RESUMO
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease affecting 30% of the world's population and is often associated with metabolic disorders such as metabolic syndrome, type 2 diabetes (T2D), and cardiovascular disease. This review is an update of the Brazilian Diabetes Society (Sociedade Brasileira de Diabetes [SBD]) evidence-based guideline for the management of MASLD in clinical practice. METHODS: The methodology was published previously and was defined by the internal institutional steering committee. The SBD Metabolic Syndrome and Prediabetes Department drafted the manuscript, selecting key clinical questions for a narrative review using MEDLINE via PubMed with the MeSH terms [diabetes] and [fatty liver]. The best available evidence was reviewed, including randomized clinical trials (RCTs), meta-analyses, and high-quality observational studies related to MASLD. RESULTS AND CONCLUSIONS: The SBD Metabolic Syndrome and Prediabetes Department formulated 9 recommendations for the management of MASLD in people with prediabetes or T2D. Screening for the risk of advanced fibrosis associated with MASLD is recommended in all adults with prediabetes or T2D. Lifestyle modification (LSM) focusing on a reduction in body weight of at least 5% is recommended as the first choice for these patients. In situations where LSMs are insufficient to achieve weight loss, the use of anti-obesity medications is recommended for those with a body mass index (BMI) ≥ 27 kg/m2. Pioglitazone and glucagon-like peptide-1 receptor agonists (GLP-1RA) monotherapy are the first-line pharmacological treatments for steatohepatitis in people with T2D, and sodium-glucose cotransporter-2 (SGLT2) inhibitors may be considered in this context. The combination of these agents may be considered in the treatment of steatohepatitis and/or fibrosis, and bariatric surgery should be considered in patients with a BMI ≥ 35 kg/m2, in which the combination of LSM and pharmacotherapy has not been shown to be effective in improving MASLD.
RESUMO
The Cerrado biome is the world's largest and most diversified tropical savanna. Despite its diversity, there remains a paucity of scientific discussion and evidence about the medicinal use of Cerrado plants. One of the greatest challenges is the complexity of secondary metabolites, such as flavonoids, present in those plants and their extraction, purification, and characterization, which involves a wide range of approaches, tools, and techniques. Notwithstanding these difficulties, the search for accurately proven medicinal plants against cancer, a leading cause of death worldwide, has contributed to this growing area of research. This study set out to extract, purify, and characterize 3-O-methylquercetin isolated from the plant Strychnos pseudoquina A.St.-Hil. (Loganiaceae) and to test it for antiproliferative activity and selectivity against different tumor and nontumor human cell lines. A combined-method approach was employed using 1H and 13C nuclear magnetic resonance, thermogravimetric analysis, differential scanning calorimetry, single-crystal X-ray diffraction, Hirshfeld surface analysis, and theoretical calculations to extensively characterize this bioflavonoid. 3-O-methylquercetin melts around 275 °C and crystallizes in a nonplanar conformation with an angle of 18.02° between the pyran ring (C) and the phenyl ring (B), unlike quercetin and luteolin, which are planar. Finally, the in vitro cytotoxicity of 3-O-methylquercetin was compared with data from quercetin, luteolin, and cisplatin, showing that structural differences influenced the antiproliferative activity and the selectivity against different tumor cell lines.
RESUMO
Upon exploration of the chemistry of the combination of ruthenium/arene with anthraquinone alizarin (L), three new complexes with the general formulas [Ru(L)Cl(η6-p-cymene)] (C1), [Ru(L)(η6-p-cymene)(PPh3)]PF6 (C2), and [Ru(L)(η6-p-cymene)(PEt3)]PF6 (C3) were synthesized and characterized using spectroscopic techniques (mass, IR, and 1D and 2D NMR), molar conductivity, elemental analysis, and X-ray diffraction. Complex C1 exhibited fluorescence, such as free alizarin, while in C2 and C3, the emission was probably quenched by monophosphines and the crystallographic data showed that hydrophobic interactions are predominant in intermolecular contacts. The cytotoxicity of the complexes was evaluated in the MDA-MB-231 (triple-negative breast cancer), MCF-7 (breast cancer), and A549 (lung) tumor cell lines and MCF-10A (breast) and MRC-5 (lung) nontumor cell lines. Complexes C1 and C2 were more selective to the breast tumor cell lines, and C2 was the most cytotoxic (IC50 = 6.5 µM for MDA-MB-231). In addition, compound C1 performs a covalent interaction with DNA, while C2 and C3 present only weak interactions; however, internalization studies by flow cytometry and confocal microscopy showed that complex C1 does not accumulate in viable MDA-MB-231 cells and is detected in the cytoplasm only after cell permeabilization. Investigations of the mechanism of action of the complexes indicate that C2 promotes cell cycle arrest in the Sub-G1 phase in MDA-MB-231, inhibits its colony formation, and has a possible antimetastatic action, impeding cell migration in the wound-healing experiment (13% of wound healing in 24 h). The in vivo toxicological experiments with zebrafish indicate that C1 and C3 exhibit the most zebrafish embryo developmental toxicity (inhibition of spontaneous movements and heartbeats), while C2, the most promising anticancer drug in the in vitro preclinical tests, revealed the lowest toxicity in in vivo preclinical screening.
Assuntos
Antineoplásicos , Complexos de Coordenação , Rutênio , Animais , Rutênio/farmacologia , Rutênio/química , Peixe-Zebra , Estrutura Molecular , Complexos de Coordenação/química , Antineoplásicos/química , Linhagem Celular Tumoral , Antraquinonas/farmacologiaRESUMO
BACKGROUND: Breast cancer is one of the most common types among women. Its incidence progressively increases with age, especially after age 50. Platinum compounds are not efficient in the treatment of breast cancer, highlighting the use of other metals for the development of new chemotherapeutic agents. OBJECTIVE: This paper aims to obtain three new ruthenium compounds that incorporate sulfur amino acids in their structures and to investigate their cytotoxic activity in breast tumor cell lines. METHODS: Complexes with general formula [Ru(AA)(dppb)(bipy)] (complexes 1 and 2) or [Ru(AA)(dppb) (bipy)]PF6 (complex 3), where AA = L-cysteinate (1), D-penicillaminate (2), and L-deoxyalliinate (3), dppb = 1,4-bis(diphenylphosphino)butane and 2,2´-bipyridine, were obtained from the cis-[RuCl2(dppb)(bipy)] precursor. The cytotoxicity of the complexes on MDA-MB-231 (triple negative human breast cancer); MCF-7 (double positive human breast cancer) and V79 (hamster lung fibroblast) was performed by the MTT (4,5- dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide) method. The control agent was the cisplatin, which is a commercially available drug for cancer treatment. RESULTS: In complexes (1) and (2), the ligands are coordinated to the metal center by nitrogen and sulfur atoms, while in complex (3), coordination is through the oxygen and nitrogen atoms. These suggestions are based on the infrared and 31P{1H} NMR data. For complexes (1) and (2), their X-ray structures were determined confirming this suggestion. The three complexes are stable in a mixture of DMSO (80%) and biological medium (20%) for at least 48h and presented cytotoxicity against the MDA-MB-231 and MCF-7 tumor cells with reasonable selectivity indexes. CONCLUSION: Our work demonstrated that ruthenium complexes containing sulfur amino acids, bipyridines and bisphosphines showed cytotoxicity against the MDA-MB-231 and MCF-7 cancer cell lines, in vitro, and that they interact weakly with the DNA (Deoxyribonucleic Acid) and the HSA (Human Serum Albumin) biomolecules.
Assuntos
Aminoácidos/farmacologia , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Complexos de Coordenação/farmacologia , Rutênio/farmacologia , Enxofre/farmacologia , Aminoácidos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , DNA/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Rutênio/química , Albumina Sérica Humana/química , Relação Estrutura-Atividade , Enxofre/químicaRESUMO
AIM: To evaluate the performance of FibroMeterVirus3G combined to the first generation tests aspartate aminotransferase-to-platelet ratio index (APRI) or Forns index to assess significant fibrosis in chronic hepatitis C (CHC). METHODS: First generation tests APRI or Forns were initially applied in a derivation population from Rio de Janeiro in Brazil considering cut-offs previously reported in the literature to evaluate significant fibrosis. FibroMeterVirus3G was sequentially applied to unclassified cases from APRI or Forns. Accuracy of non-invasive combination of tests, APRI plus FibroMeterVirus3G and Forns plus FibroMeterVirus3G was evaluated in the Brazilian derivation population. APRI plus FibroMeterVirus3G combination was validated in a population of CHC patients from Angers in France. All patients were submitted to liver biopsy staged according to METAVIR score by experienced hepatopathologists. Significant fibrosis was considered as METAVIR F ≥ 2. The fibrosis stage classification was used as the reference for accuracy evaluation of non-invasive combination of tests. Blood samples for the calculation of serum tests were collected on the same day of biopsy procedure or within a maximum 3 mo interval and stored at -70 °C. RESULTS: Seven hundred and sixty CHC patients were included (222 in the derivation population and 538 in the validation group). In the derivation population, the FibroMeterVirus3G AUROC was similar to APRI AUROC (0.855 vs 0.815, P = 0.06) but higher than Forns AUROC (0.769, P < 0.001). The best FibroMeterVirus3G cut-off to discriminate significant fibrosis was 0.61 (80% diagnostic accuracy; 75% in the validation population, P = 0.134). The sequential combination of APRI or Forns with FibroMeterVirus3G in derivation population presented similar performance compared to FibroMeterVirus3G used alone (79% vs 78% vs 80%, respectively, P = 0.791). Unclassified cases of significant fibrosis after applying APRI and Forns corresponded to 49% and 54%, respectively, of the total sample. However, the combination of APRI or Forns with FibroMeterVirus3G allowed 73% and 77%, respectively, of these unclassified cases to be correctly evaluated. Moreover, this combination resulted in a reduction of FibroMeterVirus3G requirement in approximately 50% of the entire sample. The stepwise combination of APRI and FibroMeterVirus3G applied to the validation population correctly identified 74% of patients with severe fibrosis (F ≥ 3). CONCLUSION: The stepwise combination of APRI or Forns with FibroMeterVirus3G may represent an accurate lower cost alternative when evaluating significant fibrosis, with no need for liver biopsy.
RESUMO
Hepatitis C virus (HCV) chronically infects 0.5-3% of the world population. A large group of patients develop cirrhosis and its complications. Since 2011, telaprevir and boceprevir are used, improving the disease evolution. One of the main side effects of these drugs is skin eruption. We report a 53-year-old patient with cirrhosis due to HCV who started the classic treatment associated with telaprevir. In the ninth week, he presented a severe rash that required the interruption of this drug. We emphasize the importance of early recognition and appropriate management of adverse skin reaction.
RESUMO
Emilia coccinea (Sims) G. Don (Asteraceae) is a weed species quite frequently in the Brazilian farming, is also considered horticultural plant for having medicinal properties. The study of their germination can contribute to their management in areas where it is unwanted, also can help their production in medicinal gardens. The objective this work was to study, in three trials, the germination of E. coccinea as a function of temperature, light, storage and sowing depth. In the first test, the fruits-seed had been submitted at different temperatures (10, 20, 30, 40 and 20-30C) and light qualities (white, red, far red and dark), in the second, the newly harvested and stored fruits-seed (3, 6, 9 and 12 months) had been submitted at same light qualities listed above and incubated in camera at 30C. For the third test the fruits-seed had been seeded in sand+soil under different depths (0, 1, 2, 3 and 4 cm). The experimental design in all trials was completely randomized with four replications of 50 seeds, where evaluated the percentage and speed of germination and seedling emergence. The germination of E. coccinea is maximized under the temperature of 30 or 20-30C, under white light. With nine months of storage the fruits-seeds lost completely the far red and dark light sensibility. The seedling emergence is greater when the seeds are at the substrate surface.
Emilia coccinea (Sims) G. Don (Asteraceae) é uma espécie daninha bastante frequente nas lavouras brasileiras, sendo também considerada hortícula por apresentar propriedades medicinais. O estudo da sua germinação pode contribuir para o seu manejo em áreas onde é indesejada, ao tempo que pode auxiliar a sua produção em hortas medicinais. O objetivo deste trabalho foi estudar, em três ensaios, o comportamento germinativo de sementes de E. coccinea em função da luz, temperatura, armazenamento e profundidade de semeadura. No primeiro ensaio os aquênios (frutos-semente) foram submetidos a diferentes temperaturas (10, 20, 30, 40 e 20-30ºC) e qualidades de luz (branca, vermelha, vermelhodistante e escuro), no segundo, os aquênios recém-colhidos e armazenados por 3, 6, 9 e 12 meses foram submetidos às mesmas qualidades de luz citadas anteriormente e incubados à 30ºC, para o terceiro ensaio os aquênios foram semeados em substrato areia+solo em diferentes profundidades (0, 1, 2, 3 e 4 cm). O delineamento experimental em todos os ensaios foi inteiramente casualizado com quatro repetições de 50 sementes, nos quais avaliou-se a porcentagem e velocidade de germinação e emergência de plântulas. A germinação de E. coccinea é maximizada sob a temperatura constante de 30ºC ou alternada de 20-30ºC, sob a luz branca. Aos nove meses de armazenamento, os aquênios perdem completamente a fotodormência.
RESUMO
Emilia coccinea (Sims) G. Don (Asteraceae) is a weed species quite frequently in the Brazilian farming, is also considered horticultural plant for having medicinal properties. The study of their germination can contribute to their management in areas where it is unwanted, also can help their production in medicinal gardens. The objective this work was to study, in three trials, the germination of E. coccinea as a function of temperature, light, storage and sowing depth. In the first test, the fruits-seed had been submitted at different temperatures (10, 20, 30, 40 and 20-30C) and light qualities (white, red, far red and dark), in the second, the newly harvested and stored fruits-seed (3, 6, 9 and 12 months) had been submitted at same light qualities listed above and incubated in camera at 30C. For the third test the fruits-seed had been seeded in sand+soil under different depths (0, 1, 2, 3 and 4 cm). The experimental design in all trials was completely randomized with four replications of 50 seeds, where evaluated the percentage and speed of germination and seedling emergence. The germination of E. coccinea is maximized under the temperature of 30 or 20-30C, under white light. With nine months of storage the fruits-seeds lost completely the far red and dark light sensibility. The seedling emergence is greater when the seeds are at the substrate surface.
Emilia coccinea (Sims) G. Don (Asteraceae) é uma espécie daninha bastante frequente nas lavouras brasileiras, sendo também considerada hortícula por apresentar propriedades medicinais. O estudo da sua germinação pode contribuir para o seu manejo em áreas onde é indesejada, ao tempo que pode auxiliar a sua produção em hortas medicinais. O objetivo deste trabalho foi estudar, em três ensaios, o comportamento germinativo de sementes de E. coccinea em função da luz, temperatura, armazenamento e profundidade de semeadura. No primeiro ensaio os aquênios (frutos-semente) foram submetidos a diferentes temperaturas (10, 20, 30, 40 e 20-30ºC) e qualidades de luz (branca, vermelha, vermelhodistante e escuro), no segundo, os aquênios recém-colhidos e armazenados por 3, 6, 9 e 12 meses foram submetidos às mesmas qualidades de luz citadas anteriormente e incubados à 30ºC, para o terceiro ensaio os aquênios foram semeados em substrato areia+solo em diferentes profundidades (0, 1, 2, 3 e 4 cm). O delineamento experimental em todos os ensaios foi inteiramente casualizado com quatro repetições de 50 sementes, nos quais avaliou-se a porcentagem e velocidade de germinação e emergência de plântulas. A germinação de E. coccinea é maximizada sob a temperatura constante de 30ºC ou alternada de 20-30ºC, sob a luz branca. Aos nove meses de armazenamento, os aquênios perdem completamente a fotodormência.