374 research outputs found
Evaluation of polygenic determinants of non-alcoholic fatty liver disease (NAFLD) by a candidate genes resequencing strategy
NAFLD is a polygenic condition but the individual and cumulative contribution of identified genes remains to be established. To get additional insight into the genetic architecture of NAFLD, GWAS-identified GCKR, PPP1R3B, NCAN, LYPLAL1 and TM6SF2 genes were resequenced by next generation sequencing in a cohort of 218 NAFLD subjects and 227 controls, where PNPLA3 rs738409 and MBOAT7 rs641738 genotypes were also obtained. A total of 168 sequence variants were detected and 47 were annotated as functional. When all functional variants within each gene were considered, only those in TM6SF2 accumulate in NAFLD subjects compared to controls (P = 0.04). Among individual variants, rs1260326 in GCKR and rs641738 in MBOAT7 (recessive), rs58542926 in TM6SF2 and rs738409 in PNPLA3 (dominant) emerged as associated to NAFLD, with PNPLA3 rs738409 being the strongest predictor (OR 3.12, 95% CI, 1.8-5.5, P 0.28 was associated with a 3-fold increased risk of NAFLD. Interestingly, rs61756425 in PPP1R3B and rs641738 in MBOAT7 genes were predictors of NAFLD severity. Overall, TM6SF2, GCKR, PNPLA3 and MBOAT7 were confirmed to be associated with NAFLD and a score based on these genes was highly predictive of this condition. In addition, PPP1R3B and MBOAT7 might influence NAFLD severity
Statin liver safety in non-alcoholic fatty liver disease: A systematic review and metanalysis
Aims Statin liver safety in non-alcoholic fatty liver disease (NAFLD) patients is not well defined. We analysed differences in liver function tests, including alanine transaminase aminotransferase (ALT), aspartate transaminase (AST) and gamma-glutamyl transpeptidase (GGT) in NAFLD patients treated or not treated with statins. Methods We performed a systematic review of MEDLINE via PubMed and EMBASE databases and metanalysis of clinical studies investigating levels of ALT, AST and GGT in NAFLD according to statin treatment. Mean difference (MD) and percentage MD were calculated between the two groups. Results We included 22 studies with 2345 NAFLD patients. Overall, 16 were before-after interventional, five were cross-sectional and one was combined cross-sectional/interventional study. In all interventional studies, except one, patients had raised ALT, AST and GGT at baseline. Interventional studies showed reduced ALT values with an MD reduction of -27.2 U/L (95% CI -35.25/-19.15) and a percentage MD reduction of -35.41% (95% CI -44.78/-26.04). Also, AST values were reduced after statin treatment in interventional studies with an MD of -18.82 U/L (95% CI -25.63/-12.02) (percentage -31.78%, 95% CI -41.45/-22.11). Similarly, GGT levels were reduced after statin treatment with an MD of -19.93 U/L (95% CI -27.10/-12.77) (percentage -25.57%, 95% CI -35.18/-15.97). Cross-sectional studies showed no difference in AST and GGT values between patients treated with and without statins. Conclusion In interventional studies, ALT, AST and GGT were reduced after statin treatment with a percentage mean difference of -35.41%, -31.78% and -25.57%, respectively, while observational studies showed a null effect, suggesting liver safety of statins in NAFLD patients
HDL-mediated cholesterol efflux and plasma loading capacities are altered in subjects with metabolically-but not genetically driven non-alcoholic fatty liver disease (NAFLD)
Background. Non-alcoholic fatty liver disease (NAFLD) increases the risk of atherosclerosis but this risk may differ between metabolically- vs. genetically-driven NAFLD. High-density lipoprotein (HDL)-mediated cholesterol efflux (CEC) and plasma loading capacity (CLC) are key factors in atherogenesis. Aims. To test whether CEC and CLC differ between metabolically- vs. genetically-determined NAFLD. Methods: CEC and CLC were measured in 19 patients with metabolic NAFLD and wild-type PNPLA3 genotype (Group M), 10 patients with genetic NAFLD carrying M148M PNPLA3 genotype (Group G), and 10 controls PNPLA3 wild-types and without NAFLD. CEC and CLC were measured ex vivo by isotopic and fluorimetric techniques using cellular models. Results: Compared with Group G, Group M showed reduced total CEC (-18.6%; p < 0.001) as well as that mediated by cholesterol transporters (-25.3% ABCA1; -16.3% ABCG1; -14.8% aqueous diffusion; all p < 0.04). No difference in CEC was found between Group G and controls. The presence of metabolic syndrome further impaired ABCG1-mediated CEC in Group M. Group M had higher plasma-induced CLC than Group G and controls (p < 0.001). Conclusions: Metabolically-, but not genetically-, driven NAFLD associates with dysfunctional HDL-meditated CEC and abnormal CLC. These data suggest that the mechanisms of anti-atherogenic protection in metabolic NAFLD are impaired.Background. Non-alcoholic fatty liver disease (NAFLD) increases the risk of atherosclerosis but this risk may differ between metabolically-vs. genetically-driven NAFLD. High-density lipoprotein (HDL)-mediated cholesterol efflux (CEC) and plasma loading capacity (CLC) are key factors in atherogenesis. Aims. To test whether CEC and CLC differ between metabolically-vs. genetically-determined NAFLD. Methods: CEC and CLC were measured in 19 patients with metabolic NAFLD and wild-type PNPLA3 genotype (Group M), 10 patients with genetic NAFLD carrying M148M PNPLA3 genotype (Group G), and 10 controls PNPLA3 wild-types and without NAFLD. CEC and CLC were measured ex vivo by isotopic and fluorimetric techniques using cellular models. Results: Compared with Group G, Group M showed reduced total CEC (−18.6%; p < 0.001) as well as that mediated by cholesterol transporters (−25.3% ABCA1; −16.3% ABCG1; −14.8% aqueous diffusion; all p < 0.04). No difference in CEC was found between Group G and controls. The presence of metabolic syndrome further impaired ABCG1-mediated CEC in Group M. Group M had higher plasma-induced CLC than Group G and controls (p < 0.001). Conclusions: Metabolically-, but not genetically-, driven NAFLD associates with dysfunctional HDL-meditated CEC and abnormal CLC. These data suggest that the mechanisms of anti-atherogenic protection in metabolic NAFLD are impaired
emission rates in absorptions at rest on Li, Li, Be, C and O
An experimental study of the reaction
on Li, Li, Be, C and O -shell nuclei is
presented. The data were collected by the FINUDA spectrometer operating at the
DANE -factory (LNF-INFN, Italy). Emission rates for the reaction in
the mentioned nuclei are measured and compared with the few existing data. The
spectra of several observables are discussed; indications of Quasi-Free
absorptions by a pair embedded in the nucleus can be obtained from
the study of the missing mass distributions.Comment: Version accepted by PR
Proton spectra from Non-Mesonic Weak Decay of p-shell Lambda-Hypernuclei and evidence for the two-nucleon induced process
New spectra from the FINUDA experiment of the Non Mesonic Weak Decay (NMWD)
proton kinetic energy for 9(Lambda)Be, 11(Lambda)B, 12(Lambda)C, 13(Lambda)C,
15 (Lambda)N and 16(Lambda)O are presented and discussed along with the
published data on 5(Lambda)He and 7(Lambda)Li. Exploiting the large mass number
range and the low energy threshold (15 MeV) for the proton detection of FINUDA,
an evaluation of both Final State Interactions (FSI) and the two nucleon
induced NMWD contributions to the decay process has been done. Based on this
evaluation, a linear dependence of FSI on the hypernuclear mass number A is
found and for the two nucleon stimulated decay rate the experimental value of
Gamma2/Gammap=0.43+-0.25 is determined for the first time. A value for the two
nucleon stimulated decay rate to the total decay rate
Gamma2/GammaNMWD=0.24+-0.10 is also extracted.Comment: 11 pages and 2 figure
A study of the proton spectra following the capture of in Li and C with FINUDA
Momenta spectra of protons emitted following the capture of in Li
and C have been measured with 1% resolution. The C spectrum is
smooth whereas for Li a well defined peak appears at about 500 MeV/. The
first observation of a structure in this region was identified as a strange
tribaryon or, possibly, a -nuclear state. The peak is correlated with a
coming from decay in flight, selected by setting momenta
larger than 275 MeV/. The could be produced, together with a 500
MeV/ proton, by the capture of a in a deuteron-cluster substructure of
the Li nucleus. The capture rate for such a reaction is (1.62\pm
0.23_{stat} ^{+0.71}_{-0.44}(sys))%/K^-_{stop}, in agreement with the existing
observations on He targets and with the hypothesis that the Li nucleus
can be interpreted as a cluster.Comment: 21 pages, 10 figures. Accepted for publication in NP
Proprotein convertase subtilisin kexin type 9 inhibitors reduce platelet activation modulating ox-LDL pathways
Background: Proprotein convertase subtilisin kexin type 9 inhibitors (PCSK9i) lower LDL-cholesterol and slow atherosclerosis preventing cardiovascular events. While it is known that circulating PCSK9 enhances platelet activation (PA) and that PCSK9i reduce it, the underlying mechanism is not still clarified. Methods: In a multicenter before–after study in 80 heterozygous familial hypercholesterolemia (HeFH) patients on treatment with maximum tolerated statin dose ± ezetimibe, PA, soluble-NOX2-derived peptide (sNOX2-dp), and oxidized-LDL (ox-LDL) were measured before and after six months of PCSK9i treatment. In vitro study investigates the effects of plasma from HeFH patients before and after PCK9i on PA in washed platelets (wPLTs) from healthy subjects. Results: Compared to baseline, PCSK9i reduced the serum levels of LDL-c, ox-LDL, Thromboxane (Tx) B2, sNOX2-dp, and PCSK9 (p Conclusions: PCSK9i treatment reduces PA modulating NOX2 activity and in turn ox-LDL formation in HeFH patients
Correlated pairs from the reaction
Correlated pairs emitted after the absorption of negative kaons
at rest in light nuclei and are
studied. -hyperons and deuterons are found to be preferentially
emitted in opposite directions. The invariant mass spectrum of
shows a bump whose mass is 32516 MeV/c. The bump mass (binding
energy), width and yield are reported. The appearance of a bump is discussed in
the realm of the [] clustering process in nuclei. The experiment was
performed with the FINUDA spectrometer at DANE (LNF).Comment: 13 pages, 5 figures, accepted for publication in Phys. Lett.
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