Novel pharmacological approaches in abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a severe vascular disease and a major public health issue with an unmet medical need for therapy. This disease is featured by a progressive dilation of the abdominal aorta, boosted by atherosclerosis, ageing, and smoking as major risk factors. Aneurysm growth increases the risk of aortic rupture, a life-threatening emergency with high mortality rates. Despite the increasing progress in our knowledge about the etiopathology of AAA, an effective pharmacological treatment against this disorder remains elusive and surgical repair is still the unique available therapeutic approach for high-risk patients. Meanwhile, there is no medical alternative for patients with small aneurysms but close surveillance. Clinical trials assessing the efficacy of antihypertensive agents, statins, doxycycline, or anti-platelet drugs, among others, failed to demonstrate a clear benefit limiting AAA growth, while data from ongoing clinical trials addressing the benefit of metformin on aneurysm progression are eagerly awaited. Recent preclinical studies have postulated new therapeutic targets and pharmacological strategies paving the way for the implementation of future clinical studies exploring these novel therapeutic strategies. This review summarises some of the most relevant clinical and preclinical studies in search of new therapeutic approaches for AAA.

Volviéndonos mejores: necesidad de acción inmediata ante el reto de la obesidad. Una postura de profesionales de la salud.

La creciente epidemia de obesidad ha sido uno de los retos más importantes de salud pública en México durante los últimos años. Con apoyo de la Federación Mundial de Obesidad, en 2021 formamos un grupo de profesionales para identificar y resumir las acciones prioritarias en las que puede enfocarse nuestro país para hacer frente a esta epidemia. Al proceso de desarrollo y discusión de este grupo se sumaron más de 1 000 profesionales de la salud para retomar recomendaciones de documentos y guías de alto nivel previamente publicados. En conmemoración del Día Mundial de la Obesidad, en este 2022 se presenta esta postura como insumo para el desarrollo de acciones en el ámbito profesional y de los diferentes sectores, en la que se incluyen 10 recomendaciones de acción, desde la perspectiva poblacional hasta la atención individualizada, y se enfatiza en la importancia de la participación social, de las intervenciones integrales con visión centrada en la persona y de la sostenibilidad planetaria, además de mejorar la educación y las campañas de difusión, propiciar un ambiente promotor de entornos activos y blindar de conflictos de interés los esfuerzos de prevención y control. La postura hace un llamado para abordar la obesidad de manera seria, con base en la evidencia científica, oportuna e integral, con enfoque de curso de vida, de forma ética y sensible, y sin perpetuar las barreras del estigma de peso en la sociedad.

DPP-4 as a Possible Biomarker of Inflammation Before Abdominal Surgery for Chronic Pathology: Our Experience with Elective Cholecystectomy.

Background and objectives: Dipeptidyl-Peptidase 4 (DPP-4) is a protein expressed in numerous cells and tissues. Recently it has shown its involvement as a catalyst in the inflammatory response in various pulmonary, autoimmune, intestinal and other pathologies. The objective of this study was to compare the preoperative serum levels of DPP-4 in patients with and without surgical finding of perivesicular inflammation. Materials and methods: a cross-sectional analytical study nested in a prospective cohort, including patients scheduled for elective cholecystectomy, without surgical complications, that were 18-70 years of age, with low cardiovascular risk, without a history of peritonitis, pancreatitis, or jaundice and underwent ERCP protocol, type 2 diabetes mellitus, acute inflammatory (Protein C Reactive < 3 mg/L, leucocytes < 10 1000/mm3), neoplastic, nephrologic or liver disease, the use of anti-inflammatory drugs, steroids and/or antibiotics, the use of pacemakers or metallic implants and without major amputations and whom agreed to participate by providing their informed consent. Ethical and Research register: 45-16. Prior to surgery we compiled anthropometric data and a blood sample to determine the serum levels of DPP-4. The presence of perivesicular inflammation was determined in the surgery. The data was analyzed using the statistical program Rstudio. Results: High BMI values were observed (27.8 ± 6.4); waist circumference (94.7 ± 15.1) and percentage of fat mass (34.7 ± 11.7), showing a cumulative frequency of 65.9% for overweight/obesity. In 27.3% of the interventions, intraoperative perivesicular inflammation findings were reported. The serum levels of DPP-4 were lower in the group of patients with perivesicular inflammation (3947.6 ± 1659.5 vs. 3053.2 ± 1469.6, LC95% of the difference: 160.4-1628.3), being statistically significant (P = 0.018). Conclusions: In the subacute or chronic phases of cholecystitis, there appears to be a constant consumption of DPP-4, which would modulate a better immune response that could be related to the reduction of postoperative complications, so the use of Serum levels of DPP-4 as an early biomarker could improve the diagnostic accuracy of this pathology and the surgical approach.

Identification of new therapeutic targets related to endoplasmic reticulum stress and mitochondrial dysfunction to reduce the risk of rupture in degenerative ascending aortic aneurysm. / Identificación de nuevas dianas terapéuticas relacionadas con el estrés del retículo endoplasmático y con la disfunción mitocondrial para reducir el riesgo de rotura en el aneurisma de aorta ascendente degenerativo.

BACKGROUND: Ascending Thoracic Aortic Aneurysm (ATAA) is a progressive dilation of the aorta that can be complicated by its dissection leading to death in 80-90% of the patients. When associated with aging and atherosclerosis, the outcome is worse and reconstructive surgery is the only effective therapy. Our objective was to characterize differential expressed genes (DEG) involved in endoplasmic reticulum (ER) and mitochondria dysfunction in patients with degenerative ATAA. METHODS: A transcriptomic analysis was performed by RNA sequencing using RNA isolated from ATAA of patients classified as degenerative (n=13) and multi-organ healthy donors (n=6). DEGs related to ER stress and mitochondrial dysfunction were identified with the DESeq2 package. Enriched pathway (Reactome) and protein interaction (PPI) analysis was performed with the clusterProfiles package. PPI of the selected DEGs was analyzed based on the string database and visualized by Cytoscape software. RESULTS: Histology revealed a complete disorganization of the extracellular matrix (ECM) and cell loss in the aortic wall of ATAA patients where the upregulation of 15 DEGs and the downregulation of 13 DEGs that encode proteins related to ER stress (ATF4, EIF2AK3, HSPA5, ERN1, SEL1L), mitochondrial dysfunction (DNML1, IMMT, MT-CO3, MT-CYB, MT ND2, TIMM17B, MT-ERF1, TOMM5) and ECM was detected. The results of GO term and enriched pathway analysis indicated that these DEGs are mainly enriched in pathways related to aortic diseases. CONCLUSIONS: Our data show that proteins related to mitochondrial dysfunction and ER stress might be therapeutic targets for the treatment of ATAA.

Targeting mitochondrial stress with Szeto-Schiller 31 prevents experimental abdominal aortic aneurysm: Crosstalk with endoplasmic reticulum stress.

BACKGROUND AND PURPOSE: Mitochondrial dysfunction and inflammation contribute to a myriad of cardiovascular diseases. Deleterious crosstalk of mitochondria and persistent endoplasmic reticulum (ER) stress triggers oxidative stress, which is involved in the development of vascular diseases. This study determined if inhibition of mitochondrial stress reduces aneurysm development in angiotensin II (Ang II)-infused apolipoprotein-E-deficient (ApoE-/- ) mice and its effect on ER stress. EXPERIMENTAL APPROACH: The mitochondria-targeted tetrapeptide, Szeto-Schiller 31 (SS31), ameliorated mitochondrial dysfunction and the enhanced expression of ER stress markers triggered by Ang II in ApoE-/- mice, and limited plasmatic and vascular reactive oxygen species (ROS) levels. Interestingly, SS31 improved survival, reduced the incidence and severity of abdominal aortic aneurysm (AAA), and the Ang II-induced increase in aortic diameter as evaluated by ultrasonography, resembling the response triggered by the classic ER stress inhibitors tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyrate (PBA). KEY RESULTS: Disorganization of the extracellular matrix, increased expression of metalloproteinases and pro-inflammatory markers and infiltration of immune cells induced by Ang II in the abdominal aorta were effectively reduced by SS31 and ER inhibitors. Further, C/EBP homologous protein (CHOP) deficiency in ApoE-/- mice attenuated Ang II-mediated increase in vascular diameter and incidence of AAA, suggesting its contribution to the favourable response induced by ER stress inhibition. CONCLUSIONS AND IMPLICATIONS: Our data demonstrate that inhibition of mitochondrial stress by SS31 limits AAA formation and increases survival through a reduction of vascular remodelling, inflammation and ROS, and support that attenuation of ER stress contributes to the favourable response elicited by SS31.

Dietary Patterns and Their Association with Metabolic Syndrome and Their Components in Middle-Class Adults from Damascus, Syria: A Cross-Sectional Study.

Prior to the 2016 crisis in Syria, a study conducted in Aleppo found the prevalence of metabolic syndrome to be 39.6%, which is known to be favoured by age and poor lifestyle (including physical inactivity and the consumption of hypercaloric foods, rich in saturated fats, concentrated carbohydrates, and salt), so the objective of this study was to identify the association of different dietary patterns with metabolic syndrome and their components. A cross-sectional analytical study was carried out in 104 adults aged 40 to 65 years who did not suffer from previous diseases. The sample was chosen from middle-class citizens of the city of Damascus who were contacted by telephone; they were explained about the study, the information that would be collected, and the studies that should be carried out in the clinical analysis laboratory of the Private University of Syria. A nutritional and food study was carried out using previously validated forms containing 62 items in which the food intake of the participants was studied. We apply principal component analysis and factor analysis to detect nutritional components and dietary patterns. Dietary pattern 3 (foods with simple carbohydrates and saturated fat) increased glucose levels, while dietary patterns 1 (high intake of calories, protein, and saturated fat) and 5 (fast food) increased serum triglyceride levels. In addition, pattern 1 (carbonated beverages, grains, chicken, and meat) was associated with elevated LDL cholesterol levels and the presence of the metabolic syndrome. The study findings suggest that the presence of metabolic syndrome and its components are associated with dietary patterns high in calories, protein, simple carbohydrates, and saturated fat.

Factors Associated with Dietary Restriction and Emotional and Uncontrolled Eating in Adults from Spanish-Speaking Countries during the COVID-19 Confinement: Results of the CoV-Eat Project.

The first COVID-19 confinement has led to changes in the population's behaviour. However, little has been analysed about the changes in eating behaviour beyond the decrease in adherence to healthy dietary patterns. The aim of the CoV-Eat project was to identify factors related to each of the following eating behaviours (EB): cognitive restraints (CR), uncontrolled eating (UE), and emotional eating (EE) in adults from Spanish-speaking countries. Participants completed an anonymous online survey. EB was assessed using the Three-Factor Eating Questionnaire and the scores were classified into tertiles. Socio-demographic characteristics and lifestyle habits including physical activity, sleep quality, screen use, smoking consumption, and relationship with food were also collected. A total of 9849 participants from 21 countries were included in this study. The median of CR, UE, and EE behaviours was 15, 24, and 9, respectively. We observed that higher age, days of confinement, number of times leaving home in the last week, changes in sleep quality, and their relationship with food were negatively associated with CR, EE, and UE, while being a man was positively associated with an increased in all these EBs. A higher household income was negatively associated with a higher score of CR, and a higher education level (>primary) was positively associated with a medium score of EE. Lower physical activity was a factor negatively associated with a medium score of EE and UE. Higher screen use showed the same negative association for a medium score of EE and UE and a high score of CR. In addition, higher tobacco consumption was found to be a protective factor against having a medium or high score of CR and EE. In conclusion, some sociodemographic characteristics and lifestyle changes may be important factors for EB and should be considered in emergency situations such as confinement to prevent risky eating behaviour.

DPP-4 Levels Are Increased in Subjects with Poor Sleep Quality.

Background: Up to 30% of the population has sleep disturbances, generating a negative health impact, a situation that is often not known and no medical attention is sought. It has been observed that after a total deprivation of sleep, the levels of dipeptidyl peptidase 4 (DPP-4) tend to increase. The aim of this study was to compare serum levels of DPP-4 in healthy subjects, with adequate and poor-quality sleep needing medical/pharmacological treatment. Materials and Methods: Cross-sectional study of subjects scheduled for elective surgery with low cardiometabolic risk. Subjects between 18-70 years of age were included, without previous diagnosed pathology (diabetes mellitus type 2; neoplasm; nephropathy; and liver disease) and major amputations, and who signed informed consent. The study protocol was aproved in the Local Committee for Ethics and Research, number 45-16. Anthropometry was performed (% body fat; waist and neck circumferences), and sleep quality assessment (Pittsburgh Sleep Quality Index [PSQI]) to classify them as worthy or not worthy of medical/pharmacological care. Serum DPP-4 was determined by Enzime Linked Immunosorbent Assay (ELISA). The statistical analysis was done in RStudio Software. Results: Fifty seven subjects (2017-2018) were included, with a combined frequency of overweight/obesity of 66.6% and with abdominal circumference values of 93.2 ± 13.6, higher than that proposed by the International Diabetes Federation. The PSQI was 8.3 ± 4.1, and 56.1% were classified as worthy of medical/pharmacological attention. When comparing the levels of DPP-4, these were higher in this group 2385.0 ± 2082.0 versus not worthy 1716.7 ± 1261.7 pg/mL, being statistically significant (P = 0.035). Conclusions: The elevated levels of DPP-4 in person with poor quality sleep worthy of medical/pharmacological treatment could be an early indicator of metabolic disorders, which need to be evaluated in depth.

Volviéndonos mejores: necesidad de acción inmediata ante el reto de la obesidad. Una postura de profesionales de la salud / Becoming better: the need for immediate action to address obesity. A position statement from health professionals

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Abstract: In recent decades, the growing obesity epidemic in Mexico has become one of the most important public health challenges faced by the country. With support from the World Obesity Federation, we formed a working group in 2021 to identify and summarize priority actions that Mexico can take to face this epidemic. More than 1 000 health professionals joined the development and discussion process. Recommendations from previously published, high-level documents and guidelines were taken into account. In commemoration of World Obesity Day 2022, this statement is presented as input for health care professionals to develop actions to address obesity. The statement includes 10 recommendations that include population-level and individual-level actions. It emphasizes the importance of social participation, comprehensive interventions with a person- centered perspective, planetary sustainability, on improving education and communication campaigns, as well as fostering a built environment that promotes active living, and shielding prevention and control efforts from conflicts of interest. The statement calls for obesity to be treated seriously, based on scientific evidence, in a timely and comprehensive manner, employing a life-course and ethical approach that does not perpetuate weight stigma in society.