Two Birds with One Stone: Drug Regime Targets Viral Pathogenesis Phases and COVID-19 ARDS at the Same Time.

BACKGROUND: Severe COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a kind of viral pneumonia induced by infection with the coronavirus that causes ARDS. It involves symptoms that are a combination of viral pneumonia and ARDS. Antiviral or immunosuppressive medicines are used to treat many COVID-19 patients. Several drugs are now undergoing clinical studies in order to see if they can be repurposed in the future. MATERIAL AND METHODS: In this study, in silico biomarker-targeted methodologies, such as target/molecule virtual screening by docking technique and drug repositioning strategy, as well as data mining approach and meta-analysis of investigational data, were used. RESULTS: In silico findings of used combination of drug repurposing and high-throughput docking methods presented acetaminophen, ursodiol, and ß-carotene as a three-drug therapy regimen to treat ARDS induced by viral pneumonia in addition to inducing direct antiviral effects against COVID-19 viral infection. CONCLUSION: In the current study, drug repurposing and high throughput docking methods have been employed to develop combination drug regimens as multiple-molecule drugs for the therapy of COVID-19 and ARDS based on a multiple-target therapy strategy. This approach offers a promising avenue for the treatment of COVID-19 and ARDS, and highlights the potential benefits of drug repurposing in the fight against the current pandemic.

Visceral and body adiposity are negatively associated with vitamin A nutritional status independently of Body Mass Index and recommended intake of vitamin A in Brazilian Women.

Vitamin A (VA) has a negative association with body mass index (BMI) since it is involved in the regulation of body adiposity via nuclear receptors. However, few studies have investigated the relationship between VA nutritional status and the way body adipose is stored, which is the aim of this cross-sectional analytical study with Brazilian adult women in different BMI classes with the intake of VA recommended. VA nutritional status was assessed by serum retinol and ß-carotene measurements, dietary intake, and diagnosis of night blindness (NB). Results: 268 women with mean age of 38.00±5.80 years. According to the BMI, 30.97% were normal weight, 14.18% overweight, 25.37% class I obesity, 14.55% class II, and 14.93% class III.The prevalence of low serum of ß-carotene, retinol, and presence of NB in the total sample was 73.5%, 45.9%, and 20.1%, respectively. A total of 86.7% of normal weight women had inadequate visceral adiposity index (VAI) and 41.0% had inadequate body adiposity index (BAI).VAI was the body adiposity marker with the highest association with low serum retinol and b-carotene concentrations (P<.001). There was presence of NB in 100% of cases of inadequacy of BAI (P<.001). High visceral and body adiposity were associated with compromised VA nutritional status regardless of BMI and the recommended intake of VA. Additional measures to assess body adiposity, and especially its distribution, may collaborate in clinical practice to identify women at risk of compromising their VA nutritional status even when they are classified as normal weight according to their BMI.

Orange-fleshed sweet potato (Ipomoea batatas) extract attenuates lipopolysaccharide-induced inflammation in RAW264.7 cells via inactivation of MAPKs and IkB signalling

@#Introduction: Orange-fleshed sweet potato (OFSP) is an excellent source of b-carotene. Due to its health benefits, b-carotene-rich plants are receiving attention. This study aimed to assess the inhibitory effect of the ethanol extract of steamed OFSP on lipopolysaccharide (LPS)-induced inflammation in murine macrophage cell line (RAW 264.7 cells). Methods: b-carotene, total phenolics and total flavonoids of OFSP were measured by high performance liquid chromatography (HPLC), the Folin- Ciocalteu assay and the aluminum chloride colorimetry, respectively. RAW264.7 cell monolayers were pre-treated with 0.5-2.0 mg/mL ethanol extract from steamed OFSP prior to co-incubation with or without LPS for 24 h. Culture media and cell lysate were collected to measure nitric oxide, interleukin-6 (IL-6), IL-1b, tumour necrosis factor-α, inducible nitric oxide synthase, cyclooxygenase-2, mitogen- activated protein kinases (MAPKs) and inhibitory kappa B (IkB), respectively. Results: The ethanol extract from steamed OFSP significantly suppressed LPS- induced production of such pro-inflammatory mediators by the inactivation of MAPKs and IkB signalling pathway. The ethanol extract from steamed OFSP contained 226 μg/g DW (dry weight) of b-carotene, 2.13 mg gallic acid equivalent/g DW of total polyphenolics and 0.24 mg quercetin equivalents/g DW of total flavonoids. Conclusion: These results indicated that bioactive compounds in steamed OFSP have anti-inflammatory potential.

Effect of combined consumption of Lactobacillus brevis KB290 and ß-carotene on minor diarrhoea-predominant irritable bowel syndrome-like symptoms in healthy subjects: a randomised, double-blind, placebo-controlled, parallel-group trial.

People with non-pathological diarrhoea-predominant irritable bowel syndrome (IBS-D)-like symptoms are present at a significant level even in healthy populations, but established prophylaxis is lacking. Previously, we have found that co-administration of Lactobacillus brevis KB290 (KB290) and ß-carotene (ßC) attenuated murine colitis (potential cause of IBS-D-like symptoms) significantly. Here, we investigated the effect of KB290 and ßC on minor IBS-D-like symptoms in healthy volunteers. After a 4-week run-in period, subjects received a KB290 + ßC or placebo capsule for 12 weeks, followed by a 4-week washout period. The KB290 + ßC group showed a significant improvement in intensity of abdominal pain and stool frequency compared with the placebo group. The KB290 + ßC group showed a significantly higher serum concentration of anti-inflammatory cytokine, interleukin-10, compared with the placebo group. In conclusion, we demonstrated that consumption of KB290 + ßC improves minor IBS-D-like symptoms and inflammatory status in healthy volunteers. (UMIN000018002).

Proteome rebalancing in transgenic Camelina occurs within the enlarged proteome induced by ß-carotene accumulation and storage protein suppression.

Oilseed crops are global commodities for their oil and protein seed content. We have engineered the oilseed Camelina sativa to exhibit increased protein content with a slight decrease in oil content. The introduction of a phytoene synthase gene with an RNAi cassette directed to suppress the storage protein 2S albumin resulted in seeds with an 11-24 % elevation in overall protein. The phytoene synthase cassette alone produced enhanced ß-carotene content of an average 275 ± 6.10 µg/g dry seed and an overall altered seed composition of 11 % less protein and comparable nontransgenic amounts of both oil and carbohydrates. Stacking an RNAi to suppress the major 2S storage protein resulted in seeds that contain elevated protein and slight decrease in oil and carbohydrate amounts showing that Camelina rebalances its proteome within an enlarged protein content genotype. In both ß-carotene enhanced seeds with/without RNAi2S suppression, the seed size was noticeably enlarged compared to nontransgenic counterpart seeds. Metabolic analysis of maturing seeds indicate that the enhanced ß-carotene trait had the larger effect than the RNAi2S suppression on the seed metabolome. The use of a GRAS (generally regarded as safe) ß-carotene as a visual marker in a floral dip transformation system, such as Camelina, might eliminate the need for costly regulatory and controversial antibiotic resistance markers. ß-carotene enhanced RNAi2S suppressed Camelina seeds could be further developed as a rapid heterologous protein production platform in a nonfood crop leveraging its enlarged protein content and visual marker.

Atividade antioxidante de extratos de folhas de ora-pro-nóbis (Pereskia aculeata Mill. ) usando métodos espectrofotométricos e voltamétricos in vitro / Antioxidant activity of ora-pro-nobis (Pereskia aculeata Mill. ) leaves extracts using spectrophotometric and voltammetric assays in vitro

Atualmente tem crescido a busca por plantas como fontes naturais de antioxidantes. Plantas com esta propriedade podem ser utilizadas para melhorar a qualidade de alimentos, seja para fins nutritivos ou de conservação, como também para a prevenção de doenças relacionadas ao aparecimento de radicais livres. A Pereskia aculeata Mill. (Ora-pro-nóbis) é uma espécie da família Cactaceae e suas folhas são consumidas por muitas pessoas. Neste contexto, este trabalho estudou o teor de fenóis totais (método Folin-Ciocalteau) e de proantocianidinas (vanilina sulfúrica), correlacionando-os com a atividade antioxidante (radical DPPH, sistema b-caroteno/ácido linoleico e voltametria por pulso diferencial) de extratos em acetona 80%, etanol 70% e água das folhas da espécie P. aculeata Mill., apresentando o extrato em acetona 80% maior teor de fenóis totais e proantocianidinas. Com relação à atividade antioxidante frente ao radical DPPH, o extrato em acetona 80% se apresentou ligeiramente melhor que o em etanol 70%. A técnica de voltametria por pulso diferencial mostrou que o extrato em acetona 80% apresenta constituintes com maior potencial redutor que o extrato em etanol 70%. Os dados obtidos a partir da voltametria corroboram com os resultados obtidos pelo método tradicional de DPPH. Os extratos em etanol 70% e em água apresentaram melhor atividade antioxidante pelo sistema b-caroteno/ácido linoleico, o que sugere a presença de outra classe de compostos que atuam na inibição do b- caroteno. Portanto, as folhas da espécie Pereskia aculeata podem ser consideradas como fonte potencial de compostos antioxidantes.

Currently, the search for plants as natural sources of antioxidants has been growing because they can be used to improve the nutritive or preservation properties of food, as soon as for the prevention of diseases related to free radicals. The Pereskiaaculeata Mill. (Ora-pro-nóbis,) is a specie of Cactaceae family and its leaves are consumed by many people. In this context, this paper studied the total phenols (Folin-Ciocalteu) and proanthocyanidins (vanillin sulfuric) correlating with the antioxidant activity (DPPH, b-carotene/linoleic acid system and differential pulse voltammetry) of extracts of 80% acetone, 70% ethanol and water of Pereskiaaculeata Mill. leaves. The 80% acetone extract showed higher total phenols and proanthocyanidins. Regarding to the antioxidant activity by DPPH radical scavenger, the 80% acetone extract was slightly better than 70% ethanol extract. The differential pulse voltammetry technique displayed that the 80% acetone extract presented constituents with greater reducing potential than the ones presented in 70% ethanol extract, what can corroborate the results obtained. The 70% ethanol and water extracts has shown better antioxidant activity by b-carotene/linoleic acid system, what probably suggests the presence of another compounds classes that are responsible for the inhibition the b-carotene. Therefore, the Pereskiaaculeata Mill. showed that its leaves may be considered as a potential source of antioxidant compounds.

Capacidade antioxidante de frutas / Antioxidant capacity of the fruits

Extratos aquoso e acetônico de 15 frutas foram submetidos a ensaios para investigar a habilidade de seqüestrar o radical estável 1,1-difenil-2-picrilhidrazil (DPPH) e a capacidade de inibir a oxidação em sistema modelo β-caroteno/ácido linoléico. Todas as frutas exibiram propriedade antioxidante, entretanto a ação foi diferenciada entre elas. O extrato aquoso da acerola, caju, mamão "Formosa", mamão Havaí, laranja pêra e goiaba foram os mais eficazes (superior a 70 por cento), enquanto que o do abacaxi, laranja cravo, manga rosa, melão espanhol, melão japonês, melão orange flesh e pinha apresentaram ação moderada (60-70 por cento) e o da manga espada e melancia exibiram a mais fraca capacidade de seqüestrar o radical DPPH. Os extratos acetônico da acerola, caju, pinha e goiaba exibiram uma forte capacidade de seqüestrar o radical DPPH (superior a 70 por cento). Em sistema modelo β-caroteno/ácido linoléico, o extrato aquoso da pinha e o acetônico da goiaba exibiram moderada capacidade antioxidante (60-70 por cento) enquanto que a acerola (extrato aquoso) e o mamão formosa (extrato acetônico) os menores percentuais. Frente à capacidade antioxidante exibida, as frutas podem ser apontadas como fontes de antioxidantes naturais, destacando-se a acerola, caju, mamão Formosa, mamão Havaí, goiaba, laranja pêra, e a pinha por terem apresentado uma potente capacidade antioxidante.

Aqueous and acetone extracts from 15 fruits have been screened for antioxidant activity using DPPH method and ß-carotene/linoleic acid model. All fruits studied showed antioxidant activity, but in different extent. Acerola, cashew-apple, papaya "formosa", papaya "solo", orange and guava showed the higher antioxidant activity (>70 percent) in DPPH method, followed by pineapple, bergamont, mango "rosa", melon "reticulares", melon "inodorus", melon "orange flesh" and sugar-apple aqueous extract (moderate, 60-70 percent) and mango "espada" and watermelon aqueous extract, the lowest activity. Acerola, cashew-apple, sugar-apple and guava acetone extracts exhibited higher scavenging activity toward DPPH radicals (>70 percent).β-carotene/linoleic acid model index of sugar-apple aqueous extract and guava acetone extract demonstrated moderate antioxidant activity (60-70 percent), meanwhile acerola aqueous extract and papaya "formosa" acetone extract the lower. According to antioxidant activity, fruits can be indicated as natural antioxidants sources, pointing out acerola, cashew-apple, papaya "solo", papaya "formosa", guava, orange and sugar-apple as the highest in antioxidant capacity.