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Lung cancer (LC) represents the leading cause of global cancer deaths, with cigarette smoking being considered a major risk factor. Nicotine is a major hazardous compound in cigarette smoke (CS), which stimulates LC progression and non-small cell lung cancer (NSCLC) specifically through activation of the nicotinic acetylcholine receptor (α7nAChR)-mediated cell-signaling pathways and molecular genes involved in proliferation, angiogenesis, and metastasis. Chalcones (CHs) and their derivatives are intermediate plant metabolites involved in flavonol biosynthesis. Isoliquiritigenin (ILTG), licochalcone A-E (LicoA-E), and echinatin (ECH) are the most common natural CHs isolated from the root of Glycyrrhiza (also known as licorice). In vitro and/or vivo experiments have shown that licorice CHs treatment exhibits a range of pharmacological effects, including antioxidant, anti-inflammatory, and anticancer effects. Despite advances in NSCLC treatment, the mechanisms of licorice CHs in nicotine-induced NSCLC treatment remain unknown. Therefore, the aim of this paper is to review experimental studies through the PubMed/Medline database that reveal the effects of licorice CHs and their potential mechanisms in nicotine-induced NSCLC treatment.
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Kojic acid is a wonderful fungal secondary metabolite that has several applications in the food, medical, and agriculture sectors. Many human diseases become resistant to normal antibiotics and normal treatments. We need to search for alternative treatment sources and understand their mode of action. Aspergillus flavus ASU45 (OL314748) was isolated from the caraway rhizosphere as a non-aflatoxin producer and identified genetically using 18S rRNA gene sequencing. After applying the Box-Behnken statistical design to maximize KA production, the production raised from 39.96 to 81.59 g/l utilizing (g/l) glucose 150, yeast extract 5, KH2PO4 1, MgSO4.7H2O 2, and medium pH 3 with a coefficient (R2) of 98.45%. Extracted KA was characterized using FTIR, XRD, and a scanning electron microscope. Crystalized KA was an effective antibacterial agent against six human pathogenic bacteria (Bacillus cereus, Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, Serratia marcescens, and Serratia plymuthica). KA achieves high inhibition activity against Bacillus cereus, K. pneumonia, and S. plymuthica at 100 µg/ml concentration by 2.75, 2.85, and 2.85 compared with chloramphenicol which gives inhibition zones 1, 1.1, and 1.6, respectively. Crystalized KA had anticancer activity versus three types of cancer cell lines (Mcf-7, HepG2, and Huh7) and demonstrated high cytotoxic capabilities on HepG-2 cells that propose strong antitumor potent of KA versus hepatocellular carcinoma. The antibacterial and anticancer modes of action were illustrated using the molecular docking technique. Crystalized kojic acid from a biological source represented a promising microbial metabolite that could be utilized as an alternative antibacterial and anticancer agent effectively.
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Antibacterianos , Antineoplásicos , Aspergillus flavus , Simulação de Acoplamento Molecular , Pironas , Aspergillus flavus/efeitos dos fármacos , Aspergillus flavus/metabolismo , Aspergillus flavus/genética , Pironas/farmacologia , Pironas/química , Pironas/metabolismo , Antibacterianos/farmacologia , Antibacterianos/química , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Testes de Sensibilidade Microbiana , Linhagem Celular Tumoral , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/metabolismo , Bactérias/classificaçãoRESUMO
BACKGROUND: Azo dyes represent a common textile dye preferred for its high stability on fabrics in various harsh conditions. Although these dyes pose high-risk levels for all biological forms, fungal laccase is known as a green catalyst for its ability to oxidize numerous dyes. METHODS: Trichoderma isolates were identified and tested for laccase production. Laccase production was optimized using Plackett-Burman Design. Laccase molecular weight and the kinetic properties of the enzyme, including Km and Vmax, pH, temperature, and ionic strength, were detected. Azo dye removal efficiency by laccase enzyme was detected for Congo red, methylene blue, and methyl orange. RESULTS: Eight out of nine Trichoderma isolates were laccase producers. Laccase production efficiency was optimized by the superior strain T. harzianum PP389612, increasing production from 1.6 to 2.89 U/ml. In SDS-PAGE, purified laccases appear as a single protein band with a molecular weight of 41.00 kDa. Km and Vmax values were 146.12 µmol guaiacol and 3.82 µmol guaiacol/min. Its activity was stable in the pH range of 5-7, with an optimum temperature range of 40 to 50 °C, optimum ionic strength of 50 mM NaCl, and thermostability properties up to 90 °C. The decolorization efficiency of laccase was increased by increasing the time and reached its maximum after 72 h. The highest efficiency was achieved in Congo red decolorization, which reached 99% after 72 h, followed by methylene blue at 72%, while methyl orange decolorization efficiency was 68.5%. CONCLUSION: Trichoderma laccase can be used as an effective natural bio-agent for dye removal because it is stable and removes colors very well.
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Compostos Azo , Corantes , Lacase , Temperatura , Lacase/metabolismo , Lacase/química , Lacase/isolamento & purificação , Compostos Azo/metabolismo , Corantes/metabolismo , Corantes/química , Cinética , Concentração de Íons de Hidrogênio , Vermelho Congo/metabolismo , Concentração Osmolar , Hypocreales/enzimologia , Hypocreales/metabolismo , Biodegradação Ambiental , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/química , Proteínas Fúngicas/isolamento & purificaçãoRESUMO
Asthma is considered a chronic inflammatory disorder associated with airway hyperresponsiveness (AHR). Increased oxidative stress (OS) is a clinical feature of asthma, which promotes the inflammatory responses in bronchial/airway epithelial cells. Smokers and nonsmokers with asthma have been shown to have increases in several OS and inflammatory biomarkers. However, studies suggest significant differences in OS and inflammation biomarkers between smokers and nonsmokers. A few studies suggest associations between antioxidant intake from diet/supplements and asthma in patients with different smoking status. Evidence is lacking on the protective role of antioxidant vitamin and/or mineral consumption against asthma by smoking status with respect to inflammation and OS biomarkers. Therefore, the aim of this review is to highlight current knowledge regarding the relations between antioxidant intake, asthma, and its associated biomarkers, according to smoking status. This paper can be used to guide future research directions towards the health consequences of antioxidant intake in smoking and nonsmoking asthmatics.
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Most heavy metals and industrial chemicals such as nicotine and lead cause harm to the reproduction process through a decrease in sperm motility, fertilization process, and sperm binding to the oocyte. Salvia officinalis L. (sage) has been reported to enhance serum testosterone levels and other certain biochemical enzymes. Thus, the current study is aimed at evaluating the potential health benefits of S. officinalis L. methanol extract on lead and nicotine hydrogen tartrate-induced sperm quality degeneration in male rats and also identifying some of the non-polar volatile bioactive compounds that might be attributed to the bioactivity of S. officinalis extract using gas chromatography-mass spectrometry (GC/MS). In the study, fifty-four mature male albino rats of about 220-250â g [were divided randomly and equally into 9â groups (n=6)]. Sperm quality degeneration was induced through the oral administration of 1.5â g/L of lead acetate in drinking water or peritoneal injection of 0.50â mg/kg (animal weight) nicotine hydrogen tartrate for sixty days. Two doses (200 & 400â mg/kg b.w.) of S. officinalis L. were used. The rats were anesthetized after the experimental period and then sacrificed. Blood samples were collected while the epididymis, testicle, and accessory sex organs (prostates and seminal vesical) were taken for histopathological studies. Twelve major compounds were identified through the GC/MS analysis of S. officinalis L. methanol extract. Lead and nicotine toxicity had a great effect on the rats' sperm quality causing a significant (p<0.05) decrease in the quantity of sperm and sperm motility as well as an upsurge in the abnormalities of the sperm and a reduction in the length & diameter of seminiferous tubules and size & weight of sexual organs (accessory sex glands, epididymis, and testis). The administration of S. officinalis L. methanol extract, however, had a positive impact on the sexual organ weights, semen quality & quantity, and rats' fertility, thus, ameliorating the adversative effects of both lead and nicotine. Further evaluation and isolation of the bioactive components are recommended as potential drug leads.
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Metanol , Salvia officinalis , Ratos , Masculino , Animais , Nicotina/farmacologia , Análise do Sêmen , Tartaratos/farmacologia , Ratos Wistar , Contagem de Espermatozoides/métodos , Motilidade dos Espermatozoides , Sementes , Espermatozoides , Extratos Vegetais/farmacologiaRESUMO
Flavonoids are the largest group of polyphenols, represented by many compounds that exhibit high anticancer properties. Quercetin (Q) and its main derivatives (rutin, quercitrin, isoquercitrin, isorhamnetin, tamarixetin, rhamnetin, and hyperoside) in the class of flavonols have been documented to exert anticancer activity. Q has been shown to be useful in the treatment of non-small cell lung cancer (NSCLC), as demonstrated by in vitro/in vivo studies, due to its antitumor, anti-inflammatory, anti-proliferative, anti-angiogenesis, and apoptotic properties. Some flavonoids (flavone, anthocyanins, and proanthocyanidins) have been demonstrated to be effective in nicotine-induced NSCLC treatment. However, the molecular mechanisms of quercetin derivatives (QDs) in nicotine-induced NSCLC treatment remain unclear. Thus, this review aims to summarize the available literature on the therapeutic effects of QDs in nicotine-induced NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Quercetina/farmacologia , Quercetina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Nicotina/farmacologia , Nicotina/uso terapêutico , Antocianinas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Flavonoides/farmacologiaRESUMO
The human population is increasing by 0.96% annually and is estimated to reach from 7.3 to 9 billion in 2050 and 11 billion in 2100. The world's agriculture is under pressure to produce more food and ensure food security. On the other hand, around 40% of the cultivable land is already degraded due to various factors including urbanization, soil sealing, soil acidification, salinization, soil erosion, and contamination. Arbuscular mycorrhizal fungi (AMF) constitute a unique group of root obligate symbiont that exchange mutual benefits with about 90% of terrestrial plants and represents a key link between plants and soil mineral nutrients. Literature is scanty on the studies on massive inoculation of AMF in food crops in agronomic settings, and thereby achieving efficient uptake and minimization of the major soil nutrients, eventually meeting our food demand under increasing and inevitable stressed environments. Given above, this review aimed to (i) introduce agricultural soil-contamination, and the relation of soil microbiome with the health of soils and plants; (ii) briefly overview AMF; (iii) highlight AMF role as a bioinoculant, and enhancer of efficient uptake and loss-minimization of nutrients; (iv) appraise literature available on AMF role in the regulation of growth and nutrition mainly in vegetable, horticultural crops and fruit trees; (v) enlighten the role and major mechanisms underlying AMF-mediated regulation of plant growth and nutrition under major biotic and abiotic stresses; (vi) highlight AMF role in the minimization of greenhouse gas emissions; and (vii) list major aspects so far unexplored in the current context.
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Micorrizas , Produtos Agrícolas , Humanos , Micorrizas/fisiologia , Nutrientes , Raízes de Plantas/microbiologia , Solo , Microbiologia do SoloRESUMO
Flap options for upper limb reconstruction have increased due to better understanding of its vascular anatomy. The posterior interosseus artery flap (PIAF) is used to cover defects of the wrist, hand, proximal thumb, and first web space. This flap has many advantages but requires good knowledge about the anatomy of the posterior interosseus artery (PIOA) and its perforators. METHODS: Twenty upper extremity cadaveric specimens were injected with red latex, Fine dissection of the PIOA and its perforators took place; the perforators were counted, measured, described and photographed. Twenty patients with dorsal hand defects, had PIAF. Cases have Post-operative care and followed up for 6 months post-operative. RESULTS: The PIOA was constant in all cadaveric dissections and gave off 4-8 septocutaneous perforators along its course between the extensor carpi ulnaris (ECU) and extensor digitorum (EDM) muscles. The mean distance of the distal most perforator in the middle third forearm from the ulnar styloid was 10.39 ± 1.54 cm. The anastomosis between the PIOA and the anterior interosseus artery (AIOA) was there in all specimens. Venous congestion occurred in 10% of the cases and was managed conservatively. Necrosis of the distal third of the flap was inevitable in one case; excellent results were obtained in the other cases 90%. CONCLUSIONS: The posterior interosseus artery flap is an excellent perforator flap for hand reconstruction preserving the ulnar and radial artery; but it has a possible complications such as venous congestion or partial flap necrosis that could be managed conservatively. LEVEL OF EVIDENCE: II.
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Hiperemia , Retalho Perfurante , Cadáver , Humanos , Necrose , Retalho Perfurante/irrigação sanguínea , Artéria Ulnar/cirurgiaRESUMO
Thermosensitive liposomes loaded with cisplatin and doxorubicin composed of DPPC, DSPC, and DPPE-PEG5000 with different ratios were prepared by thin film hydration method. The Differential Scanning Calorimetry (DSC) curves showed that the liposomes composed of DPPC-DSPC-DPPE-PEG5000 with phospholipid ratio 95:5:0.05 w/w were a suitable formulation as thermosensitive liposomes with a DSC peak at 42.1 °C. The effect of doxorubicin and cisplatin encapsulated non-thermosensitive and thermosensitive liposomes on cellular proliferation and IC50 in SKBR3 & MDA-MB-231 breast cancer and PC-3 & LNcaP prostate cancer cell lines was investigated. The results showed that doxorubicin loaded into thermosensitive liposomes showed 20-fold decrease in the IC50 at 42 °C while comparing it with the same at 37 °C. Also, the results showed a more than 35-fold and 12-fold decrease in the IC50 of cisplatin thermosensitive liposomes at 42 °C, while compared with free cisplatin and cisplatin thermosensitive liposomes at any temperature. The in vivo results showed that the effect of doxorubicin encapsulated thermosensitive liposomes at hyperthermic conditions during the treatment as the tumor growth inhibition was measured 1.5-fold higher than any of the liposomal formulations of doxorubicin. It was also noticed that the tumor volume reduced to 150 mm3 in doxorubicin thermosensitive liposomes (G8) after 3 weeks during the treatment, but increased to 196 mm3 after 4 weeks. The Kaplan-Meir curve showed the 100% survival of the animals from G8 (thermosensitive liposomes containing doxorubicin plus hyperthermia) after 12 weeks. The flow cytometry data revealed more than 25% apoptotic cells and 6.25% necrotic cells in the tumor cells from the tissues of the G8 group of the animals. The results clearly indicate the superior efficacy of doxorubicin and cisplatin containing thermosensitive liposomes treatment during hyperthermia.
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Antineoplásicos , Neoplasias , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Cisplatino/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Lipossomos/química , Masculino , Neoplasias/tratamento farmacológico , FosfolipídeosRESUMO
In traditional medicine, different parts of plants, including fruits, have been used for their anti-inflammatory and anti-oxidative properties. Plant-based foods, such as fruits, seeds and vegetables, are used for therapeutic purposes due to the presence of flavonoid compounds. Proanthocyanidins (PCs) and anthocyanins (ACNs) are the major distributed flavonoid pigments in plants, which have therapeutic potential against certain chronic diseases. PCs and ACNs derived from plant-based foods and/or medicinal plants at different nontoxic concentrations have shown anti-non-small cell lung cancer (NSCLC) activity in vitro/in vivo models through inhibiting proliferation, invasion/migration, metastasis and angiogenesis and by activating apoptosis/autophagy-related mechanisms. However, the potential mechanisms by which these compounds exert efficacy against nicotine-induced NSCLC are not fully understood. Thus, this review aims to gain insights into the mechanisms of action and therapeutic potential of PCs and ACNs in nicotine-induced NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Proantocianidinas , Antocianinas/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Flavonoides/farmacologia , Humanos , Neoplasias Pulmonares/patologia , Nicotina/efeitos adversos , Plantas , Proantocianidinas/farmacologia , Proantocianidinas/uso terapêuticoRESUMO
The involvement of hydrogen peroxide (H2 O2 ) combined with sulfur (S) was studied in the protection of the photosynthetic performance of wheat (Triticum aestivum L.) under drought stress. The mechanisms of S-assimilation, the activity of antioxidants, glucose sensitivity, water and osmotic relations and abscisic acid (ABA) content were the focus. The combined application of 50 µM H2 O2 and 100 mg S kg-1 soil (sulfur) resulted in a marked increase in S-assimilation and activity of antioxidant enzymes, with decreased glucose sensitivity and ABA content causing improvement in the structure and function of the photosynthetic apparatus under drought stress. The photosynthetic performance, pigment system (PS) II activity, and growth were improved conspicuously by H2 O2 in the presence of S, as H2 O2 induced S-assimilation capacity, the activity of antioxidant enzymes, and GSH synthesis under drought stress. Our study shows that H2 O2 is more effective in the reversal of drought stress in the presence of S through its influence on S-assimilation, glucose sensitivity, and antioxidant system. These results provide evidence for the effectiveness of H2 O2 in improving photosynthesis under drought stress in the presence of S.
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Secas , Triticum , Antioxidantes/metabolismo , Cloroplastos/metabolismo , Peróxido de Hidrogênio/metabolismo , Fotossíntese , Enxofre/metabolismoRESUMO
Beta glucan (ß-glucan) has promising bioactive properties. Consequently, the use of ß-glucan as a food additive is favored with the dual-purpose potential of increasing the fiber content of food products and enhancing their health properties. Our aim was to evaluate the biological activity of ß-glucan (antimicrobial, antitoxic, immunostimulatory, and anticancer) extracted from Saccharomyces cerevisiae using a modified acid-base extraction method. The results demonstrated that a modified acid-base extraction method gives a higher biological efficacy of ß-glucan than in the water extraction method. Using 0.5 mg dry weight of acid-base extracted ß-glucan (AB extracted) not only succeeded in removing 100% of aflatoxins, but also had a promising antimicrobial activity against multidrug-resistant bacteria, fungi, and yeast, with minimum inhibitory concentrations (MIC) of 0.39 and 0.19 mg/mL in the case of resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, respectively. In addition, AB extract exhibited a positive immunomodulatory effect, mediated through the high induction of TNFα, IL-6, IFN-γ, and IL-2. Moreover, AB extract showed a greater anticancer effect against A549, MDA-MB-232, and HepG-2 cells compared to WI-38 cells, at high concentrations. By studying the cell death mechanism using flow-cytometry, AB extract was shown to induce apoptotic cell death at higher concentrations, as in the case of MDA-MB-231 and HePG-2 cells. In conclusion, the use of a modified AB for ß-glucan from Saccharomyces cerevisiae exerted a promising antimicrobial, immunomodulatory efficacy, and anti-cancer potential. Future research should focus on evaluating ß-glucan in various biological systems and elucidating the underlying mechanism of action.
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Extração Líquido-Líquido , Saccharomyces cerevisiae/química , beta-Glucanas/isolamento & purificação , beta-Glucanas/farmacologia , Ácidos , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/farmacologia , Imunomodulação/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Extração Líquido-Líquido/métodos , Testes de Sensibilidade Microbiana , Espectroscopia de Infravermelho com Transformada de Fourier , beta-Glucanas/químicaRESUMO
Currently, the world is still facing a COVID-19 (coronavirus disease 2019) classified as a highly infectious disease due to its rapid spreading. The shortage of X-ray machines may lead to critical situations and delay the diagnosis results, increasing the number of deaths. Therefore, the exploitation of deep learning (DL) and optimization algorithms can be advantageous in early diagnosis and COVID-19 detection. In this paper, we propose a framework for COVID-19 images classification using hybridization of DL and swarm-based algorithms. The MobileNetV3 is used as a backbone feature extraction to learn and extract relevant image representations as a DL model. As a swarm-based algorithm, the Aquila Optimizer (Aqu) is used as a feature selector to reduce the dimensionality of the image representations and improve the classification accuracy using only the most essential selected features. To validate the proposed framework, two datasets with X-ray and CT COVID-19 images are used. The obtained results from the experiments show a good performance of the proposed framework in terms of classification accuracy and dimensionality reduction during the feature extraction and selection phases. The Aqu feature selection algorithm achieves accuracy better than other methods in terms of performance metrics.
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BACKGROUND: We studied the efficacy and safety of selenium supplementation in patients who had peripartum cardiomyopathy (PPCM) and selenium deficiency. METHODS: We randomly assigned 100 PPCM patients with left ventricular ejection fraction (LVEF) < 45% and selenium deficiency (< 70 µg/L) to receive either oral Selenium (L-selenomethionine) 200 µg/day for 3 months or nothing, in addition to recommended therapy, in an open-label randomised trial. The primary outcome was a composite of persistence of heart failure (HF) symptoms, unrecovered LV systolic function (LVEF < 55%) or death from any cause. RESULTS: Over a median of 19 months, the primary outcome occurred in 36 of 46 patients (78.3%) in the selenium group and in 43 of 54 patients (79.6%) in the control group (hazard ratio [HR] 0.69; 95% confidence interval [CI] 0.43-1.09; p = 0.113). Persistence of HF symptoms occurred in 18 patients (39.1%) in the selenium group and in 37 patients (68.5%) in the control group (HR 0.53; 95% CI 0.30-0.93; p = 0.006). LVEF < 55% occurred in 33 patients (71.7%) in the selenium group and in 38 patients (70.4%) in the control group (HR 0.91; 95% CI 0.57-1.45; p = 0.944). Death from any cause occurred in 3 patients (6.5%) in the selenium group and in 9 patients (16.7%) in the control group (HR 0.37; 95% CI 0.10-1.37; p = 0.137). CONCLUSIONS: In this study, selenium supplementation did not reduce the risk of the primary outcome, but it significantly reduced HF symptoms, and there was a trend towards a reduction of all-cause mortality. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03081949.
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Cardiomiopatias/tratamento farmacológico , Deficiências Nutricionais/tratamento farmacológico , Suplementos Nutricionais , Insuficiência Cardíaca/tratamento farmacológico , Transtornos Puerperais/tratamento farmacológico , Selênio/deficiência , Selenometionina/uso terapêutico , Adulto , Cardiomiopatias/diagnóstico , Cardiomiopatias/mortalidade , Cardiomiopatias/fisiopatologia , Deficiências Nutricionais/diagnóstico , Deficiências Nutricionais/mortalidade , Deficiências Nutricionais/fisiopatologia , Suplementos Nutricionais/efeitos adversos , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Nigéria , Período Periparto , Gravidez , Estudo de Prova de Conceito , Estudos Prospectivos , Transtornos Puerperais/diagnóstico , Transtornos Puerperais/mortalidade , Transtornos Puerperais/fisiopatologia , Selenometionina/efeitos adversos , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos , Adulto JovemRESUMO
Two new series of ethyl benzoate bearing pyrrolizine and indolizine moieties 8-11 were synthesized and evaluated for their anti-inflammatory and anticancer activities. Among these derivatives, compounds 9a, 10b and 11b displayed in vivo anti-inflammatory and analgesic activity comparable to ibuprofen. The acute ulcerogenicity and histopathological studies revealed better GIT safety profile than ibuprofen. Mechanistic study of these compounds revealed inhibitory activity against COX-1/2 with preferential inhibition of COX-2. Evaluation of cytotoxic activity of the new compounds using MTT assay revealed potent to moderate activity against three human (MCF-7, A2780 and HT29) cancer cell lines (IC50â¯=â¯0.02-23.35⯵M). Compounds 9a, 10a,b and 11a,b exhibited high cytotoxic selectivity against MCF-7 cells (SIâ¯=â¯4-84). Although the indolizine bearing derivatives 8-11b exhibited higher selectivity to COX-2 than their corresponding pyrrolizine analogs 8-11a, but they were less active and selective against MCF-7 cells. Cell cycle analysis and annexin V-FITC/PI assay revealed G1 cell cycle arrest and induction of apoptosis in MCF-7 cells by compound 9a. The docking study revealed nice fitting of the new compounds into the active site of COX-1/2 with higher affinity to COX-2. Compounds 8-11 displayed drug-likeness score in the range of 0.67-1.56 compared to 1.06 for licofelone. These results suggested that compounds 9a, 10b and 11b could be promising agents in future research as anti-inflammatory and anticancer agents.
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Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/farmacologia , Benzoatos/farmacologia , Desenho de Fármacos , Indolizinas/farmacologia , Pirróis/farmacologia , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Benzoatos/síntese química , Benzoatos/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Edema/tratamento farmacológico , Edema/patologia , Humanos , Indolizinas/química , Inflamação/tratamento farmacológico , Inflamação/patologia , Estrutura Molecular , Dor/induzido quimicamente , Dor/tratamento farmacológico , Dor/patologia , Pirróis/química , Ratos , Ratos Sprague-Dawley , Relação Estrutura-AtividadeRESUMO
Gut microbiota is well known as playing a critical role in inflammation and asthma development. The very low-calorie ketogenic diet (VLCKD) is suggested to affect gut microbiota; however, the effects of VLCKD during pregnancy and lactation on the infant gut microbiota are unclear. The VLCKD appears to be more effective than caloric/energy restriction diets for the treatment of several diseases, such as obesity and diabetes. However, whether adherence to VLCKD affects the infant gut microbiota and the protective effects thereof on asthma remains uncertain. The exact mechanisms underlying this process, and in particular the potential role of short chain fatty acids (SCFAs), are still to be unravelled. Thus, the aim of this review is to identify the potential role of SCFAs that underlie the effects of VLCKD during pregnancy and lactation on the infant gut microbiota, and explore whether it incurs significant implications for reducing asthma.
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Asma/metabolismo , Dieta Cetogênica/métodos , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal , Asma/dietoterapia , Asma/microbiologia , Restrição Calórica/métodos , Feminino , Humanos , Lactente , Gravidez , Fenômenos Fisiológicos da Nutrição Pré-NatalRESUMO
This study examined the role of seed ageing in the control of anti-nutritional factors in cowpea (Vigna unguiculata L.). In differently aged seeds of three cultivars of V. unguiculata (V240, V78 and V585), germination ability and vigour were studied. Effort was also made to assay trypsin inhibitor, phenol and phytic acid, perform protein profiling in these seeds. High vigour lots (V240 and V585) registered maximum increases in germination of aged seeds. The contents of nutritional factors such as total protein and carbohydrate declined with decrease in seed vigour lots. Anti-nutritional factors such as phytic acid, phenolic content and trypsin inhibitor activity decreased and varied in low and high vigour seed lots. Polypeptide banding pattern significantly varied in the high, medium and low vigour seeds. Notably, proteins with the highest relative mobility of 0.98 and lowest molecular weight of 11.5 kDa and lowest relative mobility of 0.17 and highest molecular weight of 102.0 kDa were observed in all the vigour lots. Results implied the decline in vigour of V. unguiculata seeds under conditions of controlled ageing can be related to the decline in content of major nutritional factors (total carbohydrates and proteins) required for the growing embryo during seed germination. Additionally, decreases in the contents of anti-nutritional factors phytic acid and phenols, and the activity of trypsin inhibitor in particular are connected with the decrease in seed vigour irrespective of V. unguiculata cultivars. The use of short duration controlled ageing technique can, at least partially, reduce the negative effects of anti-nutritional factors, and eventually improve the nutritional quality of V. unguiculata seeds.
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This study aimed to improve current understanding on ethylene-insensitive 3-like (EIL) members, least explored in woody plants such as poplar (Populus trichocarpa Torr. & Grey). Herein, seven putative EIL members were identified in P. trichocarpa genome and were roughly annotated either as EIN3-like sequence associated with ethylene pathway or EIL3-like sequences related with sulfur (S)-pathway. Motif-distribution pattern of proteins also corroborated this annotation. They were distributed on six chromosomes (chr1, 3, 4 and 8-10), and were revealed to encode a protein of 509-662 residues with nuclear localization. The presence of ethylene insensitive 3 (EIN3; PF04873) domain (covering first 80-280 residues from N-terminus) was confirmed by Hidden Markov Model-based search. The first half of EIL proteins (â¼80-280 residues including EIN3 domain) was substantially conserved. The second half (â¼300-600 residues) was considerably diverged. Additionally, first half of proteins harbored acidic, proline-rich and glutamine-rich sites, and supported the essentiality of these regions in the transcriptional-activation and protein-function. Moreover, identified six segmental and one-tandem duplications demonstrated the negative or purifying selective nature of mutations. Furthermore, expression profile analysis indicated the possibility of a crosstalk between EIN3- and EIL3-like genes, and co-expression networks implicated their interactions with very diverse panels of biological molecules.
Assuntos
Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Populus/genética , Fatores de Transcrição/genética , Sequência de Aminoácidos , Sequência Conservada , Duplicação Gênica , Redes Reguladoras de Genes , Família Multigênica , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Populus/química , Populus/metabolismo , Alinhamento de Sequência , Transdução de Sinais , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , TranscriptomaRESUMO
MAIN CONCLUSION: Solanum tuberosum genome analysis revealed 12 StSULTR genes encoding 18 transcripts. Among genes annotated at group level ( StSULTR I-IV), group III members formed the largest SULTRs-cluster and were potentially involved in biotic/abiotic stress responses via various regulatory factors, and stress and signaling proteins. Employing bioinformatics tools, this study performed genome-wide identification and expression analysis of SULTR (StSULTR) genes in potato (Solanum tuberosum L.). Very strict homology search and subsequent domain verification with Hidden Markov Model revealed 12 StSULTR genes encoding 18 transcripts. StSULTR genes were mapped on seven S. tuberosum chromosomes. Annotation of StSULTR genes was also done as StSULTR I-IV at group level based mainly on the phylogenetic distribution with Arabidopsis SULTRs. Several tandem and segmental duplications were identified between StSULTR genes. Among these duplications, Ka/Ks ratios indicated neutral nature of mutations that might not be causing any selection. Two segmental and one-tandem duplications were calculated to occur around 147.69, 180.80 and 191.00 million years ago (MYA), approximately corresponding to the time of monocot/dicot divergence. Two other segmental duplications were found to occur around 61.23 and 67.83 MYA, which is very close to the origination of monocotyledons. Most cis-regulatory elements in StSULTRs were found associated with major hormones (such as abscisic acid and methyl jasmonate), and defense and stress responsiveness. The cis-element distribution in duplicated gene pairs indicated the contribution of duplication events in conferring the neofunctionalization/s in StSULTR genes. Notably, RNAseq data analyses unveiled expression profiles of StSULTR genes under different stress conditions. In particular, expression profiles of StSULTR III members suggested their involvement in plant stress responses. Additionally, gene co-expression networks of these group members included various regulatory factors, stress and signaling proteins, and housekeeping and some other proteins with unknown functions.