HCV derived from sera of HCV-infected patients induces pro-fibrotic effects in human primary fibroblasts by activating GLI2

Hepatitis C virus (HCV) infection is a leading cause of liver fibrosis, especially in developing countries. The process is characterized by the excess accumulation of ECM that may lead, over time, to hepatic cirrhosis, liver failure and also to hepatocarcinoma. The direct role of HCV in promoting fibroblasts trans-differentiation into myofibroblasts, the major fibrogenic cells, has not been fully clarified. In this study, we found that HCV derived from HCV-infected patients infected and directly induced the trans-differentiation of human primary fibroblasts into myofibroblasts, promoting fibrogenesis. This effect correlated with the activation of GLI2, one of the targets of Hedgehog signaling pathway previously reported to be involved in myofibroblast generation. Moreover, GLI2 activation by HCV correlated with a reduction of autophagy in fibroblasts, that may further promoted fibrosis. GLI2 inhibition by Gant 61 counteracted the pro-fibrotic effects and autophagy inhibition mediated by HCV, suggesting that targeting HH/GLI2 pathway might represent a promising strategy to reduce the HCV-induced fibrosis

Combined carriership of TLR9-1237C and CD14-260T alleles enhances the risk of developing chronic relapsing pouchitis

AIM: To investigate the single nucleotide polymorphisms (SNPs) in genes involved in bacterial recognition and the susceptibility to pouchitis or pouchitis severity. METHODS: Analyses of CD14 -260C>T, CARD15/NOD2 3020insC, Toll-like receptor (TLR)4 +896A>G, TLR9 -1237T>C, TLR9+2848G>A, and IRAKM + 22148G>A SNPs were performed in 157 ileal-pouch anal anastomosis (IPAA) patients (79 patients who did not develop pouchitis, 43 infrequent pouchitis patients, 35 chronic relapsing pouchitis patients) and 224 Italian Caucasian healthy controls. RESULTS: No significant differences were found in SNP frequencies between controls and IPAA patients. However, a significant difference in carriership frequency of the TLR9-1237C allele was found between the infrequent pouchitis and chronic relapsing pouchitis groups [P = 0.028, oddos ratio (OR) = 3.2, 95%CI = 1.2-8.6]. This allele uniquely represented a 4-locus TLR9 haplotype comprising both studied TLR9 SNPs in Caucasians. Carrier trait analysis revealed an enhanced combined carriership of the alleles TLR9 -1237C and CD14 -260T in the chronic relapsing pouchitis and infrequent pouchitis group (P = 0.018, OR = 4.1, 95%CI = 1.4 -12.3). CONCLUSION: There is no evidence that the SNPs predispose to the need for IPAA surgery. The significant increase of the combined carriership of the CD14 -260T and TLR9 -1237C alleles in the chronic relapsing pouchitis group suggests that these markers identify a subgroup of IPAA patients with a risk of developing chronic or refractory pouchitis

TOpic: rare and special cases, the real "Strange cases"

Introduction: The bladder hernia represents approximately 1-3% of all inguinal hernias, where patients aged more than 50 years have a higher incidence (10%). Many factors contribute to the development of a bladder hernia, including the presence of a urinary outlet obstruction causing chronic bladder distention, the loss of bladder tone, pericystitis, the perivesical bladder fat protrusion and the obesity

Oral beclometasone dipropionate in the treatment of extensive and left-sided active ulcerative colitis: a multicentre randomised study.

AIM: To explore the efficacy and safety of the topically acting steroid beclometasone dipropionate (BDP) in an oral controlled release formulation in the treatment of extensive or left-sided ulcerative colitis. METHODS: In a multicentre, randomised, parallel-group, single-blind study, patients with active mild to moderate ulcerative colitis were randomised to a 4-week treatment with BDP 5 mg/day o.d. vs. 5-ASA 0.8 g t.d.s. The primary efficacy variable was the decrease of Disease Activity Index (DAI) (clinical symptoms and endoscopic appearance of mucosa). Safety was evaluated by monitoring adverse events, vital signs, haematochemical parameters and adrenal function

Oral beclometasone dipropionate in the treatment of active ulcerative colitis: a double-blind placebo-controlled study.

AIM: To evaluate efficacy and safety of oral beclometasone dipropionate (BDP) when added to 5-ASA in the treatment of patients with active ulcerative colitis. METHODS: In a 4-week, placebo-controlled, double-blind study, patients with extensive or left-sided mild to moderate active ulcerative colitis were randomized to receive oral 5-ASA (3.2 g/day) plus BDP (5 mg/day) or placebo. Clinical, endoscopic and histologic features, and haematochemical parameters were recorded at baseline and at the end of the study

Editorial: microbial fermentation for improved sensory properties and functionality of sustainable foods

Growing awareness of the health and climate crises has led consumers to reduce meat and alcohol consumption, and government organizations to act on it, driving academic and industry research toward plant-based foods. One of the major challenges in transitioning from animal- to plant-based diets is to replicate the unique sensory characteristics of animal-based foods. Therefore, there is a need for innovation in flavor, texture, and trigeminal sensations to meet the expectations of the growing consumer groups. In this framework, the main objective of this Research Topic was to explore our current understanding of flavor and functionally active microbes in the production of novel foods, with a focus on microbial secondary metabolites

Temperature-Dependent Thévenin Model of a Li-Ion Battery for Automotive Management and Control

This paper focuses on the analysis of Li-ion battery behavior at different temperatures through the Thévenin electrical circuit model. First, evaluations for both steady-state and dynamic battery applications are provided, then an overview of the different battery models to describe their dynamic behavior is analyzed. The focus is dedicated to the double polarization Thévenin-based equivalent circuit model since it represents an optimal trade-off between accuracy and computation effort, which justifies its implementation in a Battery Management System (BMS) for automotive real-time monitoring and control. The model is composed of a voltage source, one series resistor and two series RC blocks. The Hybrid Pulse Power Characterization test (HPPC) is performed inside a climatic chamber to extract the electrical parameters of the model and their dependency from both temperature and State Of Charge (SOC). The load-current effects on the battery performance are not considered for the simplicity and lightness of the presented model. The presented procedure has broader validity and is mostly independent of cell format and Li-ion chemistry, despite a specific cylindrical battery cell is chosen for the study. The results of the test are suitable for the future implementation of a proper algorithm for SOC and State Of Health SOH estimations. Moreover, they provide an effective electrical and thermal characterization of the cell to evaluate the heat generation rate inside the cell

Dynamic Electro-Thermal Li-ion Battery Model for Control Algorithms

This paper presents a fast and effective approach to evaluate the heat generation of a Li-ion battery system. The thermal characterization of Li-ion batteries is a relevant topic for the correct monitoring of the battery pack. In particular, a reduced-order model, that estimates the thermal dynamics of a Li-ion battery cell, is reported. The proposed approach relies on the definition of a boundary-value problem for heat conduction, in the form of a linear partial differential equation with the integration of Equivalent Circuit Model. The model is based on the double polarization Thévenin equivalent circuit model since it represents an optimal trade-off between accuracy and computation effort, which justifies its implementation in a Battery Management System (BMS) for automotive real-time monitoring and control. The resulting model predicts the temperature dynamics at the external surface in relation with the rate of the internal heat generation. In this paper, the model is applied to estimate the temperature of a cylindrical cell during a discharging transient and it uses electrical data acquired from experimental tests and is validated Computational fluid dynamics simulation. The results of the test are suitable for the future implementation of a proper algorithm for State of Charge SOC and State of Health SOH estimations