DEFB1 polymorphisms and salivary hBD-1 concentration in Oral Lichen Planus patients and healthy subjects

The aetiology of Oral Lichen Planus (OLP), a chronic inflammatory disease of oral mucosa, is not yet well understood. Since innate immunity may be hypothesized as involved in the susceptibility to OLP, we studied human beta defensin 1 (hBD-1) an antimicrobial peptide constitutively expressed in the saliva, looking at functional genetic variants possibly able to diminish hBD-1 production an consequently conferring major susceptibility to OLP

Advances in the monitoring of geo-structure subjected to climate loading

The paper presents results achieved within the project MAGIC, a project funded by the European Commission under the Marie-Curie Industry Academia Partnerships and Pathways (IAPP) scheme. The project MAGIC aims to advance the state-of-the art in the monitoring of geo-structures subjected to climate loading by filling some of the gaps in current monitoring technologies. The project involves a partnership between academic and industrial partners to boost knowledge transfer and promote the development of ‘industrial’ instruments and services. The paper presents developments concerning the measurement of pore-water tension (suction in excess of 100 kPa) and the integration of geotechnical and geophysical monitoring

Impact of DEFB1 gene regulatory polymorphisms on hBD-1 salivary concentration

Human \u3b2-defensin 1 (hBD-1) is an antimicrobial peptide involved in epithelial defence of various tissues, also present in the saliva. Individual genetic variations within the DEFB1 gene, encoding for hBD-1, could influence gene expression and protein production

Gamma-Ray Burst observations by the high-energy charged particle detector on board the CSES-01 satellite between 2019 and 2021

In this paper we report the detection of five strong Gamma-Ray Bursts (GRBs) by the High-Energy Particle Detector (HEPD-01) mounted on board the China Seismo-Electromagnetic Satellite (CSES-01), operational since 2018 on a Sun-synchronous polar orbit at a $\sim$ 507 km altitude and 97$^\circ$ inclination. HEPD-01 was designed to detect high-energy electrons in the energy range 3 - 100 MeV, protons in the range 30 - 300 MeV, and light nuclei in the range 30 - 300 MeV/n. Nonetheless, Monte Carlo simulations have shown HEPD-01 is sensitive to gamma-ray photons in the energy range 300 keV - 50 MeV, even if with a moderate effective area above $\sim$ 5 MeV. A dedicated time correlation analysis between GRBs reported in literature and signals from a set of HEPD-01 trigger configuration masks has confirmed the anticipated detector sensitivity to high-energy photons. A comparison between the simultaneous time profiles of HEPD-01 electron fluxes and photons from GRB190114C, GRB190305A, GRB190928A, GRB200826B and GRB211211A has shown a remarkable similarity, in spite of the different energy ranges. The high-energy response, with peak sensitivity at about 2 MeV, and moderate effective area of the detector in the actual flight configuration explain why these five GRBs, characterised by a fluence above $\sim$ 3 $\times$ 10$^{-5}$ erg cm$^{-2}$ in the energy interval 300 keV - 50 MeV, have been detected.Comment: Accepted for publication in The Astrophysical Journal (ApJ

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists

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

The ACSL3-LPIAT1 signaling drives prostaglandin synthesis in non-small cell lung cancer.

Enhanced prostaglandin production promotes the development and progression of cancer. Prostaglandins are generated from arachidonic acid (AA) by the action of cyclooxygenase (COX) isoenzymes. However, how cancer cells are able to maintain an elevated supply of AA for prostaglandin production remains unclear. Here, by using lung cancer cell lines and clinically relevant KrasG12D-driven mouse models, we show that the long-chain acyl-CoA synthetase (ACSL3) channels AA into phosphatidylinositols to provide the lysophosphatidylinositol-acyltransferase 1 (LPIAT1) with a pool of AA to sustain high prostaglandin synthesis. LPIAT1 knockdown suppresses proliferation and anchorage-independent growth of lung cancer cell lines, and hinders in vivo tumorigenesis. In primary human lung tumors, the expression of LPIAT1 is elevated compared with healthy tissue, and predicts poor patient survival. This study uncovers the ACSL3-LPIAT1 axis as a requirement for the sustained prostaglandin synthesis in lung cancer with potential therapeutic value

Restriction of extracellular lipids renders pancreatic cancer dependent on autophagy.

BACKGROUND KRAS is the predominant oncogene mutated in pancreatic ductal adenocarcinoma (PDAC), the fourth cause of cancer-related deaths worldwide. Mutant KRAS-driven tumors are metabolically programmed to support their growth and survival, which can be used to identify metabolic vulnerabilities. In the present study, we aimed to understand the role of extracellularly derived fatty acids in KRAS-driven pancreatic cancer. METHODS To assess the dependence of PDAC cells on extracellular fatty acids we employed delipidated serum or RNAi-mediated suppression of ACSL3 (to inhibit the activation and cellular retention of extracellular fatty acids) followed by cell proliferation assays, qPCR, apoptosis assays, immunoblots and fluorescence microscopy experiments. To assess autophagy in vivo, we employed the KrasG12D/+;p53flox/flox;Pdx1-CreERT2 (KPC) mice crossed with Acsl3 knockout mice, and to assess the efficacy of the combination therapy of ACSL3 and autophagy inhibition we used xenografted human cancer cell-derived tumors in immunocompromised mice. RESULTS Here we show that depletion of extracellularly derived lipids either by serum lipid restriction or suppression of ACSL3, triggers autophagy, a process that protects PDAC cells from the reduction of bioenergetic intermediates. Combined extracellular lipid deprivation and autophagy inhibition exhibits anti-proliferative and pro-apoptotic effects against PDAC cell lines in vitro and promotes suppression of xenografted human pancreatic cancer cell-derived tumors in mice. Therefore, we propose lipid deprivation and autophagy blockade as a potential co-targeting strategy for PDAC treatment. CONCLUSIONS Our work unravels a central role of extracellular lipid supply in ensuring fatty acid provision in cancer cells, unmasking a previously unappreciated metabolic vulnerability of PDAC cells