Ethnobotanical Surveys of Plants Used by Quilombola Communities in Brazil: A Scoping Review.

Quilombola communities play a crucial role in maintaining biodiversity through traditional management models. The use of medicinal plants within these communities reflects a deep reservoir of knowledge, passed down through generations. The objective of this study was to conduct a scoping review to systematically analyze and synthesize the existing literature on the medicinal plants used by Quilombola communities in Brazil, with a focus on their therapeutic applications and cultural significance. The Population, Concept, and Context (PCC) strategy was utilized, where the population refers to the Quilombolas, the concept pertains to medicinal plants, and the context involves illness. A total of 888 studies were initially identified, but only 10 met the inclusion criteria, covering 297 plant species from 80 different families. These plants are employed in a wide range of therapeutic applications, with decoction, alcohol maceration, and infusion being the most common methods of preparation. The study highlights the rich ethnopharmacological knowledge held by Quilombola communities and underscores the need for greater recognition and integration of this traditional knowledge into public health practices. The conclusion emphasizes the importance of preserving and validating the use of medicinal plants by these communities, which could serve as a foundation for future pharmacological discoveries and the development of culturally appropriate health interventions.

(Bio)políticas públicas a pessoas que vivem com hiv/aids por uma ótica queer e desconstrucionista: desafios e iniquidades / (Bio)public policies for people living with hiv/aids from a queer and deconstructionist perspective: challenges and inequities

Resumo Este trabalho apresenta uma revisão crítica das políticas e ações público-governamentais no que tange ao enfrentamento da epidemia HIV/AIDS no Brasil. Apoia-se principalmente sobre orientações, documentos, relatórios e boletins do Ministério da Saúde, analisados por uma ótica queer e desconstrucionista consciente e crítica no que concerne à inserção de sujeitos historicamente marginalizados em políticas e serviços públicos de saúde no país. Pretende-se discutir e relacionar a imbricação entre o biopoder, as necropolíticas e o microcosmo da teoria queer no que diz respeito especialmente a práticas sexuais dissidentes. Analisando o acesso e a equidade em saúde, e afunilando para dados qualitativos e quantitativos das atividades de promoção e prevenção em saúde realizadas pelos Centros de Acolhimento Temporários (CTAs) e pelas Redes de Atenção à Saúde (RAS), surge uma breve elaboração teórica sobre as temáticas mencionadas, embasadas por discussões que perpassam a obra foucaultiana e sua influência sobre Teoria Queer e análises biopolíticas. Indivíduos que são considerados população-chave nas bases de estratégias preventivas continuam sendo negligenciados pelas políticas públicas ou enfrentam dificuldades no acesso aos serviços de saúde. Essas grandes contradições podem estar contribuindo para o aumento significativo no número de novas infecções pelo HIV/AIDS entre segmentos demográficos mais suscetíveis e vulneráveis socioeconômica-política-culturalmente.

Abstract This work presents a critical review of public-governmental policies and actions regarding combating the HIV/AIDS epidemic in Brazil. It is mainly based on guidelines, documents, reports, and bulletins from the Ministry of Health, analyzed from a conscious and critical queer and deconstructionist perspective regarding the inclusion of historically marginalized subjects in public health policies and services in the country. It intends to discuss and relate the overlap between the biopower, the necropolitics, and the microcosm of queer theory with regards especially to dissident sexual practices. Analyzing access and equity in health and focusing on qualitative and quantitative data on health promotion and prevention activities carried out by Temporary Reception Centers (TRC)s and Health Care Networks (HCN), the basis for a brief theoretical elaboration on the themes mentioned emerges, based on discussions that permeate Foucault's work and its influence on Queer Theory and biopolitical analyses. Individuals who are considered a key population in the basis of preventive strategies continue to be neglected by public policies or face difficulties in accessing health services. These major contradictions may be contributing to the significant increase in the number of new HIV/AIDS infections among the most susceptible and socio-economically-politically-culturally vulnerable demographic segments.

Effects of chemotherapeutic drugs on the antioxidant capacity of human erythroleukemia cells with MDR phenotype.

In this work, we identified that different chemotherapeutic drugs may select cells with different antioxidant capacities. For this, we evaluated the sensitivity of two multidrug-resistant (MDR) erythroleukemia cell lines: Lucena (resistant to vincristine, VCR) and FEPS (resistant to daunorubicin, DNR) derived from the same sensitive cell K562 (non-MDR) to hydrogen peroxide. In addition, we evaluated how the cell lines respond to the oxidizing agent in the absence of VCR/DNR. In absence of VCR, Lucena drastically decreases cell viability when exposed to hydrogen peroxide, while FEPS is not affected even without DNR. To analyze whether selection by different chemotherapeutic agents may generate altered energetic demands, we analyzed the production of reactive oxygen species (ROS) and the relative expression of the glucose transporter 1 gene (glut1). We observed that the selection through DNR apparently generates a higher energy demand than VCR. High levels of transcription factors genes expression (nrf2, hif-1α, and oct4) were kept even when the DNR is withdrawn from the FEPS culture for one month. Together, these results indicate that DNR selects cells with greater ability to express the major transcription factors related to the antioxidant defense system and the main extrusion pump (ABCB1) related to the MDR phenotype. Taking into account that the antioxidant capacity of tumor cells is closely related to resistance to multiple drugs, it is evident that endogenous antioxidant molecules may be targets for the development of new anticancer drugs.

New Mechanistic Insight on the PIM-1 Kinase Inhibitor AZD1208 Using Multidrug Resistant Human Erythroleukemia Cell Lines and Molecular Docking Simulations.

BACKGROUND: PIM-1 is a kinase which has been related to the oncogenic processes like cell survival, proliferation, and multidrug resistance (MDR). This kinase is known for its ability to phosphorylate the main extrusion pump (ABCB1) related to the MDR phenotype. OBJECTIVE: In the present work, we tested a new mechanistic insight on the AZD1208 (PIM-1 specific inhibitor) under interaction with chemotherapy agents such as Daunorubicin (DNR) and Vincristine (VCR). MATERIALS AND METHODS: In order to verify a potential cytotoxic effect based on pharmacological synergism, two MDR cell lines were used: Lucena (resistant to VCR) and FEPS (resistant to DNR), both derived from the K562 non-MDR cell line, by MTT analyses. The activity of Pgp was ascertained by measuring accumulation and the directional flux of Rh123. Furthermore, we performed a molecular docking simulation to delve into the molecular mechanism of PIM-1 alone, and combined with chemotherapeutic agents (VCR and DNR). RESULTS: Our in vitro results have shown that AZD1208 alone decreases cell viability of MDR cells. However, co-exposure of AZD1208 and DNR or VCR reverses this effect. When we analyzed the ABCB1 activity AZD1208 alone was not able to affect the pump extrusion. Differently, co-exposure of AZD1208 and DNR or VCR impaired ABCB1 activity, which could be explained by compensatory expression of abcb1 or other extrusion pumps not analyzed here. Docking analysis showed that AZD1208 is capable of performing hydrophobic interactions with PIM-1 ATP- binding-site residues with stronger interaction-based negative free energy (FEB, kcal/mol) than the ATP itself, mimicking an ATP-competitive inhibitory pattern of interaction. On the same way, VCR and DNR may theoretically interact at the same biophysical environment of AZD1208 and also compete with ATP by the PIM-1 active site. These evidences suggest that AZD1208 may induce pharmacodynamic interaction with VCR and DNR, weakening its cytotoxic potential in the ATP-binding site from PIM-1 observed in the in vitro experiments. CONCLUSION: Finally, the current results could have a pre-clinical relevance potential in the rational polypharmacology strategies to prevent multiple-drugs resistance in human leukemia cancer therapy.

Modeling drug-drug interactions of AZD1208 with Vincristine and Daunorubicin on ligand-extrusion binding TMD-domains of multidrug resistance P-glycoprotein (ABCB1).

In the present study, the molecular docking mechanism based on pharmacodynamic interactions between the ligands AZD1208 and recognized chemotherapy agents (Vincristine and Daunorubicin) with human ATP-binding cassette (ABC) transporters (ABCB1) was investigated. For the first time, were combined an in silico approaches like molecular docking and ab initio computational simulation based on Density Functional Theory (DFT) to explain the drug-drug interaction mechanism of aforementioned chemotherapy ligands with the transmembrane ligand extrusion binding domains (TMDs) of ABCB1. In this regard, the theoretical pharmacodynamic interactions were characterized by using the Gibbs free energy (FEB, kcal/mol) from the best ABCB1-ligand docking complexes. The molecular docking results pointing that for the three chemotherapy ABCB1-ligand complexes are mainly based in non-covalent hydrophobic and hydrogen-bond interactions showing a similar toxicodynamic behavior in terms of strength of interaction (FEB, kcal/mol) and very close free binding energies when compared with the FEB-values of the ABCB1 specific-inhibitor (Rhodamine B) = -6.0 kcal/mol used as theoretical docking control to compare with FEB (AZD1208-ABCB1) ∼ FEB (Vincristine-ABCB1) ∼ FEB (Daunorubicin-ABCB1) -6.2 kcal/mol as average. Ramachandran plot suggests that the 3D-crystallographic structure from ABCB1 transporter can be efficiently-modeled with conformationally-favored Psi versus Phi dihedral angles for all key TMDs-residues. Though, the results of DFT-simulation corroborate the existence of drug-drug interaction between (AZD1208/Vincristine) > (AZD1208/Daunorubicin). These theoretical pieces of evidence have preclinical relevance potential in the design of the new drugs to understand the polypharmacology influence in the molecular mechanism of multiple-drugs resistance, contributing with a higher success in chemotherapy and prognosis of cancer patients.