-Egger regression, and weighted median estimators. A battery of sensitivity analyses was performed, including horizontal pleiotropy assessment, heterogeneity test, Steiger test, and leave-one-out analysis. Furthermore, replication analysis and meta-analysis were conducted with another GWAS dataset of IPF containing 4,125 IPF cases and 20,464 control subjects. Mediation analyses were used to identify the mediating role of confounders in the effect of metabolites on IPF.
There were four metabolites associated with the elevated risk of IPF, namely glucose (odds ratio OR = 2.49, 95% confidence interval 95%CI = 1.13-5.49, P = 0.024), urea (OR = 6.24, 95% CI = 1.77-22.02, P = 0.004), guanosine (OR = 1.57, 95%CI = 1.07-2.30, P = 0.021), and ADpSGEGDFXAEGGGVR (OR = 1.70, 95%CI = 1.00-2.88, P = 0.0496). Of note, the effect of guanosine on IPF was found to be mediated by gastroesophageal reflux disease. Reverse Mendelian randomization analysis displayed that IPF might slightly elevate guanosine levels in the blood.
Conclusively, hyperglycemia may confer a promoting effect on IPF, highlighting that attention should be paid to the relationship between diabetes and IPF, not solely to the diagnosis of diabetes. Additionally, urea, guanosine, and ADpSGEGDFXAEGGGVR also facilitate the development of IPF. This study may provide a reference for analyzing the potential mechanism of IPF and carry implications for the prevention and treatment of IPF.
Abstract
Background
Idiopathic pulmonary fibrosis (IPF) is a chronic diffuse interstitial lung disease, of which the etiology has been poorly understood. Several studies have focused on the ...relationship between IPF and diabetes mellitus (DM) in the past years but have failed to reach a consensus. This meta-analysis aimed to examine the association between diabetes to IPF.
Methods
We accumulated studies investigating the association between DM and IPF from databases including Medline, Cochrane Library, Embase, Web of Science, and China National Knowledge Infrastructure. RevMan 5.3 and the Newcastle–Ottawa Scale (NOS) were utilized to analyze the data and assess the quality of the included studies. The value of odds ratio (OR) with 95% confidence interval (CI) was used as the measure to estimate the risk of DM in IPF. Heterogeneity was assessed by
I
2
statistics. We also performed subgroup analysis, meta-regression, and Egger’s test for bias analysis.
Results
Nine case–control studies with 5096 IPF patients and 19,095 control subjects were included in the present meta-analysis, which indicated a positive correlation between DM and IPF (OR 1.65, 95% CI 1.30–2.10;
P
< 0.0001). Meta-regression and subgroup analysis negated the influence of covariates like cigarette smoking, age and gender, but the heterogeneity existed and could not be fully explained.
Conclusion
IPF and DM may be associated, but the causal relationship remains indeterminate till now. Further rigorously designed studies are required to confirm the present findings and investigate the possible mechanisms behind the effect of DM on IPF.
(−)-Epigallocatechin-3-gallate (EGCG) is the main bioactive catechin in green tea. The antitumor activity of EGCG has been confirmed in various types of cancer, including lung cancer. However, the ...precise underlying mechanisms are still largely unclear. In the present study, we investigated the metabolite changes in A549 cells induced by EGCG
in vitro
utilizing liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. The result revealed 33 differentially expressed metabolites between untreated and 80 μM EGCG-treated A549 cells. The altered metabolites were involved in the metabolism of glucose, amino acid, nucleotide, glutathione, and vitamin. Two markedly altered pathways, including glycine, serine and threonine metabolism and alanine, aspartate and glutamate metabolism, were identified by MetaboAnalyst 5.0 metabolic pathway analysis. These results may provide potential clues for the intramolecular mechanisms of EGCG’s effect on A549 cells. Our study may contribute to future molecular mechanistic studies of EGCG and the therapeutic application of EGCG in cancer management.
Acute respiratory distress syndrome (ARDS) is a serious life threatening clinical critical illness. ARDS-related pulmonary fibrosis is a common complication of ARDS. The occurrence of early pulmonary ...fibrosis indicates a higher incidence and mortality of multiple organ failure. LPS-induced ARDS-related pulmonary fibrosis model in mice was established in this study. And we have explored the anti-pulmonary fibrosis effects and molecular mechanisms of the Citrus Alkaline Extracts (CAE) in vivo and in vitro.
Pulmonary fibrosis mouse model and lung epithelial cell injury model were established in this study. H&E, Masson and Sirius Red staining were used to estimate lung tissue damage. Immunohistochemistry and western blotting were used to analyze proteins expression. Protein-protein interaction was observed by Co-Immunoprecipitation. Systemic impact of CAE on signaling pathway was examined by RNA-seq.
Through H&E, Masson and Sirius Red staining, it was convincingly indicated that therapeutic administration of CAE alleviated lung injury and fibrosis, while pretreated administration of CAE showed weak improvement. In vitro experiments showed that CAE had dual regulation to E-cadherin and N-cadherin, the important indicators of epithelial-mesenchymal transition (EMT). And it was further demonstrated that CAE reversed TGF-β1-induced EMT mainly through Wnt/β-catenin, Stat3/6 and COX2/PGE2 signals. Through RNA-Seq, we discovered important mechanisms by which CAE exerts its therapeutic effect. And network pharmacology analysis demonstrated core potential targets of CAE in EMT.
Thus, this study provides new therapeutic effects of CAE in anti-fibrosis, and offers potential mechanisms for CAE in LPS-induced pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal lung disease with a poor prognosis and limited treatment options. The incidence of IPF increases with age, and the mechanisms ...related to aging such as cellular senescence have been strongly implicated in disease pathology. Therefore, a better understanding of fibroblasts senescence might provide a new therapeutic strategy to prevent and treat pulmonary fibrosis. In this study, we aimed to explore the effects of citrus alkaline extracts (CAE) on the fibroblasts senescence, and elucidate the underlying mechanism to ameliorate pulmonary fibrosis. We demonstrated that CAE mitigated the collagen deposition by the initial early treatment, suggesting a potential preventive effect of CAE on pulmonary fibrosis. The expression of senescence biomarkers P16INK4a and P21, concomitant with down-regulation of the myofibroblasts marker α-SMA, and the number of senescence-associated β-galactosidase (SA-β-Gal) positive cells were decreased by CAE treatment, indicating a significant inhibitory effect of CAE on fibroblast senescence. Additionally, CAE down-regulated the expression of the senescence-associated secretory phenotype (SASP) in etoposide-induced senescent fibroblasts. Further studies indicated that COX-2 activation was required for CAE to inhibit the lung fibroblast senescence through a P53-dependent pathway. Results showed that the anti-senescence effect of CAE was abrogated when COX-2 was knocked down or inhibited by COX-2 inhibitor NS-398 or indomethacin in lung fibroblasts. Meanwhile, the anti-fibrotic and anti-senescence effect of CAE were abolished due to disruption of COX-2 in vivo. Collectively, our results provided a novel insight into the potential mechanism of CAE to inhibit the fibroblasts activation through preventing cellular senescence.
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