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Abstract The COVID-19 pandemic has caused significant mortality and morbidity for millions of people. Severe Acute Respiratory Syndrome-2 (SARS-CoV-2) virus is capable of causing severe and fatal diseases. We evaluated the antiviral properties of Aspergillus tamarii SP73-EGY isolate extract against low pathogenic coronavirus (229E), Adeno-7- and Herpes-2 viruses. The extract showed a high selectivity index (SI = 43.4) and a significant inhibition of 229E (IC50 = 8.205 μg/ml). It was stronger than the drug control, remdesivir (IC50 = 38.2 μg/ml, SI = 7.29). However, the extract showed minimal efficacy against Adeno-7- and Herpes-2-Viruses (IC50 = 22.52, 47.79 μg/ml, and SI = 6.75, 5.08, respectively). It exhibited profound efficacy against the highly pathogenic SARS-CoV-2 (IC50 = 8.306 μg/ml, SI = 42.2). Kojic acid, the primary component of the extract, showed substantial antiviral activity against SARS-CoV-2 (IC50 = 23.4 μg/ml, SI = 5.6), Remdesivir (IC50 = 4.55 μg/ml, SI = 61.45). Therefore, the extract demonstrated the most notable antiviral characteristics against coronavirus infection. Co-infecting microorganisms may contribute to immune system deterioration and airway injury caused by SARS-CoV-2. The extract showed significant efficacy against E. coli and P. aeruginosa , with an inhibition range of 3.5–10 mm at a concentration of 200 mg/ml. A molecular docking study showed that hexadecanoic, Kojic, octanoic acids, and 4(4-Methylbenzylidene)cyclohexane-1,3-dione have stronger binding affinity to the SARS-CoV-2 Mpro than Remdesivir. Molecular dynamics simulations were employed to examine the structural stability and flexibility of these complexes. This confirmed the high binding affinities of Kojic acid and 4(4-Methylbenzylidene)cyclohexane-1,3-dione, thereby proving their potential as novel anti-SARS-CoV-2.

Abstract Cisplatin is a chemotherapeutic drug, which exhibits undesirable side effects. Chitosan nanoparticles are promising for drug delivery. The aim of this study was to determine the effect of the brown alga Turbinaria triquetra ethyl acetate fraction and polysaccharides, either loaded on chitosan nanoparticles or free, against podocyturia and cisplatin nephrotoxicity in rats. Sixty-six male rats were distributed into 11 equal groups: untreated control, chitosan (CSNPs), ethyl acetate fraction (EAE), polysaccharide (PS), EAE loaded on chitosan nanoparticles (EAE-CSNPs), PS loaded on chitosan nanoparticles (PS-CSNPs), Cisplatin or cis-diamminedichloroplatinum(II) (CDDP), CDDP + EAE, CDDP + PS, CDDP + EAE-CSNPs, and CDDP + PS-CSNPs. Serum urea, creatinine, creatinine clearance, renal malondialdehyde, nitric oxide, paraoxonase 1, renal nephrin, and podocin, and their renal mRNA gene expressions, as well as urinary nephrin and podocin were determined. The results indicated that the ethyl acetate fraction and polysaccharides, either free or loaded, efficiently attenuated podocyturia and cisplatin nephrotoxicity compared to the Cis group. However, the improvement was higher in the nephrotoxic groups treated with EAE-CSNPs and PS-CSNPs. The current study revealed that chitosan nanoencapsulation showed ameliorative effects against podocyturia and cisplatin nephrotoxicity in rats compared to free extracts, offering a new therapeutic strategy for attenuating podocyturia and CDDP-induced nephrotoxicity.

Objective Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of lymphoma. Circulating cell-free DNA (cfDNA) is the promising liquid biopsy in malignancy.Method Assessment of cfDNA concentration and DNA integrity index (DII) in 30 newly diagnosed DLBCL patients and correlating them with the international prognostic index.Results Circulating cfDNA concentration was significantly higher in newly diagnosed DLBCL patients than controls, while DII was significantly lower. There was a significant correlation between cfDNA concentration and adverse prognostic factors.Conclusion cfDNA concentration is potentially strong diagnostic and prognostic marker of DLBCL, however DII is only useful as a diagnostic biomarker.

Abstract This study presents a sophisticated numerical simulation model for a forced circulation solar water heating system (FC-SWHs), specifically designed for the unique climatic conditions of Algeria. The model aims to cater to the hot water needs of single-family houses, with a daily consumption of 246 L. Utilizing a dynamic approach based on TRNSYS modeling, the system’s performance in Ain Temouchent’s climate was scrutinized. The model’s validation was conducted against literature results for the collector outlet temperature. Key findings include a maximum monthly average outlet temperature of 38 °C in September and a peak cumulative useful energy gain of 250 W in August. The auxiliary heating system displayed seasonal energy consumption variations, with the highest rate of 500 kJ/hr in May to maintain the water temperature at 60 °C. The energy input at the storage tank’s inlet and the consistent high-level energy output at the hot water outlet were analyzed, with the former peaking at 500 W in May. The system ensured an average water tank temperature (hot, middle and bottom) and water temperature after the mixer, suitable for consumption, ranging between 55 °C and 57 °C. For applications requiring cooler water, the mixer’s exit temperature was maintained at 47 °C. The study’s key findings reveal that the TRNSYS model predicts equal inlet and outlet flow rates for the tank, a condition that is particularly significant when the system operates with high-temperature water, starting at 55 °C. The flow rate at this temperature is lower, at 7 kg/hr, while the water mass flow rate exiting the mixer is higher, at 10.5 kg/hr. In terms of thermal performance, the system’s solar fraction (SF) and thermal efficiency were evaluated. The results indicate that the lowest average SF of 54% occurs in July, while the highest average SF of over 84% is observed in September. Throughout the other months, the SF consistently stays above 60%. The thermal efficiency of the system varies, ranging from 49 to 73% in January, 43–62% in April, 48–66% in July, and 53–69% in October. The novelty of this research lies in its climate-specific design, which addresses Algeria’s solar heating needs and challenges. Major contributions include a thorough analysis of energy efficiency metrics, seasonal auxiliary heating demands, and optimal system operation for residential applications, supporting Algeria’s goal of sustainable energy independence.

Abstract Nutritional status assessment, including amino acids, carnitine, and acylcarnitine profile, is an important component of diabetes care management, influencing growth and metabolic regulation. A designed case–control research included 100 Egyptian participants (50 T1DM and 50 healthy controls) aged 6 to 18 years old. The participants' nutritional status was assessed using the Body Mass Index (BMI) Z-score. Extended metabolic screening (EMS) was performed using a high-performance liquid chromatography-electrospray ionization-mass spectroscopy system to evaluate the levels of 14 amino acids, free carnitine, and 27 carnitine esters. T1DM children had considerably lower anthropometric Z-scores than the control group, with 16% undernutrition and 32% short stature. Total aromatic amino acids, phenylalanine, phenylalanine/tyrosine ratio, proline, arginine, leucine, isoleucine, free carnitine, and carnitine esters levels were considerably lower in the diabetic group, suggesting an altered amino acid and carnitine metabolism in type 1 diabetes. BMI Z-score showed a significant positive correlation with Leucine, Isoleucine, Phenylalanine, Citrulline, Tyrosine, Arginine, Proline, free carnitine, and some carnitine esters (Acetylcarnitine, Hydroxy-Isovalerylcarnitine, Hexanoylcarnitine, Methylglutarylcarnitine, Dodecanoylcarnitine, Tetradecanoylcarnitine, and Hexadecanoylcarnitine). HbA1c% had a significant negative correlation with Total aromatic amino acids, Branched-chain amino acid/Total aromatic amino acids ratio, Glutamic Acid, Citrulline, Tyrosine, Arginine, Proline, and certain carnitine esters (Propionylcarnitine, Methylglutarylcarnitine, Decanoylcarnitine, Octadecanoylcarnitine and Octadecenoylcarnitine), suggest that dysregulated amino acid and carnitine metabolism may be negatively affect the glycaemic control in children with TIDM. In conclusion, regular nutritional assessments including EMS of T1DM patients are critical in terms of diet quality and protein content for improved growth and glycemic management.

Abstract This is an interim analysis of the Beta-blocker (Propranolol) use in traumatic brain injury (TBI) based on the high-sensitive troponin status (BBTBBT) study. The BBTBBT is an ongoing double-blind placebo-controlled randomized clinical trial with a target sample size of 771 patients with TBI. We sought, after attaining 50% of the sample size, to explore the impact of early administration of beta-blockers (BBs) on the adrenergic surge, pro-inflammatory cytokines, and the TBI biomarkers linked to the status of high-sensitivity troponin T (HsTnT). Patients were stratified based on the severity of TBI using the Glasgow coma scale (GCS) and HsTnT status (positive vs negative) before randomization. Patients with positive HsTnT (non-randomized) received propranolol (Group-1; n = 110), and those with negative test were randomized to receive propranolol (Group-2; n = 129) or placebo (Group-3; n = 111). Propranolol was administered within 24 h of injury for 6 days, guided by the heart rate (> 60 bpm), systolic blood pressure (≥ 100 mmHg), or mean arterial pressure (> 70 mmHg). Luminex and ELISA-based immunoassays were used to quantify the serum levels of pro-inflammatory cytokines (Interleukin (IL)-1β, IL-6, IL-8, and IL-18), TBI biomarkers [S100B, Neuron-Specific Enolase (NSE), and epinephrine]. Three hundred and fifty patients with comparable age (mean 34.8 ± 9.9 years) and gender were enrolled in the interim analysis. Group 1 had significantly higher baseline levels of IL-6, IL-1B, S100B, lactate, and base deficit than the randomized groups (p = 0.001). Group 1 showed a significant temporal reduction in serum IL-6, IL-1β, epinephrine, and NSE levels from baseline to 48 h post-injury (p = 0.001). Patients with severe head injuries had higher baseline levels of IL-6, IL-1B, S100B, and HsTnT than mild and moderate TBI (p = 0.01). HsTnT levels significantly correlated with the Injury Severity Score (ISS) (r = 0.275, p = 0.001), GCS (r = − 0.125, p = 0.02), and serum S100B (r = 0.205, p = 0.001). Early Propranolol administration showed a significant reduction in cytokine levels and TBI biomarkers from baseline to 48 h post-injury, particularly among patients with positive HsTnT, indicating the potential role in modulating inflammation post-TBI. Trial registration: ClinicalTrials.gov NCT04508244. It was registered first on 11/08/2020. Recruitment started on 29 December 2020 and is ongoing. The study was partly presented at the 23rd European Congress of Trauma and Emergency Surgery (ECTES), April 28–30, 2024, in Estoril, Lisbon, Portugal.

A serious challenge of the chronic administration of dexamethasone (DEX) is a delay in wound healing. Thus, this study aimed to investigate the potential of Tadalafil (TAD)-loaded proniosomal gel to accelerate the healing process of skin wounds in DEX-challenged rabbits. Skin wounds were induced in 48 rabbits of 4 groups (n = 12 per group) and skin wounds were treated by sterile saline (control), TAD-loaded proniosomal gel topically on skin wound, DEX-injected rabbits, and DEX+TAD-loaded proniosomal gel for 4 weeks. The optical photography, transmission electron microscopy, in vitro release profile, and stability studies revealed the successful preparation of the selected formula with good stability. DEX administration was associated with uncontrolled oxido-inflammatory reactions, suppression in immune response in skin wounds, and consequently failure in the healing process. TAD-loaded proniosomal gel-treated rabbits manifested a marked enhancement in the rate of wound closure than control and DEX groups (p < 0.05). The TAD-loaded proniosomal gel successfully antagonized the impacts of DEX by dampening MDA production, and enhancing total antioxidant capacity, coupled with modulation of inflammatory-related genes, inducible nitric oxide synthase, tumor necrosis factor-alpha, interleukin-1β, and matrix metalloproteinase 9, during all healing stages (p < 0.05). This was in combination with significant amplification of immune response-related genes, CD68 and CD163 (p < 0.05). Moreover, the histopathological, Masson's Trichrome-stain, and immune-histochemical studies indicated a successful tissue recovery with the formation of new blood vessels in groups treated with TAD-loaded proniosomal gel, as manifested by well-organized collagen fibers, upregulation of transforming growth factor β1, and vascular endothelial growth factor immune expression in skin tissues (p < 0.05). Overall, the topical application of TAD-loaded proniosomal gel is useful in improving the delayed wound healing linked to DEX therapy via regulating the release of inflammatory/macrophage activation mediators and enhanced antioxidant capacity, angiogenesis, and vascularity.

Background Underlying immunological mechanisms in children with moderate-to-severe asthma are complex and unclear. We aimed to investigate the association between blood inflammatory parameters and asthma burden in children with moderate-to-severe asthma. Methods Blood inflammatory parameters (eosinophil and neutrophil counts and inflammatory mediators using multiplex immunoassay technology) were measured in children (6–17 years) with moderate-to-severe asthma from the SysPharmPediA cohort across four European countries. Based upon low/high blood eosinophil (LBE/HBE) counts of

Abstract Worldwide, particularly in developing nations, helminth infections are the leading causes of livestock illness and mortality. Parascaris (P.) equorum, a parasitic worm from the Ascarididae family, significantly impacts the production, health, and working performance of equines. This study aimed to investigate the impact of intraperitoneal sensitization of P. equorum on the immune system, oxidative stress, and histology in Wistar rats. After acclimatization for 7 days, we divided the rats into five groups, each consisting of six rats. Group I, serving as the control, was administered distilled water, followed by groups II (day 7), III (day 14), IV (day 21), and V (day 33). The rats were euthanized every day mentioned (Days 7–33). On day 0, a dosage of 1ml/100 gm rat (containing 500 μg/ml protein content) emulsified crude antigen extract with an incomplete Freund’s adjuvant (1:1 volume), followed by a second dose of the same antigen concentration on day 7. To assess the allergenicity of this nematode, we measured a whole blood profile, serum levels of IFN-γ, IL-5, IL-10, IL-13, and IL-33, total immunoglobulins IgE and IgG, and oxidative stress markers. Also, we examined histological changes in the liver, kidney, and spleen. The results showed that values of total leukocyte count, granulocytes, monocytes, and lymphocytes were significantly (P

Abstract Background Lichen planus (LP) is a chronic inflammatory disease with uncertain etiology. Interleukin-18 (IL-18) is an interferon gamma (INFγ) inducing agent. It is a pro-inflammatory cytokine that was found to play a role in the pathogenesis of some autoimmune disorders. Material and methods This study included 50 patients with classic cutaneous lichen planus (CLP) and 50 healthy volunteers serving as controls. Venous blood samples were withdrawn from the study subjects under complete aseptic precautions. Blood samples were examined for single nucleotide polymorphisms (SNPs) of IL-18 gene at promoter -137(G/C) and -656 (G/T) using polymerase chain reaction (PCR) and IL-18 level was assessed using enzyme linked immunosorbent assay (ELISA). Results The mean level of IL-18 was significantly higher in CLP patients (31.63 ± 4.90) compared to control subjects (13.95 ± 6.82). Significantly high levels of IL-18 were found among patients with diabetes, hypertension (p

Heat stress, low mango yields and inconsistent fruit quality are main challenges for growers. Recently, licorice-root extract (LRE) has been utilized to enhance vegetative growth, yield, and tolerance to abiotic stresses in fruit trees. Potassium sorbate (PS) also plays a significant role in various physiological and biochemical processes that are essential for mango growth, quality and abiotic stress tolerance. This work aimed to elucidate the effects of foliar sprays containing LRE and PS on the growth, yield, fruit quality, total chlorophyll content, and antioxidant enzymes of ‘Osteen’ mango trees. The mango trees were sprayed with LRE at 0, 2, 4 and 6 g/L and PS 0, 1, 2, and 3 mM. In mid-May, the mango trees were sprayed with a foliar solution, followed by monthly applications until 1 month before harvest. The results showed that trees with the highest concentration (6 g/L) of LRE exhibited the maximum leaf area, followed by those treated with the highest concentration (3 mM) of PS. Application of LRE and PS to Osteen mango trees significantly enhanced fruit weight, number of fruits per tree, yield (kg/tree), yield increasing%, and reduced number of sun-burned fruits compared to the control. LRE and PS foliar sprays to Osteen mango trees significantly enhanced fruit total soluble solids ˚Brix, TSS/acid ratio, and vitamin C content compared to the control. Meanwhile, total acidity percentage in ‘Osteen’ mango fruits significantly decreased after both LRE and PS foliar sprays. ‘Osteen’ mango trees showed a significant increase in leaf area, total chlorophyll content, total pigments, and leaf carotenoids. Our results suggest that foliar sprays containing LRE and PS significantly improved growth parameters, yield, fruit quality, antioxidant content, and total pigment concentration in ‘Osteen’ mango trees. Moreover, the most effective treatments were 3 mM PS and 6 g/L LRE. LRE and PS foliar spray caused a significant increase in yield percentage by 305.77%, and 232.44%, in the first season, and 242.55%, 232.44% in the second season, respectively.

Abstract Silver and titanium-silver nanoparticles have unique properties that make the textile industry progress through the high quality of textiles. Preparation of AgNPs and TiO2-Ag core–shell nanoparticles in different concentrations (0.01% and 0.1% OWF) and applying it to cotton fabrics (Giza 88 and Giza 94) by using succinic acid 5%/SHP as a cross-linking agent. Ultra-violet visible spectroscopy (UV–Vis), X-ray diffraction (XRD), dynamic light scattering (DLS), zeta potential, transmission electron microscopy (TEM), scanning electron microscopy/energy-dispersive X-ray (SEM–EDX) are tools for AgNPs and TiO2-AgNPs characterization and the treated cotton. The resulting AgNPs and TiO2-AgNPs were added to cotton fabrics at different concentrations. The antimicrobial activities, UV protection, self-cleaning, and the treated fabrics' mechanical characteristics were investigated. Silver nanoparticles and titanium dioxide-silver nanoparticles core–shell were prepared to be used in the treatment of cotton fabrics to improve their UV protection properties, self-cleaning, elongation and strength, as well as the antimicrobial activities to use the produced textiles for medical and laboratory uses and to increase protection for medical workers taking into account the spread of infection. The results demonstrated that a suitable distribution of prepared AgNPs supported the spherical form. Additionally, AgNPs and TiO2-AgNPs have both achieved stability, with values of (− 20.8 mV and − 30 mV, respectively). The synthesized nanoparticles spread and penetrated textiles' surfaces with efficiency. The findings demonstrated the superior UV protection value (UPF 50+) and self-cleaning capabilities of AgNPs and TiO2-AgNPs. In the treatment with 0.01% AgNPs and TiO2-AgNPs, the tensile strength dropped, but the mechanical characteristics were enhanced by raising the concentration to 0.1%. The results of this investigation demonstrated that the cotton fabric treated with TiO2-AgNPs exhibited superior general characteristics when compared to the sample treated only with AgNPs.

Abstract Coumarins are heterocycles of great interest in the development of valuable active structures in chemistry and biological domains. The ability of coumarins to inhibit biofilm formation of Gram positive bacterium (Staphylococcus aureus), Gram negative bacterium (Escherichia coli) as well as the methicillin-resistant S. aureus (MRSA) has been previously described. In the present work, new hybrid coumarin-heterocycles have been synthesized via the reaction of coumarin-6-sulfonyl chloride and 6-aminocoumarin with different small heterocycle moieties. The biological efficacy of the new compounds was evaluated towards their ability to inhibit biofilm formation and their anti-inflammatory properties. The antimicrobial activities of the newly synthesized compounds were tested against Gram positive bacterium (S. aureus ATCC 6538), Gram negative bacterium (E. coli ATCC 25922), yeast (Candida albicans ATCC 10231) and the fungus (Aspergillus niger NRRL-A326). Compounds 4d, 4e, 4f, 6a and 9 showed significant MIC and MBC values against S. aureus, E. coli, C. albicans, and methicillin-resistant S. aureus (MRSA) with especial incidence on compound 9 which surpasses all the other compounds giving MIC and MBC values of (4.88 and 9.76 µg/mL for S. aureus), (78.13 and 312.5 µg/mL for E. coli), (9.77 and 78.13 µg/mL for C. albicans), and (39.06 and 76.7 µg/mL for MRSA), respectively. With reference to the antibiofilm activity, compound 9 exhibited potent antibiofilm activity with IC50 of 60, 133.32, and 19.67 µg/mL against S. aureus, E. coli, and MRSA, (respectively) considering the reference drug (neomycin). Out of all studied compounds, the anti-inflammatory results indicated that compound 4d effectively inhibited nitric oxide production in lipopolysaccharide-(LPS-) stimulated RAW264.7 macrophage cells, giving NO% inhibition of 70% compared to Sulindac (55.2%)

Abstract Dimensionally stable anodes of titanium (Ti) metal coated with mixed metal oxides (MMO) are widely used in several electrochemical applications, especially chloro-alkali electrolysis. Herein, we deposited MMO coatings on Ti substrates in different compositions, namely, (60%RuO2-40%TiO2), (60%RuO2-30%TiO2-10%IrO2), and (60%RuO2-20%TiO2-15%IrO2-5%Ta2O5), where RuO2 has the same percentage ratio in all coatings. The aim was to use these electrodes for chlorine evolution reaction (CER) and oxygen evolution reaction (OER) applications. Electrochemical characterization of the coated samples was performed to identify the best Ti/MMO electrodes with the highest efficiencies among the various prepared combinations. The role of IrO2 and Ta2O5 in enhancing corrosion resistance and electrochemical efficacy was up for debate. Scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) analyses were exploited to determine the surface morphology, chemical composition, crystallinity, surface composition, and chemical states of the acquired coatings. The differential scanning calorimetry (DSC) method was used to evaluate the apparent activation energy ( $${{\text{E}}}_{{\text{a}}}$$ E a ) of the deposited MMO. Additionally, the electrochemical performance of our designed coatings was scrutinized by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), a current on–off test, a CV stability test (ST), and an accelerated stability test (AST). Furthermore, linear sweep voltammetry (LSV) was incorporated to assess the catalytic efficacy of the prepared anodes toward the CER in a brine solution of pH 2 and the OER in 1 M H2SO4. It became clear that the CER and OER incurred almost the same potential value (1.1 V) on both Ti/RuO2-TiO2 and Ti/RuO2-TiO2-IrO2 electrodes. However, on the Ti/RuO2-TiO2-IrO2-Ta2O5 anode, there was a 0.2 V potential difference between the CER occurring at 1.1 V and the OER happening at 1.3 V.

Abstract Sofosbuvir is one of the crucial drugs used in the treatment of chronic hepatitis C virus (HCV) in adults and children with compensated liver disease, including cirrhosis. It may be used alone or with other drugs. Ribavirin is an antiviral medication used to treat HCV infection. It is not effective when used alone and must be used in combination with other medications, such as sofosbuvir. This study pertains to a comprehensive assessment of the deleterious effects of sofosbuvir (an antiviral drug against chronic HCV) or sofosbuvir combined with ribavirin (an antiviral drug against RNA and DNA viruses) on several biological activities of the body, including hematological, hormonal, biochemical, histological, and immunohistochemical examinations during a long-standing period on male healthy rats. In addition, fertility assessments were performed, including sperm collections and semen parameter investigations. This study was conducted on 21 male rats divided into three equal groups. Group I (control group) received distilled water; group II (sofosbuvir group) received sofosbuvir (4 mg/kg); and group III (sofosbuvir + ribavirin) received sofosbuvir (4 mg/kg) plus ribavirin (30 ml/kg). All groups received the specific drug for six months. Blood and tissue samples were collected for hematological, hormonal, biochemical, histological, and immunohistochemical examinations. In addition, sperm collection and assessments of semen parameters were performed. Results revealed that sofosbuvir causes a highly significant decrease in the mean of most hematological, immunological, hormonal, and biochemical parameters, except for a few numbers of parameters such as neutrophils, monocytes, basophils, cortisol, GOT, and lipase, which exhibit a significant increase. The same occurred in the sofosbuvir + ribavirin group, but at much higher levels, as most hematological, immunological, hormonal, and biochemical parameters exhibit a highly significant decrease except for monocytes, triglyceride, and lipase, which exhibit a significant increase. When compared to the sofosbuvir group alone, the sofosbuvir + ribavirin group demonstrated a highly significant decline in the mean of most hematological, immunological, hormonal, and biochemical parameters except lymphocytes and triglycerides, which exhibit a substantial increase. For the reproductive parameters, both groups exhibit a significant decrease in the total sperm motility percentage. Finally, it can be concluded that sofosbuvir causes acute pancreatitis and combined immunodeficiency. Ribavirin is associated with hormonal deficiency, which indicates the occurrence of hypopituitarism. Moreover, sofosbuvir and ribavirin synergistically affect myelosuppression and cause iron-deficiency anemia. However, sofosbuvir, or its combination with ribavirin, is associated with a reduced risk of hepatocellular carcinoma. Besides, adding ribavirin to be combined with sofosbuvir improved the immunodeficiency caused by sofosbuvir; this confirms that using ribavirin with sofosbuvir reduces the side effects of both alone.

Background/Objectives: Despite the availability of antiepileptic drugs (AEDs) that can manage seizures, they often come with cognitive side effects. Furthermore, the role of oxidative stress and neuroinflammatory responses in epilepsy and the limitations of current AEDs necessitate exploring alternative therapeutic options. Medicinal plants, e.g., Lavandula dentata L., are rich in phenolic compounds and may provide neuroprotective and anti-inflammatory benefits. However, limited research evaluates their effectiveness in modulating neuroinflammation and histopathological changes in epilepsy models. Therefore, the current study hypothesized that treating Lavandula dentata L. extract or essential oils may reduce neuroinflammatory responses and mitigate histopathological changes in the brain, providing a natural alternative or adjunct therapy for epilepsy management. Methods: Five groups of male Wistar rats were used: control, pilocarpine-treated epileptic, valproic acid (VPA-treated epileptic), L. dentata extract, and essential oils. Numerous electrolyte levels, monoamine levels, neurotransmitter levels, and the mRNA expression of specific gate channel subtypes were evaluated in homogenate brain tissue. Additionally, histological changes in various brain regions were investigated. Results: The investigation revealed that the extract and essential oils obtained from L. dentata L. exhibited the ability to improve the modulation of electrolytes and ions across voltage- and ligand-gated ion channels. Furthermore, it was revealed that they could decrease neuronal excitability by facilitating repolarization. Moreover, L. dentata’s oil and ethanol extract re-balances T-reg/Th-17 cytokines, restoring the pro/anti-inflammatory cytokines and Treg markers, e.g., FOXP3 and CTLA-4, to their normal level. Conclusions: The present work confirms that the extract and essential oils of L. dentata L. have different activities to ameliorate the progression of histopathological alterations. Therefore, when used in conjunction with other AEDs, the extract and essential oils of L. dentata can slow the progression of epileptogenesis.

Background: The increasing prevalence of drug resistance in cancer therapy underscores the urgent need for novel therapeutic approaches. Dual enzyme inhibitors, targeting critical kinases such as CDK2 and TRKA, represent a promising strategy. The goal of this investigation was to design, synthesize, and evaluate a set of pyrazolo[1,5-a]pyrimidine derivatives for their dual inhibition potential toward CDK2 and TRKA kinases, along with their potential antiproliferative against cancer cell lines. Methods: A set of pyrazolo[1,5-a]pyrimidine derivatives (6a–t, 11a–g, and 12) was synthesized and subjected to in vitro enzymatic assays to determine their inhibitory activity against CDK2 and TRKA kinases. Selected compounds were further assessed for antiproliferative effects across the set of 60 cell lines from the NCI, representing various human cancer types. Additionally, simulations of molecular docking were conducted to explore the modes of binding for the whole active compounds and compare them with known inhibitors. Results: Compounds 6t and 6s exhibited potent dual inhibitory activity, showing an IC50 = 0.09 µM and 0.23 µM against CDK2, and 0.45 µM against TRKA, respectively. These results were comparable to reference inhibitors ribociclib (CDK2, IC50 = 0.07 µM) and larotrectinib (TRKA, IC50 = 0.07 µM). Among the studied derivatives, compound 6n displayed a notable broad-spectrum anticancer activity, achieving a mean growth inhibition (GI%) of 43.9% across 56 cell lines. Molecular docking simulations revealed that the synthesized compounds adopt modes of binding similar to those of the lead inhibitors. Conclusions: In this study, prepared pyrazolo[1,5-a]pyrimidine derivatives demonstrated significant potential as dual CDK2/TRKA inhibitors, and showed potent anticancer activity toward diverse cancer cell lines. These findings highlight their potential as key compounds for the design of novel anticancer therapeutics.

Background Four months after SARS-CoV-2 infection, 22%–50% of COVID-19 patients still experience complaints. Long COVID is a heterogeneous disease and finding subtypes could aid in optimising and developing treatment for the individual patient.Methods Data were collected from 95 patients in the P4O2 COVID-19 cohort at 3–6 months after infection. Unsupervised hierarchical clustering was performed on patient characteristics, characteristics from acute SARS-CoV-2 infection, long COVID symptom data, lung function and questionnaires describing the impact and severity of long COVID. To assess robustness, partitioning around medoids was used as alternative clustering.Results Three distinct clusters of patients with long COVID were revealed. Cluster 1 (44%) represented predominantly female patients (93%) with pre-existing asthma and suffered from a median of four symptom categories, including fatigue and respiratory and neurological symptoms. They showed a milder SARS-CoV-2 infection. Cluster 2 (38%) consisted of predominantly male patients (83%) with cardiovascular disease (CVD) and suffered from a median of three symptom categories, most commonly respiratory and neurological symptoms. This cluster also showed a significantly lower forced expiratory volume within 1 s and diffusion capacity of the lung for carbon monoxide. Cluster 3 (18%) was predominantly male (88%) with pre-existing CVD and diabetes. This cluster showed the mildest long COVID, and suffered from symptoms in a median of one symptom category.Conclusions Long COVID patients can be clustered into three distinct phenotypes based on their clinical presentation and easily obtainable information. These clusters show distinction in patient characteristics, lung function, long COVID severity and acute SARS-CoV-2 infection severity. This clustering can help in selecting the most beneficial monitoring and/or treatment strategies for patients suffering from long COVID. Follow-up research is needed to reveal the underlying molecular mechanisms implicated in the different phenotypes and determine the efficacy of treatment.

Abstract This study aims to study the effect of substituting soybean oil (SO) with rice bran oil (RBO) at different levels (25%, 50%, and 75%) on the physical and chemical properties, fatty acid composition, and oxidative stability of SO, also, study the effect of storing SO, RBO, and their blend oils at ambient temperature for a period of 12 months on the content of free fatty acids (% FFA), peroxide value (PV), and thiobarbituric acid (TBA). RBO demonstrated good quality, as evidenced by its initial low values of % FFA, PV, and TBA. Furthermore, RBO was found to be an excellent source of γ-oryzanol, whereas the other oils lacked this compound. Consequently, increasing the proportion of RBO in SO resulted in the least degradation, while pure SO exhibited the highest degree of degradation. Moreover, the blend oils demonstrated an inhibitory effect against oxidation, allowing for a prolonged storage period without the use of industrial antioxidants. Throughout the entire storage period, the % FFA and PV of all tested blend oil samples remained within the limits recommended for human consumption. TBA exhibited a similar trend to PV. However, an incremental increase in TBA values was observed as the storage period of the oils extended. In SO, TBA levels increased from 0.533 mg malonaldehyde/kg oil at the beginning to 1.446 mg malonaldehyde/kg oil after 12 months of storage. In RBO, TBA levels increased from 0.336 mg malonaldehyde/kg oil at the beginning to 0.882 mg malonaldehyde/kg oil after 12 months of storage.

Abstract Mangiferin (MF) is a natural C-glucosylxantone compound that has many substantial curative potentials against numerous illnesses including cancers. The present study's goal is to appraise the chemo preventive possessions of MF on azoxymethane (AOM)-mediated colonic aberrant crypt foci (ACF) in rats. Rats clustered into 5 groups, negative control (A), inoculated subcutaneously with normal saline twice and nourished on 0.5% CMC; groups B-E injected twice with 15 mg/kg azoxymethane followed by ingestion of 0.5% CMC (B, cancer control); intraperitoneal inoculation of 35 mg/kg 5-fluorouracil (C, reference rats) or nourished on 30 mg/kg (D) and 60 mg/kg (E) of MF. Results of gross morphology of colorectal specimens showed significantly lower total colonic ACF incidence in MF-treated rats than that of cancer controls. The colon tissue examination of cancer control rats showed increased ACF availability with bizarrely elongated nuclei, stratified cells, and higher depletion of the submucosal glands compared to MF-treated rats. Mangiferin treatment caused increased regulation of pro-apoptotic (increased Bax) proteins and reduced the β-catenin) proteins expression. Moreover, rats fed on MF had significantly higher glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and lower malondialdehyde (MDA) concentrations in their colonic tissue homogenates. Mangiferin supplementation significantly down-shifted pro-inflammatory cytokines (transforming growth factor-α and interleukine-6) and up-shifted anti-inflammatory cytokines (interleukine-10) based on serum analysis. The chemo-protective mechanistic of MF against AOM-induced ACF, shown by lower ACF values and colon tissue penetration, could be correlated with its positive modulation of apoptotic cascade, antioxidant enzymes, and inflammatory cytokines originating from AOM oxidative stress insults.

Objectives: This study aimed to assess the effectiveness of ridge preservation using a polycaprolactone (PCL) scaffold combined with platelet-rich fibrin (PRF) to promote bone regeneration before implantation. Materials and Methods: This prospective study was conducted at Al-Azhar University in Egypt. It included 30 participants requiring the extraction of their last mandibular premolar before constructing an implant-supported overdenture. The participants were divided into three groups: Group A was treated with a PCL scaffold and PRF as ridge preservative materials, Group B was treated with PRF alone, and Group C (control) was treated with no preservative material. Bone samples were collected for histomorphometric analysis at implant placement. Results: The participants’ mean age was 65.3 ± 4.27 years, and 18 (60%) were male. Postoperative alveolar bone lengths differed significantly between Groups A and B (P = 0.001). However, alveolar bone width changes did not differ significantly among groups. In contrast, the postoperative bone density and loss differed significantly among groups (P = 0.001). Conclusion: Combining two ridge preservation techniques (PCL and PRF) enhanced participants’ alveolar bone remodelling by decreasing its resorption and maintaining its width.

Objectives To investigate the predictive value of different immunological markers on treatment outcomes after bacillus Calmette-Guerin (BCG) induction in high-risk non-muscle-invasive bladder cancer (NMIBC). Patients and Methods Patients who underwent transurethral resection of bladder tumors for NMIBC were assessed for study eligibility. Urine and blood samples were taken from patients at baseline (immediately before the first dose of induction). Urine samples were evaluated for interleukin (IL)-6, IL-8, IL-10, IL-11, and interferon- γ by solid-phase enzyme-linked immunosorbent assay (ELISA). Blood samples were evaluated for epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 (HER2) using quantitative reverse transcriptase-polymerase chain reaction analysis. Each marker was assessed in relation to tumor recurrence. Results Between June 2016 and December 2019, 160 patients were included. Tumor recurrence occurred in 47 (29.38%) patients over a median (IQR) follow-up of 24 (12: 49) months. Using univariate analysis, the following urinary cytokines were associated with higher recurrence: urinary IL-6, 8, 10, 11, and interferon-γ. Also, serum EGFR and HER2 were associated with higher recurrence. On multivariate Cox regression analysis, significant variables include HER2 [HR (95%CI): 2.675 (1.367-5.233), p= 0.004], and IL-11 [HR (95%CI): 0.889 (0.825-0.957), p= 0.002]. Conclusions Serum HER2 and urinary IL-11 could be applied in clinical practice to predict BCG failure in patients with high-risk NMIBC, so those patients could be offered other modalities (radical cystectomy) early with better survival. Further studies are recommended to establish their exact role.

Abstract Gouty arthritis is one of the most common metabolic disorders affecting people. Plant based drugs can lower the risk of this health disorder. The anti-gouty potential of Eucalyptus torquata flowers methanol extract (ETME) was evaluated in vitro via measuring the inhibitory effects of five pro-inflammatory enzymes; xanthine oxidase (XO), hyaluronidase, lipoxygenase (5-LOX), cyclooxygenases COX-1, and COX-2, in addition to evaluating the inhibition of histamine release, albumin denaturation, membrane stabilization, tyrosinase, and protease inhibitory activities. Also, its antioxidant potential was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assays and ferric reducing power assay (FRAP). HPLC–PDA-MS/MS was used to identify the metabolites in the tested extract. The latter exhibited substantial anti-arthritic properties in all assays with comparable potential to the corresponding reference drugs. HPLC–MS/MS analysis of this bioactive extract tentatively annotated 46 metabolites including phloroglucinols, gallic and ellagic acids derivatives, terpenes, flavonoids, fatty acids, and miscellaneous metabolites. Our study highlights the medicinal importance of E. torquata as an anti-gouty candidate and opens new avenues of gouty management.

Abstract This work responds to what was reported in various audio-visual media channels and to queries and explanations from individuals and local residents on the causes of gaseous and thermal emissions from the Earth near the vicinity of the village of Al-Hindaw in Dakhla city, New Valley Governorate, Egypt. At the location of the fume exit area, magnetic, seismic, and electromagnetic geophysical investigations were carried out to identify the factor(s) responsible for the event in question. Rock samples were collected and studied geochemically and radiographically to assess their chemical compositions, as well as the quantity of organic chemicals that may have contributed to the burning and temperature increase. In light of the results of the geochemical and geophysical research, it is believed that the self-ignitions are the result of near-surface reactions and oxidation instead of volcanic activity, such as the presence of magma or other comparable phenomena.

Introduction Postoperative sore throat (POST) is a fairly common side effect of general anesthesia. The K-Y jelly is a well-known lubricant used in many medical procedures.

Background: Tadalafil is a PDE-5 (phosphodiesterase inhibitor) inhibitor that supports endogenous nitric oxide's vasodilatory actions and aids in erection maintenance. The penile duplex has proven to be very useful for imaging superficial structures and for determining the reasons of erectile dysfunction (ED). Objectives: To assess the effect of daily oral tadalafil 5mg for 3 months on penile duplex parameters in erectile dysfunction patients. Patients and Methods: A case control study involved 30 Egyptian patients ED. Appropriate clinical history and penile duplex examination before and after treatment with daily oral tadalafil mg for 3 months were performed. Results: The mean age of the patients was 53.17 ± 7.8 years. We founded that there was significant (p < 0.001) improvement in the level of erection after treatment. The rate of erection E1 and E2 was decreased from 53.3% to 3.3%. Likewise, the rate of E3-E5 was increased from 46.7% to 96.7%. Moreover, the mean duration of erection was elongated from 24.7 ± 5.3 to become 37.4 ± 3.8 and this was statistically significant (p < 0.001). Also, the mean peak systolic volume (PSV) was significantly (p = 0.001) increased after treatment (38.4 ± 9.1 cm/s) compared with the pre-treatment levels (23.9 ± 6.1 cm/s). Unlikely, the mean end diastolic volume (EDV) was insignificantly (p = 0.340) lower in post-treatment (2.25 ± 0.5 mL) compared with pre-treatment levels (2.97 ± 0.4 mL). Likely, the mean resistant index (RI) showed insignificant difference (p = 0.965) after treatment (0.9 ± 0.02) compared with before treatment (0.9 ± 0.08). For penile artery diameter, there was significant (p = 0.009) increase in the diameter after treatment (0.9 ± 0.1 mm) compared with before treatment (0.8 ± 0.1 mm). Conclusion: Oral daily tadalafil 5mg for 3 months is considered an effective treatment for ED according to penile duplex parameters.

The aim of this study is to evaluate the anti-HPV potential of a Moringa olifera Lam seed, Nigella sativa L. seed, and Musa Acuminata peel herbal mixture in the form of polymer film-forming systems. A clinical trial conducted in outpatient clinics showed that the most significant outcome was wart size and quantity. Compared to the placebo group, the intervention group’s size and number of warts were considerably better according to the results. Chemical profiling assisted by LC-HRMS led to the dereplication of 49 metabolites. Furthermore, network pharmacology was established for the mixture of three plants; each plant was studied separately to find out the annotated target genes, and then, we combined all annotated genes of all plants and filtered the genes to specify the genes related to human papilloma virus. In a backward step, the 24 configured genes related to HPV were used to specify only 30 compounds involved in HPV infection based on target genes. CA2 and EGFR were the top identified genes with 16 and 12 edges followed by PTGS2, CA9, and MMP9 genes with 11 edges each. A molecular docking study for the top active identified compounds of each species was conducted in the top target HPV genes, CA2 and EGFR, to investigate the mode of interaction between these compounds and the targets’ active sites.

Equine influenza is a highly contagious viral disease, specially among 1-5 years old naive horses. Vaccination is considered the best way to control the disease spread and outbreaks. Although foals are the main animal used for evaluation of equine influenza vaccines, guinea pigs were chosen as an alternative model in the present work, as they have a negligible antibody titer against equine influenza virus and are cheaper and easier to handle than foals. Five equine influenza vaccine batches were evaluated in two animal models, foals and guinea pigs, by injection of two doses/animal with 4 weeks apart using 2 mL/animal/dose and evaluation of immune responses by hemagglutination inhibition test and enzyme-linked immunosorbent assay. On the 7th week post vaccination, equine influenza antibodies titers reached maximum values of 9-10.2 and 8.7-10 hemagglutination inhibition units for foals and guinea pigs, respectively; sample/negative ratios were 0.126-0.464 and 0.128-0.445 for both animals, respectively. The use of guinea pigs as an animal model for the evaluation of equine influenza vaccines could be recommended instead of foals.

Abstract Bacterial resistance to conventional antibiotics is a serious challenge that requires novel antibacterial agents. Moreover, wastewater from dairy farms might contain countless number of pathogens, organic contaminants and heavy metals that consider a threat to the terrestrial and aquatic environment. Therefore, the development of cost-effective, highly operation-convenient, recyclable multifunctional antimicrobial agents became an urgent necessity. Layered double hydroxides (LDH) have shown promising results as antibacterial agents. However, more work is required to further investigate and improve the antimicrobial performance of LDH structures against pathogens. In this study three Zn–Fe based LDH were investigated for real dairy wastewater disinfection. The three LDH samples were cobalt substituted Zn–Fe LDH (CoZnFe), magnesium substituted Zn–Fe LDH (MgZnFe) and MgZnFe-Triazol LDH (MgZnFe-Tz) nanocomposite. Seventy-five wastewater samples were collected from a dairy farm sewage system. The sensitivity of isolated pathogens was tested against two commonly used disinfectants (Terminator and TH4) and was assessed against the three LDH samples at different concentrations. The overall prevalence of S. agalactiae, S. dysgalactiae and Staph. aureus was significantly at 80.0% (P-value = 0.008, X2 = 9.700). There was variable degree of resistance to the tested disinfectants, whereas the antimicrobial activity of CoZnFe LDH was increased significantly at a concentration of 0.005 mg/L followed by MgZnFe LDH while MgZnFe-Tz LDH showed minor antibacterial potency. It was concluded that CoZnFe LDH showed a better biocidal activity in killing the isolated resistant pathogens, making it a good choice tool in combating the zoonotic microbes in wastewater sources.

Background: Multiple factors negatively affect parental attitudes towards vaccinating children against COVID-19, particularly anxiety. This represents a barrier to long-term control of the pandemic. Objective(s): To study parental attitudes towards COVID-19 vaccination of children and adolescents and its association with anxiety. Methods: A cross-sectional study using an online electronic survey collected from 361 caregivers of children and adolescents (5-17 years old) was conducted. The Arabic version of Parental Attitudes about Childhood Vaccines (PACV) Questionnaire for assessing vaccine hesitancy among parents and the Arabic version of Beck Anxiety Inventory (BAI-A) for assessing anxiety symptoms were used. Results: 18% of the parents were hesitant towards vaccinating their children against COVID-19, 54.8% preferred that their children would develop natural immunity by acquiring the infection, 62.0%, 68.4%, and 41.8% were concerned that their children might have a serious side effect after the shot, they might not be safe or the vaccine might not prevent the disease respectively. Hesitance was higher among the unvaccinated and those who received the first and second dose with no intention to finish the booster one (p =0.004 and 0.001 respectively). Higher hesitancy was found among parents with severe anxiety (p=0.017). Conclusion: A significantly higher hesitancy towards COVID-19 vaccination of children was found among parents having severe anxiety, young age, and higher education.

Abstract Nonalcoholic fatty liver disease (NAFLD) has been linked with a number of extra hepatic diseases and could be a potential risk factor of decreasing bone mineral density. To determine whether Upper Egyptian patients with NAFLD are at risk of developing osteoporosis. Cross sectional study was done on a total 100 individuals; 50 patients diagnosed with NAFLD (based on ultrasound imaging) crossed-matched with 50 individuals without NAFLD based on age, sex and body mass index. Bone mineral density, serum calcium and phosphorus levels, serum parathyroid hormone, serum vitamin D and fasting insulin level were assessed. Osteoporosis was prevalent in NAFLD patients versus to controls (19/50 vs. 0/50; P

Background: Glucocorticoids are widely used in the clinical setting. The direct impacts of glucocorticoids on bones involve both transient and early rise in bone resorption and long-term inhibition of bone formation. Leptin enhances the differentiation of human bone marrow stromal cells into osteoblasts, suppresses the generation of osteoclasts and attenuates the reduction in bone formation. Objectives: This study aimed to assess the effects of prednisolone on causing osteoporosis in rats and the effects of leptin on osteoporotic rats. Material and Methods: The study was performed on 21 adult male white albino rats. They were divided equally into; control, osteoporotic and treated groups. The osteoporotic and treated groups were given 5 mg/kg/day oral prednisolone for 3 months. The treated group was given10 μg/kg/day intraperitoneal (IP) leptin for the next 2 months. Blood samples were collected for determination of serum calcium, phosphorous, alkaline phosphatase and osteocalcin levels. Bone of the right femur was used for histopathological examination. Results: The osteoporotic group had a highly significant decrease in serum calcium and phosphorus, in addition to significant increase serum alkaline phosphatase and osteocalcin. Also, there was decrease in cortical bone thickness and number of osteocyte-containing lacunae and increased number of osteocyte-free lacunae in osteoporotic group. Treatment with leptin improved both biochemical and structural changes in prednisolone induced osteoporosis. Conclusions: Leptin antagonizes the effects of glucocorticiods induced osteoporosis. It normalizes serum calcium and phosphorus. It improves bone mineral density and bone size.

Abstract Because of the COVID-19 outbreak, Mass gathering restrictions were imposed. The lockdown of the Higher Education Institutions was obligatory to save lives. In February 2021 in Egypt, HEIs were allowed to ease the lockdown restrictions on a case-by-case basis gradually. In this paper, we propose a risk evaluation of planned regular mass gathering events during the pandemic, such as students gathering on-campus during indoor exams, by implementing WHO COVID-19 Strategic Preparedness and Response Plan through Intra-Action Review guidance. This one-group posttest-only design study was done on October 6 University campus during indoor students' exams in Giza, Egypt. We conducted IAR to implement the WHO's COVID- 19 SPRP; Country-level coordination; risk communication; surveillance, rapid response teams; points of entry; infection prevention control; laboratories; supply chain; case management; essential health services, and other possible topics. Between February-21, 2021; April-10, 2021, 25,927 students attended the on-campus living exams. Our result suggests that the high level of Readiness–Capacity during mass gatherings will reduce COVID-19 transmission. The most compelling evidence is the significance of synchronization between the ten pillars in preventing COVID-19 transmission. These findings may be used to influence decision-making for continual improvement of the operational planning guidelines during the outbreaks.

Abstract Engineered nanoparticles have enabled the development of novel uses, particularly in disease management. In this investigation, we synthesized and studied three distinct nanomaterials: solid lipid nanoparticles (SLNPs), chitosan nanoparticles (CSNPs), and carbon nanotubes (CNTs), either alone or loaded with two antifungals, nystatin, and fluconazole. The purpose of this study is to investigate the different properties of the produced nanomaterials, either alone or in combination with antifungals. Drug release studies revealed that about 55% from SLNPs, 43% from CSNPs and 97% from CNTs of nystatin drug were released at the longest time point assessed (12 h). In addition, about 89% from SLNPs, 84% from CSNPs and 81% from CNTs of fluconazole drug were released at the longest time point assessed (12 h). This research will expand the understanding of nanomaterials as a viable technique for the management of different fungal diseases that harm several agricultural crops.

Introduction Tympanoplasty is the main treatment of mucosal type of chronic suppurative otitis media.

Selective COX-1 inhibitors are preferential therapeutic targets for platelet aggregation and clotting responses. In this study, we examined the selective COX-1-inhibitory activities of four newly synthesized compounds, 10–13, along with their abilities to inhibit platelet aggregation against ADP and collagen. The target compounds 10–13 were synthesized using the conventional method, sonication, and microwave-assisted methods. Microanalytical and spectral data were utilized to elucidate the structures of the new compounds 10–13. Additionally, a spectral NMR experiment [NOESY] was conducted to emphasize the configuration around the double bond of the imine group C=N. The obtained results revealed no observed correlation between any of the neighboring protons, suggesting that the configuration at the C=N double bond is E. Biological results revealed that all the screened compounds 10–13 might serve as selective COX-1 inhibitors. They showed IC50 values ranging from 0.71 μM to 4.82 μM against COX-1 and IC50 values ranging from 9.26 μM to 15.24 μM against COX-2. Their COX-1 selectivity indices ranged between 2.87 and 18.69. These compounds show promise as promising anti-platelet aggregation agents. They effectively prevented platelet aggregation induced by ADP with IC50 values ranging from 0.11 μM to 0.37 μM, surpassing the standard aspirin with an IC50 value of 0.49 μM. Additionally, they inhibited the platelet aggregation induced by collagen with IC50 values ranging from 0.12 μM to 1.03 μM, demonstrating superior efficacy compared to aspirin, which has an IC50 value of 0.51 μM. In silico molecular modeling was performed for all the target compounds within the active sites of COX-1 and COX-2 to rationalize their selective inhibitory activities towards COX-1. It was found that the binding interactions of the designed compounds within the COX-1 active site had remained unaffected by the presence of celecoxib. Molecular modeling and DFT calculations using the B3LYP/6-31+G (d,p) level were performed to study the stability of E-forms with respect to Z-forms for the investigated compounds. A strong correlation was observed between the experimental observations and the quantum chemical descriptors.

Abstract New Schiff base ligand, derived from antiviral valacyclovir, and its novel Cr(III), Mn(II), Co(II), Ni(II), Cu(II), Zn(II) complexes have been synthesized. By using a variety of analytical and spectroscopic techniques, the type of bonding between the ligand and the metal ions in the recently formed complexes was clarified. The Schiff base ligand act as a bidentate and coordinated with the metal ions through the azomethine-N and the phenolic-O centers, in a mono-deprotonated form. Except for the Zn(II) complex, which displayed a tetrahedral geometry, all complexes displayed octahedral geometry. The TGA findings supported that the stability and decomposition properties of the metal complexes were entirely distinct from one another. The thermogram showed decomposition of all investigated metal complexes above 200 °C in three, four or five steps, and indicated the high thermal stability of these complexes. According to XRD patterns, the particles of these complexes were located at the nanoscale. Moreover, for all the samples analyzed, the TEM images showed uniform and homogeneous surface morphology. The biological activity revealing the high efficiencies of the screened complexes as antibacterial and antitumor agents. The antimicrobial activity of the ligand and its complexes was examined against a variety of pathogenic bacteria and fungi including Escherichia coli, Staphylococcus aureus and Candida albicans. The data obtained revealed that the metal ion in the complexes enhanced the antimicrobial activity compared to the free ligand. The high efficiencies toward S. aureus, E. coli, and C. albicans appeared by Cu(II) complex 23, Ni(II) complex 20, and Ni(II) complex 19, respectively. The antitumor activity of the ligand and its complexes was tested against Hepatocellular carcinoma cell line (HepG-2 cells), the residue 28 which produced after heating the Cu(II) complex 25 at 200 °C for 1 h, exhibited strong inhibition of HepG-2 cell growth. The results of the DNA cleavage investigation demonstrated the ability of investigated Cu(II) complex to degrade DNA. The docking findings showed strong interactions of both the ligand and its examined Cu(II) complex, revealing their ability to cleavage DNA and their potent inhibitory effects on tumor cells. The electrical conductivity study confirmed that the ligand and its investigated complexes had semiconducting properties.

Abstract In order to understand the characteristics of bio-convection and moving microorganisms in flows of magnetized Walters-B nano-liquid, we developed a model employing Riga plate with stretchy sheet. The Buongiorno phenomenon is likewise employed to describe nano-liquid motion in the Walters-B fluid. Expending correspondence transformations, the partial differential equation (PDE) control system has been transformed into an ordinary differential equation (ODE) control system. The COMSOL program is used to generate mathematical answers for non-linear equations by employing the Galerkin finite element strategy (G-FEM). Utilizing logical and graphical metrics, temperature, velocity, and microbe analysis are all studied. Various estimates of well-known physical features are taken into account while calculating nanoparticle concentrations. It is demonstrated that this model's computations directly relate the temperature field to the current Biot number and parameter of the Walters-B fluid. The temperature field is increased to increase the approximations of the current Biot number and parameter of the Walters-B fluid.

Abstract Objective The current study aimed to translate the Australian Type 2 Diabetes Risk Assessment tool (AUSDRISK) into the Arabic language and evaluate the reliability and validity of the resultant Arabic version among Egyptians. The AUSDRISK was translated into Arabic language using the World Health Organization (WHO) forward and backward translation protocol. Using the WHO cluster sampling, a sample of 18+ years 719 Egyptians was randomly selected through a population-based household survey. Each participant was interviewed to fill the AUSDRISK Arabic version risk score and undergo confirmatory testing for fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT). Test-retest reliability and convergent validity were computed. Results Most of the study participants were physically active (60.5%) and females (69.3%). The Arabic version of the AUSDRISK reflected statistically significant perfect positive correlation (r = 1 and p

Background: H.pylori is a Gram-negative bacterium known to be associated with peptic ulcer disease, gastric cancer, gastric lymphoma. Recently it was detected in mucosa of patients with CRS, but relation with bilateral nasal polyposis has not been demonstrated yet. Objectives: H. pyloriis a pathogen that lives in the gastrointestinal tract (GIT) and has extragastric manifestations. Nasal polypi may be one of these manifestations. This study aims to detect the relation between H.pylori and bilateral nasal polypi. Patients and methods: This study includes 80 cases of nasal polypi, 40 of them were de novo bilateral nasal polypi and 40 were recurrent nasal polypi, biopsies of nasal polypi were taken under sterile conditions and stained with Giemsa stain and Hematoxylin and eosin(H&E) stain. Stool analysis was done to detect presence of H.pylori using rapid urease test. Results: Both groups are age and sex matched. Nasal polyp biopsies showed positive results in 10 % of denovo group and 15 % of recurrent group with p value 0.449 which is not statistically significant. Stool antigen test showed positive results in 52.5 % of denovo group and 60 % of recurrent group with p value 0.449 which is not statistically significant. Conclusion: There is no statistically significant relation between H.pylori and the pathogenesis of bilateral nasal polypi, further studies with large number of patients is recommended.

Abstract The development of new natural drugs for Helicobacter pylori (H. pylori) management has recently received significant attention. Iris confusa (I. confusa) was long used for the treatment of bacterial infections and gastritis. This study aimed at evaluating its effect on management of H. pylori infection and exploring its bioactive metabolites. The inhibitory potential of the polar (PF), non-polar (NPF) fractions and the isolated compounds against H. pylori using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay in addition to their cyclooxygenases (COX-1 and COX-2), and nitric oxide (NO) inhibitory activities were assessed. The most biologically active compound was tested for its selective H. pylori inosine-5′-monophosphate dehydrogenase (HpIMPDH) inhibitory potential. Chromatographic purification of PF and NPF allowed isolation of tectoridin, orientin, irigenin, tectorigenin, isoarborinol and stigmasterol. The PF exhibited significant anti-H. pylori (MIC 62.50 µg/mL), COX-1, COX-2 (IC50 of 112.08 ± 0.60 and 47.90 ± 1.50 µg/mL respectively, selectivity index SI of 2.34), and NO (IC50 47.80 ± 0.89 µg/mL) inhibitory activities, while irigenin was the most potent isolated compound. Irigenin was found to have a promising activity against HpIMPDH enzyme (IC50 of 2.07 ± 1.90 μM) with low activity against human hIMPDH2 (IC50 > 10 μM) than clarithromycin, assuring its selectivity. Overall, I. confusa and its isolated compounds may serve as a potential source of plant-based drugs for H. pylori control. This study scientifically validated the claimed anti-bacterial activity of I. confusa and revealed irigenin potential as a novel lead exhibiting anti H. pylori activity in a first record.

Abstract Currently, the humanity is in a fierce battle against various health-related challenges especially those associated with human malignancies. This created the urge to develop potent and selective inhibitors for tumor cells through targeting specific oncogenic proteins possessing crucial roles in cancer progression and survive. In this respect, new series of pyrazole-thiazol-4-one hybrids (9a–p) were synthesized as potential anticancer agents. All the synthesized molecules exhibited potent antiproliferative actions against breast cancer (BC) T-47D and MDA-MB-231 cell lines with IC50 ranges 3.14–4.92 and 0.62–58.01, respectively. Moreover, the most potent anti-proliferative counterparts 9g and 9k were assessed against EGFR. They displayed nanomolar inhibitory activity, IC50 267 ± 12 and 395 ± 17 nM, respectively. Worth noting, both compounds 9g and 9k induced apoptosis in MDA-MB-231 cells, and resulted in a cell cycle arrest at G2/M phase. Furthermore, an in silico analysis including docking and molecular dynamic simulations was performed.

Staphylococcus aureus (S. aureus) remains one of the most frequently occurring community-acquired as well as hospital-acquired pathogens with high rates of hospital-acquired infections. S.aureus is an important pathogenic bacterium. It resides predominantly in the anterior nares, and extra-nasal sites including the skin, perineum, and pharynx, and less frequent in the gastrointestinal tract and the vagina. About 30% of the general population is nasal carriers of the bacterium. Infections caused by this organism could be exogenous or endogenous in origin, and they include impetigo, cellulitis, osteomyelitis, endocarditis, toxic shock syndrome (TSS), septicemia, and pneumonia. Healthcare-associated infections by S. aureus are about 20% worldwide. S. aureus infection at NICU remains a major health challenge as colonized healthcare workers, patients, and contaminated surfaces serve as reservoir for infection. The incidence of healthcare-associated infections caused by S. aureus continues to increase worldwide. The goal of this study is to assess the nasal carriage of S. aureus isolated from neonates and health care workers (HCWs) in the NICU of Beni Suef University Hospital. Also, our study provides valuable insights documenting important factors that affect susceptibility and outcomes of neonatal sepsis which is a global public health issue.

A cross-sectional, analytical study conducted over a period of 6 months from April to September 2021 after the approval of REC on 50 patients with confirmed positive of COVID-19 by SARS-CoV-2 nucleic acid RT-PCR recruited from Isolation departments and intensive care units (ICUs), Beni-Suef University hospital. The goal of this study was to assess the serum level of (IL-18) as a biomarker of COVID-19 disease progression. All participants underwent complete blood count (CBC), C- reactive protein (CRP), fibrinogen, D-dimer and liver enzymes and measurement of serum IL- 18 level. All patients had been followed until hospital discharge or death. Forty-two patients (84%) recovered and discharged from the hospital while eight cases (16%) died due to different etiologies: 2 patients due to suppurative lung infection, another 2 because of multi organ failure, 2 patients owing to respiratory failure and alveolar damage, and the last 2 patients with cardiac comorbidity after ischemic heart disease and hypertension. There were a significant higher level of CRP, D-dimer, ferritin, and IL-18 among died as compared with recovered COVID-19 patients. Platelets count was significantly higher among recovered as compared with died COVID-19 patients. Correlation test showed a significant positive strong linear relationship between CRP level and IL-18, D-dimer level, and IL-18, and between ferritin level and IL-18. High values of IL-18 in patients’ serum helped to assess the poor prognosis which was statistically significant with 81.5% sensitivity and 57.5% specificity at a cutoff point level ≥ 230.75. Elevated serum levels of IL-18 were associated with fatal outcome in the COVID-19 infected patients and showed strong correlation with other inflammatory markers.

Abstract Pseudomonas aeruginosa (P. aeruginosa) is an important opportunistic pathogen that is responsible for many clinical infections in both animals and humans. This study aimed to detect the prevalence of P. aeruginosa in dairy farm's that possess a great importance to dairy industry where it shares in milk spoilage. Evaluation of the efficacy of commonly used disinfectants to control the pathogen in dairy environment and finding a way to overcome high resistance to the used agents. Samples (n = 250) were collected from different environmental components, milk, and milkers' hands. Pathogens were isolated, biofilm was detected and their sensitivity against two commonly used disinfectants and against silver nanoparticles and Virokill AgNPs at different concentrations and contact times were tested. The pathogen significantly prevailed in milk samples (70.0%, P

Breast cancer is a serious threat to the health and lives of women. Two novel series of N′-(2-oxoindolin-3-ylidene)-6-methylimidazo[2,1-b]thiazole-5-carbohydrazides and 1-(aryl)-3-(6-methylimidazo[2,1-b]thiazol-5-yl)ureas were designed, synthesized and investigated for their anticancer efficacy against the MCF-7 breast cell line. Three compounds of the first series showed potent activity toward MCF-7 with IC50 in the range 8.38–11.67 µM, respectively, as compared to Sorafenib (IC50 = 7.55 µM). N′-(1-butyl-2-oxoindolin-3-ylidene)-6-methylimidazo[2,1-b]thiazole-5-carbohydrazide inhibited VEGFR-2 with IC50 = 0.33 µM when compared with Sorafenib (IC50 = 0.09 µM). Furthermore, this compound was introduced to PCR assessment, where it increased Bax, caspase 8, caspase 9 and cytochrome C levels by 4.337-, 2.727-, 4.947- and 2.420-fold, respectively, while it decreased levels of Bcl-2, as the anti-apoptotic gene, by 0.359-fold when compared to the untreated control MCF-7. This compound was also arrested in the G2/M phase by 27.07%, compared with 11.31% for the control MCF-7. Furthermore, it induced early and late apoptosis in MCF-7. In addition, a molecular docking study in the VEGFR-2 active site was performed to assess the binding profile for the most active compounds. Moreover, ADME parameters of the targeted compounds were also evaluated.

Objectives: The aim of this study was to determine the association between neutrophils and monocytes CD 64 molecules and cases of bronchiolitis with an associated bacterial infection. Methods: Blood samples were obtained from patients younger than 2 years old diagnosed with bronchiolitis. Complete blood count (CBC), blood culture, procalcitonin, and CD64 surface expression in neutrophils and monocytes were examined using flow cytometry. We also assessed CBC, procalcitonin, and CD64 levels in neutrophils and monocytes in 31 healthy control subjects. Results : Sixty-two patients with lower respiratory tract infections were included in the first group. The patients were divided into 34 with non-bacterial infections and 28 with possible bacterial infections. We found a significant increase in the number of positive cells in the Mean Fluorescence Intensity (MFI) of both nCD64 and mCD64 in the Possible Bacterial Infection (PBI) group. Procalcitonin levels correlated with nCD64 and nCD64%, but not with mCD64. The AUC of nCD64 was 0.873 (at a cut-off point of 4489.4; the MFI had a specificity of 73% and a sensitivity of 94%). Conclusion: Neutrophil CD64 may be a marker for bacterial infection in children with bronchiolitis.

Abstract This study aimed to evaluate the efficacy of magnetic nanocomposite of cefotax against MRSA. A total of 190 samples were collected from milk, farm personnel and different environmental components from the dairy farm under the study to isolate S. aureus. Cefotax based magnetic nanoparticles was synthetized by the adsorption method and marked using Fourier-transform infrared spectrum (FT-IR), and X-ray diffraction (XRD), then it was characterized using Scanning and Transmission Electron Microscope (SEM and TEM). The obtained results revealed that number of positive samples of S. aureus isolation were 63 (33.1%), mainly from feed manger followed by milk machine swabs (60.0 and 53.3%, respectively) at X2 = 48.83 and P