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1.
Reprod Sci ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38691315

RESUMEN

The current study aimed to evaluate the serum levels of nitric oxide (NO) and adropin in males with non-alcoholic fatty liver disease (NAFLD) induced erectile dysfunction (ED) and NAFLD patients without ED and controls. The current study selected 165 participants from the hepatology department from November 2021 to November 2022. The patients were either suffering from NAFLD with normal liver functions or non-alcoholic steatohepatitis with abnormal liver functions. They were diagnosed by abdominal ultrasonography. Participants were evaluated using the validated Arabic version of the International Index of Erectile Function (ArIIEF-5), the Arabic form of the Generalized Anxiety Disorder-7 (GAD-7) questionnaire and the Patient Health Questionnaire-9 (PHQ-9). Noteworthy, there were significant positive correlations between ArIIEF-5 score, NO, adropin and total testosterone (r = 0.380, p = 0.001; r = 0.507, p = < 0.001; r = 0.246, p = 0.038, respectively). Meanwhile, there were significant negative correlations between ArIIEF-5 score, creatinine, duration of the disease and scores of GAD-7 and PHQ-9 (r = -0.656, p = < 0.001; r = -0.368, p = 0.002; r = -0.663, p = < 0.001; r = -0.248, p = 0.037, respectively). Finally, a linear regression analysis revealed that GAD-7, creatinine, and adropin were the only strong independent predictors of ArIIEF-5, as the 95% confidence interval in the form of upper and lower bounds was -0.349, -0.843, p < 0.001, -6.507, -18.402, p < 0.001, 0.476, 0.117, and p 0.002, respectively. Impaired NO and adropin levels play a potential role in the development of ED in patients with NAFLD.

2.
bioRxiv ; 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38746414

RESUMEN

SARS-CoV-2 continues to be a public health burden, driven in-part by its continued antigenic diversification and resulting emergence of new variants. While increasing herd immunity, current vaccines, and therapeutics have improved outcomes for some; prophylactic and treatment interventions that are not compromised by viral evolution of the Spike protein are still needed. Using a rationally designed SARS-CoV-2 Receptor Binding Domain (RBD) - ACE2 fusion protein and differential selection process with native Omicron RBD protein, we developed a recombinant human monoclonal antibody (hmAb) from a convalescent individual following SARS-CoV-2 Omicron infection. The resulting hmAb, 1301B7 potently neutralized a wide range of SARS-CoV-2 variants including the original Wuhan and more recent Omicron JN.1 strain, as well as SARS-CoV. Structure determination of the SARS-CoV-2 EG5.1 Spike/1301B7 Fab complex by cryo-electron microscopy at 3.1Å resolution demonstrates 1301B7 contacts the ACE2 binding site of RBD exclusively through its VH1-69 heavy chain, making contacts using CDRs1-3, as well as framework region 3 (FR3). Broad specificity is achieved through 1301B7 binding to many conserved residues of Omicron variants including Y501 and H505. Consistent with its extensive binding epitope, 1301B7 is able to potently diminish viral burden in the upper and lower respiratory tract and protect mice from challenge with Omicron XBB1.5 and Omicron JN.1 viruses. These results suggest 1301B7 has broad potential to prevent or treat clinical SARS-CoV-2 infections and to guide development of RBD-based universal SARS-CoV-2 prophylactic vaccines and therapeutic approaches.

3.
Int J Pharm ; 656: 124078, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38569978

RESUMEN

The role of tumor stroma in solid tumors has been widely recognized in cancer progression, metastasis and chemoresistance. Cancer-associated fibroblasts (CAFs) play a crucial role in matrix remodeling and promoting cancer cell stemness and resistance via reciprocal crosstalk. Residual tumor tissue after surgical removal as well as unresectable tumors face therapeutic challenges to achieve curable outcome. In this study, we propose to develop a dual delivery approach by combining p21-activated kinase 1 (PAK1) inhibitor (FRAX597) to inhibit tumor stroma and chemotherapeutic agent paclitaxel (PTX) to kill cancer cells using electrospun nanofibers. First, the role of the PAK1 pathway was established in CAF differentiation, migration and contraction using relevant in vitro models. Second, polycaprolactone polymer-based nanofibers were fabricated using a uniaxial electrospinning technique to incorporate FRAX597 and/or PTX, which showed a uniform texture and a prolonged release of both drugs for 16 days. To test nanofibers, stroma-rich 3D heterospheroid models were set up which showed high resistance to PTX nanofibers compared to stroma-free homospheroids. Interestingly, nanofibers containing PTX and FRAX597 showed strong anti-tumor effects on heterospheroids by reducing the growth and viability by > 90 % compared to either of single drug-loaded nanofibers. These effects were reflected by reduced intra-spheroidal expression levels of collagen 1 and α-smooth muscle actin (α-SMA). Overall, this study provides a new therapeutic strategy to inhibit the tumor stroma using PAK1 inhibitor and thereby enhance the efficacy of chemotherapy using nanofibers as a local delivery system for unresectable or residual tumor. Use of 3D models to evaluate nanofibers highlights these models as advanced in vitro tools to study the effect of controlled release local drug delivery systems before animal studies.


Asunto(s)
Nanofibras , Paclitaxel , Quinasas p21 Activadas , Paclitaxel/administración & dosificación , Paclitaxel/farmacología , Nanofibras/administración & dosificación , Quinasas p21 Activadas/antagonistas & inhibidores , Quinasas p21 Activadas/metabolismo , Humanos , Línea Celular Tumoral , Esferoides Celulares/efectos de los fármacos , Poliésteres/química , Poliésteres/administración & dosificación , Fibroblastos Asociados al Cáncer/efectos de los fármacos , Fibroblastos Asociados al Cáncer/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Movimiento Celular/efectos de los fármacos , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/farmacología , Liberación de Fármacos , Diferenciación Celular/efectos de los fármacos
4.
Arch Virol ; 169(5): 99, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38625394

RESUMEN

H9N2 avian influenza viruses (AIVs) affect both poultry and humans on a global level, and they are especially prevalent in Egypt. In this study, we sequenced the entire genome of AIV H9N2 isolated from chickens in Egypt in 2021, using next-generation sequencing (NGS) technology. Phylogenetic analysis of the resulting sequences showed that the studied strain was generally monophyletic and grouped within the G1 sublineage of the Eurasian lineage. Four segments (polymerase basic 2 [PB2], polymerase basic 1 [PB1], polymerase acidic [PA], and non-structural [NS]) were related to Egyptian genotype II, while the nucleoprotein (NP), neuraminidase (NA), matrix (M), and haemagglutinin (HA) segments were related to Egyptian genotype I. Molecular analysis revealed that HA protein contained amino acid residues (191H and 234L) that suggested a predilection for attaching to human-like receptors. The antigenic sites of HA had two nonsynonymous mutations: V194I at antigenic site A and M40K at antigenic site B. Furthermore, the R403W and S372A mutations, which have been observed in H3N2 and H2N2 strains that caused human pandemics, were found in the NA protein of the detected strain. The internal proteins contained virulence markers: 504V in the PB2 protein, 622G, 436Y, 207K, and 677T in the PB1 protein, 127V, 550L, and 672L in PA protein, and 64F and 69P in the M protein. These results show that the detected strain had undergone intrasubtype reassortment. Furthermore, it contains changes in the viral proteins that make it more likely to be virulent, raising a question about the tendency of AIV H9N2 to become highly pathogenic in the future for both poultry and humans.


Asunto(s)
Antígenos de Grupos Sanguíneos , Subtipo H9N2 del Virus de la Influenza A , Gripe Aviar , Animales , Humanos , Aves de Corral , Subtipo H9N2 del Virus de la Influenza A/genética , Egipto/epidemiología , Pollos , Granjas , Subtipo H3N2 del Virus de la Influenza A , Gripe Aviar/epidemiología , Filogenia
5.
PLoS One ; 19(4): e0301086, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38662719

RESUMEN

There is still a great global need for efficient treatments for the management of SARS-CoV-2 illness notwithstanding the availability and efficacy of COVID-19 vaccinations. Olive leaf is an herbal remedy with a potential antiviral activity that could improve the recovery of COVID-19 patients. In this work, the olive leaves major metabolites were screened in silico for their activity against SARS-CoV-2 by molecular docking on several viral targets such as methyl transferase, helicase, Plpro, Mpro, and RdRp. The results of in silico docking study showed that olive leaves phytoconstituents exhibited strong potential antiviral activity against SARS-CoV-2 selected targets. Verbacoside demonstrated a strong inhibition against methyl transferase, helicase, Plpro, Mpro, and RdRp (docking scores = -17.2, -20, -18.2, -19.8, and -21.7 kcal/mol.) respectively. Oleuropein inhibited 5rmm, Mpro, and RdRp (docking scores = -15, -16.6 and -18.6 kcal/mol., respectively) respectively. Apigenin-7-O-glucoside exhibited activity against methyl transferase and RdRp (docking score = -16.1 and -19.4 kcal/mol., respectively) while Luteolin-7-O-glucoside inhibited Plpro and RdRp (docking score = -15.2 and -20 kcal/mol., respectively). The in vitro antiviral assay was carried out on standardized olive leaf extract (SOLE) containing 20% oleuropein and IC50 was calculated. The results revealed that 20% SOLE demonstrated a moderate antiviral activity against SARS-CoV-2 with IC50 of 118.3 µg /mL. Accordingly, olive leaf could be a potential herbal therapy against SARS-CoV-2 but more in vivo and clinical investigations are recommended.


Asunto(s)
Antivirales , Iridoides , Simulación del Acoplamiento Molecular , Olea , Extractos Vegetales , Hojas de la Planta , Polifenoles , SARS-CoV-2 , Olea/química , Antivirales/farmacología , Antivirales/química , SARS-CoV-2/efectos de los fármacos , Hojas de la Planta/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Iridoides/farmacología , Iridoides/química , Humanos , Glucósidos Iridoides/farmacología , Glucósidos Iridoides/química , Glucósidos/farmacología , Glucósidos/química , Metiltransferasas/metabolismo , Metiltransferasas/antagonistas & inhibidores , COVID-19/virología , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Proteasas 3C de Coronavirus/metabolismo , Proteasas 3C de Coronavirus/química , Simulación por Computador , Tratamiento Farmacológico de COVID-19 , Luteolina/farmacología , Luteolina/química , ARN Helicasas/metabolismo , ARN Helicasas/antagonistas & inhibidores , Apigenina/farmacología , Apigenina/química
6.
Front Cell Infect Microbiol ; 14: 1363407, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38590437

RESUMEN

Introduction: Influenza A virus (IAV) infection can cause the often-lethal acute respiratory distress syndrome (ARDS) of the lung. Concomitantly, acute kidney injury (AKI) is frequently noticed during IAV infection, correlating with an increased mortality. The aim of this study was to elucidate the interaction of IAV with human kidney cells and, thereby, to assess the mechanisms underlying IAV-mediated AKI. Methods: To investigate IAV effects on nephron cells we performed infectivity assays with human IAV, as well as with human isolates of either low or highly pathogenic avian IAV. Also, transcriptome and proteome analysis of IAV-infected primary human distal tubular kidney cells (DTC) was performed. Furthermore, the DTC transcriptome was compared to existing transcriptomic data from IAV-infected lung and trachea cells. Results: We demonstrate productive replication of all tested IAV strains on primary and immortalized nephron cells. Comparison of our transcriptome and proteome analysis of H1N1-type IAV-infected human primary distal tubular cells (DTC) with existing data from H1N1-type IAV-infected lung and primary trachea cells revealed enrichment of specific factors responsible for regulated cell death in primary DTC, which could be targeted by specific inhibitors. Discussion: IAV not only infects, but also productively replicates on different human nephron cells. Importantly, multi-omics analysis revealed regulated cell death as potential contributing factor for the clinically observed kidney pathology in influenza.


Asunto(s)
Lesión Renal Aguda , Subtipo H1N1 del Virus de la Influenza A , Virus de la Influenza A , Gripe Humana , Infecciones por Orthomyxoviridae , Muerte Celular Regulada , Humanos , Proteoma/metabolismo , Subtipo H3N2 del Virus de la Influenza A/fisiología , Replicación Viral/fisiología , Riñón/patología , Infecciones por Orthomyxoviridae/patología
7.
Arch Pathol Lab Med ; 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38599589

RESUMEN

CONTEXT.­: Mass COVID-19 vaccination is mandated in vulnerable populations in our renal transplant waitlist cohort. However, the anti-human leukocyte antigen (anti-HLA) profile after COVID-19 vaccination is controversial, and the side effects are yet to be discerned. OBJECTIVE.­: To evaluate the status of HLA antibodies in waitlist renal transplant patients before and 3 weeks after each vaccination and if comorbidities are associated with the HLA antibody profile. DESIGN.­: A total of 59 waitlisted kidney transplant patients were included in this study. The anti-HLA antibodies were analyzed before and 6 months after their last COVID-19 vaccination. The mean fluorescence intensity change in the anti-HLA antibody levels was used to classify patients into 3 groups: high inducers, low inducers, and noninducers. RESULTS.­: There were significant HLA antibody profile changes after COVID-19 vaccination, showing 21 antibodies generated against HLA class I antigens and 7 against HLA class II antigens to their baseline. Compared with the noninducers, the high and low inducers showed a higher prevalence of COVID-19 infection, COVID-19 vaccine type, and background hypertension history. CONCLUSIONS.­: Our data suggest that COVID-19 vaccination propagates anti-HLA class I and II antibodies for waitlisted renal transplant patients. The clinical significance of these antibodies needs further study. Furthermore, comorbidities, such as history of COVID-19 infection and hypertension, supplemented this effect. Anti-HLA antibody monitoring may be warranted in vaccinated, waitlisted renal transplant patients with COVID-19 vaccinations, and a history of COVID-19 infection or hypertension.

8.
J Genet Eng Biotechnol ; 22(1): 100334, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38494269

RESUMEN

BACKGROUND: One of the most dangerous problems that the world faced recently is viral respiratory pathogens. Marine creatures, including Echinodermata, specially Asteroidea class (starfish) have been extensively studied due to their miscellaneous bioactivities, excellent pharmacological properties, and complex secondary metabolites, including steroids, steroidal glycosides, anthraquinones, alkaloids, phospholipids, peptides, and fatty acids. These chemical constituents show antiviral activities against a wide range of viruses, including respiratory viruses. RESULTS: The present study aimed at the identification of potential antiviral compounds from some starfish species. The bioactive compounds from Pentaceraster cumingi, Astropecten polyacanthus, and Pentaceraster mammillatus were extracted using two different solvents (ethyl acetate and methanol). The antiviral activity against influenza A/H1N1 virus showed that ethyl acetate extract from Pentaceraster cumingi has the highest activity, where the selective index was 150.8. The bioactive compounds of this extract were identified by GC/MS analysis. The molecular docking study highlighted the virtual mechanism of binding of the identified compounds towards polymerase basic protein 2 and neuraminidase for H1N1 virus. Interestingly, linoleic acid showed promising binding energy of -10.12 Kcal/mol and -24.20 Kcal/mol for the selected two targets, respectively, and it formed good interactive modes with the key amino acids inside both proteins. CONCLUSION: The molecular docking analysis showed that linoleic acid was the most active antiviral compound from P. cumingi. Further studies are recommended for in-vitro and in-vivo evaluation of this compound against influenza A/H1N1 virus.

9.
Anal Chem ; 96(9): 3727-3732, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38395621

RESUMEN

Processing liquid chromatography-mass spectrometry-based metabolomics data using computational programs often introduces additional quantitative uncertainty, termed computational variation in a previous work. This work develops a computational solution to automatically recognize metabolic features with computational variation in a metabolomics data set. This tool, AVIR (short for "Accurate eValuation of alIgnment and integRation"), is a support vector machine-based machine learning strategy (https://github.com/HuanLab/AVIR). The rationale is that metabolic features with computational variation have a poor correlation between chromatographic peak area and peak height-based quantifications across the samples in a study. AVIR was trained on a set of 696 manually curated metabolic features and achieved an accuracy of 94% in a 10-fold cross-validation. When tested on various external data sets from public metabolomics repositories, AVIR demonstrated an accuracy range of 84%-97%. Finally, tested on a large-scale metabolomics study, AVIR clearly indicated features with computational variation and thus guided us to manually correct them. Our results show that 75.3% of the samples with computational variation had a relative intensity difference of over 20% after correction. This demonstrates the critical role of AVIR in reducing computational variation to improve quantitative certainty in untargeted metabolomics analysis.


Asunto(s)
Metabolómica , Programas Informáticos , Incertidumbre , Metabolómica/métodos , Cromatografía Liquida/métodos , Cromatografía Líquida con Espectrometría de Masas
10.
Front Cell Infect Microbiol ; 14: 1357866, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38375361

RESUMEN

Following virus recognition of host cell receptors and viral particle/genome internalization, viruses replicate in the host via hijacking essential host cell machinery components to evade the provoked antiviral innate immunity against the invading pathogen. Respiratory viral infections are usually acute with the ability to activate pattern recognition receptors (PRRs) in/on host cells, resulting in the production and release of interferons (IFNs), proinflammatory cytokines, chemokines, and IFN-stimulated genes (ISGs) to reduce virus fitness and mitigate infection. Nevertheless, the game between viruses and the host is a complicated and dynamic process, in which they restrict each other via specific factors to maintain their own advantages and win this game. The primary role of the non-structural protein 1 (NS1 and Nsp1) of influenza A viruses (IAV) and the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respectively, is to control antiviral host-induced innate immune responses. This review provides a comprehensive overview of the genesis, spatial structure, viral and cellular interactors, and the mechanisms underlying the unique biological functions of IAV NS1 and SARS-CoV-2 Nsp1 in infected host cells. We also highlight the role of both non-structural proteins in modulating viral replication and pathogenicity. Eventually, and because of their important role during viral infection, we also describe their promising potential as targets for antiviral therapy and the development of live attenuated vaccines (LAV). Conclusively, both IAV NS1 and SARS-CoV-2 Nsp1 play an important role in virus-host interactions, viral replication, and pathogenesis, and pave the way to develop novel prophylactic and/or therapeutic interventions for the treatment of these important human respiratory viral pathogens.


Asunto(s)
COVID-19 , Virus de la Influenza A , Humanos , Inmunidad Innata , Virus de la Influenza A/genética , Interferones/inmunología , SARS-CoV-2/metabolismo , Replicación Viral
11.
Front Chem ; 12: 1330810, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38370094

RESUMEN

This study introduces environmentally-friendly nanocellulose-based membranes for AZO dye (methylene blue, MB) removal from wastewater. These membranes, made of cellulose nanocrystals (CNCs), carboxymethyl cellulose (CMC), zeolite, and citric acid, aim to offer eco-friendly water treatment solutions. CNCs, obtained from sugarcane bagasse, act as the foundational material for the membranes. The study aims to investigate both the composition of the membranes (CMC/CNC/zeolite/citric acid) and the critical adsorption factors (initial MB concentration, contact time, temperature, and pH) that impact the removal of the dye. After systematic experimentation, the optimal membrane composition is identified as 60% CNC, 15% CMC, 20% zeolites, and 5% citric acid. This composition achieved a 79.9% dye removal efficiency and a 38.3 mg/g adsorption capacity at pH 7. The optimized membrane exhibited enhanced MB dye removal under specific conditions, including a 50 mg adsorbent mass, 50 ppm dye concentration, 50 mL solution volume, 120-min contact time, and a temperature of 25°C. Increasing pH from neutral to alkaline enhances MB dye removal efficiency from 79.9% to 94.5%, with the adsorption capacity rising from 38.3 mg/g to 76.5 mg/g. The study extended to study the MB adsorption mechanisms, revealing the chemisorption of MB dye with pseudo-second-order kinetics. Chemical thermodynamic experiments determine the Freundlich isotherm as the apt model for MB dye adsorption on the membrane surface. In conclusion, this study successfully develops nanocellulose-based membranes for efficient AZO dye removal, contributing to sustainable water treatment technologies and environmental preservation efforts.

12.
Exp Clin Transplant ; 22(Suppl 1): 290-298, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38385415

RESUMEN

OBJECTIVES: Renal complications of COVID-19 are not yet well studied. We aimed to evaluate acute kidney injury prevalence among hospitalized patients with COVID-19 infection and explore its effect on patient outcomes. MATERIALS AND METHODS: We retrospectively evaluated 586 hospitalized patients with COVID-19. Of these patients, 267 (45.5%) developed acute kidney injury, as classified according to the Kidney Disease Improving Global Outcomes guidelines. We compared this group with 319 patients (54.5%) without acute kidney injury. RESULTS: Most patients in both study groups were men; mean age was 60.8 ± 14 versus 51.7 ± 16 years. Comorbid conditions that were substantially predominant among patients with acute kidney injury were diabetes mellitus (64% vs 42.9%), hypertension (72.6% vs 43.5%), and ischemic heart disease (25% vs 14.7%). Fever, cough, shortness of breath, and dehydration were the main presentations among patients with acute kidney injury, and patients in this group had greater prevalence of radiological findings concordant with COVID-19 (86.8% vs 59.8%). Sepsis, volume depletion, shock, arrhythmias, and acute respiratory distress syndrome were higher in patients with acute kidney injury. Anticoagulation (85% vs 59.2%), vasopressors, plasma infusions, antimicrobials, and steroids were more frequently used in patients with acute kidney injury. More patients with acute kidney injury had acute respiratory failure requiring mechanical ventilation (62.3% vs 32.9%), with higher overall mortality rate (63.2% vs 31.1%). CONCLUSIONS: We found more frequent prevalence of acute kidney injury associated with severe COVID-19 than shown in reports from Chinese, European, and North American cohorts. Patients with COVID-19 who developed acute kidney injury had risk factors such as hypertension and diabetes, greater need for mechanical ventilation, were males, and were older age. Mortality was high in this population, especially among older patients and those who developed Kidney Disease Improving Global Outcomes stage 3 disease.


Asunto(s)
Lesión Renal Aguda , COVID-19 , Hipertensión , Masculino , Humanos , Persona de Mediana Edad , Anciano , Femenino , COVID-19/diagnóstico , COVID-19/terapia , SARS-CoV-2 , Estudios Retrospectivos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Factores de Riesgo , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/terapia
13.
BMC Complement Med Ther ; 24(1): 49, 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38254071

RESUMEN

BACKGROUND: The continuous evolution of drug-resistant influenza viruses highlights the necessity for repurposing naturally-derived and safe phytochemicals with anti-influenza activity as novel broad-spectrum anti-influenza medications. METHODS: In this study, nitrogenous alkaloids were tested for their viral inhibitory activity against influenza A/H1N1 and A/H5N1 viruses. The cytotoxicity of tested alkaloids on MDCK showed a high safety range (CC50 > 200 µg/ml), permitting the screening for their anti-influenza potential. RESULTS: Herein, atropine sulphate, pilocarpine hydrochloride and colchicine displayed anti-H5N1 activities with IC50 values of 2.300, 0.210 and 0.111 µg/ml, respectively. Validation of the IC50 values was further depicted by testing the three highly effective alkaloids, based on their potent IC50 values against seasonal influenza A/H1N1 virus, showing comparable IC50 values of 0.204, 0.637 and 0.326 µg/ml, respectively. Further investigation suggests that colchicine could suppress viral infection by primarily interfering with IAV replication and inhibiting viral adsorption, while atropine sulphate and pilocarpine hydrochloride could directly affect the virus in a cell-free virucidal effect. Interestingly, the in silico molecular docking studies suggest the abilities of atropine, pilocarpine, and colchicine to bind correctly inside the active sites of the neuraminidases of both influenza A/H1N1 and A/H5N1 viruses. The three alkaloids exhibited good binding energies as well as excellent binding modes that were similar to the co-crystallized ligands. On the other hand, consistent with in vitro results, only colchicine could bind correctly against the M2-proton channel of influenza A viruses (IAVs). This might explicate the in vitro antiviral activity of colchicine at the replication stage of the virus replication cycle. CONCLUSION: This study highlighted the anti-influenza efficacy of biologically active alkaloids including colchicine. Therefore, these alkaloids should be further characterized in vivo (preclinical and clinical studies) to be developed as anti-IAV agents.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Subtipo H5N1 del Virus de la Influenza A , Virus de la Influenza A , Gripe Humana , Humanos , Colchicina/farmacología , Pilocarpina , Gripe Humana/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Estaciones del Año , Fitoquímicos/farmacología , Atropina , Antivirales/farmacología
14.
J Prosthodont ; 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38288528

RESUMEN

PURPOSE: Attempts have been made to decontaminate the implant surface by using diode lasers. However, the parameters that provide efficient decontamination without altering the topography or surface characteristics of titanium implants are still unclear. The aim of the present study was to evaluate the effect of altering the power of diode laser (940 nm) application on the hydrophilicity, surface topography, and chemical composition of sandblasted, large grit, acid-etched (SLA) treated titanium alloy implant surface. MATERIALS AND METHODS: Thirty-six SLA-treated titanium discs (Dentis Co., Ltd.) were used in this study. The hydrophilicity of all discs was measured by using a contact angle goniometer (190 CA; Rame-hart Co, Ltd). Discs were randomly divided into four groups (n = 9 each) based on the power of the diode laser used. Group I (control, no lasing group), group II: treated with 1 W power, group III: 2 W power, and group IV: 3 W power. The chemical composition of the SLA discs was evaluated by using energy dispersive x-ray spectroscopy (EDX) before laser application. Hydrophilicity was reevaluated after the application of laser irradiation. The surface topography of all discs was examined. Changes in the chemical composition of the titanium discs were investigated following the lasing procedure. Morphometric analysis of the surface area (µm2 ) of the indentations created following laser application was also evaluated. Data were collected and the Shapiro-Wilk test of normality was used. Comparisons between the four study groups were done by using the Kruskal-Wallis test, while that to evaluate the morphometric analysis of the surface area was done by using One-way ANOVA (P < 0.05). RESULTS: The average contact angle of the drop of distilled water to the SLA discs significantly decreased after laser treatment (P < 0.05). The largest contact angle was measured in the control group, followed by the 1 W group, and the 2 W group. The smallest angle was measured in the 3 W group. Considerable surface alterations such as melting and flattening were observed on examination of the surface topography of the 3 W group followed by the 2 W group. The least changes were observed in association with the 1 W group in comparison to the control group. The EDX analysis showed the appearance of peaks of the oxygen and carbon elements after the lasing procedure with the highest percentage in the 3 W group. The average of the surface area of the created indentations significantly increased with increasing the power of the diode laser used (P < 0.05). CONCLUSIONS: The application of diode laser (940 nm) with 2 W and 3 W powers significantly altered the hydrophilicity, the surface topography, and the chemical composition of titanium discs. Diode laser (940 nm) with 1 W power can be safely used on SLA titanium implant surfaces with no damaging effect on the surface topography or hydrophilicity.

15.
Urologia ; 91(1): 154-158, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37334432

RESUMEN

INTRODUCTION: We aimed to assess the sexual and the reproductive functions in males post COVID-19 infection in Beni-Suef Governorate. METHODS: One hundred men were recruited in the current study. All participants were assessed by the Arabic validated version of the International Index of the Erectile Function 5 (ArIIEF-5), semen analysis, and Hospital Depression and Anxiety Scale (HADS). Finally, morning testosterone serum level was measured. RESULTS: There were significant decreases in the sperm total motility, the ArIIEF-5 score, and serum total testosterone in the post COVID-19 patients after 3 months when compared to the controls. However, there were significant increases in the sperm total motility, the ArIIEF-5 score, and serum total testosterone in the post COVID-19 patients after 6 months group when compared to the post COVID-19 patients after 3 months group. Moreover, there was a significant increase in the HADS score in the post COVID-19 patients after 3 months when compared to the controls. In contrast, there was a significant decrease in the HADS score in the post COVID-19 patients after 6 months when compared to the post COVID-19 patients after 3 months. CONCLUSION: Our study had shown temporary impairment of sexual and reproductive functions in post COVID-19 convalescent males especially after 6 months from the onset of the infection.


Asunto(s)
COVID-19 , Disfunción Eréctil , Humanos , Masculino , Estudios Transversales , Testosterona , Egipto , Semen
16.
Nat Prod Res ; : 1-8, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37990847

RESUMEN

Influenza is a contagious viral infection of the respiratory tract, affecting nearly 10% of the world's population, each year. The aim of this study was to extract and identify antiviral compounds against the influenza-A virus (H1N1) from different species of Egyptian marine algae. Three samples of marine macroalgae species were extracted and the antiviral activity of the extracts were tested on Madin Darby Canine Kidney cells. The bioactive compounds present in the most active fractions were identified using gas chromatography-mass spectrometry (GC-MS), then the binding potentials of the identified compounds were examined towards neuraminidase (NA) of the influenza-A virus using molecular docking. The methanolic extract of Sargassum aquifolium showed promising in-vitro antiviral activity with a selectivity index (SI) value of 101. The GC-MS analysis showed twelve compounds and the molecular docking analysis found that tetradecanoic acid showed the strongest binding affinities towards the NA enzyme.

17.
J Genet Eng Biotechnol ; 21(1): 145, 2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38012348

RESUMEN

BACKGROUND: Viral infections cause damage and long-term injury to infected human tissues, demanding therapy with antiviral and wound healing medications. Consequently, safe phytochemical molecules that may control viral infections with an ability to provide wound healing to viral-induced tissue injuries, either topically or systemically, are advantageous. Herein, we hypothesized that epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, might be effective as a wound healing, antiviral, and antifibrotic therapy. RESULTS: The antiviral activities of EGCG against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Herpes simplex virus type 2 (HSV-2) as well as its wound healing activities against different monolayer tissue (continuous and primary) systems were investigated. Consider its possible wound-healing advantages as well. To determine the safe concentrations of EGCG in green monkey kidney (Vero) and Vero-E6 cell lines, MTT assay was performed and showed high CC50 values of 405.1 and 322.9 µM, respectively. The antiviral activities of EGCG against SARS-CoV-2 and HSV-2, measured as half-maximal concentration 50 (IC50) concentrations, were 36.28 and 59.88 µM, respectively. These results confirm that the EGCG has remarkable viral inhibitory activities and could successfully suppress the replication of SARS-CoV-2 and HSV-2 in vitro with acceptable selectivity indices (SI) of 11.16 and 5.39, respectively. In parallel, the EGCG exhibits significant and dose/time-dependent anti-migration effects in human breast cancer cells (MCF-7), its resistant variation (MCF-7adr), and human skin fibroblast (HSF) indicating their potential to heal injuries in different internal and topical mammalian systems. CONCLUSIONS: The EGCG has proven to be an efficient antiviral against SARS-CoV-2 and HSV-2, as well as a wound-healing phytochemical. We assume that EGCG may be a promising option for slowing the course of acute cellular damage induced by systemic (Coronavirus Disease 2019 (COVID-19)) or topical (HSV-2) viral infections.

18.
Microorganisms ; 11(11)2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38004788

RESUMEN

Repurposing vitamins as antiviral supporting agents is a rapid approach used to control emerging viral infections. Although there is considerable evidence supporting the use of vitamin supplementation in viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the specific role of each vitamin in defending against coronaviruses remains unclear. Antiviral activities of available vitamins on the infectivity and replication of human coronaviruses, namely, SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), and human coronavirus 229E (HCoV-229E), were investigated using in silico and in vitro studies. We identified potential broad-spectrum inhibitor effects of Hydroxocobalamin and Methylcobalamin against the three tested CoVs. Cyanocobalamin could selectively affect SARS-CoV-2 but not MERS-CoV and HCoV-229E. Methylcobalamin showed significantly higher inhibition values on SARS-CoV-2 compared with Hydroxocobalamin and Cyanocobalamin, while Hydroxocobalamin showed the highest potent antiviral activity against MERS-CoV and Cyanocobalamin against HCoV-229E. Furthermore, in silico studies were performed for these promising vitamins to investigate their interaction with SARS-CoV-2, MERS-CoV, and HCoV-229E viral-specific cell receptors (ACE2, DPP4, and hAPN protein, respectively) and viral proteins (S-RBD, 3CL pro, RdRp), suggesting that Hydroxocobalamin, Methylcobalamin, and Cyanocobalamin may have significant binding affinity to these proteins. These results show that Methylcobalamin may have potential benefits for coronavirus-infected patients.

19.
Vaccines (Basel) ; 11(11)2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-38005960

RESUMEN

Despite the panzootic nature of emergent highly pathogenic avian influenza H5Nx viruses in wild migratory birds and domestic poultry, only a limited number of human infections with H5Nx viruses have been identified since its emergence in 1996. Few countries with endemic avian influenza viruses (AIVs) have implemented vaccination as a control strategy, while most of the countries have adopted a culling strategy for the infected flocks. To date, China and Egypt are the two major sites where vaccination has been adopted to control avian influenza H5Nx infections, especially with the widespread circulation of clade 2.3.4.4b H5N1 viruses. This virus is currently circulating among birds and poultry, with occasional spillovers to mammals, including humans. Herein, we will discuss the history of AIVs in Egypt as one of the hotspots for infections and the improper implementation of prophylactic and therapeutic control strategies, leading to continuous flock outbreaks with remarkable virus evolution scenarios. Along with current pre-pandemic preparedness efforts, comprehensive surveillance of H5Nx viruses in wild birds, domestic poultry, and mammals, including humans, in endemic areas is critical to explore the public health risk of the newly emerging immune-evasive or drug-resistant H5Nx variants.

20.
Sci Rep ; 13(1): 19193, 2023 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-37932329

RESUMEN

Infectious diseases trigger fear and anxiety among patients leading to disturbance in psychological health of patients. Psychological symptoms were found during SARS-COV-1 epidemic which raise the curiosity about their presence with SARS-COV-2 infection. The current study aimed to estimate the prevalence and severity of psychiatric disorders (depression, anxiety, and stress) among COVID-19 patients and their associated significant predictors. A cross-sectional study was conducted among 382 patients infected with COVID-19 in South Sinai governorate, Egypt, during the period June 2021 through January 2022. Patients with positive PCR test for COVID-19 were included if no more than 6 months have passed after being isolated in the hospital or at home. The patients were being contacted after being cured from COVID-19. The Arabic version of the Depression Anxiety Stress was used to assess the psychological status of patients. Multivariate linear regression analysis was done to detect the predictors of psychiatric symptoms among patients. A total of 382 participants with mean age of 41.5 ± 15.0 years old, of whom 72.5% were males were included in the study. 91.6% of participants had all the three studied psychological disorders; depression, anxiety and stress with most of participants had either severe or extremely severe conditions (13.9 and 75.7 for anxiety, 22.8 and 46.3% for depression, 38.5 and % 19.6 for stress, respectively). Healthcare workers had higher prevalence rates of depression, anxiety and stress. In bivariate analysis, educational level, HCWs and visiting healthcare facility were significantly affecting DASS scores. In linear regression analysis, hospital admission was the main predictor of the three psychological disorders. In Conclusion, majority of patients affected with COVID-19 suffered from symptoms of anxiety, depression and stress within six months after being infected. Hospital admission was found to be the main predictor of the presence of psychiatric disorders with prolonged recovery time from COVID-19 infection. More attention should be paid to COVID-19 patient's mental health as psychological care and presence of psychiatric in the isolation hospitals should be considered.


Asunto(s)
COVID-19 , Masculino , Humanos , Adulto , Persona de Mediana Edad , Femenino , Depresión/psicología , Prevalencia , Estudios Transversales , Egipto , SARS-CoV-2 , Encuestas y Cuestionarios , Ansiedad/psicología , Personal de Salud/psicología , Estrés Psicológico/psicología
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