Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression

The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD) has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs) and cholesterol accumulation. Excess cholesterol autoxidizes to oxysterols during oxidative stress conditions. We hypothesize that interaction of FAs and cholesterol derivatives may primarily impair mitochondrial function and affect biogenesis adaptation during NAFLD progression. We demonstrated that the accumulation of specific non-enzymatic oxysterols in the liver of animals fed high-fat+high-cholesterol diet induces mitochondrial damage and depletion of proteins of the respiratory chain complexes. When tested in vitro, 5α-cholestane-3β,5,6β-triol (triol) combined to FFAs was able to reduce respiration in isolated liver mitochondria, induced apoptosis in primary hepatocytes, and down-regulated transcription factors involved in mitochondrial biogenesis. Finally, a lower protein content in the mitochondrial respiratory chain complexes was observed in human non-alcoholic steatohepatitis. In conclusion, hepatic accumulation of FFAs and non-enzymatic oxysterols synergistically facilitates development and progression of NAFLD by impairing mitochondrial function, energy balance and biogenesis adaptation to chronic injury

Trans-arterial radioembolization in intermediate-advanced hepatocellular carcinoma: systematic review and meta-analyses.

Published onlineJournal ArticleThis is the final version of the article. Available from Impact Journals via the DOI in this record.Trans-arterial radioembolization (TARE) is a recognized, although not explicitly recommended, experimental therapy for unresectable hepatocellular carcinoma (HCC).A systematic literature review was performed to identify published studies on the use of TARE in intermediate and advanced stages HCC exploring the efficacy and safety of this innovative treatment.Twenty-one studies reporting data on overall survival (OS) and time to progression (TTP), were included in a meta-analysis. The pooled post-TARE OS was 63% (95% CI: 56-70%) and 27% (95% CI: 21-33%) at 1- and 3-years respectively in intermediate stage HCC, whereas OS was 37% (95% CI: 26-50%) and 13% (95% CI: 9-18%) at the same time intervals in patients with sufficient liver function (Child-Pugh A-B7) but with an advanced HCC because of the presence of portal vein thrombosis. When an intermediate and advanced case-mix was considered, OS was 58% (95% CI: 48-67%) and 17% (95% CI: 12-23%) at 1- and 3-years respectively. As for TTP, only four studies reported data: the observed progression probability was 56% (95% CI: 41-70%) and 73% (95% CI: 56-87%) at 1 and 2 years respectively. The safety analysis, focused on the risk of liver decompensation after TARE, revealed a great variability, from 0-1% to more than 36% events, influenced by the number of procedures, patient Child-Pugh stage and treatment duration.Evidence supporting the use of radioembolization in HCC is mainly based on retrospective and prospective cohort studies. Based on this evidence, until the results of the ongoing randomized trials become available, radioembolization appears to be a viable treatment option for intermediate-advanced stage HCC.The present study was funded by ASBM Srl through an unrestricted grant to CERGAS, Bocconi University, Via Roentgen 1, 20136 Milan, Italy

Patent landscape report of a cutting-edge solid propellant

This thesis endeavors to present a comprehensive overview of the global state of solid propellant technology. Its genesis lies in the imperative to furnish contextual backing for a patent conceived, titled " Photo-polymerization for additive manufacturing of composite solid propellants", aimed at subsequent coherent market analysis. Solid propellants represent pivotal constituents utilized as propulsion fuel in rockets, missiles, and analogous systems. Comprised of solid chemical compounds—such as polymers, aluminum compounds, or graphite dioxide—combined with oxidizers and adjunctive additives, these materials furnish a steadfast energy source and exhibit prolonged stability, rendering them versatile for multifarious applications encompassing rocketry, launcher mechanisms, fire extinguishing agents, and airbag expansion. This work assumes the form of a Patent Landscape Report (PLR), wherein meticulous data processing and manipulation from a discerningly curated Patent Database will distill pertinent information and delineate trends germane to solid propellant technology. Patents are recognized as potent repositories of information, and PLRs are purposefully devised to distill intrinsic insights from these documents, thereby evaluating the extant technological progress within a sector and furnishing strategic support to companies and institutions within the field. Additionally, this endeavor aspires to provide an encompassing contextual understanding of solid propellants by delineating the distinct stages within the production process. Moreover, it endeavors to proffer an exhaustive introduction to the realm of patents, facilitating a robust foundational understanding pivotal for a more nuanced comprehension of the ensuing analytical processes. The exploration and analysis of the collected data will be executed utilizing R, an opensource programming language widely acclaimed for its prowess in data manipulation and visualization. Such an approach ensures comprehensive visual reinforcement for this scholarly pursuit. Subsequently, the outcomes gleaned from the varied analyses will be synthesized, thereby spotlighting key trends and insights in the conclusive and final deliberation

Quality assessment of studies comparing percutaneous ablative treatments in hepatocellular carcinoma.

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Glucose intolerance and hepatocellular carcinoma: recent findings for old diseases

In the last years, an increasing number of evidences on the influence of metabolic syndrome on the occurrence of hepatocellular carcinoma (HCC) have been developed. Type 2 mellitus diabetes (T2MD) has been found to increase the occurrence of primary liver tumors and to define a more aggressive carcinogenetic process. Furthermore, several preclinical and observational studies and a recent meta-analysis have shown that anti-diabetic drugs can modify the risk of HCC development in patients with T2DM. However, despite these evidences, underlying molecular mechanisms linking both pathological conditions have to be completely cleared yet. The study published by Gao et al. has found a possible molecular link between the two conditions, describing the predisposition to T2DM and HCC given by the haploinsufficiency of nuclear receptor coactivator 5 (NCOA5) in murine models. The authors have generated Ncoa5+/– (haploinsufficient) male mice and shown that 94% of male mutant mice developed HCC within 18 months of age, this in contrast with Ncoa5+/+ and Ncoa5+/– female mice. These results suggest that NCOA5 haploinsufficiency is linked to HCC development in male mice. Moreover, mutant male mice showed significantly elevated levels of fasting blood glucose and markedly decreased glucose tolerance and insulin sensitivity compared to Ncoa5+/+ littermates. This well-constructed work sheds light on the molecular link between T2DM and HCC and opens the way to further biological and clinical studies in the field of liver tumor prevention and treatment

Designing Of Curricula Of Environmental Engineering And Constructions Engineering For Sustainability

The experience carried out at the University of Florence, Department of Civil and Environmental Engineering, in designing two new undergraduate curricula in “Environmental Engineering” and “Civil and Building Engineering for sustainability”, is reported. The bachelor in Environmental Engineering aims to train engineers capable of working in the field of protection of environment, territory and natural resources. The bachelor in Civil and Building Engineering for sustainability aims to train engineers capable of working in the field of structures, infrastructures, and constructions in general, as well as management and safety of construction processes. The development of the two curricula was based preliminarily on a national and international survey of degree programs of the same type and with shared learning outcomes. Subsequently, labour market needs were identified starting from discussions with all stakeholders, students and professors included. Teaching methods and methods for assessing students\u27 preparation have also been revised and the teaching plan of both curricula is characterized in the third year by the presence of multidisciplinary laboratories, focused on the most characterizing themes of each programme and the different disciplines with integrative and specific in-depth characteristics. Finally, a thorough design of the two courses contents has been initiated, based on the definition of the general educational objectives and the specific disciplines