We present an integrated analysis of bank erosion in a high‐curvature bend of the gravel bed Cecina River (central Italy). Our analysis combines a model of fluvial bank erosion with groundwater flow and bank stability analyses to account for the influence of hydraulic erosion on mass failure processes, the key novel aspect being that the fluvial erosion model is parameterized using outputs from detailed hydrodynamic simulations. The results identify two mechanisms that explain how most bank retreat usually occurs after, rather than during, flood peaks. First, in the high curvature bend investigated here the maximum flow velocity core migrates away from the outer bank as flow discharge increases, reducing sidewall boundary shear stress and fluvial erosion at peak flow stages. Second, bank failure episodes are triggered by combinations of pore water and hydrostatic confining pressures induced in the period between the drawdown and rising phases of multipeaked flow events.

The onset of neurodegenerative diseases involves a complex interplay of pathological mechanisms, including protein aggregation, oxidative stress, and impaired autophagy. This review focuses on the intricate connection between oxidative stress and autophagy in neurodegenerative disorders, highlighting autophagy as pivotal in disease pathogenesis. Reactive oxygen species (ROS) play dual roles in cellular homeostasis and autophagy regulation, with disruptions of redox signaling contributing to neurodegeneration. The activation of the Nrf2 pathway represents a critical antioxidant mechanism, while autophagy maintains cellular homeostasis by degrading altered cell components. The interaction among p62/SQSTM1, Nrf2, and Keap1 forms a regulatory pathway essential for cellular stress response, whose dysregulation leads to impaired autophagy and aggregate accumulation. Targeting the Nrf2-p62/SQSTM1 pathway holds promise for therapeutic intervention, mitigating oxidative stress and preserving cellular functions. Additionally, this review explores the potential synergy between the endocannabinoid system and Nrf2 signaling for neuroprotection. Further research is needed to elucidate the involved molecular mechanisms and develop effective therapeutic strategies against neurodegeneration.

Curcumin, a polyphenolic compound derived from Curcuma longa, has gained significant attention for its potential therapeutic benefits, particularly counteracting inflammation, oxidative stress, and metabolic disorders. Its chemical structure, featuring conjugated double bonds between two aromatic rings, allows it to act as an electron donor, thereby mitigating free radical formation. Despite its poor solubility in water, curcumin is stable in acidic environments and undergoes significant metabolism in both the liver and the gut. Intestinal microbiota, particularly at the colon level, further metabolizes curcumin into several derivatives, including dihydrocurcumin and tetrahydrocurcumin, which exhibit antioxidant and anti-inflammatory properties. Studies suggest that curcumin can reduce body mass index (BMI) and improve other body composition parameters, especially when used in combination with lifestyle changes, though its bioavailability is low due to its rapid metabolism and the resulting low blood concentration. In obesity, dysfunctional adipose tissue remodeling and chronic inflammation play critical roles in the development of metabolic complications. Curcumin’s anti-inflammatory properties are related to the inhibition of the NF-κB pathway, leading to the reduction in inflammatory markers in adipocytes and macrophages. Additionally, curcumin modulates oxidative stress by activating the NRF2 pathway, enhancing cellular antioxidant defenses. Emerging evidence also supports curcumin’s potential in improving gut health by modulating microbiota composition, enhancing intestinal barrier function, and reducing systemic inflammation. This interaction with the gut–brain axis highlights the broader implications of curcumin in neuroprotection, as it positively affects cognitive function and mitigates neuroinflammation in neurodegenerative diseases like Alzheimer’s. disease. Thus, curcumin holds promise as a multifaceted agent in the management of obesity and associated diseases.

Microglial cells polarized towards a proinflammatory phenotype are considered the main cellular players of neuroinflammation, underlying several neurodegenerative diseases. Many studies have suggested that imbalance of the gut microbial composition is associated with an increase in the pro-inflammatory cytokines and oxidative stress that underlie chronic neuroinflammatory diseases, and perturbations to the gut microbiota were detected in neurodegenerative conditions such as Parkinson’s disease and Alzheimer’s disease. The importance of gut-brain axis has been uncovered and the relevance of an appropriate microbiota balance has been highlighted. Probiotic treatment, rebalancing the gut microbioma, may reduce inflammation. We show that Milmed yeast, obtained from S. cerevisiae after exposure to electromagnetic millimeter wavelengths, induces a reversal of LPS-M1 polarized microglia towards an anti-inflammatory phenotype, as demonstrated morphologically by the recovery of resting phenotype by microglia, by the decrease in the mRNAs of IL-1β, IL-6, TNF-α and in the expression of iNOS. Moreover, Milmed stimulated the secretion of IL-10 and the expression of Arginase-1, cell markers of M2 anti-inflammatory polarized cells. The present findings data suggest that Milmed may be considered to be a probiotic with diversified anti-inflammatory activity, capable of directing the polarization of microglial cells.

Background/Objectives: Inflammation and oxidative stress are the main pathogenetic pathways involved in the development of several chronic degenerative diseases. Our study is aimed at assessing the antioxidant and anti-inflammatory activity of hydroalcoholic extracts obtained from wheat and its derivatives. Methods: The content of total phenolic and total flavonoid compounds and antioxidant activity were carried out by ABTS and DPPH assays. The ability of wheat extracts to promote microglia polarization towards an anti-inflammatory phenotype was evaluated analyzing the increased expression of anti-inflammatory markers by real-time qPCR and immunofluorescence assays. Antioxidant activity of all the extracts was evaluated in C. elegans by analyzing ROS levels and the expression of the antioxidant enzymes GST-4 and SOD-3 by real-time qPCR and fluorescence experiments. The expression of key genes involved in the innate immune response and stress resistance pathways—daf-16, sek-1, and pmk-1—was evaluated by real-time qPCR. Results: Wheat extracts showed the ability to polarize microglia cells towards an anti-inflammatory phenotype, even after the addition of LPS. An antioxidant response was detected both in microglia and in Caenorhabditis elegans nematode, where the extracts also implemented an anti-stress resilience response and stimulated the innate immunity. Conclusions: The present study shows that wheat seeds, flour, chaff, and pasta present anti-inflammatory as well as antioxidant activities and may be considered as prospective positive health agents for the preparation of functional foods. Moreover, the valorization of by-products from agricultural and agro-industrial activities would also have significant implications in terms of circular economy.

Endocannabinoids have attracted great interest for their ability to counteract the neuroinflammation underlying Alzheimer’s disease (AD). Our study aimed at evaluating whether this activity was also due to a rebalance of autophagic mechanisms in cellular and animal models of AD. We supplied URB597, an inhibitor of Fatty-Acid Amide Hydrolase (FAAH), the degradation enzyme of anandamide, to microglial cultures treated with Aβ_25-35, and to Tg2576 transgenic mice, thus increasing the endocannabinoid tone. The addition of URB597 did not alter cell viability and induced microglia polarization toward an anti-inflammatory phenotype, as shown by the modulation of pro- and anti-inflammatory cytokines, as well as M1 and M2 markers; moreover microglia, after URB597 treatment released higher levels of Bdnf and Nrf2, confirming the protective role underlying endocannabinoids increase, as shown by RT-PCR and immunofluorescence experiments. We assessed the number and area of amyloid plaques in animals administered with URB597 compared to untreated animals and the expression of autophagy key markers in the hippocampus and prefrontal cortex from both groups of mice, via immunohistochemistry and ELISA. After URB597 supply, we detected a reduction in the number and areas of amyloid plaques, as detected by Congo Red staining and a reshaping of microglia activation as shown by M1 and M2 markers’ modulation. URB597 administration restored autophagy in Tg2576 mice via an increase in BECN1 (Beclin1), ATG7 (Autophagy Related 7), LC3 (light chain 3) and SQSTM1/p62 (sequestrome 1) as well as via the activation of the ULK1 (Unc-51 Like Autophagy Activating Kinase 1) signaling pathway, suggesting that it targets mTOR/ULK1-dependent autophagy pathway. The potential of endocannabinoids to rebalance autophagy machinery may be considered as a new perspective for therapeutic intervention in AD.