The constant changes in cancer cell bioenergetics are widely known as metabolic reprogramming. Re... more The 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 effect...
International Journal of Environmental Research and Public Health, 2021
Diabetes mellitus (DM) is considered one of the most massive epidemics of the twenty-first centur... more 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 yes-associated protein (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ)... more 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.
Diabetes Mellitus (DM) is an inflammatory clinical entity with different mechanisms involved in i... more 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 eati...
Currently, conventional therapies in cancer are improving; chemotherapy, radiotherapy and surgery... more Currently, conventional therapies in cancer are improving; chemotherapy, radiotherapy and surgery have increased survival significantly. New therapies have arisen with the same goal; immunotherapy has appeared as a promising option in the fight against cancer stimulating the immune system by inducing innate and adaptive responses. These responses include release of pro-inflammatory cytokines, making the immune system capable to eliminate or protect against multiple tumors. Nowadays, many of these therapies are being used in clinical settings, such as checkpoint inhibitors, monoclonal anti cytotoxic T-Lymphocyte associated protein 4 (CTL-4) and programmed death protein 1 (PD1), with inspiring results; however, they may decrease immunotolerance, limiting their use. At the same time, chemotherapy works by passive transport across the cell membrane, limiting its capacity to penetrate in tumor cells. For these reasons, bacteria employment represents one of the best candidates for cancer treatment. They can surpass these barriers with their selective colonization which also has an oncolytic effect by increasing proliferation and immunostimulation in the tumor environment. Attenuated strains, such as Mycobacterium bovis, Clostridium, Salmonella typhimirium and Listeria monocytogenes have been studied showing promising results in experimental models. However, their application in clinical trials has shown the need to maximize their therapeutic effect. Genetic engineering and synthetic biology are necessary to prove the scope that this novel approach has against cancer due to implications of cancer therapy and public health.
Background: A growing body of evidence suggests that cigarette smoking can cause the onset of met... more Background: 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 me...
Background: Hypertension (HTN) is a prominent cardiovascular risk factor, affecting over 1 billio... more Background: Hypertension (HTN) is a prominent cardiovascular risk factor, affecting over 1 billion people worldwide. Identification of closely associated cardiometabolic conditions may be crucial for its early detection. The objective of this study was to identify factors associated with HTN and prehypertension (PHT) in an adult population sample from Maracaibo City, Venezuela. Methods: A randomized multi-staged sampling cross-sectional study was performed in 2230 individuals from Maracaibo City Metabolic Syndrome Prevalence Study database. PHT and HTN were defined according to JNC-7 criteria. Multiple logistic regression analysis was used to assess the main risk factors for each condition. Results: 52.6% (n=1172) of the subjects were female, the prevalence of HTN was 32% (n=714), while the prevalence of PHT was 31.1% (n=693). The main risk factors for HTN were age ≥60 years (odds ratio [OR]: 40.99; 95%CI: 16.94-99.19; p<0.001) and the local indigenous ethnic group (OR: 3.06; 95%...
Background: Insulin resistance (IR) evaluation is a fundamental goal in clinical and epidemiologi... more Background: 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 accordin...
Objetivo: Determinar el comportamiento de la presión arterial en niños de 9 a 16 años y comprobar... more Objetivo: Determinar el comportamiento de la presión arterial en niños de 9 a 16 años y comprobar si existe asociación entre la presencia de HTA con diversos factores considerados como posibles riesgos por la literatura. Material y método: Estudio de tipo no experimental, exploratorio, descriptivo y transversal. La muestra estuvo constituida por 109 alumnos de ambos sexos. La variable "presión arterial" se obtuvo mediante la técnica estandarizada de medición de presión arterial del Ministerio de Salud de Chile en dos ocasiones. Resultados: Se observaron alteraciones de la presión arterial en el 19,6 % del total con una cantidad de cuatro niños hipertensos, equivalente al 3,6 %. Discusión y conclusiones: No se encontró asociación entre los factores de riesgo estudiados y la HTA; lo anterior podría atribuirse a que probablemente estos factores actúan a largo plazo. Los datos sobre colesterol fueron obtenidos mediante una ficha encuesta, no por medio de exámenes de laboratorio, ya que la muestra obtenida fue pequeña.
Objective: High Blood Pressure (BP) is one of the principal cardiovascular risks. Nevertheless, i... more Objective: High Blood Pressure (BP) is one of the principal cardiovascular risks. Nevertheless, it is not included in the physical examination of people younger than 15 years old, which does not allow high BP early detection. The aim of the study is to determine the presence of elevated arterial blood pressure in children's from 9 to 16 years old, and to verify if there exists an association with risk factors considered by literature.
The constant changes in cancer cell bioenergetics are widely known as metabolic reprogramming. Re... more The 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 effect...
International Journal of Environmental Research and Public Health, 2021
Diabetes mellitus (DM) is considered one of the most massive epidemics of the twenty-first centur... more 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 yes-associated protein (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ)... more 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.
Diabetes Mellitus (DM) is an inflammatory clinical entity with different mechanisms involved in i... more 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 eati...
Currently, conventional therapies in cancer are improving; chemotherapy, radiotherapy and surgery... more Currently, conventional therapies in cancer are improving; chemotherapy, radiotherapy and surgery have increased survival significantly. New therapies have arisen with the same goal; immunotherapy has appeared as a promising option in the fight against cancer stimulating the immune system by inducing innate and adaptive responses. These responses include release of pro-inflammatory cytokines, making the immune system capable to eliminate or protect against multiple tumors. Nowadays, many of these therapies are being used in clinical settings, such as checkpoint inhibitors, monoclonal anti cytotoxic T-Lymphocyte associated protein 4 (CTL-4) and programmed death protein 1 (PD1), with inspiring results; however, they may decrease immunotolerance, limiting their use. At the same time, chemotherapy works by passive transport across the cell membrane, limiting its capacity to penetrate in tumor cells. For these reasons, bacteria employment represents one of the best candidates for cancer treatment. They can surpass these barriers with their selective colonization which also has an oncolytic effect by increasing proliferation and immunostimulation in the tumor environment. Attenuated strains, such as Mycobacterium bovis, Clostridium, Salmonella typhimirium and Listeria monocytogenes have been studied showing promising results in experimental models. However, their application in clinical trials has shown the need to maximize their therapeutic effect. Genetic engineering and synthetic biology are necessary to prove the scope that this novel approach has against cancer due to implications of cancer therapy and public health.
Background: A growing body of evidence suggests that cigarette smoking can cause the onset of met... more Background: 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 me...
Background: Hypertension (HTN) is a prominent cardiovascular risk factor, affecting over 1 billio... more Background: Hypertension (HTN) is a prominent cardiovascular risk factor, affecting over 1 billion people worldwide. Identification of closely associated cardiometabolic conditions may be crucial for its early detection. The objective of this study was to identify factors associated with HTN and prehypertension (PHT) in an adult population sample from Maracaibo City, Venezuela. Methods: A randomized multi-staged sampling cross-sectional study was performed in 2230 individuals from Maracaibo City Metabolic Syndrome Prevalence Study database. PHT and HTN were defined according to JNC-7 criteria. Multiple logistic regression analysis was used to assess the main risk factors for each condition. Results: 52.6% (n=1172) of the subjects were female, the prevalence of HTN was 32% (n=714), while the prevalence of PHT was 31.1% (n=693). The main risk factors for HTN were age ≥60 years (odds ratio [OR]: 40.99; 95%CI: 16.94-99.19; p<0.001) and the local indigenous ethnic group (OR: 3.06; 95%...
Background: Insulin resistance (IR) evaluation is a fundamental goal in clinical and epidemiologi... more Background: 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 accordin...
Objetivo: Determinar el comportamiento de la presión arterial en niños de 9 a 16 años y comprobar... more Objetivo: Determinar el comportamiento de la presión arterial en niños de 9 a 16 años y comprobar si existe asociación entre la presencia de HTA con diversos factores considerados como posibles riesgos por la literatura. Material y método: Estudio de tipo no experimental, exploratorio, descriptivo y transversal. La muestra estuvo constituida por 109 alumnos de ambos sexos. La variable "presión arterial" se obtuvo mediante la técnica estandarizada de medición de presión arterial del Ministerio de Salud de Chile en dos ocasiones. Resultados: Se observaron alteraciones de la presión arterial en el 19,6 % del total con una cantidad de cuatro niños hipertensos, equivalente al 3,6 %. Discusión y conclusiones: No se encontró asociación entre los factores de riesgo estudiados y la HTA; lo anterior podría atribuirse a que probablemente estos factores actúan a largo plazo. Los datos sobre colesterol fueron obtenidos mediante una ficha encuesta, no por medio de exámenes de laboratorio, ya que la muestra obtenida fue pequeña.
Objective: High Blood Pressure (BP) is one of the principal cardiovascular risks. Nevertheless, i... more Objective: High Blood Pressure (BP) is one of the principal cardiovascular risks. Nevertheless, it is not included in the physical examination of people younger than 15 years old, which does not allow high BP early detection. The aim of the study is to determine the presence of elevated arterial blood pressure in children's from 9 to 16 years old, and to verify if there exists an association with risk factors considered by literature.
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