Ashraf Abu-Seida

Antiviral culinary plants are potential bioresources for preventive nutraceuticals and/or antiviral drugs in COVID-19. Structure-based virtual screening was undertaken to screen 173 compounds previously reported from Vernonia amygdalina and Occinum gratissimum for direct interaction with the active site of the 3-Chymotrypsin-Like Protease (3CLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on docking scores and comparison with reference inhibitors, a hit-list of 10 top phytocompounds was defined, which also had strong interactions with the catalytic centre of 3CLpro from three related strains of coronavirus (SARS-CoV, MERS-CoV, HKU4). Among these, six compounds (neoandrographolide, vernolide, isorhamnetin, chicoric acid, luteolin, and myricetin) exhibited the highest binding tendencies to the equilibrated conformers of SARS-CoV-2 3CLpro in an in-depth docking analysis to 5 different representative conformations from the cluster analysis of the molecular dynamics simulation (MDS) trajectories of the protein. In silico drug-likeness analyses revealed two drug-like terpenoids viz: neoandrographolide and vernolide as promising inhibitors of SARS-CoV-2 3CLpro. These structures were accommodated within the substrate-binding pocket; and interacted with the catalytic dyad (Cys145 and His41), the oxyanion loop (residues 138–145), and the S1/S2 sub-sites of the enzyme active site through the formation of an array of hydrogen bonds and hydrophobic interactions. Molecular dynamics simulation and binding free energy calculation revealed that the terpenoid-enzyme complexes exhibit strong interactions and structural stability. Therefore, these compounds may stabilize the conformation of the flexible oxyanion loop; and thereby interfere with the tetrahedral oxyanion intermediate formation during the proteolytic activity of the enzyme. © 2021 Elsevier Ltd

Long non-coding RNAs (LncRNAs) have recently been considered promising biomarkers for oncogenesis due to their epigenetic regulatory effects. HOTAIR is one of the oncogenic LncRNAs that was previously studied in different non-hematological malignancies. The current study set out to detect the expression level of HOTAIR LncRNA in AML patients concerning their clinical characteristics, laboratory data, FLT3-ITD, and NPM1 mutations, as well as treatment outcome. This study included quantitative detection of HOTAIR gene expression in 47 cases of AML using quantitative reverse transcription polymerase chain reaction, as well as NPM1 and FLT3-ITD genotyping.

Objectives:Substance dependence is commonly seen among Egyptian young adults. Unfortunately limited data are available about the prevalence of comorbidity of mental disorders and substance dependence in this age group. In addition, substance dependence is correlated with many psychopathologic factors such as low self-esteem, childhood abuse, and stressful life events, etc. which could aggravate the load of the disorder.

Methods:

A case control study that included 80 patients diagnosed with substance dependence according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, text revised (DSM-IV-TR). The sample was recruited from Kasr Al-Ainy Psychiatry and Addiction Hospital. Subjects were divided into 2 groups: group 1 (cases with the diagnosis of comorbid substance dependence and other mental disorder) and group 2 (cases with the diagnosis of substance dependence only). They were examined using Addiction Severity Index (ASI) and Rosenberg Self-Esteem Scale (RES).

Results:

Patients in group 1 had significantly higher levels of impairment and disability in scores of ASI: drug use, social impairment, and psychiatric problems. They had higher percentage of psychopathologic factors, for example, history of childhood abuse. There was no significant difference in the presence of comorbid personality disorder, or history of stressful life events.

Conclusions:

Comorbidity of mental disorders with substance dependence is associated with more impairment and functional deterioration. Young adults with substance dependence have high levels of associated psychopathologic factors, such as childhood abuse, stressful life events, and deliberate self-harm.

Supramolecular chemistry has gained an increasing attention in different disciplines of pharmaceutical community. Methacholine chloride (MCh) is a parasympathomimetic bronchoconstrictor which is a gold standard diagnostic tool for asthma through methacholine challenge test. The determination of MCh is a substantial analytical problem due to the lack of chromophore in its structure, therefore direct spectrophotometry becomes not possible for MCh quantification. In this work, we have exploited the high spectral absorptivity of 4-sulfocalix[4]arene (SCX4) and its exceptional complexation towards choline-mimetic guests to develop a method to quantify MCh. The host guest interaction between MCh and SCX4 produces an inclusion complex that can be investigated using different UV-spectrophotometric methods [dual wavelength method (DWM), ratio difference method (RDM) and ratio derivative method (1DD)]. The proposed methods are based on measurement of the manipulated absorbance of the formed complex peak after resolving the overlap from the host SCX4 spectrum followed by quantitation of MCh. Validation of the methods was performed in compliance with ICH guidelines, regression analysis showed good linearity over the concentration ranges of 10.0–150.0 μM for DWM and 10.0–170.0 μM for RDM and 1DD. The limit of quantification and detection were estimated to be 7.5 μM, 2.5 μM for DWM, 5.2 μM, 1.6 μM for RDM and 5.0 μM, 1.7 μM for 1DD, respectively. The complexation binding ratio and stability constant were calculated to be 1:1 and 7.20 × 104 ± 1.60 M−1, respectively, using continuous variation Job's method. Also, these methods have been used to determine MCh in Povocholine® formulation and in spiked human plasma. Moreover, the greenness of the proposed analytical procedures was evaluated by National Environmental Methods Index and Analytical Eco-Scale and the promising junction between the supramolecular chemistry and the eco-friendly spectrophotometric approaches was highlighted.

The newly emerged human coronavirus, SARS-CoV-2, had begun to spread last year and sparked worldwide. In this study, molecular docking is utilized to test some previously approved drugs against the SARS-CoV-2 nonstructural protein 15 (Nsp15). We screened 23 drugs, from which three (saquinavir, valrubicin and aprepitant) show a paramount predicted binding affinity (-9.1, -9.6 and -9.2 kcal/mol, respectively) against SARS-CoV-2 Nsp15. Moreover, saquinavir and aprepitant make nonbonded interactions with Leu201 in the active site cavity of Nsp15, while the drug valrubicin interacts with Arg199 and Leu201. This binding pattern may be effective against the targeted protein, leading to Nsp15 blockage and virus abolition. Additionally, the pharmacological properties of the screened drugs are known since they have been approved against different viruses. © 2021

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An improved scheduling the disinfection process of the new coronavirus (COVID-19) is introduced. The scheduling aims at achieving the best utilization of the available day time, which is calculated as the total disinfection time minus the total loss travelling time. In this regard, a new application problem is presented, which is called a travelling disinfection-man problem (TDP). The new problem (TDP) in network optimization resemble somehow the famous travelling salesman problems (TSP) but with basic distinct variations where a disinfection group is likely to select a route to reach a subset of predetermined places to be disinfected with the most utilization of the available day working hours. A nonlinear binary model is introduced with a detailed real application case study involving the improving the scheduling of coronavirus disinfection process for five contaminated faculties in Ain Shams University in Cairo, and the case study is solved using a novel discrete binary gaining-sharing knowledge-based optimization algorithm (DBGSK).

BackgroundThe African Surgical OutcomeS-2 (ASOS-2) trial tested an enhanced postoperative surveillance intervention to reduce postoperative mortality in Africa. We undertook a concurrent evaluation to understand the process of intervention delivery.
Methods
Mixed-methods process evaluation, including field notes, interviews, and post-trial questionnaire responses. Qualitative analysis used the framework method with subsequent creation of comparative case studies, grouping hospitals by intervention fidelity. A post-trial questionnaire was developed using initial qualitative analyses. Categorical variables were summarised as count (%) and continuous variables as median (inter-quartile range [IQR]). Odds ratios (OR) were used to rank influences by impact on fidelity.
Results
The dataset included eight in-depth case studies, and 96 questionnaire responses (response rate 67%) plus intervention fidelity data for each trial site. Overall, 57% (n=55/96) of hospitals achieved intervention delivery using an inclusive definition of fidelity. Delivery of the ASOS-2 interventions and data collection presented a significant burden to the investigators, outstripping limited resources. The influences most associated with fidelity were: surgical staff enthusiasm for the trial (OR=3.0; 95% confidence interval [CI], 1.3–7.0); nursing management support of the trial (OR=2.6; 95% CI, 1.1–6.5); performance of a dummy run (OR=2.6; 95% CI, 1.1–6.1); nursing colleagues seeing the value of the intervention(s) (OR=2.1; 95% CI, 0.9–5.7); and site investigators' belief in the effectiveness of the intervention (OR=3.2; 95% CI, 1.2–9.4).
Conclusions
ASOS-2 has proved that coordinated interventional research across Africa is possible, but delivering the ASOS-2 interventions was a major challenge for many investigators. Future improvement science efforts must include better planning for intervention delivery, additional support to investigators, and promotion of strong inter-professional teamwork.
Clinical trial registration
ClinicalTrials gov NCT03853824.

Salvadora persica L. (toothbrush tree, Miswak) is well recognized in most Middle Eastern and African countries for its potential role in dental care, albeit the underlying mechanism for its effectiveness is still not fully understood. A comparative MS and NMR metabolomics approach was employed to investigate the major primary and secondary metabolites composition of S. persica in context of its organ type viz., root or stem to rationalize for its use as a tooth brush. NMR metabolomics revealed its enrichment in nitrogenous compounds including proline-betaines i.e., 4-hydroxy-stachydrine and stachydrine reported for the first time in S. persica. LC/MS metabolomics identified flavonoids (8), benzylurea derivatives (5), butanediamides (3), phenolic acids (8) and 5 sulfur compounds, with 21 constituents reported for the first time in S. persica. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) of either NMR or LC/MS dataset clearly separated stem from root specimens based on nitrogenous compounds abundance in roots and is justifying for its preference as toothbrush versus stems. The presence of betaines at high levels in S. persica (9−12 μg/mg dry weight) offers novel insights into its functioning as an osmoprotectant that maintains the hydration of oral mucosa. Additionally, the previously described anti-inflammatory activity of stachydrine along with the antimicrobial effects of sulfonated flavonoids, benzylisothiocynate and ellagic acid derivatives are likely contributors to S. persica oral hygiene health benefits. Among root samples, variation in sugars and organic acids levels were the main discriminatory criterion. This study provides the first standardization of S. persica extract using qNMR for further inclusion in nutraceuticals.

The presence of colloids and bacteria in groundwater affects contaminant migration either by facilitation or retardation. The co-transport of contaminant and colloidal particles had been simulated using various finite difference schemes which may suffer from the known and common numerical dispersion problem. In this study, a random walk particle tracking (RWPT) scheme is developed to simulate the co-transport of contaminants, colloids, and bacteria in porous media. Processes modeled include colloidal deposition to and release from solid matrix, bacterial attachment to and detachment from solid matrix, and contaminant sorption onto and desorption from mobile and immobile colloidal particles and bacterial cells as well as solid matrix. Also, the biological processes between contaminant and bacterial cells including bacterial growth, decay, and contaminant utilization are simulated. The developed model is verified against MT3D-MS for reactive contaminant transport with solid matrix, and reaction processes have been verified with solution of a developed analytical solution of mass balance equations. The biological processes are incorporated into the developed RWPT model which is verified against TVD finite difference model developed by (El-Kordy 2008). The results show good performance of RWPT technique in simulating contaminant transport in the presence of colloids and bacteria. The effects of various physical and biological parameters on contaminant transport are investigated. The results show that at least 50,000 particles are required to simulate each constituent mass in case of consideration of biological processes in contaminant transport simulation. On the other hand, 10,000 particles are found to be sufficient to simulate each constituent mass for case of contaminant transport undergoing physical and chemical processes only. The results indicate that contaminant utilization increases by increasing the ratio of initial concentrations of bacterial cells and contaminant, the ratio of the half-saturation constant to initial contaminant concentration, and the ratio of the maximum growth rate to the yield coefficient. It is also found from the results that higher contaminant utilization occurs at early time and decreases as time progresses.

A fast, sensitive and selective RP-HPLC method was developed for extensive investigation of nitroxinil’s stability. The stability of the studied drug was tested under different stress conditions, namely hydrolytic, oxidative, photolytic and thermal. Separation of nitroxinil and its degradation products was achieved in less than 5 min using Venusil XBP C18 (150 × 2.1 mm id, 5 um particle size) column and isocratic mobile phase composed of 0.1% triethylamine pH 2.5 (adjusted with phosphoric acid) and acetonitrile mixture in a ratio of (70:30; v/v). UV detection at 270 nm was employed for monitoring nitroxinil degradation behavior over a linearity range of 1–75 µg/mL. Plackett–Burman experimental design was adopted for robustness testing of the developed chromatographic method. LC-mass identification of nitroxinil’s hydrolytic and oxidative degradations was attempted, and the suggested mechanism was deduced. The proposed method was successfully applied in determination of the drug in raw material and pharmaceutical dosage form.