Cigarette Smoke Affects Keratinocytes SRB1 Expression and Localization via H2O2 Production and HNE Protein Adducts Formation

Scavenger Receptor B1 (SR-B1), also known as HDL receptor, is involved in cellular cholesterol uptake. Stratum corneum (SC), the outermost layer of the skin, is composed of more than 25% cholesterol. Several reports support the view that alteration of SC lipid composition may be the cause of impaired barrier function which gives rise to several skin diseases. For this reason the regulation of the genes involved in cholesterol uptake is of extreme significance for skin health. Being the first shield against external insults, the skin is exposed to several noxious substances and among these is cigarette smoke (CS), which has been recently associated with various skin pathologies. In this study we first have shown the presence of SR-B1 in murine and human skin tissue and then by using immunoblotting, immunoprecipitation, RT-PCR, and confocal microscopy we have demonstrated the translocation and the subsequent lost of SR-B1 in human keratinocytes (cell culture model) after CS exposure is driven by hydrogen peroxide (H2O2) that derives not only from the CS gas phase but mainly from the activation of cellular NADPH oxidase (NOX). This effect was reversed when the cells were pretreated with NOX inhibitors or catalase. Furthermore, CS caused the formation of SR-B1-aldheydes adducts (acrolein and 4-hydroxy-2-nonenal) and the increase of its ubiquitination, which could be one of the causes of SR-B1 loss. In conclusion, exposure to CS, through the production of H2O2, induced post-translational modifications of SR-B1 with the consequence lost of the receptor and this may contribute to the skin physiology alteration as a consequence of the variation of cholesterol uptake

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Comment on "Everolimus induces G₁ cell cycle arrest through autophagy-mediated protein degradation of cyclin D1 in breast cancer cells"

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Correlative study of squash smear cytology with histopathology in a rare case of anaplastic giant cell ependymoma of the pineal

Anaplastic giant cell ependymoma (AGCE) is a very rare neoplasm. Its cytological features, helpful for the intraoperative diagnosis, have been reported only once. AGCE is characterized by giant cells with intranuclear inclusions, besides other findings, observable in ependymal neoplasms, such as intracytoplasmic vacuoles, epithelial and glial features of the tumor cells and ependymal pseudorosettes. These findings can be detected also in intraoperative squash smear. Herein we describe a pineal AGCE, highlighting the cytological and histological correlations and underlining some useful diagnostic clues of this unusual entity

Correlative study of squash smear cytology with histopathology in a rare case of anaplastic giant cell ependymoma of the pineal

Anaplastic giant cell ependymoma (AGCE) is a very rare neoplasm. Its cytological features, helpful for the intraoperative diagnosis, have been reported only once. AGCE is characterized by giant cells with intranuclear inclusions, besides other findings, observable in ependymal neoplasms, such as intracytoplasmic vacuoles, epithelial and glial features of the tumor cells and ependymal pseudorosettes. These findings can be detected also in intraoperative squash smear. Herein we describe a pineal AGCE, highlighting the cytological and histological correlations and underlining some useful diagnostic clues of this unusual entity

mTOR inhibitor CCI-779 (Rapamycin ester) induces autophagy but increases cisplatin-induced cell death.

<p>Me21 melanoma cells were treated for 24 hours with cisplatin, with or without 100 nM CCI-779 (R), in the presence or absence of 3-MA (4 mM). (<b>A</b>) Autophagy was evaluated by Western blot analysis of LC3. A typical experiment out of 4 is shown; densitometric analysis (normalized to Ponceau S staining) of LC3-II is reported below. (<b>B</b>) Total cell numbers are presented as percentage over control cells; the columns also show the relative number of adhering cells (white) and floating dead cells (black); S.E. values and statistical analysis refer to detached cells; (<b>C</b>) caspase-3/-7 activity. Data are reported as means ± S.E. of 3 experiments. *<i>P</i><0.05.</p