Melatonin as a Promising Anti-Inflammatory Agent in an In Vivo Animal Model of Sepsis-Induced Rat Liver Damage.

Melatonin (MLT), earlier described as an effective anti-inflammatory agent, could be a beneficial adjunctive drug for sepsis treatment. This study aimed to determine the effects of MLT application in lipopolysaccharide (LPS)-induced sepsis in Wistar rats by determining the levels of liver tissue pro-inflammatory cytokines (TNF-α, IL-6) and NF-κB as well as hematological parameters indicating the state of sepsis. Additionally, an immunohistological analysis of CD14 molecule expression was conducted. Our research demonstrated that treatment with MLT prevented an LPS-induced increase in pro-inflammatory cytokines TNF-α and IL-6 and NF-κB levels, and in the neutrophil to lymphocyte ratio (NLR). On the other hand, MLT prevented a decrease in the blood lymphocyte number induced by LPS administration. Also, treatment with MLT decreased the liver tissue expression of the CD14 molecule observed after sepsis induction. In summary, in rats with LPS-induced sepsis, MLT was shown to be a significant anti-inflammatory agent with the potential to change the liver's immunological marker expression, thus ameliorating liver function.

In silico approach for the development of novel antiviral compounds based on SARS-COV-2 protease inhibition.

The COVID-19 pandemic emerged in 2019, bringing with it the need for greater stores of effective antiviral drugs. This paper deals with the conformation-independent, QSAR model, developed by employing the Monte Carlo optimization method, as well as molecular graphs and the SMILES notation-based descriptors for the purpose of modeling the SARS-CoV-3CLpro enzyme inhibition. The main purpose was developing a reproducible model involving easy interpretation, utilized for a quick prediction of the inhibitory activity of SAR-CoV-3CLpro. The following statistical parameters were present in the best-developed QSAR model: (training set) R 2 = 0.9314, Q 2 = 0.9271; (test set) R 2 = 0.9243, Q 2 = 0.8986. Molecular fragments, defined as SMILES notation descriptors, that have a positive and negative impact on 3CLpro inhibition were identified on the basis of the results obtained for structural indicators, and were applied to the computer-aided design of five new compounds with (4-methoxyphenyl)[2-(methylsulfanyl)-6,7-dihydro-1H-[1,4]dioxino[2,3-f]benzimidazol-1-yl]methanone as a template molecule. Molecular docking studies were used to examine the potential inhibition effect of designed molecules on SARS-CoV-3CLpro enzyme inhibition and obtained results have high correlation with the QSAR modeling results. In addition, the interactions between the designed molecules and amino acids from the 3CLpro active site were determined, and the energies they yield were calculated. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-022-02170-8.

Melatonin modulates acute cardiac muscle damage induced by carbon tetrachloride - involvement of oxidative damage, glutathione, and arginine and nitric oxide metabolism.

The present study was designed to evaluate the cardioprotective effects of melatonin (a single dose of 50 mg·kg-1), a naturally occurring polypharmacological molecule, in Wistar rats acutely exposed to carbon tetrachloride (CCl4). This was done for the first time by tracking different biochemical parameters that reflect rat heart antioxidative and oxidative capacities, nitric oxide and arginine metabolism, and the glutathione cycle. Additionally, the extrinsic apoptosis pathway related parameters were studied. Acute exposure to CCl4 led to an increase in the studied tissue oxidant parameters (hydrogen peroxide, malondialdehyde, and carbonylated protein content), as well as the activity alteration of antioxidant (catalase, superoxide dismutase, and peroxidase) and glutathione-metabolizing (glutathione peroxidase, S-transferase, and reductase) enzymes. Furthermore, CCl4 caused a disturbance in the tissue myeloperoxidase, nitric oxide, citrulline, arginase, and inducible nitric oxide synthase content and activities and in two apoptosis-related parameters, caspase-3 and FAS ligand. Melatonin as a post-treatment prevented the changes induced by CCl4 to a differing extent, and in some cases, it was so potent that it completely abolished any tissue disturbances. This study is a promising starting point for further research directed to the development of melatonin treatment in cardiac tissue associated diseases.

Quality of life in patients related to gender differences before and after coronary artery bypass surgery.

OBJECTIVES: The different aspects of quality of life (QOL) in patients of different sex structure have been examined as well as the presumption that sex structure could be a predictor of QOL changes after coronary artery bypass grafting (CABG). METHODS: The study included 243 consecutive patients who underwent an elective CABG. The QOL analysis was performed by using structured interviews with the Nottingham Health Profile (NHP) questionnaire part 1. RESULTS: Compared to men, women had worse preoperative QOL (in all sections except the section of sleep) and worse postoperative QOL (in all sections). Six months after CABG the QOL statistically improved in men and in women. Multivariate analysis showed that being female was an independent predictor of QOL worsening in section of pain [P=0.001, odds ratio (OR)=3.93, 95% confidence interval (CI) 1.74-8.88]. CONCLUSIONS: Compared to men, women have worse preoperative and postoperative QOL. Female sex was an independent predictor of QOL worsening six months after CABG.

Predictors of worsening of patients' quality of life six months after coronary artery bypass surgery.

BACKGROUND: The possibility to predict the change in (the) quality of life after coronary artery bypass surgery (CABG) being unclear, the aim was to evaluate the change of quality of life and predictors of worsening of quality of life in patients six months after CABG. METHODS: We studied 208 consecutive patients, who underwent elective CABG. The Nottingham Health Profile Questionnaire part 1 was used as the model for quality of life determination. The questionnaire contains 38 subjective statements divided into six sections: physical mobility, social isolation, emotional reaction, energy, pain, and sleep. We distributed the questionnaire to all patients before CABG and six months after CABG. One hundred ninety-two patients filled in the postoperative questionnaire. RESULTS: The comparison between mean preoperative and postoperative scores showed an improvement in all sections of quality of life (p < 0.001). New York Heart Association functional class was significantly improved after CABG (2.23 +/- 0.65 vs. 1.58 +/- 0.59, p<0.001). Independent predictors of patients worsened by CABG were as follows: female gender in the pain section (p = 0.002; OR = 4.27; CI 1.74-10.47), diabetes mellitus in the physical mobility section (p = 0.003; OR = 8.09; CI 2.04-32.09), low ejection fraction in the physical mobility (p = 0.047; OR = 0.73; CI 0.56-0.95) and emotional reaction (p = 0.03; OR = 0.86; CI 0.60-0.93) sections, and postoperative complications in the social isolation (p = 0.002; OR = 4.63; CI 1.79-11.99), sleep (p = 0.03; OR = 2.71; CI 1.12-6.51), and pain (p = 0.005; OR = 3.39; CI 1.45-7.97) sections. CONCLUSION: The predictive factors for quality of life worsening six months after CABG are female gender, diabetes mellitus, low ejection fraction, and the presence of postoperative complications.