NLRP3 Contributes to Sarcopenia Associated to Dependency Recapitulating Inflammatory-Associated Muscle Degeneration.

Sarcopenia, a complex and debilitating condition characterized by progressive deterioration of skeletal muscle, is the primary cause of age-associated disability and significantly impacts healthspan in elderly patients. Despite its prevalence among the aging population, the underlying molecular mechanisms are still under investigation. The NLRP3 inflammasome is crucial in the innate immune response and has a significant impact on diseases related to inflammation and aging. Here, we investigated the expression of the NLRP3 inflammasome pathway and pro-inflammatory cytokines in skeletal muscle and peripheral blood of dependent and independent patients who underwent hip surgery. Patients were categorized into independent and dependent individuals based on their Barthel Index. The expression of NLRP3 inflammasome components was significantly upregulated in sarcopenic muscle from dependent patients, accompanied by higher levels of Caspase-1, IL-1ß and IL-6. Among older dependent individuals with sarcopenia, there was a significant increase in the MYH3/MYH2 ratio, indicating a transcriptional shift in expression from mature to developmental myosin isoforms. Creatine kinase levels and senescence markers were also higher in dependent patients, altogether resembling dystrophic diseases and indicating muscle degeneration. In summary, we present evidence for the involvement of the NLRP3/ASC/NEK7/Caspase-1 inflammasome pathway with activation of pro-inflammatory SASP in the outcome of sarcopenia in the elderly.

The RNA editor ADAR2 promotes immune cell trafficking by enhancing endothelial responses to interleukin-6 during sterile inflammation.

Immune cell trafficking constitutes a fundamental component of immunological response to tissue injury, but the contribution of intrinsic RNA nucleotide modifications to this response remains elusive. We report that RNA editor ADAR2 exerts a tissue- and stress-specific regulation of endothelial responses to interleukin-6 (IL-6), which tightly controls leukocyte trafficking in IL-6-inflamed and ischemic tissues. Genetic ablation of ADAR2 from vascular endothelial cells diminished myeloid cell rolling and adhesion on vascular walls and reduced immune cell infiltration within ischemic tissues. ADAR2 was required in the endothelium for the expression of the IL-6 receptor subunit, IL-6 signal transducer (IL6ST; gp130), and subsequently, for IL-6 trans-signaling responses. ADAR2-induced adenosine-to-inosine RNA editing suppressed the Drosha-dependent primary microRNA processing, thereby overwriting the default endothelial transcriptional program to safeguard gp130 expression. This work demonstrates a role for ADAR2 epitranscriptional activity as a checkpoint in IL-6 trans-signaling and immune cell trafficking to sites of tissue injury.

Benefits of the Neurogenic Potential of Melatonin for Treating Neurological and Neuropsychiatric Disorders.

There are several neurological diseases under which processes related to adult brain neurogenesis, such cell proliferation, neural differentiation and neuronal maturation, are affected. Melatonin can exert a relevant benefit for treating neurological disorders, given its well-known antioxidant and anti-inflammatory properties as well as its pro-survival effects. In addition, melatonin is able to modulate cell proliferation and neural differentiation processes in neural stem/progenitor cells while improving neuronal maturation of neural precursor cells and newly created postmitotic neurons. Thus, melatonin shows relevant pro-neurogenic properties that may have benefits for neurological conditions associated with impairments in adult brain neurogenesis. For instance, the anti-aging properties of melatonin seem to be linked to its neurogenic properties. Modulation of neurogenesis by melatonin is beneficial under conditions of stress, anxiety and depression as well as for the ischemic brain or after a brain stroke. Pro-neurogenic actions of melatonin may also be beneficial for treating dementias, after a traumatic brain injury, and under conditions of epilepsy, schizophrenia and amyotrophic lateral sclerosis. Melatonin may represent a pro-neurogenic treatment effective for retarding the progression of neuropathology associated with Down syndrome. Finally, more studies are necessary to elucidate the benefits of melatonin treatments under brain disorders related to impairments in glucose and insulin homeostasis.

Inflammaging: Implications in Sarcopenia.

In a world in which life expectancy is increasing, understanding and promoting healthy aging becomes a contemporary demand. In the elderly, a sterile, chronic and low-grade systemic inflammation known as "inflammaging" is linked with many age-associated diseases. Considering sarcopenia as a loss of strength and mass of skeletal muscle related to aging, correlations between these two terms have been proposed. Better knowledge of the immune system players in skeletal muscle would help to elucidate their implications in sarcopenia. Characterizing the activators of damage sensors and the downstream effectors explains the inference with skeletal muscle performance. Sarcopenia has also been linked to chronic diseases such as diabetes, metabolic syndrome and obesity. Implications of inflammatory signals from these diseases negatively affect skeletal muscle. Autophagic mechanisms are closely related with the inflammasome, as autophagy eliminates stress signaling sent by damage organelles, but also acts with an immunomodulatory function affecting immune cells and cytokine release. The use of melatonin, an antioxidant, ROS scavenger and immune and autophagy modulator, or senotherapeutic compounds targeting senescent cells could represent strategies to counteract inflammation. This review aims to present the many factors regulating skeletal muscle inflammaging and their major implications in order to understand the molecular mechanisms involved in sarcopenia.

Chronic Treatment with Melatonin Improves Hippocampal Neurogenesis in the Aged Brain and Under Neurodegeneration.

Adult hippocampal neurogenesis is altered during aging and under different neuropsychiatric and neurodegenerative diseases. Melatonin shows neurogenic and neuroprotective properties during aging and neuropathological conditions. In this study, we evaluated the effects of chronic treatment with melatonin on different markers of neurodegeneration and hippocampal neurogenesis using immunohistochemistry in the aged and neurodegenerative brains of SAMP8 mice, which is an animal model of accelerated senescence that mimics aging-related Alzheimer's pathology. Neurodegenerative processes observed in the brains of aged SAMP8 mice at 10 months of age include the presence of damaged neurons, disorganization in the layers of the brain cortex, alterations in neural processes and the length of neuronal prolongations and ß-amyloid accumulation in the cortex and hippocampus. This neurodegeneration may be associated with neurogenic responses in the hippocampal dentate gyrus of these mice, since we observed a neurogenic niche of neural stem and progenitor/precursors cells in the hippocampus of SAMP8 mice. However, hippocampal neurogenesis seems to be compromised due to alterations in the cell survival, migration and/or neuronal maturation of neural precursor cells due to the neurodegeneration levels in these mice. Chronic treatment with melatonin for 9 months decreased these neurodegenerative processes and the neurodegeneration-induced neurogenic response. Noticeably, melatonin also induced recovery in the functionality of adult hippocampal neurogenesis in aged SAMP8 mice.

ADAR1 Prevents Autoinflammatory Processes in the Heart Mediated by IRF7.

BACKGROUND: ADAR1 (adenosine deaminase acting on RNA-1)-mediated adenosine to inosine (A-to-I) RNA editing plays an essential role for distinguishing endogenous from exogenous RNAs, preventing autoinflammatory ADAR1 also regulates cellular processes by recoding specific mRNAs, thereby altering protein functions, but may also act in an editing-independent manner. The specific role of ADAR1 in cardiomyocytes and its mode of action in the heart is not fully understood. To determine the role of ADAR1 in the heart, we used different mutant mouse strains, which allows to distinguish immunogenic, editing-dependent, and editing-independent functions of ADAR1. METHODS: Different Adar1-mutant mouse strains were employed for gene deletion or specific inactivation of ADAR1 enzymatic activity in cardiomyocytes, either alone or in combination with Ifih1 (interferon induced with helicase C domain 1) or Irf7 (interferon regulatory factor 7) gene inactivation. Mutant mice were investigated by immunofluorescence, Western blot, RNAseq, proteomics, and functional MRI analysis. RESULTS: Inactivation of Adar1 in cardiomyocytes resulted in late-onset autoinflammatory myocarditis progressing into dilated cardiomyopathy and heart failure at 6 months of age. Adar1 depletion activated interferon signaling genes but not NFκB (nuclear factor kappa B) signaling or apoptosis and reduced cardiac hypertrophy during pressure overload via induction of Irf7. Additional inactivation of the cytosolic RNA sensor MDA5 (melanoma differentiation-associated gene 5; encoded by the Ifih1 gene) in Adar1 mutant mice prevented activation of interferon signaling gene and delayed heart failure but did not prevent lethality after 8.5 months. In contrast, compound mutants only expressing catalytically inactive ADAR1 in an Ifih1-mutant background were completely normal. Inactivation of Irf7 attenuated the phenotype of Adar1-deficient cardiomyocytes to a similar extent as Ifih1 depletion, identifying IRF7 as the main mediator of autoinflammatory responses caused by the absence of ADAR1 in cardiomyocytes. CONCLUSIONS: Enzymatically active ADAR1 prevents IRF7-mediated autoinflammatory reactions in the heart triggered by endogenous nonedited RNAs. In addition to RNA editing, ADAR1 also serves editing-independent roles in the heart required for long-term cardiac function and survival.

[Metabolic profile and concentration of ghrelin and obestatin in children and adolescents with obesity]. / Perfil metabólico, concentración de grelina y obestatina en niños y adolescentes con obesidad.

Background: It has been pointed out that ghrelin and obestatin could have an impact on the genesis of obesity, since they estimulate and inhibit apetite and, therefore, food consumption. Objective: To compare the metabolic profile, lipid profile and the concentrations of ghrelin and obestatin in children with normal weight or obesity. Material and methods: Cross-sectional design with 97 normal weight or obese children, 6 to 18 years of age, who did not present systemic diseases. The serum concentrations of glucose, insulin, total cholesterol, triglycerides, high (HDL), low (LDL) and very low density (VLDL) lipoproteins, aspartate aminotransferase (AST), alanine aminotransferase (ALT), ghrelin and obestatin were determined. Descriptive statistics were performed. Student's t test was used to compare groups, and correlation coefficients of ghrelin and obestatin values with biochemical and anthropometric variables. A p value of ≤ 0.05 was significant. Results: 55 children with normal weight and 42 with obesity were included; mean age was 10.7 years. Triglycerides, LDL, VLDL, ALT and insulin were higher, and HDL lower in obese children (p < 0.05). Ghrelin values were higher in normal weight children (p < 0.05), and there was no difference in obestatin values. Conclusions: The lower concentration of ghrelin in obese children may indicate a negative feedback to regulate energy consumption. Children and adolescents with obesity show metabolic and lipid profile alterations that place them at risk of early development of cardiovascular risk factors.

Introducción: se ha señalado que la grelina y la obestatina podrían incidir en la génesis de la obesidad al estimular o inhibir el apetito y, por ende, el consumo de alimentos. Objetivo: comparar el perfil metabólico, el perfil de lípidos y las concentraciones de grelina y obestatina en niños con normopeso u obesidad. Material y métodos: diseño transversal con 97 niños de 6 a 18 años con normopeso u obesidad que no presentaran enfermedades sistémicas. Se determinaron las concentraciones séricas de glucosa, insulina, colesterol total, triglicéridos, lipoproteínas de colesterol de alta (HDL), baja (LDL) y muy baja densidad (VLDL), aspartato aminotransferasa (AST), alanina aminotransferasa (ALT), grelina y obestatina. Se usó estadística descriptiva. Se utilizó la prueba t de Student para comparar grupos, y coeficientes de correlación de los valores de grelina y obestatina con las variables bioquímicas y antropométricas. Un valor de p ≤ 0.05 fue significativo. Resultados: se incluyeron 55 niños con normopeso y 42 con obesidad; la edad promedio fue de 10.7 años. Los triglicéridos, LDL, VLDL, ALT y la insulina fueron superiores, y el HDL inferior en niños con obesidad (p < 0.05). Los valores de la grelina fueron superiores en niños con normopeso (p < 0.05) y no hubo diferencia en los de la obestatina. Conclusiones: la menor concentración de grelina en niños con obesidad puede indicar una retroalimentación negativa para regular el consumo de energía. Los niños y adolescentes con obesidad muestran alteraciones metabólicas y del perfil de lípidos que los ponen en riesgo de desarrollar tempranamente factores de riesgo cardiovascular.

Herramienta gráfica con recomendaciones de alimentación para personas con obesidad sometidas a Cirugía Bariátrica y Metabólica / Graphic tool with feeding recommendations for people with obesity undergoing Bariatric and Metabolic Surgery

RESUMEN Objetivo: diseñar y evaluar la comprensión de una Herramienta Gráfica (HG) con recomendaciones de alimentación para personas con obesidad sometidas a Cirugía Bariátrica y Metabólica (CByM), con base en las guías propuestas por la American Society for Metabolic and Bariatric Surgery (ASMBS), American Association of Clinical Endocrinologists (AACE) y The Obesity Society (TOS), así como las recomendaciones del Colegio Mexicano de Cirugía para Obesidad y Enfermedades Metabólicas (CMCOEM) para el uso educativo de la persona profesional en nutriología-paciente. Metodología: se elaboró una HG nombrada "HG de alimentación pos-CByM" considerando las guías nutricionales propuestas por la ASMBS, AACE y TOS en conjunto con las recomendaciones de la CMCOEM. Además de realizar cuatro gráficos representando las fases que componen dicha HG, se incorporó una fase donde se aplicó un cuestionario de autollenado a tres grupos diferentes: 27 estudiantes de medicina, 8 pacientes posquirúrgicos y 16 pacientes prequirúrgicos. Se buscó identificar si el mensaje percibido era claro y conciso. Resultados: >70 % de la población intervenida entiende el mensaje de la HG diseñada, no existe significancia estadística entre los grupos entrevistados (p<0.05). Sin diferencia significativa (p<0.05) entre pacientes pre y posquirúrgicos, en ninguna de las respuestas. Conclusión: la educación en nutrición bariátrica es esencial para que las personas comprendan la transición de las fases posteriores a la intervención, los grupos, consistencia, tolerancia y porción de los alimentos. Esta HG puede ser de utilidad en la consulta nutricional exclusivamente para pacientes que se someterán a este tipo de cirugía o ya están en el proceso de recuperación.

ABSTRACT: Objectives: The purpose of this study is to Design and evaluate a graphic tool (GT) with feeding recommendations for people with obesity after bariatric surgery, based on the guidelines proposed by the American Society for Metabolic and Bariatric Surgery (ASMBS), American Association of Clinical Endocrinologists (AACE) y The Obesity Society (TOS) as well as the recommendations of the Mexican College of Surgery for Obesity and Metabolic Diseases (CMCOEM) for the educational use of the nutritionist-Bariatric patient. Methods: A GT named "Graphic tool for post bariatric surgery feeding" was elaborated based on the nutritional guidelines proposed by the ASMBS, AACE and TOS in conjunction with the recommendations of the CMCOEM. In addition to making four graphs representing each of the phases that conform the GT, a self-administered questionnaire was incorporate, it was carried out in three different groups: 27 medical students, 16 pre surgical patients and 8 postsurgical patients. We sought to identify if the perceived message was clear and brief. Results: More than 70% of the intervened population understood the message of the HG designed, there was no statistical significance among the groups interviewed (p <0.05) without significant difference (p <0.05) between pre and postsurgical patients, in none of the answers. Conclusion: Bariatric nutrition education is essential for the patient to understand the transition of the postsurgical phases, the food groups, the consistency, tolerance and portion of the food. This GT can be useful in the nutritional consultation exclusively for patients who will undergo this type of surgery or are already in the process of recovery.

Nature versus nurture? Consequences of short captivity in early stages.

Biological changes occurring as a consequence of domestication and/or captivity are not still deeply known. In Atlantic salmon (Salmo salar), endangered (Southern Europe) populations are enhanced by supportive breeding, which involves only 6 months of captive rearing following artificial spawning of wild-collected adults. In this work, we assess whether several fitness-correlated life-history traits (migratory behavior, straying rate, age at maturity, and growth) are affected by early exposure to the captive environment within a generation, before reproduction thus before genetic selection. Results showed significant differences in growth and migratory behavior (including straying), associated with this very short period of captivity in natural fish populations, changing even genetic variability (decreased in hatchery-reared adults) and the native population structure within and between rivers of the species. These changes appeared within a single generation, suggesting very short time of captivity is enough for initiating changes normally attributed to domestication. These results may have potential implications for the long-term population stability/viability of species subjected to restoration and enhancement processes and could be also considered for the management of zoo populations.

Cardiac regeneration in non-mammalian vertebrates.

The heart is a robust organ, capable of pumping nutrients and transferring oxygen throughout the body via a network of capillaries, veins and arteries, for the entirety of a human's life. However, the fragility of mammalian hearts is also evident when it becomes damaged and parts of the organ fail to function. This is due to the fact that rather than replenishing the damaged areas with functional cellular mass, fibrotic scar tissue is the preferred replacement, resulting in an organ with functional deficiencies. Due to the mammalian hearts incapability to regenerate following damage and the ever-increasing number of people worldwide suffering from heart disease, tireless efforts are being made to discover ways of inducing a regenerative response in this most important organ. One such avenue of investigation involves studying our distantly related non-mammalian vertebrate cousins, which over the last decade has proved to us that cardiac regeneration is possible. This review will highlight these organisms and provide insights into some of the seminal discoveries made in the heart regeneration field using these amazing chordates.

Amylin S20G mutation in Mexican population.

Diabetes Mellitus type 2 (DM2) is a group of metabolic disorders characterized by defective insulin action or secretion or both with a 10.6% incidence in Mexican Mestizo population, DM2 is also classified within the localized misfolding diseases due to the amyloid pancreatic deposits found in 90% of the DM2 necropsies. The pancreatic amyloid main component is a protein known as human islet amyloid polypeptide (hIAPP) or amylin, the most common mutation is the S20G in Asian population with a polymorphic frequency in DM2 Asian patients. The aim of this study was to search this mutation in Mexican Mestizo general population (104) and DM2 patients (100). This is the first molecular study of hIAPP gene in Mexican population and in which we developed an alternative more effective antisense primer for the analysis of the NFGAILSS region in hIAPP exon 3 critical for the amyloid beta structure formation. We did not find the mutation in any of the 204 analyzed samples, thus the findings show that S20G is not a common mutation in Mexican Mestizo population.

Palatine perforation induced by cocaine.

Worldwide, the use of cocaine has an increased over the years, various secondary effects have been described. Here we present a 48 years old female with a 2-month evolution bucconasal ulcer in the hard palate induced by cocaine usage accompanied by swallow and phonation dysfunctions. Ethiopathogenesis, differential diagnoses and treatment are discussed.

Perforación en bóveda palatina por consumo de cocaína / Palatine perforation induced by cocaine

El consumo de cocaína va en aumento en la población mundial, los efectos del consumo de esta droga pueden ocasionar efectos secundarios. Se presenta un caso de paciente femenino de 48 años de edad que presenta una úlcera crónica buco-nasal de 2 meses de evolución, la cual le ocasiona problemas para la deglución y fonación. Se discuten la etiopatogenia, diagnóstico diferencial y tratamiento

Worldwide, the use of cocaine has an increased over the years, various secondary effects have been described. Here we present a 48 years old female with a 2-month evolution bucconasal ulcer in the hard palate induced by cocaine usage accompanied by swallow and phonation dysfunctions. Ethiopathogenesis, differential diagnoses and treatment are discussed