Tumor immune microenvironment modulation by cholesterol in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is considered one of the most aggressive tumors worldwide. The consumption of lipid-enriched diets, mainly high cholesterol, induces oxidative stress and chronic inflammation, leading to HCC progression. Moreover, fatty acids and cholesterol could display differential responses on immune cells inside the tumor immune microenvironment (TIME). Tumor-associated macrophages (TAMs) represent one of the most critical leukocytes in the tumor microenvironment (TME) displaying pro-tumoral responses and one of the mainly cholesterol donors to cancer cells. Immunotherapy or cholesterol regulators, alone or combined, would represent an effective strategy for HCC treatment. Nonetheless, steatotic etiology from non-alcoholic fatty liver disease (NAFLD)-HCC tumors has been unexpectedly resulting in highly aggressive behavior

The hepatocyte growth factor induces an anti-inflammatory and repairing response in the cholestasis-induced colon damage

Aim: Cholestasis remains a partially characterized disease. Evidence has been gained that it is a systemic disease that begins in the liver but significantly impacts other organs and systems such as the kidney, heart, and intestine, among others. One of the primary damage mechanisms is the generation of reactive oxygen species (ROS), which eventually leads to oxidative stress, impacting canalicular morphology and actin cytoskeleton changes that could worsen the problem. These characteristics are also observed in the kidney and intestine. The work focused on addressing the intestine effects of intrahepatic cholestasis induced by α-naphthyl isothiocyanate (ANIT) and the protective response of the hepatocyte growth factor (HGF). Methods: The 10- to 12-week-old CD1 male mice were treated with ANIT and then treated or not with HGF; intestine damage was addressed by histology, immunohistochemistry (IHC) of specific markers, oxidative stress, and apoptosis. Results: Results show changes in the intestine histology, particularly the colon and ileum, induced by the cholestasis. HGF treatment restored the histology presentation and reverted the oxidative damage, clearly indicating a healing response. This observation was supported by an increment in anti-inflammatory macrophages (CD163+) in the HGF treatment. Conclusions: The data prove that HGF induces a protective and repairing response in the intestine under cholestatic challenges

Baseline and post-stress seasonal changes in immunocompetence and redox state maintenance in the fishing bat Myotis vivesi.

Little is known of how the stress response varies when animals confront seasonal life-history processes. Antioxidant defenses and damage caused by oxidative stress and their link with immunocompetence are powerful biomarkers to assess animal´s physiological stress response. The aim of this study was A) to determine redox state and variation in basal (pre-acute stress) immune function during summer, autumn and winter (spring was not assessed due to restrictions in collecting permit) in the fish-eating Myotis (Myotis vivesi; Chiroptera), and B) to determine the effect of acute stress on immunocompetence and redox state during each season. Acute stress was stimulated by restricting animal movement for 6 and 12 h. The magnitude of the cellular immune response was higher during winter whilst that of the humoral response was at its highest during summer. Humoral response increased after 6 h of movement restriction stress and returned to baseline levels after 12 h. Basal redox state was maintained throughout the year, with no significant changes in protein damage, and antioxidant activity was modulated mainly in relation to variation to environment cues, increasing during high temperatures and decreasing during windy nights. Antioxidant activity increased after the 6 h of stressful stimuli especially during summer and autumn, and to a lesser extent in early winter, but redox state did not vary. However, protein damage increased after 12 h of stress during summer. Prolonged stress when the bat is engaged in activities of high energy demand overcame its capacity to maintain homeostasis resulting in oxidative damage

Fructose Consumption and Hepatocellular Carcinoma Promotion

Hepatocellular carcinoma (HCC) accounts for 85% of primary liver cancer, the third most common cause of cancer-related deaths worldwide. Its incidence has been increasing in both men and women. In Western countries, high-calorie diets, mainly rich in carbohydrates such as fructose, represent a significant concern due to their repercussions on the population’s health. A high-fructose diet is related to the development of Metabolic-Associated Fatty Liver Disease (MAFLD), formerly named Non-Alcoholic Fatty Liver Disease (NAFLD), and the progression of HCC as it potentiates the lipogenic pathway and the accumulation of lipids. However, fructose metabolism seems to be different between the stages of the disease, carrying out a metabolic reprogramming to favor the proliferation, inflammation, and metastatic properties of cancer cells in HCC. This review focuses on a better understanding of fructose metabolism in both scenarios: MAFLD and HCC

Acute stress stimuli impact on physiological markers.

<p>Change in SOD, CAT and GPx activity (mean ± SD). Asterisks indicate significant differences in the response between basal and post-stress levels based on Student’s t-tests. Bold numbers inside bars indicate sample sizes.</p

Le Miroir des sports : publication hebdomadaire illustrée

21 octobre 19301930/10/21 (N565)-1930/10/21

Graphic representation of principal component analysis plotting PC1 against PC2.

<p>A) Period 1 basal disregard-PCA, B) Period 1 basal between groups-PCA, C) Period 1 six hours Post-stress disregard-PCA, D) Period 1 six hours Post-stress between groups-PCA, E) Period 2 basal disregard-PCA, F) Period 2 basal between groups-PCA, G) Period 2 six hours Post-stress disregard-PCA, H) Period 2 six hours Post-stress between groups-PCA.</p

Seasonal swelling response after 6 hours of PHA post injection.

<p>A) P1, pink arrows represent seasonal variation in the swelling response in females; black arrows represent seasonal changes in the swelling response in males; different letters indicate significant differences among seasons within a period; asterisks indicate differences between periods for a given season. B) P2, pink arrows represent females and black arrows represent males; no significant differences were found. C) Combined data from P2 (estimated mean ± SE).</p

Seasonal swelling response after 24 hours of PHA injection.

<p>A) Data separated by sex from P1. B) Combined data from P1 (estimated marginal mean ± SE). C) Data separated by sex from P2. Pink arrows represent seasonal variation in the swelling response in females; black arrows represent seasonal changes in swelling response in males; D) Combined data from P2 (estimated marginal mean ± SE); different letters indicate significant differences among seasons.</p

Seasonal swelling response after 12 hours of PHA injection.

<p>A) Data separated by sex from P1. B) Combined data from P1 (estimated marginal mean ± SE). C) Data separated by sex from P2. Pink arrows represent seasonal variation in the swelling response in females; black arrows represent seasonal changes in swelling response in males. D) Combined data from P2 (estimated marginal mean ± SE); different letters indicate significant differences among seasons.</p