Furthermore, 59Fe export from BCECs was elevated after treatment with VPA. In conclusion, we present first time evidence stating that Fpn expression is epigenetically regulated in BCECs, which may have implications for pharmacological induction of iron transport through the BBB.Astrocytes are functionally diverse glial cells that maintain blood-brain barrier (BBB) integrity, provide metabolic and trophic support, and react to pathogens or harmful stimuli through inflammatory response. Impairment of astrocyte functions has been implicated in hepatic encephalopathy (HE), a neurological complication associated with hyperammonemia. Although hyperammonemia is more common in adults, ammonia gliotoxicity has been mainly studied in cultured astrocytes derived from neonate animals. However, these cells can sense and respond to stimuli in different ways from astrocytes obtained from adult animals. Thus, the aim of this study was to investigate the direct effects of ammonia on astrocyte cultures obtained from adult rats compared with those obtained from neonate rats. Eganelisib cell line Our main findings pointed that ammonia increased the gene expression of proteins associated with BBB permeability, in addition to cause an inflammatory response and decrease the release of trophic factors, which were dependent on p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor κB (NFκB) pathways and aquaporin 4, in both neonatal and mature astrocytes. Considering the age, mature astrocytes presented an overall increase of the expression of inflammatory signaling components and a decrease of the expression of cytoprotective pathways, compared with neonatal astrocytes. Importantly, ammonia exposure in mature astrocytes potentiated the expression of the senescence marker p21, inflammatory response, activation of p38 MAPK/NFκB pathways, and the decrease of cytoprotective pathways. In this regard, ammonia can trigger and/or accelerate the inflammaging of mature astrocytes, a phenomenon characterized by an age-related chronic and low-grade inflammation, which may be implicated in HE neurological symptoms.Purpose of review Bariatric surgery is today the most effective therapy for weight loss and reduction of comorbidity burden in patients with severe obesity. However, bariatric surgery does not benefit equally all the patients. A consistent variability in outcomes has been observed. Predicting responses to bariatric surgery could be an important tool in clinical practice, by improving patients’ selection or by identifying patients in which more aggressive follow-up and post-operative intervention should be applied. Predictive factors for weight loss, weight regain, diabetes remission and recurrence are briefly reviewed in this paper. Recent findings Many pre-operative factors have been proposed as negative or positive predictors of body weight reduction after surgery. However, none of these factors has been consistently demonstrated to have a sufficiently strong predictive power to influence eligibility to bariatric surgery itself. Weight regain can occur after bariatric surgery and its probability seems to be more influenced by post-operative behavioral factors than by pre-operative predictors. Several effective scores have been developed to predict diabetes remission after surgery, however long-term maintenance and diabetes recurrence after surgery seem again more influenced by post-operative behaviors and weight loss maintenance. In general, more attention and active interventions to pre-operative and post-operative eating behaviors and lifestyle modifications are probably more important at the clinical level than the search of pre-operative predictors of long-term outcomes.Purpose of review High-protein diets in the management of obesity have been around for many years and have been rigorously tested for their ability to induce weight loss. Comparably less is known about their effects on the maintenance of lost weight. Recent findings Several small and a few large randomized trials have evaluated the efficacy of high-protein diets (20-35% of calories from protein; 1.2-1.9 g/kg∙day) compared with normal-protein diets (10-20% of calories from protein; 0.8-1.3 g/kg∙day), consumed mostly ad libitum during weight loss maintenance, i.e., after clinically significant weight loss. Most of these studies indicate that weight regain in the short term (3-12 months) is lower by 1-2 kg with high-protein diets than low-protein diets. This effect is attenuated with longer periods of observation, likely because of decreasing dietary compliance. In line with findings during the active weight loss phase, studies assessing the efficacy of protein-rich diets to improve weight loss maintenance report beneficial effects in the short term, which nevertheless dissipate over time.We provide an innovative, bioengineering, mechanobiology-based approach to rapidly (2-h) establish the in vivo metastatic likelihood of patient tumor-samples, where results are in direct agreement with clinical histopathology and patient outcomes. Cancer-related mortality is mostly due to local recurrence or to metastatic disease, thus early prediction of tumor-cell-fate may critically affect treatment protocols and survival rates. Metastasis and recurrence risks are currently predicted by lymph-node status, tumor size, histopathology and genetic testing, however, these are not infallible and results may require days/weeks. We have previously observed that subpopulations of invasive cancer-cells will rapidly (1-2 h) push into the surface of physiological-stiffness, synthetic polyacrylamide gels, reaching to cell-scale depths, while normal or noninvasive cells do not considerably indent gels. Here, we evaluate the mechanical invasiveness of established breast and pancreatic cell lines and of tumor-cells from fresh, suspected pancreatic cancer tumors. The mechanical invasiveness matches the in vitro metastatic potential in cell lines as determined with Boyden chamber assays. Moreover, the mechanical invasiveness directly agrees with the clinical histopathology in primary-site, pancreatic-tumors. Thus, the rapid, patient-specific, early prediction of metastatic likelihood, on the time-scale of initial resection/biopsy, can directly affect disease management and treatment protocols.