A consensus reverse docking approach for identification of a competitive inhibitor of acetyltransferase enhanced intracellular survival protein from Mycobacterium tuberculosis.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), which remains a significant global health challenge. The emergence of multidrug-resistant (MDR) Mtb strains imposes the development of new therapeutic strategies. This study focuses on the identification and evaluation of potential inhibitors against Mtb H37Ra through a comprehensive screening of an in-house chemolibrary. Subsequently, a promising pyrimidine derivative (LQM495) was identified as promising and then further investigated by experimental and in silico approaches. In this context, computational techniques were used to elucidate the potential molecular target underlying the inhibitory action of LQM495. Then, a consensus reverse docking (CRD) protocol was used to investigate the interactions between this compound and several Mtb targets. Out of 98 Mtb targets investigated, the enhanced intracellular survival (Eis) protein emerged as a target for LQM495. To gain insights into the stability of the LQM495-Eis complex, molecular dynamics (MD) simulations were conducted over a 400 ns trajectory. Further insights into its binding modes within the Eis binding site were obtained through a Quantum mechanics (QM) approach, using density functional theory (DFT), with B3LYP/D3 basis set. These calculations shed light on the electronic properties and reactivity of LQM495. Subsequently, inhibition assays and kinetic studies of the Eis activity were used to investigate the activity of LQM495. Then, an IC50 value of 11.0 ± 1.4 µM was found for LQM495 upon Eis protein. Additionally, its Vmax, Km, and Ki parameters indicated that it is a competitive inhibitor. Lastly, this study presents LQM495 as a promising inhibitor of Mtb Eis protein, which could be further explored for developing novel anti-TB drugs in the future.

Design, synthesis, antiviral evaluation, and In silico studies of acrylamides targeting nsP2 from Chikungunya virus.

The Togaviridae family comprises several New- and Old-World Alphaviruses that have been responsible for thousands of human illnesses, including the RNA arbovirus Chikungunya virus (CHIKV). Firstly, it was reported in Tanzania in 1952 but rapidly it spread to several countries from Europe, Asia, and the Americas. Since then, CHIKV has been circulating in diverse countries around the world, leading to increased morbidity rates. Currently, there are no FDA-approved drugs or licensed vaccines to specifically treat CHIKV infections. Thus, there is a lack of alternatives to fight against this viral disease, making it an unmet need. Structurally, CHIKV is composed of five structural proteins (E3, E2, E1, C, and 6k) and four non-structural proteins (nsP1-4), in which nsP2 represents an attractive antiviral target for designing novel inhibitors since it has an essential role in the virus replication and transcription. Herein, we used a rational drug design strategy to select some acrylamide derivatives to be synthesized and evaluated against CHIKV nsP2 and also screened on CHIKV-infected cells. Thus, two regions of modifications were considered for these types of inhibitors, based on a previous study of our group, generating 1560 possible inhibitors. Then, the 24 most promising ones were synthesized and screened by using a FRET-based enzymatic assay protocol targeting CHIKV nsP2, identifying LQM330, 333, 336, and 338 as the most potent inhibitors, with Ki values of 48.6 ± 2.8, 92.3 ± 1.4, 2.3 ± 1.5, and 181.8 ± 2.5 µM, respectively. Still, their Km and Vmax kinetic parameters were also determined, along with their competitive binding modes of CHIKV nsP2 inhibition. Then, ITC analyses revealed KD values of 127, 159, 198, and 218 µM for LQM330, 333, 336, and 338, respectively. Also, their ΔH, ΔS, and ΔG physicochemical parameters were determined. MD simulations demonstrated that these inhibitors present a stable binding mode with nsP2, interacting with important residues of this protease, according to docking analyzes. Moreover, MM/PBSA calculations displayed that van der Waals interactions are mainly responsible for stabilizing the inhibitor-nsP2 complex, and their binding energies corroborated with their Ki values, having -198.7 ± 15.68, -124.8 ± 17.27, -247.4 ± 23.78, and -100.6 ± 19.21 kcal/mol for LQM330, 333, 336, and 338, respectively. Since Sindbis (SINV) nsP2 is similar to CHIKV nsP2, these best inhibitors were screened against SINV-infected cells, and it was verified that LQM330 presented the best result, with an EC50 value of 0.95 ± 0.09 µM. Even at 50 µM concentration, LQM338 was found to be cytotoxic on Vero cells after 48 h. Then, LQM330, 333, and 336 were evaluated against CHIKV-infected cells in antiviral assays, in which LQM330 was found to be the most promising antiviral candidate in this study, exhibiting an EC50 value of 5.2 ± 0.52 µM and SI of 31.78. The intracellular flow cytometry demonstrated that LQM330 is able to reduce the CHIKV cytopathogenic effect on cells, and also reduce the percentage of CHIKV-positive cells from 66.1% ± 7.05 to 35.8% ± 5.78 at 50 µM concentration. Finally, qPCR studies demonstrated that LQM330 was capable of reducing the number of viral RNA copies/µL, suggesting that CHIKV nsP2 is targeted by this inhibitor as its mechanism of action.

Dataset of Schinus terebinthifolius essential oil microencapsulated by spray-drying.

Schinus terebinthifolius Raddi has been extensively studied due to its antioxidant, anti-inflammatory and antibiotic properties. Recently, its seeds have been tested against some insect pests as an insecticide, repellent and antifungal agent. Microencapsulation by spray-drying is widely used in the food and drug industries, as well as in the microencapsulation of essential oils, since it protects the oils against several effects, such as oxidation and thermal degradation, thus optimising its use. The aim was to microencapsulate S. terebinthifolius essential oil by spray-drying maltodextrin and arabic gum as encapsulating agents and SiO2 as a colloidal adjuvant. The morphology of the microcapsules was analysed by scanning electron microscopy (SEM), which evidenced mainly regular spherical-shaped particles with sizes between 5 and 10 µm. The thermal stability was studied by thermogravimetric analysis-differential scanning calorimetry (TGA-DSC), and the microcapsules were stable at temperatures up to 200°C. The microencapsulating agents and the spray-drying technique produced microcapsules capable of protecting the essential oil against external effects, such as thermal degradation.

Propolis in Oral Healthcare: Antibacterial Activity of a Composite Resin Enriched With Brazilian Red Propolis.

The aim of this study was to obtain a Brazilian red propolis (BRP) enriched composite resin and to perform the characterization of its antibacterial activity, mechanical, and physical-chemical properties. Brazilian red propolis ethyl acetate extract (EABRP) was characterized by LC-ESI-Orbitrap-FTMS, UPLC-DAD, antibacterial activity, total flavonoids content, and radical scavenging capacity. BRP was incorporated to a commercial composite resin (RC) to obtain BRP enriched composite at 0.1, 0.15 and 0.25% (RP10, RP15 and RP25, respectively). The antibacterial activity RPs was evaluated against Streptococcus mutans by contact direct test and expressed by antibacterial ratio. The RPs were characterized as its cytotoxicity against 3T3 fibroblasts, flexural strength (FS), Knoop microhardness (KHN), post-cure depth (CD), degree of conversion (DC%), water sorption (Wsp), water solubility (Wsl), average roughness (Ra), and thermal analysis. Were identified 50 chemical compounds from BRP extract by LC-ESI-Orbitrap-FTMS. EABRP was bacteriostatic and bactericide at 125 and 500 µg/ml, respectively. The RP25 exhibited antibacterial ratio of 90.76% after 1 h of direct contact with S. mutans (p < 0.0001) while RC no showed significative antibacterial activity (p = 0.1865), both compared with cell control group. RPs and RC no showed cytotoxicity. RPs exhibited CD from 2.74 to 4.48 mm, DC% from 80.70 to 83.96%, Wsp from 17.15 to 21.67 µg/mm3, Wsl from 3.66 to 4.20 µg/mm3, Ra from 14.48 to 20.76 nm. RPs showed thermal resistance between 448-455°C. The results support that propolis can be used on development of modified composite resins that show antibacterial activity and that have compatible mechanical and physical-chemical properties to the indicate for composite resins.

Layered double hydroxides for controlled fluoride release.

This study aims to develop a nano-sized fluoridated layered double hydroxide (LDH)-based release system via hydrothermal treatment for the controlled delivery of fluoride (F-) ions in the oral environment. The synthesis of conventional LDH-type (C-LDH) precursor nanomaterials was conducted using a co-precipitation method at constant pH, and the nanoparticulate-LDH (N-LDH) was synthesized by a hydrothermal procedure. Fluoride LDH (F-LDH) products were obtained through indirect synthesis using the precursor ion-exchange technique by varying the agitation time (2 and 24 h) and temperature (25 and 40 °C) to produce 12 material samples. The materials were characterized by energy dispersive x-ray, hexamethyldisilazane, digital radiography x-ray, Fourier-transform infrared, thermogravimetric analysis, and scanning electron microscopy. Additionally, the F-release kinetic profile was evaluated for 21 d in neutral and acid media with mathematical model analysis. Products with varying F-quantities were obtained, revealing specific release profiles. In general, there was a higher F-release in the acid medium, with emphasis on F-LDH-8. Fluoride-LDH and controlled fluoride delivery was successfully obtained, proving the potential of these nanomaterials as alternative anti-caries agents.

Polyphenols and Brazilian red propolis incorporated into a total-etching adhesive system help in maintaining bonding durability.

OBJECTIVES: The aim of this study was to evaluate the degree of conversion and bond strength of a commercial dental adhesive modified by the incorporation of quercetin, resveratrol (RES), and Brazilian red propolis (BRP). METHODS: BRP markers were identified using ultra-performance liquid chromatography coupled with a diode array detector, and the antioxidant activity (AAO) of the three substances was analyzed. Single Bond 2 adhesive (3M ESPE) was modified by adding BRP, quercetin, and RES, separately, at 20 µg/mL, 250 µg/mL, and 500 µg/mL, respectively. The degree of conversion (DC) was measured using near-infrared spectroscopy 24 h after photopolymerization. Measurements of the resin-dentin microtensile bond strength (µTBS) were carried out after 1 day and 1 year. Student's t test and ANOVA with Tukey's test were used for data analysis (α = 0.05). RESULTS: The markers daidzein, liquiritigenin, pinobanksin, isoliquiritigenin, formononetin, pinocembrin, and biochanin A were found in the ethanolic extract of BRP. Quercetin, RES, and BRP showed high AAO. The DC of the tested adhesives remained adequate for this category of material, with a slight increase in the DC of adhesives with quercetin and BRP (P > 0.05). Comparisons between µTBS measurements made at 1 day and 1 year showed that, contrary to the control group, µTBS values for all modified adhesives were maintained after 1 year in distilled water (P > 0.05). CONCLUSIONS: These findings suggest that quercetin, RES, or BRP might be useful in adhesive dentistry to help improve hybrid layer resistance. CLINICAL SIGNIFICANCE: Dentin bonding agents with quercetin, RES, and BRP have potential to increase the longevity of composite restorations.

Layered double hydroxides for controlled fluoride release

Abstract This study aims to develop a nano-sized fluoridated layered double hydroxide (LDH)-based release system via hydrothermal treatment for the controlled delivery of fluoride (F-) ions in the oral environment. The synthesis of conventional LDH-type (C-LDH) precursor nanomaterials was conducted using a co-precipitation method at constant pH, and the nanoparticulate-LDH (N-LDH) was synthesized by a hydrothermal procedure. Fluoride LDH (F-LDH) products were obtained through indirect synthesis using the precursor ion-exchange technique by varying the agitation time (2 and 24 h) and temperature (25 and 40 °C) to produce 12 material samples. The materials were characterized by energy dispersive x-ray, hexamethyldisilazane, digital radiography x-ray, Fourier-transform infrared, thermogravimetric analysis, and scanning electron microscopy. Additionally, the F-release kinetic profile was evaluated for 21 d in neutral and acid media with mathematical model analysis. Products with varying F-quantities were obtained, revealing specific release profiles. In general, there was a higher F-release in the acid medium, with emphasis on F-LDH-8. Fluoride-LDH and controlled fluoride delivery was successfully obtained, proving the potential of these nanomaterials as alternative anti-caries agents.

FOODS, NUTRACEUTICALS AND MEDICINAL PLANTS USED AS COMPLEMENTARY PRACTICE IN FACING UP THE CORONAVIRUS (COVID-19) SYMPTOMS: A REVIEW / ALIMENTOS, NUTRACÊUTICOS E PLANTAS MEDICINAIS UTILIZADOS COMO PRÁTICA COMPLEMENTAR NO ENFRENTAMENTO DOS SINTOMAS DO CORONAVÍRUS (COVID-19): UMA REVISÃO

The present prospective work of scientific articles related to foods and natural products with anti-Covid activity in databases in order to present a scientific community, to governments and society as main foods, nutraceuticals and medicinal plants as strategies used by countries during the COVID-19 pandemic. A review of articles on food, medicinal plants and biotechnology was carried out in databases of scientific articles such as: CAPES journals, PubMed, Elsevier's Science Direct, Willey on library library, Taylor & Francis Springer-Nature database, BMC, Hindawi, Scielo, ACS - American Chemical Society, Google Scholar, in addition to the Patent Database "The LENS" and "Questel-Orbit". Foods used in daily life such as garlic, ginger, turmeric, sour orange, vegetables, lactobacilli demonstrate proven anti-virus action. Medicinal plants used by Traditional Chinese, Korean and Indian Medicine also demonstrate anti-Covid activity and used during the coronavirus outbreak. Some medicinal plants, green propolis extract, red propolis extract, royal gelly, polen, honey have also been cited as anti-covid, natural anti-inflammatory and immunomodulatory products.

O presente trabalho prospectou artigos científicos relacionadas à alimentos e produtos naturais com atividade anti-Covid com o intuito de apresentar, à comunidade científica, aos governos e à sociedade, dados sobre as principais estratégias nutracêuticas, biotecnológicas e plantas medicinais utilizadas em alguns países durante o enfrentamento da pandemia COVID-19. A revisão de artigos sobre alimentos, plantas medicinais e produtos biotecnológicos foi realizada nas bases de dados periódicos da CAPES, PubMed, Science Direct, Willey on line library, Springer-Nature, Taylor & Francis, BMC, Hindawi, Scielo, ACS ­ American Chemical Society, Google acadêmico, "The LENS" e Questel-Orbit. Alimentos de uso frequente como alho, gengibre, cúrcuma, laranja azeda, vegetais e lactobacilos demonstraram ação anti-coronavirus comprovada. Foram descritos usos de plantas medicinais da Medicina tradicional Chinesa, Coreana, Indiana bastante utilizadas durante a pandemia. Algumas plantas medicinais e nutracêuticos como: extrato de própolis verde e extrato de própolis vermelha brasileiras, geleia real, pólen e mel também foram citados como produtos anti-covid, antiinflamatórios naturais e imunomodulatórios.

Morphology and distribution of antennal sensilla of Automeris liberia (Lepidoptera: Saturniidae).

The lepidopteran species Automeris liberia from the Saturniidae family is a polyphagous insect responsible for defoliating plants, such as the oil palm (Elaeis guineensis Jaquim). The antennae of insects play an important role in survival in various environments. Antennae are the main olfactory and sensory organs of insects and have different sensilla to detect chemical cues, movement, humidity and temperature. The olfactory structures present in the antennae are responsible for certain insect behavior, which is influenced by chemical communication. The morphology, distribution and location of the sensilla in the antennae of male and female A. liberia were investigated by scanning electron microscopy to understand the olfactory mechanisms relevant to insect-insect communication and insect-plant communication, among others. The results showed that the flagellum, scape and pedicel length and the number of antennomeres differed between the sexes and demonstrating the existence of sexual dimorphism in the antennae males (bipectinate) and females (filiform). According to the morphological data, seven types of sensilla were identified along the surface of the antennae, classified as trichodea, chaetica, basiconica, coeloconica, squamiformia, styloconica and Böhm's bristles. Among the sensilla chaetica, basiconica and Böhm's bristles, two subtypes based on length were identified in both sexes. The sensilla trichodea exhibited dimorphism since three subtypes were observed in males, while in females, only one subtype was observed, according to the length of the sensilla. Sensilla trichodea subtypes I and II were specific to males, while subtype III was observed in both sexes. These types of sensilla are involved in the recognition of pheromone molecules. Therefore, morphological study of the localization of the sensilla in the antennae will provide useful and relevant results for electrophysiological studies and behavioral tests. This information can help to understand the chemical communication of insects and helps in research directed strategies for pest control.

Hepatic fatty acid profile of rats fed a triheptanoin-based ketogenic diet / Perfil de ácidos grasos de hígados de ratones alimentados con una dieta cetogénica basada en triheptanoína

Objective: the aim of this study was to evaluate the influence of consumption of a ketogenic diet supplemented with triheptanoin, a medium-chain anaplerotic triacylglycerol, on the liver fatty acid profile of Wistar rats. Methods: three groups of male Wistar rats (n=10) were submitted to an AIN-93 control diet, a triheptanoin-based ketogenic diet, or a soybean oil-based ketogenic diet for 60 days. Excised livers were subjected to lipid extraction and methylation to obtain fatty acids methyl esters, which were subjected to gas chromatography-mass spectrometry. Results and discussion: compared to the rats fed the control diet, those fed ketogenic diets showed a significant reduction in the concentrations of 9-hexadecenoic and 9-octadecenoic acids, whereas those fed triheptanoin showed increased levels of octadecanoic acid. Conclusion: changes in the liver fatty acid profiles of the rats fed a triheptanoin-based or a soybean oil-based ketogenic diet did not seem to be related to the dietary fat source, but rather to the characteristics of the ketogenic diets themselves (AU)

Objetivo: el objetivo de este estudio fue evaluar la influencia del consumo de una dieta cetogénica complementada con triheptanoína, un triacilglicerol de cadena media y anaplerótico, en el perfil de ácidos grasos del hígado de ratones Wistar. Métodos: tres grupos de ratones Wistar machos (n=10) fueron sometidos durante 60 días a una dieta AIN-93 de control, una dieta cetogénica basada en triheptanoína o una dieta cetogénica a base de aceite de soja. Los hígados fueron escindidos y sometidos a extracción de lípidos y metilación para obtener los ésteres metílicos de ácidos grasos, que se sometieron a cromatografía de gas-espectrometría de masa. Resultados y discusión: en comparación con los ratones alimentados con la dieta de control, los de ambas dietas cetogénicas mostraron una reducción significativa en las concentraciones de los ácidos grasos 9-hexadecenoico y 9-octadecenoico, mientras que los alimentados con triheptanoína mostraron niveles de ácido octadecenoico aumentados. Conclusión: los cambios en los perfiles de ácidos grasos del hígado de los ratones alimentados con dietas cetogénicas no están relacionados con la fuente de grasa de la dieta (triheptanoína o aceite de soja), sino más bien con la concentración total de lípidos (AU)

Valor nutritivo de peixes da costa marítima de Alagoas, Brasil / Nutritive values of fishes from maritime coast of Alagoas, Brazil

Foram investigados o perfil de ácidos graxos, a composição centesimal, o valor calórico e o teor de colesterol em duas espécies de peixes marinhos do Estado de Alagoas: carapeba-listrada (Eugerres plumieri Cuvier,1830) e a cavala (Scomberomorus cavalla Cuvier, 1829), analisando-se 20 amostras de cada espécie. Elevado teor de umidade foi observado na amostra de carapeba-listrada, assim como os maiores valores de proteínas e cinzas, em base úmida, foram detectados nesta citada espécie. Quanto aos lipídeos, os valores obtidos para as duas espécies foram iguais, em base úmida. As amostras de cavala apresentaram o maior valor calórico, bem como o teor de colesterol mais elevado em base úmida. No perfil de ácidos graxos, a cavala apresentou percentuais mais elevados de monoinsaturado oleico (7,74%) e de poli-insaturados: linoleico (6,91%), α-linolênico (2,90%), EPA (10,82%), e DHA (4,50%). A relação poli-insaturados/saturados foi mais elevada na cavala (0,95), bem como o somatório dos teores de EPA + DHA (15,32). Na avaliação da qualidade nutricional dos lipídeos, as espécies estudadas mostraram os índices de n-6/n-3, hipocolesterolêmicos /hipercolesterol êmicos (HH), índice de aterogenicidade (IA) e índice de trombogenicidade (IT) favoráveis para o consumo alimentar. Considerando-se os resultados obtidos, a espécie cavala pode ser considerada boa fonte de ácidos graxos, principalmente o ácido ômega-3 e pelo seu valor em HH.

Composição centesimal, colesterol e perfil de ácidos graxos dos peixes tainha (Mugil cephalus) e camurim (Centropomus undecimalis) da Lagoa de Mundaú, AL/Brasil / Proximate composition, cholesterol and fatty acid of the fished species of estuario tainha (Mugil cephalus) and camurim (Centropomus undecimalis) from Mundaú Lagoon, Al/Brazil

O objetivo do trabalho foi caracterizar a composição centesimal , o teor, o perfil de ácidos graxos e o valor calórico em filés de tainha(Mugil cephalus Linnaeus,1758) e de camuriim(Centropomus undecimalis Bloch,1792)...