Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition that affects 25% of the world’s population. There is a clear difference in both geographical distribution and sex in childbearing age. These differences are reduced when women become older and senescence begins. The factors that affect the likelihood of developing NAFLD in a premenopausal woman are an imbalance of sex hormones (especially in estradiol and androgen), microbiome dysregulation, insulin resistance, early menarche, the length of time that the woman breastfeeds for and polycystic ovarian syndrome (PCOS). The aim of this review is to identify various physical ailments that may not appear to be serious to young women but that then affect the onset of NAFLD in perimenopause and can degenerate into NASH. These conditions should also be considered in future clinical management, as well as in research opportunities, in order to customize the monitoring and treatment of NAFLD, considering gender medicine for those women who had early metabolic symptoms that were not considered to be significant at the time.

Plasmonic nanostructures, featuring near infrared (NIR)-absorption, are rising as efficient nanosystems for in vitro photothermal (PT) studies and in vivo PT treatment of cancer diseases. Among the different materials, new plasmonic nanostructures based on Cu2−xS nanocrystals (NCs) are emerging as valuable alternatives to Au nanorods, nanostars and nanoshells, largely exploited as NIR absorbing nanoheaters. Even though Cu2−xS plasmonic properties are not linked to geometry, the role played by their size, shape and surface chemistry is expected to be fundamental for an efficient PT process. Here, Cu2−xS NCs coated with a hydrophilic mesoporous silica shell (MSS) are synthesized by solution-phase strategies, tuning the core geometry, MSS thickness and texture. Besides their loading capability, the silica shell has been widely reported to provide a more robust plasmonic core protection than organic molecular/polymeric coatings, and improved heat flow from the NC to the environment due to a reduced interfacial thermal resistance and direct electron–phonon coupling through the interface. Systematic structural and morphological analysis of the core-shell nanoparticles and an in-depth thermoplasmonic characterization by using a pump beam 808 nm laser, are carried out. The results suggest that large triangular nanoplates (NPLs) coated by a few tens of nanometers thick MSS, show good photostability under laser light irradiation and provide a temperature increase above 38 °C and a 20% PT efficiency upon short irradiation time (60 s) at 6 W/cm2 power density.

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition characterized from hypertriglyceridemia and hepatic fat accumulation, in the absence of alcohol intake. NAFLD starts as steatosis (NAFL), and the continued injury relative to the toxic fat induces inflammation, steatohepatitis (NASH), and HCC. One of the factors determining liver degeneration during the evolution of NAFLD is a modification of Wnt/Frizzled (FZD) signaling. In particular, an inhibition of Wnt signaling and an overexpression of a specific FZD receptor protein, namely, the FZD7, have been observed in NAFLD. Actually, the prognosis and the follow-up of NAFLD is not easy, and the liver biopsy is the gold standard for an accurate detection of liver fibrosis. In this study, the modulation of the FZD7 expression levels in plasma-derived exosomes of NAFLD-affected patients, before and after specific lifestyle interventions, were experimentally evaluated by Western blotting analysis. The experimental data were analyzed by an accurate statistical study that indicated, in the exosomes derived from plasma of NAFLD patients with moderate or severe steatosis, an average expression level of FZD7 that was significantly higher than healthy subjects at baseline; conversely, the values were normalized after 90 days of specific lifestyle interventions. The overall results suggested that the FZD7 delivered by exosomes represents a good candidate as a new and effective biomarker for diagnosis and prognosis of NAFLD.

Inflammasome activation plays a crucial role in the progression to more severe stages of non-alcoholic fatty liver disease (NAFLD), representing a promising therapeutic target. MCC950 is a small molecule acting as a potent and specific inhibitor of the canonical and non-canonical activation of the NLRP3 inflammasome, but its short plasmatic half-life limits its use. Herein, we report, for the first time, the encapsulation of MCC950 in poly(ethylene glycol) (PEG) liposomes (LPs) that are specifically functionalized with an antibody against Frizzled 1 (FZD1), a g-coupled protein involved in the WNT pathway and overexpressed on inflammasome-activated macrophages. MCC950, encapsulated into PEG-LP formulations conjugated with an anti-FZD1 antibody, inhibits the NLRP3 inflammasome activation at concentrations 10 times lower than that of the free drug in THP-1 cells. Luminescent carbon dots (CDs) were also co-encapsulated with MCC950 in LPs to obtain optically traceable nanoformulations that have proved the enhanced ability of the targeted LPs to be internalized into THP-1 cells with respect to their nontargeted counterparts. Our results suggest that MCC950 encapsulation into targeted LPs represents a valuable strategy to achieve reformulation of the NLRP3 inhibitor, able to significantly curtail the threshold of MCC950 doses for inhibiting inflammasome activation, thus offering a new therapeutic approach.

IntroductionPaclitaxel (PTX) interferes with microtubule architecture by binding to β-tubulin, thereby blocking progression at the G2/M phase and inducing apoptosis. This study aimed to investigate molecular processes underlying PTX-mediated resistance in gastric cancer (GC) cells. MethodsPTX-mediated resistance involves many processes, and in this work some of the factors involved in the resistance mechanism were identified by comparing two GC lines with PTX induced resistance to their sensitive counterparts. ResultsThus, the key feature of PTX-resistant cells was the overexpression of pro-angiogenic factors such as VEGFA, VEGFC, and Ang2, known to support tumor cell growth. A second relevant change detected in PTX-resistant lines was the elevated level of TUBβIII, a tubulin isoform that opposes microtubule stabilization. A third identified factor contributing to PTX-resistance was P-glycoprotein (P-gp), a transporter responsible for chemotherapy efflux from the cells, highly expressed in PTX-resistant lines.Discussion These findings were in line with a greater sensitivity of resistant cells to treatment with both Ramucirumab and Elacridar. Ramucirumab significantly reduced the expression of angiogenic molecules and TUBβIII, while Elacridar restored the access of chemotherapy, recovering its anti-mitotic and pro-apoptotic effects. Finally, this study highlighted the role played by exosomes in spreading factors responsible for resistance in the tumor microenvironment.