Wrong alimentary behaviors and so-called “junk food” are a driving force for the rising incidence of non-alcoholic fatty liver disease (NAFLD) among children and adults. The “junk food” toxicity can be studied in “cafeteria” (CAF) diet animal model. Young rats exposed to CAF diet become obese and rapidly develop NAFLD. We have previously showed that bergamot (Citrus bergamia Risso et Poiteau) flavonoids, in the form of bergamot polyphenol fraction (BPF), effectively prevent CAF diet-induced NAFLD in rats. Here, we addressed if BPF can accelerate therapeutic effects of weight loss induced by a normocaloric standard chow (SC) diet. 21 rats fed with CAF diet for 16 weeks to induce NAFLD with inflammatory features (NASH) were divided into three groups. Two groups were switched to SC diet supplemented or not with BPF (CAF/SC±BPF), while one group continued with CAF diet (CAF/CAF) for 10 weeks. BPF had no effect on SC diet-induced weight loss, but it accelerated hepatic lipid droplets clearance and reduced blood triglycerides. Accordingly, BPF improved insulin sensitivity, but had little effect on leptin levels. Interestingly, the inflammatory parameters were still elevated in CAF/SC livers compared to CAF/CAF group after 10 weeks of dietary intervention, despite over 90% hepatic fat reduction. In contrast, BPF supplementation decreased hepatic inflammation by reducing interleukin 6 (Il6) mRNA expression and increasing anti-inflammatory Il10, which correlated with fewer Kupffer cells and lower inflammatory foci score in CAF/SC+BPF livers compared to CAF/SC group. These data indicate that BPF mediates a specific anti-inflammatory activity in livers recovering from NASH, while it boosts lipid-lowering and anti-diabetic effects of the dietary intervention.

Dietary flavonoids stimulate autophagy and prevent liver dysfunction, but the upstream signaling pathways triggered by these compounds are not well understood. Certain polyphenols bind directly to NRH-quinone oxidoreductase 2 (NQO2) and inhibit its activity. NQO2 is highly expressed in the liver, where it participates in quinone metabolism, but recent evidence indicates that it may also play a role in the regulation of oxidative stress and autophagy. Here, we addressed a potential role of NQO2 in autophagy induction by flavonoids. The pro-autophagic activity of seven flavonoid aglycons correlated perfectly with their ability to inhibit NQO2 activity, and flavones such as apigenin and luteolin showed the strongest activity in all assays. The silencing of NQO2 strongly reduced flavone-induced autophagic flux, although it increased basal LC3-II levels in HepG2 cells. Both flavones induced AMP kinase (AMPK) activation, while its reduction by AMPK beta (PRKAB1) silencing inhibited flavone-induced autophagy. Interestingly, the depletion of NQO2 levels by siRNA increased the basal AMPK phosphorylation but abrogated its further increase by apigenin. Thus, NQO2 contributes to the negative regulation of AMPK activity and autophagy, while its targeting by flavones releases pro-autophagic signals. These findings imply that NQO2 works as a flavone receptor mediating autophagy and may contribute to other hepatic effects of flavonoids.

BackgroundVaccine administration is a recommended, safe, and effective measure to protect pregnant women against vaccine-preventable diseases (VPDs). Despite available guidance, maternal immunization rates for vaccination against influenza and with the reduced antigen content tetanus-diphtheria-acellular pertussis vaccine (Tdap) in Italy remain incredibly low. The primary goal of the study was to explore what Italian pregnant women knew about VPDs and immunization during pregnancy and what factors affected their decision to be vaccinated.MethodsThis cross-sectional study took place between October 2021 and April 2022 in the Southern part of Italy. All consecutive pregnant women, from those attending the selected facilities on randomly selected days, were approached to request participation. The inclusion criteria for participation were age ≥18 years, the ability to understand, speak, and read Italian, and being pregnant at any gestational age. The questionnaire, using a combination of checkboxes and free text answers, consisted of 32 items divided into five parts and lasted ~10 min.ResultsThe results showed that 61% knew that the influenza vaccine is recommended and 48.7% knew that influenza could be risky during pregnancy; 74.1% wrongly reported that the Measles-Mumps-Rubella (MMR) vaccine is recommended during pregnancy. Seven out of 10 pregnant women believed that strong evidence supported the safety of vaccinations during pregnancy, and more than half (55.6%) thought they were at increased risk of severe illness with COVID-19. Women in the sample believed that vaccines received during pregnancy pose a risk of adverse events to the unborn child with a median value of 6 (IQR 3–9), on a scale ranging from 1 to 10. Similarly, the fear of contracting pertussis and influenza during pregnancy showed a median value of 6 (IQR 3–9) and 5 (IQR 3–8), respectively. Only 21.1% and 36.5% of women received influenza and Tdap vaccines during pregnancy.ConclusionUnrealistic risk perception with a negative attitude toward vaccines in pregnancy and a low percentage of vaccinated pregnant women confirm the urgency of training women to make informed choices to increase overall vaccine uptake.

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