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Viral coinfection among HIV-positive patients, coupled with the development of AIDS, remains a major public health problem. The synergism between the presence of HIV and other viruses has consequences in relation to changes in the severity of the infection, as well as changes in the natural course of both infections. Several polymorphisms present in genes that encode cytokines have a relevant influence on their transcription and consequently on the production of such immunological molecules. The present study evaluated the influence of SNPs located in the promoter regions of genes encoding the cytokines INF-ɣ, TNF, IL-6, IL-4, and IL-2, as well as their respective plasma concentrations, in patients infected with HIV and/or EBV in the state of Pará. Additionally, this study described the epidemiological profile and compared CD4+ and CD8+ T lymphocyte counts among the groups studied. The associative analysis between the SNPs and plasma cytokine concentrations in different groups showed statistical relevance for three polymorphisms: rs2069762 ( IL2 ), where the GG genotype demonstrated higher IL-2 levels in HIV mono-infected individuals; rs2243250 ( IL4 ), where the CT genotype showed higher IL-4 levels in the control group; and rs2069705 ( IFNG ), where the TT genotype showed higher IFN-γ levels in the coinfected group. Regarding SNP associations with CD4+/CD8+ counts, significant findings were observed in HIV mono-infected individuals: the rs2069705 ( IFNG ) polymorphism was linked to higher CD4+ counts with the CT genotype, and rs1799964 ( TNF ) was associated with higher CD8+ counts with the CC genotype. Therefore, this study provides evidence that the rs2069705 ( IFNG ) SNP is associated with elevated IFN-γ levels, which may have pathogenic consequences, as depletion of this cytokine is concerning for people living with HIV due to its antiviral properties.

Swietenia macrophylla King is a plant commonly known as Brazilian mahogany. The wood from its stem is highly prized for its exceptional quality, while its leaves are valued for their high content of phragmalin-type limonoids, a subclass of compounds known for their significant biological activities, including antimalarial, antitumor, antiviral, and anti-inflammatory properties. In this context, twelve isolated limonoids from S. macrophylla leaves were employed as standards in mass spectrometry-based molecular networking to unveil new potential mass spectrometry signatures for phragmalin-type limonoids. Consequently, ultra-performance liquid chromatography coupled with high-resolution mass spectrometry was utilized for data acquisition. Subsequently, the obtained data were analyzed using the Global Natural Products Social Molecular Networking platform based on spectral similarity. In summary, this study identified 24 new putative phragmalin-type limonoids for the first time in S. macrophylla . These compounds may prove valuable in guiding future drug development efforts, leveraging the already established biological activities associated with limonoids.

Margaritaria nobilis L.f. (Phyllanthaceae), a native Brazilian tree occurring mainly in the Amazon, is used in folk medicine for the treatment of abscesses (bark) and cancer-like symptoms (leaves). The present study evaluates the safety of its acute oral administration and its effects on nociception and plasma leakage. The chemical constitution of the leaf's ethanolic extract is determined by ultra-performance liquid chromatography-high-resolution mass spectrometry (LC-MS. Its acute oral toxicity is evaluated in female rats at a dose of 2000 mg/kg, evaluating the occurrence of deaths and Hippocratic, behavioral, hematological, biochemical, and histopathological changes, as well as food and water consumption and weight gain. Antinociceptive activity is evaluated in male mice with acetic-acid-induced peritonitis (APT) and formalin (FT) tests. An open field (OF) test is performed to verify possible interferences in the animals' consciousness or locomotion. LC-MS analysis shows the presence of 44 compounds classified as phenolic acid derivatives, flavonoids and O-glycosylated derivatives, and hydrolyzable tannins. No deaths or significant behavioral, histological, or biochemical changes are observed in the toxicity assessment. In nociception tests, M. nobilis extract significantly reduces abdominal contortions in APT, demonstrating selectivity for inflammatory components (FT second phase), not interfering in neuropathic components (FT first phase) or consciousness and locomotion levels in OF. Additionally, M. nobilis extract inhibits plasma acetic-acid-induced leakage. These data demonstrate the low toxicity of M. nobilis ethanolic extract, as well as its effectiveness in modulating inflammatory nociception and plasma leakage, possibly related to the flavonoids and tannins present in its composition.

Deguelia nitidula (Benth.) A.M.G.Azevedo & R.A.Camargo (Fabaceae) is an herbaceous plant distributed in the Brazilian Amazon, and it is called "raiz do sol" (sun roots). On Marajó Island, quilombola communities use its prepared roots to treat skin diseases commonly caused by fungi, viruses, and bacteria. Thus, in this study, the extract, and its fractions from D. nitidula roots were used to perform in vitro cytotoxic and antibacterial assays against Staphylococcus aureus strains. Thereafter, liquid chromatography-mass spectrometry (LC-MS) was used for the metabolite annotation process. The ethanolic extract of D. nitidula roots show significant bactericidal activity against S. aureus with IC 50 82 μg.mL -1 and a selectivity index (SI) of 21.35. Furthermore, the SREFr2 and SREFr3 fractions show a potent bactericidal activity, i.e., MIC of 46.8 μg.mL -1 for both, and MBC of 375 and 93.7 μg.mL -1 , respectively. As showcased, SREFr3 shows safe and effective antibacterial activity mainly in respect to the excellent selectivity index (SI = 82.06). On the other hand, SREFr2 shows low selectivity (SI = 6.8), which characterizes it as not safe for therapeutic use. Otherwise, due to a limited amount of reference MS 2 spectra in public libraries, up to now, it was not possible to perform a complete metabolite annotation. Despite that, our antibacterial results for SREFr3 and correlated substructures of amino acid derivatives show that the roots of D. nitidula are a natural source of specialized metabolites, which can be isolated in the future, and then used as a support for further bio-guided research, as well as natural drug development.

Momordica charantia L. (Cucurbitaceae) is a plant known in Brazil as "melão de São Caetano", which has been related to many therapeutic applications in folk medicine. Herein, we describe antibacterial activities and related metabolites for an extract and fractions obtained from the leaves of that species. An ethanolic extract and its three fractions were used to perform in vitro antibacterial assays. In addition, liquid chromatography coupled to mass spectrometry and the molecular networking approach were used for the metabolite annotation process. Overall, 25 compounds were annotated in the ethanolic extract from M. charantia leaves, including flavones, terpenes, organic acids, and inositol pyrophosphate derivatives. The ethanolic extract exhibited low activity against Proteus mirabilis (MIC 312.5 µg·mL -1 ) and Klebsiella pneumoniae (MIC 625 µg·mL -1 ). The ethyl acetate phase showed interesting antibacterial activity (MIC 156.2 µg·mL -1 ) against Klebsiella pneumoniae , and it was well justified by the high content of glycosylated flavones. Therefore, based on the ethyl acetate phase antibacterial result, we suggest that M. charantia leaves could be considered as an alternative antibacterial source against K. pneumoniae and can serve as a pillar for future studies as well as pharmacological application against the bacteria.

Margaritaria nobilis is a shrubby species widely distributed in Brazil from the Amazon to the Atlantic Rainforest. Its bark and fruit are used in the Peruvian Amazon for disinfecting abscesses and as a tonic in pregnancy, respectively, and its leaves are used to treat cancer symptoms. From analyses via UHPLC-MS/MS, we sought to determine the chemical profile of the ethanolic extract of M. nobilis leaves by means of putative analyses supported by computational tools and spectral libraries. Thus, it was possible to annotate 44 compounds, of which 12 are phenolic acid derivatives, 16 are O -glycosylated flavonoids and 16 hydrolysable tannins. Among the flavonoids, although they are known, except for kaempferol, which has already been isolated from this species, the other flavonoids ( 10 , 14 , 15 , 21 , 24 - 26 , 28 - 30 , 33 - 35 , 40 and 41 ) are being reported for the first time in the genus. Among the hydrolysable tannins, six ellagitannins present the HHDP group ( 6 , 19 , 22 , 31 , 38 and 43 ), one presents the DHHDP group ( 5 ), and four contain oxidatively modified congeners ( 12 , 20 , 37 and 39 ). Through the annotation of these compounds, we hope to contribute to the improved chemosystematics knowledge of the genus. Furthermore, supported by a metric review of the literature, we observed that many of the compounds reported here are congeners of authentically bioactive compounds. Thus, we believe that this work may help in understanding future pharmacological activities.

Tools to identify good practices in the design, implementation, and evaluation of physical activity community-based interventions (PACIs) are key to address the physical inactivity pandemic. Existing tools tend to be extensive and with limited applicability to assess small-scale PACIs. This work aimed to report the development and preliminary validity results of a simple, practical, and user-friendly tool to evaluate PACIs in local/municipal contexts. Eighty-six good practice characteristics defined by the World Health Organization (WHO), the Joint Action Framework on Chronic Diseases (CHRODIS), and an umbrella review of good practice characteristics of diet and physical activity interventions were initially extracted and refined in four rounds of revision from an expert panel using a Delphi-type methodology and rated on their relative importance. A pilot application was conducted, and data on the tool usability and applicability were collected through three semi-structured interviews with specialists and coordinators of local/municipal PACIs. For preliminary validation, the refined tool was applied to five community-based programs mostly aimed at an elderly population. The final tool included thirty-four selected characteristics, with a brief explanation and practical examples for each, under three main sections: design, evaluation, and implementation. Each characteristic has a rating (i.e., somewhat important, highly important, mandatory) and a percentage weight. Preliminary validation of this tool pointed to an adequate evaluation of good practice characteristics of municipal PACIs in a reliable, practical, and user-friendly way. Given its adequacy, this tool can support the definition of quality standards for PACIs, encouraging their dissemination and adoption at a regional or national level.

To raise perceived capability (C), opportunity (O) and motivation (M) for physical activity (PA) behaviour (B) among adults, the Portuguese Directorate-General of Health developed a mass media campaign named "Follow the Whistle", based on behaviour change theory and social marketing principles. Comprehensive formative and process evaluation suggests this media-led campaign used best-practice principles. The campaign adopted a population-wide approach, had clear behavioural goals, and clear multi-strategy implementation. We assessed campaign awareness and initial impact using pre ( n = 878, 57% women) and post-campaign ( n = 1319, 58% women) independent adult population samples via an online questionnaire, comprising socio-demographic factors, campaign awareness and recall, and psychosocial and behavioural measures linked to the COM-B model. PA was assessed with IPAQ and the Activity Choice Index. The post-campaign recall was typical of levels following national campaigns (24%). Post-campaign measures were higher for key theory-based targets (all p < 0.05), namely self-efficacy, perceived opportunities to be more active and intrinsic motivation. The impact on social norms and self-efficacy was moderated by campaign awareness. Concerning PA, effects were found for vigorous activity ( p < 0.01), but not for incidental activity. Overall the campaign impacted key theory-based intermediate outcomes, but did not influence incidental activity, which highlights the need for sustained and repeated campaign efforts.

Apoptosis is one of the main types of regulated cell death, a complex process that can be triggered by external or internal stimuli, which activate the extrinsic or the intrinsic pathway, respectively. Among various factors involved in apoptosis, several genes and their interactive networks are crucial regulators of the outcomes of each apoptotic phase. Furthermore, mitochondria are key players in determining the way by which cells will react to internal stress stimuli, thus being the main contributor of the intrinsic pathway, in addition to providing energy for the whole process. Other factors that have been reported as important players of this intricate molecular network are miRNAs, which regulate the genes involved in the apoptotic process. Imbalance in any of these mechanisms can lead to the development of several illnesses, hence, an overall understanding of these processes is essential for the comprehension of such situations. Although apoptosis has been widely studied, the current literature lacks an updated and more general overview on this subject. Therefore, here, we review and discuss the mechanisms of apoptosis, highlighting the roles of genes, miRNAs, and mitochondria involved in this type of cell death.