BackgroundNeuregulin 4 (Nrg4) is a secreted adipokine recently identified as playing an important role in modulating systemic energy metabolism and the development of obesity-associated disorders. However, information is not available regarding the association between circulating Nrg4 and risk of metabolic syndrome (MetS) in humans.MethodsWe measured serum Nrg4 in 1212 obese adult subjects (aged 40 years or older), with a waist circumference greater than 90 cm for men or 80 cm for women, recruited from the community.ResultsMetS subjects had lower levels of circulating Nrg4 than healthy controls (P < 0.01). The prevalence of MetS was higher in subjects with lower levels of circulating Nrg4 compared to those with higher values (67.3 % vs. 57.4 %, P < 0.05). Likewise, subjects with low levels of circulating Nrg4 had high prevalence of raised fasting glucose and blood pressure, but there was no association with raised triglycerides and reduced HDL-c. In multivariable logistic regression analyses, increased serum Nrg4 was significantly associated with reduced risk of MetS (OR: 0.603; 95 % CI, 0.439–0.828; P = 0.002), adjusting for age, gender, current smoking, alcohol consumption, physical activity, BMI, systolic blood pressure, fasting glucose, triglyceride, HDL-c, HOMA-IR, and body fat mass; however, such associations with serum Nrg4 were not noted for each component of MetS.ConclusionsThese findings indicate that circulating Nrg4 concentrations are inversely associated with risk of MetS in obese Chinese adults, suggesting that circulating Nrg4 concentrations may be a protective factor in the development of MetS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0703-6) contains supplementary material, which is available to authorized users.

Background Reversible N 6 -methyladenosine (m 6 A) modifications in messenger RNAs can be categorized under the field of “RNA epigenetics.” However, the potential role of m 6 A-related genes in gastric cancer (GC) prognosis has not been systematically researched. Aims This study was aimed at providing insights into the prognostic role of m 6 A-related gene expression, at both mRNA and protein levels. Methods Kaplan–Meier (KM) plotter database and The Cancer Genome Atlas (TCGA) database were used to explore the prognostic significance of individual m 6 A-related genes in overall survival (OS) and progression-free survival at the mRNA level. For independent validation, the protein level of genes significantly associated with prognosis in both databases was further detected in 450 paired GC and corresponding adjacent non-tumor tissues using tissue microarray (TMA)-based immunohistochemistry (IHC). The relationship between the FTO and ALKBH1 expression and the clinicopathological characteristics was explored. Results Among nine m 6 A-related genes, aberrantly high mRNA expression of FTO and ALKBH1 was associated with poor OS in the KM and TCGA cohorts. However, the TMA-IHC indicated that protein expression of FTO and ALKBH1 was markedly downregulated in GC tissues. A lower protein level of ALKBH1 was closely correlated with larger tumor sizes (≥ 5 cm) and more advanced TNM stages, while lower FTO protein expression was associated with shorter OS in GC patients. Conclusions Aberrant expression of demethylase genes, FTO and ALKBH1 , has a distinct prognostic value in GC patients, indicating that FTO and ALKBH1 may play vital roles in GC progression and metastasis. Electronic supplementary material The online version of this article (10.1007/s10620-018-5452-2) contains supplementary material, which is available to authorized users.

The development of vaccination and novel therapy for hepatitis C virus (HCV) has been hampered by the lack of suitable small-animal models. GB virus B (GBV-B), closely related to HCV, causes viral hepatitis in common marmosets (Callithrix jacchue jacchus) and might represent an attractive surrogate model for HCV infection. However, differences exist between GBV-B and HCV in spite of a short genetic distance between the two viruses. Here we report common marmosets infected with two HCV/GBV-B chimeras containing HCV structural genes coding for either whole core and envelope proteins (CE1E2p7) or full envelope proteins (E1E2p7) substituted for the counterpart elements of GBV-B. Na€ ıve animals intrahepatically injected with chimeric RNA transcripts or intravenously injected with sera from primary infected animals produced high levels of circulating infectious chimeric viruses and they developed chronic infection. Tacrolimus-treated marmosets inoculated with a CE1E2p7 chimera had higher viral loads and long-term persistent infection. A moderate elevation of serum aspartate aminotransferase (AST) levels was observed in parallel with viral replication. Chimeras recovered from liver samples revealed 1/958 adaptive viral mutations. Histopathological changes typical of viral hepatitis were observed in liver tissues from all types of HCV chimeras-infected marmosets. HCV core and E2 proteins were detected in liver tissues from infected animals by immunohistochemical staining. Fluctuations of chimeric virus replication in marmosets with spontaneous and sporadic viral clearance might be related to specific antibody and T-cell response to HCV proteins in vivo. Replication of CE1E2p7 chimera was observed in primary hepatocyte cultures by immunofluorescent staining in vitro. Conclusion: Infectious HCV chimeras causing chronic hepatitis in marmosets might constitute a small primate model suitable for evaluation of virus-cell interaction, vaccination, and antiviral therapy against HCV infection. (HEPATOLOGY 2014;59:789-802)

ImportanceThe efficacy and safety of time-restricted eating (TRE) on nonalcoholic fatty liver disease (NAFLD) remain uncertain.ObjectiveTo compare the effects of TRE vs daily calorie restriction (DCR) on intrahepatic triglyceride (IHTG) content and metabolic risk factors among patients with obesity and NAFLD.Design, Setting, and ParticipantsThis 12-month randomized clinical trial including participants with obesity and NAFLD was conducted at the Nanfang Hospital in Guangzhou, China, between April 9, 2019, and August 28, 2021.InterventionsParticipants with obesity and NAFLD were randomly assigned to TRE (eating only between 8:00 am and 4:00 pm) or DCR (habitual meal timing). All participants were instructed to maintain a diet of 1500 to 1800 kcal/d for men and 1200 to 1500 kcal/d for women for 12 months.Main Outcomes and MeasuresThe primary outcome was change in IHTG content measured by magnetic resonance imaging; secondary outcomes were changes in body weight, waist circumference, body fat, and metabolic risk factors. Intention-to-treat analysis was used.ResultsA total of 88 eligible patients with obesity and NAFLD (mean [SD] age, 32.0 [9.5] years; 49 men [56%]; and mean [SD] body mass index, 32.2 [3.3]) were randomly assigned to the TRE (n = 45) or DCR (n = 43) group. The IHTG content was reduced by 8.3% (95% CI, −10.0% to −6.6%) in the TRE group and 8.1% (95% CI, −9.8% to −6.4%) in the DCR group at the 6-month assessment. The IHTG content was reduced by 6.9% (95% CI, −8.8% to −5.1%) in the TRE group and 7.9% (95% CI, −9.7% to −6.2%) in the DCR group at the 12-month assessment. Changes in IHTG content were comparable between the 2 groups at 6 months (percentage point difference: −0.2; 95% CI, −2.7 to 2.2; P = .86) and 12 months (percentage point difference: 1.0; 95% CI, −1.6 to 3.5; P = .45). In addition, liver stiffness, body weight, and metabolic risk factors were significantly and comparably reduced in both groups.Conclusions and RelevanceAmong adults with obesity and NAFLD, TRE did not produce additional benefits for reducing IHTG content, body fat, and metabolic risk factors compared with DCR. These findings support the importance of caloric intake restriction when adhering to a regimen of TRE for the management of NAFLD.Trial RegistrationClinicalTrials.gov Identifiers: NCT03786523 and NCT04988230