The RAGE Axis: A Relevant Inflammatory Hub in Human Diseases.

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.

Emerging and multifaceted potential contributions of polyphenols in the management of type 2 diabetes mellitus.

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.

The First Population-Level Description of Women Diagnosed With Invasive Breast Cancer in Costa Rica From 2008 to 2012: A Cross-Sectional Study.

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.

Community Health Worker-led Implementation of the Stanford Youth Diabetes Coaching Program in Underserved Latinx Communities.

BACKGROUND: The Stanford Youth Diabetes Coaching Program (SYDCP) is an evidence-based program led by health care professionals to teach healthy youth who then coach family members with diabetes or other chronic conditions. This purpose of this study is to evaluate a Community Health Worker (CHW)-led implementation of the SYDCP for low-income Latinx students from underserved agricultural communities. METHOD: CHWs were trained and virtually led 10 training sessions virtually during the COVID-19 for Latinx students who were recruited from high schools in agricultural regions of Washington state. Feasibility measures include recruitment, retention, class attendance, and successful coaching of a family member or friend. Acceptability was measured by responses on the post-training survey. Effectiveness was evaluated by pre-post changes in measures used in prior studies of the SYDCP such as level of activation and diabetes knowledge. RESULTS: Thirty-four students were recruited, 28 completed the training and 23 returned both pre- and post-surveys. Over 80% of students attended 7 or more classes. All met with a family or friend and 74% met with them weekly. Approximately 80% of the students rated the program's usefulness as "very good" or "excellent." Pre-post increases in diabetes knowledge, nutrition-related behaviors, resilience, and activation were significant and similar to those observed in prior published studies of the SYDCP. CONCLUSIONS: Findings support the feasibility, acceptability, and effectiveness of a CHW-led implementation of the SYDCP in underserved Latinx communities using a virtual remote model.

Contributions of the receptor for advanced glycation end products axis activation in gastric cancer.

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.

Association between diabetes and cancer. Current mechanistic insights into the association and future challenges.

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.

Receptor of advanced glycation end-products axis and gallbladder cancer: A forgotten connection that we should reconsider.

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.

The RAGE/multiligand axis: a new actor in tumor biology.

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.

Changes in the airway after mentoplasty (genioplasty): systematic review / Cambios en la vía aérea después de una mentoplastia (genioplastia): una revisión sistemática

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.

A Multicomponent Health Education Campaign Led by Community Health Workers to Increase Influenza Vaccination among Migrants and Refugees.

OBJECTIVES: To evaluate the impact of a Community Health Worker (CHW)-led influenza campaign on knowledge and attitudes about vaccination in Latinx migrant and refugee populations. METHODS: Twelve online workshops were conducted with 183 participants and 24 CHWs between January 12 and May 12, 2021. Participants were Latinx families living in underserved communities throughout Washington state. The initiative also included radio, animated videos, advertisements, social media, and educational materials. RESULTS: Analysis of pre and post workshop surveys from 155 participants showed statistically significant improvements in all questions about the definition of influenza, symptoms, and risks: and in 7 of 9 questions about treatments and vaccines. Analysis of 2 open-ended questions showed increases in words key to understanding influenza, such as "virus," "illness," "death," and "contagious." There were significant increases in rates of participants identifying vaccination and antibiotics as cures for influenza. CONCLUSIONS: CHW-led workshops can be an effective way to increase knowledge about influenza and influenza vaccine. Future curriculum should emphasize the difference between viruses and bacteria, and the use of vaccination for prevention as opposed to treatment for illness.

Pattern recognition receptors and their roles in the host response to Helicobacter pylori infection.

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.

Receptor for advanced glycation end-products axis and coronavirus disease 2019 in inflammatory bowel diseases: A dangerous liaison?

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.

Advanced-glycation end-products axis: A contributor to the risk of severe illness from COVID-19 in diabetes patients.

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.

Counting the Unsung by Promoting Participation in the 2020 US Census: A Survey of Migrant Workers in Washington State.

INTRODUCTION: Participation in the United States Census is critical for determining congressional representation and federal funding, but in every census there are groups systematically undercounted due to socioeconomic and demographic factors. Migrants and refugees are a group particularly threatened by being undercounted, including Hispanic migrant workers living in more rural areas. METHODS AND RESULTS: To gather information to promote migrant participation in the census, the Community Health Worker Coalition for Migrants and Refugees in Washington state conducted a systematic survey of 71 migrant workers in seven urban and suburban Washington communities. The results showed that while most participants had heard of the census, basic knowledge about the census was limited and people wanted more information. CONCLUSIONS AND RECOMMENDATIONS: A strong, coordinated outreach approach should be carried out to educate people in migrant communities about the census. This may involve one-on-one structured conversations, radio telenovelas, and community conversations organized by the trusted leaders.

Correlation of Oral Health Education by Community Health Workers with Changes in Oral Health Practices in Migrant Populations in Washington State.

INTRODUCTION: An important question for oral health education is whether knowledge gained during lay-led workshops is retained and applied in daily practice. This study assessed the knowledge retention and changes in oral health practices several months after oral health education workshops were held for migrant farmworkers by Community Health Workers (CHWs). METHODS AND RESULTS: Follow-up surveys were conducted with 32 participants 1 to 43 months post participation (60% between 6 and 21 months). The results showed a high degree of retention, in such areas as general oral health knowledge, and brushing/flossing frequency and technique among this sample. There was no relationship between length of time since the educational workshop and knowledge retained or behaviors changed. CONCLUSIONS AND RECOMMENDATIONS: An interactive, lay-led oral health education program run by CHWs can be an effective way to deliver sustained improvements in oral health knowledge and changes in oral health practice in migrant populations.

Contribution of RAGE axis activation to the association between metabolic syndrome and cancer.

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.

Healthy eating recommendations: good for reducing dietary contribution to the body's advanced glycation/lipoxidation end products pool?

The present review aims to give dietary recommendations to reduce the occurrence of the Maillard reaction in foods and in vivo to reduce the body's advanced glycation/lipoxidation end products (AGE/ALE) pool. A healthy diet, food reformulation and good culinary practices may be feasible for achieving the goal. A varied diet rich in fresh vegetables and fruits, non-added sugar beverages containing inhibitors of the Maillard reaction, and foods prepared by steaming and poaching as culinary techniques is recommended. Intake of supplements and novel foods with low sugars, low fats, enriched in bioactive compounds from food and waste able to modulate carbohydrate metabolism and reduce body's AGE/ALE pool is also recommended. In conclusion, the recommendations made for healthy eating by the Spanish Society of Community Nutrition (SENC) and Harvard University seem to be adequate to reduce dietary AGE/ALE, the body's AGE/ALE pool and to achieve sustainable nutrition and health.

Diabetes mellitus contribution to the remodeling of the tumor microenvironment in gastric cancer.

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.