Endothelial Dysfunction, Inflammation, and Oxidative Stress in COVID-19-Mechanisms and Therapeutic Targets.

The outbreak of the COVID-19 pandemic represents an ongoing healthcare emergency responsible for more than 3.4 million deaths worldwide. COVID-19 is the disease caused by SARS-CoV-2, a virus that targets not only the lungs but also the cardiovascular system. COVID-19 can manifest with a wide range of clinical manifestations, from mild symptoms to severe forms of the disease, characterized by respiratory failure due to severe alveolar damage. Several studies investigated the underlying mechanisms of the severe lung damage associated with SARS-CoV-2 infection and revealed that the respiratory failure associated with COVID-19 is the consequence not only of acute respiratory distress syndrome but also of macro- and microvascular involvement. New observations show that COVID-19 is an endothelial disease, and the consequent endotheliopathy is responsible for inflammation, cytokine storm, oxidative stress, and coagulopathy. In this review, we show the central role of endothelial dysfunction, inflammation, and oxidative stress in the COVID-19 pathogenesis and present the therapeutic targets deriving from this endotheliopathy.

A study of oxidative stress and pulmonary damage after silica instillation in rats and the effect of curcumin administration.

BACKGROUND: The authors' aim was to study the dynamics of oxidative stress in experimental exposure to silica dust, to evaluate the histopathological findings in the phase preceding the formation of fibrous/fibrohyaline pulmonary nodules, and to assess the effects of curcumin administration. MATERIAL AND METHODS: The research was performed on 48 male Wistar rats with an average weight of 320 g. Overall, 38 rats were instilled with a single dose of 0.3 ml suspension containing 30 mg of a SiO2/ml saline solution, and were sacrificed 30, 90 and 120 days after instillation; 14 of those sacrificed on days 90 and 120 also received curcumin. The control group included 10 animals which were instilled with a saline solution. Malondialdehyde (MDA), carbonyl proteins (CPs), total thiolic proteins (TPs) and reduced glutathione (GSH) were determined in blood and the lung tissue. The standard technique for pulmonary toxicology developed by Porter was applied to semi-quantitatively assess the histopathological findings. RESULTS: It was found that MDA had increased significantly early on in both biological environments and remained elevated, and adding curcumin proved beneficial, while CPs only increased moderately in the lung tissue without a curcumin impact. Moreover, TPs dropped abruptly, significantly and persistently in the lung tissue and blood, and were not influenced by curcumin. Finally, GSH decreased significantly and intensely in the lung tissue and blood, with curcumin lowering the levels towards those found within the control group. The histopathological examination identified nodules of a cellular type, without any fibrosis, but with spots of associated lipoproteinosis. The early lesions in the airways and vessels were suggestive of a remodeling process. Curcumin diminished the occurrence of alveolitis but not the remodeling process. CONCLUSIONS: The study confirms the early onset of oxidative stress in experimental silicosis. It also simultaneously and dynamically researches markers of oxidative stress in blood and the lung tissue. Curcumin proved beneficial on oxidative stress and lesions in the alveolar epithelia, but ineffective in preventing vascular and airway remodeling. Med Pr. 2021;72(3):239-47.

Diabetes and Obesity-Cumulative or Complementary Effects On Adipokines, Inflammation, and Insulin Resistance.

BACKGROUND: Diabetes and obesity are increasingly significant public health issues. The aim of this study was to evaluate the relationship between adipocytokines (leptin, ghrelin, and chemerin), inflammation (sVCAM1-soluble vascular adhesion molecule 1, sICAM1-soluble intercellular adhesion molecule 1), and insulin resistance in the presence of obesity and diabetes mellitus. METHODS: 88 subjects, with a mean age of 61.96 ± 10.15 years, 75% of whom were women, were evaluated (in order to consider different associations between obesity and diabetes, subjects were categorized into four groups). RESULTS: Overall, we found significant correlations between sICAM1-sVCAM1 rho = 0.426 and ghrelin-chemerin rho = -0.224. In the obesity + diabetes group, leptin correlated with sICAM1 rho = 0.786, and sVCAM1 negatively with glycemia/insulin rho = -0.85. Significant differences were found between the groups regarding sVCAM1 (p = 0.0134), leptin (p = 0.0265) and all insulin resistance scores, with differences influenced by the subjects' gender. In conclusion, although there are currently many unknown aspects of the release and the role of various adipokines, in particular chemerin, its implication in early glucose metabolism dysregulation disorders seems very likely.

Effects of Lycium barbarum L. Polysaccharides on Inflammation and Oxidative Stress Markers in a Pressure Overload-Induced Heart Failure Rat Model.

Despite recent advances in disease management and prevention, heart failure (HF) prevalence is still high. Hypertension, inflammation and oxidative stress are being investigated as important causative processes in HF. L. barbarum L. polysaccharides (LBPs) are widely used for their anti-inflammatory and antioxidant properties. Thus, the aim of the present study was to evaluate the effects of LBPs on inflammation and oxidative stress markers in a pressure overload-induced HF rat model, surgically induced by abdominal aorta banding in Wistar rats (AAB) (n = 28). Also, control rats (n = 10) were subjected to a sham operation. After echocardiographic confirmation of HF (week 24), AAB rats were divided into three groups: rats treated with LBPs for 12 weeks: 100 mg/kg body weight /day (AAB_100, n = 9), 200 mg/kg body weight /day (AAB_200, n = 7) and no-treatment group (control AAB, n = 12). After 12 weeks of treatment with LBPs, the decline of cardiac function was prevented compared to the control AAB rats. Treatment with 200 mg/kg body weight /day LBPs significantly reduced the inflammation as seen by cytokine levels (IL-6 and TNF-α) and the plasma lipid peroxidation, as seen by malondialdehyde levels. These results suggest that LBPs present anti-inflammatory and antioxidant effects with utility in a HF animal model and encourage further investigation of the cardioprotective effects of these polysaccharides.

DNA Methylation and Micro-RNAs: The Most Recent and Relevant Biomarkers in the Early Diagnosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a frequently encountered cancer type, and its alarming incidence is explained by genetic and epigenetic alterations. Epigenetic changes may represent diagnostic and prognostic biomarkers of HCC. In this review we discussed deoxyribonucleic acid (DNA) hypomethylation, DNA hypermethylation, and aberrant expression of small non-coding ribonucleic acid (RNA), which could be useful new biomarkers in the early diagnosis of HCC. We selected the articles on human subjects published in English over the past two years involving diagnostic markers detected in body fluids, cancer diagnosis made on histopathological exam, and a control group of those with benign liver disease or without liver disease. These biomarkers need further investigation in clinical trials to develop clinical applications for early diagnosis and management of HCC.

New Thiazolyl-triazole Schiff Bases: Synthesis and Evaluation of the Anti-Candida Potential.

In the context of the dangerous phenomenon of fungal resistance to the available therapies, we present here the chemical synthesis of a new series of thiazolyl-triazole Schiff bases B1-B15, which were in vitro assessed for their anti-Candida potential. Compound B10 was found to be more potent against Candida spp. when compared with the reference drugs Fluconazole and Ketoconazole. A docking study of the newly synthesized Schiff bases was performed, and results showed good binding affinity in the active site of co-crystallized Itraconazole-lanosterol 14α-demethylase isolated from Saccharomyces cerevisiae. An in silico ADMET (absorption, distribution, metabolism, excretion, toxicity) study was done in order to predict some pharmacokinetic and pharmacotoxicological properties. The Schiff bases showed good drug-like properties. The results of in vitro anti-Candida activity, a docking study and ADMET prediction revealed that the newly synthesized compounds have potential anti-Candida activity and evidenced the most active derivative, B10, which can be further optimized as a lead compound.