Metabolic Roles of HIF1, c-Myc, and p53 in Glioma Cells.

The metabolic reprogramming that promotes tumorigenesis in glioblastoma is induced by dynamic alterations in the hypoxic tumor microenvironment, as well as in transcriptional and signaling networks, which result in changes in global genetic expression. The signaling pathways PI3K/AKT/mTOR and RAS/RAF/MEK/ERK stimulate cell metabolism, either directly or indirectly, by modulating the transcriptional factors p53, HIF1, and c-Myc. The overexpression of HIF1 and c-Myc, master regulators of cellular metabolism, is a key contributor to the synthesis of bioenergetic molecules that mediate glioma cell transformation, proliferation, survival, migration, and invasion by modifying the transcription levels of key gene groups involved in metabolism. Meanwhile, the tumor-suppressing protein p53, which negatively regulates HIF1 and c-Myc, is often lost in glioblastoma. Alterations in this triad of transcriptional factors induce a metabolic shift in glioma cells that allows them to adapt and survive changes such as mutations, hypoxia, acidosis, the presence of reactive oxygen species, and nutrient deprivation, by modulating the activity and expression of signaling molecules, enzymes, metabolites, transporters, and regulators involved in glycolysis and glutamine metabolism, the pentose phosphate cycle, the tricarboxylic acid cycle, and oxidative phosphorylation, as well as the synthesis and degradation of fatty acids and nucleic acids. This review summarizes our current knowledge on the role of HIF1, c-Myc, and p53 in the genic regulatory network for metabolism in glioma cells, as well as potential therapeutic inhibitors of these factors.

Caracterización del bienestar en hogares mexicanos de niñas y niños con diarrea, Ensanut Continua 2022.

OBJETIVO: Analizar el nivel de bienestar en los hogares mexicanos de niñas y niños menores de cinco años que presentaron enfermedad diarreica aguda (EDA) en las últimas dos semanas en México, según la Encuesta Nacional de Salud y Nutrición Continua 2022 (Ensanut Continua 2022). Material y métodos. La encuesta se realizó entre julio y diciembre de 2022. Variable dependiente: ocurrencia de EDA. Variable independiente: nivel de bienestar de los hogares. Se realizó análisis bivariado y regresiones logísticas crudas y ajustadas. RESULTADOS: Se estima que 9.4% de los menores de cinco años presentaron EDA, de quienes 76.4% (IC95%: 69.0,82.5) pertenecía a hogares con nivel de bienestar bajo-medio. La EDA fue más frecuente en los niños y niñas de un año de edad (razón de momios ajustada [RMa] 3.00; IC95%: 1.76,5.11), en comparación con quienes tenían menor edad y en los hogares donde el agua para beber no es tratada (RMa 2.13; IC95%: 1.11,4.08). CONCLUSIONES: Se requiere fortalecer las medidas sanitarias preventivas de EDA en niñas y niños de un año de edad, principalmente implementar acciones para asegurar la disponibilidad de agua potable o el tratamiento adecuado para beberla, y planear, ejecutar y evaluar acciones de política pública integrales y multisectoriales para coadyuvar en garantizar el derecho humano a la salud durante la niñez.

Porcentaje de infección respiratoria aguda en menores de cinco años en México. Ensanut Continua 2022.

OBJETIVO: Estimar el porcentaje de infección respiratoria aguda (IRA) en menores de cinco años en las últimas dos semanas en México, de acuerdo con los datos de la Encuesta Nacional de Salud y Nutrición Continua 2022 (Ensanut Continua 2022). Material y métodos. Se analizaron datos de la Ensanut Continua 2022. RESULTADOS: El porcentaje de IRA fue de 27.6% (IC95%: 25.2,30.1). La prevalencia fue mayor en el primer tercil socioeconómico (44.1% [IC95%: 38.0,50.4]). El signo de alarma IRA más identificado fue "verse más enfermo" 33.0% (IC95%: 30.1,36.0) y el menos identificado fue "salir pus del oído" (1.5% [IC95%: 0.9,2.7]). CONCLUSIONES: Las IRA afectan cerca de una tercera parte de los niños y las niñas menores de cinco años en México, particularmente de los hogares con menores capacidades económicas. Es necesario fortalecer las estrategias de prevención, entre ellas la vacunación, el control y la promoción de la salud.

Porcentaje de enfermedad diarreica aguda en menores de cinco años en México. Ensanut Continua 2022.

OBJETIVO: Estimar el porcentaje de enfermedad diarreica aguda (EDA) en menores de cinco años en las últimas dos semanas, de acuerdo con los datos de la Encuesta Nacional de Salud y Nutrición Continua 2022. Material y métodos. Se analizaron los datos de menores de cinco años incluidos en la Encuesta Nacional de Salud y Nutrición Continua 2022 respecto a la EDA en las últimas dos semanas. Se compararon los datos con los de ediciones previas de la encuesta. RESULTADOS: El porcentaje de EDA en México fue de 9.4% (IC95%: 7.9,11.2), similar al de 2000, con diferencias por grupo etario. Durante el episodio de EDA, 38.7% (IC95%: 27.7,51.0) de las personas cuidadoras ofrecen menor cantidad de alimentos a la habitual. CONCLUSIONES: El elevado porcentaje de EDA en menores de cinco años en México en el 2022 evidencia la necesidad de fortalecer estrategias de prevención y promoción de la salud.

Vacunación en adultos y adultos mayores en México.

OBJETIVO: Estimar la prevalencia del antecedente de vacunación en adultos de 20 a 59 años y mayores de 60 años mediante autorreporte. Material y métodos. Análisis de datos obtenidos de la Encuesta Nacional de Salud y Nutrición 2022 (Ensanut 2022). RESULTADOS: El 27.4% de los adultos de 20-39 años refirió haber recibido vacuna doble viral (sarampión y rubeola [SR]) y 57.3% de adultos de 20-59 años cualquier vacuna con toxoide tetánico (Td) en los últimos diez años. En mujeres de 29 a 49 años, 18.7% (IC95%: 17.0,20.5) y 58.46% (IC95%: 56.2,60.7) habían sido vacunadas con vacuna SR y Td, respectivamente. En mayores de 60 años, 48.8% (IC95%: 45.9,51.7), 24.4% (IC95%: 22.2,26.8) y 49.1% (IC95%: 46.1,52.2) informaron haber recibido cualquier vacuna conteniendo Td, vacuna antineumococo y vacuna antiinfluenza estacional desde septiembre del año anterior a la encuesta, respectivamente. Conclusión. Los resultados de este estudio muestran que una proporción considerable de adultos, mujeres en edad fértil y adultos mayores no estaban protegidos contra enfermedades prevenibles por vacunación en 2022.

Role of Glycolytic and Glutamine Metabolism Reprogramming on the Proliferation, Invasion, and Apoptosis Resistance through Modulation of Signaling Pathways in Glioblastoma.

Glioma cells exhibit genetic and metabolic alterations that affect the deregulation of several cellular signal transduction pathways, including those related to glucose metabolism. Moreover, oncogenic signaling pathways induce the expression of metabolic genes, increasing the metabolic enzyme activities and thus the critical biosynthetic pathways to generate nucleotides, amino acids, and fatty acids, which provide energy and metabolic intermediates that are essential to accomplish the biosynthetic needs of glioma cells. In this review, we aim to explore how dysregulated metabolic enzymes and their metabolites from primary metabolism pathways in glioblastoma (GBM) such as glycolysis and glutaminolysis modulate anabolic and catabolic metabolic pathways as well as pro-oncogenic signaling and contribute to the formation, survival, growth, and malignancy of glioma cells. Also, we discuss promising therapeutic strategies by targeting the key players in metabolic regulation. Therefore, the knowledge of metabolic reprogramming is necessary to fully understand the biology of malignant gliomas to improve patient survival significantly.

Knowledge, attitudes, perceptions, and COVID-19 hesitancy in a large public university in Mexico city during the early vaccination rollout.

BACKGROUND: Vaccination against COVID-19 is a primary tool for controlling the pandemic. However, the spread of vaccine hesitancy constitutes a significant threat to reverse progress in preventing the disease. Studies conducted in Mexico have revealed that vaccination intention in Mexico among the general population ranges from 62 to 82%. OBJECTIVE: To know the prevalence of COVID-19 vaccine hesitancy and associated factors among academics, students, and administrative personnel of a public university in Mexico City. METHODS: We administered an online survey investigating sociodemographic aspects, knowledge, attitudes, practices, and acceptance/hesitancy regarding the COVID-19 vaccine. Using generalized linear Poisson models, we analyzed factors associated with vaccine hesitancy, defined as not intending to be vaccinated within the following six months or refusing vaccination. RESULTS: During May and June 2021, we studied 840 people, prevalence of vaccine hesitancy was 6%. Hesitancy was significantly associated with fear of adverse effects, distrust of physician's recommendations, lack of knowledge regarding handwashing, age younger than 40 years, refusal to use face masks, and not having received influenza vaccination during the two previous seasons. CONCLUSIONS: Vaccine hesitancy in this population is low. Furthermore, our results allowed us the identification of characteristics that can improve vaccine promotion.

Crosstalk of the Wnt/ß-Catenin Signaling Pathway in the Induction of Apoptosis on Cancer Cells.

The Wnt/ß-catenin signaling pathway plays a major role in cell survival and proliferation, as well as in angiogenesis, migration, invasion, metastasis, and stem cell renewal in various cancer types. However, the modulation (either up- or downregulation) of this pathway can inhibit cell proliferation and apoptosis both through ß-catenin-dependent and independent mechanisms, and by crosstalk with other signaling pathways in a wide range of malignant tumors. Existing studies have reported conflicting results, indicating that the Wnt signaling can have both oncogenic and tumor-suppressing roles, depending on the cellular context. This review summarizes the available information on the role of the Wnt/ß-catenin pathway and its crosstalk with other signaling pathways in apoptosis induction in cancer cells and presents a modified dual-signal model for the function of ß-catenin. Understanding the proapoptotic mechanisms induced by the Wnt/ß-catenin pathway could open new therapeutic opportunities.

Anti-proliferative, pro-apoptotic and anti-invasive effect of the copper coordination compound Cas III-La through the induction of reactive oxygen species and regulation of Wnt/ß-catenin pathway in glioma.

Gliomas are the most aggressive neoplasms that affect the central nervous system, being glioblastoma multiforme (GBM) the most malignant. The resistance of GBM to therapies is attributed to its high rate of cell proliferation, angiogenesis, invasion, and resistance to apoptosis; thus, finding alternative therapeutic approaches is vital. In this work, the anti-proliferative, pro-apoptotic, and anti-invasive effect of the copper coordination compound Casiopeina III-La (Cas III-La) on human U373 MG cells was determined in vitro and in vivo. Our results indicate that Cas III-La exerts an anti-proliferative effect, promoting apoptotic cell death and inactivating the invasive process by generating reactive oxygen species (ROS), inactivating GSK3ß, activating JNK and ERK, and promoting the nuclear accumulation of ß-catenin. The inhibition of ROS generation by N-acetyl-l-cysteine not only recovered cell migration and viability, but also reduced ß-catenin accumulation and JNK and ERK activation. Additionally, Cas III-La significantly reduced tumor volume, cell proliferation and mitotic indices, and increased the apoptotic index in mice xenotransplanted with U373 glioma cells. Thus, Cas III-La is a promising agent to treat GBM.

Autophagy as a Potential Therapy for Malignant Glioma.

Glioma is the most frequent and aggressive type of brain neoplasm, being anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM), its most malignant forms. The survival rate in patients with these neoplasms is 15 months after diagnosis, despite a diversity of treatments, including surgery, radiation, chemotherapy, and immunotherapy. The resistance of GBM to various therapies is due to a highly mutated genome; these genetic changes induce a de-regulation of several signaling pathways and result in higher cell proliferation rates, angiogenesis, invasion, and a marked resistance to apoptosis; this latter trait is a hallmark of highly invasive tumor cells, such as glioma cells. Due to a defective apoptosis in gliomas, induced autophagic death can be an alternative to remove tumor cells. Paradoxically, however, autophagy in cancer can promote either a cell death or survival. Modulating the autophagic pathway as a death mechanism for cancer cells has prompted the use of both inhibitors and autophagy inducers. The autophagic process, either as a cancer suppressing or inducing mechanism in high-grade gliomas is discussed in this review, along with therapeutic approaches to inhibit or induce autophagy in pre-clinical and clinical studies, aiming to increase the efficiency of conventional treatments to remove glioma neoplastic cells.

Autophagic and Apoptotic Pathways as Targets for Chemotherapy in Glioblastoma.

Glioblastoma multiforme is the most malignant and aggressive type of brain tumor, with a mean life expectancy of less than 15 months. This is due in part to the high resistance to apoptosis and moderate resistant to autophagic cell death in glioblastoma cells, and to the poor therapeutic response to conventional therapies. Autophagic cell death represents an alternative mechanism to overcome the resistance of glioblastoma to pro-apoptosis-related therapies. Nevertheless, apoptosis induction plays a major conceptual role in several experimental studies to develop novel therapies against brain tumors. In this review, we outline the different components of the apoptotic and autophagic pathways and explore the mechanisms of resistance to these cell death pathways in glioblastoma cells. Finally, we discuss drugs with clinical and preclinical use that interfere with the mechanisms of survival, proliferation, angiogenesis, migration, invasion, and cell death of malignant cells, favoring the induction of apoptosis and autophagy, or the inhibition of the latter leading to cell death, as well as their therapeutic potential in glioma, and examine new perspectives in this promising research field.

Multiple molecular and cellular mechanisms of action of lycopene in cancer inhibition.

Epidemiological studies suggest that including fruits, vegetables, and whole grains in regular dietary intake might prevent and reverse cellular carcinogenesis, reducing the incidence of primary tumours. Bioactive components present in food can simultaneously modulate more than one carcinogenic process, including cancer metabolism, hormonal balance, transcriptional activity, cell-cycle control, apoptosis, inflammation, angiogenesis and metastasis. Some studies have shown an inverse correlation between a diet rich in fruits, vegetables, and carotenoids and a low incidence of different types of cancer. Lycopene, the predominant carotenoid found in tomatoes, exhibits a high antioxidant capacity and has been shown to prevent cancer, as evidenced by clinical trials and studies in cell culture and animal models. In vitro studies have shown that lycopene treatment can selectively arrest cell growth and induce apoptosis in cancer cells without affecting normal cells. In vivo studies have revealed that lycopene treatment inhibits tumour growth in the liver, lung, prostate, breast, and colon. Clinical studies have shown that lycopene protects against prostate cancer. One of the main challenges in cancer prevention is the integration of new molecular findings into clinical practice. Thus, the identification of molecular biomarkers associated with lycopene levels is essential for improving our understanding of the mechanisms underlying its antineoplastic activity.

Antiapoptotic Effects of EGb 761.

Ginkgo biloba extracts have long been used in Chinese traditional medicine for hundreds of years. The most significant extract obtained from Ginkgo biloba leaves has been EGb 761, a widely used phytopharmaceutical product in Europe. EGb 761 is a well-defined mixture of active compounds, which contains two main active substances: flavonoid glycosides (24-26%) and terpene lactones (6-8%). These compounds have shown antiapoptotic effects through the protection of mitochondrial membrane integrity, inhibition of mitochondrial cytochrome c release, enhancement of antiapoptotic protein transcription, and reduction of caspase transcription and DNA fragmentation. Other effects include the reduction of oxidative stress (which has been related to the occurrence of vascular, degenerative, and proliferative diseases), coupled to strong induction of phase II-detoxifying and cellular defense enzymes by Nrf2/ARE activation, in addition to the modulation of transcription factors, such as CREB, HIF-1 α , NF- κ B, AP-1, and p53, involved in the apoptosis process. This work reviews experimental results about the antiapoptotic effects induced by the standardized extract of Ginkgo biloba leaves (EGb 761).

Copper compound induces autophagy and apoptosis of glioma cells by reactive oxygen species and JNK activation.

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive of the primary brain tumors, with a grim prognosis despite intensive treatment. In the past decades, progress in research has not significantly increased overall survival rate. METHODS: The in vitro antineoplastic effect and mechanism of action of Casiopeina III-ia (Cas III-ia), a copper compound, on rat malignant glioma C6 cells was investigated. RESULTS: Cas III-ia significantly inhibited cell proliferation, inducing autophagy and apoptosis, which correlated with the formation of autophagic vacuoles, overexpression of LC3, Beclin 1, Atg 7, Bax and Bid proteins. A decrease was detected in the mitochondrial membrane potential and in the activity of caspase 3 and 8, together with the generation of intracellular reactive oxygen species (ROS) and increased activity of c-jun NH(2)-terminal kinase (JNK). The presence of 3-methyladenine (as selective autophagy inhibitor) increased the antineoplastic effect of Cas III-ia, while Z-VAD-FMK only showed partial protection from the antineoplastic effect induced by Cas III-ia, and ROS antioxidants (N-acetylcysteine) decreased apoptosis, autophagy and JNK activity. Moreover, the JNK -specific inhibitor SP600125 prevented Cas III-ia-induced cell death. CONCLUSIONS: Our data suggest that Cas III-ia induces cell death by autophagy and apoptosis, in part due to the activation of ROS -dependent JNK signaling. These findings support further studies of Cas III-ia as candidate for treatment of human malignant glioma.