RESUMO
The aim to access linked tetravanadate [V4O12]4- anion with mixed copper(II) complexes, using α-amino acids and phenanthroline-derived ligands, resulted in the formation of four copper(II) complexes [Cu(dmb)(Gly)(OH2)]2[Cu(dmb)(Gly)]2[V4O12]·9H2O (1) [Cu(dmb)(Lys)]2[V4O12]·8H2O (2), [Cu(dmp)2][V4O12]·C2H5OH·11H2O (3), and [Cu(dmp)(Gly)Cl]·2H2O (4), where dmb = 4,4'-dimethioxy-2,2'-bipyridine; Gly = glycine; Lys = lysine; and dmp = 2,9-dimethyl-1,10-phenanthroline. The [V4O12]4- anion is functionalized with mixed copper(II) units in 1 and 2; while in 3, it acts as a counterion of two [Cu(dmp)]2+ units. Compound 4 crystallized as a unit that did not incorporate the vanadium cluster. All compounds present magnetic couplings arising from Cuâ¯O/Cuâ¯Cu bridges. Stability studies of water-soluble 3 and 4 by UV-Vis spectroscopy in cell culture medium confirmed the robustness of 3, while 4 appears to undergo ligand scrambling over time, resulting partially in the stable species [Cu(dmp)2]+ that was also identified by electrospray ionization mass spectrometry at m/z = 479. The in vitro cytotoxicity activity of 3 and 4 was determined in six cancer cell lines; the healthy cell line COS-7 was also included for comparative purposes. MCF-7 cells were more sensitive to compound 3 with an IC50 value of 12 ± 1.2 nmol. The tested compounds did not show lipid peroxidation in the TBARS assay, ruling out a mechanism of action via reactive oxygen species formation. Both compounds inhibited cell migration at 5 µM in wound-healing assays using MCF-7, PC-3, and SKLU-1 cell lines, opening a new window to study the anti-metastatic effect of mixed vanadium-copper(II) systems.
Assuntos
Antineoplásicos , Complexos de Coordenação , Humanos , Cobre/farmacologia , Cobre/química , Antineoplásicos/química , Fenantrolinas/química , Vanádio/farmacologia , DNA/química , Células MCF-7 , Ânions , Fenômenos Magnéticos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , LigantesRESUMO
Obesity is an increasing global public health problem. A strategy to treat obesity is the use of functional foods. Edible and medicinal mushrooms contain diverse bioactive compounds showing important antihyperlipidemic, antioxidant, and prebiotic properties. We analysed the effects of adding (10%) of Pleurotus ostreatus (Po, basidiomata), Ganoderma lucidum (Gl, basidiomata), or Ustilago maydis (Um, galls), milled, to a high fat plus saccharose diet (HFD + S) for 6 months in a model of obesity with Wistar rats. We assessed weight gain, body composition, lipid parameters, endoplasmic reticulum stress (proteins and inflammatory markers: BiP, XBP-1, JNK, p-JNK, TNF-α), and adiponectin in subcutaneous adipose tissue (SAT). The consumption of edible and medicinal mushrooms decreased weight gain (-17.2-30.1%) and fat mass (-23.7-43.1%), maintained fat-free mass, reduced levels of serum biochemical parameters (TC: -40.1-44.1%, TG: -37.7-51.6%, LDL-C: -64.5-71.1%), and prevented adipocyte hypertrophy (-30.9-36.9%) and collagen deposition (-70.9-73.7%) in SAT. Compared with the HFD + S group, mushroom consumption by Wistar rats significantly reduced the expression of proteins associated with endoplasmic reticulum stress and inflammation (BiP: -72.2-88.2%; XBP-1: -71.5-81.8%; JNK: -71.2-90.0%; p-JNK: -37.3-81.0%; TNF-α: -80.7-91.5%), whereas significantly increased adiponectin protein expression (246.4-654.2%) in SAT. These effects outperformed those obtained through the commercial lipid-lowering drug atorvastatin, contributing synergistically to prevent further obesity-related dysfunctions, such as insulin resistance derived from inflammation and ER stress in adipose tissue. Bioactive compounds from edible, functional and medicinal mushrooms represent new emerging therapies for obesity treatments using natural products.
Assuntos
Agaricales , Pleurotus , Reishi , Ratos , Animais , Ratos Wistar , Pleurotus/química , Adiponectina , Fator de Necrose Tumoral alfa/farmacologia , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Inflamação/tratamento farmacológico , Aumento de Peso , Estresse do Retículo Endoplasmático , Lipídeos/farmacologiaRESUMO
Breast cancer (BC) can be classified into various histological subtypes, each associated with different prognoses and treatment options, including surgery, radiation, chemotherapy, and endocrine therapy. Despite advances in this area, many patients still face treatment failure, the risk of metastasis, and disease recurrence, which can ultimately lead to death. Mammary tumors, like other solid tumors, contain a population of small cells known as cancer stem-like cells (CSCs) that have high tumorigenic potential and are involved in cancer initiation, progression, metastasis, tumor recurrence, and resistance to therapy. Therefore, designing therapies specifically targeting at CSCs could help to control the growth of this cell population, leading to increased survival rates for BC patients. In this review, we discuss the characteristics of CSCs, their surface biomarkers, and the active signaling pathways associated with the acquisition of stemness in BC. We also cover preclinical and clinical studies that focus on evaluating new therapy systems targeted at CSCs in BC through various combinations of treatments, targeted delivery systems, and potential new drugs that inhibit the properties that allow these cells to survive and proliferate.
Assuntos
Neoplasias da Mama , Neoplasias Mamárias Animais , Animais , Humanos , Feminino , Neoplasias da Mama/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Mamárias Animais/metabolismo , Transdução de Sinais , Células-Tronco Neoplásicas/patologiaRESUMO
Two novel Iron (II) complexes featuring tetrapodal bis(benzimidazole)amino thio- and selenoether ligands (LS and LSe) were synthesized, characterized, and tested as electrocatalysts for the hydrogen evolution reaction. The bromide complexes [Fe(LS,LSe)Br2] (1-2) are highly insoluble, but their DMSO solvates were characterized by single crystal X-ray diffraction, revealing an octahedral coordination environment that does not feature coordination of the chalcogen atoms. The corresponding triflate derivatives [Fe(LS,LSe)(MeCN)3]OTf2 (1c-2c) were employed for electrocatalytic proton reduction, with 1c exhibiting higher activity, thus suggesting that the thioether may participate as a more competent pendant ligand for proton transfer.
Assuntos
Ferro , Prótons , Ferro/química , Hidrogênio , Compostos Ferrosos/química , Cristalografia por Raios X , LigantesRESUMO
PURPOSE: Worldwide, gastric cancer (GC) is the 5th cancer with the highest incidence and the 4th in mortality. To reduce it, one strategy is to diagnose preneoplastic lesions (PNL): atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia (DYS); to form risk groups on which to focus surveillance efforts as are first-degree relatives (FDR). The aim of this study was to determine prevalence of gastric PNL in FDR of patients with GC, and to study association with sex, age, and Helicobacter pylorii (Hp) infection. METHODS: Cross-sectional study. One hundred and ten FDR, aged between 50 and 65 years, 54.5 female, obtained through convenience sampling, were studied. Biodemographic data survey and upper gastrointestinal endoscopy with histological study were applied according to Sidney protocol, and focal lesions found. Diagnosis of these lesions and condition of mucosa was carried out by applying OLGA and OLGIM systems. Descriptive statistics, estimation of prevalence, odds ratio (OR), and 95% confidence intervals (95CI) were calculated. RESULTS: Median age of study group was 56.5 years. Prevalence of PNL, AG, IM, and DYS were 86.4%, 82.7%, 54.5%, and 12.7% respectively. Advanced stages of OLGA and OLGIM were verified in 18.0% and 16.3% respectively. No association with sex, age, and Hp infection were found ([OR 3.10; 95CI 1.0; 9.64]; [OR 0.74; 95CI 0.26; 2.14]; [OR 0.58; 95CI 0.12; 2.77]) respectively. CONCLUSION: FDR of patients with GC have a high prevalence of PNL, which makes them a risk group in which endoscopic surveillance should be applied.
Assuntos
Gastrite Atrófica , Infecções por Helicobacter , Helicobacter pylori , Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/diagnóstico , Estudos Transversais , Prevalência , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/patologia , Gastrite Atrófica/epidemiologia , Gastrite Atrófica/complicações , Gastrite Atrófica/diagnóstico , Fatores de Risco , Hiperplasia/complicações , Metaplasia/epidemiologia , Metaplasia/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/diagnóstico , Mucosa Gástrica/patologiaRESUMO
Ni4O4 cubanes [(µ3-L1O)NiCl(MeOH)]4 (1) and [(µ3-L2O)NiCl(H2O)]4 (2) (L1OH = 1-H-2-benzimidazolylmethanol, L2OH = 1-methyl-2-benzimidazolylmethanol) self-assemble from commercially available 1-H- and 1-methyl-2-benzimidazolylmethanol and NiCl2·6H2O in high yields under mild conditions. Both complexes were characterised spectroscopically and by X-ray crystallography. The cubanes oxidise water electrocatalytically to dioxygen at neutral pH in aqueous potassium phosphate buffer solutions.
RESUMO
Introducción: Mantener una calidad de vida laboral trae como beneficio una mayor productividad. Objetivo: Conocer si la calidad de vida laboral es predictor significativo del nivel de desempeño laboral autopercibido por los médicos que laboran en el Instituto Mexicano del Seguro Social de Bienestar, en el estado de Chiapas, México. Material y métodos. El estudio tuvo un enfoque cuantitativo, transversal y predictivo. La población estuvo formada por 445 médicos. El tipo de muestreo fue no probabilístico por conveniencia, ya que se seleccionó a los médicos que laboran en el Instituto Mexicano del Seguro Social (IMMSS) Bienestar, en el estado de Chiapas. La muestra fue de 169 médicos que representan el 37.97% de la población. Se realizó un análisis de regresión lineal simple por el método de pasos sucesivos. Resultados. Se encontró que la variable nivel de calidad de vida laboral explicó el 64.9% de la varianza de la variable dependiente nivel de desempeño laboral. De igual manera, se determinó que existe una influencia lineal positiva y significativa entre las variables. Se encontró que la variable calidad de vida laboral es un predictor significativo del desempeño laboral de manera muy importante (ß = .806). Conclusiones. Se encontró que la calidad de vida laboral influye en el desempeño laboral de los médicos que laboran en el Instituto Mexicano del Seguro Social de Bienestar, en el estado de Chiapas de manera muy importante. En la medida que los médicos encuestados mejoren su calidad de vida laboral influirá en su desempeño laboral.
Introduction: Maintaining a quality of working life brings as a benefit a greater productivity. Objective: To know if the quality of work life is a significant predictor of the level of self-perceived work performance by the doctors who work at the Mexican Institute of Social Security of Well-being, in the state of Chiapas. Material and methods: The study had a quantitative, cross-sectional and predictive approach. The population consisted of 445 doctors. The type of sampling was non-probabilistic for convenience, since the doctors who work in the Mexican Institute of Social Security (IMMSS) Bienestar, in the state of Chiapas, were selected. The sample consisted of 169 physicians who represent 37.97% of the population. A simple linear regression analysis was carried out by the method of successive steps. Results: It was found that the variable level of working life described 64.9% of the variance of the dependent variable level of job performance. Similarly, it was determined that there is a positive and significant linear influence between the variables. The quality of work life variable was found to be a significant predictor of work performance in a very important way (ß = .806). Conclusions: It was found that the quality of work life influences the work performance of the doctors who work in the Mexican Institute of Social Security of Well-being, in the state of Chiapas in a very important way. To the extent that the surveyed doctors improve their quality of work life, it will influence their work performance.
RESUMO
Prevention of hyperlipidemia and associated diseases is a health priority. Natural products, such as the medicinal mushroom Ganoderma lucidum (Gl), have demonstrated hypocholesterolemic, prebiotic and antidiabetic properties. However, the underlying transcriptomic mechanisms by which Gl exerts bioactivities are not completely understood. We report a comprehensive hepatic and renal transcriptome profiling of C57BL/6 mice under the consumption of a high-cholesterol diet and two standardized Gl extracts obtained from basidiocarps cultivated on conventional substrate (Gl-1) or substrate containing acetylsalicylic acid (ASA; Gl-2). We showed that Gl extracts modulate relevant metabolic pathways involving the restriction of lipid biosynthesis and the enrichment of lipid degradation and secretion. The Gl-2 extract exerts a major modulation over gene expression programs showing the highest similarity with simvastatin druggable-target-genes and these are enriched more in processes related to human obesity alterations in the liver. We further show a subset of Gl-modulated genes correlated with Lactobacillus enrichment and the reduction of circulating cholesterol-derived fats. Moreover, Gl extracts induce a significant decrease of macrophage lipid storage, which occurs concomitantly with the down-modulation of Fasn and Elovl6. Collectively, this evidence suggests a new link between Gl hypocholesterolemic and prebiotic activity, revealing thereby that standardized Mexican Gl extracts are a novel transcriptome modulator to prevent metabolic disorders associated with hypercholesterolemia.
Assuntos
Colesterol na Dieta/administração & dosagem , Microbioma Gastrointestinal/fisiologia , Lipogênese/genética , Reishi/química , Transcriptoma/fisiologia , Animais , Anticolesterolemiantes/administração & dosagem , Rim/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Lipogênese/efeitos dos fármacos , Fígado/metabolismo , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Camundongos , Camundongos Endogâmicos C57BL , Prebióticos/administração & dosagem , Células RAW 264.7 , Transcriptoma/efeitos dos fármacosRESUMO
Liver fibrosis is a complex process associated to most types of chronic liver disease, which is characterized by a disturbance of hepatic tissue architecture and the excessive accumulation of extracellular matrix. Resolvin E1 (RvE1) is a representative member of the eicosapentaenoic omega-3 lipid derivatives, and is a drug candidate of the growing family of endogenous resolvins. Considering the aforementioned, the main objective of this study was to analyze the hepatoprotective effect of RvE1 in a rat model of liver fibrosis. Male Sprague-Dawley rats received diethylnitrosamine (DEN, 70 mg/mg body weight intraperitoneally (i.p)) as an inductor of liver fibrosis once weekly and RvE1(100 ng/body weight i.p) twice weekly for four weeks. RvE1 suppressed the alterations induced by DEN, normalizing the levels of alanine aminotransferase (ALT), albumin, and lactate dehydrogenase (LDH), and ameliorated DEN injury by decreasing the architecture distortion, inflammatory infiltration, necrotic areas, and microsteatosis. RvE1 also limited DEN-induced proliferation through a decrease in Ki67-positive cells and cyclin D1 protein expression, which is related to an increase of the levels of cleaved caspase-3. Interestingly, we found that RvE1 promotes higher nuclear translocation of nuclear factor κB (NF-κB)p65 than DEN. RvE1 also increased the levels of nuclear the nuclear factor erythroid 2-related factor 2 (Nrf2), but with no antioxidant effect, measured as an increase in glutathione disulfide (GSSG) and a decrease in the ratio of glutathione (GSH)/GSSG. Taken together, these results suggest that RvE1 modulates the fibrogenesis, steatosis, and cell proliferation in a model of DEN induced fibrosis.