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1.
PLoS Pathog ; 17(3): e1009413, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33705496

RESUMO

SARS-CoV-2 virus is transmitted in closed settings to people in contact with COVID-19 patients such as healthcare workers and household contacts. However, household person-to-person transmission studies are limited. Households participating in an ongoing cohort study of influenza incidence and prevalence in rural Egypt were followed. Baseline enrollment was done from August 2015 to March 2017. The study protocol was amended in April 2020 to allow COVID-19 incidence and seroprevalence studies. A total of 290 households including 1598 participants were enrolled and followed from April to October 2020 in four study sites. When a participant showed respiratory illness symptoms, a serum sample and a nasal and an oropharyngeal swab were obtained. Swabs were tested by RT-PCR for SARS-CoV-2 infection. If positive, the subject was followed and swabs collected on days three, six, nine, and 14 after the first swab day and a serum sample obtained on day 14. All subjects residing with the index case were swabbed following the same sampling schedule. Sera were collected from cohort participants in October 2020 to assess seroprevalence. Swabs were tested by RT-PCR. Sera were tested by Microneutralization Assay to measure the neutralizing antibody titer. Incidence of COVID-19, household secondary attack rate, and seroprevalence in the cohort were determined. The incidence of COVID-19 was 6.9% and the household secondary attack rate was 89.8%. Transmission within households occurred within two-days of confirming the index case. Infections were asymptomatic or mild with symptoms resolving within 10 days. The majority developed a neutralizing antibody titer by day 14 post onset. The overall seroprevalence among cohort participants was 34.8%. These results suggest that within-household transmission is high in Egypt. Asymptomatic or mild illness is common. Most infections seroconvert and have a durable neutralizing antibody titer.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/transmissão , Adolescente , Adulto , COVID-19/sangue , COVID-19/epidemiologia , COVID-19/virologia , Criança , Estudos de Coortes , Egito/epidemiologia , Família , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/fisiologia , Estudos Soroepidemiológicos , Adulto Jovem
2.
Anim Biotechnol ; 34(7): 2657-2673, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35981058

RESUMO

This study investigated the role of ξ Potential on Monometallic (MM) and Bimetallic (BM) Calcium Oxide/Magnetite Iron Oxides nanoparticles to stimulate the immune response. Metallic nanoparticles (MNPs) were biosynthesis using Pseudomonas fluorescens S48. MNPs characterization was carried out by UV-Vis spectra, XRD analysis, Zeta potential and Particles size, SEM-EDS, and TEM, and the concentrations were calculated by ICP-AES. The immune system activity was measured by estimation of lymphocytes transformation, phagocytic activity. The end point was in evaluating the toxicity of Metallic NPs by comet assay. SEM-EDS and TEM micrographs showed that MM CaO and Fe3O4 represent a perfect example of zero-dimensional (0-D) NPs with cubic and spherical particles in shape, while BM CaO/Fe3O4 NPs appeared in the form of Core-shell structure. The variations effect of novelty MM, BM CaO/Fe3O4 NPs in enhancing immune activity were based on the ξ Potential whereas negatively and positively charged. These findings demonstrate that the cationic CaO/Fe3O4 NPs are inefficient in stimulating the immune system which causes a high cytotoxic effect. But the anionic CaO/Fe3O4 NPs have advantages in targeting the immune system because of enhanced delivery to the cells through adsorptive endocytosis as well as the half-life clearance from the blood.


Assuntos
Óxido Ferroso-Férrico , Nanopartículas de Magnetita , Animais , Óxido Ferroso-Férrico/química , Óxidos , Nanopartículas de Magnetita/química , Imunidade
3.
Anim Biotechnol ; 34(7): 2582-2595, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35930359

RESUMO

Sperm motility, normal morphology, viability, spermatozoa DNA damage, and lipid peroxidation are all affected by semen cryopreservation. The goal of this study was to see how effective cupric oxide nanoparticles (CuONPs) are as a cryo-extender additive on post-thawed sperm parameters. An artificial vagina was used to collect semen samples from five mature Zaraibi bucks (2-3 years). Ejaculates were pooled and separated into two fractions (A&B), a fraction (A) was left without being centrifuged and a fraction (B) was centrifuged to remove seminal plasma. Both fractions were diluted with tris egg yolk citrate extender (TECE) and then divided into five equal aliquots, each supplemented with (0, 10, 20, 40, and 60 ppm/ml) CuONPs. The findings revealed that removing seminal plasma before cryopreservation harms sperm parameters. Sperm motility, viability index, membrane integrity, biochemical antioxidant marker, DNA integrity, and MDA level improved after supplementation with CuONPs up to 60 ppm/ml, the most prominent significant positive effect was obtained with the highest dose (60 ppm/ml) without removal of the seminal plasm compared to control group. In conclusion: The presence of seminal plasma with a high concentration of CuONPs (up to 60 ppm/ml) may help to mitigate the negative effects of cryo-preservation.


Assuntos
Nanopartículas , Preservação do Sêmen , Feminino , Masculino , Animais , Sêmen , Cabras , Motilidade dos Espermatozoides , Preservação do Sêmen/veterinária , Espermatozoides , Criopreservação/veterinária , Crioprotetores/farmacologia
4.
Chem Biodivers ; 20(4): e202201045, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36811152

RESUMO

Cestrum diurnum L. (Solanaceae) is a fragrant ornamental tree cultivated in different parts around the world. In this study, the essential oil (EO) of the aerial parts was extracted by hydrodistillation (HD), steam distillation (SD) and microwave-assisted hydro-distillation (MAHD). GC/MS analysis of the three EOs revealed that phytol represents the major component in SD-EO and MAHD-EO (40.84 and 40.04 %, respectively); while in HD-EO it only represented 15.36 %. The SD-EO showed a strong antiviral activity against HCoV-229E with IC50 of 10.93 µg/mL, whereas, MAHD-EO and HD-EO showed a moderate activity with IC50 values of 119.9 and 148.2 µg/mL, respectively. The molecular docking of EO major components: phytol, octadecyl acetate and tricosane showed a strong binding to coronavirus 3-CL (pro). Moreover, the three EOs (50 µg/mL) decreased the levels of NO, IL-6 and TNF-α and suppressed IL-6 and TNF-α gene expression in LPS-induced inflammation model in RAW264.7 macrophage cell lines.


Assuntos
Cestrum , Coronavirus Humano 229E , Óleos Voláteis , Cestrum/química , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Interleucina-6 , Lipopolissacarídeos/farmacologia , Simulação de Acoplamento Molecular , Óleos Voláteis/química , Extratos Vegetais/química , Fator de Necrose Tumoral alfa , Antivirais/química , Antivirais/farmacologia
5.
Molecules ; 28(10)2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37241923

RESUMO

Infectious diseases caused by viruses and bacteria are a major public health concern worldwide, with the emergence of antibiotic resistance, biofilm-forming bacteria, viral epidemics, and the lack of effective antibacterial and antiviral agents exacerbating the problem. In an effort to search for new antimicrobial agents, this study aimed to screen antibacterial and antiviral activity of the total methanol extract and its various fractions of Pulicaria crispa (P. crispa) aerial parts. The P. crispa hexane fraction (HF) was found to have the strongest antibacterial effect against both Gram-positive and Gram-negative bacteria, including biofilm producers. The HF fraction reduced the expression levels of penicillin binding protein (PBP2A) and DNA gyrase B enzymes in Staphylococcus aureus and Pseudomonas aeruginosa, respectively. Additionally, the HF fraction displayed the most potent antiviral activity, especially against influenza A virus, affecting different stages of the virus lifecycle. Gas chromatography/mass spectrometry (GC/MS) analysis of the HF fraction identified 27 compounds, mainly belonging to the sterol class, with ß-sitosterol, phytol, stigmasterol, and lupeol as the most abundant compounds. The in silico study revealed that these compounds were active against influenza A nucleoprotein and polymerase, PBP2A, and DNA gyrase B. Overall, this study provides valuable insights into the chemical composition and mechanism of action of the P. crispa HF fraction, which may lead to the development of more effective treatments for bacterial and viral infections.


Assuntos
Asteraceae , Pulicaria , Vírus , Antibacterianos/farmacologia , Antibacterianos/química , Antivirais/farmacologia , Pulicaria/química , DNA Girase/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Testes de Sensibilidade Microbiana , Bactérias , Biofilmes , Extratos Vegetais/farmacologia , Extratos Vegetais/química
6.
Wound Repair Regen ; 30(4): 448-452, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35470510

RESUMO

Pemphigus vulgaris (PV) is an autoimmune bullous skin disease. Aquaporin 3 (AQP3) is a glycerol/water channel involved in several physiological functions. Evaluation of the tissue expression and localization of AQP3 in the skin of PV patients. Twenty-seven PV patients and 30 controls were included. The patients were subjected to history taking, clinical evaluation, Autoimmune Bullous Skin Disorder Intensity Score and 4-mm punch biopsy. The biopsies were stained using anti-human AQP3 antibody and the immunofluorescence pattern and intensity were evaluated using a scoring system and ImageJ software analysis. AQP3 was expressed in the basal epidermis in 27 (100%) and in the suprabasal epidermis in 19 PV patients (70.4%). It was expressed in all controls in basal and suprabasal layers. Intensity of AQP3 immunofluorescence was strong in 2 (7.4%), moderate in 19 (70.4%) and weak in 6 patients (22.2%) while it was strong in 18 (60%) and moderate in 12 controls (40%). AQP3 expression was significantly lower in patients than controls in the suprabasal epidermis (p = 0.001). Patients with extensive disease had significantly weaker AQP3 intensity than those with marked disease (p = 0.005) Downregulation of AQP3 in patients with PV, especially in the suprabasal layers and in extensive clinical disease, suggests a potential role of AQP3 in the pathogenesis of PV.


Assuntos
Aquaporina 3 , Doenças Autoimunes , Pênfigo , Dermatopatias , Aquaporina 3/genética , Aquaporina 3/metabolismo , Doenças Autoimunes/patologia , Regulação para Baixo , Epiderme/patologia , Humanos , Pênfigo/metabolismo , Pênfigo/patologia , Dermatopatias/metabolismo , Dermatopatias/patologia , Cicatrização
7.
Molecules ; 27(18)2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36144662

RESUMO

We synthesized a set of small molecules using a molecular hybridization approach with good yields. The antiviral properties of the synthesized conjugates against the SAR-CoV-2 virus were investigated and their cytotoxicity was also determined. Among all the synthesized conjugates, compound 9f showed potential against SARS-CoV-2 and low cytotoxicity. The conjugates' selectivity indexes (SIs) were determined to correlate the antiviral properties and cytotoxicity. The observed biological data were further validated using computational studies.


Assuntos
Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , Antivirais/uso terapêutico , Humanos , Simulação de Acoplamento Molecular
8.
Dermatology ; 237(6): 896-901, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33091918

RESUMO

BACKGROUND: Lichen planus (LP) is a chronic autoimmune inflammatory mucocutaneous disease. Interleukin (IL)-17 is the signature cytokine of T-helper 17 cells, involved in the aetiology of many autoimmune and inflammatory disorders. Vitamin D has an immune-regulatory role and suppresses IL-17 production via direct transcriptional inhibition of IL-17 gene expression. OBJECTIVE: To explore the relationship of IL-17 and vitamin D levels with LP, and the possible inter-relationship between IL-17 and vitamin D. METHODS: The study enrolled 30 patients with LP and 30 healthy controls. Blood samples and skin biopsies were taken from all participants for evaluation of serum vitamin D, and serum and tissue IL-17 levels using enzyme-linked immunosorbent assay (ELISA). RESULTS: Patients had significantly higher serum and tissue IL-17 (p < 0.001 for both), as well as significantly lower serum vitamin D levels and more deficient patterns of vitamin D status than controls (p < 0.001 for both). In the patient group, there was a statistically significant positive correlation between extent of the disease and serum IL-17. There was no direct statistical correlation between IL-17 levels and serum vitamin D in either patients or controls. CONCLUSION: This study confirms a previously suggested role of IL-17 in the pathogenesis of LP and suggests its relation to the extent and severity of the disease. We also found an association between vitamin D deficiency and LP. However, a direct relationship between IL-17 and vitamin D deficiency could not be clarified.


Assuntos
Interleucina-17/metabolismo , Líquen Plano/metabolismo , Vitamina D/sangue , Adulto , Idoso , Estudos de Casos e Controles , Egito , Feminino , Humanos , Líquen Plano/etiologia , Líquen Plano/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Adulto Jovem
9.
Lasers Surg Med ; 53(4): 482-487, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32865828

RESUMO

BACKGROUND AND OBJECTIVES: Primary cutaneous amyloidosis (PCA) is a pruritic disease characterized by amyloid deposition in the skin. Interleukin-31 (IL-31) is a pruritus-mediating cytokine. Fractional carbon dioxide (CO2 ) laser has shown efficacy in the treatment of PCA regarding the clinical appearance, histological pattern, and pruritus. The aim of this study is to assess the effect of fractional CO2 laser on pruritus associated with PCA, and analyze whether this effect is related to IL-31 and IL-31 receptor (R) expression. STUDY DESIGN/MATERIALS AND METHODS: The study included 24 patients with PCA and 24 healthy controls. Each patient received four fractional CO2 laser sessions, 4 weeks apart, using the superficial ablative mode. Skin biopsies were taken from patients before and after treatment, as well as controls, for assessment of IL-31 and IL-31R by real-time polymerase chain reaction. RESULTS: Treatment resulted in significant improvement of all clinical parameters, including pruritus (P < 0.001). Patients before treatment had significantly higher IL-31 and IL-31R than controls (P = 0.000 for both). In addition, there was a statistically significant decrease in IL-31 and IL-31R after treatment than their values before treatment (P = 0.000 for both). CONCLUSION: This study confirms the therapeutic efficacy of fractional CO2 laser in treatment of PCA. Reduction of IL-31 and its receptor seems to be one of the involved mechanisms; however, its relation to improvement of pruritus is still not clear. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.


Assuntos
Amiloidose Familiar , Lasers de Gás , Dermatopatias Genéticas , Humanos , Lasers de Gás/uso terapêutico , Prurido/etiologia , Resultado do Tratamento
10.
Dermatol Surg ; 47(11): 1480-1485, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34468410

RESUMO

BACKGROUND/OBJECTIVES: Microneedling has shown satisfactory effects in scar rejuvenation. Comparisons of its results with fractional laser are limited. This study aims to compare the efficacy and safety of automated microneedling versus fractional carbon dioxide (CO2) laser in treatment of traumatic scars on clinical and histochemical bases. MATERIALS AND METHODS: Thirty patients with traumatic facial scars were randomized to treatment with 4 monthly sessions of either automated microneedling or fractional CO2 laser. Assessment of scars was performed at baseline and 3 months after the last treatment session, clinically by the modified Vancouver Scar Scale (mVSS) and histochemically by quantitative assessment of collagen and elastic fibers. RESULTS: Both groups showed improvement in mVSS, collagen, and elastin contents after treatment. Percentage improvement of collagen and elastin content was higher after treatment by a laser compared with microneedling, in case of the collagen content. Percentage increase in the collagen content after treatment was higher in atrophic scars of the laser group than those of the microneedling group. CONCLUSION: In this small study, microneedling was as safe as fractional CO2 laser for rejuvenation of traumatic scars with comparable clinical effects. Fractional CO2 laser is more powerful in stimulating neocollagenesis. Automated microneedling is effective for treatment of hypertrophic scars.


Assuntos
Cicatriz/terapia , Técnicas Cosméticas , Lasers de Gás/uso terapêutico , Atrofia , Cicatriz/etiologia , Cicatriz/patologia , Cicatriz Hipertrófica/etiologia , Cicatriz Hipertrófica/terapia , Técnicas Cosméticas/efeitos adversos , Técnicas Cosméticas/instrumentação , Face , Humanos , Lasers de Gás/efeitos adversos , Agulhas , Estudos Prospectivos , Método Simples-Cego , Pele/lesões , Resultado do Tratamento
11.
Int J Mol Sci ; 22(16)2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34445763

RESUMO

Unfortunately, COVID-19 is still a threat to humankind and has a dramatic impact on human health, social life, the world economy, and food security. With the limited number of suggested therapies under clinical trials, the discovery of novel therapeutic agents is essential. Here, a previously identified anti-SARS-CoV-2 compound named Compound 13 (1,2,5-Oxadiazole-3-carboximidic acid, 4,4'-(methylenediimino) bis,bis[[(2-hydroxyphenyl)methylene]hydrazide) was subjected to an iterated virtual screening against SARS-CoV-2 Mpro using a combination of Ligand Designer and PathFinder. PathFinder, a computational reaction enumeration tool, was used for the rapid generation of enumerated structures via default reaction library. Ligand designer was employed for the computerized lead optimization and selection of the best structural modification that resulted in a favorable ligand-protein complex. The obtained compounds that showed the best binding to Mpro were re-screened against TMPRSS2, leading to the identification of 20 shared compounds. The compounds were further visually inspected, which resulted in the identification of five shared compounds M1-5 with dual binding affinity. In vitro evaluation and enzyme inhibition assay indicated that M3, an analogue of Compound 13 afforded by replacing the phenolic moiety with pyridinyl, possesses an improved antiviral activity and safety. M3 displayed in vitro antiviral activity with IC50 0.016 µM and Mpro inhibition activity with IC50 0.013 µM, 7-fold more potent than the parent Compound 13 and potent than the antivirals drugs that are currently under clinical trials. Moreover, M3 showed potent activity against human TMPRSS2 and furin enzymes with IC50 0.05, and 0.08 µM, respectively. Molecular docking, WaterMap analysis, molecular dynamics simulation, and R-group analysis confirmed the superiority of the binding fit to M3 with the target enzymes. WaterMap analysis calculated the thermodynamic properties of the hydration site in the binding pocket that significantly affects the biological activity. Loading M3 on zinc oxide nanoparticles (ZnO NPs) increased the antiviral activity of the compound 1.5-fold, while maintaining a higher safety profile. In conclusion, lead optimized discovery following an iterated virtual screening in association with molecular docking and biological evaluation revealed a novel compound named M3 with promising dual activity against SARS-CoV-2. The compound deserves further investigation for potential clinical-based studies.


Assuntos
Antivirais/farmacologia , Tratamento Farmacológico da COVID-19 , Proteases 3C de Coronavírus/antagonistas & inibidores , Descoberta de Drogas/métodos , Inibidores de Proteases/farmacologia , Antivirais/uso terapêutico , COVID-19/virologia , Proteases 3C de Coronavírus/metabolismo , Ensaios Enzimáticos , Humanos , Concentração Inibidora 50 , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores de Proteases/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/enzimologia , Serina Endopeptidases/metabolismo
12.
Molecules ; 26(20)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34684763

RESUMO

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, the causative agent of coronavirus disease (COVID-19)) has caused relatively high mortality rates in humans throughout the world since its first detection in late December 2019, leading to the most devastating pandemic of the current century. Consequently, SARS-CoV-2 therapeutic interventions have received high priority from public health authorities. Despite increased COVID-19 infections, a vaccine or therapy to cover all the population is not yet available. Herein, immunoinformatics and custommune tools were used to identify B and T-cells epitopes from the available SARS-CoV-2 sequences spike (S) protein. In the in silico predictions, six B cell epitopes QTGKIADYNYK, TEIYQASTPCNGVEG, LQSYGFQPT, IRGDEVRQIAPGQTGKIADYNYKLPD, FSQILPDPSKPSKRS and PFAMQMAYRFNG were cross-reacted with MHC-I and MHC-II T-cells binding epitopes and selected for vaccination in experimental animals for evaluation as candidate vaccine(s) due to their high antigenic matching and conserved score. The selected six peptides were used individually or in combinations to immunize female Balb/c mice. The immunized mice raised reactive antibodies against SARS-CoV-2 in two different short peptides located in receptor binding domain and S2 region. In combination groups, an additive effect was demonstrated in-comparison with single peptide immunized mice. This study provides novel epitope-based peptide vaccine candidates against SARS-CoV-2.


Assuntos
Vacinas contra COVID-19/química , COVID-19/prevenção & controle , Epitopos de Linfócito B/química , Epitopos de Linfócito T/química , SARS-CoV-2/metabolismo , Sequência de Aminoácidos , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/metabolismo , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/metabolismo , Feminino , Humanos , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos/química , Peptídeos/imunologia , Peptídeos/metabolismo , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo
13.
Molecules ; 26(21)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34770969

RESUMO

Flavonoids are important secondary plant metabolites that have been studied for a long time for their therapeutic potential in inflammatory diseases because of their cytokine-modulatory effects. Five flavonoid aglycones were isolated and identified from the hydrolyzed aqueous methanol extracts of Anastatica hierochuntica L., Citrus reticulata Blanco, and Kickxia aegyptiaca (L.) Nabelek. They were identified as taxifolin (1), pectolinarigenin (2), tangeretin (3), gardenin B (4), and hispidulin (5). These structures were elucidated based on chromatographic and spectral analysis. In this study, molecular docking studies were carried out for the isolated and identified compounds against SARS-CoV-2 main protease (Mpro) compared to the co-crystallized inhibitor of SARS-CoV-2 Mpro (α-ketoamide inhibitor (KI), IC50 = 66.72 µg/mL) as a reference standard. Moreover, in vitro screening against SARS-CoV-2 was evaluated. Compounds 2 and 3 showed the highest virus inhibition with IC50 12.4 and 2.5 µg/mL, respectively. Our findings recommend further advanced in vitro and in vivo studies of the examined isolated flavonoids, especially pectolinarigenin (2), tangeretin (3), and gardenin B (4), either alone or in combination with each other to identify a promising lead to target SARS-CoV-2 effectively. This is the first report of the activity of these compounds against SARS-CoV-2.


Assuntos
Proteases 3C de Coronavírus/efeitos dos fármacos , Flavonas/farmacologia , SARS-CoV-2/efeitos dos fármacos , Animais , Antivirais/farmacologia , Brassicaceae/metabolismo , Chlorocebus aethiops , Cromonas/farmacologia , Proteases 3C de Coronavírus/metabolismo , Descoberta de Drogas/métodos , Flavonas/metabolismo , Flavonoides/farmacologia , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Extratos Vegetais/farmacologia , Inibidores de Proteases/química , Quercetina/análogos & derivados , Quercetina/farmacologia , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidade , Células Vero , Tratamento Farmacológico da COVID-19
14.
Molecules ; 26(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34641388

RESUMO

In response to the urgent need to control Coronavirus disease 19 (COVID-19), this study aims to explore potential anti-SARS-CoV-2 agents from natural sources. Moreover, cytokine immunological responses to the viral infection could lead to acute respiratory distress which is considered a critical and life-threatening complication associated with the infection. Therefore, the anti-viral and anti-inflammatory agents can be key to the management of patients with COVID-19. Four bioactive compounds, namely ferulic acid 1, rutin 2, gallic acid 3, and chlorogenic acid 4 were isolated from the leaves of Pimenta dioica (L.) Merr (ethyl acetate extract) and identified using spectroscopic evidence. Furthermore, molecular docking and dynamics simulations were performed for the isolated and identified compounds (1-4) against SARS-CoV-2 main protease (Mpro) as a proposed mechanism of action. Furthermore, all compounds were tested for their half-maximal cytotoxicity (CC50) and SARS-CoV-2 inhibitory concentrations (IC50). Additionally, lung toxicity was induced in rats by mercuric chloride and the effects of treatment with P. dioca aqueous extract, ferulic acid 1, rutin 2, gallic acid 3, and chlorogenic acid 4 were recorded through measuring TNF-α, IL-1ß, IL-2, IL-10, G-CSF, and genetic expression of miRNA 21-3P and miRNA-155 levels to assess their anti-inflammatory effects essential for COVID-19 patients. Interestingly, rutin 2, gallic acid 3, and chlorogenic acid 4 showed remarkable anti-SARS-CoV-2 activities with IC50 values of 31 µg/mL, 108 µg/mL, and 360 µg/mL, respectively. Moreover, the anti-inflammatory effects were found to be better in ferulic acid 1 and rutin 2 treatments. Our results could be promising for more advanced preclinical and clinical studies especially on rutin 2 either alone or in combination with other isolates for COVID-19 management.


Assuntos
Anti-Inflamatórios/farmacologia , Antivirais/farmacologia , Tratamento Farmacológico da COVID-19 , Pimenta , Extratos Vegetais/farmacologia , SARS-CoV-2/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Antivirais/química , Chlorocebus aethiops , Ácido Clorogênico/isolamento & purificação , Ácido Clorogênico/farmacologia , Ácidos Cumáricos/isolamento & purificação , Ácidos Cumáricos/farmacologia , Ácido Gálico/isolamento & purificação , Ácido Gálico/farmacologia , Humanos , Masculino , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Pimenta/química , Extratos Vegetais/química , Ratos , Rutina/isolamento & purificação , Rutina/farmacologia , Células Vero
15.
Indian J Crit Care Med ; 25(1): 29-33, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33603298

RESUMO

INTRODUCTION: Hydrocortisone showed to be effective in reducing the time until reversal of shock when added to standard therapy in managing septic shock. Hyperglycemia is one of the common adverse effects associated with corticosteroid treatment. However, the difference in hyperglycemia risk with different methods of hydrocortisone administration is not clear. The objective of this study was to evaluate the risk of hyperglycemia of intermittent hydrocortisone boluses vs continuous infusion in septic shock patients. MATERIALS AND METHODS: This was a retrospective observational study. Data were collected from the electronic medical records of eligible patients admitted to intensive care units. All patients admitted with septic shock who received noradrenaline and hydrocortisone were included. Only patients who exceeded 200 mg/day of hydrocortisone were excluded. The primary outcome was mean blood glucose. RESULTS: A total of 108 patients (with 3,021 blood glucose readings) were included in the final analysis. Seventy-six patients received hydrocortisone as intermittent boluses (70.3%), and 32 patients (29.7%) received continuous infusion. For the primary outcome, no statistically or clinically significant difference was found in the blood glucose estimated marginal mean: 8.58 mmol/L (95% confidence interval [CI]; 8.01-9.16) in the bolus group and 8.9 mmol/L (95% CI; 7.99-9.82) in the infusion group with a mean difference of 0.32 mmol/L (95% CI; -0.77 to 1.41). For secondary outcomes, no difference was found between the two groups in mortality, length of stay, reversal of shock, or hypoglycemic events. CONCLUSION: Intermittent boluses of hydrocortisone were not associated with a higher risk of hyperglycemia than continuous infusion in septic shock patients. HOW TO CITE THIS ARTICLE: Mitwally H, Saad MO, Mahmoud S, Mohamed A. Hyperglycemia Risk Evaluation of Hydrocortisone Intermittent Boluses vs Continuous Infusion in Septic Shock: A Retrospective Study. Indian J Crit Care Med 2021;25(1):29-33.

16.
J Virol ; 93(2)2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30381492

RESUMO

Recently, two genetically distinct influenza viruses were detected in bats in Guatemala and Peru. We conducted influenza A virus surveillance among four bat species in Egypt. Out of 1,202 swab specimens, 105 were positive by real-time PCR. A virus was successfully isolated in eggs and propagated in MDCK cells in the presence of N-tosyl-l-phenylalanine chloromethyl ketone-treated trypsin. Genomic analysis revealed that the virus was phylogenetically distinct from all other influenza A viruses. Analysis of the hemagglutinin gene suggested a common ancestry with other H9 viruses, and the virus showed a low level of cross-reactivity with serum raised against H9N2 viruses. Bats were seropositive for the isolated viruses. The virus replicated in the lungs of experimentally infected mice. While it is genetically distinct, this virus shares several avian influenza virus characteristics suggesting a more recent avian host origin.IMPORTANCE Through surveillance, we isolated and characterized an influenza A virus from Egyptian fruit bats. This virus had an affinity to avian-like receptors but was also able to infect mice. Our findings indicate that bats may harbor a diversity of influenza A viruses. Such viruses may have the potential to cross the species barrier to infect other species, including domestic birds, mammals, and, possibly, humans.


Assuntos
Quirópteros/virologia , Vírus da Influenza A/classificação , Infecções por Orthomyxoviridae/imunologia , RNA Viral/genética , Análise de Sequência de RNA/métodos , Animais , Anticorpos Antivirais/metabolismo , Galinhas , Cães , Egito , Vírus da Influenza A/genética , Vírus da Influenza A/isolamento & purificação , Pulmão/virologia , Células Madin Darby de Rim Canino , Infecções por Orthomyxoviridae/virologia , Filogenia
17.
Arch Virol ; 162(3): 687-700, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27864633

RESUMO

Highly pathogenic avian influenza (HPAI) H5N1 influenza viruses emerged as a human pathogen in 1997 with expected potential to undergo sustained human-to-human transmission and pandemic viral spread. HPAI H5N1 is endemic in Egyptian poultry and has caused sporadic human infection. The first outbreak in early 2006 was caused by clade 2.2 viruses that rapidly evolved genetically and antigenically. A sharp increase in the number of human cases was reported in Egypt in the 2014/2015 season. In this study, we analyzed and characterized three isolates of HPAI H5N1 viruses isolated from infected humans in Egypt in 2014/2015. Phylogenetic analysis demonstrated that the nucleotide sequences of eight segments of the three isolates were clustered with those of members of clade 2.2.1.2. We also found that the human isolates from 2014/2015 had a slight, non-significant difference in their affinity for human-like sialic acid receptors. In contrast, they showed significant differences in their replication kinetics in MDCK, MDCK-SIAT, and A549 cells as well as in embryonated chicken eggs. An antiviral bioassay study revealed that all of the isolates were susceptible to amantadine. Therefore, further investigation and monitoring is required to correlate the genetic and/or antigenic changes of the emerging HPAI H5N1 viruses with possible alteration in their characteristics and their potential to become a further threat to public health.


Assuntos
Virus da Influenza A Subtipo H5N1/isolamento & purificação , Influenza Humana/virologia , Doenças das Aves Domésticas/virologia , Animais , Galinhas , Surtos de Doenças , Egito/epidemiologia , Humanos , Virus da Influenza A Subtipo H5N1/classificação , Virus da Influenza A Subtipo H5N1/genética , Virus da Influenza A Subtipo H5N1/patogenicidade , Influenza Humana/epidemiologia , Filogenia , Aves Domésticas , Doenças das Aves Domésticas/epidemiologia , Virulência
18.
Australas J Dermatol ; 58(2): e36-e39, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-26437741

RESUMO

Proopiomelanocortin (POMC) and melanocortin 1 receptor (MC1R) are regulators of melanogenesis and pigmentation. Our objective was to estimate their levels, searching for a possible role of the melanocortin system in vitiligo. This study included 40 vitiligo patients and 40 controls. Skin biopsies were taken from lesional and non-lesional skin of patients and from the non-sun exposed skin of controls to detect the expression of POMC and MC1R using quantitative real-time polymerase chain reaction. Both factors were significantly lower in lesional than non-lesional skin and controls, while they were significantly higher in non-lesional skin than in controls. There was a statistically significant positive correlation between lesional levels of POMC and MC1R, as well as between non-lesional levels of POMC and MC1R in the patients. On the other hand, we found a statistically significant negative correlation between the lesional and non-lesional levels of POMC, as well as between the lesional and non-lesional levels of MC1R in the patients. As a conclusion, the melanocortin system could play a role in the pathogenesis of vitiligo or could be affected as the end result of the disease.


Assuntos
Pró-Opiomelanocortina/genética , Receptor Tipo 1 de Melanocortina/genética , Vitiligo/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Pele , Vitiligo/patologia , Adulto Jovem
19.
J Clin Pediatr Dent ; 41(2): 120-125, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28288289

RESUMO

AIM: To assess the effect of four different children's drinks on color stability of resin dental composites. STUDY DESIGN: A total of one hundred and twenty specimens were prepared from Grandio SO, Filtek Z350 XT and Filtek Z250 XT (forty specimens each). Specimens were thermocycled, then each group was further subdivided into four subgroups (n=10) according to the immersion media which were chocolate milk, mango juice, orange fizzy drink, and water (control). The initial color parameters of each specimen were recorded before immersion (baseline) and color change values were recorded three and seven days after immersion in each solution using a digital spectrophotometer. Atomic force microscope was used to measure the surface roughness in randomly selected samples after one week immersion in children's drinks. RESULTS: All the children's drinks produced color changes in the examined resin dental composites, yet there was no statistical significant difference between the effects of tested drinks on the color changes (mean ΔE) of the three different dental composites (P>0.05). CONCLUSIONS: All tested children's drinks caused clinically unacceptable color changes of the tested resin dental composites. Immersion in chocolate milk and orange fizzy led to the highest color changes in the tested resin dental composites.


Assuntos
Bebidas , Resinas Compostas/química , Cor , Humanos , Espectrofotometria , Propriedades de Superfície
20.
J Phys Ther Sci ; 28(4): 1142-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27190442

RESUMO

[Purpose] Interprofessional education (IPE) is an important academic approach for preparing health-care professionals to provide patient care in a collaborative team environment. This study aimed to measure the perceptions and readiness toward IPE among female undergraduate health-care students at King Saud University (KSU). [Subjects and Methods] A cross-sectional study carried out using a survey in the form of an electronic questionnaire: The Readiness for Interprofessional Learning Scale (RIPLS). The questionnaire was distributed to the students via e-mail and social media networks. [Results] The RIPLS was completed by 296 female health-care students at KSU who valued the importance of IPE. The differences between health-care disciplines in the perceptions and readiness toward IPE were statistically significant, but there were no differences between students of different years of study in their perception and readiness toward IPE. [Conclusion] Administering a course of interprofessional teamwork in the health-care curriculum is a major challenge for the clinical education community. IPE offers an opportunity to address the multi-disciplinary concept in hospitals. Our findings indicate that undergraduate health-care students have high perception and readiness toward IPE.

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