Ashraf Abu-Seida

There are current attempts to find a safe substitute or adjuvant for Sorafenib (Sorf), the standard treatment for advanced hepatocellular carcinoma (HCC), as it triggers very harsh side effects and drug-resistance. The therapeutic properties of Bee Venom (BV) and its active component, Melittin (Mel), make them suitable candidates as potential anti-cancer agents per-se or as adjuvants for cancer chemotherapy. Hence, this study aimed to evaluate the combining effect of BV and Mel with Sorf on HepG2 cells and to investigate their molecular mechanisms of action. Docking between Mel and different tumor-markers was performed. The cytotoxicity of BV, Mel and Sorf on HepG2 and THLE-2 cells was conducted. Combinations of BV/Sorf and Mel/Sorf were performed in non-constant ratios on HepG2. Expression of major cancer-related genes and oxidative stress status was evaluated and the cell cycle was analyzed. The computational analysis showed that Mel can bind to and inhibit XIAP, Bcl2, MDM2, CDK2 and MMP12. Single treatments of BV, Mel and Sorf on HepG2 showed lower IC50than on THLE-2. All combinations revealed a synergistic effect at a combination index (CI) < 1. Significant upregulation (p < 0.05) of p53, Bax, Cas3, Cas7 and PTEN and significant downregulation (p < 0.05) of Bcl-2, Cyclin-D1, Rac1, Nf-κB, HIF-1a, VEGF and MMP9 were observed. The oxidative stress markers including MDA, SOD, CAT and GPx showed insignificant changes, while the cell cycle was arrested at G2/M phase. In conclusion, BV and Mel have a synergistic anticancer effect with Sorf on HepG2 that may represent a new enhancing strategy for HCC treatment.

The effects of a multistrain potential probiotic (Protexin®), acids, and a bacterin from multidrug-resistant E. coli O26, O78, S. Enteritidis (1,9,12 g.m1,7), and S. Typhimurium (1,4,5,12.i.1,2) on the immune response, haematological parameters, cytokines, and growth parameters of broiler chickens challenged with bacterin live serotypes were investigated. Two experiments were designed using 300 one-day-old chicks (Arbor Acres) randomly assigned to 15 groups. The first experiment comprised 9 groups, including positive and negative control groups and other groups received Protexin®, acids, and the bacterin (0.2 ml/SC), either alone or in combination, on the 1st day. The second experiment contained 6 groups, including positive and negative control groups and other groups received a combination of Protexin®, acids, and the bacterin (0.5 ml/SC) on the 8th day. All the groups except the negative control groups were challenged on the 8th and 16th days in both experiments, respectively, with mixed live bacterin serotypes. The groups that received Protexin®, acids, and the bacterin either alone or in combination revealed significant improvements in the immune response to the bacterin (p ≤ 0.05). The groups in the 1st experiment and most the 2nd experiment groups showed a reduced mortality rate and decreased levels IFN-γ, IL-4, and IL-12 cytokines (p ≤ 0.05). Moreover, these groups demonstrated increases in haematological parameters and reduced rates of infection-caused anaemia. These groups showed significant increases in growth performance parameters, such as body weight, weight gain, and the feed conversion ratio (FCR) (p ≤ 0.05). There was a beneficial effect on 1-day-old chickens produced by combining Protexin®, acids, and the bacterin (0.2 ml/SC).

Background: Hepatitis C virus (HCV) infected adolescents with beta-thalassemia major (BTM) are considered a potential population for HCV micro-elimination model development where BTM may negatively impact the pharmacokinetic exposure parameters of sofosbuvir/ledipasvir (SOF/LED). Objectives: The study aimed at studying the effect of BTM on SOF/LED and SOF metabolite (GS-331007) pharmacokinetics. Methods: A prospective, controlled study recruiting BTM and control HCV infected adolescents (Clinicaltrials.gov identifier-NCT04353986). Pharmacokinetic exposure to GS-331007 and LED was the primary pharmacokinetic outcome. No-effect boundaries were set to 90% confidence interval (CI) of exposure geometric mean ratio (GMR) within 70–143%. Dose suitability was based on the 90% CI of exposure GMR within 50-200% compared to adults. The percentage of patients achieving sustained virologic response 12 weeks post-treatment (SVR12) was the primary efficacy endpoint. Results: Thirteen patients were enrolled per study group. All patients were included in the pharmacokinetic analysis (n=26). BTM patients showed lower GS-331007 and LED exposure that could, respectively, be as low as 45.4% and 36.1% compared to their control group. GS-331007 exposure in BTM patients was nearly half (56.8%, 90% CI 45.3–71.2%) that observed in adults. Despite that low drug exposure in 46.2% of BTM patients may alert dose unsuitability, they achieved SVR12. Moreover, patients with total bilirubin ≥1.93 mg/dL were predicted to have low GS-331007 exposure (0.913 receiver operating characteristic area under the curve with sensitivity and specificity >80%). Conclusion and Relevance: The identified systematically lower drug exposure in BTM patients might partially explain relapses or treatment failures among BTM patients reported in other studies. BTM may be a hurdle towards implementing HCV micro-elimination model that may necessitate dose-adjustment. © 2021 Elsevier Masson SAS

COVID-19 pandemic continues to be a global health crisis. The gut microbiome critically affects the immune system, and some respiratory infections are associated with changes in the gut microbiome; here, we evaluated the role of nutritional and lifestyle habits that modulate gut microbiota on COVID-19 outcomes in a longitudinal cohort study that included 200 patients infected with COVID-19. Of these, 122 cases were mild and seventy-eight were moderate, according to WHO classification. After detailed explanation by a consultant in clinical nutrition, participants responded to a written questionnaire on daily sugar, prebiotic intake in food, sleeping hours, exercise duration and antibiotic prescription, during the past 1 year before infection. Daily consumption of prebiotic-containing foods, less sugar, regular exercise, adequate sleep and fewer antibiotic prescriptions led to a milder disease and rapid virus clearance. Additionally, data on these factors were compiled into a single score, the ESSAP score (Exercise, Sugar consumption, Sleeping hours, Antibiotics taken, and Prebiotics consumption; 0–11 points), median ESSAP score was 5 for both mild and moderate cases; however, the range was 4–8 in mild cases, but 1–6 in moderate (P = 0·001, OR: 4·2, 95 % CI 1·9, 9·1); our results showed a negative correlation between regular consumption of yogurt containing probiotics and disease severity (P = 0·007, OR: 1·6, 95 % CI 1·1, 2·1). Mild COVID-19 disease was associated with 10–20 min of daily exercise (P = 0·016), sleeping at least 8 h daily, prescribed antibiotics less than 5 times per year (P = 0·077) and ate plenty of prebiotic-containing food.

This paper introduces families of bilateral filters for image denoising and sharpness enhancements, JPEG deblocking, and texture filtering. While the Gaussian distribution dictates the application of the bilateral filters, we introduce a wide variety of kernels based on Riemann-Lebesgue’s theorem. The derivation of the bilateral filters are established in both adaptive and non-adaptive approaches. The adaptation of the filters is adjusted via computing the variances (inflection points) using different methods based on applications. For image denoising and sharpness, the variance estimated using Laplacian-of-Gaussian filter followed by affine mapping. The variance is computed as a proportion of intensity differences across the boundary in JPEG deblocking. In texture filtering, the variance is calculated form modified relative variations. We carry out extensive experiments in three different applications and compare the results using different bilateral filters. The proposed filters are giving better results, compared with standard bilateral and adaptive bilateral filters.

Ochrosia elliptica Labill is a small tropical evergreen tree native to Oceania belonging to the Apocynaceae family. Eight alkaloids, two flavonoid glycosides and three phenolic acids were identified by LC/MS analysis. On the other hand, the quality and uniformity of the plant leaves were assessed through the determination of the total phenolic and flavonoid, in addition to total ash, acid-insoluble ash, water-soluble ash and moisture content. The total ethanolic and aqueous extracts of the leaves of O. elliptica as well as their fractions were investigated for their antinociceptive (analgesic) using tail-flick test and antimicrobial activities using agar well diffusion assay. Among the tested fractions, the results showed that the n-butanol fraction exhibited high potency as antinociceptive compared to indomethacin drug and as antifungal compared to amphotericin B.

Copper iodide is an attractive p-type transparent material suitable for optoelectronic applications. This work reports on the synthesis of copper iodide (CuI) by iodination of sputtered Cu films previously deposited on glass and silicon substrates. The crystalline phase and surface morphology were studied by X-ray diffraction (XRD) and scanning electron microscopy (SEM), respectively. The prepared CuI films crystallize in the zinc blende structure (γ-phase) at different amounts of iodine and exhibit preferential orientation along the <111> direction. Moreover, detailed investigation of the microstructure via high-resolution transmission electron microscopy (HR-TEM) revealed the presence and details of alternating twin crystallographic domains between adjacent grains. The electrical properties of the CuI films were characterized by Hall effect measurements and revealed a p-type carrier behavior for all films. The electrical behavior was discussed and attributed to the change in intrinsic point defects. In addition, the electronic bandgap and luminescence properties were investigated using optical transmission and photoluminescence (PL). The CuI films showed a wide band gap (about 3.05 eV) with an average transmittance of about (66 %) in the visible region. Moreover, the PL showed a blue emission ranging from 400 to 440 nm originating from the excitonic recombination and radiative point defects.

Reusing by-products such as cow bones in agriculture can be achieved thorough pyrolysis. The potential of bone-derived biochar as a promising material for metals immobilization in contaminated mining soils has not yet been sufficiently explored. Therefore, cow bones were used as biochar feedstock were pyrolyzed at 500 °C (CBL) and 800 °C (CBH) and. The two biochars were applied to a mine contaminated soil at 0 (control), 2.5, 5 and 10%, w/w, dosages; then, the soils were incubated and cultivated by maize in the greenhouse. Cadmium (Cd) and zinc (Zn) bioavailability and their sequentially extracted fractions (acid soluble, reducible, oxidizable, and residual fraction), soil microbial function, and plant health attributes were analyzed after maize harvesting. Bone-derived biochar enhanced the content of dissolved organic carbon (up to 74%), total nitrogen (up to 26%), and total phosphorus (up to 27%) in the soil and improved the plant growth up to 55%, as compared to the control. The addition of CBL altered the acid soluble fraction of both metals to the residual fraction and, thus, reduced the content of Zn (55 and 40%) and Cd (57 and 67%) in the maize roots and shoots, respectively as compared to the control. The CBL enhanced the β-glucosidase (51%) and alkaline phosphatase activities (71%) at the lower doses (2.5–5%) as compared to control, while the activities of these enzymes decreased with the higher application doses. Also, CBL improved the antioxidants activity and maize growth at the 2.5–5% application rate. However, the activity of the dehydrogenase significantly decreased (77%), particularly with CBH. We conclude that CBL, applied at 2.5–5% dose, can be utilized as a potential low cost and environmental friendly amendment for stabilization of toxic metals in contaminated mining soils and producing food/feed/biofuel crops with lower metal content.

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Background: SARS-CoV-2, an emerging strain of coronavirus, has affected millions of people from all the continents of world and received worldwide attention. This emerging health crisis calls for the urgent development of specific therapeutics against COVID-19 to potentially reduce the burden of this emerging pandemic. Purpose: This study aims to evaluate the anti-viral efficacy of natural bioactive entities against COVID-19 via molecular docking and molecular dynamics simulation. Methods: A library of 27 caffeic-acid derivatives was screened against 5 proteins of SARS-CoV-2 by using Molegro Virtual Docker 7 to obtain the binding energies and interactions between compounds and SARS-CoV-2 proteins. ADME properties and toxicity profiles were investigated via www.swissadme.ch web tools and Toxtree respectively. Molecular dynamics simulation was performed to determine the stability of the lead-protein interactions. Results: Our obtained results has uncovered khainaoside C, 6-O-Caffeoylarbutin, khainaoside B, khainaoside C and vitexfolin A as potent modulators of COVID-19 possessing more binding energies than nelfinavir against COVID-19 Mpro, Nsp15, SARS-CoV-2 spike S2 subunit, spike open state and closed state structure respectively. While Calceolarioside B was identified as pan inhibitor, showing strong molecular interactions with all proteins except SARS-CoV-2 spike glycoprotein closed state. The results are supported by 20 ns molecular dynamics simulations of the best complexes. Conclusion: This study will hopefully pave a way for development of phytonutrients-based antiviral therapeutic for treatment or prevention of COVID-19 and further studies are recommended to evaluate the antiviral effects of these phytochemicals against SARS-CoV-2 in in vitro and in vivo models. © 2020 Elsevier GmbH

Abstract Farmed marine fish constitute 20% of the total farmed fish production in Egypt, and the Deeba Triangle produces a relatively large portion of this percentage. Last year, several private fish farms in the Deeba Triangle have suffered severe economic losses due to acute fish mass kills. This study aimed to investigate the hidden aetiologies behind these colossal mass fish kills and to propose an emergency control strategy. Several tons of dead farmed fish were remarkably scattered throughout affected ponds and at the vicinity of impacted fish farms. Moribund farmed European seabass (Dicentrarchus labrax), thin-lipped grey mullet (Liza ramada) and gilthead seabream (Sparus aurata) have exhibited skin darkness, emaciation, congested gills and fins, ascites, skin erosions and ulcerations. Internally, moribund fish emitted unpleasant odour upon opening the abdomen together with severe congestion and haemorrhages in kidneys and brain. Mottled atrophied spleens were the most prominent findings, while the gastrointestinal tracts were filled with whitish caseous material. The liver was pale with multiple whitish nodules. Photobacterium damselae was the most retrievable bacterial pathogen from most infected fish and trash fish. Photobacterium damselae subspecies piscicida and Photobacterium damselae subspecies damselae were definitively identified from examined moribund fish using both conventional morpho-chemical and molecular assays. Data analysis has revealed that the poor water quality was profoundly incriminated in triggering the bacterial infections with a fate of mass mortalities. Conclusively, adopting various strict biosecurity strategies will be the key factors in prevention of future episodes of mass kills.

This study aimed to formulate and statistically optimize cubosomal formulations loaded with voriconazole to enhance and control its ocular bioavailability. The independent variables of the employed central composite face-centered design were the percentages of monoolein and Pluronic F127. Particle size, zeta potential, drug content, entrapment efficiency and drug release parameters were adopted as dependent responses. The conducted factorial analysis resulted in an optimum formulation composed of 15% monoolein and 1.2% Pluronic F127. The optimum cubosomal formulation showed well-dispersed vesicles with a particle size of 160 nm and a relatively high drug loading (0.81%). Then, it was coated with chitosan to further enhance its precorneal residence time. The chitosan-coated formulation showed high mucoadhesive properties, in addition to being safe and biocompatible. Moreover, it showed higher Cmax, Tmax, AUC(0-8), AUC(0-∞), MRT, T1/2 and HVDt50%Cmax when compared to voriconazole suspension. It showed also higher concentration in the vitreous humor when compared to the drug suspension which indicates deeper penetration into the ocular tissue. Finally, the chitosan-coated optimum cubosomal formulation could be considered an efficient ocular nanocarrier for voriconazole.

The most challenging threat facing the global community today is the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite global efforts to develop suitable treatments, very few specific antiviral agents have been suggested and the virus remains a serious global health risk. In vivo animal experiments have demonstrated that bioactive mycochemical constituents of Inonotus obliquus have immunomodulatory, antimicrobial, and antiviral properties. The present study investigates the antiviral potential of I. obliquus terpenoids against COVID-19 using a molecular docking study. The in silico study elucidates the ability of most of the terpenoid components to interact with the receptor-binding domain of SARS-CoV-2 spike glycoprotein with excellent affinity. Additionally, we found that both betulinic acid and inonotusane C could bind and stably interact with the spike protein near the host cell recognition site of angiotensin-converting enzyme 2. © 2021 by Begell House, Inc.

The gaining sharing knowledge based optimization algorithm (GSK) is recently developed metaheuristic algorithm, which is based on how humans acquire and share knowledge during their life-time. This paper investigates a modified version of the GSK algorithm to find the best feature subsets. Firstly, it represents a binary variant of GSK algorithm by employing a probability estimation operator (Bi-GSK) on the two main pillars of GSK algorithm. And then, the chaotic maps are used to enhance the performance of the proposed algorithm. Ten different types of chaotic maps are considered to adapt the parameters of the GSK algorithm that make a proper balance between exploration and exploitation and save the algorithm from premature convergence. To check the performance of proposed approaches of GSK algorithm, twenty-one benchmark datasets are taken from the UCI repository for feature selection. The performance is measured by calculating different type of measures, and several metaheuristic algorithms are adopted to compare the obtained results. The results indicate that Chebyshev chaotic map shows the best result among all chaotic maps which improve the performance accuracy and convergence rate of the original algorithm. Moreover, it outperforms the other metaheuristic algorithms in terms of efficiency, fitness value and the minimum number of selected features.

Parasitic infection may cause massive losses in Clarias gariepinus fries and fingerlings. Therefore, this study aimed to characterize the digenetic trematodes species (two adults’ flukes and one metacercariae) infecting African catfish Clarias gariepinus, as well as their histopathological impacts on infected fish. The intestinal flukes were identified as Orientocreadium batrachoides and Masenia bangweulensis based on their morphological and molecular characteristics. Sequencing of their 28S (LSU rRNA) and 18S rRNA (SSU rRNA) genes confirmed that these trematodes belong to the families Orientocreadiidae and Cephalogonimidae, respectively. The metacercariae trematode infecting skin and muscles were only morphologically identified as Cyanodiplostomum sp. The gene expression levels of MHC II increased in naturally infected fish either with O. batrachoides or Cyanodiplostomum sp. alone, compared with uninfected catfish. In addition, lysozyme levels in individual fish serum increased in catfish infected either with O. batrachoides or Cyanodiplostomum sp. alone. Histopathological examination of the skin revealed embedded parasitic cysts that displaced tissue in the dermis. Surrounding tissues were infiltrated with melanomacrophages and displayed dermal edema. Histopathological analysis showed O. batrachoides or M. bangweulensis between the gastric folds of the stomach of infected catfish, causing infiltration of mononuclear inflammatory cells in the lamina propria.

The objective of this study was to develop mixed micelles of Lornoxicam, using a Pluronic® mixture of L121 and P123. The technique used for the preparation was thin-film hydration according to a Box Behnken design with three central points for each formula. The independent variables studied were Pluronic®: drug ratio, Pluronic® L121: Pluronic® P123 ratio and amount of soya-bean lecithin. The studied dependent variables were: percent entrapment efficiency (% EE), particle size (PS), poly-dispersity index (PDI), zeta potential (ZP) and in vitro LX released (after 2, 10 h). Numerical optimization was used to statistically optimize the formulae using Design-Expert® software. Choosing the best formula was in terms of maximizing % EE, ZP (as absolute value) and in vitro release, while minimizing PS and PDI. Characterization of best formula was performed by Transmission electron microscopy, Differential scanning calorimetry, Fourier transform infrared spectroscopy, stability testing, ex vivo permeation and skin deposition studies using rat skin. The in vivo pharmacodynamics activities of the optimized formula were examined on male rats and mice and related to that of the oral commercial product. The optimized formula demonstrated to be non-irritant, with considerably improved anti-inflammatory and analgesic activities. Higher in vivo skin permeation was confirmed using confocal laser scanning microscopy. In conclusion, the obtained results proved that mixed micelles could be promising method for transdermal drug delivery.

The high mortality rate among Nile tilapia (Oreochromis niloticus) and African catfish (Clarias gariepinus) polycultured in earthen ponds in Manzala, Egypt, was investigated. Mortality has been linked to poor water quality parameters accompanied with bacterial infections. Moribund farmed fishes exhibited general septicemic signs. Fish from both species (45 each) were sampled and analyzed bacteriologically. Vibrio alginolyticus (32.3%), Enterococcus faecalis (29.4%), Aeromonas caviae (23.5%), and A. veronii (14.7%) were isolated from moribund fishes using selective media and further identified by biochemical tests. 16S rRNA gene sequencing and phylogenetic analysis confirmed the identity of these isolates. Experimental infection of O. niloticus with different bacterial isolates resulted in clinical signs of hemorrhagic septicemia and mortality rates of 80%, 60%, 40%, and 30%, respectively, for E. faecalis, A. veronii, V. alginolyticus, and A. caviae. Water parameter analysis revealed marked divergence from typical values. In addition, different bacterial isolates (including Staphylococcus sciuri, S. aureus, E. faecalis, A. veronii, A. caviae, and V. alginolyticus) were identified and isolated from water samples. BLAST analysis of water bacterial isolates displayed a 100% similarity score with relevant fish isolates, indicating that the water was the likely source of infections. Histopathological examination revealed signs of bacterial infection in both fish species. In addition, common circulatory and degenerative changes with melanophore aggregation, and lymphocytic depletion in hematopoietic organs were recorded.