Examinando por Autor "Navarro, Carla"
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Ítem Advanced Glycation End Products: New Clinical and Molecular Perspectives(MDPI, 2021) Salazar, Juan; Navarro, Carla; Ortega, Ángel; Nava, Manuel; Morillo, Daniela; Torres, Wheeler; Hernández, Marlon; Cabrera, Mayela; Angarita, Lissé; Ortiz, Rina; Chacín, Maricarmen; D'Marco, Luis; Bermúdez, ValmoreDiabetes 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.Ítem Cigarette smoking and metabolic syndrome components: a cross-sectional study from Maracaibo City, Venezuela [version 1; referees: 1 approved with reservations](F1000 Research Ltda, 2018-05-22) Bermudez, Valmore; Olivar, Luis Carlos; Torres, Wheeler; Navarro, Carla; Gonzalez, Robys; Morocho, Alicia; Mindiola, Andres; Chacin, Maricarmen; Arias, Victor; Añez, Roberto; Salazar, Juan; Riaño Garzon, Manuel; Diaz Camargo, Edgar; Judith Bautista, Maria; Rojas, JoselynBackground: A growing body of evidence suggests that cigarette smoking can cause the onset of metabolic syndrome prior to cardiovascular diseases. Therefore, the objective of this study was to evaluate the relationship between smoking habit and metabolic syndrome components in an adult population from Maracaibo city, Venezuela. Methods: The Maracaibo City Metabolic Syndrome Prevalence Study is a descriptive, cross-sectional study with random and multi-stage sampling. In this sub-study, 2212 adults from both genders were selected. On the basis of their medical background, they were classified as smokers, non-smokers and former smokers. Metabolic syndrome was defined according to Harmonizing 2009 criteria, using population-specific abdominal circumference cut-off points. The association between risk factors was evaluated using a logistic regression model. Results: In the studied population, 14.8% were smokers, 15.4% were former smokers. In the multivariate analysis, the presence of metabolic syndrome (smokers: OR, 1.54; 95% CI, 1.11–2.14; p=0.010) and its components were related to cigarette smoking, with the exception of hyperglycemia. High blood pressure was inversely associated with current smoking status (smokers: OR, 0.70 (0.51–0.95); p=0.025).Ítem Intrinsic and environmental basis of aging: A narrative review(Elsevier Ltd., 2023) Navarro, Carla; Salazar, Juan; Díaz, María P.; Chacin, Maricarmen; Santeliz, Raquel; Vera, Ivana; D'Marco, Luis; Parra, Heliana; Bernal, Mary Carlota; Castro, Ana; Escalona, Daniel; García-Pacheco, Henry; Bermúdez, ValmoreLongevity has been a topic of interest since the beginnings of humanity, yet its aetiology and precise mechanisms remain to be elucidated. Aging is currently viewed as a physiological phenomenon characterized by the gradual degeneration of organic physiology and morphology due to the passage of time where both external and internal stimuli intervene. The influence of intrinsic factors, such as progressive telomere shortening, genome instability due to mutation buildup, the direct or indirect actions of age-related genes, and marked changes in epigenetic, metabolic, and mitochondrial patterns constitute a big part of its underlying endogenous mechanisms. On the other hand, several psychosocial and demographic factors, such as diet, physical activity, smoking, and drinking habits, may have an even more significant impact on shaping the aging process. Consequentially, implementing dietary and exercise patterns has been proposed as the most viable alternative strategy for attenuating the most typical degenerative aging changes, thus increasing the likelihood of prolonging lifespan and achieving successful aging.Ítem Metabolic Reprogramming in Cancer Cells: Emerging Molecular Mechanisms and Novel Therapeutic Approaches(MDPI, 2022) Navarro, Carla; Ortega, Ángel; Santeliz, Raquel; Garrido, Bermary; Chacín, Maricarmen; Galban, Néstor; Vera, Ivana; Bautista de Sanctis, Juan; Bermúdez, ValmoreThe constant changes in cancer cell bioenergetics are widely known as metabolic reprogramming. Reprogramming is a process mediated by multiple factors, including oncogenes, growth factors, hypoxia-induced factors, and the loss of suppressor gene function, which support malignant transformation and tumor development in addition to cell heterogeneity. Consequently, this hallmark promotes resistance to conventional anti-tumor therapies by adapting to the drastic changes in the nutrient microenvironment that these therapies entail. Therefore, it represents a revolutionary landscape during cancer progression that could be useful for developing new and improved therapeutic strategies targeting alterations in cancer cell metabolism, such as the deregulated mTOR and PI3K pathways. Understanding the complex interactions of the underlying mechanisms of metabolic reprogramming during cancer initiation and progression is an active study field. Recently, novel approaches are being used to effectively battle and eliminate malignant cells. These include biguanides, mTOR inhibitors, glutaminase inhibition, and ion channels as drug targets. This review aims to provide a general overview of metabolic reprogramming, summarise recent progress in this field, and emphasize its use as an effective therapeutic target against cancer.Ítem Microbiota and Diabetes Mellitus: Role of Lipid Mediators(MDPI, 2020) Salazar, Juan; Angarita, Lissé; Morillo, Valery; Navarro, Carla; Martínez, María Sofía; Chacín, Maricarmen; Torres, Wheeler; Rajotia, Arush; Rojas, Milagros; Cano, Clímaco; Añez, Roberto; Rojas, Joselyn; Bermúdez, ValmoreDiabetes 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.Ítem Optimal cutoff for the evaluation of insulin resistance through triglyceride-glucose index: A cross-sectional study in a Venezuelan population [version 1; referees: awaiting peer review](F1000 Research Ltd., 2017-08-07) Salazar, Juan; Bermúdez, Valmore; Calvo, María; Olivar, Luis; Luzardo, Eliana; Navarro, Carla; Mencia, Heysa; Martínez, María; Rivas-Ríos, José; Wilches-Durán, Sandra; Cerda, Marcos; Graterol, Modesto; Graterol, Rosemily; Garicano, Carlos; Hernández, Juan; Rojas, JoselynBackground: Insulin resistance (IR) evaluation is a fundamental goal in clinical and epidemiological research. However, the most widely used methods are difficult to apply to populations with low incomes. The triglyceride-glucose index (TGI) emerges as an alternative to use in daily clinical practice. Therefore the objective of this study was to determine an optimal cutoff point for the TGI in an adult population from Maracaibo, Venezuela. Methods: This is a sub-study of Maracaibo City Metabolic Syndrome Prevalence Study, a descriptive, cross-sectional study with random and multi-stage sampling. For this analysis, 2004 individuals of both genders ≥18 years old with basal insulin determination and triglycerides < 500 mg/dl were evaluated.. A reference population was selected according to clinical and metabolic criteria to plot ROC Curves specific for gender and age groups to determine the optimal cutoff point according to sensitivity and specificity.The TGI was calculated according to the equation: ln [Fasting triglyceride (mg / dl) x Fasting glucose (mg / dl)] / 2. Results: The TGI in the general population was 4.6±0.3 (male: 4.66±0.34 vs. female: 4.56±0.33, p=8.93x10 ). The optimal cutoff point was 4.49, with a sensitivity of 82.6% and specificity of 82.1% (AUC=0.889, 95% CI: 0.854-0.924). There were no significant differences in the predictive capacity of the index when evaluated according to gender and age groups. Those individuals with TGI≥4.5 had higher HOMA2-IR averages than those with TGI <4.5 (2.48 vs 1.74, respectively, p<0.001). Conclusions: The TGI is a measure of interest to identify IR in the general population. We propose a single cutoff point of 4.5 to classify individuals with IR. Future studies should evaluate the predictive capacity of this index to determine atypical metabolic phenotypes, type 2 diabetes mellitus and even cardiovascular risk in our population.Ítem The YAP/TAZ Signaling Pathway in the Tumor Microenvironment and Carcinogenesis: Current Knowledge and Therapeutic Promises(MDPI, 2022) Ortega, Ángel; Vera, Ivana; Diaz, Maria P.; Navarro, Carla; Rojas, Milagros; Torres, Wheeler; Parra, Heliana; Salazar, Juan; De Sanctis, Juan B.; Bermúdez, ValmoreThe 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.