Structural characterization of a proanthocyanidin-rich fraction from Hancornia speciosa leaves and its effect on the release of pro-inflammatory cytokines and oxidative stress in THP-1 cells.

Ethnopharmacological Relevance: In Brazil, the leaves of Hancornia speciosa Gomes have a traditional use for treating hypertension and diabetes. Experimental investigations have confirmed the anti-hypertensive and hypoglycemic properties of extracts derived from H. speciosa leaves across various experimental models.

Machine Learning-Based Virtual Screening of Antibacterial Agents against Methicillin-Susceptible and Resistant .

The application of computer-aided drug discovery (CADD) approaches has enabled the discovery of new antimicrobial therapeutic agents in the past. The high prevalence of methicillin-resistant(MRSA) strains promoted this pathogen to a high-priority pathogen for drug development. In this sense, modern CADD techniques can be valuable tools for the search for new antimicrobial agents.

A high level of scientific evidence is available to guide treatment of primary shoulder stiffness: The SIAGASCOT consensus.

Purpose: Shoulder stiffness (SS) is a condition characterised by active and passive restricted glenohumeral range of motion, which can occur spontaneously in an idiopathic manner or be associated with a known underlying aetiology. Several treatment options are available and currently no consensus has been obtained on which treatment algorithm represents the best choice for the patient. Herein we present the results of a national consensus on the treatment of primary SS.

Relationship between trunk control and gross motor development of infants in the first year of life: A systematic review.

Objective: to verify the relationship between the level of trunk control and the acquisition of gross motor skills in the first year of life.

Methods: a searching strategy was developed using the PICO tool and performed in the databases PubMed, Cochrane Library, Virtual Library in Health, Embase, and Scopus, from September 2020 to July 2022. The methodological quality of the articles was evaluated by the Ottawa Quality Assessment Scale Cohort Studies (NOS).

Quantitative Chemical Composition, Anti-Oxidant Activity, and Inhibition of TNF Release by THP-1 Cells Induced by Extracts of and .

This study investigated the similarities between and , plant species that are traditionally used in Brazil to treat rheumatism and arthritis, whose anti-inflammatory effects are supported by scientific evidence. The contents of - and -aconitic acid, homoorientin, chicoric acid, swertisin, caffeoyl-feruloyl-tartaric acid, and di-feruloyl-tartaric acid were quantified by UPLC-DAD in various hydroethanolic extracts from the leaves, whereas their anti-oxidant activity and their effect on TNF release by LPS-stimulated THP-1 cells were assessed to evaluate potential anti-inflammatory effects. The 50% and 70% ethanol extracts showed higher concentrations of the analyzed markers in two commercial samples and a cultivated specimen of , as well as in a commercial lot of .

Natural Products and Derivatives as Potential Inhibitors: A Comprehensive Review.

(ZIKV) is an arbovirus whose infection in humans can lead to severe outcomes. This article reviews studies reporting the anti-ZIKV activity of natural products (NPs) and derivatives published from 1997 to 2022, which were carried out with NPs obtained from plants (82.4%) or semisynthetic/synthetic derivatives, fungi (3.

From primordial clocks to circadian oscillators.

Circadian rhythms play an essential part in many biological processes, and only three prokaryotic proteins are required to constitute a true post-translational circadian oscillator. The evolutionary history of the three Kai proteins indicates that KaiC is the oldest member and a central component of the clock. Subsequent additions of KaiB and KaiA regulate the phosphorylation state of KaiC for time synchronization.

Oral sub-chronic treatment with Terminalia phaeocarpa Eichler (Combretaceae) reduces liver PTP1B activity in a murine model of diabetes.

Ethnopharmacological Relevance: The endemic Brazilian medicinal plants of the genus Terminalia (Combretaceae), popularly known as capitão, comprising the similar species Terminalia phaeocarpa Eichler and Terminalia argentea, are traditionally and indistinguishably used in the country to treat diabetes.

Aim Of The Study: The present work investigated the effect of 28 days of treatment with the crude ethanolic extract (CEE) and its derived ethyl acetate fraction (EAF) from T. phaeocarpa leaves in a mice model of diabetes.

Effects of Lipophilicity and Structural Features on the Antiherpes Activity of Digitalis Cardenolides and Derivatives.

There is growing interest in exploring Digitalis cardenolides as potential antiviral agents. Hence, we herein investigated the influence of structural features and lipophilicity on the antiherpes activity of 65 natural and semisynthetic cardenolides assayed in vitro against HSV-1. The presence of an α,β-unsaturated lactone ring at C-17, a β-hydroxy group at C-14 and C-3β-OR substituents were considered essential requirements for this biological activity.

Definition of chemical markers for Hancornia speciosa Gomes by chemometric analysis based on the chemical composition of extracts, their vasorelaxant effect and α-glucosidase inhibition.

Ethnopharmacological Relevance: Hancornia speciosa Gomes (Apocynaceae) is a tree found in the Brazilian savannah, traditionally used to treat several diseases, including diabetes and hypertension. The anti-hypertensive activity of H. speciosa leaves (HSL) has been demonstrated in different models and is credited to the vasodilator effect and ACE (angiotensin-converting enzyme) inhibition.

Activation of RAS/MAPK pathway confers MCL-1 mediated acquired resistance to BCL-2 inhibitor venetoclax in acute myeloid leukemia.

Despite high initial response rates, acute myeloid leukemia (AML) treated with the BCL-2-selective inhibitor venetoclax (VEN) alone or in combinations commonly acquires resistance. We performed gene/protein expression, metabolomic and methylation analyses of isogenic AML cell lines sensitive or resistant to VEN, and identified the activation of RAS/MAPK pathway, leading to increased stability and higher levels of MCL-1 protein, as a major acquired mechanism of VEN resistance. MCL-1 sustained survival and maintained mitochondrial respiration in VEN-RE cells, which had impaired electron transport chain (ETC) complex II activity, and MCL-1 silencing or pharmacologic inhibition restored VEN sensitivity.

cis-Aconitic Acid, a Constituent of Echinodorus grandiflorus Leaves, Inhibits Antigen-Induced Arthritis and Gout in Mice.

-Aconitic acid is a constituent from the leaves of , a medicinal plant traditionally used in Brazil to treat inflammatory conditions, including arthritic diseases. The present study aimed to investigate the anti-arthritic effect of -aconitic acid in murine models of antigen-induced arthritis and monosodium urate-induced gout. The possible underlying mechanisms of action was evaluated in THP-1 macrophages.

Choosing patient-reported outcome measures for shoulder pathology.

This study was designed to identify the most frequent shoulder patient-reported outcome measures (PROMs) reported in high-quality literature.A systematic review was performed to identify shoulder PROMs, and their diffusion within the scientific literature was tested with a subsequent dedicated search in MEDLINE.506 studies were included in the final data analysis, for a total number of 36,553 patients.

BCL-2 Inhibitor ABT-737 Effectively Targets Leukemia-Initiating Cells with Differential Regulation of Relevant Genes Leading to Extended Survival in a NRAS/BCL-2 Mouse Model of High Risk-Myelodysplastic Syndrome.

During transformation, myelodysplastic syndromes (MDS) are characterized by reducing apoptosis of bone marrow (BM) precursors. Mouse models of high risk (HR)-MDS and acute myelogenous leukemia (AML) post-MDS using mutant NRAS and overexpression of human BCL-2, known to be poor prognostic indicators of the human diseases, were created. We have reported the efficacy of the BCL-2 inhibitor, ABT-737, on the AML post-MDS model; here, we report that this BCL-2 inhibitor also significantly extended survival of the HR-MDS mouse model, with reductions of BM blasts and lineage negative/Sca1+/KIT+ (LSK) cells.

Stem Cells in Orthopedic Web Information: An Assessment with the DISCERN Tool.

Objective: Regenerative medicine is experiencing a strong expansion worldwide, including the treatment of some common orthopedic pathologies, with an increase in physicians adopting these technologies. This growing interest has been associated with an equally significant spread of websites dedicated to public information on this topic, often lacking scientific bases. This study aims to evaluate the quality of information on the World Wide Web about stem cells for cartilage disorders in orthopedic practice.

TNF-α inhibition, antioxidant effects and chemical analysis of extracts and fraction from Brazilian guaraná seed powder.

Paullinia cupana Kunth., commonly named Guaraná, is a plant from Brazil used as stimulant. The aim of this study was to evaluate the potential of extracts and tannins-rich and methylxanthines-free fraction from guaraná in the anti-inflammatory and antioxidant effect in vitro.

Polyphenol-rich extract and fractions of Terminalia phaeocarpa Eichler possess hypoglycemic effect, reduce the release of cytokines, and inhibit lipase, α-glucosidase, and α-amilase enzymes.

Ethnopharmacological Relevance: species of Terminalia (Combretaceae) are used to treat diabetes and metabolic disorders in Asia, Africa, and America. Terminalia phaeocarpa Eichler is an endemic tree from Brazil, popularly known as capitão. This species is closely related to Terminalia argentea Mart.

Liposomes co-encapsulating doxorubicin and glucoevatromonoside derivative induce synergic cytotoxic response against breast cancer cell lines.

Cancer is one of the main causes of death in the world and thus a global public health problem. Among the treatments available for cancer are surgery, radiotherapy, and chemotherapy. Currently, there is increased interest in the combination of two or more antitumor agents to achieve a synergistic effect in cancer therapy.

Cytotoxicity of glucoevatromonoside alone and in combination with chemotherapy drugs and their effects on Na,K-ATPase and ion channels on lung cancer cells.

Cardiac glycosides (CGs) are useful drugs to treat cardiac illnesses and have potent cytotoxic and anticancer effects in cultured cells and animal models. Their receptor is the Na,K ATPase, but other plasma membrane proteins might bind CGs as well. Herein, we evaluated the short- and long-lasting cytotoxic effects of the natural cardenolide glucoevatromonoside (GEV) on non-small-cell lung cancer H460 cells.

Bioguided chemical characterization of pequi (Caryocar brasiliense) fruit peels towards an anti-diabetic activity.

Pequi fruit peels are an underexploited source of polyphenols. The anti-diabetic potential of an extract and fractions from the peels were evaluated in a panel of assays. The extract and fractions thereof inhibited the release of cytokines involved in insulin resistance - TNF, IL-1β, and CCL2 - by lipopolysaccharide-stimulated THP-1 cells.

How directed evolution reshapes the energy landscape in an enzyme to boost catalysis.

The advent of biocatalysts designed computationally and optimized by laboratory evolution provides an opportunity to explore molecular strategies for augmenting catalytic function. Applying a suite of nuclear magnetic resonance, crystallography, and stopped-flow techniques to an enzyme designed for an elementary proton transfer reaction, we show how directed evolution gradually altered the conformational ensemble of the protein scaffold to populate a narrow, highly active conformational ensemble and accelerate this transformation by nearly nine orders of magnitude. Mutations acquired during optimization enabled global conformational changes, including high-energy backbone rearrangements, that cooperatively organized the catalytic base and oxyanion stabilizer, thus perfecting transition-state stabilization.