Diabetes Mellitus (DM) is an inflammatory clinical entity with different mechanisms involved in its physiopathology. Among these, the dysfunction of the gut microbiota stands out. Currently, it is understood that lipid products derived from the gut microbiota are capable of interacting with cells from the immune system and have an immunomodulatory effect. In the presence of dysbiosis, the concentration of lipopolysaccharides (LPS) increases, favoring damage to the intestinal barrier. Furthermore, a pro-inflammatory environment prevails, and a state of insulin resistance and hyperglycemia is present. Conversely, during eubiosis, the production of short-chain fatty acids (SCFA) is fundamental for the maintenance of the integrity of the intestinal barrier as well as for immunogenic tolerance and appetite/satiety perception, leading to a protective effect. Additionally, it has been demonstrated that alterations or dysregulation of the gut microbiota can be reversed by modifying the eating habits of the patients or with the administration of prebiotics, probiotics, and symbiotics. Similarly, different studies have demonstrated that drugs like Metformin are capable of modifying the composition of the gut microbiota, promoting changes in the biosynthesis of LPS, and the metabolism of SCFA.
Arterial hypertension is the most prevalent chronic disease in the adult population of developed countries and it constitutes a significant risk factor in the development of cardiovascular disease, contributing to the emergence of many comorbidities, among which heart failure excels, a clinical syndrome that nowadays represents a major health problem with uncountable hospitalizations and the indolent course of which progressively worsens until quality of life decreases and lastly death occurs prematurely. In the light of this growing menace, each day more efforts are invested in the field of cardiovascular pharmacology, searching for new therapeutic options that allow us to modulate the physiological systems that appear among these pathologies. Therefore, in the later years, the study of natriuretic peptides has become so relevant, which mediate beneficial effects at the cardiovascular level such as diuresis, natriuresis, and decreasing cardiac remodeling; their metabolism is mediated by neprilysin, a metalloproteinase, widely expressed in the human and capable of catalyzing many substrates. The modulation of these functions has been studied by decades, giving room to Sacubitril, the first neprilysin inhibitor, which in conjunction with an angiotensin receptor blocker has provided a high efficacy and tolerability among patients with heart failure, for whom it has already been approved and recommended. Nonetheless, in the matter of arterial hypertension, significant findings have arisen that demonstrate the potential role that it will play among the pharmacological alternatives in the upcoming years.
En ejercicio de las atribuciones que me confiere el Decreto Nº 1.656 de fecha 16 de marzo de 2015, publicado en la Gaceta Oficial de la República Bolivariana de Venezuela Nº 40.621 de la misma fecha, de conformidad con lo dispuesto en el Artículo 77 numeral 19, del Decreto con Rango, Valor y Fuerza de Ley Orgánica de la Administración Pública y artículo 28 numeral 9º del Reglamento Orgánico del Ministerio del Poder Popular para la Salud, en concordancia con lo previsto en los artículos 17 y 18 de la Ley de Publicaciones Oficiales.
How to cite this article: Calvo MJ, Martínez MS, Torres W, Chávez-Castillo M, Luzardo E, Villasmil N, Salazar J, Velasco M, Bermúdez V. Omega-3 polyunsaturated fatty acids and cardiovascular health: a molecular view into structure and function. Vessel Plus 2017;1:116-28.Given the notorious impact of cardiovascular disease (CVD) as the current leading cause of mortality worldwide, the prevention, identification and management of CV risk factors represents a priority in daily clinical practice. Several studies have shown the beneficial effects of dietary omega-3 polyunsaturated fatty acids (PUFAs) on CV health. Their derivatives, eicosapentaenoic acid and docosahexaenoic acid, intervene in multiple metabolic pathways, including: regulation of the inflammatory response, by reducing the synthesis of pro-inflammatory cytokines; regulation of platelet aggregation, activation and adhesion, by modulating thromboxane A2 and plasminogen activator inhibitor-1 activity; regulation of the coagulation pathways, by reducing the carboxylation of vitamin K-dependent coagulation factors; improvement of endothelial function, given their effects on prostaglandin synthesis and endothelial nitric oxide synthase; reduction of serum lipids, through their effects on the hepatic synthesis of triacylglycerides, beta-oxidation of fatty acids and lipoprotein catabolism; and improvement of myocardial function via their membrane-stabilizing effects, and an increase in fluidity, size and distribution of membrane lipid rafts. Nevertheless, these effects appear to vary according to the type of PUFA ingested, dietary sources, daily dosing and individual factors inherent to the subject. Therefore, further studies are required to determine the ideal supplementation for each kind of patient and their particular CV profiles. Key words:Cardiovascular disease, omega-3 polyunsaturated fatty acids, eicosapentaenoic acid, docosahexaeonic acid ABSTRACTArticle history:
Diabetes mellitus (DM) is considered one of the most massive epidemics of the twenty-first century due to its high mortality rates caused mainly due to its complications; therefore, the early identification of such complications becomes a race against time to establish a prompt diagnosis. The research of complications of DM over the years has allowed the development of numerous alternatives for diagnosis. Among these emerge the quantification of advanced glycation end products (AGEs) given their increased levels due to chronic hyperglycemia, while also being related to the induction of different stress-associated cellular responses and proinflammatory mechanisms involved in the progression of chronic complications of DM. Additionally, the investigation for more valuable and safe techniques has led to developing a newer, noninvasive, and effective tool, termed skin fluorescence (SAF). Hence, this study aimed to establish an update about the molecular mechanisms induced by AGEs during the evolution of chronic complications of DM and describe the newer measurement techniques available, highlighting SAF as a possible tool to measure the risk of developing DM chronic complications.
The yes-associated protein (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ) are transcriptional coactivators, members of the Hippo signaling pathway, which play a critical role in cell growth regulation, embryonic development, regeneration, proliferation, and cancer origin and progression. The mechanism involves the nuclear binding of the un-phosphorylated YAP/TAZ complex to release the transcriptional enhanced associate domain (TEAD) from its repressors. The active ternary complex is responsible for the aforementioned biological effects. Overexpression of YAP/TAZ has been reported in cancer stem cells and tumor resistance. The resistance involves chemotherapy, targeted therapy, and immunotherapy. This review provides an overview of YAP/TAZ pathways’ role in carcinogenesis and tumor microenvironment. Potential therapeutic alternatives are also discussed.
Introduction. Insulin allergy is a rare complication of insulin therapy, especially in type 1 diabetes mellitus (T1DM). Key manifestations are hypersensitivity-related symptoms and poor metabolic control. T1DM, as well as insulin allergy, may develop in the context of autoimmune polyendocrine syndrome (APS), further complicating management. Case Report. A 17-year-old male patient, diagnosed with T1DM, was treated with various insulin therapy schemes over several months, which resulted in recurrent anaphylactoid reactions and poor glycemic control, after which he was referred to our Endocrinology and Immunology Department. A prick test was carried out for all commercially available insulin presentations and another insulin scheme was designed but proved unsuccessful. A desensitization protocol was started with Glargine alongside administration of Prednisone, which successfully induced tolerance. Observation of skin lesions typical of vitiligo prompted laboratory workup for other autoimmune disorders, which returned positive for autoimmune gastritis/pernicious anemia. These findings are compatible with APS type 4. Discussion. To our knowledge, this is the first documented case of insulin allergy in type 4 APS, as well as this particular combination in APS. Etiopathogenic components shared by insulin allergy and APS beg for further research in immunogenetics to further comprehend pathophysiologic aspects of these diseases.
: Aging is a time-dependent inevitable process, in which cellular homeostasis is affected, which has an impact on tissue function. This represents a risk factor for the development of numerous non-transmissible diseases. In consequence, the scientific community continues to search for therapeutic measures capable of improving quality of life and delaying cellular aging. At the center of this research is metformin, a widely used drug in Type 2 Diabetes Mellitus treatment that has a reduced adverse effects profile. Furthermore, there is evidence that this drug has beneficial health effects that go beyond its anti-hyperglycemic properties. Among these effects, its geronto-protection capability stands out. There is growing evidence that points out to an increased life expectancy as well as quality of life in model organisms treated with metformin. Therefore, there is an abundance of research centered on elucidating the mechanism through which metformin has its anti-aging effects. Among these, the AMPK, mTORC1, SIRT1, FOXO, NF.kB, and DICER1 pathways can be mentioned. Furthermore, studies have highlighted the possibility of a role for gut microbiome in these processes. The next step is the design of clinical essays that have as a goal evaluating the efficacy and safety of metformin as an anti-aging drug in humans to create a paradigm in the medical horizon. The question being if metformin is in fact the new anti-aging therapy in humans?
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