Blockade of thromboxane A2 signaling attenuates ethanol-induced myocardial inflammatory response in mice.

BACKGROUND: Alcohol-associated cardiomyopathy (ACM) is a cardiac muscle disease characterized by inflammation and oxidative stress. Thromboxane-prostanoid receptor (TP-R) plays an important role in the pathogenesis of cardiovascular disease. Herein, we hypothesize that TP-R mediates alcohol-induced early cardiac injury. METHODS: Eight-week-old male C57BL/6 wild-type mice were fed a chronic ethanol (ET) or control diet (CON) for 10 days followed by a single binge of ethanol or maltose-dextrin through oral gavage. A cohort of ethanol-fed mice received SQ 29,548 (SQ), a TP-R antagonist. RNA sequencing, real-time PCR, and western blot analysis were performed on left ventricle to investigate alterations in genes and/or proteins mediating oxidative stress, inflammation, and cardiac remodeling. Sirius Red staining was performed to measure myocardial fibrosis. RESULTS: RNA-sequencing analysis of myocardium from CON and ET groups identified 142 genes that were significantly altered between the two groups. In particular, the gene expression of thioredoxin-interacting protein (TXNIP), a component of NLR family pyrin domain containing 3 (NLRP3) signaling, which mediates oxidative stress and inflammatory response, was upregulated in response to ethanol exposure. The myocardial protein levels of TP-R and thromboxane A2 synthase were increased upon alcohol exposure. Ethanol increased the levels of 4-hydroxynonenal, a marker of oxidative stress, with a concomitant increase in the protein levels of TXNIP and NLRP3, and administration of SQ attenuated these effects. Additionally, ethanol increased the protein levels of pro-inflammatory mediators, including tumor necrosis factor alpha and the NLRP3 downstream product, secretory interleukin 1 beta, and SQ blunted these effects. Finally, the Sirius red staining of the myocardium revealed an increase in collagen deposition in ethanol-fed mice which was attenuated by TP-R antagonism. CONCLUSION: This study demonstrates that ethanol promotes the NLRP3 signaling pathway within the myocardium, leading to a pro-inflammatory milieu that potentially initiates early myocardial remodeling, and TP-R antagonism attenuates this effect.

Evaluation of inflammatory cytokines in drug-naïve major depressive disorder: A systematic review and meta-analysis.

Objective: Altered levels of peripheral inflammatory and proinflammatory cytokine markers affect the different clinical stages of major depressive disorder (MDD). A concrete understanding of the causal mechanism of MDD is a prerequisite in developing treatment strategies and preventive plans. Here we aimed to conduct an updated systematic review and meta-analysis of studies assessing the association of C-reactive protein (CRP), INF-γ, MCP-1, and TNF-α in the peripheral fluid of drug-naïve MDD patients and healthy controls (HCs). Methods: We extracted articles from PubMed, ProQuest, PsycINFO, Web of Science, and Scopus databases from inception until 14 February 2021, to find relevant studies. In this meta-analysis, we included a total of 23 eligible studies (1,366 MDD patients and 1,342 controls) in the final meta-analysis. The Cochran's chi-square Q-test and I2-index were applied to measure the heterogeneity and inconsistency of all combined results. We selected a random-effect model during the analysis and measured publication biases using the funnel plot. We performed Bonferroni adjustment for multiple testing. Results: We found a high level of TNF-α in MDD patients than in control subjects Standardized Mean Difference (SMD) with a random-effects model: 1.04, 95% CI: 0.69-1.39, z = 5.84, p < 0.001). The levels of CRP (SMD with a random-effects model: 0.18, 95% CI: -0.85-1.23, z = 0.35, p = 0.73), INF-ɤ (SMD with a random-effects model: -0.05, 95% CI: -2.72-2.62, z = 0.03, p = 0.97), and MCP-1 (SMD with a random-effects model: 0.70, 95% CI: -0.09-1.49, z = 1.73, p = 0.08) were not significantly varies between MDD patients and HCs. Conclusion: The present study findings suggest the upregulated level of peripheral TNF-α but not CRP, INF-γ, and MCP-1 involve in depression. The elevated inflammatory cytokines confirmed the inflammatory state of depression. Therefore, inflammatory cytokines might serve as potential risk assessment markers in MDD.

Increased serum resistin but not G-CSF levels are associated in the pathophysiology of major depressive disorder: Findings from a case-control study.

BACKGROUND: Many studies have predicted major depressive disorder (MDD) as the leading cause of global health by 2030 due to its high prevalence, disability, and illness. However, the actual pathophysiological mechanism behind depression is unknown. Scientists consider alterations in cytokines might be tools for understanding the pathogenesis and treatment of MDD. Several past studies on several inflammatory cytokine expressions in MDD reveal that an inflammatory process is activated, although the precise causes of that changes in cytokine levels are unclear. Therefore, we aimed to investigate resistin and G-CSF in MDD patients and controls to explore their role in the pathogenesis and development of depression. METHODS: We included 220 participants in this study. Among them, 108 MDD patients and 112 age-sex matched healthy control (HCs). We used DSM-5 to evaluate study participants. Also, we applied the Ham-D rating scale to assess the severity of patients. Serum resistin and G-CSF levels were measured using ELISA kits (BosterBio, USA). RESULTS: The present study observed increased serum resistin levels in MDD patients compared to HCs (13.82 ± 1.24ng/mL and 6.35 ± 0.51ng/mL, p <0.001). However, we did not find such changes for serum G-CSF levels between the groups. Ham-D scores showed a significant correlation with serum resistin levels but not G-CSF levels in the patient group. Furthermore, ROC analysis showed a fairly predictive performance of serum resistin levels in major depression (AUC = 0.746). CONCLUSION: The present study findings suggest higher serum resistin levels are associated with the pathophysiology of MDD. This elevated serum resistin level may serve as an early risk assessment indicator for MDD. However, the role of serum G-CSF in the development of MDD is still unclear despite its neuroprotective and anti-inflammatory effects.

Effect of COVID-19 pandemic on mental health among Bangladeshi healthcare professionals: A cross-sectional study.

The COVID-19 has been spreading across the world since December 2019. The pandemic has created tremendous fear of death from infection and awful psychological pressure on healthcare professionals (HCPs). The measures of psychological effects of the COVID-19 outbreak on the Bangladeshi HCPs are unknown. The present study aimed to assess the mental health outcomes of Bangladeshi HCPs and associated risk factors. We conducted this cross-sectional study from July 15 to September 20, 2020. A total of 355 HCPs aged between 20 and 60 years residing in Bangladesh participated in this study. All the participants completed a self-administered questionnaire through Google Forms consisting of socio-demographic characteristics and mental health outcomes. We measure loneliness, depression, anxiety, and sleep disturbance using the UCLA loneliness scale-8, patient health questionnaire-9, 7-item generalized anxiety disorder scale, Pittsburgh sleep quality index. The present study observed the prevalence of loneliness, depression, anxiety, and sleep disturbance among HCPs were 89%, 44%, 78%, and 87%, respectively. The factors significantly associated with the development of mental health problems among HCPs were working environment, economic condition, education level, area of residence, marital status, gender differences, professional category, body mass index, and smoking habit. Moreover, we have seen significant correlations among the different mental health outcomes. In Bangladesh, a large portion of HCPs reported mental health issues during the COVID-19 pandemic. COVID-19 pandemic incredibly impacted the psychological health of Bangladeshi healthcare professionals. Appropriate supportive programs and interventional initiatives might help the HCPs with mental health problems during and after this pandemic.