ABSTRACT
Background: Endometriosis is a chronic inflammatory disease defined as the presence of endometrial tissue outside the uterus, which causes pelvic pain and infertility. Cytokines appear to play vital roles in the development and progression of endometriosis and associated infertility. Tumor necrosis factoralpha (TNF-alpha) is a multifunctional pro-inflammatory cytokine, responsible for autoimmune and inflammatory disorders. TNF- alpha plays an important role in endometrial physiology as well as during early implantation. In addition, this cytokine has a considerable pathophysiological function in diseases such as menorrhagia, endometriosis, or infertility due to its regulatory impact on proliferation, differentiation, and angiogenesis in the human endometrium. In women with endometriosis, TNF-alpha levels increases in peritoneal fluid and serum significantly. In the present study, we focused on finding novel small molecules that can directly block TNFalpha- hTNFR1 (human TNF receptor 1) interaction. Method(s): In this regard, TNF-alpha inhibiting capacity of natural carotenoids was investigated in terms of blocking TNF-alpha-hTNFR1 interaction with the help of a combination of in silico approaches, based on virtual screening, molecular docking, and molecular dynamics (MD) simulation. Result(s): A total of 125 carotenoids were selected out of 1204 natural molecules, based on their pharmacokinetics properties, and they all met Lipinski's rule of five. Among them, sorgomol, strigol, and orobanchol had the most favorable DELTAG with the best pharmacokinetics properties and were selected for MD simulation studies, which explored the complex stability and the impact of ligands on protein conformation. It was shown that sorgomol formed the most hydrogen bonds, resulting in the highest binding energy with the lowest RMSD and RMSF. Conclusion(s): Our results showed that sorgomol was the most appropriate candidate as a TNF-alpha inhibitor. In conclusion, the present study could serve to expand possibilities to develop new therapeutic small molecules against TNF-alpha which plays an important role in the inflammation of endometriosis.
ABSTRACT
Background and Objective: In the epidemic of COVID-19, intensive care units usually bear a heavy burden due to overcrowding of patients who need hospitalization, which can be due to liver involvement in these patients. This study was conducted to assess the relationship between liver enzymes in COVID-19 patients and the need for hospitalization in the intensive care unit, as well as to investigate its relationship with the length of stay in the intensive care unit. Methods: In this analytical cross-sectional study, 622 hospitalized patients with COVID-19 who referred to Firoozgar Hospital were investigated in terms of length of stay, recovery or death and its relationship with abnormal liver enzymes. Findings: The mean level of AST and ALT in people hospitalized in ICU was 49 (95% CI: 43.4-54.6) and 29.2 (95% CI: 24.1-34.2), respectively, and it was 42.5 (95% CI: 36.7-48.3) and 31.2 (95% CI: 25.8-36.6), respectively, in the general ward. The mean level of AST and ALT in patients hospitalized for less than 7 days was 49.4 (95% CI: 43.9-54.8) and 27 (95% CI: 21.6-32.3), respectively, and in patients hospitalized for more than 7 days was 41.6 (95% CI: 35.6-47.5) and 32.2 (95% CI: 37.3-27.1), respectively. None of the abnormal data was significant based on hospital department and length of stay. Conclusion: The results of this study did not show any significant relationship between the need for admission to ICU and the abnormal levels of liver enzymes. Furthermore, no relationship was found between the length of stay and the severity of liver involvement based on the assessment of abnormal liver enzymes.
ABSTRACT
Coronavirus 2 (SARS-CoV-2) leads to Coronavirus disease 2019, is recognized as a lethal epidemic in 2020. SARS-CoV-2 is an enveloped, non-segmented, positive sense RNA virus that belongs to the beta-corona family of viruses. The genome of this virus is about 30 kb representing 16 non-structural proteins (Nsp1-16), four structural proteins (N, M, E, S) and nine accessory proteins are encoded by its genome, which are involved in survival and pathogenesis the viruses. In order to produce medicines and vaccines for SARS-CoV-2, it is essential to fully understand the genomic structure of the virus and function of its proteins. This review collects and investigates the functional properties of SARS-CoV-2 proteins that have been reported to date. © 2021, University of Defence, Faculty of Military Health Sciences. All rights reserved.
ABSTRACT
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [COVID-19] quickly turned into a pandemic. Gastrointestinal involvement, especially liver diseases, is one of the main complications of COVID-19 patients. Objectives: The current study aimed to evaluate the high incidence of liver involvement in COVID-19 hospitalized patients and its association with mortality. Methods: A total of 560 hospitalized patients with a confirmed diagnosis of COVID-19 were included. Death was considered as the outcome. In addition to liver enzymes, demographic, clinical, and other laboratory data were also collected. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels_ 40 were considered as abnormal. To investigate the association between abnormal levels of liver enzymes and death, multiple regression logistic was used. Results: According to the findings, 29.1% (95% CI = 25.3% - 32.9%) of patients had high levels (_ 40 IU) of ALT, and 45.1% (95% CI = 40.9% - 49.3%) had high levels of AST (_ 40 IU). The frequency (based on %) of high levels of AST (_ 40 U/liter) was significantly higher in patients who died [67.3% (95% CI = 54.5% - 80.1%] of COVID-19 than those who survived [44.9% (95% CI = 39.7% - 50.0%)] (Pvalue < 0.001). No significant difference was detected in ALT between expired [29.1% (95% CI = 16.7% - 41.5%)] and survived patients [30.7% (95% CI = 25.9% - 35.5%] (P-value = 0.791). AST was found to have an independent association with death in multiple logistic regression (Wald = 4.429, OR (95% CI) = 1.014 (1.008 - 1.020), P-value = 0.035). Conclusions: Liver involvement is a common finding in COVID-19 hospitalized patients. Higher levels of AST were significantly associated with an increased mortality rate in COVID-19 patients.