A Novel PHOX/CD38/MCOLN1/TFEB Axis Important For Macrophage Activation During Bacterial Phagocytosis [preprint]

Macrophages are a key and heterogenous class of phagocytic cells of the innate immune system, which act as sentinels in peripheral tissues and are mobilized during infection. Macrophage activation in the presence of bacterial cells and molecules entails specific and complex programs of gene expression. How such triggers elicit the gene expression programs is incompletely understood. We previously discovered that transcription factor TFEB is a key contributor to macrophage activation during bacterial phagocytosis. However, the mechanism linking phagocytosis of bacterial cells to TFEB activation remained unknown. In this article, we describe a previously unknown pathway that links phagocytosis with the activation of TFEB and related transcription factor TFE3 in macrophages. We find that phagocytosis of bacterial cells causes an NADPH oxidase (PHOX)-dependent oxidative burst, which activates enzyme CD38 and generates NAADP in the maturing phagosome. Phago-lysosome fusion brings Ca2+ channel TRPML1/MCOLN1 in contact with NAADP, causing Ca2+ efflux from the lysosome, calcineurin activation, and TFEB nuclear import. This drives TFEB-dependent expression of important pro-inflammatory cytokines, such as IL-1α, IL-1β, and IL-6. Thus, our findings reveal that TFEB activation is a key regulatory event for the activation of macrophages. These findings have important implications for infections, cancer, obesity, and atherosclerosis

Psychometric properties of the Persian version of the overall anxiety severity and impairment scale (OASIS)

Objectives: This study was conducted to assess the psychometric properties of the Persian version of the overall anxiety severity and impairment scale (OASIS), a measure designed to evaluate the severity and functional impairments associated with clinical and subsyndromal anxiety. Methods: Using a descriptive-analytic framework, first, the OASIS was translated into Persian according to the forward-backward translation guidelines. Then, a total of 463 students of Guilan University of Medical Sciences in the academic year 2017 - 18 were selected using the convenience sampling method. Participants completed seven measures (i.e., OASIS, anxiety and stress subscales of depression anxiety stress scales-21, Beck anxiety inventory, openness subscale of NEO five-factor inventory, positive affect and negative affect scales, Connor-Davidson resilience scale, and state subscale of state-trait anxiety inventory), and the data were analyzed by SPSS V. 20.0 for windows and Lisrel V. 8.80. Results: Internal consistency reliability of the OASIS was acceptable (Cronbach�s α = 0.877). The exploratory factor analysis indicated that all items were loaded on a single factor (loadings = 0.799 - 0.849). The confirmatory factor analysis revealed that the single-factor model has resulted in an adequate model fit. The OASIS was positively correlated with the anxiety- and negative affect-related scales, whereas it was negatively correlated with the resilience- and positive affect-related scales. Correlations with the openness subscale were not significant. Conclusions: In line with previous studies, the findings showed that the psychometric properties of the Persian version of the OASIS are acceptable. Therefore, it seems that the measure can be used in clinical practices and research studies in Iran. Copyright © 2020, Author(s)

Spinach consumption and nonalcoholic fatty liver disease among adults: a case�control study

Background: Spinach has high antioxidants and polyphenols and showed protective effects against liver diseases in experimental studies. We aimed to assess the association between dietary intake of spinach and odds of nonalcoholic fatty liver disease (NAFLD) in a case�control study among Iranian adults. Methods: Totally 225 newly diagnosed NAFLD patients and 450 controls, aged 20�60 years, were recruited in this study. Participants� dietary intakes were collected using a valid and reliable 168-item semi-quantitative food frequency questionnaire (FFQ). The logistic regression test was used for assessing the association between total, raw, and boiled dietary spinach with the odds of NAFLD. Results: The mean (SD) age and BMI of participants (53 male) were 38.1 (8.8) years and 26.8 (4.3) kg/m2, respectively. In the final adjusted model for potential confounders, the odds (95 CI) of NAFLD in individuals in the highest tertile of daily total and raw spinach intake was 0.36 (0.19�0.71), P_trend = 0.001 and 0.47 (0.24�0.89), P_trend = 0.008, respectively compared with those in the lowest tertile. Furthermore, in the adjusted analyses, an inverse association was observed between the highest yearly intake versus no raw spinach consumption and odds of NAFLD (OR 0.41; 95% CI 0.18�0.96), P for trend = 0.013. However, there was no significant association between higher boiled spinach intake and odds of NAFLD. Conclusions: The present study found an inverse association between total and raw spinach intake with the odds of NAFLD. © 2021, The Author(s)

The heat-pipe resembling action of boiling bubbles in endovenous laser ablation

Endovenous laser ablation (EVLA) produces boiling bubbles emerging from pores within the hot fiber tip and traveling over a distal length of about 20 mm before condensing. This evaporation-condensation mechanism makes the vein act like a heat pipe, where very efficient heat transport maintains a constant temperature, the saturation temperature of 100°C, over the volume where these non-condensing bubbles exist. During EVLA the above-mentioned observations indicate that a venous cylindrical volume with a length of about 20 mm is kept at 100°C. Pullback velocities of a few mm/s then cause at least the upper part of the treated vein wall to remain close to 100°C for a time sufficient to cause irreversible injury. In conclusion, we propose that the mechanism of action of boiling bubbles during EVLA is an efficient heat-pipe resembling way of heating of the vein wall

TFEB regulates murine liver cell fate during development and regeneration

It is well established that pluripotent stem cells in fetal and postnatal liver (LPCs) can differentiate into both hepatocytes and cholangiocytes. However, the signaling pathways implicated in the differentiation of LPCs are still incompletely understood. Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is known to be involved in osteoblast and myeloid differentiation, but its role in lineage commitment in the liver has not been investigated. Here we show that during development and upon regeneration TFEB drives the differentiation status of murine LPCs into the progenitor/cholangiocyte lineage while inhibiting hepatocyte differentiation. Genetic interaction studies show that Sox9, a marker of precursor and biliary cells, is a direct transcriptional target of TFEB and a primary mediator of its effects on liver cell fate. In summary, our findings identify an unexplored pathway that controls liver cell lineage commitment and whose dysregulation may play a role in biliary cancer

Phase equilibria of carbon dioxide clathrate hydrates in the presence of methanol/ethylene glycol + single salt aqueous solutions: experimental measurement and prediction

International audienceExperimental hydrate dissociation conditions of carbon dioxide in the presence of methanol + single salt (methanol + CaCl2 and methanol + KCl) and ethylene glycol + single salt (ethylene glycol + CaCl2 and ethylene glycol + KCl) aqueous solutions are reported at different temperatures and various concentrations of the aforementioned hydrate inhibitors in aqueous solutions. All the experimental data were measured using an isochoric pressure-search method. These experimental data are compared with some selected dissociation data from the literature for carbon dioxide clathrate hydrates in the presence of pure water to show the inhibition effect of the studied aqueous solutions. A previously reported thermodynamic model is employed to predict the experimental results and a brief discussion is made on the reliability of the predicted data