Sarcoidosis in an Italian province. Prevalence and environmental risk factors.

BACKGROUND AND AIM: Sarcoidosis is a systemic granulomatous inflammatory disease whose causes are still unknown and for which epidemiological data are often discordant. The aim of our study is to investigate prevalence and spatial distribution of cases, and identify environmental exposures associated with sarcoidosis in an Italian province. METHODS: After georeferentiation of cases, the area under study was subdivided with respect to Municipality and Health Districts and to the altitude in order to identify zonal differences in prevalence. The bioaccumulation levels of 12 metals in lichen tissues were analyzed, in order to determine sources of air pollution. Finally, the analysis of the correlation between metals and between pickup stations was performed. RESULTS: 223 patients were identified (58.3% female and 41.7% male of total) and the mean age was 50.6±15.4 years (53.5±15.5 years for the females and 46.5±14.4 for the males). The mean prevalence was 49 per 100.000 individuals. However, we observed very heterogeneous prevalence in the area under study. The correlations among metals revealed different deposition patterns in lowland area respect to hilly and mountain areas. CONCLUSIONS: The study highlights a high prevalence of sarcoidosis cases, characterized by a very inhomogeneous and patchy distribution with phenomena of local aggregation. Moreover, the bioaccumulation analysis was an effective method to identify the mineral particles that mostly contribute to air pollution in the different areas, but it was not sufficient to establish a clear correlation between the onset of sarcoidosis and environmental risk factors.

Down-modulation of SEL1L, an unfolded protein response and endoplasmic reticulum-associated degradation protein, sensitizes glioma stem cells to the cytotoxic effect of valproic acid.

Valproic acid (VPA), an histone deacetylase inhibitor, is emerging as a promising therapeutic agent for the treatments of gliomas by virtue of its ability to reactivate the expression of epigenetically silenced genes. VPA induces the unfolded protein response (UPR), an adaptive pathway displaying a dichotomic yin yang characteristic; it initially contributes in safeguarding the malignant cell survival, whereas long-lasting activation favors a proapoptotic response. By triggering UPR, VPA might tip the balance between cellular adaptation and programmed cell death via the deregulation of protein homeostasis and induction of proteotoxicity. Here we aimed to investigate the impact of proteostasis on glioma stem cells (GSC) using VPA treatment combined with subversion of SEL1L, a crucial protein involved in homeostatic pathways, cancer aggressiveness, and stem cell state maintenance. We investigated the global expression of GSC lines untreated and treated with VPA, SEL1L interference, and GSC line response to VPA treatment by analyzing cell viability via MTT assay, neurosphere formation, and endoplasmic reticulum stress/UPR-responsive proteins. Moreover, SEL1L immunohistochemistry was performed on primary glial tumors. The results show that (i) VPA affects GSC lines viability and anchorage-dependent growth by inducing differentiative programs and cell cycle progression, (ii) SEL1L down-modulation synergy enhances VPA cytotoxic effects by influencing GSCs proliferation and self-renewal properties, and (iii) SEL1L expression is indicative of glioma proliferation rate, malignancy, and endoplasmic reticulum stress statuses. Targeting the proteostasis network in association to VPA treatment may provide an alternative approach to deplete GSC and improve glioma treatments.

Red and white wine differently affect collagen-induced platelet aggregation.

Moderate consumption of wine is associated with reduced cardiovascular events, but the mechanism is not fully elucidated. Aim of the study was to seek if consumption of red or white wine, that are known to have different amount of polyphenols, differently influenced platelet aggregation. 20 healthy subjects were randomly allocated to consume for two weeks 300 ml of red or white wine; both wines had the same concentration of alcohol. At baseline and 12 hours after last drink collagen-induced platelet aggregation was performed. At baseline no difference of laboratory values was observed between the two groups. At the end of treatment subjects given red wine had lower response to platelet agonist than those given white wine (<0.005). No ethanol could be found in plasma 12 hours after last drink. This study shows that red and white wine have different effect on platelet activation likely because of the different content of polyphenols present in the two types of wine.