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OBJECTIVES: The control chart is a classic statistical technique in epidemiology for identifying trends, patterns, or alerts. One meaningful use is monitoring and tracking Infant Mortality Rates, which is a priority both domestically and for the World Health Organization, as it reflects the effectiveness of public policies and the progress of nations. This study aims to evaluate the applicability and performance of this technique in Brazilian cities with different population sizes using infant mortality data. RESULTS: In this article, we evaluate the effectiveness of the statistical process control chart in the context of Brazilian cities. We present three categories of city groups, divided based on population size and classified according to the quality of the analyses when subjected to the control method: consistent, interpretable, and inconsistent. In cities with a large population, the data in these contexts show a lower noise level and reliable results. However, in intermediate and small-sized cities, the technique becomes limited in detecting deviations from expected behaviors, resulting in reduced reliability of the generated patterns and alerts.
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Cidades , Mortalidade Infantil , Densidade Demográfica , Humanos , Brasil/epidemiologia , Lactente , Mortalidade Infantil/tendências , Cidades/epidemiologia , Cidades/estatística & dados numéricos , Recém-NascidoRESUMO
Cancer is the second leading cause of death worldwide and is considered a major public health problem. Despite the significant advances in cancer research, the conventional cancer treatment approaches often lead to serious side effects that affect the quality of life of cancer patients. Thus, searching for new alternatives for cancer treatment is crucial to minimize these problems. Chalcone-sulfonamide hybrids display a range of biological activities and have been widely investigated for their anticancer potential, being considered promising molecules for cancer treatment. This systematic review aimed to summarize the information available in the literature about the anticancer potential of chalcones-sulfonamides in vitro and in vivo and their mechanisms of action. Our analysis demonstrated that chalcones-sulfonamides have relevant cytotoxic potential against different cancer cell lines in vitro, especially against the human colorectal carcinoma cell line HCT-116. These molecules have also reduced tumor growth in vivo. Some chalcones-sulfonamides had improved cytotoxicity after chemical modification and could become more selective or even more potent than reference chemotherapeutics. The mechanisms underlying these effects demonstrated that chalcones-sulfonamides may lead to cell death by different pathways, predominantly via apoptosis or necroptosis. This review may encourage researchers to advance studies with chalcones-sulfonamides, especially to elucidate their mechanisms of action, contributing to the development of new alternatives to cancer treatment.
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Antineoplásicos , Chalconas , Sulfonamidas , Animais , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Chalconas/farmacologia , Chalconas/química , Ensaios de Seleção de Medicamentos Antitumorais , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Sulfonamidas/química , Sulfonamidas/farmacologiaRESUMO
The solvation thermodynamics (ST) formalism proposed by A. Ben-Naim is a mathematically rigorous and physically grounded theory for describing properties related to solvation. It considers the solvation process as the transfer of a molecule ("solute") from a fixed position in the ideal gas phase to a fixed position within the solution. Thus, it removes any contribution to the solvation process that is not related to the interactions between this molecule and its environment in the solution. Because ST is based on statistical thermodynamics, the natural variable is number density, which leads to the amount (or "molar") concentration scale. However, this choice of concentration scale is not unique in classical thermodynamics and the solvation properties can be different for commonly used concentration scales. We proposed and performed experiments with diethylamine in a water/hexadecane heterogeneous mixture to confront the predictions of the ST, based on the amount (or "molar") concentration scale, and the Fowler-Guggenheim formalism, based on the mole fraction scale. By means of simple acid-base titration and 1H NMR measurements, it was established that the predictions of differences in the solvation Gibbs energy and the partition ratio (or "partition coefficient") of diethylamine between water and hexadecane are consistent with the ST formalism. Additionally, with current literature data, we have shown additional experimental support for the ST. However, due to the arbitrariness of the relative amount of solvents in the partition ratio, the choice of a single concentration scale within the classical thermodynamics is still not possible.
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Cancer is highlighted as a major global health challenge in the XXI century. The cyclooxygenase-2 (COX-2) enzyme rises as a widespread tumor progression marker. Celecoxib (CXB) is a selective COX-2 inhibitor used in adjuvant cancer therapy, but high concentrations are required in humans. In this sense, the development of nanocarriers has been proposed once they can improve the biopharmaceutical, pharmacokinetic and pharmacological properties of drugs. In this context, this article reviews the progress in the development of CXB-loaded nanocarriers over the past decade and their prospects. Recent advances in the field of CXB-loaded nanocarriers demonstrate the use of complex formulations and the increasing importance of in vivo studies. The types of CXB-loaded nanocarriers that have been developed are heterogeneous and based on polymers and lipids together or separately. It was found that the work on CXB-loaded nanocarriers is carried out using established techniques and raw materials, such as poly (lactic-co-glicolic acid), cholesterol, phospholipids and poly(ethyleneglycol). The main improvements that have been achieved are the use of cell surface ligands, the simultaneous delivery of different synergistic agents, and the presence of materials that can provide imaging properties and other advanced features. The combination of CXB with other anti-inflammatory drugs and/or apoptosis inducers appears to hold effective pharmacological promise. The greatest advance to date from a clinical perspective is the ability of CXB to enhance the cytotoxic effects of established chemotherapeutic agents.
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Pseudomonas aeruginosa is a frequent cause of antimicrobial-resistant hospital-acquired pneumonia, especially in critically ill patients. Inflammation triggered by P. aeruginosa infection is necessary for bacterial clearance but must be spatially and temporally regulated to prevent further tissue damage and bacterial dissemination. Emerging data have shed light on the pro-resolving actions of angiotensin-(1-7) [Ang-(1-7)] signaling through the G protein-coupled receptor Mas (MasR) during infections. Herein, we investigated the role of the Ang-(1-7)/Mas axis in pneumonia caused by P. aeruginosa by using genetic and pharmacological approach and found that Mas receptor-deficient animals developed a more severe form of pneumonia showing higher neutrophilic infiltration into the airways, bacterial load, cytokines, and chemokines production and more severe pulmonary damage. Conversely, treatment of pseudomonas-infected mice with Ang-(1-7) was able to decrease neutrophilic infiltration in airways and lungs, local and systemic levels of pro-inflammatory cytokines and chemokines, and increase the efferocytosis rates, mitigating lung damage/dysfunction caused by infection. Notably, the therapeutic association of Ang-(1-7) with antibiotics improved the survival rates of mice subjected to lethal inoculum of P. aeruginosa, extending the therapeutic window for imipenem. Mechanistically, Ang-(1-7) increased phagocytosis of bacteria by neutrophils and macrophages to accelerate pathogen clearance. Altogether, harnessing the Ang-(1-7) pathway during infection is a potential strategy for the development of host-directed therapies to promote mechanisms of resistance and resilience to pneumonia.
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Angiotensina I , Antibacterianos , Camundongos Endogâmicos C57BL , Fragmentos de Peptídeos , Proto-Oncogene Mas , Infecções por Pseudomonas , Pseudomonas aeruginosa , Receptores Acoplados a Proteínas G , Animais , Angiotensina I/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Camundongos , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/metabolismo , Infecções por Pseudomonas/microbiologia , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/genética , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/patologia , Pneumonia Bacteriana/metabolismo , Citocinas/metabolismo , Camundongos Knockout , Pneumonia/tratamento farmacológico , Pneumonia/metabolismo , Pneumonia/microbiologia , Masculino , Pulmão/microbiologia , Pulmão/metabolismo , Pulmão/patologia , Transdução de Sinais/efeitos dos fármacos , Infiltração de Neutrófilos/efeitos dos fármacosRESUMO
Withanolides are steroidal lactones commonly found in plants of the Solanaceae family that have significant medicinal value. In this study, three withanolides extracted from Iochroma arborescens leaves were isolated and characterized. These included withaphysalin F (3: ) and two newly identified epimeric compounds: 18R- and 18S-O-methyl-withaphysalin F (1: and 2: ). Their structures were elucidated by NMR, IR, MS, CD, and X-ray diffraction analysis, and their potential against cell proliferation and migration was investigated. The cytotoxic assay revealed activity against different tumor and non-tumor cell lines. (18S)-O-methyl-withaphysalin F (2: ) presented cell death effects after at least 6 hours of exposure. MDA-MB-231 cells were exposed to 0.06 and 0.6 µM of (18S)-O-methyl-withaphysalin F (2: ), and reductions in cell adhesion, migration, and clonogenicity were observed. Morphological analysis revealed negative regulation in filopodia, salience, and roughness, as well as alterations in cellular microarchitecture. These results provide clues as to the effects of (18S)-O-methyl-withaphysalin F (2: ), allowing new molecular modifications to improve potency and selectivity and increase our antineoplastic arsenal.
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Antineoplásicos Fitogênicos , Movimento Celular , Proliferação de Células , Humanos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Vitanolídeos/farmacologia , Vitanolídeos/isolamento & purificação , Vitanolídeos/química , Solanaceae/química , Estrutura Molecular , Folhas de Planta/químicaRESUMO
Objective: Minimally invasive surgery (MIS) is the standard approach for the staging and treatment of early-stage endometrial cancer (EC) and often includes use of a uterine manipulator. Uterine perforation is a known risk in this setting, and the impact of perforation and tumor spillage on cancer recurrence is largely unknown. The aim of this study was to assess the association between uterine perforation and/or tumor spillage at the time of MIS for low-grade, early-stage EC on disease recurrence. Methods: A retrospective single-center cohort study was conducted including patients who underwent MIS for management of low-grade and early-stage EC with use of a uterine manipulator. Rates of disease recurrence were compared between patients with and without documented uterine perforation and/or tumor spillage at the time of surgery. Statistical significance was defined as p < 0.05. Results: 408 patients with low-grade and early-stage EC were identified from the tumor registry and included in the study. Uterine perforation and/or tumor spillage was documented in 5.9 % (24/408) of cases. Recurrent disease was noted in 8.1 % (33/408) of the entire cohort. Most patients had isolated local recurrence (23/33; 69.7 %), while 9.1 % (3/33) had distant recurrence and 21.2 % (7/33) had both local and distant recurrence. There was no association between uterine perforation and/or tumor spillage and recurrence rates (p = 0.67). The trend in disease free survival was shorter among patients with these complications. Conclusions: Our analysis did not demonstrate a statistically significant difference in disease recurrence rates among patients with early-stage, low-grade EC based on uterine perforation and/or tumor spillage at the time of surgery.
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Malaria is a serious public health problem, being an endemic disease in 84 countries, mainly in Africa. This review explores the application of capillary electrophoresis (CE) techniques for analyzing antimalarial drugs, highlighting methods from 2000 to 2023 for the analysis of pharmaceutical formulations and human biological samples. The versatility, selectivity, high efficiency, cost-effectiveness, and high analytical frequency of CE techniques have become attractive choices for pharmaceutical analysis, focusing on quality control and impurity analysis applications. The evolution of achiral and chiral electromigration methods has been described based on the features of each mode of separation: capillary zone electrophoresis (CZE), micellar electrokinetic chromatography, microemulsion electrokinetic chromatography, and capillary electrochromatography. As expected, CZE is reported in most articles owing to its compatibility with drug properties and separation mode. However, it is necessary to perform other separation modes for a few drugs that are present in neutral form. After exhaustive research using different databases and statistical analyses, 27 articles using CE techniques for antimalarial drug analysis were found and are mentioned in this review.
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Antimaláricos , Eletroforese Capilar , Antimaláricos/análise , Antimaláricos/química , Eletroforese Capilar/métodos , Humanos , Malária/tratamento farmacológico , Composição de Medicamentos/métodosRESUMO
The filamentous bacteriophage M13KO7 (M13) is the most used in phage display (PD) technology and, like other phages, has been applied in several areas of medicine, agriculture, and in the food industry. One of the advantages is that they can modulate the immune response in the presence of pathogenic microorganisms, such as bacteria and viruses. This study evaluated the use of phage M13 in the chicken embryos model. We inoculated 13-day-old chicken embryos with Salmonella Pullorum (SP) and then evaluated survival for the presence of phage M13 or E. coli ER2738 (ECR) infected with M13. We found that the ECR bacterium inhibits SP multiplication in 0.32 (M13-infected ECR) or 0.44 log UFC/mL (M13-uninfected ECR) and that the ECR-free phage M13 from the PD library can be used in chicken embryo models. This work provides the use of the chicken embryo as a model to study systemic infection and can be employed as an analysis tool for various peptides that M13 can express from PD selection. KEY POINTS: ⢠SP-infected chicken embryo can be a helpful model of systemic infection for different tests. ⢠Phage M13 does not lead to embryonic mortality or cause serious injury to embryos. ⢠Phage M13 from the PD library can be used in chicken embryo model tests.
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Bacteriófago M13 , Escherichia coli , Animais , Embrião de Galinha , Escherichia coli/virologia , Escherichia coli/genética , Bacteriófago M13/genética , Técnicas de Visualização da Superfície Celular/métodos , Salmonella , Galinhas , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/microbiologiaRESUMO
This study evaluated the chemical profile, antimicrobial activity, and the presence of potentially toxic elements in geopropolis extracts produced by Melipona scutellaris in the Recôncavo region of Bahia, Brazil. It was found that the major chemical compounds belong to the class of phenolic compounds, with emphasis on the presence of gallic acid. In this study, no potentially toxic elements were found in the analysed geopropolis. Regarding the antimicrobial potential, gram-positive bacteria were susceptible to the action of geopropolis extract at concentrations of 0.25 to 2.5 mg.mL-1, highlighting its microbiological activity against Streptococcus mitis (ATCC 00456) and Candida albicans (CCMB 251). Thus, this geopropolis extract can be used as a bacteriostatic rather than a bactericide. Our results suggest the potential for the economic and therapeutic use of M. scutellaris geopropolis, adding value to one of the meliponiculture products.
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BACKGROUND: Breastfeeding benefits both the mother and infant and is a topic of attention in public health. After childbirth, untreated medical conditions or lack of support lead many mothers to discontinue breastfeeding. For instance, nipple damage and mastitis affect 80% and 20% of US mothers, respectively. Lactation consultants (LCs) help mothers with breastfeeding, providing in-person, remote, and hybrid lactation support. LCs guide, encourage, and find ways for mothers to have a better experience breastfeeding. Current telehealth services help mothers seek LCs for breastfeeding support, where images help them identify and address many issues. Due to the disproportional ratio of LCs and mothers in need, these professionals are often overloaded and burned out. OBJECTIVE: This study aims to investigate the effectiveness of 5 distinct convolutional neural networks in detecting healthy lactating breasts and 6 breastfeeding-related issues by only using red, green, and blue images. Our goal was to assess the applicability of this algorithm as an auxiliary resource for LCs to identify painful breast conditions quickly, better manage their patients through triage, respond promptly to patient needs, and enhance the overall experience and care for breastfeeding mothers. METHODS: We evaluated the potential for 5 classification models to detect breastfeeding-related conditions using 1078 breast and nipple images gathered from web-based and physical educational resources. We used the convolutional neural networks Resnet50, Visual Geometry Group model with 16 layers (VGG16), InceptionV3, EfficientNetV2, and DenseNet169 to classify the images across 7 classes: healthy, abscess, mastitis, nipple blebs, dermatosis, engorgement, and nipple damage by improper feeding or misuse of breast pumps. We also evaluated the models' ability to distinguish between healthy and unhealthy images. We present an analysis of the classification challenges, identifying image traits that may confound the detection model. RESULTS: The best model achieves an average area under the receiver operating characteristic curve of 0.93 for all conditions after data augmentation for multiclass classification. For binary classification, we achieved, with the best model, an average area under the curve of 0.96 for all conditions after data augmentation. Several factors contributed to the misclassification of images, including similar visual features in the conditions that precede other conditions (such as the mastitis spectrum disorder), partially covered breasts or nipples, and images depicting multiple conditions in the same breast. CONCLUSIONS: This vision-based automated detection technique offers an opportunity to enhance postpartum care for mothers and can potentially help alleviate the workload of LCs by expediting decision-making processes.
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Objective: To characterize cases of Surgical Site Infections (SSI) in patients undergoing hip and knee arthroplasties. Method: A cross-sectional, retrospective, and quantitative study conducted in a public, teaching, and high-complexity hospital in the southern region of Brazil. Data collection took place between 2020 and 2022 from records contained in 91 medical records and post-discharge forms within 90 days after surgery for prosthesis implan-tation. Data were analyzed by descriptive statistics and SSI incidence rate. Results: 49 (53.8%) knee arthroplasty records and 42 (46.2%) hip arthroplasty records were analyzed. Five cases developed infection, all detected at the post-arthroplasty knee outpatient visit, resulting in an SSI incidence rate in arthroplasties of 5.5% (n=5). Infections were characterized as deep incisional (40%; n=2), organ or cavity (40%; n=2), and superficial (20%; n=1), resul-ting in readmission in 80% of cases and a corresponding average hospitalization time of 11 days (SD=4.2). Conclusion: The significant rate of SSI in clean surgeries points to the need to intensify good surgical practices. Outpatient surveillance is emphasized as a strategy for building realistic indicators and providing support for prevention efforts. (AU)
Objetivo: Caracterizar los casos de Infecciones del Sitio Quirúrgico (ISQ) en pacientes sometidos a artroplastia de cadera y rodilla. Método: Investigación transversal, retrospectiva y cuantitativa realizada en un hospital público, docente y de alta complejidad en la región sur de Brasil. La reco-lección de datos se realizó entre 2020 y 2022 en registros contenidos en 91 historias clínicas y formularios posteriores al alta hospitalaria en un período de hasta 90 días después de la cirugía destinada al implante de la prótesis. Los datos fueron analizaron mediante estadística descriptiva y tasa de incidencia de ISQ. Resultados: Se analizaron 49 (53,8%) registros de artroplastia de rodilla y 42 (46,2%) de cadera. Cinco casos evolucionaron con infección, todos detectados en el seguimiento ambulatorio después de la artroplastia de rodilla, lo que resultó en una tasa de incidencia de ISQ en artroplastias del 5,5% (n=5). Las infecciones se caracterizaron como incisionales profundas (40%; n=2), de órgano o cavidad (40%; n=2) y superficiales (20%; n=1); resultando en reingreso en el 80% de los casos y el correspondiente tiempo promedio de hospitalización de 11 días (SD=4,2). Conclusión: La tasa significativa de ISQ en cirugías limpias apunta a la necesidad de intensificar las buenas prácticas quirúrgicas. Se reitera la vigilancia ambulatoria como estrategia para la construcción realista de indicadores y apoyo a la prevención. (AU)
Objetivo: Caracterizar os casos de Infecções de Sítio Cirúrgico (ISC) em pacientes submetidos a artroplastias de quadril e joelho. Método:Pesquisa transversal, retrospectiva e quantitativa realizada em um hospital público, de ensino e de alta complexidade da região sul do Brasil. A coleta de dados ocorreu entre 2020 e 2022 em registros contidos em 91 prontuários e fichas pós alta hospitalar no período de até 90 dias após a cirurgia destinada ao implante da prótese. Os dados foram analisados por estatística descritiva e taxa de incidência de ISC. Resultados: Foram analisados 49 (53,8%) regis-tros de artroplastia de joelho e 42 (46,2%) de quadril. Cinco casos evoluíram com infecção, todos detectados no retorno ambulatorial pós artroplastia de joelho, resultando em taxa de incidência de ISC em artroplastias de 5,5% (n=5). As infecções foram caracterizadas como incisional profunda (40%; n=2), de órgão ou cavidade (40%; n=2) e superficial (20%; n=1); decorrendo em reinternação em 80% dos casos e correspondente tempo médio de hospitaliza-ção de 11 dias (DP=4,2). Conclusão: O expressivo índice de ISC em cirurgias limpas direciona para a necessidade de intensificar boas práticas cirúrgicas. Reitera-se a vigilância ambulatorial como estratégia para a construção realística de indicadores e subsídio para a prevenção. (AU)
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Humanos , Infecção da Ferida Cirúrgica , Artroplastia de Quadril , Artroplastia do Joelho , Ortopedia , Artroplastia de Substituição , Segurança do Paciente , Monitoramento EpidemiológicoRESUMO
This review covers the know-how of the Grupo de Química Analítica e Quimiometria regarding the analysis of fatty acids by capillary electrophoresis acquired over its 20 years of existence. Therefore, the fundamentals, advantages, and applications of this technique for analyzing different fatty acids in samples such as food, oils, cosmetics, and biological matrices are presented and discussed. Capillary electrophoresis is, thus, shown as an interesting and valuable separation technique for the target analysis of these analytes as an alternative to the gas chromatography coupled to flame ionization detection, as it offers advantages over the latter such as low analysis times, low sample and reagent consumption, the use of a nondedicated column, and simpler sample preparation. In addition, the methods shown in this literature review can be useful for quality control, adulteration, and health-related research by regulatory agencies.
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Eletroforese Capilar , Ácidos Graxos , Ácidos Graxos/análise , Eletroforese Capilar/métodos , Cromatografia Gasosa/métodos , Óleos , Contaminação de MedicamentosRESUMO
It is reported the synthesis, characterization by elemental analysis, thermogravimetry; electronic absorption, infrared, excitation, and emission spectroscopies of the [Eu(12C4)(phen)2(X)n]X2 complexes, where 12C4 = 12-crown-4, phen = 1,10-phenanthroline, and X = F-, Cl-, Br-, SCN-, ClO4-, and NO3-. It is verified that the polarizability of the anion X- exerts remarkable effects on the emission process. As a general trend, lower wavenumbers for the 7F0â5L6, 7F0â5D2 and 7F0â5D1 transitions are associated with the anions with higher volumes and, consequently, higher polarizability. The molecular modeling results performed with quantum methods (RHF and DFT) suggest some relationships between the calculated structures, electronic, and luminescence properties with the presence of the LMCT (ligand-to-metal charge transfer) states, which explains the differences in the emission spectra of these complexes due to the coordinated anion.
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Investigation of the endophytic fungi Nigrospora sphaerica, Nigrospora oryzae, and Pseudofusicoccum stromaticum MeOH fractions isolated from the leaves of Vochysia divergens, a medicinal species from the Brazilian Pantanal, led to the identification of five compounds, namely a new compound (1E,8Z)-10,11-dihydroxy-5,5,8-trimethyl-4-oxocycloundeca-1,8-diene-1-carbaldehyde (1) and four known compounds: 5-methylmellein (2), sclerone (3), daldinone A (4), and lasiodiplodin (5). All compounds were identified using spectroscopic methods, and 1 was corroborated with mass spectrometry, while the known compounds were compared with data in the literature. The relative configuration of compound 1 was determined based on theoretical conformational studies as well as the J experimental values between the hydroxymethyne hydrogens. The antimicrobial activity of the compounds was evaluated. Promising results were obtained for compounds 2, 4, and 5 since they inhibited the bacterium Pseudomonas aeruginosa, an opportunistic pathogen, suggesting the potential of these microorganisms as a source of new antibacterial agents.
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Anti-Infecciosos , Anti-Infecciosos/química , Fungos/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Folhas de Planta/microbiologia , Brasil , Endófitos/metabolismoRESUMO
Dementia is the most prevalent neurodegenerative disorder, characterized by progressive loss of memory and cognitive function. Inflammation is a major aspect in the progression of brain disorders, and inflammatory events have been associated with accelerated deterioration of cognitive function. In the present work, we investigated the impact of low-grade repeated inflammation stimuli induced by lipopolysaccharide (LPS) in hippocampal function and spatial memory. Adult male Wistar rats received a weekly injection of LPS (500 ug/kg) for sixteen weeks, eliciting systemic inflammation. Animals submitted to LPS presented impaired spatial memory and neuroinflammation. While neuronal synaptic markers such as synaptophysin and PSD-95 were unaltered, critical aspects of astrocyte homeostatic functions, such as glutamate uptake and glutathione content, were reduced. Also, glucose uptake and astrocyte lactate transporters were altered, suggesting a disturbance in the astrocyte-neuron coupling. Our present work demonstrates that long-term repeated systemic inflammation can lead to memory impairment and hippocampal metabolic disorders, especially regarding astrocyte function.
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Astrócitos , Lipopolissacarídeos , Ratos , Animais , Masculino , Lipopolissacarídeos/toxicidade , Ratos Wistar , Transtornos da Memória/metabolismo , Inflamação/induzido quimicamente , Homeostase , HipocampoRESUMO
Nonalcoholic fatty liver disease (NAFLD), which is linked to western diet (WD) intake, affects 30% of the world's population and involves the crosstalk of liver steatosis, hypertrophy/inflammation of adipose tissue and deregulation of gut microbiome. Glyphosate and 2,4-D are some of the most applied herbicides worldwide, and their roles in NAFLD have not been investigated. Thus, the present study evaluated whether glyphosate and 2,4-D, in single or mixed exposure, alter WD-induced NAFLD in a mouse model. Male C57Bl/6 mice (n = 10/group) received a fat (30% lard, 0.02% cholesterol), and sucrose-rich diet (20%) and high sugar solution (23.1 and 18.9 g/L of fructose and glucose) for 6 months. Simultaneously, animals received glyphosate (0.05 or 5 mg/kg/day), 2,4-D (0.02 or 2 mg/kg/day), or their combination (0.05 +0.02 or 5 +2 mg/kg/day) by intragastrical administration (5 ×/week). Doses were based on the Acceptable Daily Intake (ADIs) or No Observed Adverse Effect Level (NOAEL) levels. Herbicide exposures featured differential responses. WD-induced obesity, hypercholesterolemia, and hyperglycemia remained unaltered. Compared to the group receiving only WD, only the concomitant exposure to WD and 2,4-D (2 mg) enhanced the percentage of mice with moderate/severe hepatic inflammation, CD68 macrophage infiltration, and malondialdehyde levels in the liver. In line, this herbicide modulated immune response- (including Cd4, C8b, Cd28, Cxcr3, Cxcr6) and oxidative stress-related (such as Gsta1, Gsta2, Gsta4, Gstm1, Gstm2, Gstm3, Gstm4, Nqo1, Gpx2) genes in the hepatic transcriptome analysis. This exposure also enriched pro-inflammatory Deferribacteres phylum in fecal microbiome. In general, the herbicide mixtures did not feature the same effects attributed to 2,4-D isolated exposure. Our findings indicate that 2,4-D, at a dose within the toxicological limits, was able to induce disturbances in mainly at the liver and gut axes involved in NAFLD development in male mice.
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Herbicidas , Hepatopatia Gordurosa não Alcoólica , Masculino , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Fígado , Inflamação , Tecido Adiposo , Dieta Ocidental/efeitos adversos , Herbicidas/toxicidade , Ácido 2,4-Diclorofenoxiacético/toxicidade , Camundongos Endogâmicos C57BL , GlifosatoRESUMO
Hydrogels made with depolymerized guar gum, oxidized with theoretical oxidation degrees of 20, 35 and 50â¯%, were obtained via Schiff's base reaction with N-succinyl chitosan. The materials obtained were subjected to characterization by FT-IR, rheology, swelling, degradation, and morphology. Additionally, their gelation time categorized all three hydrogels as injectable. The materials' swelling degrees in Phosphate-Buffered Saline (PBS) were in the range of 26-35â¯g of fluid/g gel and their pore size distribution was heterogeneous, with pores varying from 67 to 93⯵m. All hydrogels degraded in PBS solution, but maintained around 40â¯% of their initial mass after 28â¯days, which was more than enough time for wound healing. The biomaterials were also flexible, self-repairing, adhesive and cytocompatible and presented intrinsic actions, regardless of the presence of additives or antibiotics, against gram-positive (Staphylococcus aureus, Staphylococcus epidermidis) and gram-negative bacteria (Escherichia coli). However, the most pronounced bactericidal effect was against resistant Staphylococcus aureus - MRSA. In vivo assays, performed with 50â¯% oxidized gum gel, demonstrated that this material exerted anti-inflammatory effects, accelerating the healing process and restoring tissues by approximately 99â¯% within 14â¯days. In conclusion, these hydrogels have unique characteristics, making them excellent candidates for wound-healing dressings.
Assuntos
Quitosana , Staphylococcus aureus Resistente à Meticilina , Hidrogéis/farmacologia , Quitosana/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Bandagens , Bactérias , Antibacterianos/farmacologia , Staphylococcus aureusRESUMO
The development of chronic kidney disease has been associated with comorbidities resulting from the consumption of Westernized dietary (WD) patterns, including obesity and other metabolic dysfunctions. Kidneys also have a crucial role in the metabolism and excretion of xenobiotics, including herbicides. There is limited knowledge regarding the simultaneous exposure to WD and glyphosate (glypho) and 2,4-D, the most used herbicides globally. Thus, this study examined whether exposure to glypho and/or 2,4-D, either individually or in mixed, could impact the early effects of WD intake on kidney histology and gene expression in a rodent model. Male C57BL6J mice were fed a WD containing 20% lard, 0.2% cholesterol, 20% sucrose, and high sugar solution with 23.1 and 18.9 g/L of D-fructose and D-glucose for six months. During this period, the mice also received glypho (0.05 or 5 mg/kg/day), 2,4-D (0.02 or 2 mg/kg/day), or a mixture of both (0.05 +0.02, 5 +2 mg/kg/day) via intragastric administration five times per week. The doses were within or below the established regulatory limits. While single or mixed exposures did not alter WD-induced obesity, tubular lipid vacuolation, or increased serum creatinine levels; the exposure to higher doses of the mixture (5 +2) reduced the mesangial matrix area and tubular cell proliferation, while increasing the density of F4/80 macrophages in the renal interstitium. In terms of transcriptomic analysis, the herbicide mixture altered the expression of 415 genes in the kidney, which were found to be associated with immune response processes, particularly those related to phagocyte activity. While discrete, findings indicate that herbicide mixtures, rather than single exposures, might induce minor deleterious effects on the kidneys of obese mice under WD intake.