RESUMO
Background: A significant aspect of the SARS-CoV-2 pathology involves oxidative stress, characterized by an imbalance between the production of harmful free radicals and the body's antioxidant defenses. With the ongoing evolution of SARS-CoV-2, the investigation into non-virus-specific therapeutic options, such as antioxidant therapy, has gained importance. Objectives: This systematic review and meta-analysis aimed to summarize data from randomized control trials (RCTs) to evaluate the effectiveness and safety of antioxidant therapy in patients with SARS-CoV-2 infection. Methods: We searched the peer-reviewed indexed literature on MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, EMBASE, International Pharmaceutical Abstracts, and Scopus, from inception to July 2023. Results: The search identified 3306 articles from which 25 were included for quantitative synthesis, with 5 studies eligible for meta-analysis. Antioxidant therapies included zinc, vitamin A, vitamin C, and combination treatments. Zinc interventions showed mixed results regarding intensive care unit admissions and hospital stays. Vitamin A studies indicated improvements in inflammatory markers. Vitamin C studies displayed inconsistent effects on clinical improvement and hospitalization. Combination treatments suggested benefits in symptom clearance and cytokine storm reduction. Meta-analysis of vitamin C studies found no significant difference in C-reactive protein concentrations (-0.50; 95% CI: -3.63, 2.63; I2 = 0%), intensive care unit stay duration (pooled mean difference: 1.44; 95% CI: 0.07, 2.81; I2 = 0%), or mortality (pooled odds ratio: 0.55; 95% CI: 0.28, 1.09; I2 = 0%), with a slight trend favoring reduced hospitalization duration (pooled mean difference: -2.37; 95% CI: -2.99, -1.76; I2 = 49%). Of the 25 studies, 8 were high quality with low bias, 6 had some concerns, and 11 were low quality with high bias. Conclusions: The review presents mixed efficacy of antioxidant therapies for SARS-CoV-2, with some studies indicating potential benefits. Further well-designed large-scale RCTs are warranted to determine the definitive role of antioxidants in SARS-CoV-2 treatment.This systematic review was registered at PROSPERO as CRD42023430805.
RESUMO
OBJECTIVE: Adipose tissue is a very dynamic metabolic organ that plays an essential role in regulating whole-body glucose homeostasis. Dysfunctional adipose tissue hypertrophy with obesity is associated with fibrosis and type 2 diabetes. Yes-associated protein 1 (YAP) is a transcription cofactor important in the Hippo signaling pathway. However, the role of YAP in adipose tissue and glucose homeostasis is unknown. METHODS: To study the role of YAP with metabolic stress, we assessed how increased weight and insulin resistance impact YAP in humans and mouse models. To further investigate the in vivo role of YAP specifically in adipose tissue and glucose homeostasis, we developed adipose tissue-specific YAP knockout mice and placed them on either chow or high fat diet (HFD) for 12-14 weeks. To further study the direct role of YAP in adipocytes we used 3T3-L1 cells. RESULTS: We found that YAP protein levels increase in adipose tissue from humans with type 2 diabetes and mouse models of diet-induced obesity and insulin resistance. This suggests that YAP signaling may contribute to adipocyte dysfunction and insulin resistance under metabolic stress conditions. On an HFD, adipose tissue YAP knockout mice had improved glucose tolerance compared to littermate controls. Perigonadal fat pad weight was also decreased in knockout animals, with smaller adipocyte size. Adipose tissue fibrosis and gene expression associated with fibrosis was decreased in vivo and in vitro in 3T3-L1 cells treated with a YAP inhibitor or siRNA. CONCLUSIONS: We show that YAP is increased in adipose tissue with weight gain and insulin resistance. Disruption of YAP in adipocytes prevents glucose intolerance and adipose tissue fibrosis, suggesting that YAP plays an important role in regulating adipose tissue and glucose homeostasis with metabolic stress.