Targeting the vital non-structural proteins (NSP12, NSP7, NSP8 and NSP3) from SARS-CoV-2 and inhibition of RNA polymerase by natural bioactive compound naringenin as a promising drug candidate against COVID-19.

The prevalence of SARS-CoV-2-induced respiratory infections is now a major challenge worldwide. There is currently no specific antiviral drug to prevent or treat this disease. Infection with COVID-19 seriously needs to find effective therapeutic agents. In the present study, naringenin, as a potential inhibitor candidate for RNA Polymerase SARS-CoV-2 was compared with remdesivir (FDA-approved drug) and GS-441,524 (Derivative of the drug remdesivir) by screening with wild-type and mutant SARS-CoV-2 NSP12 (NSP7-NSP8) and NSP3 interfaces, then complexes were simulated by molecular dynamics (MD) simulations to gain their stabilities. The docking results displayed ​scores of -3.45 kcal/mol and -4.32 kcal/mol against NSP12 and NSP3, respectively. Our results showed that naringenin had ΔG values more negative than the ΔG values of Remdesivir (RDV) and GS-441,524. Hence, naringenin was considered to be a potential inhibitor. Also, the number of hydrogen bonds of naringenin with NSP3 and later NSP12 are more than Remdesivir and its derivative. In this research, Mean root mean square deviation (RMSD) values of NSP3 and NSP12with naringenin ligand (5.55±1.58 nm to 3.45±0.56 nm and 0.238±0.01 to 0.242±0.021 nm, respectively showed stability in the presence of ligand. The root mean square fluctuations (RMSF) values of NSP3 and NSP12 amino acid units in the presence of naringenin in were 1.5 ± 0.31 nm and 0.118±0.058, respectively. Pharmacokinetic properties and prediction of absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of naringenin and RDV showed that ​these two compounds had no potential cytotoxicity.

Integrated neural network and evolutionary algorithm approach for liver fibrosis staging: Can artificial intelligence reduce patient costs?

Background and Aim: Staging liver fibrosis is important, and liver biopsy is the gold standard diagnostic tool. We aim to design and evaluate an artificial neural network (ANN) method by taking advantage of the Teaching Learning-Based Optimization (TLBO) algorithm for the prediction of liver fibrosis stage in blood donors and hepatitis C patients. Methods: We propose a method based on a selection of machine learning classification methods including multilayer perceptron (MLP) neural network, Naive Bayesian (NB), decision tree, and deep learning. Initially, the synthetic minority oversampling technique (SMOTE) is performed to address the imbalance in the dataset. Afterward, the integration of MLP and TLBO is implemented. Results: We propose a novel algorithm that reduces the number of required patient features to seven inputs. The accuracy of MLP using 12 features is 0.903, while that of the proposed MLP with TLBO is 0.891. Besides, the diagnostic accuracy of all methods, except the model designed with the Bayesian network, increases when the SMOTE balancer is applied. Conclusion: The decision tree-based deep learning methods show the highest levels of accuracy with 12 features. Interestingly, with the use of TLBO and seven features, MLP reached an accuracy rate of 0.891, which is quite satisfactory when compared with those of similar studies. The proposed model provides high diagnostic accuracy, while reducing the required number of properties from the samples. The results of our study show that the recruited algorithm of our study is more straightforward, with a smaller number of required properties and similar accuracy.

Cardiovascular health in kratom users; a narrative review.

BACKGROUND: Kratom, also known as Mitragyna speciosa, is a plant that originates in Southeast Asia and possesses unique pharmacological characteristics. It is commonly consumed in the form of tea made by boiling the leaves or using the leaves to create the powder. According to its pain-relieving effects, the prevalence of kratom use around the world has increased, which has various implications for healthcare providers. Mitragynine is a well-known active compound in kratom. OBJECTIVE: This review aims to provide a comprehensive perspective on the cardiovascular effects of mitragynine and its potential cardiotoxicity through the literature. METHOD: Authors searched PubMed, Scopus, and Google Scholar databases using appropriate search strategies for each database. After the screening, all relevant studies were included. RESULTS: Although kratom may have the potential for therapeutic benefits, it has been associated with multi-organ damage and cardiac toxicity in some cases. According to the available data, tachycardia and hypertension are the most common adverse effects. Other possible cardiovascular effects include atherosclerosis, ventricular arrhythmia, cardiomyopathy, dose-dependent prolonged QTc interval, myocarditis, cardiomegaly, and cardiopulmonary arrest. CONCLUSION: While prior research has indicated the possible negative effects of mitragynine overdose on the cardiovascular system, there are no definitive conclusions, and additional investigations are needed.

Prognostic value of fragmented QRS in acute pulmonary embolism: a cross-sectional-analytic study of the Iranian population.

BACKGROUND: Acute Pulmonary embolism (APE) is considered one of the deadliest cardiovascular diseases. Electrocardiographic (ECG) abnormalities in pulmonary embolism (PE) are increasingly reported. A growing number of studies have recommended that ECG plays a crucial role in the prognostic assessment of PE patients. However, there is scarce data on the prognostic importance of fragmented QRS (fQRS) on outcomes in patients with APE. This study aims to investigate the prognostic value of fQRS in APE patients. MATERIALS AND METHODS: This is a cross-sectional-analytic study. This study included 280 patients diagnosed with APE admitted to Shahid Madani hospital, Tabriz, Iran. Computed tomography pulmonary angiography (CTPA) was used to diagnose APE. A checklist was prepared for all patients, demographic, clinical characteristics, and Major Adverse Cardiopulmonary events (MACPE), including in-hospital mortality, need for thrombolysis, mechanical ventilation, and surgical embolectomy, were recorded. Patients were divided into two groups: patients who manifested fQRS on their ECG and patients who did not; Then, demographic, clinical characteristics, and MACPE were compared in the two groups, as mentioned earlier. Furthermore, all statistical analyses were carried out using SPSS software. RESULTS: 48 patients (17.14%) had fQRS(+) on their ECG, and 232 patients (82.86%) did not have it on their ECG. In data analysis, 22 patients (8.7%) had in-hospital mortality, 35 patients (13.9%) needed thrombolysis, nine patients (3.9%) required mechanical ventilation, and 13 patients (5.1%) needed surgical embolectomy. fQRS was not significantly associated with in-hospital mortality (P = 0.225), need for thrombolysis (P = 0.684), mechanical ventilation (P = 1.000), and surgical embolectomy (P = 1.000). Demographic and clinical characteristics were also similar in both groups. CONCLUSIONS: This study does not support the idea that fQRS on ECG is a valuable predictor of in-hospital mortality, the need for thrombolysis, mechanical ventilation, and surgical embolectomy.

Lipoprotein (a) as a predictor of diabetic retinopathy in patients with type 2 diabetes: A systematic review.

BACKGROUND: Lipoprotein a (LP(a)), an LDL-like lipoprotein, known as a risk factor for cardiovascular diseases, has a controversial association with diabetic retinopathy in patients with type 2 diabetes-the current systematic review aimed to critically assess the association between LP(a) and diabetic retinopathy. METHODS: A systematic review of relevant studies was conducted after a thorough search in PubMed, Scopus, and Google Scholar electronic databases. We used English observational, case-control, and prospective cohort studies published up to August 2022, including type 2 diabetic patients as the population, diabetic retinopathy as the outcome, and LP(a) as the intervention. RESULT: 17 relevant studies, including 4688 patients with diabetes, were included in this systematic review. While in 13 studies, Lipoprotein(a) was recognized as a risk factor for diabetic retinopathy, only three studies reported no evidence of a relationship between the two. Also, another study showed a mixed outcome of the relationship between LP(a) and diabetic retinopathy. CONCLUSION: High serum lipoprotein(a) in patients with type 2 diabetes is considered a risk factor for diabetic retinopathy. However, further large-scaled cohort studies are still required to validate this finding.

Association of clinical characteristics, antidiabetic and cardiovascular agents with diabetes mellitus and COVID-19: a 7-month follow-up cohort study.

BACKGROUND: The prognostic factors of long-term outcomes in hospitalized patients with diabetes mellitus and COVID-19 are lacking. METHODS: In this retrospective cohort study, we evaluated patients aged ≥ 18-years-old with the COVID-19 diagnosis who were hospitalized between Feb 20 and Oct 29, 2020, in the Sina Hospital, Tehran, Iran. 1323 patients with COVID-19 entered in the final analysis, of whom 393 (29.7%) patients had diabetes. We followed up patients for incurring in-hospital death, severe COVID-19, in-hospital complications, and 7-month all-cause mortality. By doing univariate analysis, variables with unadjusted P-value < 0.1 in univariate analyses were regarded as the confounders to include in the logistic regression models. We made adjustments for possible clinical (model 1) and both clinical and laboratory (model 2) confounders. RESULTS: After multivariable regression, it was revealed that preadmission use of sulfonylureas was associated with a borderline increased risk of severity in both models [model 1, OR (95% CI):1.83 (0.91-3.71), P-value: 0.092; model 2, 2.05 (0.87-4.79), P-value: 0.099] and major adverse events (MAE: each of the severe COVID-19, multi-organ damage, or in-hospital mortality) in model 1 [OR (95% CI): 1.86 (0.90-3.87), P-value: 0.094]. Preadmission use of ACEIs/ARBs was associated with borderline increased risk of MAE in the only model 1 [OR (95% CI):1.83 (0.96-3.48), P-value: 0.066]. CONCLUSIONS: Preadmission use of sulfonylureas and ACEIs/ARBs were associated with borderline increased risk of in-hospital adverse outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-021-00901-4.