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Smoking globally kills over half of long-term smokers and causes about 7 million annual deaths. The World Health Organization Framework Convention for Tobacco Control (FCTC) is the main global policy strategy to combat smoking, but its effectiveness is uncertain. Our interrupted time series analyses compared before- and after-FCTC trends in the numbers and prevalence of smokers below the age of 25 years (when smoking initiation occurs and during which response to interventions is greatest) and on cessation at 45-59 years (when quitting probably occurs) in 170 countries, excluding China. Contrasting the 10 years after FCTC ratification with the income-specific before-FCTC trends, we observed cumulative decreases of 15.5% (95% confidence interval = -33.2 to -0.7) for the numbers of current smokers and decreases of -7.5% (95% CI = -10.6 to -4.5) for the prevalence of smoking below age 25 years. The quit ratio (comparing the numbers of former and ever smokers) at 45-59 years increased by 1.8% (1.2 to 2.3) 10 years after FCTC ratification. Countries raising taxes by at least 10 percentage points concurrent with ratification observed steeper decreases in all three outcomes than countries that did not. Over a decade across 170 countries, the FCTC was associated with 24 million fewer young smokers and 2 million more quitters.

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INTRODUCTION: The tobacco industry claims that tobacco taxes are responsible for increased illicit trade in Chile, which they estimated at 37% in 2022. However, the evolution of cigarette consumption, estimated from population surveys, and of tax-paying cigarettes shows a decreasing penetration of illicit trade since 2018. METHODS: A gap analysis was used to estimate the evolution of illicit trade based on an arithmetic identity stating that total national cigarette consumption over a given period is equal to the registered consumption as paying taxes plus the cigarettes that are consumed nationally without paying taxes. RESULTS: Illicit trade penetration in Chile was around 10% in 2020, less than half of what the tobacco industry claimed. In addition, the evolution of real prices of cigarettes, calculated using tax collection data, indicates that real prices net of tobacco taxes increased significantly during 2015-2021, a period with no changes in tobacco taxation. The cheapest cigarettes, presumably competing with illicit cigarettes, registered the most significant price increase. CONCLUSIONS: Claims of increasing illicit trade penetration in Chile are unfounded and are not supported by data on consumption and tax-paying cigarettes.

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Store-operated calcium entry (SOCE) is an important process in calcium signaling. Its role in physiological and pathological events is well recognized. However, in cancerous systems, the importance of SOCE in relation to the degree of cancer aggressiveness, as well as its regulation by ligands such as purinergic molecules, are not well documented. This study aimed to characterize a differential effect of the P2Y2 receptor (promoted by UTP of 10 µM and inhibited by ARC118925XX of 1 µM) on intracellular calcium response between metastatic (SKOV-3) and non-metastatic (CAOV-3) ovarian cell lines in conditions of normal (1.5 mM) and zero extracellular calcium concentration. The sustained calcium influx observed exclusively in SKOV-3 cells was associated with the presence of SOCE (promoted by thapsigargin (74.81 ± 0.94 ΔF) and sensitive to 2-APB (20.60 ± 0.85 ΔF)), whereas its absence in CAOV-3 cells (26.2 ± 6.1 ΔF) was correlated with a low expression of ORAI1. The relevance of SOCE in metastatic SKOV-3 cells was further corroborated when 2-APB significantly inhibited (40.4 ± 2.8% of covered area) UTP-induced cell migration (54.6 ± 3.7% of covered area). In conclusion, our data suggest that SOCE activation elicited by the P2Y2 receptor is involved in the aggressiveness of ovarian cancer cells.

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Reactive oxygen species (ROS) are intimately linked to bioenergetics and redox biology, contributing to cellular functioning and physiological signaling, but also acting as toxic agents during oxidative stress. Hence, the balance between pro-oxidant reactions and the activity of antioxidant defenses sustains a basal oxidative status, controls the increase of redox signaling, and mediates potential pathological events during oxidative stress. Maternal experience, especially during nursing, requires high energetic demands and expenditure to ensure the well-being of the offspring. The mother must adapt from satisfying her own needs to additionally fulfilling those of her descendants. Oxidative stress has been proposed as one of the reproductive trade-off hallmarks. However, the oxidative shielding hypothesis has also been proposed in the context of reproduction. The reproductive experience induces a wide range of well-documented changes in the female brain, which potentially lead to protection against the enhanced oxidative activity. To date, the metabolic and cellular mechanisms that underlie lactation-induced neuroprotection against oxidants are unknown. The neuroendocrine changes in the brain of the lactating dam promote diminished propensity to excitotoxic brain injury and stress, as well as enhanced neuroprotection and plasticity. In addition to review studies on the oxidant balance due to motherhood, we included new data from our laboratory, addressing the importance of measuring pro-oxidant reactions in separated brain regions. The hippocampus of lactating rats exhibits lower levels of pro-oxidant reactions than that of virgin rats, supporting the oxidative shielding hypothesis in lactation.

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Glutamate is one of the most abundant amino acids in the blood. Besides its role as a neurotransmitter in the brain, it is a key substrate in several metabolic pathways and a primary messenger that acts through its receptors outside the central nervous system (CNS). The two main types of glutamate receptors, ionotropic and metabotropic, are well characterized in CNS and have been recently analyzed for their roles in non-neural organs. Glutamate receptor expression may be particularly important for tumor growth in organs with high concentrations of glutamate and might also influence the propensity of such tumors to set metastases in glutamate-rich organs, such as the liver. The study of glutamate transporters has also acquired relevance in the physiology and pathologies outside the CNS, especially in the field of cancer research. In this review, we address the recent findings about the expression of glutamatergic system components, such as receptors and transporters, their role in the physiology and pathology of cancer in non-neural organs, and their possible use as biomarkers and therapeutic targets.

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Introducción: Los tumores apendiculares representan aproximadamente 1% de los tumores malignos del intestino grueso. Más del 50% de las neoplasias primarias del apéndice se manifiestan inicialmente como apendicitis aguda. Métodos: Se reporta caso de paciente masculino que presentó adenocarcinoma invasor en biopsia de pieza quirúrgica de apéndice cecal tras apendicectomía, tomando la decisión de realizar hemicolectomía derecha laparoscópica diferida. Discusión: En este caso y como en la mayoría de los reportes de la bibliografía mundial, el adenocarcinoma simula un cuadro de AA. En un metaanálisis y una revisión sistemática de 2.771 pacientes diagnosticados de masa apendicular inflamatoria (flemón o absceso), Andersson et al. encontró 31 con tumores malignos. Estas lesiones se detectan en el 0,9% al 1,4% de las apendicectomías realizadas para tratar la AA. Conclusión: Este subtipo histológico presenta mayor incidencia de metástasis en los ganglios linfáticos y la supervivencia global era del 47,5%. Es por ello por lo que abogamos por la resección colónica como tratamiento definitivo del adenocarcinoma de apéndice cecal.

INTRODUCTION: Appendulular tumors represent approximately 1% of malignant tumors of the large intestine. More than 50% of the primary neoplasms of the appendix initially manifest as acute appendicitis. Methods: Men's patient who presented invading adenocarcinoma in Cecal Appendix Surgical Party Biopsy after appendectomy, making the decision to perform deferred laparoscopic right hemicolectomy, is reported. Discussion: In this case and as in most world literature reports, adenocarcinoma simulates an AA picture. In a meta -analysis and a systematic review of 2,771 diagnosed patients of inflammatory appendicular mass (phlegmon or abscess), Andersson et al. He found 31 with malignant tumors. These lesions are detected at 0.9% to 1.4% of appendectomies made to treat the AA. Conclusion: This histological subtype has a greater incidence of metastasis in lymph nodes and global survival was 47.5%. That is why we advocate colonic resection as a definitive treatment of cecal appendix adenocarcinoma.

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Resumen La intususcepción intestinal es la invaginación de un segmento de intestino en el interior de otro segmento inmediato, asociado a una alteración en la pared intestinal, siendo en intestino delgado más común por patologías benignas y en intestino grueso por patologías malignas. Presentamos caso de paciente femenino de 30 años, con dolor abdominal de 1 semana de evolución y datos de oclusión intestinal, se somete a laparotomía de urgencia, donde se encuentra intususcepción intestinal en íleon terminal. La intususcepción intestinal generalmente se va a presentar como un cuadro de obstrucción intestinal. El tratamiento es la resección del segmento afectado.

Abstract The intestinal intussusception is the invagination of one segment of the bowel into an immediately adjacent segment, associated to an alteration into the wall, the small intestinal is the most associated a benign pathology and large intestinal by malignant pathologies. We present the case of a 30-year-old female patient, who came to the emergency room due to intense abdominal pain of 1 week of evolution and evidence of intestinal occlusion, who underwent emergency laparotomy, where intestinal intussusception was found in the terminal ileum. Generally, the clinical presentation like an intestinal obstruction. Treatment is resection of the affected segment.

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BACKGROUND/AIM: During pregnancy, maternal liver can be affected by ethanol (ETOH) intake, whose effects depend on concentration levels ingested. This study aims to describe histological and serum marker characteristics of maternal liver during two metabolic conditions: gestation (G), and sustained ETOH intake, in early and late pregnancy. MATERIALS AND METHODS: Wistar rats were fed with Lieber-DeCarli diet during pregnancy, following an experimental protocol that allows a semi-chronic intake of ETOH (5%). Liver and serum samples were processed for histological characterization and biochemical profiling. Hematoxylin/eosin and Schiff's Periodic Acid staining were used. RESULTS: During pregnancy, a significant elevation in ballooned and edamatous hepatocytes, and a significant increase in micro and macrovesicular deposits were observed in rats fed with the ETOH diet at gestation days 3G, 8G and 15G. These changes were reverted by 20G. Liver glycogen content increased significantly at 15G. Serum metabolites in pregnant rats fed with the ETOH diet showed a significant reduction in urea (from 3G to 15G), an increase in albumin and uric acid at 20G, and a reduction in creatinine. Number of offsprings and weight of male newborns were reduced by 20% and 14%, respectively. Liver function markers in serum showed no significant changes. CONCLUSION: ETOH diet intake promotes hepatic histological changes and histological modifications during pregnancy. These results support the assumption that pregnancy is an adaptive procedure that is associated with nutritional conditions and has a strong influence on hepatic histology. They suggest that pregnancy promotes a state of resilience to the liver function during the sustained intake of 5% ETOH.

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The mouse N. alstoni spontaneously develops the condition of obesity in captivity when fed regular chow. We aim to study the differences in metabolic performance and thermoregulation between adult lean and obese male mice. The experimental approach included indirect calorimetry using metabolic cages for VO2 intake and VCO2 production. In contrast, the body temperature was measured and analyzed using intraperitoneal data loggers. It was correlated with the relative presence of UCP1 protein and its gene expression from interscapular adipose tissue (iBAT). We also explored in this tissue the relative presence of Tyrosine Hydroxylase (TH) protein, the rate-limiting enzyme for catecholamine biosynthesis present in iBAT. Results indicate that obese mice show a daily rhythm persists in estimated parameters but with differences in amplitude and profile. Obese mice presented lower body temperature, and a low caloric expenditure, together with lower VO2 intake and VCO2 than lean mice. Also, obese mice present a reduced thermoregulatory response after a cold pulse. Results are correlated with a low relative presence of TH and UCP1 protein. However, qPCR analysis of Ucp1 presents an increase in gene expression in iBAT. Histology showed a reduced amount of brown adipocytes in BAT. The aforementioned indicates that the daily rhythm in aerobic metabolism, thermoregulation, and body temperature control have reduced amplitude in obese mice Neotomodon alstoni.

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Inflammation mediated by the innate immune system is a physiopathological response to diverse detrimental circumstances such as microbe infections or tissular damage. The molecular events that underlie this response involve the assembly of multiprotein complexes known as inflammasomes. These assemblages are essentially formed by a stressor-sensing protein, an adapter protein and a non-apoptotic caspase (1 or 11). The coordinated aggregation of these components mediates the processing and release of pro-inflammatory interleukins (IL-ß and IL-18) and cellular death by pyroptosis induction. The inflammatory response is essential for the defense of the organism; for example, it triggers tissue repair and the destruction of pathogen microbe infections. However, when inflammation is activated chronically, it promotes diverse pathologies in the lung, liver, brain and other organs. The nervous system is one of the main tissues where the inflammatory process has been characterized, and its implications in health and disease are starting to be understood. Thus, the regulation of inflammasomes in specific cellular types of the central nervous system needs to be thoroughly understood to innovate treatments for diverse pathologies. In this review, the presence and participation of inflammasomes in pathological conditions in different types of glial cells will be discussed.

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The purinergic system is fundamental in the tumor microenvironment, since it regulates tumor cell interactions with the immune system, as well as growth and differentiation in autocrine-paracrine responses. Here, we investigated the role of the adenosine A2B receptor (A2BR) in ovarian carcinoma-derived cells' (OCDC) properties. From public databases, we documented that high A2BR expression is associated with a better prognostic outcome in ovarian cancer patients. In vitro experiments were performed on SKOV-3 cell line to understand how A2BR regulates the carcinoma cell phenotype associated with cell migration. RT-PCR and Western blotting revealed that the ADORA2B transcript (coding for A2BR) and A2BR were expressed in SKOV-3 cells. Stimulation with BAY-606583, an A2BR agonist, induced ERK1/2 phosphorylation, which was abolished by the antagonist PSB-603. Pharmacological activation of A2BR reduced cell migration and actin stress fibers; in agreement, A2BR knockdown increased migration and enhanced actin stress fiber expression. Furthermore, the expression of E-cadherin, an epithelial marker, increased in BAY-606583-treated cells. Finally, cDNA microarrays revealed the pathways mediating the effects of A2BR activation on SKOV-3 cells. Our results showed that A2BR contributed to maintaining an epithelial-like phenotype in OCDC and highlighted this purinergic receptor as a potential biomarker.

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Background: Low Protein-High Carbohydrate (LPHC) diet during pregnancy is considered a nutritional and health problem related to the development of maternal metabolic alterations, such as fatty liver and obesity in the perinatal and postnatal period. It is known that increase in visceral adiposity tissue (VAT) modulates maternal metabolic rate, with the respiratory quotient (RQ) being a parameter related to that variable; however, it is unknown whether LPHC intake during pregnancy affects the VAT and the RQ. In this study, we examine if consumption of LPHC during pregnancy modifies the VAT and RQ in early and late periods of pregnancy. Methods: This is a longitudinal and cross-sectional study with Wistar rats during gestation (G) (3, 8, 15, and 20) and nonpregnant rats. Rats were fed with a control diet with 63/18% carbohydrate/protein and an experimental diet with 79/6% carbohydrate/protein. We studied water and food consumption and metabolic parameters such as RQ and energy expenditure (EE), calculated by indirect calorimetry. In the cross-sectional study, we determined visceral fat, as well as the concentration of free fatty acids, insulin, glucose, and lipid profile in serum. Results: Nonpregnant rats with LPHC intake decreased significantly in VAT (86%) and the RQ (18%); in pregnant rats in early (8G) and late pregnancy (15G) in LPHC diet, both parameters (VAT and RQ) (25%-92%) increased during light time. When comparing time points during pregnancy in the control and LPHC groups, the RQ increased in 15G during daytime compared to 8G during the night period (17 and 5%, respectively). In late pregnancy, LPHC intake and triacylglyceride levels increased and cholesterol and glucose decreased (45 and 26%, respectively), in comparison to nonpregnant rats. Conclusions: LPHC intake in nonpregnant rats decreases the RQ and VAT. Interestingly, the opposite occurs in early pregnancy: the RQ and VAT increased, and this correlates with free fatty acid (FFA) levels. The increase in RQ and VAT during light time in early pregnancy increased mobilization of carbohydrate and protein metabolism. These results suggest that LPHC intake during pregnancy increases the glucose metabolism as a compensatory mechanism for energy needs in the fetus and the mother in early pregnancy.

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Anorexia nervosa (AN) is an eating disorder characterized by self-starvation and excessive weight loss with a notorious prevalence in young women. The neurobiology of AN is unknown but murine models, like dehydration induced anorexia (DIA), reproduce weight loss and avoidance of food despite its availability. Astrocytes are known to provide homeostatic support to neurons, but it is little explored if anorexia affects this function. In this study, we tested if DIA disrupts glutamate-glutamine homeostasis associated with astrocytes in the prefrontal cortex (PFC) of young female rats. Our results showed that anorexia reduced the redox state, as well as endogenous glutamate and glutamine. These effects correlated with a reduced expression of the glutamate transporters (GLT-1 and GLAST) and glutamine synthetase, all of them are preferentially expressed by astrocytes. Accordingly, the expression of GFAP was reduced. Anorexia reduced the astrocyte density, promoted a de-ramified morphology, and augmented the de-ramified/ramified astrocyte ratio in the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC), but not in the motor cortex (M2). The increase of a de-ramified phenotype correlated with increased expression of vimentin and nestin. Based on these results, we conclude that anorexia disrupts glutamate-glutamine homeostasis and the redox state associated with astrocyte dysfunction.

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We have developed and characterized a model of isoproterenol (ISO)-induced myocardial necrosis, identifying three stages of cardiac damage: a pre-infarction (0-12 h), infarction (24 h), and post-infarction period (48-96 h). Using this model, we have previously found alterations in calcium homeostasis and their relationship with oxidant stress in mitochondria, which showed deficient oxygen consumption and coupled ATP synthesis. Therefore, the present study was aimed at assessing the mitochondrial ability to transport and oxidize cytoplasmic reducing equivalents (NADH), correlating the kinetic parameters of the malate-aspartate shuttle, oxidant stress, and mitochondrial functionality. Our results showed only discreet effects during the cardiotoxic ISO action on the endogenous malate-aspartate shuttle activity, suggesting that endogenous mitochondrial NADH oxidation capacity (Nohl dehydrogenase) was not affected by the cellular stress. On the contrary, the reconstituted system showed significant enhancement in maximal capacity of the malate-aspartate shuttle activity only at later times (post-infarction period), probably as a compensatory part of cardiomyocytes' response to the metabolic and functional consequences of the infarcted tissue. Therefore, these findings support the notion that heart damage associated with myocardial infarction suffers a set of sequential biochemical and metabolic modifications within cardiomyocytes, where mitochondrial activity, controlling the redox state, could play a relevant role.

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The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that heterodimerizes with the AhR nuclear translocator (ARNT) to modulate CYP1A1 expression, a gene involved in the biotransformation of benzo[a]pyrene (BaP). The AhR pathway shows daily variations under the control of the circadian timing system. Daytime restricted feeding (DRF) entrains the expression of genes involved in the processing of nutrients and xenobiotics to food availability. Therefore, we evaluate if temporal AhR, ARNT, and CYP1A1 hepatic expression in rats are due to light/dark cycles or fasting/feeding cycles promoted by DRF. Our results show that AhR oscillates throughout the 24 h period in DRF and ad libitum feeding rats (ALF), showing maximum expression at the same time points. DRF modified the peak of ARNT expression at ZT5; meanwhile, ALF animals showed a peak of maximum expression at ZT17. An increased expression of CYP1A1 was linked to the meal time in both groups of animals. Although a high CYP1A1 expression has been previously associated with BaP genotoxicity, our results show that, compared with the ALF group, DRF attenuated the BaP-CYP1A1 induction potency, the liver DNA-BaP adducts, the liver concentration of unmetabolized BaP, and the blood aspartate aminotransferase and alanine aminotransferase activities when BaP is administered prior to the acrophase of CYP1A1 expression. These results demonstrate that DRF modifies the ARNT and CYP1A1 expression and protects from BaP toxicity.

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The episodes of cerebral dysfunction, known as encephalopathy, are usually coincident with liver failure. The primary metabolic marker of liver diseases is the increase in blood ammonium, which promotes neuronal damage. In the present project, we used an experimental model of hepatic encephalopathy in male rats by portacaval anastomosis (PCA) surgery. Sham rats had a false operation. After 13 weeks of surgery, the most distinctive finding was vacuolar/spongiform neurodegeneration exclusively in the molecular layer of the cerebellum. This cerebellar damage was further characterized by metabolic, histopathological, and behavioral approaches. The results were as follows: (a) Cellular alterations, namely loss of Purkinje cells, morphological changes, such as swelling of astrocytes and Bergmann glia, and activation of microglia; (b) Cytotoxic edema, shown by an increase in aquaporin-4 and N-acetylaspartate and a reduction in taurine and choline-derivate osmolytes; (c) Metabolic adjustments, noted by the elevation of circulating ammonium, enhanced presence of glutamine synthetase, and increase in glutamine and creatine/phosphocreatine; (d) Inflammasome activation, detected by the elevation of the marker NLRP3 and microglial activation; (e) Locomotor deficits in PCA rats as assessed by the Rotarod and open field tests. These results lead us to suggest that metabolic disturbances associated with PCA can generate the cerebellar damage that is similar to morphophysiological modifications observed in amyloidogenic disorders. In conclusion, we have characterized a distinctive cerebellar multi-disruption accompanied by high levels of ammonium and associated with spongiform neurodegeneration in a model of hepatic hypofunctioning.

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BACKGROUND & AIMS: Evening chronotype has been linked with obesity, diabetes and metabolic syndrome (MetS) in middle-aged and older adults. However, few studies have analyzed this association in young adults. The aim of this study was to assess potential associations between individual chronotype and cardiometabolic outcomes in young adults of two independent populations from Europe and America. METHODS: Total population comprised 2 223 young adults (18-29 years old), 525 from Spain (Europe) and 1 698 from Mexico (America). Anthropometric, body composition and biochemical analyses were performed. Circadian preference was determined using the Morningness-Eveningness Questionnaire (MEQ). RESULTS: In these two young adult populations, a higher metabolic risk was found in those individuals with evening chronotypes, whereas those with neither or morning chronotypes showed lower cardiometabolic risk. Evening chronotypes showed lipid alterations with increased levels of triglycerides in both populations, VLDL-c in Spaniards and total cholesterol and LDL-c in Mexicans. Among the Mexican population, evening chronotypes showed higher MetS risk and more obesity traits than the other two chronotypes; no significant differences for the same comparison were found among the equivalent Spanish chronotypes. Evening chronotypes showed lower carbohydrates and higher fat intake in Spaniards, while they had lower fiber intake in Mexicans. The associations between MEQ score and cardiometabolic risk were independent of the dietary characteristics. Lifestyle factors differed among chronotypes with more smokers and habitual drinkers among evening chronotypes than in neither or morning chronotypes (P < 0.05). CONCLUSIONS: This study performed in two American and European independent populations shows that even in apparently healthy young adults, evening chronotypes have increased cardiometabolic risk and lipid alterations as compared to neither or morning chronotypes.

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Cancer is a complex expression of an altered state of cellular differentiation associated with severe clinical repercussions. The effort to characterize this pathological entity to understand its underlying mechanisms and visualize potential therapeutic strategies has been constant. In this context, some cellular (enhanced duplication, immunological evasion), metabolic (aerobic glycolysis, failure in DNA repair mechanisms) and physiological (circadian disruption) parameters have been considered as cancer hallmarks. The list of these hallmarks has been growing in recent years, since it has been demonstrated that various physiological systems misfunction in well-characterized ways upon the onset and establishment of the carcinogenic process. This is the case with the purinergic system, a signaling pathway formed by nucleotides/nucleosides (mainly adenosine triphosphate (ATP), adenosine (ADO) and uridine triphosphate (UTP)) with their corresponding membrane receptors and defined transduction mechanisms. The dynamic equilibrium between ATP and ADO, which is accomplished by the presence and regulation of a set of ectonucleotidases, defines the pro-carcinogenic or anti-cancerous final outline in tumors and cancer cell lines. So far, the purinergic system has been recognized as a potential therapeutic target in cancerous and tumoral ailments.

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