Interplay between the Glymphatic System and the Endocannabinoid System: Implications for Brain Health and Disease.

The intricate mechanisms governing brain health and function have long been subjects of extensive investigation. Recent research has shed light on two pivotal systems, the glymphatic system and the endocannabinoid system, and their profound role within the central nervous system. The glymphatic system is a recently discovered waste clearance system within the brain that facilitates the efficient removal of toxic waste products and metabolites from the central nervous system. It relies on the unique properties of the brain's extracellular space and is primarily driven by cerebrospinal fluid and glial cells. Conversely, the endocannabinoid system, a multifaceted signaling network, is intricately involved in diverse physiological processes and has been associated with modulating synaptic plasticity, nociception, affective states, appetite regulation, and immune responses. This scientific review delves into the intricate interconnections between these two systems, exploring their combined influence on brain health and disease. By elucidating the synergistic effects of glymphatic function and endocannabinoid signaling, this review aims to deepen our understanding of their implications for neurological disorders, immune responses, and cognitive well-being.

La sucralosa promueve la polarización a macrófagos proinflamatorios M1

RESUMEN La sucralosa es un edulcorante no calórico de amplio consumo a nivel mundial, es considerado como un aditivo seguro, debido a que es eliminado en periodos cortos de tiempo. Recientemente se evidenció su bioacumulación en tejido adiposo, donde se encuentran inmersos macrófagos, células del sistema inmune involucradas en el desarrollo de la inflamación sistémica de bajo grado. A la fecha, no se cuenta con suficiente información para demostrar si los edulcorantes potencian los procesos inflamatorios alterando la función de células presentes en tejido y/o contribuyen en el desarrollo de patologías metabólicas. Por lo anterior, en nuestro trabajo se evaluó el efecto de la sucralosa en la viabilidad de los macrófagos diferenciados de la línea celular monocítica THP-1, por azul de tripán y ensayos de MTT, así como su efecto en la polarización M1/M2 por PCR según la expresión de IRF4, IRF5, STAT1, STAT6, perfil de expresión de IL-6, IL-12, TNF-α, TGF-β, IL-10 y SOCS3 por qPCR, y la cuantificación de la quimiocina IP-10 por ELISA. Los resultados indicaron que la sucralosa no tiene efectos citotóxicos, pero disminuye el número de células viables metabólicamente activas determinadas por MTT de manera dependiente de la concentración. La sucralosa incrementa la concentración de la quimiocina IP-10 y la expresión génica del factor de transcripción IRF5 y disminuye la expresión de IRF4 y STAT6, favoreciendo la polarización hacia poblaciones M1. La bioacumulación de sucralosa en tejido adiposo, y su interacción con macrófagos, podría inducir su polarización a M1.

ABSTRACT Sucralose is a non-nutritive sweetener widely consumed worldwide; it is considered a safe additive because it is eliminated quickly. Recently its bioaccumulation in adipose tissue was evidenced, where macrophages, cells of the immune system involved in developing low-grade systemic inflammation, are found. To date, there is a paucity of information regarding whether sweeteners potentiate inflammatory processes by altering the function of cells present in tissue and/or contribute to the development of metabolic pathologies. We evaluate the effect of sucralose on the viability of differentiated macrophages of the monocytic cell line THP-1, by trypan blue and MTT assays, respectively, as well as its effect on M1/ M2 by PCR according to the expression of IRF4, IRF5, STAT1, STAT6, expression profile of IL6, IL-12, TNF-α, TGF-β, IL-10 and SOCS3 by qPCR, and the quantification of the chemokine IP-10 by ELISE. The results indicated that sucralose has no cytotoxic effects but decreases the number of metabolically active viable cells determined by MTT of macrophages in a concentration-dependent manner. Sucralose increased the concentration of the chemokine IP-10 and the gene expression of the transcription factors IRF5 and decreased the expression of IRF4 and STAT 6 gene expression, favoring polarization towards M1 populations. The bioaccumulation of sucralose in adipose tissue, and its interaction with macrophages, could induce its polarization to M1.

Association of Total and High Molecular Weight Adiponectin with Components of Metabolic Syndrome in Mexican Children

Objective: Childhood obesity linked to metabolic alterations, tend to appear simultaneously with altered adipocytokines, suggesting a role in pathogenetic development. Low circulating level of total and high molecular weight (HMW) adiponectin have been associated with components of the metabolic syndrome (MetS) and could represent an independent risk factor with potential use as a biomarker. To examine the prevalence of MetS in Mexican school children and to investigate the association of total and HMW adiponectin levels with biochemical parameters related to MetS. Methods: The study included a population of boys and girls, from 8 to 11 years old. Anthropometric and biochemical parameters were evaluated according to weight and MetS status. A correlation analysis was fitted to establish an association between adiponectin concentrations and metabolic indicators. Results: One-hundred and fifty five children participated (59.4% females) from 8-11 years of age. The prevalence of MetS was of 10.3%. Impaired biochemical parameters, including total and HMW adiponectin, were associated with obesity. The adiponectin level was significantly lower in MetS than in non-MetS subjects (4.5 vs. 5.4 µg/mL). Total- but not HMW adiponectin concentration was negatively correlated with blood pressure, fasting insulin, fasting blood sugar and Homeostatic Model Assessment for Insulin Resistance. Conclusion: In young children, the total adiponectin level is associated with impaired biochemical parameters of carbohydrate metabolism and could be an excellent early predictor of metabolic complications.

Risk assessment of genetically modified crops for nutrition and health.

The risk assessment of genetically modified (GM) crops for human nutrition and health has not been systematic. Evaluations for each GM crop or trait have been conducted using different feeding periods, animal models, and parameters. The most common result is that GM and conventional sources induce similar nutritional performance and growth in animals. However, adverse microscopic and molecular effects of some GM foods in different organs or tissues have been reported. Diversity among the methods and results of the risk assessments reflects the complexity of the subject. While there are currently no standardized methods to evaluate the safety of GM foods, attempts towards harmonization are on the way. More scientific effort is necessary in order to build confidence in the evaluation and acceptance of GM foods.

Pancreatic response of rats fed genetically modified soybean.

Mice fed genetically modified (GM) soybean were not affected in nutritional performance, but pancreatic microscopic features were disturbed. The mechanisms for these contradictory findings are unknown. This study analysed the histology of acinar pancreatic cells and the expression of pancreatitis-associated protein (PAP) and trypsinogen mRNA in rats fed GM soy protein. Two bioassays were run, each one with 34 Wistar rats distributed into two groups fed with non-GM or GM-soy protein (18% protein) for 0, 1, 3, 5, 15 and 30 days. Nutritional evaluation, plasma amylase levels, pancreatic histological analysis and quantification of PAP and trypsinogen mRNAs levels using quantitative real-time RT-PCR were done. No differences in nutritional performance among rats fed non-GM and GM diets were found. The GM, but not the non-GM, diet induced zymogen-granule depletion after 15 days feeding, returning to normal levels after 30 days (P < 0.05). Acinar disorganization started as early as 5 days after initiation of the GM diet and it recovered after 30 days. Levels of PAP mRNA significantly increased in the GM diet between day 1 and day 3 and decreased to the basal level by day 15. Trypsinogen mRNA peaked at two different times; at day 1 and at day 15, decreasing to basal levels after 30 days. Plasma amylase levels remained unchanged at all times. This indicates that GM soy protein intake affected pancreas function, evidenced by the early acute PAP mRNA increased levels and pancreas cellular changes followed by recuperation of acinar cells after 30 days.