Sex-based differences in natural killer T cell-mediated protection against diet-induced steatohepatitis in Balb/c mice.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is prevalent in Western countries, evolving into metabolic dysfunction-associated steatohepatitis (MASH) with a sexual dimorphism. Fertile women exhibit lower MASLD risk than men, which diminishes post-menopause. While NKT-cell involvement in steatohepatitis is debated, discrepancies may stem from varied mouse strains used, predominantly C57BL6/J with Th1-dominant responses. Exploration of steatohepatitis, encompassing both genders, using Balb/c background, with Th2-dominant immune response, and CD1d-deficient mice in the Balb/c background (lacking Type I and Type II NKT cells) can clarify gender disparities and NKT-cell influence on MASH progression. METHODS: A high fat and choline-deficient (HFCD) diet was used in male and female mice, Balb/c mice or CD1d-/- mice in the Balb/c background that exhibit a Th2-dominant immune response. Liver fibrosis and inflammatory gene expression were measured by qPCR, and histology assessment. NKT cells, T cells, macrophages and neutrophils were assessed by flow cytometry. RESULTS: Female mice displayed milder steatohepatitis after 6 weeks of HFCD, showing reduced liver damage, inflammation, and fibrosis compared to males. Male Balb/c mice exhibited NKT-cell protection against steatohepatitis whereas CD1d-/- males on HFCD presented decreased hepatoprotection, increased liver fibrosis, inflammation, neutrophilic infiltration, and inflammatory macrophages. In contrast, the NKT-cell role was negligible in early steatohepatitis development in both female mice, as fibrosis and inflammation were similar despite augmented liver damage in CD1d-/- females. Relevant, hepatic type I NKT levels in female Balb/c mice were significantly lower than in male. CONCLUSIONS: NKT cells exert a protective role against experimental steatohepatitis as HFCD-treated CD1d-/- males had more severe fibrosis and inflammation than male Balb/c mice. In females, the HFCD-induced hepatocellular damage and the immune response are less affected by NKT cells on early steatohepatitis progression, underscoring sex-specific NKT-cell influence in MASH development.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common liver condition today. In its more advanced form, called metabolic dysfunction-associated steatohepatitis (MASH), adult men are more often affected than women, though this difference vanishes after menopause. Various factors contribute to MASH, including a specific immune cell type called NKT cells, which has not been deeply researched yet. To explore the role of NKT cells in steatohepatitis, we used male and female mice with or without NKT cells (CD1d^−/− mice), feeding them a high-fat diet that induces steatohepatitis. Our findings revealed that female mice had less severe steatohepatitis compared to males. Interestingly, we observed a protective role of NKT cells during steatohepatitis, as male mice without these cells had more damage, inflammation, and fibrosis than those with NKT cells. However, in females, even though those lacking NKT cells showed more liver damage and immune alterations, NKT did not seem to play a major role in early steatohepatitis progression. Notably, females had much fewer NKT cells in their livers compared to males, possibly explaining this difference. In conclusion, NKT cells seem to slow down steatohepatitis progression, especially in male mice. In females, their impact on early steatohepatitis advance appears more limited.

A cyclin-dependent kinase-mediated phosphorylation switch of disordered protein condensation.

Cell cycle transitions result from global changes in protein phosphorylation states triggered by cyclin-dependent kinases (CDKs). To understand how this complexity produces an ordered and rapid cellular reorganisation, we generated a high-resolution map of changing phosphosites throughout unperturbed early cell cycles in single Xenopus embryos, derived the emergent principles through systems biology analysis, and tested them by biophysical modelling and biochemical experiments. We found that most dynamic phosphosites share two key characteristics: they occur on highly disordered proteins that localise to membraneless organelles, and are CDK targets. Furthermore, CDK-mediated multisite phosphorylation can switch homotypic interactions of such proteins between favourable and inhibitory modes for biomolecular condensate formation. These results provide insight into the molecular mechanisms and kinetics of mitotic cellular reorganisation.

Physiological functions and roles in cancer of the proliferation marker Ki-67.

What do we know about Ki-67, apart from its usefulness as a cell proliferation biomarker in histopathology? Discovered in 1983, the protein and its regulation of expression and localisation throughout the cell cycle have been well characterised. However, its function and molecular mechanisms have received little attention and few answers. Although Ki-67 has long been thought to be required for cell proliferation, recent genetic studies have conclusively demonstrated that this is not the case, as loss of Ki-67 has little or no impact on cell proliferation. In contrast, Ki-67 is important for localising nucleolar material to the mitotic chromosome periphery and for structuring perinucleolar heterochromatin, and emerging data indicate that it also has critical roles in cancer development. However, its mechanisms of action have not yet been fully identified. Here, we review recent findings and propose the hypothesis that Ki-67 is involved in structuring cellular sub-compartments that assemble by liquid-liquid phase separation. At the heterochromatin boundary, this may control access of chromatin regulators, with knock-on effects on gene expression programmes. These changes allow adaptation of the cell to its environment, which, for cancer cells, is a hostile one. We discuss unresolved questions and possible avenues for future exploration.

Ki-67 regulates global gene expression and promotes sequential stages of carcinogenesis.

Ki-67 is a nuclear protein that is expressed in all proliferating vertebrate cells. Here, we demonstrate that, although Ki-67 is not required for cell proliferation, its genetic ablation inhibits each step of tumor initiation, growth, and metastasis. Mice lacking Ki-67 are resistant to chemical or genetic induction of intestinal tumorigenesis. In established cancer cells, Ki-67 knockout causes global transcriptome remodeling that alters the epithelial-mesenchymal balance and suppresses stem cell characteristics. When grafted into mice, tumor growth is slowed, and metastasis is abrogated, despite normal cell proliferation rates. Yet, Ki-67 loss also down-regulates major histocompatibility complex class I antigen presentation and, in the 4T1 syngeneic model of mammary carcinoma, leads to an immune-suppressive environment that prevents the early phase of tumor regression. Finally, genes involved in xenobiotic metabolism are down-regulated, and cells are sensitized to various drug classes. Our results suggest that Ki-67 enables transcriptional programs required for cellular adaptation to the environment. This facilitates multiple steps of carcinogenesis and drug resistance, yet may render cancer cells more susceptible to antitumor immune responses.

Hábitos alimentarios y psicológicos en personas que realizan ejercicio físico / Nutritional and psychological habits in people who practice exercise

Introducción: La distorsión de la imagen corporal se ha convertido en un problema mundial. La delgadez como patrón de belleza para las mujeres, y la musculación para los hombres, se han relacionado con el incremento de los Trastornos de la Conducta Alimentaria (TCA). La práctica de ejercicio físico con fines estéticos o adictivos ha incrementado, así como la popularización de los gimnasios. Objetivos: Analizar los comportamientos ortoréxicos, conocer la influencia del género en los comportamientos psicológicos y analizar los hábitos de alimentación de una muestra que practica actividad física. Métodos: Estudio observacional, descriptivo y retrospectivo en el que se realizó un cuestionario ad hoc, incorporando el test de Adherencia a Dieta Mediterránea, el Inventario de Expresión de Ira Estado-Rasgo (STAXI-2), el Cuestionario de Comedor Emocional (EEQ) adaptado y la versión española del Multidimensional Body Self Relations Questionnaire (MBSRQ). Además se realizó una valoración antropométrica a cada participante. Resultados: 264 sujetos fueron incluidos en el estudio (156 hombres), de 35,9 años (±11,1 años). Con IMC medio de 23,8 kg/m2 (±3,1 kg/m2 ) y un porcentaje de grasa corporal total 20,8 (±8,7%). La puntuación media la Adherencia a la Dieta Mediterránea, fue 5,9 (±2,4). Se encontraron comportamientos de carácter ortorexico y obsesivo, y diferencias entre géneros, para algunos marcadores estudiados. Conclusiones: Los hábitos analizados ponen de manifiesto una tendencia al culto al cuerpo, más próximo al extremo patológico que al aspecto saludable, provocando alteraciones sobre la percepción, que traen como consecuencia la realización de dietas y la aparición de alteraciones como los TCA (AU)

Introduction: The distorted body image has become a global problem. The thinness as a standard of beauty for women, and fitness for men, has been linked to an increase in eating behavior disorders. The physical exercise with aesthetic or addictive purposes has increased, as well as the popularity of gyms. Aim: To analyze the orthorexics behavior, to know the influence of gender on psychological behavior and to analyze eating habits in a sample practicing physical activity. Methods: Observational, descriptive and retrospective study in which an ad hoc questionnaire was performed, incorporating Adherence to Mediterranean diet test, the State-Trait Anger Expression Inventory (STAXI-2), Emotional Eater Questionnaire (EEQ) and adapted the Spanish version of the Multidimensional Body Self Relations Questionnaire (MBSRQ). Besides, anthropometric assessment was performed in each participant. Results: 264 subjects were included in the study (156 men), 35.9 years (± 11.1 years). With mean BMI of 23.8 kg/m2 (± 3.1 kg/m2 ) and total body fat percentage 20.8 (± 8.7%). The average score Adherence to the Mediterranean diet was 5.9 (± 2.4). Orthorexic and obsessive behaviors were found, and between genders for some markers studied. Conclusion: The habits analyzed show a tendency to body worship, closer to a pathological condition rather than to a healthy aspect, causing alterations on perception, that result in dieting and alterations such as eating disorders (AU)

[Nutritional and psychological habits in people who practice exercise]. / Hábitos alimentarios y psicológicos en personas que realizan ejercicio físico.

INTRODUCTION: The distorted body image has become a global problem. The thinness as a standard of beauty for women, and fitness for men, has been linked to an increase in eating behavior disorders. The physical exercise with aesthetic or addictive purposes has increased, as well as the popularity of gyms. AIM: To analyze the orthorexics behavior, to know the influence of gender on psychological behavior and to analyze eating habits in a sample practicing physical activity. METHODS: Observational, descriptive and retrospective study in which an ad hoc questionnaire was performed, incorporating Adherence to Mediterranean diet test, the State-Trait Anger Expression Inventory (STAXI-2), Emotional Eater Questionnaire (EEQ) and adapted the Spanish version of the Multidimensional Body Self Relations Questionnaire (MBSRQ). Besides, anthropometric assessment was performed in each participant. RESULTS: 264 subjects were included in the study (156 men), 35.9 years (± 11.1 years). With mean BMI of 23.8 kg/m2 (± 3.1 kg/m2) and total body fat percentage 20.8 (± 8.7%). The average score Adherence to the Mediterranean diet was 5.9 (± 2.4). Orthorexic and obsessive behaviors were found, and between genders for some markers studied. CONCLUSION: The habits analyzed show a tendency to body worship, closer to a pathological condition rather than to a healthy aspect, causing alterations on perception, that result in dieting and alterations such as eating disorders.

Introducción: La distorsión de la imagen corporal se ha convertido en un problema mundial. La delgadez como patrón de belleza para las mujeres, y la musculación para los hombres, se han relacionado con el incremento de los Trastornos de la Conducta Alimentaria (TCA). La práctica de ejercicio físico con fines estéticos o adictivos ha incrementado, así como la popularización de los gimnasios. Objetivos: Analizar los comportamientos ortoréxicos, conocer la influencia del género en los comportamientos psicológicos y analizar los hábitos de alimentación de una muestra que practica actividad física. Métodos: Estudio observacional, descriptivo y retrospectivo en el que se realizó un cuestionario ad hoc, incorporando el test de Adherencia a Dieta Mediterránea, el Inventario de Expresión de Ira Estado-Rasgo (STAXI-2), el Cuestionario de Comedor Emocional (EEQ) adaptado y la versión española del Multidimensional Body Self Relations Questionnaire (MBSRQ). Además se realizó una valoración antropométrica a cada participante. Resultados: 264 sujetos fueron incluidos en el estudio (156 hombres), de 35,9 años (±11,1 años). Con IMC medio de 23,8 kg/m2 (±3,1 kg/m2) y un porcentaje de grasa corporal total 20,8 (±8,7%). La puntuación media la Adherencia a la Dieta Mediterránea, fue 5,9 (±2,4). Se encontraron comportamientos de carácter ortorexico y obsesivo, y diferencias entre géneros, para algunos marcadores estudiados. Conclusiones: Los hábitos analizados ponen de manifiesto una tendencia al culto al cuerpo, más próximo al extremo patológico que al aspecto saludable, provocando alteraciones sobre la percepción, que traen como consecuencia la realización de dietas y la aparición de alteraciones como los TCA.