PPAR-Targeted Therapies in the Treatment of Non-Alcoholic Fatty Liver Disease in Diabetic Patients.

Peroxisome proliferator-activated receptors (PPAR), ligand-activated transcription factors of the nuclear hormone receptor superfamily, have been identified as key metabolic regulators in the liver, skeletal muscle, and adipose tissue, among others. As a leading cause of liver disease worldwide, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) cause a significant burden worldwide and therapeutic strategies are needed. This review provides an overview of the evidence on PPAR-targeted treatment of NAFLD and NASH in individuals with type 2 diabetes mellitus. We considered current evidence from clinical trials and observational studies as well as the impact of treatment on comorbid metabolic conditions such as obesity, dyslipidemia, and cardiovascular disease. Future areas of research, such as possible sexually dimorphic effects of PPAR-targeted therapies, are briefly reviewed

COVID-19 in Liver Transplant Recipients: A Systematic Review.

Liver transplant (LT) recipients are considered a vulnerable population amidst the COVID-19 pandemic. To date, available data have been heterogeneous and scarce. Therefore, we conducted a systematic literature review identifying English-language articles published in PubMed between November 2019 and 30 May 2021. We aimed to explore three areas: (1) outcome and clinical course; (2) immunological response after COVID-19 in LT recipients; and (3) vaccination response. After systematic selection, 35, 4, and 5 articles, respectively, were considered suitable for each area of analysis. Despite the heterogeneity of the reports included in this study, we found that gastrointestinal symptoms were common in LT recipients. The outcome of the LT population was not per se worse compared to the general population, although careful management of immunosuppressive therapy is required. While a complete therapy discontinuation is not encouraged, caution needs to be taken with use of mycophenolate mofetil (MMF), favoring tacrolimus (TAC) use. Although data conflicted about acquired immunity after SARS-CoV-2 infection, vaccine immunogenicity appeared to be low, suggesting that the level of surveillance should be kept high in this population

Biochar as a catalyst for hydrogen production from methane conversion

Please click Additional Files below to see the full abstrac

Hepatocellular Carcinoma in Cirrhotic Versus Non-Cirrhotic Patients: A Retrospective Study of 483 Patients

Background and Aim: Although cirrhosis is a classical risk factor for the development of hepatocellular carcinoma (HCC), its absence does not exclude this risk. We aimed to assess the clinical characteristics and outcomes of cirrhotic HCC (C-HCC) and non-cirrhotic HCC (NC-HCC) patients. Methods: Patients consecutively included in a prospective HCC cohort (University Hospital Bern) were analysed. They were categorised into two groups, based on the basis of histology or combined radiological and laboratory characteristics. Results: 20.4% of patients were NC-HCC. This group was characterized by a higher median age and a higher female prevalence compared to the C-HCC group. Non-alcoholic fatty liver disease (NAFLD) (25.7%) and HBV infection (14.9%) were the main risk factors in this group, whereas alcohol abuse (26%) and HCV (21.6%) in C-HCC, P<0.001. 19.4% of them were diagnosed during a screening programme. Resection was performed in 54.5% of NC HCC patients despite the advanced stage (BCLC stage B and C). No statistically significant difference in survival rate was observed between C and NC-HCC patients (24 months vs. 33.9 months, P=0.162). In multivariate analysis, in the NC-HCC group each unit increase in BMI was associated with mortality while liver transplantation and resection were positively associated with survival. In the C-HCC group, the BCLC stage C was negatively associated with survival while all the therapeutic lines were negative factors for mortality. Conclusion: NC-HCC patients were diagnosed more often outside a screening programme. The patients were older, with a higher female prevalence and despite an advanced stage, were often amenable to surgery

Carbon Monoliths with Hierarchical Porous Structure for All-Vanadium Redox Flow Batteries

Carbon monoliths were tested as electrodes for vanadium redox batteries. The materials were synthesised by a hard-templating route, employing sucrose as carbon precursor and sodium chloride crystals as the hard template. For the preparation process, both sucrose and sodium chloride were ball-milled together and molten into a paste which was hot-pressed to achieve polycondensation of sucrose into a hard monolith. The resultant material was pyrolysed in nitrogen at 750 &#9702;C, and then washed to remove the salt by dissolving it in water. Once the porosity was opened, a second pyrolysis step at 900 &#9702;C was performed for the complete conversion of the materials into carbon. The products were next characterised in terms of textural properties and composition. Changes in porosity, obtained by varying the proportions of sucrose to sodium chloride in the initial mixture, were correlated with the electrochemical performances of the samples, and a good agreement between capacitive response and microporosity was indeed observed highlighted by an increase in the cyclic voltammetry curve area when the SBET increased. In contrast, the reversibility of vanadium redox reactions measured as a function of the difference between reduction and oxidation potentials was correlated with the accessibility of the active vanadium species to the carbon surface, i.e., was correlated with the macroporosity. The latter was a critical parameter for understanding the differences of energy and voltage efficiencies among the materials, those with larger macropore volumes having the higher efficiencies.This work was supported by ICEEL and Region Grand Est and J.F.V.-V. was hired with these fundings. This work was partly supported by a grant overseen by the French National Research Agency (Pc2TES ANR-16-CE06-0012-01), and the authors involved in it (AC, BK and VF) acknowledge the support of the project's coordinator, Mrs Fouzia Achchaq. This study was partly supported by TALiSMAN project (2019-000214), funded by European Regional Development Fund (ERDF)

Use of statins after liver transplantation is associated with improved survival: results of a nationwide study

BACKGROUND There is limited information on the effects of statins on the outcomes of liver transplantation (LT), regarding either their use by LT recipients or donors. AIM To analyse the association between statin exposure and recipient and graft survival. METHODS We included adult LT recipients with deceased donors in a nationwide prospective database study. Using a multistate modelling approach, we examined the effect of statins on the transition hazard between LT, biliary and vascular complications and death, allowing for recurring events. The observation time was 3 years. RESULTS We included 998 (696 male, 70%, mean age 54.46 ± 11.14 years) LT recipients. 14% of donors and 19% of recipients were exposed to statins during the study period. During follow-up, 141 patients died; there were 40 re-LT and 363 complications, with 66 patients having two or more complications. Treatment with statins in the recipient was modelled as a concurrent covariate and associated with lower mortality after LT (HR = 0.35; 95% CI 0.12-0.98; p = 0.047), as well as a significant reduction of re-LT (p = 0.004). However, it was not associated with lower incidence of complications (HR = 1.25; 95% CI = 0.85-1.83; p = 0.266). Moreover, in patients developing complications, statin use was significantly associated with decreased mortality (HR = 0.10; 95% CI = 0.01-0.81; p = 0.030), and reduced recurrence of complications (HR = 0.43; 95% CI = 0.20-0.93; p = 0.032). CONCLUSIONS Statin use by LT recipients may confer a survival advantage. Statin administration should be encouraged in LT recipients when clinically indicated

Use of statins after liver transplantation is associated with improved survival: results of a nationwide study.

BACKGROUND There is limited information on the effects of statins on the outcomes of liver transplantation (LT), regarding either their use by LT recipients or donors. AIM To analyse the association between statin exposure and recipient and graft survival. METHODS We included adult LT recipients with deceased donors in a nationwide prospective database study. Using a multistate modelling approach, we examined the effect of statins on the transition hazard between LT, biliary and vascular complications and death, allowing for recurring events. The observation time was 3 years. RESULTS We included 998 (696 male, 70%, mean age 54.46 ± 11.14 years) LT recipients. 14% of donors and 19% of recipients were exposed to statins during the study period. During follow-up, 141 patients died; there were 40 re-LT and 363 complications, with 66 patients having two or more complications. Treatment with statins in the recipient was modelled as a concurrent covariate and associated with lower mortality after LT (HR = 0.35; 95% CI 0.12-0.98; p = 0.047), as well as a significant reduction of re-LT (p = 0.004). However, it was not associated with lower incidence of complications (HR = 1.25; 95% CI = 0.85-1.83; p = 0.266). Moreover, in patients developing complications, statin use was significantly associated with decreased mortality (HR = 0.10; 95% CI = 0.01-0.81; p = 0.030), and reduced recurrence of complications (HR = 0.43; 95% CI = 0.20-0.93; p = 0.032). CONCLUSIONS Statin use by LT recipients may confer a survival advantage. Statin administration should be encouraged in LT recipients when clinically indicated

The impact of perceived donor liver quality on post-transplant outcome.

BACKGROUND We analysed the impact of perceived liver donor quality on transplant recipient outcomes. METHODS this prospective cohort study included all deceased liver donors during 2008-2018 in the Swiss Transplant Cohort Study. Perceived low-quality liver donors were defined when refused for ≥5 top listed recipients or for all recipients in at least one centre before being transplanted. The effect of liver donor quality on relisting or recipient death at 1 week and 1 year after transplantation was analysed using Kaplan-Meier and Cox proportional hazard models. A 1:3 matching was also performed using a recipient score. RESULTS Of 973 liver donors, 187 (19.2%) had perceived poor-quality. Males, obesity, donation after circulatory death and alanine aminotransferase values were significantly associated with perceived poor-quality, with no significant effect of the perceived quality on re-listing or death within the first week and first year post-transplant [(aHR) = 1.45, 95% CI: (0.6, 3.5), P = 0.41 and aHR = 1.52 (95% CI 0.98-2.35), P = 0.06], adjusting by recipient age and gender, obesity, diabetes, prior liver transplantation and model for end-stage liver disease (MELD) score. At 1 year, prior liver transplantation and higher MELD score associated with higher risk of re-listing or death. CONCLUSION Comparable post-transplant outcomes with different perceived quality liver donors stresses the need to improve donor selection in liver transplantation

The He II Emitting Nebula N44C in the LMC: Optical/UV Spectroscopy of the Nebula and its Ionizing Star

We present HST spectroscopy and imaging, along with new ground-based spectroscopy and ROSAT HRI imaging, of the He II emitting nebula N44C and its ionizing star. A GHRS spectrogram of the ionizing star yields a spectral type of about O7 for the star. The lack of P Cygni profiles for Si IV and C IV indicates that the star is not a supergiant. The nebular abundances in the ionized gas are consistent with average abundances for LMC H II regions, with the possible exception that nitrogen may be enhanced. Enrichment by a former evolved companion star is not evident. A long-slit echelle spectrogram in H-alpha + [N II] shows no evidence for high-velocity gas in N44C. This rules out high-velocity shocks as the source of the nebular He II emission. A 108 ks ROSAT HRI image of N44C shows no X-ray point source to a 3-sigma upper limit L(X) < 10^34 erg s^-1 in the 0.1-2.0 keV band. Based on new measurements of the electron density in the He II emitting region, we derive recombination timescales of approximately 20 yrs for He^+2 and approximately 4 yrs for Ne^+4. If N44C is a fossil X-ray ionized nebula, this places severe constraints on when the putative X-ray source could have turned off. The presence of strong [Ne IV] emission in the nebula is puzzling if the ionizing source has turned off. It is possible the system is related to the Be X-ray binaries, although the O star in N44C does not show Be characteristics at the present time. Monitoring of X-rays and He II emission from the nebula, as well as a radial velocity study of the ionizing star, are needed to fully understand the emission line spectrum of N44C.Comment: 37 pages, 7 figures (1 color .gif image); accepted for publication in the 10 Dec 2000 Astrophysical Journal. Complete PostScript and PDF versions can also be obtained at http://ocotillo.as.arizona.edu/~dgarnet

Abrogation of Cbl–PI3K Interaction Increases Bone Formation and Osteoblast Proliferation

Cbl is an adaptor protein and E3 ligase that plays both positive and negative roles in several signaling pathways that affect various cellular functions. Tyrosine 737 is unique to Cbl and phosphorylated by Src family kinases. Phosphorylated CblY737 creates a binding site for the p85 regulatory subunit of phosphatidylinositol 3 kinase (PI3K) that also plays an important role in the regulation of bone homeostasis. To investigate the role of Cbl–PI3K interaction in bone homeostasis, we examined knock-in mice in which the PI3K binding site on Cbl was ablated due to the substitution of tyrosine 737 to phenylalanine (CblYF/YF, YF mice). We previously reported that bone volume in these mice is increased due to decreased osteoclast function (Adapala et al., J Biol Chem 285:36745–36758, 19). Here, we report that YF mice also have increased bone formation and osteoblast numbers. In ex vivo cultures bone marrow-derived YF osteoblasts showed increased Col1A expression and their proliferation was also significantly augmented. Moreover, proliferation of MC3T3-E1 cells was increased after treatment with conditioned medium generated by culturing YF bone marrow stromal cells. Expression of stromal derived factor-1 (SDF-1) was increased in YF bone marrow stromal cells compared to wild type. Increased immunostaining of SDF-1 and CXCR4 was observed in YF bone marrow stromal cells compared to wild type. Treatment of YF condition medium with neutralizing anti-SDF-1 and anti-CXCR4 antibodies attenuated MC3T3-E1 cell proliferation. Cumulatively, these results show that abrogation of Cbl–PI3K interaction perturbs bone homeostasis, affecting both osteoclast function and osteoblast proliferation