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Veratrum maackii (VM), a perennial plant in the Melanthiaceae family, has anti-hypertensive, anti-cholinergic, anti-asthmatic, anti-tussive, anti-fungal, anti-melanogenesis, and anti-tumor activities. Here, we investigated the therapeutic effect of VM on benign prostatic hyperplasia (BPH) in human normal prostate cell line (WPMY-1) and a testosterone propionate-induced BPH animal model. WPMY-1 cells were treated with VM (1-10 µg/mL) and testosterone propionate (100 nM). BPH in rats was generated via daily subcutaneous injections of testosterone propionate (3 mg/kg) dissolved in corn oil, for 4 weeks. VM (150 mg/kg) was administered daily for 4 weeks by oral gavage concurrently with the testosterone propionate. All rats were sacrificed and the prostates were dissected, weighed, and subjected to histological, immunohistochemical, and biochemical examinations. Immunoblotting experiments indicated that WPMY-1 cells treated testosterone propionate had increased expression of prostate specific antigen (PSA) and androgen receptor (AR), and treatment with VM or finasteride blocked this effect. In rat model, VM significantly reduced prostate weight, prostatic hyperplasia, prostatic levels of dihydrotestosterone (DHT), and expression of proliferation markers such as proliferating cell nuclear antigen (PCNA) and cyclin D1, but increased the expression of pro-apoptotic Bcl-2-associated X protein (Bax) and the cleavage of caspase-3. VM administration also suppressed the testosterone propionate-induced activation of nuclear factor-kappaB (NF-κB). Our results indicate that VM effectively represses the development of testosterone propionate-induced BPH, suggesting it may be a useful treatment agent for BPH.
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Extratos Vegetais/uso terapêutico , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/tratamento farmacológico , Propionato de Testosterona/toxicidade , Veratrum , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Humanos , Masculino , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Hiperplasia Prostática/patologia , Ratos , Ratos Sprague-Dawley , Resultado do TratamentoRESUMO
Quisqualis indica (QI) has been used for treating disorders such as stomach pain, constipation, and digestion problem. This study was aimed to evaluate the therapeutic efficacy of QI extract on treating benign prostatic hyperplasia (BPH) in LNCaP human prostate cancer cell line and a testosterone-induced BPH rat model. LNCaP cells were treated with QI plus testosterone propionate (TP), and androgen receptor (AR) and prostate specific antigen (PSA) expression levels were assessed by Western blotting. To induce BPH, the rats were subjected to a daily subcutaneous injection of TP (3 mg/kg) for 4 weeks. The rats in treatment group were orally gavaged with QI (150 mg/kg) together with the TP injection. In-vitro studies showed that TP-induced increases in AR and PSA expression in LNCaP cells were reduced by QI treatment. In BPH-model rats, the prostate weight, testosterone in serum, dihydrotestosterone (DHT) concentration and 5α-reductase type 2 mRNA expression in prostate tissue were significantly reduced following the treatment with QI. TP-induced prostatic hyperplasia and the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 were significantly attenuated in QI-treated rats. In addition, QI induced apoptosis by up-regulating caspase-3 and -9 activity and decreasing the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio in prostate tissues of BPH rats. Further investigation showed that TP-induced activation of AKT and glycogen synthase kinase 3ß (GSK3ß) was reduced by QI administration. Therefore, our findings suggest that QI attenuates the BPH state in rats through anti-proliferative and pro-apoptotic activities and might be useful in the clinical treatment of BPH.
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Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Combretaceae/química , Extratos Vegetais/farmacologia , Próstata/efeitos dos fármacos , Hiperplasia Prostática/tratamento farmacológico , Animais , Di-Hidrotestosterona/sangue , Humanos , Masculino , Extratos Vegetais/uso terapêutico , Antígeno Nuclear de Célula em Proliferação , Próstata/citologia , Próstata/patologia , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/sangue , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores Androgênicos/metabolismo , Sementes/química , Testosterona/sangue , Testosterona/metabolismo , Propionato de Testosterona/toxicidadeRESUMO
Obesity increases the risk of chronic liver diseases, including viral hepatitis, alcohol-induced liver disease, and non-alcoholic steatohepatitis. In this study, we investigated the effects of obesity in acute hepatic failure using a murine model of thioacetamide (TA)-induced liver injury. Genetically obese ob/ob mice, together with non-obese ob/+ littermates, were subjected to a single intraperitoneal injection of TA, and examined for signs of hepatic injury. ob/ob mice showed a significantly higher survival rate, lower levels of serum alanine aminotransferase and aspartate aminotransferase, and less hepatic necrosis and apoptosis, compared with ob/+ mice. In addition, ob/ob mice exhibited significantly lower levels of malondialdehyde and significantly higher levels of glutathione and antioxidant enzyme activities compared with their ob/+ counterparts. Bioactivation analyses revealed reduced plasma clearance of TA and covalent binding of [(14)C]TA to liver macromolecules in ob/ob mice. Together, these data demonstrate that genetically obese mice are resistant to TA-induced acute liver injury through diminished bioactivation of TA and antioxidant effects.
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Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Obesidade/genética , Tioacetamida/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Dose Letal Mediana , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/metabolismo , Tioacetamida/metabolismoRESUMO
Nobiletin and tangeretin are polymethoxy flavonoids (PMFs), found in rich quantities in the peel of citrus fruits. In the present study, we assessed the biological effect of the PMFs on liver damage using a mouse model of binge drinking. First, we extracted PMFs from the peels of Citrus aurantium to make Citrus aurantium extract (CAE). Male C57BL/6 mice were orally treated with silymarin and CAE (50, 100, and 200 mg/kg) for 3 days prior to ethanol (5 g/kg, total of 3 doses) oral gavage. Liver injury was observed in the ethanol alone group, as evidenced by increases in serum hepatic enzymes and histopathologic alteration, as well as by hepatic oxidative status disruption. CAE improved serum marker and hepatic structure and restored oxidative status by enhancing antioxidant enzyme levels and by reducing lipid peroxidation levels. In addition, CAE evidently suppressed inflammation and apoptosis in the livers of mice administered with ethanol, by 85% (tumor necrosis factor-α) and 44% compared to the control group, respectively. Furthermore, CAE activated lipid metabolism related signals and enhanced phosphorylation of AMP-activated protein kinase (AMPK) and nuclear factor E2-related factor 2 (Nrf2) with several cytoprotective proteins including heme oxygenase-1, NAD(P)H quinone oxidoreductase 1, and γ-glutamylcysteine synthetase. Taken together, the present study demonstrated that, CAE possesses antioxidant, anti-inflammatory, and antiapoptotic activity against ethanol-induced liver injury.
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Proteínas Quinases Ativadas por AMP , Citrus , Extratos Vegetais , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Consumo Excessivo de Bebidas Alcoólicas , Citrus/química , Modelos Animais de Doenças , Etanol/farmacologia , Flavonas , Flavonoides/farmacologia , Heme Oxigenase-1/metabolismo , Inflamação/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/farmacologia , Silimarina/farmacologia , Fator de Necrose Tumoral alfaRESUMO
As the risk of gypsy moth outbreaks that have detrimental effects on forest ecosystem in the Northern Hemisphere increase due to climate change, a quantitative evaluation of the impact of gypsy moth defoliation is needed to support the adaptive forest management. To evaluate the host-specific impact of gypsy moth defoliation, radial growth and annual carbon accumulation were compared for one severely defoliated (Larix kaempferi (Lamb.) Carrière) and one moderate defoliated (Quercus acutissima Carruth.) host, in defoliated and non-defoliated site using tree-ring analysis. Finally, the resilience indices of radial growth variables were calculated to assess the ability of sampled trees to withstand defoliation. Gypsy moth defoliation mainly decreased latewood width and caused reduction in annual carbon absorption more than 40% for both tree species. However, L. kaempferi, showed the reduced growth until the year following defoliation, while Q. acutissima, showed no lagged growth depression and rapid growth recover. The findings show how each species reacts differently to gypsy moth defoliation and highlight the need of managing forests in a way that takes resilient tree species into account.
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Larix , Mariposas , Quercus , Animais , Carbono , Ecossistema , Complexo de Mariposas do Gênero Lymantria , Mariposas/fisiologia , Quercus/fisiologia , República da Coreia , ÁrvoresRESUMO
Amyotrophic lateral sclerosis (ALS) is a progressive and devastating neurodegenerative disorder characterized by the loss of upper and lower motor neurons, resulting in debilitating muscle weakness and atrophy. Currently, there are no effective treatments available for ALS, posing significant challenges in managing the disease that affects approximately two individuals per 100,000 people annually. To address the urgent need for effective ALS treatments, we conducted a drug repurposing study using a combination of bioinformatics tools and molecular docking techniques. We analyzed sporadic ALS-related genes from the GEO database and identified key signaling pathways involved in sporadic ALS pathogenesis through pathway analysis using DAVID. Subsequently, we utilized the Clue Connectivity Map to identify potential drug candidates and performed molecular docking using AutoDock Vina to evaluate the binding affinity of short-listed drugs to key sporadic ALS-related genes. Our study identified Cefaclor, Diphenidol, Flubendazole, Fluticasone, Lestaurtinib, Nadolol, Phenamil, Temozolomide, and Tolterodine as potential drug candidates for repurposing in sporadic ALS treatment. Notably, Lestaurtinib demonstrated high binding affinity toward multiple proteins, suggesting its potential as a broad-spectrum therapeutic agent for sporadic ALS. Additionally, docking analysis revealed NOS3 as the gene that interacts with all the short-listed drugs, suggesting its possible involvement in the mechanisms underlying the therapeutic potential of these drugs in sporadic ALS. Overall, our study provides a systematic framework for identifying potential drug candidates for sporadic ALS therapy and highlights the potential of drug repurposing as a promising strategy for discovering new therapies for neurodegenerative diseases.
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Ageratum conyzoides, an annual herbaceous plant that inhabits tropical and subtropical regions, has been traditionally used in Asia, Africa, and South America for phytotherapy to treat infectious and inflammatory conditions. However, the pharmacological effects of standardized ethanolic extract of Ageratum conyzoides (ACE) on benign prostatic hyperplasia (BPH) remain unexplored. The objective of this research is to examine the potential physiological impacts of ACE, a traditionally utilized remedy for inflammatory ailments, in a rat model with BPH induced by testosterone propionate (TP). Rats were subcutaneously administered TP (3 mg/kg) to induce BPH and concurrently orally administered ACE (20, 50, and 100 mg/kg) daily for 42 days. ACE markedly improved BPH characteristics, including prostate weight, prostate index, and epithelial thickness, while also suppressing androgens and related hormones. The findings were supported by a decrease in androgen receptor and downstream signals associated with BPH in the prostate tissues of the ACE groups. Furthermore, increased apoptotic signals were observed in the prostate tissue of the ACE groups, along with heightened detection of the apoptotic nucleus compared to the BPH alone group. These changes seen in the group that received finasteride were similar to those observed in this group. These findings suggest that ACE shows promise as an alternative phytotherapeutic agent for treating BPH.
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Ageratum , Apoptose , Proliferação de Células , Extratos Vegetais , Próstata , Hiperplasia Prostática , Ratos Sprague-Dawley , Masculino , Animais , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/patologia , Extratos Vegetais/farmacologia , Apoptose/efeitos dos fármacos , Próstata/efeitos dos fármacos , Próstata/patologia , Ratos , Ageratum/química , Proliferação de Células/efeitos dos fármacos , Testosterona/sangue , Propionato de Testosterona , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , FitoterapiaRESUMO
Introduction: Cissus quadrangularis is a vining plant widely used as a traditional herbal remedy for various ailments. In this study, the therapeutic effects of C. quadrangularis extract (CQR-300) on type 2 diabetes mellitus (T2DM) were investigated in a leptin receptor-mutated db/db mouse model. Methods: CQR-300 was orally administered to db/db mice (n = 6/group) at different doses (50, 100, and 200 mg/kg) for 8 weeks. Blood glucose levels and oral glucose tolerance were assessed using the AccuCheck glucometer. Enzyme-linked immunosorbent assay was performed to evaluate insulin and hemoglobin A1c (HbA1c) levels in the blood of db/db mice. Liver and pancreatic tissues from db/db mice were examined by hematoxylin and eosin (H&E) and immunohistochemical staining. The protein levels of gluconeogenesis-, lipogenesis-, and oxidative stress-related factors were evaluated using western blotting. Results and discussion: CQR-300 treatment effectively reduced body weight, blood glucose, and insulin levels. HbA1c levels were increased by leptin receptor mutation. Additionally, in the oral glucose tolerance tests, the CQR-300 treated group had a faster blood glucose recovery rate than the db/db group. H&E and Oil red-O staining of the liver showed decreased lipid accumulation in the CQR-300 treated group than the db/db group. Western blot analysis confirmed that CQR-300 effectively inhibited gluconeogenesis, lipogenesis, and oxidative stress-related factors. Our findings suggest that CQR-300 has the potential to be used as a T2DM supplement.
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Scutellaria baicalensis has been used as a traditional herbal medicine for bronchitis, hepatitis, and allergic diseases. The root of Scutellaria baicalensis contains active flavonoid components, including baicalin, baicalein, wogonoside, and wogonin, which have pharmaceutical properties. In the present study, the antiallergic properties of a standardized aqueous extract of S. baicalensis were evaluated, and the skin toxicity of its dermal application was also determined. The in vivo and in vitro assays were performed by using the ß-hexosaminidase assay in rat basophilic leukemia cells (RBL-2H3) and cutaneous skin reaction in BALB/c mice, respectively. In addition, the acute dermal irritation/corrosion test was carried out in New Zealand white rabbits, and the skin sensitization test was conducted by Buhler's method in Hartley guinea pigs to estimate the safety of the standardized aqueous extract of S. baicalensis for topical application. ß-Hexosaminidase release in RBL-2H3 was markedly decreased following treatment with the standardized aqueous extract of S. baicalensis. It also ameliorated antigen-induced ear swelling compared with the control group in BALB/c mice. In the toxicological studies, it did not induce any dermal irritation/corrosion in rabbits or skin sensitization in guinea pigs. Although still limited, these results concerning the toxicological effects of S. baicalensis could be an initial step toward the topical application of S. baicalensis extracts on hypersensitive skin.
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Antialérgicos/farmacologia , Flavonoides/farmacologia , Hipersensibilidade , Extratos Vegetais/farmacologia , Administração Tópica , Animais , Antialérgicos/química , Antialérgicos/isolamento & purificação , Linhagem Celular Tumoral , Flavanonas/química , Flavanonas/isolamento & purificação , Flavanonas/farmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Glucosídeos/química , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Cobaias , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Plantas Medicinais , Coelhos , Ratos , Scutellaria baicalensis/química , Pele/efeitos dos fármacos , beta-N-Acetil-Hexosaminidases/análiseRESUMO
The warm temperate deciduous forests in Asia have a relatively dense understory, hence, it is imperative that we understand the dynamics of transpiration in both the overstory (E O) and understory (E U) of forest stands under the influence of the Asian monsoon in order to improve the accuracy of forest water use budgeting and to identify key factors controlling forest water use under climate change. In this study, E O and E U of a temperate deciduous forest stand located in South Korea were measured during the growing season of 2008 using sap flow methods. The objectives of this study were (1) to quantify the total transpiration of the forest stand, i.e., overstory and understory, (2) to determine their relative contribution to ecosystem evapotranspiration (E eco), and (3) to identify factors controlling the transpiration of each layer. E O and E U were 174 and 22 mm, respectively. Total transpiration accounted for 55 % of the total E eco, revealing the importance of unaccounted contributions to E eco (i.e., soil evaporation and wet canopy evaporation). During the monsoon period, there was a strong reduction in the total transpiration, likely because of reductions in photosynthetic active radiation, vapor pressure deficit and plant area index. The ratio of E U to E O declined during the same period, indicating an effect of monsoon on the partitioning of E eco in its two components. The seasonal pattern of E O was synchronized with the overstory canopy development, which equally had a strong regulatory influence on E U.
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Transpiração Vegetal/fisiologia , Árvores/fisiologia , Água/fisiologia , Biometria , Meio Ambiente , Folhas de Planta/fisiologia , Caules de Planta , República da Coreia , Estações do AnoRESUMO
Two-dimensional graphene oxide (GO)-based lamellar membranes have been widely developed for desalination, water purification, gas separation, and pervaporation. However, membranes with a well-organized multilayer structure and controlled pore size remain a challenge. Herein, an easy and efficient method is used to fabricate MoO2@GO and WO3@GO nanocomposite membranes with controlled structure and interlayer spacing. Such membranes show good separation for salt and heavy metal ions due to the intensive stacking interaction and electrostatic attraction. The as-prepared composite membranes showed high rejection rates (Ë70%) toward small metal ions such as sodium (Na+) and magnesium (Mg2+) ions. In addition, both membranes also showed high rejection rates Ë99% for nickel (Ni2+) and lead (Pb2+) ions with good water permeability of 275 ± 10 L m-2 h-1 bar-1. We believe that our fabricated membranes will have a bright future in next generation desalination and water purification membranes.
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CONTEXT: The root of Platycodon grandiflorum (Jacq.) A. DC. (Campanulaceae) has been widely studied for its hepatoprotective effects against various hepatotoxicants. OBJECTIVE: The present study evaluated the protective effect of the standardized aqueous extract of P. grandiflorum (BC703) on cholestasis-induced hepatic injury in mice. MATERIALS AND METHODS: BC703 is a standardized aqueous extract of P. grandiflorum in reference to platycodin D (at least 0.8%). The mice were allocated into five groups as follows: Sham-operated, bile duct ligation (BDL) alone, and BDL with BC703 (1, 5, and 10 mg/kg BW) treated group. BC703 was given for 3 consecutive days before BDL operation. The animals were sacrificed by CO2 anesthesia post-24 h of BDL operations. RESULTS AND DISCUSSION: Serum alanine aminotransferase and serum aspartate aminotransferase increased to 395.2 ± 90.0 and 266.0 ± 45.6 Unit/L in the BDL alone group and decreased with BC703 in a dose-dependent manner. Especially the 10 mg/kg of BC703-treated mice showed a 77% decrease of serum alanine aminotransferase and 56% of aspartate aminotransferase as compared with BDL alone. Decreased antioxidant enzyme levels in BDL alone group were elevated in BC703-treated groups ranging from 7 to 29% for glutathione and from 13 to 25% for superoxide dismutase. BC703 treatment also attenuated malondialdehyde (from 3 to 32%) and nitric oxide levels (from 32 to 50%) as compared with BDL alone. Histopathological studies further confirmed the hepatoprotective effect of BC703 in BDL-induced cholestesis. CONCLUSION: BC703 could attenuate liver injury by BDL in mice, and test results indicate that BC703 might be useful in cholestatic liver injury.
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Colestase Extra-Hepática/tratamento farmacológico , Hepatopatias/prevenção & controle , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Platycodon , Substâncias Protetoras/farmacologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Colestase Extra-Hepática/sangue , Colestase Extra-Hepática/etiologia , Colestase Extra-Hepática/patologia , Cromatografia Líquida de Alta Pressão , Ducto Colédoco/cirurgia , Citoproteção , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Glutationa/metabolismo , Ligadura , Fígado/enzimologia , Fígado/patologia , Hepatopatias/sangue , Hepatopatias/etiologia , Hepatopatias/patologia , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Óxido Nítrico/metabolismo , Extratos Vegetais/análise , Extratos Vegetais/isolamento & purificação , Raízes de Plantas , Plantas Medicinais , Platycodon/química , Substâncias Protetoras/análise , Substâncias Protetoras/isolamento & purificação , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de TempoRESUMO
Owing to climate change and frequent extreme weather events, changes in spring flowering phenology have been observed in temperate forests. The flowering time response to climate change is divergent among species and is difficult to predict due to the complexity of flowering mechanisms. To compare the effects of spring warming, winter chilling, and day length on spring flowering time, we evaluated eight process-based models (two types of forcing models, two types of chilling-forcing models, and four models with the effect of day length added to the aforementioned four models). We used flowering data of seven temperate species (Cornus officinalis, Rhododendron mucronulatum, Forsythia koreana, Prunus yedoensis, Rhododendron yedoense f. poukhanense, Rhododendron schlippenbachii, and Robinia pseudoacacia) observed in nine different arboretums in South Korea over 9 years. Generally, the forcing model performed better than the sequential chilling-forcing model, regardless of the species. The performance gap between the models was reduced when day length term was included in model, but the chilling-forcing model did not outperform the forcing model. The effect of day length on flowering time differed depending on the species. Prunus yedoensis, which had a particularly low warming sensitivity compared to other species, was more dependent on day length than other species. On the other hand, day length had little effect on the flowering time of Robinia pseudoacacia and Cornus officinalis, mostly found in the early successional stage. These findings imply that the effect of chilling on flowering time would be minor for the seven species inhabiting the warm-temperate forest, and the effect of day length on flowering time was species-specific and dependent on species' temperature (warming) sensitivity and life strategy. In the future warm climate, the flowering time of day length sensitive species would not advance significantly, which may result in a phenological mismatch and endanger their life.
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Mudança Climática , Florestas , Reprodução , Estações do Ano , TemperaturaRESUMO
The global spread of the SARS coronavirus 2 (SARS-CoV-2), its manifestation in human hosts as a contagious disease, and its variants have induced a pandemic resulting in the deaths of over 6,000,000 people. Extensive efforts have been devoted to drug research to cure and refrain the spread of COVID-19, but only one drug has received FDA approval yet. Traditional drug discovery is inefficient, costly, and unable to react to pandemic threats. Drug repurposing represents an effective strategy for drug discovery and reduces the time and cost compared to de novo drug discovery. In this study, a generic drug repurposing framework (SperoPredictor) has been developed which systematically integrates the various types of drugs and disease data and takes the advantage of machine learning (Random Forest, Tree Ensemble, and Gradient Boosted Trees) to repurpose potential drug candidates against any disease of interest. Drug and disease data for FDA-approved drugs (n = 2,865), containing four drug features and three disease features, were collected from chemical and biological databases and integrated with the form of drug-disease association tables. The resulting dataset was split into 70% for training, 15% for testing, and the remaining 15% for validation. The testing and validation accuracies of the models were 99.3% for Random Forest and 99.03% for Tree Ensemble. In practice, SperoPredictor identified 25 potential drug candidates against 6 human host-target proteomes identified from a systematic review of journals. Literature-based validation indicated 12 of 25 predicted drugs (48%) have been already used for COVID-19 followed by molecular docking and re-docking which indicated 4 of 13 drugs (30%) as potential candidates against COVID-19 to be pre-clinically and clinically validated. Finally, SperoPredictor results illustrated the ability of the platform to be rapidly deployed to repurpose the drugs as a rapid response to emergent situations (like COVID-19 and other pandemics).
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Tratamento Farmacológico da COVID-19 , Reposicionamento de Medicamentos , Reposicionamento de Medicamentos/métodos , Humanos , Aprendizado de Máquina , Simulação de Acoplamento Molecular , SARS-CoV-2RESUMO
BACKGROUND: Plants have been considered a vital source of modern pharmaceutics since the paleolithic age. Contemporary chemotherapeutic drugs for cancer therapy are chemical entities sourced from plants. However, synthetic drugs or their derivatives come with severe to moderate side effects for human health. Hence, the quest to explore and discover plant-based novel anticancer drugs is ongoing. Anticancer activities are the primary method to estimate the potential and efficacy of an extract or compound for drug discovery. However, traditional in vitro anticancer activity assays often show poor efficacy due to the lack of in-vivo-like cellular environment. In comparison, the animal-based in vivo assays lack human genetic makeup and have ethical concerns. AIM: This study aimed to overcome the limitations of traditional cell-culture-based anticancer assays and find the most suitable assay for anticancer activity of plant extracts. We first reported utilizing a liver tumor microphysiological system in the anticancer effect assessment of plant extracts. METHODOLOGY: Methanolic extracts of Acer cappadocicum Gled were used to assess anticancer activity against liver tumor microphysiological system (MPS), and cell viability, liver function tests, and antioxidant enzyme activities were performed. Additionally, an embedded transepithelial electrical resistance sensor was utilized for the real-time monitoring of the liver tumor MPS. The results were also compared with the traditional cell culture model. RESULTS: The study demonstrated the superiority of the TEER sensor-based liver tumor MPS by its better anticancer activity based on cell viability and biomarker analysis compared to the traditional in vitro cell culture model. The anticancer effects of the plant extracts were successfully observed in real time, and methanolic extracts of Acer cappadocicum Gled increased the alanine transaminase and aspartate aminotransferase secretion, which may reveal the different mechanisms of these extracts and suggest a clue for the future molecular study of the anticancer pathways. CONCLUSION: Our results show that the liver tumor microphysiological system could be a better platform for plant-based anticancer activity assessment than traditional cell culture models.
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Thioacetamide (TA) is a commonly used drug that can trigger acute hepatic failure (AHF) through generation of oxidative stress. Vitamin D3 upregulated protein 1 (VDUP1) is an endogenous inhibitor of thioredoxin, a ubiquitous thiol oxidoreductase, that regulates cellular redox status. In this study, we investigated the role of VDUP1 in AHF using a TA-induced liver injury model. VDUP1 knockout (KO) and wild-type (WT) mice were subjected to a single intraperitoneal TA injection, and various parameters of hepatic injury were assessed. VDUP1 KO mice displayed a significantly higher survival rate, lower serum alanine aminotransferase and aspartate aminotransferase levels, and less hepatic damage, compared to WT mice. In addition, induction of apoptosis was decreased in VDUP1 KO mice, with the alteration of caspase-3 and -9 activities, Bax-to-Bcl-2 expression ratios, and mitogen activated protein kinase (MAPK) signaling pathway. Importantly, analysis of TA bioactivation revealed lower plasma clearance of TA and covalent binding of [¹4C]TA to liver macromolecules in VDUP1 KO mice. Furthermore, the level of oxidative stress was significantly less in VDUP1 KO mice than in their WT counterparts, as evident from lipid peroxidation assay. These results collectively indicate that VDUP1 deficiency protects against TA-induced acute liver injury via lower bioactivation of TA and antioxidant effects.
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Proteínas de Transporte/fisiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Tioacetamida/toxicidade , Tiorredoxinas/fisiologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteínas de Transporte/genética , Doença Hepática Induzida por Substâncias e Drogas/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Distribuição Aleatória , Tiorredoxinas/genéticaRESUMO
Toltrazuril (TZR) is a triazine-based antiprotozoal agent. Following a single oral administration of TZR at 10 and 20 mg/kg to male pigs, the mean TZR concentration in plasma peaked at 4.24 and 8.18 microg/ml at 15.0 and 12.0 hr post-dose, respectively. TZR absorbed was rapidly converted to the short-lived intermediary metabolite toltrazuril sulfoxide (TZR-SO), and then metabolized to the reactive toltrazuril sulfone (TZR-SO2). TZR-SO2 was actually more slowly eliminated, with average half-lives of 231 and 245 hr, compared with TZR (48.7 and 68.9 hr) or TZR-SO (51.9 and 53.2 hr) in the 10 and 20 mg/kg groups, respectively. This study demonstrates that TZR metabolizes to TZR-SO2 having a long-terminal half-life, enabling the persistent clinical efficacy in the treatment of I. suis infection. In contrast, special consideration should be given to the residual of TZR-SO2.
Assuntos
Coccidiostáticos/farmacocinética , Triazinas/farmacocinética , Administração Oral , Animais , Coccidiostáticos/administração & dosagem , Coccidiostáticos/sangue , Absorção Intestinal , Cinética , Masculino , Sulfonas/farmacocinética , Sulfóxidos/sangue , Sulfóxidos/farmacocinética , Suínos , Triazinas/administração & dosagem , Triazinas/sangueRESUMO
Vaspin is a protein present in human serum that can cause type-2 diabetes, obesity, and other cardiovascular diseases. We report fluorescent upconverting nanoparticles (UCNPs)-based lateral flow biosensor for ultrasensitive detection of Vaspin. A pair (primary and secondary) of cognate aptamers was used that has duo binding with Vaspin. UCNPs with a diameter of around 100â¯nm were used as a tag to label a detection probe (secondary aptamer). A primary aptamer (capture probe) was immobilized on the test zone. Sandwich type hybridization reactions among the conjugate probe, target Vaspin, and primary aptamer were performed on the lateral flow biosensor. In the presence of target Vaspin, UCNPs were captured on the test zone of the biosensor and the fluorescent intensity of the captured UCNPs was measured through a colorimetric app under NIR. Fluorescence intensity indicates the quantity of Vaspin present in the sample. A range of Vaspin concentration across 0.1-55â¯ngâ¯ml-1 with a Limit of detection (LOD) 39â¯pgâ¯ml-1 was tested through this UCNPs based LFSA with high sensitivity, reproducibility and repeatability, whereas it's actual range in human blood is from 0.1 to 7â¯ngâ¯ml-1. Therefore, this research provides a well-suited lateral flow strip with an ultrasensitive and low-cost approach for the early diagnosis of type-2 diabetes and this could be applied to any targets with a duo of aptamers generated.
Assuntos
Técnicas Biossensoriais/métodos , Análise Química do Sangue/métodos , Corantes Fluorescentes , Nanopartículas/química , Serpinas/análise , Aptâmeros de Nucleotídeos/análise , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diagnóstico Precoce , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacocinética , Humanos , Limite de Detecção , Ligação Proteica , Reprodutibilidade dos Testes , Serpinas/metabolismoRESUMO
Benign prostate hyperplasia (BPH) is a common disease in old-age males, accounting for approximately 77% of morbidity within the age range of 40 to 70 years. It has been shown that morbidity increases with social graying. Quisqualis indica linn (QI) has been used to treat inflammation, stomach pain, and digestion problems. In this study, we evaluated the symptom-regulating effects of QI extract on a testosterone-induced BPH rat model. After inducing BPH in rats using testosterone propionate (TP) injection, we assessed basal intraurethral pressure (IUP) and increments of IUP elicited by electrical field stimulation (5 V, 5, 10, or 20 Hz) or phenylephrine (Phe) (0.01, 0.03, 0.1 mg/kg IV). To induce BPH, 8-week-old rats were subjected to a daily subcutaneous TP (3 mg/kg) injection for 4 weeks. Finasteride (Fina) (10 mg/kg PO) was administered to the rats in the first treatment, while QI (150 mg/kg PO) was administered to those in the second group. Blood pressure was measured together with IUP, after which low urinary tract (LUT), ventral prostate (VP), testicle, and corpus spongiosum were isolated and weighed. Basal IUPs for the Fina- and QI-treated groups were 87.6 and 86.8%, respectively. LUT and VP organ weights in the QI group were lower than those in the Fina group. However, the QI group showed significantly reduced electrical stimulated or Phe-induced IUP increment compared to the Fina and BPH groups. These results proved that QI can be beneficial for BPH symptoms by inhibiting 5α-reductase and consequently decreasing prostate and releasing urinary pressure.
RESUMO
Studies on abundance and distribution at different scales are rare. We examined whether the abundance of flower flies at a site in South Korea was related to the national occupancy and global distribution (distributional extent or range size) and whether the national occupancy was related to global distribution. In global distribution, the influence of two dimensions (latitude and longitude) was analyzed separately. Flower flies were collected by malaise and pitfall traps at a forest gap in South Korea. Data regarding national occupancy and global distribution were obtained from a Korean Flower Fly Atlas. We collected 46 species from the field survey and obtained a list of 119 species from the Korean Flower Fly Atlas. Our results showed that abundance at a site was positively correlated with national occupancy, but not global distribution, and the national occupancy was positively correlated with global distribution, mainly by the latitudinal range size. Finally, our results indicated that the regional distribution of flower flies was influenced by its one-dimensional global distribution.