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Herein, a novel series of 6-amino-5-cyano-2-thiopyrimidines and condensed pyrimidines analogues were prepared. All the synthesized compounds (1a-c, 2a-c, 3a-c, 4a-r and 5a-c) were evaluated for in vitro anticancer activity by the National Cancer Institute (NCI; MD, USA) against 60 cell lines. Compound 1c showed promising anticancer activity and was selected for the five-dose testing. Results demonstrated that compound 1c possessed broad spectrum anti-cancer activity against the nine cancerous subpanels tested with selectivity ratio ranging from 0.7 to 39 at the GI50 level with high selectivity towards leukaemia. Mechanistic studies showed that Compound 1c showed comparable activity to Duvelisib against PI3Kδ (IC50 = 0.0034 and 0.0025 µM, respectively) and arrested cell cycle at the S phase and displayed significant increase in the early and late apoptosis in HL60 and leukaemia SR cells. The necrosis percentage showed a significant increase from 1.13% to 3.41% in compound 1c treated HL60 cells as well as from 1.51% to 4.72% in compound 1c treated leukaemia SR cells. Also, compound 1c triggered apoptosis by activating caspase 3, Bax, P53 and suppressing Bcl2. Moreover, 1c revealed a good safety profile against human normal lung fibroblast cell line (WI-38 cells). Molecular analysis of Duvelisib and compound 1c in PI3K was performed. Finally, these results suggest that 2-thiopyrimidine derivative 1c might serve as a model for designing novel anticancer drugs in the future.
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Antineoplásicos , Leucemia , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células , Antineoplásicos/farmacologia , Apoptose , Simulação de Acoplamento MolecularRESUMO
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.
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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 JovemRESUMO
Food waste (FW) contains many nutritional components such as proteins, lipids, fats, polysaccharides, carbohydrates, and metal ions, which can be reused in some processes to produce value-added products. Furthermore, FW can be converted into biogas, biohydrogen, and biodiesel, and this type of green energy can be used as an alternative to nonrenewable fuel and reduce reliance on fossil fuel sources. It has been demonstrated in many reports that at the laboratory scale production of biochemicals using FW is as good as pure carbon sources. The goal of this paper is to review approaches used globally to promote turning FW into useable products and green energy. In this context, the present review article highlights deeply in a transdisciplinary manner the sources, types, impacts, characteristics, pre-treatment strategies, and potential management of FW into value-added products. We find that FW could be upcycled into different valuable products such as eco-friendly green fuels, organic acids, bioplastics, enzymes, fertilizers, char, and single-cell protein, after the suitable pre-treatment method. The results confirmed the technical feasibility of all the reviewed transformation processes of FW. Furthermore, life cycle and techno-economic assessment studies regarding the socio-economic, environmental, and engineering aspects of FW management are discussed. The reviewed articles showed that energy recovery from FW in various forms is economically feasible.
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Eliminação de Resíduos , Gerenciamento de Resíduos , Alimentos , Análise Custo-Benefício , Biocombustíveis , BibliometriaRESUMO
In the current investigation, two novel series of (tetrahydro)thioquinazoline-N-arylacetamides and (tetrahydro)thioquinazoline-N-arylacetohydrazides were designed, synthesized and investigated for their antiviral activity against SARS-CoV-2. The thioquinazoline-N-arylacetamide 17g as well as the tetrahydrothioquinazoline-N-arylacetohydrazides 18c and 18f showed potent antiviral activity with IC50 of 21.4, 38.45 and 26.4 µM, respectively. In addition, 18c and 18f demonstrated potential selectivity toward the SARS-CoV-2 over the host cells with SI of 10.67 and 16.04, respectively. Further evaluation of the mechanism of action of the three derivatives 17g, 18c, and 18f displayed that they can inhibit the virus at the adsorption as well as at the replication stages, in addition to their virucidal properties. In addition, 17g, 18c, and 18f demonstrated satisfactory physicochemical properties as well as drug-likeness properties to be further optimized for the discovery of novel antiviral agents. The docking simulation on Mpro binding site predicted the binding pattern of the target compounds rationalizing their differential activity based on their hydrophobic interaction and fitting in the hydrophobic S2 subsite of the binding site.
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Aerobic pre-treatment of liquid dairy manure has previously been reported as an effective nutrient export and emissions mitigation approach. The first objective of this study was to experimentally determine the optimal intermittent aeration ratio for nutrient recovery from liquid dairy manure through an on-site pilot-scale reactor to partially reduce the required energy for the aerobic process. The second objective was to theoretically investigate the total carbon footprints of direct manure spreading on croplands and permanent manure storage in open anaerobic lagoons in response to nutrient removal by the optimal determined intermittent aerobic treatment ratio. Four scenarios (S) were included; S1 was the traditional scenario of manure spread on croplands without the aerobic pre-treatment, S2 was the modified scenario of manure spread on croplands that included the aerobic pre-treatment, S3 was the traditional scenario of manure storage in lagoons, and S4 was the modified scenario of manure storage in lagoons that included the aerobic pre-treatment. The results showed that comparable nutrient removal efficiencies could be obtained with a 5:1 intermittent aeration ratio. Total nitrogen (TN) and total phosphorus (TP) were recovered were 41.5 ± 1.3% and 37.0 ± 4.0%, respectively, in ammonium sulfate and phosphorus-rich sludge, while 55.3 ± 1.4% of the chemical oxygen demand (COD) was removed. The estimated total carbon footprint for S1, S2, S3, and S4 were 24.4, 37.9, 45.3, and 45.9 kg CO2-eqton-1, respectively. However, the total carbon footprint of S2' and S4', which used renewable-based energy to run the reactor instead of fossil-based energy used in S2 and S4, were estimated to 29.5 and 37.5 kg CO2-eqton-1, respectively. Clearly, applying the aerobic pre-treatment increased the total carbon footprint of all cases except S4', in which the total carbon footprint was mitigated by -17.2%. Accordingly, the aerobic pre-treatment is only recommended in the case of S4' from a carbon footprint point of view although it is an effective nutrient recovery technology.
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Pegada de Carbono , Esterco , Dióxido de Carbono/análise , Análise da Demanda Biológica de Oxigênio , Nitrogênio , FósforoRESUMO
New antioxidant agents are urgently required to combat oxidative stress, which is linked to the emergence of serious diseases. In an effort to discover potent antioxidant agents, a novel series of 2-thiouracil-5-sulfonamides (4-9) were designed and synthesized. In line with this approach, our target new compounds were prepared from methyl ketone derivative 3, which was used as a blocking unit for further synthesis of a novel series of chalcone derivatives 4a-d, thiosemicarbazone derivatives 5a-d, pyridine derivatives 6a-d and 7a-d, bromo acetyl derivative 8, and thiazole derivatives 9a-d. All compounds were evaluated as antioxidants against 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide (H2O2), lipid peroxidation, and 15-lipoxygenase (15-LOX) inhibition activity. Compounds 5c, 6d, 7d, 9b, 9c, and 9d demonstrated significant RSA in all three techniques in comparison with ascorbic acid and 15-LOX inhibitory effectiveness using quercetin as a standard. Molecular docking of compound 9b endorsed its proper binding at the active site pocket of the human 15-LOX which explains its potent antioxidant activity in comparison with standard ascorbic acid.
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Antioxidantes , Araquidonato 15-Lipoxigenase , Humanos , Antioxidantes/química , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Araquidonato 15-Lipoxigenase/metabolismo , Peróxido de Hidrogênio , Sulfonamidas , Ácido Ascórbico , Estrutura MolecularRESUMO
[This corrects the article DOI: 10.1016/j.jddst.2022.103921.].
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Several natural products recovered from a marine-derived Aspergillus niger were tested for their inhibitory activity against SARS CoV-2 in vitro. Aurasperone A (3) was found to inhibit SARS CoV-2 efficiently (IC50 = 12.25 µM) with comparable activity with the positive control remdesivir (IC50 = 10.11 µM). Aurasperone A exerted minimal cytotoxicity on Vero E6 cells (CC50 = 32.36 mM, SI = 2641.5) and it was found to be much safer than remdesivir (CC50 = 415.22 µM, SI = 41.07). To putatively highlight its molecular target, aurasperone A was subjected to molecular docking against several key-viral protein targets followed by a series of molecular dynamics-based in silico experiments that suggested Mpro to be its primary viral protein target. More potent anti-SARS CoV-2 Mpro inhibitors can be developed according to our findings presented in the present investigation.
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Antivirais/farmacologia , Cromonas/farmacologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Inibidores de Proteases/farmacologia , SARS-CoV-2/efeitos dos fármacos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Alanina/análogos & derivados , Alanina/farmacologia , Animais , Antivirais/isolamento & purificação , Aspergillus niger/química , Chlorocebus aethiops , Cromonas/isolamento & purificação , Proteases 3C de Coronavírus/metabolismo , Proteases Semelhantes à Papaína de Coronavírus/metabolismo , RNA-Polimerase RNA-Dependente de Coronavírus/metabolismo , Simulação de Acoplamento Molecular , Inibidores de Proteases/isolamento & purificação , RNA Helicases/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Células VeroRESUMO
Lung cancer and pandemic acute respiratory disease, COVID-19, are examples of the most worldwide widespread diseases. The aim of the current study is to develop cyclodextrin based nanosponge (CD-NS) for loading the flavonoid drug, quercitrin (QCT). This is to improve its solubility in an attempt to enhance its activity against lung cancer as well as SARS-CoV-2 virus responsible for COVID-19. Preparation of CD-NS was performed by ultrasound-assisted synthesis method. Two CDs were employed, namely, ß cyclodextrin (ßCD) and 2-hydroxy propyl-ß-cyclodextrin (2-HPßCD) that were crosslinked with diphenyl carbonate, one at a time. QCT loaded CD-NS revealed entrapment efficiency and particle size ranged between 94.17 and 99.03% and 97.10-325.90 nm, respectively. QCT loaded 2-HPßCD-NS revealed smaller particle size compared with that of QCT loaded ßCD-NS. Zeta potential absolute values of the prepared formulations were >20 mV, indicating physically stable nanosystems. The selected formulations were investigated by Fourier transform infrared spectroscopy, X-ray powder diffraction and scanning electron microscopy which proved the formation of QCT loaded CD-NS exhibiting porous structure. QCT exhibited partial and complete amorphization in ßCD-NS and 2-HPßCD-NS, respectively. In vitro release revealed an improved release of QCT from CD-NS formulations. The biological activity of free QCT and QCT loaded CD-NS was investigated against lung cancer cell line A549 as well as SARS-CoV-2 virus. The results revealed that IC50 values of free QCT against lung cancer cell line A549 and SARS-CoV-2 were higher than those exhibited by QCT loaded CD-NS by 1.57-5.35 and 5.95-26.95 folds, respectively. QCT loaded 2-HPßCD-NS revealed enhanced in vitro release and superior biological activity compared with QCT loaded ßCD-NS.
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Open anaerobic lagoons are widely used for liquid manure storage and treatment, with excess greenhouse gas (GHG) and odor emissions. In this study, liquid manure was valorized through hybrid nitrogen and phosphorous recovery as value-added products using an airlift reactor. Also, the organic load of liquid manure was reduced before discharging into anaerobic lagoons, which simultaneously mitigated GHG emissions. The results showed that 14.5% of total nitrogen (TN) was recovered as ammonium sulfate, while 38.8% of TN and 79.3% of total phosphorus (TP) were recovered as phosphorus-rich sludge. After the pre-treatment in the reactor, the odor could be controlled effectively due to a 94.2% decrease in total VFAs. In addition, 59.0% of COD was removed, which decreased the theoretical modeled GHG emissions by 51.7% compared to the traditional direct discharging. The application is promising for upgrading anaerobic lagoons of liquid manure.
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Gases de Efeito Estufa , Anaerobiose , Efeito Estufa , Esterco/análise , Metano , NutrientesRESUMO
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.
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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-19RESUMO
INTRODUCTION: Stem cell therapy at the time of ischemia/reperfusion (I/R) injury has been hypothesized to attenuate the severity of acute kidney injury and to accelerate the regeneration process in lower animal models. Data in higher animal models is limited and discordant. We aimed to explore the reno-protective effects of stem cells on I/R related renal injury in a canine model. MATERIALS AND METHODS: Twenty-seven dogs that were treated with bone marrow-derived mesenchymal stem cells (BM-MSCs) were compared with another 27 dogs treated with adipose tissue-derived MSCs (AT-MSCs) following 90 min of warm ischemia to assess IR injury. Each group was divided into three subgroups (nine dogs each), according to the stem cell dose (5, 10, 15 × 106 in 500 µl volume) injected directly into the renal cortex after reperfusion. All dogs were re-evaluated by renogram, histopathology, and pro-inflammatory markers at 2 weeks, 2, and 3 months. RESULTS: In Group I, there was a mean reduction of creatinine clearance by 78%, 64%, and 74% at the three used doses, respectively, at 2 weeks. At 3 months, these kidneys regained a mean of 84%, 92%, and 72%, respectively, of its basal function. In Group II, the reduction of clearance was much more modest with mean of 14%, 6%, and 24% respectively at 2 weeks with more intense recovery of renal function by mean of 90%, 100%, and 76%, respectively, at 3 months. Group I had significantly more tubular necrosis and delayed regeneration compared with the Group II. Expressions of pro-inflammatory markers were upregulated in both the groups with a higher and more sustained expression in Group I. CONCLUSION: Stem cells protected against ischemic reperfusion injury in a canine model. AT-MSCs provided better protection than BM-MSCs.
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PURPOSE: To compare the effectiveness of tamsulosin and solifenacin in relieving ureteral stents related symptoms. PATIENTS AND METHODS: A randomized controlled trial was conducted between January 2013 and July 2014. Inclusion criteria were patients aged 20-50 years who underwent temporary unilateral ureteral stent for drainage of calcular upper tract obstruction or after ureteroscopic lithotripsy. Patients with history of lower urinary tract symptoms before stent placement, stents that were fixed after open or laparoscopic procedures, and those who developed complications related to the primary procedure were not included. Eligible patients were randomly assigned to 1 of 3 groups using computer-generated random tables. Patients in group 1 received placebo, patients in group 2 received tamsulosin 0.4 mg once daily, and those in group 3 received solifenacin 5 mg once daily. Ureteral Stent Symptom Questionnaire (USSQ) was answered by all patients 1-2 weeks after stent placement. The primary outcome was the comparison of total score of USSQ between all groups. RESULTS: The study included 131 patients. All baseline characteristics (age, sex, side, indication, length, and duration of stent) were comparable for all groups. Total USSQ score was 61 in solifenacin group, 76 in tamsulosin group, and 83 in control group (P < 0.001). The total USSQ scores and all domains, except sexual index, were significantly better in solifenacin than in tamsulosin group (P < 0.05). CONCLUSION: The use of tamsulosin alone or solifenacin alone in patients with ureteral stents can improve the quality of life by decreasing ureteral stent-related symptoms. Solifenacin was better than tamsulosin. CLINICALTRIAL. GOV IDENTIFIER: NCT01880619.
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Antagonistas Adrenérgicos alfa/uso terapêutico , Antagonistas Colinérgicos/uso terapêutico , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Succinato de Solifenacina/uso terapêutico , Stents/efeitos adversos , Sulfonamidas/uso terapêutico , Doenças Ureterais/tratamento farmacológico , Doenças Ureterais/etiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , TansulosinaRESUMO
Free water surface constructed wetlands (FWSCWs) for the treatment of various wastewater types have evolved significantly over the last few decades. With an increasing need and interest in FWSCWs applications worldwide due to their cost-effectiveness and other benefits, this paper reviews recent literature on FWSCWs' ability to remove different types of pollutants such as nutrients (i.e., TN, TP, NH4-N), heavy metals (i.e., Fe, Zn, and Ni), antibiotics (i.e., oxytetracycline, ciprofloxacin, doxycycline, sulfamethazine, and ofloxacin), and pesticides (i.e., Atrazine, S-Metolachlor, imidacloprid, lambda-cyhalothrin, diuron 3,4-dichloroanilin, Simazine, and Atrazine) that may co-exist in wetland inflow, and discusses approaches for simulating hydraulic and pollutant removal processes. A bibliometric analysis of recent literature reveals that China has the highest number of publications, followed by the USA. The collected data show that FWSCWs can remove an average of 61.6%, 67.8%, 54.7%, and 72.85% of inflowing nutrients, heavy metals, antibiotics, and pesticides, respectively. Optimizing each pollutant removal process requires specific design parameters. Removing heavy metal requires the lowest hydraulic retention time (HRT) (average of 4.78 days), removing pesticides requires the lowest water depth (average of 0.34 m), and nutrient removal requires the largest system size. Vegetation, especially Typha spp. and Phragmites spp., play an important role in FWSCWs' system performance, making significant contributions to the removal process. Various modeling approaches (i.e., black-box and process-based) were comprehensively reviewed, revealing the need for including the internal process mechanisms related to the biological processes along with plants spp., that supported by a further research with field study validations. This work presents a state-of-the-art, systematic, and comparative discussion on the efficiency of FWSCWs in removing different pollutants, main design factors, the vegetation, and well-described models for performance prediction.
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Poluentes Químicos da Água , Áreas Alagadas , Metais Pesados , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Purificação da Água/métodos , PraguicidasRESUMO
BACKGROUND: Low-intensity shockwave therapy (Li-SWT) can improve bladder function through enhancement of angiogenesis and nerve regeneration and suppression of inflammation and overactivity. In this trial, we aimed to evaluate the efficacy of Li-SWT on persistent storage symptoms after transurethral surgery (TUS) for benign prostatic obstruction (BPO). METHODS: Between July 2020 and July 2022, 137 patients with persistent storage symptoms; urgency episodes/24 h ≥ 1 and daytime frequency ≥8, for at least three months after TUS for BPO were randomly allocated to Li-SWT versus sham versus solifenacin 10 mg/day in 3:1:1 ratio. The primary end point was the percent reduction from baseline in overactive bladder symptom score (OABSS) at 3-month follow-up. The changes in 3-day voiding diary parameters, quality of life (QoL) score, peak flow rate and residual urine at 3 and 6-month follow-up were compared. Treatment-related adverse effects were also evaluated. RESULTS: Baseline data were comparable between groups. The percent reduction from baseline in OABSS at 3-month follow-up was significantly higher in Li-SWT compared to sham (-55% versus -11%), and it was comparable between Li-SWT and solifenacin-10 (-55% versus -60%). Li-SWT achieved significant improvement like solifenacin-10 in 3-day voiding diary parameters and QoL score at 3-month follow-up. This improvement remained comparable between Li-SWT and solifenacin-10 at 6-month follow-up. No adverse effects related to Li-SWT were noted apart from tolerable pain during the procedure. Solifenacin-10 was associated with bothersome adverse effects in 73% of the patients with 11.5% discontinuation rate. CONCLUSIONS: Li-SWT ameliorates persistent storage symptoms and promotes QoL after TUS for BPO, with comparable efficacy and better tolerance compared to solifenacin.
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Hiperplasia Prostática , Qualidade de Vida , Ressecção Transuretral da Próstata , Humanos , Masculino , Idoso , Ressecção Transuretral da Próstata/métodos , Ressecção Transuretral da Próstata/efeitos adversos , Hiperplasia Prostática/terapia , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/complicações , Pessoa de Meia-Idade , Succinato de Solifenacina/administração & dosagem , Succinato de Solifenacina/uso terapêutico , Resultado do Tratamento , Seguimentos , Tratamento por Ondas de Choque Extracorpóreas/métodos , Bexiga Urinária Hiperativa/terapia , Bexiga Urinária Hiperativa/etiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Método Duplo-CegoRESUMO
The search for new molecules targeting SARS-CoV-2 has been a priority since 2020. The continuous evolution of new mutants increases the need for more research in the area. One way to find new leads is to repurpose existing drugs and molecules against the required target. Here, we present the in vitro and in silico screening of ten previously synthesized and reported compounds as anti-COVID 19 agents. The compounds were screened in vitro against VERO-E6 cells to find their Cytotoxic Concentration (CC50) and their Inhibitory Concentration (IC50). Compounds 1, 2, and 5 revealed a promising anti-SARS-CoV-2 of (IC50 = 2.4, 11.2 and 2.8 µM), respectively while compounds 3 and 7 showed moderate activity of (IC50 = 17.8 and 26.1 µM) compared to Chloroquine which showed an IC50 of 24.9 µM. Among tested compounds, 1 showed the highest selectivity (CC50/IC50) of 192.8. Docking, molecular dynamics and ADME studies were done to investigate potential interactions between compounds and SARS-CoV-2 targets as well as to study the possibility of using them as lead compounds.
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Owing to its high interest as prolific source of diverse bioactive compounds referred in our previous research work, we have scaled-up the fermentation of the marine Aspergillus terreus LGO13 on a liquid culture medium to isolate and identify the very minor/further promising bioactive secondary metabolites and to study their antibacterial, cytotoxic, and antiviral properties. Twenty-three known bioactive metabolites, including the recently discovered microbial natural product N-benzoyl-tryptophan (1), were obtained herein. Their structures were determined using HR-ESI-MS 1D/2D NMR spectroscopy and data from the literature. The biological properties of the microbial extract and the resulting compounds were examined using a set of microorganisms, cervix carcinoma KB-3-1, nonsmall cell lung cancer (NSCLC) A549, and coronavirus (SARS-CoV-2), respectively. Molecular docking (MD) simulations were used to investigate the potential targets of the separated metabolites as anti-SARS-CoV-2 drugs. According to the current study, a viral protein that may be the target of anticovid drugs is a papain-like protease (PLpro), and chaetominine (2) appears to be a viable choice against this protein. We evaluated the antiviral efficacy of chaetominine (2), fumitremorgin C (6), and azaspirofuran A (9) against SARS-CoV-2 based on MD data. Chaetominine (2) and azaspirofuran A (9) displayed intermediate selectivity indices (SI = 6.6 and 3.2, respectively), while fumitremorgin C (6) displayed a high selectivity index (SI = 19.77). These findings show that fumitremorgin C has promising antiviral action against SARS-CoV-2.
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In today's era, nanoparticles (NPs) have become an integral part of human life, finding extensive applications in various fields of science, pharmacy, medicine, industry, electronics, and communication. The increasing popularity of NP usage worldwide is a testament to their tremendous potential. However, the widespread deployment of NPs unavoidably leads to their release into the environmental matrices, resulting in persistence in ecosystems and bioaccumulation in organisms. Understanding the environmental behavior of NPs poses a significant challenge due to their nanoscale size. Given the current environmental releases of NPs, known negative consequences, and the limited knowledge available for risk management, comprehending the toxicity of NPs in ecosystems is both awaiting and crucial. The present review aims to unravel the potential environmental influences of nano-scaled materials, and provides in-depth inferences of the current knowledge and understanding in this field. The review comprehensively summarizes the sources, fate, transport, toxicity, health risks, and remediation solutions associated with NP pollution in aquatic and soil ecosystems. Furthermore, it addresses the knowledge gaps and outlines further investigation priorities for the sustainable control of NP pollution in these environments. By gaining a holistic understanding of these aspects, we can work toward ensuring the responsible and sustainable use of NPs in today's fast-growing world.
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Ecossistema , Nanopartículas , Humanos , Nanopartículas/toxicidade , Solo , Poluição Ambiental , Gestão de RiscosRESUMO
PURPOSE: To our knowledge there are no evidence-based medicine data to date to critically judge the vulnerability of a solitary kidney to warm ischemia compared to paired kidneys. MATERIALS AND METHODS: Ten dogs were exposed to open right nephrectomy to create a solitary kidney model (group 1). Ten dogs with both kidneys were considered group 2. All dogs underwent warm ischemia by open occlusion of the left renal artery for 90 minutes. Dogs were sacrificed at different intervals (3 days to 4 weeks). All dogs were reevaluated by renogram before sacrifice and histopathology of the investigated kidney. The proinflammatory markers CD95 and tumor necrosis factor-α were assessed using real-time polymerase chain reaction. RESULTS: In group 1 clearance decreased by 20% at 1 week but basal function was regained starting at week 2. In group 2 clearance decreased more than 90% up to week 2. Recovery started at week 3 and by 4 weeks there was a 23% clearance reduction. Histopathological examination in group 1 revealed significant tubular necrosis (60%) at 3 days with regeneration starting at 1 week. In group 2 there was more pronounced tubular necrosis (90%) with regeneration starting at 2 weeks. The expression of proinflammatory markers was up-regulated in each group with higher, more sustained expression in group 2. CONCLUSIONS: Solitary kidney in a canine model is more resistant to ischemia than paired kidneys based on radiological, pathological and genetic evidence.
Assuntos
Isquemia/fisiopatologia , Rim/anormalidades , Rim/irrigação sanguínea , Nefrectomia , Animais , Biópsia por Agulha , Modelos Animais de Doenças , Cães , Taxa de Filtração Glomerular , Imuno-Histoquímica , Isquemia/patologia , Distribuição Aleatória , Valores de Referência , Isquemia QuenteRESUMO
Combined veterinary antibiotics (CVAs) belonging to different antibiotics classes could cause exacerbated impacts on the anaerobic digestion (AD) process of swine manure. Four different antibiotics "two tetracyclines: tetracycline (TC) and oxytetracycline (OTC), one fluoroquinolones: norfloxacin (Norf), and one sulfonamides: sulfadiazine (SDZ)" were combined to evaluate their removal performances and its inhibition effects on AD. Results indicated that CVAs removal decreased from 84.3 to 63.7 %, with an increase in the initial concentration from 12.5 to 50 mg L-1, where the removal of CVAs occurring in the order OTC > TC > Norf > SDZ. An average of 9.5, 7.5, 9.5, and 32.1 % of the spiked TC, OTC, SDZ, and Norf were remained in the sludge, respectively. With 50 mg L-1 of CVAs, a competitive adsorption phenomenon was found to have a notable impact on biodegradation microorganisms' activity leading a 73.1 % decrease in CH4 production. CVAs caused a temporal inhibition to the acidogenic activity followed by partial inhibition to methanogenic by 66.8 %, and IC50 was 38.5 mg L-1. Moreover, CVAs resulted in acetate accumulation, while 26 % and 48 % lower in TS and COD removal, respectively, were observed. A significant reduction in the relative abundance of bacteria and archaeal genera was also mentioned. The findings of this research would provide a more in-depth understanding of AD's performance in treating swine manure contaminated with combined antibiotics.