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Herpes simplex virus type 1 (HSV-1) infection of the eyes results in herpes simplex keratitis (HSK), which has led to vision loss and even blindness in patients. However, the rate of drug resistance in HSV is on the rise; therefore, new antiviral agents with sufficient safety profiles must be developed. At present, we assessed the anti-HSV-1 activity of 502 natural compounds and their ability to reduce the HSV-1-induced cytopathic effect. We chose harmol for further studies because it exhibited the highest antiviral activity. We found that harmol inhibited both HSV-1 F and HSV-1/153 (a clinical drug-resistant strain) replication, with an EC50 of 9.34 µM and 5.84 µM, respectively. Moreover, harmol reduced HSV-1 replication in corneal tissues and viral progeny production in tears, and also alleviated early corneal surface lesions related to HSK. For example, harmol treatment preserved corneal thickness and nerve density in HSK mice. Interestingly, harmol also showed a promising antiviral effect on HSV-1/153 induced HSK in mouse model. Furthermore, harmol combined with acyclovir (ACV) treatment showed a greater antiviral effect than either one alone in vitro. Therefore, harmol may be a promising therapeutic agent for managing HSK.
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Antivirais , Modelos Animais de Doenças , Herpesvirus Humano 1 , Ceratite Herpética , Replicação Viral , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Ceratite Herpética/tratamento farmacológico , Ceratite Herpética/virologia , Camundongos , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/fisiologia , Replicação Viral/efeitos dos fármacos , Aciclovir/farmacologia , Aciclovir/uso terapêutico , Córnea/virologia , Córnea/efeitos dos fármacos , Córnea/patologia , Chlorocebus aethiops , Humanos , Feminino , Células Vero , Camundongos Endogâmicos BALB CRESUMO
Herpes simplex virus type 1 (HSV-1) is a widely disseminated virus that establishes latency in the brain and causes occasional but fatal herpes simplex encephalitis. Currently, acyclovir (ACV) is the main clinical drug used in the treatment of HSV-1 infection, and the failure of therapy in immunocompromised patients caused by ACV-resistant HSV-1 strains necessitates the requirement to develop novel anti-HSV-1 drugs. Artemisia argyi, a Traditional Chinese Medicine, has been historically used to treat inflammation, bacterial infection, and cancer. In this study, we demonstrated the antiviral effect and mechanism of ethanol extract of A. argyi leaves (hereafter referred to as 'AEE'). We showed that AEE at 10 µg/ml exhibits potent antiviral effects on both normal and ACV-resistant HSV-1 strains. AEE also inhibited the infection of HSV-2, rotavirus, and influenza virus. Transmission electron microscopy revealed that AEE destroys the membrane integrity of HSV-1 viral particles, resulting in impaired viral attachment and penetration. Furthermore, mass spectrometry assay identified 12 major components of AEE, among which two new flavones, deoxysappanone B 7,3'-dimethyl ether, and 3,7-dihydroxy-3',4'-dimethoxyflavone, exhibited the highest binding affinity to HSV-1 glycoprotein gB at the surface site critical for gB-gH-gL interaction and gB-mediated membrane fusion, suggesting their involvement in inactivating virions. Therefore, A. argyi is an important source of antiviral drugs, and the AEE may be a potential novel antiviral agent against HSV-1 infection.
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Antivirais , Artemisia , Herpesvirus Humano 1 , Extratos Vegetais , Aciclovir/farmacologia , Antivirais/química , Antivirais/farmacologia , Etanol , Herpesvirus Humano 1/efeitos dos fármacos , Envelope Viral , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Artemisia/química , Folhas de Planta/químicaRESUMO
New pollutant pharmaceutical and personal care products (PPCPs), especially antiviral drugs, have received increasing attention not only due to their increase in usage after the outbreak of COVID-19 epidemics but also due to their adverse impacts on water ecological environment. Electro-Fenton technology is an effective method to remove PPCPs from water. Novel particle electrodes (MMT/rGO/Fe3O4) were synthesized by depositing Fe3O4 nanoparticles on reduced graphene oxide modified montmorillonite and acted as catalysts to promote oxidation performance in a three-dimensional Electro-Fenton (3D-EF) system. The electrodes combined the catalytic property of Fe3O4, hydrophilicity of montmorillonite and electrical conductivity of graphene oxides, and applied for the degradation of Acyclovir (ACV) with high efficiency and ease of operation. At optimal condition, the degradation rate of ACV reached 100% within 120 min, and the applicable pH range could be 3 to 11 in the 3D-EF system. The stability and reusability of MMT/rGO/Fe3O4 particle electrodes were also studied, the removal rate of ACV remained at 92% after 10 cycles, which was just slightly lower than that of the first cycle. Potential degradation mechanisms were also proposed by methanol quenching tests and FT-ICR-MS.
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Human cytomegalovirus (HCMV) is a beta herpesvirus which large amount of people in world has interacted with. Recent studies indicated that CMV DNA is associated with several cancer types including "Glioblastoma (GBM)" which is the most common and aggressive type of primary brain cancer. In clinical studies it was shown that several antiviral medicines prolonged life span of glioblastoma patients. One of them is Acyclovir (ACV) which is a type of nucleoside analog, used to cure viral infections and might be a potential treatment supplement for Glioblastoma. In this study we aimed to investigate if ACV had cytotoxic effect on glioblastoma cell line U87 MG and also the effect of ACV on healthy cells. Furthermore it was aimed to search the effect of Rosmarinus Officinalis also known as rosemary which is an aromatic, perennial plant concurrent with ACV on glioblastoma and healthy cells.
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Aciclovir/uso terapêutico , Glioblastoma/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Rosmarinus/química , Aciclovir/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Camundongos , Extratos Vegetais/farmacologia , Survivina/genética , Survivina/metabolismo , Células Tumorais CultivadasRESUMO
Breast cancer is the most common cancer worldwide that costs lives of millions of people every year. Plant products with potential anticancer activities have become a vital source of novel agents in treating cancer. Adiantum capillus veneris (ACV) and Pteris Quadriureta (PQ) are such traditional herbs with potential pharmacological properties. In this study, both crude methanol extract and gold nanoparticles of ACV and PQ were tested for their anticancer activities in MCF7 and BT47 cell lines. By using GC-MS, we have identified 23 and 28 bioactive compounds in ACV and PQ respectively. We analysed the effects of ACV and PQ nanoparticles on various proteins involved in cell cycle and apoptosis using western blotting and PCR. With the help of flow cytometry, we measured number of cells undergoing apoptosis. We found that both the crude extract and nanoparticles have anti-proliferative and apoptosis inducing properties against MCF7 and BT47 cell lines. We also performed molecular docking to check whether there were any interactions between proteins involved in apoptosis and cell cycle and bioactive compounds present in the plant extracts. By using docking analysis, we also showed that phytol and eicosapentaenoic acid present in ACV and PQ interact with Bcl2 and cyclin D1. These findings demonstrate that ACV and PQ possess anticancer activities by modulating proteins involved in cell cycle and apoptosis. ACV and PQ that effectively modulate various oncogenic molecules can be used as promising agent for cancer therapy.
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Adiantum/metabolismo , Neoplasias da Mama/tratamento farmacológico , Pteris/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Ouro , Humanos , Células MCF-7/efeitos dos fármacos , Nanopartículas Metálicas , Simulação de Acoplamento Molecular/métodos , Fitoterapia/métodos , Extratos Vegetais/farmacologiaRESUMO
Herpes simplex virus type 1 (HSV-1) infection is very common worldwide and can cause significant health problems from periodic skin and corneal lesions to encephalitis. Appearance of drug-resistant viruses in clinical therapy has made exploring novel antiviral agents emergent. Here we show that chloride channel inhibitors, including tamoxifen and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB), exhibited extensive antiviral activities toward HSV-1 and ACV-resistant HSV viruses. HSV-1 infection induced chloride ion influx while treatment with inhibitors reduced the increase of intracellular chloride ion concentration. Pretreatment or treatment of inhibitors at different time points during HSV-1 infection all suppressed viral RNA synthesis, protein expression and virus production. More detailed studies demonstrated that tamoxifen and NPPB acted as potent inhibitors of HSV-1 early entry step by preventing viral binding, penetration and nuclear translocation. Specifically the compounds appeared to affect viral fusion process by inhibiting virus binding to lipid rafts and interrupting calcium homeostasis. Taken together, the observation that tamoxifen and NPPB can block viral entry suggests a stronger potential for these compounds as well as other ion channel inhibitors in antiviral therapy against HSV-1, especially the compound tamoxifen is an immediately actionable drug that can be reused for treatment of HSV-1 infections.
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Antivirais/farmacologia , Canais de Cloreto/antagonistas & inibidores , Herpes Simples/virologia , Herpesvirus Humano 1/fisiologia , Nitrobenzoatos/farmacologia , Tamoxifeno/farmacologia , Internalização do Vírus/efeitos dos fármacos , Animais , Canais de Cloreto/metabolismo , Chlorocebus aethiops , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 1/efeitos dos fármacos , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Células VeroRESUMO
Kidney transplant recipients are at increasing risk for reactivation of varicella-zoster virus (VZV) infection. Presentation of case: A 31-year-old male was admitted with fever, chest pain, and dyspnea. Also, the complaints accompanied by generalized maculopapular, vesicular, hemorrhagic, itching, and painful rash with pustules and crusts on an erythematous base fill the entire body for the last 10 days. Chest computed tomography scan showed diffuse miliary and ground-glass opacities. The patient had a previous history of chickenpox infection in childhood, no recent contact with individuals suffering from VZV infection, and no known pretransplant serology for VZV. Due to the high clinical suspicion of reactivated VZV with pneumonitis and severe disseminated form, we started the treatment with intravenous acyclovir (ACV) for 10 days followed by oral ACV for a total of 21 days, along with stopping mycophenolate mofetil and increasing the prednisolone dose to 10 mg/d. The clinical status was improved and the rash receded with a flaked surface for old lesions. Conclusion: We experienced a successful ACV treatment for delayed and severe VZV infection with a literature review of VZV pneumonitis among kidney transplant recipients. To the best of our knowledge, this is the first case that presented a disseminated skin form with pneumonitis of VZV from Syria. This case supports the initiation of antiviral therapy for transplant patients even after 72 hours the onset of the rash despite the lack of evidence in these circumstances.
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The studies interpreting DCI, a complication of SAH, and identifying correlations are very limited. This study aimed to investigate the effect of cilostazol on ACV and DCI after coil embolization for ruptured aneurysms (n = 432). A multivariate analysis was performed and explainable artificial intelligence approaches were used to analyze the contribution of cilostazol as a risk factor on the development of ACV and DCI with respect to global and local interpretation. The cilonimo group was significantly lower than the nimo group in ACV (13.5% vs. 29.3; p = 0.003) and DCI (7.9% vs. 20.7%; p = 0.006), respectively. In a multivariate logistic regression, the odds ratio for DCI for the cilonimo group, female sex, and aneurysm size was 0.556 (95% confidence interval (CI), 0.351-0.879; p = 0.012), 3.713 (95% CI, 1.683-8.191; p = 0.001), and 1.106 (95% CI, 1.008-1.214; p = 0.034). The risk of a DCI occurrence was significantly increased with an aneurysm size greater than 10 mm (max 80%). The mean AUC of the XGBoost and logistic regression models was 0.94 ± 0.03 and 0.95 ± 0.04, respectively. Cilostazol treatment combined with nimodipine could decrease the prevalence of ACV (13.5%) and DCI (7.9%) in patients with aSAH.
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Acyclovir (ACV) drug, a common antiviral agent, is frequently used as the primary clinical treatment method for treating hepatitis B, herpes simplex, and varicella zoster viruses due to its potent therapeutic effect. In patients with compromised immune systems, this medication can stop cytomegalovirus infections, and high doses of this drug are required; however, such prescription leads to kidney toxicity. Therefore, timely and accurate detection of ACV is crucial in many areas. Surface-Enhanced Raman Scattering (SERS) is a reliable, rapid, and precise approach for the identification of trace biomaterials and chemicals. Filter paper substrates decorated with silver nanoparticles (AgNPs) were applied as SERS biosensors to detect ACV and control its adverse effects. Initially, a chemical reduction procedure was utilized to produce AgNPs. Afterward, UV-Vis, FE-SEM, XRD, TEM, DLS, and AFM were employed to examine the properties of prepared AgNPs. In order to prepare SERS-active filter paper substrates (SERS-FPS) to detect Molecular vibrations of ACV, AgNPs prepared by immersion method were coated on filter paper substrates. Moreover, the UV-Vis DRS analysis was carried out to assess the stability of filter paper substrates and SERS-FPS. The AgNPs reacted with ACV after being coated on SERS-active plasmonic substrates and could sensitively detect ACV in small concentrations. It was discovered that the limit of detection of SERS plasmonic substrates was 10-12 M. Moreover, the mean RSD for ten repeated tests was calculated as 4.19%. The enhancement factor for detecting ACV using the developed biosensors was calculated to be 3.024 × 105 and 3.058 × 105 experimentally and via simulation, respectively. According to the Raman results, SERS-FPS for the detection of ACV, fabricated by the present methods, showed promising results for SERS-based investigations. Furthermore, these substrates showed significant disposablity, reproducibility, and chemical stability. Therefore, the fabricated substrates are capable to be employed as potential SERS biosensors to detect trace substances.
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Nanopartículas Metálicas , Análise Espectral Raman , Humanos , Análise Espectral Raman/métodos , Aciclovir , Prata/química , Nanopartículas Metálicas/química , Reprodutibilidade dos Testes , VibraçãoRESUMO
Background: Accessory cephalic vein (ACV) ligation can circumvent immature arteriovenous fistula (AVF). However, no consensus has been reached on the definite timing of ACV ligation. This study aimed to retrospectively analyze the correlation between preoperative Doppler ultrasonography (DUS)-assessed specific ACV diameter-cephalic vein diameter ratio (r) and early dysfunction of Radial artery-Cephalic vein (RC)-AVF in order to improve the early maturity rate of RC-AVF. Methods: A total of 258 patients who underwent RC-AVF at The Third Affiliated Hospital, Sun Yat-sen University from 1 June 2018 to 31 March 2022 were included in this study. The inclusion criteria were as follows: (I) cephalic vein ≥2.0 mm and radial artery ≥1.5 mm, suitable for RC-AVF establishment; (II) presence of an ACV. As per the specific r determined using preoperative DUS assessment, all patients were classified into two groups: Group A (r<0.8) and Group B (r≥0.8). Furthermore, patients in each group were divided into intervention and non-intervention subgroups based on the presence or absence of intraoperative ACV ligation, respectively. Patient data including age, sex, underlying disease, AVF side, and radial diameter were compared. The difference of maturity rate between participants in the intervention group and non-intervention group with different r values was analyzed, so as to obtain the relationship between different r values and maturity rate. Results: No statistical differences were observed between the intervention and non-intervention subgroups in the two groups in terms of sex, age, comorbidities, complications, AVF side, radial artery, cephalic vein, and ACV diameters (P>0.05). When r<0.8, the maturity rates of the intervention group and the non-intervention group were 80% and 92.98%, respectively, χ2=4.561. The difference in maturation rate between the intervention and non-intervention subgroups was insignificant (P=0.075) when r<0.8. When r≥0.8, the maturity rates of the intervention group and the non-intervention group were 89.83% and 45.45%, respectively, χ2=25.943. The difference in maturation rates between the intervention and non-intervention subgroups was significant when r≥0.8 (P<0.001). Conclusions: Preoperative DUS suggested a correlation between r≥0.8 and early immaturity of RC-AVF. Therefore, concurrent intraoperative ACV ligation should be carried out when preoperative r is ≥0.8, as it may reduce the early power dysfunction of RC-AVF.
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Oligopeptides with functional activities are of current interest in the nutraceutical and medical sectors. The development of the biosynthetic process of oligopeptides through a nonribosomal peptide synthetase (NRPS) system has become more challenging. To develop a production platform for nonribosomal peptides (NRPs), reprogramming of transcriptional regulation of the acv gene encoded ACV synthetase (ACVS) was implemented in Aspergillus oryzae using the CRISPR-Cas9 system. Awakening silent acv expression was successfully achieved by promoter substitution. Among the three exchanged promoters, AoPgpdA, AoPtef1, and PtPtoxA, the replacement of the native promoter with AoPgpdA led to the highest ACV production in A. oryzae. However, the ACV production of the AoPGpdA strain was also dependent on the medium composition, in which urea was the best nitrogen source, and a C:N ratio of 20:1 was optimal for tripeptide production. In addition to cell growth, magnesium ions are an essential element for ACV production and might participate in ACVS activity. It was also found that ACV was the growth-associated product of the engineered strain that might be a result of constitutive transcriptional control by the AoPgpdA promoter. This study offers a potential strategy for nonribosomal ACV production using the fungal system, which is applicable for redesigning bioactive oligopeptides with industrial relevance.
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Aspergillus oryzae/enzimologia , Proteínas Fúngicas/genética , Oligopeptídeos/biossíntese , Peptídeo Sintases/genética , Regiões Promotoras Genéticas , Aspergillus oryzae/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Peptídeo Sintases/metabolismoRESUMO
The validation of measuring instruments in the field of health is a requirement before they can be used safely and reliably. The action research arm test (ARAT) tool is an instrument validated in numerous countries and languages and for different populations, and its use is widespread. The objective of this research was to determine the psychometric properties of ARAT for a sample composed of post-stroke patients. To achieve this, a psychometric analysis was performed, where internal consistency tests were carried out using Cronbach's alpha, correlations between items and item-total and half-level tests to verify their reliability. Regarding validity, criteria validity tests were performed, taking the motor function dimension of the Fugl-Meyer scale as gold standard, and convergent validity tests were performed by correlation with the FIM-FAM, ECVI-38 and Lawton and Brody scales. The results showed very good internal consistency as well as good criterion and convergent validity. In conclusion, the ARAT can be considered a valid and reliable instrument for the evaluation of upper limb function in post-stroke patients.
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Idioma , Acidente Vascular Cerebral , Humanos , Psicometria/métodos , Reprodutibilidade dos Testes , Acidente Vascular Cerebral/diagnóstico , Pesquisa sobre Serviços de SaúdeRESUMO
Objectives: Quantitative evaluations of function, volume and mass are fundamental in the diagnostic workup of different cardiovascular diseases and can be exactly determined by CMRI in sinus rhythm. This does not hold true in arrhythmia as CMR is hampered by reconstruction artifacts caused by inconsistent data from multiple heartbeats. Real-time (RT) MRI at high temporal resolution might reduce these problems. Methods: Consecutive patients with atrial fibrillation were prospectively included and underwent RT and conventional CINE CMR in randomized order. 29 patients were studied at 1.5â¯T and 30 patients at 3â¯T. At 3â¯T a group of 20 subjects in sinus rhythm served as controls. RT and CINE image quality was evaluated in different planes and for different wall sections using a Likert scale (from zero to four). Volumetric analysis was performed using two types of software and differences between RT and CINE CMR were evaluated. Results: In patients with atrial fibrillation RT CMR short axis (SA) resulted in a significantly higher image quality compared to CINE imaging both at 1.5â¯T and 3â¯T (1.5â¯T: mid SA: 3.55 ± 0.5 RT vs 2.6 ± 0.9 CINE, pâ¯=â¯0.0001; 3â¯T: mid SA: 3.15 ± 0.9 RT vs 2.6 ±1.0 CINE, pâ¯=â¯0.03); This qualitative difference was more marked and significant for the long axis views (2CV and 4CV) at 1.5â¯T (1.5â¯T: 2CV: 3.2 ± 0.6 RT vs 2.65 ± 1.1 CINE; pâ¯=â¯0.011; 4CV: 2.9 ± 0.69 RT vs 2.4 ± 0.9 CINE; pâ¯=â¯0.0044). During sinus rhythm CINE images were superior concerning diagnostic quality (3â¯T mid SA: 3.35 ± 0.45 RT vs 3.8 ± 0.5 CINE, pâ¯=â¯0.008). Quantitative analysis was successful with both software packages and the results showed a good correlation (Pearson correlation between 0.679 and 0.921 for patients). RT CMR resulted in slightly lower functional volumes than CINE CMR (3â¯T: patients: EDVI 86 ± 29 ml/m2 RT vs 93 29 ml/m2± 29 CINE, Pearson râ¯=â¯0.902) but similar ejection fractions (3â¯T: patients: EF 47 ± 16% RT vs 45 ± 13% CINE, Pearson râ¯=â¯0679; controls: EF 63 ± 6 RT vs 63 ± 3 CINE, Pearson râ¯=â¯0.695). Conclusion: RT CMR improves image quality in arrhythmic patients and renders studies more comfortable. Volumetric analysis is feasible with slightly lower values relative to CINE CMR, while ejection fractions are comparable.
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Infection prevention and control team members (IPCTM) are often intimidated by aspects of ventilation as they relate to healthcare, because they consider them technical and outside their area of comfort and expertise. However, engineers, estates departments and planners need IPCTM input to ensure appropriate design and use. The main areas of importance centre on the operating theatre, the provision of air-controlled ventilated isolation rooms, and how to respond to major outbreaks/pandemics. Concentrating on basic principles of infection prevention and control, developing relationships with key departments and individuals, and applying best practice to these and other areas as they arise, are of great value. Some background, information and suggestions are provided for IPCTM with a view to providing simple practical advice in these areas.
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Dementia linked with cognitive impairments is the most prominent indication of Alzheimer's disease (AD). In the current investigation, we have examined the streptozotocin- (STZ) induced cellular toxicity in mouse neuroblastoma (N2A) cells, and Zn with the high-fat diet- (HFD) induced neurotoxicity in mouse brain. These cells and animals were pretreated with apple cider vinegar (ACV), Chrysin, and Rivastigmine to examine their protection against cellular toxicity and neurotoxicity. Experiments have affirmed that pretreatment of ACV, Chrysin, and Rivastigmine has displayed protective outcomes in MTT reduction, tau phosphorylation, amyloid aggregation, attenuated memory impairment as well as oxidative stress, and protected cholinergic hippocampal neurons from degeneration. ACV showed better antioxidant and neuroprotection potential as compared with Chrysin and Rivastigmine. So the existence of excitatory/inhibitory enzymatic activity and higher antioxidant potential indicate that ACV, as a food beverage in a regular diet, could be promising and effective against neurological complications such as AD. PRACTICAL APPLICATIONS: In the Urban lifestyle, HFD and stress are the critical factors of various chronic and prevalent diseases, including diabetes, obesity, cardiovascular, and neurodegenerative disorders like AD. We are already familiar with the multiple benefits of ACV, such as weight loss, antimicrobial activity, diabetes, skin disorders. So in the current research work, we have gauged the effectiveness of ACV against neurological complications in comparison with a synthetic flavonoid (Chrysin) and an anti-Alzheimer's drug (Rivastigmine). To enhance the pragmatic orientation of our results, we have used the ACV in our study, which is readily available in the market for domestic consumption. All the cellular, biochemical, behavioral, and histopathological data revealed that ACV had high antioxidant potential. Our findings suggest that the addition of ACV as a food additive in the daily diet may reduce the threat of multiple neurodegenerative diseases. Therefore, our study could be the precursor of a new pharmacological therapeutic approach via ACV toward cognitive impairments associated with Alzheimer's disease.
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Malus , Preparações Farmacêuticas , Ácido Acético , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Camundongos , Estresse OxidativoRESUMO
Fungal secondary metabolites are synthesized by complex biosynthetic pathways catalized by enzymes located in different subcellular compartments, thus requiring traffic of precursors and intermediates between them. The ß-lactam antibiotics penicillin and cephalosporin C serve as an excellent model to understand the molecular mechanisms that control the subcellular localization of secondary metabolites biosynthetic enzymes. Optimal functioning of the ß-lactam biosynthetic enzymes relies on a sophisticated temporal and spatial organization of the enzymes, the intermediates and the final products. The first and second enzymes of the penicillin pathway, ACV synthetase and IPN synthase, in Penicillium chrysogenum and Aspergillus nidulans are cytosolic. In contrast, the last two enzymes of the penicillin pathway, phenylacetyl-CoA ligase and isopenicillin N acyltransferase, are located in peroxisomes working as a tandem at their optimal pH that coincides with the peroxisomes pH. Two MFS transporters, PenM and PaaT have been found to be involved in the import of the intermediates isopenicillin N and phenylacetic acid, respectively, into peroxisomes. Similar compartmentalization of intermediates occurs in Acremonium chrysogenum; two enzymes isopenicillin N-CoA ligase and isopenicillin N-CoA epimerase, that catalyse the conversion of isopenicillin N in penicillin N, are located in peroxisomes. Two genes encoding MFS transporters, cefP and cefM, are located in the early cephalosporin gene cluster. These transporters have been localized in peroxisomes by confocal fluorescence microscopy. A third gene of A. chrysogenum, cefT, encodes an MFS protein, located in the cell membrane involved in the secretion of cephalosporin C, although cefT-disrupted mutants are still able to export cephalosporin by redundant transporters. The secretion of penicillin from peroxisomes to the extracellular medium is still unclear. Attempts have been made to identify a gene encoding the penicillin secretion protein among the 48 ABC-transporters of P. chrysogenum. The highly efficient secretion system that exports penicillin against a concentration gradient may involve active penicillin extrusion systems mediated by vesicles that fuse to the cell membrane. However, there is no correlation of pexophagy with penicillin or cephalosporin formation since inactivation of pexophagy leads to increased penicillin or cephalosporin biosynthesis due to preservation of peroxisomes. The penicillin biosynthesis finding shows that in order to increase biosynthesis of novel secondary metabolites it is essential to adequately target enzymes to organelles.
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Introducción: Seguir instrucciones, inhibir distracciones del entorno, planificar y ejecutar actos motores complejos, así como controlar la impulsividad; son habilidades ejecutivas fundamentales para participar de un programa de rehabilitación de manera satisfactoria. El propósito de esta revisión es concientizar al equipo rehabilitador sobre la importancia de las disfunciones ejecutivas en el proceso de rehabilitación de personas post ACV. Método: se realizó una revisión de literatura a través de las bases de datos PubMed, Embase, Web of Science y Cochrane Library, incluyendo artículos publicados hasta abril 2023. Se emplearon combinaciones de términos de búsqueda para tres categorías: ACV, funciones ejecutivas (FE), y disfunciones ejecutivas. Se seleccionaron diseños de corte transversal, ensayos clínicos y revisiones sistemáticas que incluyeran los términos funciones /disfunciones ejecutivas y ACV. Resultados: Se identificaron 174 artículos que cumplían con los criterios de búsqueda, de los cuales fueron descartados 121 por abordar conceptos distintos al objetivo de estudio y 7 artículos que se encontraban duplicados. Fueron seleccionados 46 artículos considerando su pertinencia, relevancia y actualización en el tema. Conclusión: El deterioro de las EF es un síndrome heterogéneo en el cual la interacción simultánea de múltiples procesos cognitivos, como la capacidad para razonar y resolver problemas a menudo se ve gravemente comprometida. Este deterioro puede resultar perjudicial durante el proceso rehabilitador posterior a un ACV, ya que los componentes de la función ejecutiva son principios necesarios para el funcionamiento en el mundo real.
Introduction: Following instructions, inhibiting distractions from the environment, planning and executing complex motor task, as well as controlling impulsivity are fundamental executive skills to participate in a rehabilitation program in a satisfactory manner. The purpose of this review is to make the rehabilitation team aware of the importance of executive dysfunctions in the rehabilitation process of post-stroke patients. Method: a literature review was carried out using PubMed, Embase, Web of Science and Cochrane Library databases, including articles published up to April 2023. Combinations of search terms were used for three categories: stroke, executive functions (EF) and executive dysfunctions. We selected cross-sectional designs, clinical trials and systematic review that included the terms /dysfunctions and stroke. Results: we identified 174 articles that met the search criteria, of which 121 were discarded because they addressed concepts other than the study objective and 7 articles were found to be duplicates. Forty-six articles were selected considering their pertinence, relevance and up-to-dateness in the subject. Conclusion: impaired EF is a heterogeneous syndrome in which the simultaneous interaction of multiple cognitive processes, such as the ability to reason and solve problems is often severely compromised. This impairment can be detrimental during the post-stroke rehabilitative process, as components of executive function are necessary principles for real-world functioning.
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Infection of Herpes simplex virus 1 (HSV-1) induces severe clinical disorders, such as herpes simplex encephalitis and keratitis. Acyclovir (ACV) is the current therapeutic drug against viral infection and ACV-resistant strains have gradually emerged, leading to the requirement for novel antiviral agents. In this study, we exhibited the antiviral activity of amentoflavone, a naturally occurring biflavonoid, toward HSV-1 and ACV-resistant strains. Amentoflavone significantly inhibited infection of HSV-1 (F strain), as well as several ACV-resistant strains including HSV-1/106, HSV-1/153 and HSV-1/Blue at high concentrations. Time-of-drug-addition assay further revealed that amentoflavone mainly impaired HSV-1 early infection. More detailed study demonstrated that amentoflavone affected cofilin-mediated F-actin reorganization and reduced the intracellular transportation of HSV-1 from the cell membrane to the nucleus. In addition, amentoflavone substantially decreased transcription of viral immediate early genes. Collectively, amentoflavone showed strong antiviral activity against HSV-1 and ACV-resistant strains, and amentoflavone could be a promising therapeutic candidate for HSV-1 pathogenesis.
Assuntos
Antivirais/farmacologia , Biflavonoides/farmacologia , Farmacorresistência Viral , Herpes Simples/virologia , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/fisiologia , Internalização do Vírus , Animais , Chlorocebus aethiops , Regulação Viral da Expressão Gênica , Humanos , Células VeroRESUMO
Resumen La embolia paradojal debido a una malformación arteriovenosa pulmonar (MAVP) aislada es una causa in frecuente de accidente cerebrovascular (ACV) isquémico. Las MAVP son conductos anómalos de alta circulación entre arterias y venas pulmonares, desviando sangre desoxigenada hacia la circulación sistémica y represen tan una fuente menos común de embolias paradojales, especialmente en personas jóvenes. La embolización endovascular es el tratamiento preferido para MAVP clínicamente significativas. Presentamos el caso de una mujer de 34 años con ACV isquémico talámico izquierdo. Se detectó pasaje de burbujas "en cortina" en arterias cerebrales mediante Doppler transcraneal. En ecografía intracardíaca no se encontró foramen oval permeable, motivo por el cual se avanzó con realización de angiotomografía pulmonar, la cual confirmó la presencia de MAVP. La paciente recibió tratamiento endovascular exitoso. Es esencial considerar la MAVP en el diagnóstico etio lógico del ACV isquémico, especialmente en pacientes jóvenes con signos de comunicación anormal de derecha a izquierda. Se recomienda un seguimiento periódico mediante imágenes para evaluar la posible recurrencia o cambios en la MAVP, resaltando la importancia del manejo adecuado de estas malformaciones.
Abstract Paradoxical embolism due to an isolated pulmonary arteriovenous malformation (PAVM) is a rare cause of ischemic stroke. PAVMs are abnormal high-flow connec tions between pulmonary arteries and veins, diverting deoxygenated blood into the systemic circulation and they represent a less common source of paradoxical embolisms, especially in young individuals. Endovascular embolization is the preferred treatment for clinically significant PAVMs. We present the case of a 34-year-old woman with a left thalamic ischemic stroke. Severe contrast passage was detected in cerebral arteries through transcranial Doppler. Intracardiac ultrasound did not reveal a patent foramen ovale, prompting further investigation with pulmonary CT angiography, confirming the presence of PAVM. The patient underwent successful endovascular treatment. It is essential to consider PAVM in the etiological di agnosis of ischemic stroke, especially in young patients with signs of abnormal right-to-left communication. Periodic follow-up imaging is recommended to assess potential recurrence or changes in PAVM, emphasizing the importance of appropriate management of these malformations.
RESUMO
This review discusses the epidemiologic and clinical aspects of herpes viruses other than cytomegalovirus in patients who have undergone hematopoietic stem cell transplantation.