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In 1992, a transcendental report suggested that the receptor of advanced glycation end-products (RAGE) functions as a cell surface receptor for a wide and diverse group of compounds, commonly referred to as advanced glycation end-products (AGEs), resulting from the non-enzymatic glycation of lipids and proteins in response to hyperglycemia. The interaction of these compounds with RAGE represents an essential element in triggering the cellular response to proteins or lipids that become glycated. Although initially demonstrated for diabetes complications, a growing body of evidence clearly supports RAGE's role in human diseases. Moreover, the recognizing capacities of this receptor have been extended to a plethora of structurally diverse ligands. As a result, it has been acknowledged as a pattern recognition receptor (PRR) and functionally categorized as the RAGE axis. The ligation to RAGE leads the initiation of a complex signaling cascade and thus triggering crucial cellular events in the pathophysiology of many human diseases. In the present review, we intend to summarize basic features of the RAGE axis biology as well as its contribution to some relevant human diseases such as metabolic diseases, neurodegenerative, cardiovascular, autoimmune, and chronic airways diseases, and cancer as a result of exposure to AGEs, as well as many other ligands.
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Produtos Finais de Glicação Avançada , Inflamação , Receptor para Produtos Finais de Glicação Avançada , Humanos , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Inflamação/metabolismo , Transdução de Sinais , Neoplasias/metabolismo , Animais , Doenças Cardiovasculares/metabolismo , Doenças Neurodegenerativas/metabolismo , Doenças Metabólicas/metabolismo , Doenças Autoimunes/metabolismoRESUMO
Type 2 diabetes mellitus (T2DM) is recognized as a serious public health concern with a considerable impact on human life, long-term health expenditures, and substantial health losses. In this context, the use of dietary polyphenols to prevent and manage T2DM is widely documented. These dietary compounds exert their beneficial effects through several actions, including the protection of pancreatic islet ß-cell, the antioxidant capacities of these molecules, their effects on insulin secretion and actions, the regulation of intestinal microbiota, and their contribution to ameliorate diabetic complications, particularly those of vascular origin. In the present review, we intend to highlight these multifaceted actions and the molecular mechanisms by which these plant-derived secondary metabolites exert their beneficial effects on type 2 diabetes patients.
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INTRODUCTION: Breast cancer is the leading cause of cancer-related deaths among women worldwide. In Costa Rica, it ranks first in incidence and fourth in terms of mortality. However, there is a lack of comprehensive information on treatment patterns and outcomes for breast cancer patients in Costa Rica. METHODS: This study utilized data from the National Tumor Registry, which was merged with the Costa Rica Social Security Fund (CCSS) to ensure comprehensive access to clinical information. The study is prospective and focused on patients diagnosed with breast cancer between January 2008 and December 2012. This combined dataset allowed for a more comprehensive analysis of patient characteristics, treatment patterns, and outcomes related to breast cancer in Costa Rica. RESULTS: Among the 4775 patients diagnosed during this period, 3160 met the inclusion criteria for our study. The average age at diagnosis was 59.1 years, with 32.5% of patients being over the age of 65. Most of the patients (55.4%) identified themselves as homemakers, while 46.5% underwent core needle biopsy for diagnosis. Approximately 60% of women were diagnosed with early-stage disease (IA, IIA, and IIB), while 1.7% had metastatic disease, mainly affecting the bone. The mean interval between diagnosis and surgery was 72 days. Most patients (88.7%) received surgery as their initial treatment, and over half (54.4%) received some form of adjuvant therapy. Additionally, 85.6% of patients completed their prescribed treatment. CONCLUSION: This study provides a comprehensive and detailed description of the characteristics and treatment patterns among breast cancer patients in Costa Rica. The findings contribute to our understanding of the disease in this population and can serve as a foundation for further research and improvement in breast cancer management and care.
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Neoplasias da Mama , Segunda Neoplasia Primária , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Estudos Transversais , Costa Rica/epidemiologia , Estudos ProspectivosRESUMO
Compelling shreds of evidence derived from both clinical and experimental research have demonstrated the crucial contribution of receptor for advanced glycation end products (RAGE) axis activation in the development of neoplasms, including gastric cancer (GC). This new actor in tumor biology plays an important role in the onset of a crucial and long-lasting inflammatory milieu, not only by supporting phenotypic changes favoring growth and dissemination of tumor cells, but also by functioning as a pattern-recognition receptor in the inflammatory response to Helicobacter pylori infection. In the present review, we aim to highlight how the overexpression and activation of the RAGE axis contributes to the proliferation and survival of GC cells as and their acquisition of more invasive phenotypes that promote dissemination and metastasis. Finally, the contribution of some single nucleotide polymorphisms in the RAGE gene as susceptibility or poor prognosis factors is also discussed.
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Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Receptor para Produtos Finais de Glicação Avançada/genética , Neoplasias Gástricas/genética , Infecções por Helicobacter/complicações , Receptores de Reconhecimento de Padrão , Produtos Finais de Glicação AvançadaRESUMO
Compelling pieces of epidemiological, clinical, and experimental research have demonstrated that Diabetes mellitus (DM) is a major risk factor associated with increased cancer incidence and mortality in many human neoplasms. In the pathophysiology context of DM, many of the main classical actors are relevant elements that can fuel the different steps of the carcinogenesis process. Hyperglycemia, hyperinsulinemia, metabolic inflammation, and dyslipidemia are among the classic contributors to this association. Furthermore, new emerging actors have received particular attention in the last few years, and compelling data support that the microbiome, the epigenetic changes, the reticulum endoplasmic stress, and the increased glycolytic influx also play important roles in promoting the development of many cancer types. The arsenal of glucose-lowering therapeutic agents used for treating diabetes is wide and diverse, and a growing body of data raised during the last two decades has tried to clarify the contribution of therapeutic agents to this association. However, this research area remains controversial, because some anti-diabetic drugs are now considered as either promotors or protecting elements. In the present review, we intend to highlight the compelling epidemiological shreds of evidence that support this association, as well as the mechanistic contributions of many of these potential pathological mechanisms, some controversial points as well as future challenges.
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Diabetes Mellitus Tipo 2 , Hiperglicemia , Neoplasias , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Neoplasias/etiologia , Neoplasias/complicações , Fatores de Risco , Hiperglicemia/complicações , Inflamação/complicaçõesRESUMO
Compelling evidence derived from clinical and experimental research has demonstrated the crucial contribution of chronic inflammation in the development of neoplasms, including gallbladder cancer. In this regard, data derived from clinical and experimental studies have demonstrated that the receptor of advanced glycation end-products (RAGE)/AGEs axis plays an important role in the onset of a crucial and long-lasting inflammatory milieu, thus supporting tumor growth and development. AGEs are formed in biological systems or foods, and food-derived AGEs, also known as dietary AGEs are known to contribute to the systemic pool of AGEs. Once they bind to RAGE, the activation of multiple and crucial signaling pathways are triggered, thus favoring the secretion of several proinflammatory cytokines also involved in the promotion of gallbladder cancer invasion and migration. In the present review, we aimed to highlight the relevance of the association between high dietary AGEs intakes and high risk for gallbladder cancer, and emerging data supporting that dietary intervention to reduce gallbladder cancer risk is a very attractive approach that deserves much more research efforts.
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Neoplasias da Vesícula Biliar , Produtos Finais de Glicação Avançada , Humanos , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Neoplasias da Vesícula Biliar/etiologia , Inflamação , CitocinasRESUMO
The receptor for advanced glycation end-products (RAGE) is a multiligand binding and single-pass transmembrane protein which actively participates in several chronic inflammation-related diseases. RAGE, in addition to AGEs, has a wide repertoire of ligands, including several damage-associated molecular pattern molecules or alarmins such as HMGB1 and members of the S100 family proteins. Over the last years, a large and compelling body of evidence has revealed the active participation of the RAGE axis in tumor biology based on its active involvement in several crucial mechanisms involved in tumor growth, immune evasion, dissemination, as well as by sculpturing of the tumor microenvironment as a tumor-supportive niche. In the present review, we will detail the consequences of the RAGE axis activation to fuel essential mechanisms to guarantee tumor growth and spreading.
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Produtos Finais de Glicação Avançada , Neoplasias , Biologia , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Neoplasias/metabolismo , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Receptores Imunológicos , Proteínas S100 , Microambiente TumoralRESUMO
SUMMARY: The aim of this research was to evaluate the changes obtained with the mentoplasty technique in the increase of the airway imaging. A systemic review was performed using the parameters of the prism matrix, in the PubMed, Science Direct, Redalyc database, covering the years 1984 to 2019 with the use of defined inclusion criteria. The authors independently applied the selected parameter of data extraction, study selection and risk-to-bias assessment. A total of 1,251 articles were obtained among the 3 databases, of which 10 met the inclusion criteria. The variables studied were: type of research, sample size, sex, age, dento-skeletal diagnosis, airway classification, diagnosis of obstructive sleep apnea syndrome (OSAS), type of imaging evaluation, variables evaluated in the image, pre and post-operative values, surgical technique and type of fixation used, other surgical procedures applied, and complications. In the cases of linear evaluation with cephalometric analysis (9 articles) they used PAS (posterior airspace), MP-H (mandibular plane to the hyoid) and SNB (saddle-nasion-point B), and SCSA (section area as the most relevant points, smallest cross section) and VT (total volume) in the volumetric evaluations (2 articles). The average change in posterior airspace achieved by the cited authors is 4.2 mm with standard deviation of 1.4 mm with the use of advancement mentoplasty. The most widely used technique was mentoplasty with a horizontal osteotomy by 5 authors. Based on the research there is a positive relationship between the increase in the airway and the advancement mentoplasty procedure, however, more standardized studies associated with the way of measuring and evaluating the relationship between advancement and the airway are necessary.
RESUMEN: El objetivo de esta investigación fue evaluar los cambios obtenidos con la técnica de mentoplastia en el incremento de la via aérea. Una revisión sistemática fue realizada utilizando parámetros de la matriz prisma, en PubMed, Science Direct, Redalyc database, cubriendo los años 1984 a 2019 con criterios de inclusión definidos. Los autores aplicaron de forma independiente los parámetros de selección y extracción de datos, selección de estudios y riesgos de sesgo. Un total de 1251 artículos fueron obtenidos de las 3 bases de dato, donde 10 artículos cumplieron los criterios de inclusión. Las variables estudiadas fueron: tipo de investigación, tamaño de la muestra, genero, edad, diagnóstico dento esqueletal, clasificación de la vía aérea, diagnostico de síndrome de apnea del sueño (SAOS), tipo de evaluación de la imagen, variables evaluadas en la imagen en pre y postoperatorio, técnica quirúrgica y tipo de fijación utilizada, otros procedimientos quirúrgicos y complicaciones. En el caso de la evaluación linear con cefalometria (9 artículos), usaron PAS (posterior airspace), MP-H (plano mandibular hacia el hueso hioide) y SNB (silla turca-nasion- punto B) y SCSA (sección de puntos mas relevantes, menores transfversales) y el VT (volumen total) en las evaluaciones volumétricas (2 artículos). El promedio de cambio posterior de la vía aérea citado por autores fue de 4,2 mm con una desviación estándar de 1,4 mm con el uso de la mentoplastia de avance. La técnica mas habitual fue la mentoplastia con osteotomía horizontal (5 autores). Basados en esta investigación existe una relación positiva entre el incremento de la vía aérea y el avance con genioplastia; sin embargo, mas estudios estandarizados junto con medidas definidas y la evaluación correcta del avance y la vía área son necesarios.
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Humanos , Faringe/anatomia & histologia , Queixo/anatomia & histologia , Mentoplastia , Avanço Mandibular , Mandíbula/anatomia & histologiaRESUMO
Helicobacter pylori (H. pylori) infection is highly prevalent, affecting 4.4 billion people globally. This pathogen is a risk factor in the pathogenesis of more than 75% of worldwide cases of gastric cancer. Pattern recognition receptors are essential in the innate immune response to H. pylori infection. They recognize conserved pathogen structures and myriad alarmins released by host cells in response to microbial components, cytokines or cellular stress, thus triggering a robust proinflammatory response, which is crucial in H. pylori-induced gastric carcinogenesis. In this review, we intend to highlight the main pattern recognition receptors involved in the recognition and host response to H. pylori, as well as the main structures recognized and the subsequent inflammatory response.
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Infecções por Helicobacter , Receptores de Reconhecimento de Padrão , Infecções por Helicobacter/imunologia , Helicobacter pylori , Humanos , Receptores de Reconhecimento de Padrão/imunologiaRESUMO
Compelling evidence supports the crucial role of the receptor for advanced glycation end-products (RAGE) axis activation in many clinical entities. Since the beginning of the coronavirus disease 2019 pandemic, there is an increasing concern about the risk and handling of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in inflammatory gastrointestinal disorders, such as inflammatory bowel diseases (IBD). However, clinical data raised during pandemic suggests that IBD patients do not have an increased risk of contracting SARS-CoV-2 infection or develop a more severe course of infection. In the present review, we intend to highlight how two potentially important contributors to the inflammatory response to SARS-CoV-2 infection in IBD patients, the RAGE axis activation as well as the cross-talk with the renin-angiotensin system, are dampened by the high expression of soluble forms of both RAGE and the angiotensin-converting enzyme (ACE) 2. The soluble form of RAGE functions as a decoy for its ligands, and soluble ACE2 seems to be an additionally attenuating contributor to RAGE axis activation, particularly by avoiding the transactivation of the RAGE axis that can be produced by the virus-mediated imbalance of the ACE/angiotensin II/angiotensin II receptor type 1 pathway.
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COVID-19 , Doenças Inflamatórias Intestinais , Produtos Finais de Glicação Avançada , Humanos , Peptidil Dipeptidase A/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Sistema Renina-Angiotensina , SARS-CoV-2RESUMO
Compelling pieces of evidence derived from both clinical and experimental research has demonstrated the crucial role of the receptor for advanced-glycation end-products (RAGE) in orchestrating a plethora of proinflammatory cellular responses leading to many of the complications and end-organ damages reported in patients with diabetes mellitus (DM). During the coronavirus disease 2019 (COVID-19) pandemic, many clinical reports have pointed out that DM increases the risk of COVID-19 complications, hospitalization requirements, as well as the overall severe acute respiratory syndrome coronavirus 2 case-fatality rate. In the present review, we intend to focus on how the basal activation state of the RAGE axis in common preexisting conditions in DM patients such as endothelial dysfunction and hyperglycemia-related prothrombotic phenotype, as well as the contribution of RAGE signaling in lung inflammation, may then lead to the increased mortality risk of COVID-19 in these patients. Additionally, the cross-talk between the RAGE axis with either another severe acute respiratory syndrome coronavirus 2 receptor molecule different of angiotensin-converting enzyme 2 or the renin-angiotensin system imbalance produced by viral infection, as well as the role of this multi-ligand receptor on the obesity-associated low-grade inflammation in the higher risk for severe illness reported in diabetes patients with COVID-19, are also discussed.
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Far beyond the compelling proofs supporting that the metabolic syndrome represents a risk factor for diabetes and cardiovascular diseases, a growing body of evidence suggests that it is also a risk factor for different types of cancer. However, the involved molecular mechanisms underlying this association are not fully understood, and they have been mainly focused on the individual contributions of each component of the metabolic syndrome such as obesity, hyperglycemia, and high blood pressure to the development of cancer. The Receptor for Advanced Glycation End-products (RAGE) axis activation has emerged as an important contributor to the pathophysiology of many clinical entities, by fueling a chronic inflammatory milieu, and thus supporting an optimal microenvironment to promote tumor growth and progression. In the present review, we intend to highlight that RAGE axis activation is a crosswise element on the potential mechanistic contributions of some relevant components of metabolic syndrome into the association with cancer.
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Regulação da Expressão Gênica , Síndrome Metabólica/complicações , Síndrome Metabólica/metabolismo , Neoplasias/complicações , Neoplasias/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Animais , Progressão da Doença , Humanos , Hiperglicemia/metabolismo , Hipertensão/metabolismo , Inflamação , Fator de Crescimento Insulin-Like I/metabolismo , Leptina/metabolismo , Ligantes , Camundongos , Obesidade/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Ratos , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas Wnt/metabolismoRESUMO
Compelling pieces of evidence derived from both clinical and experimental research has demonstrated the crucial contribution of diabetes mellitus (DM) as a risk factor associated with increased cancer incidence and mortality in many human neoplasms, including gastric cancer (GC). DM is considered a systemic inflammatory disease and therefore, this inflammatory status may have profound effects on the tumor microenvironment (TME), particularly by driving many molecular mechanisms to generate a more aggressive TME. DM is an active driver in the modification of the behavior of many cell components of the TME as well as altering the mechanical properties of the extracellular matrix (ECM), leading to an increased ECM stiffening. Additionally, DM can alter many cellular signaling mechanisms and thus favoring tumor growth, invasion, and metastatic potential, as well as key elements in regulating cellular functions and cross-talks, such as the microRNAs network, the production, and cargo of exosomes, the metabolism of cell stroma and resistance to hypoxia. In the present review, we intend to highlight the mechanistic contributions of DM to the remodeling of TME in GC.
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Betacoronavirus , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Pneumonia/etiologia , Receptor para Produtos Finais de Glicação Avançada/fisiologia , Angiotensina II/fisiologia , Enzima de Conversão de Angiotensina 2 , COVID-19 , Humanos , Pandemias , Peptidil Dipeptidase A/fisiologia , Receptor Tipo 1 de Angiotensina/fisiologia , SARS-CoV-2RESUMO
The formation of advanced glycation end-products (AGEs) is a key pathophysiological event linked not only to the onset and progression of diabetic complications, but also to neurodegeneration, cardiovascular diseases, cancer, and others important human diseases. AGEs contributions to pathophysiology are mainly through the formation of cross-links and by engaging the receptor for advanced glycation end-products (RAGE). Polyphenols are secondary metabolites found largely in fruits, vegetables, cereals, and beverages, and during many years, important efforts have been made to elucidate their beneficial effects on human health, mainly ascribed to their antioxidant activities. In the present review, we highlighted the beneficial actions of polyphenols aimed to diminish the harmful consequences of advanced glycation, mainly by the inhibition of ROS formation during glycation, the inhibition of Schiff base, Amadori products, and subsequent dicarbonyls group formation, the activation of the glyoxalase system, as well as by blocking either AGEs-RAGE interaction or cell signaling.
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Antígenos de Neoplasias/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Polifenóis/metabolismo , Antígenos de Neoplasias/química , Regulação Enzimológica da Expressão Gênica , Produtos Finais de Glicação Avançada/química , Humanos , Proteínas Quinases Ativadas por Mitógeno/química , Espécies Reativas de Oxigênio/metabolismoRESUMO
A compelling body of evidence has demonstrated that gastric cancer has a very particular tumor microenvironment, a signature very suitable to promote tumor progression and metastasis. Recent investigations have provided new insights into the multiple molecular mechanisms, defined by genetic and epigenetic mechanisms, supporting a very active cross talk between the components of the tumor microenvironment and thus defining the fate of tumor progression. In this review, we intend to highlight the role of very active contributors at gastric cancer TME, particularly cancer-associated fibroblasts, bone marrow-derived cells, tumor-associated macrophages, and tumor-infiltrating neutrophils, all of them surrounded by an overtime changing extracellular matrix. In addition, the very active cross talk between the components of the tumor microenvironment, defined by genetic and epigenetic mechanisms, thus defining the fate of tumor progression, is also reviewed.
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Neoplasias Gástricas , Microambiente Tumoral , Fibroblastos Associados a Câncer , Matriz Extracelular , Humanos , Macrófagos , Neutrófilos , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Microambiente Tumoral/genéticaRESUMO
The highly toxic species of Chromium in its hexavalent state is an important hazard to the flora and fauna, causing a rupture in balance especially in aquatic environments. The removal of Cr(VI) ions from aqueous solutions using fungal biomass of Rhizopus sp. was investigated under batch experiments. The biomass was produced and treated with NaCl to compare pre-treated and untreated biosorbents capacity. Adsorption of Cr(VI) was investigated with a 23 experimental design to determine the best operational parameters including pH [2.0-4.0], temperature [20-40⯰C] and agitation [50-150â¯rpm]. Maximum Cr(VI) uptake (99%) indicated that pH 2.0 is the optimal for Cr(VI) removal. Linear and non-linear kinetic models were evaluated. The best fitting for linear kinetics was the pseudo-second order linear equation and the Elovich model in its non-linear form, suggesting chemisorption as the controlling step of adsorption. Results followed Langmuir isotherm equation, the qm was 9.95 (mg·g-1) for Rhizopus sp. + NaCl. Thermodynamic parameters were calculated using the adsorption equilibrium constant obtained from Langmuir isotherm and indicated that the adsorption process was spontaneous and endothermic. The surface characteristics of the biomass were analyzed by Fourier transform infrared (FTIR) spectra; the analysis showed the involvement of amino groups in the bonding with Cr(VI). SEM and EDX analysis confirmed the presence of Cr in the biomass after adsorption. The results of these experiments may be utilized for modeling, simulation, and scale-up processes in the future.
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Poluentes Químicos da Água , Purificação da Água , Adsorção , Biodegradação Ambiental , Cromo , Concentração de Íons de Hidrogênio , Cinética , Rhizopus , TermodinâmicaRESUMO
OBJECTIVE: The hypoxic milieu at tumor microenvironment is able to drive the behavior of infiltrating tumor cells. Considering that hypoxia-mediated HMGB1 release is known to promote tumor growth, as well to enhance the pro-tumoral profile of M2 macrophages by a RAGE-dependent mechanism, it is tempting to evaluate the potential contribution of HMGB1 under hypoxia to restrain M2 macrophages mobility. METHODS: CCR-2 expression was evaluated in M2 polarized macrophages by western blotting and immunocytochemistry. The secreted levels of CCL-2 and the migration capability were evaluated using an ELISA and a chemotaxis assay, respectively. RESULTS: HMGB1, under hypoxic conditions, markedly reduce both the production of CCL-2 and the expression of its receptor CCR-2; and reduced the migration capacity of M2 macrophages. CONCLUSIONS: These results provided new insights into the mechanisms that regulate M2 macrophages mobility at the tumor microenvironment.