Interplay among Oxidative Stress, Autophagy, and the Endocannabinoid System in Neurodegenerative Diseases: Role of the Nrf2- p62/SQSTM1 Pathway and Nutraceutical Activation.

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.

Targeting Tumor Necrosis Factor Alpha to Mitigate Lung Injury Induced by Mustard Vesicants and Radiation.

Pulmonary injury induced by mustard vesicants and radiation is characterized by DNA damage, oxidative stress, and inflammation. This is associated with increases in levels of inflammatory mediators, including tumor necrosis factor (TNF)α in the lung and upregulation of its receptor TNFR1. Dysregulated production of TNFα and TNFα signaling has been implicated in lung injury, oxidative and nitrosative stress, apoptosis, and necrosis, which contribute to tissue damage, chronic inflammation, airway hyperresponsiveness, and tissue remodeling.

Perinatal S-Adenosylmethionine Supplementation Represses Expression by the Cellular Epigenetic Memory of CpG and Non-CpG Methylation in Adult TgCRD8 Mice.

DNA methylation, the main epigenetic modification regulating gene expression, plays a role in the pathophysiology of neurodegeneration. Previous evidence indicates that 5'-flanking hypomethylation of , a gene involved in the amyloidogenic pathway in Alzheimer's disease (AD), boosts the AD-like phenotype in transgenic TgCRND8 mice. Supplementation with S-adenosylmethionine (SAM), the methyl donor in the DNA methylation reactions, reverts the pathological phenotype.

A Multimethodological Approach for the Valorization of "Senatore Cappelli" Wheat Milling By-Products as a Source of Bioactive Compounds and Nutraceutical Activity.

Wheat is the third most cultivated cereal in the world and represents the major contributor to human nutrition. Milling wheat by-products such as husks (17-20% of the total processing output weight), even if still containing high-value-added bioactive compounds, are often left untreated or unused, thus resulting in environmental and human health burdens. In these regards, the present study is aimed at evaluating in a multimethodological approach the nutraceutical properties of durum wheat husks belonging to the ancient cultivar "Senatore Cappelli", thus assessing their potential as bioactive compound sources in terms of phytochemical, cytotoxic, and nutraceutical properties.

Milmed Yeast Alters the LPS-Induced M1 Microglia Cells to Form M2 Anti-Inflammatory Phenotype.

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.

Neuropeptide Y Promotes Human M2 Macrophage Polarization and Enhances p62/SQSTM1-Dependent Autophagy and NRF2 Activation.

Neuropeptide Y (NPY) is an abundantly expressed peptide capable of modulating innate and adaptive immune responses and regulating chemotaxis and cytokine secretion by macrophages. Abnormal regulation of NPY is involved in the development of atherosclerosis. The inflammatory infiltrate within atherosclerotic plaque is characterized by accumulation of macrophages, which are subject to reprogram their phenotypes in response to environmental signals.

Fatty Acid Amide Hydrolase (FAAH) Inhibition Modulates Amyloid-Beta-Induced Microglia Polarization.

The ability of endocannabinoid (eCB) to change functional microglial phenotype can be explored as a possible target for therapeutic intervention. Since the inhibition of fatty acid amide hydrolase (FAAH), the main catabolic enzyme of anandamide (AEA), may provide beneficial effects in mice model of Alzheimer's disease (AD)-like pathology, we aimed at determining whether the FAAH inhibitor URB597 might target microglia polarization and alter the cytoskeleton reorganization induced by the amyloid-β peptide (Aβ). The morphological evaluation showed that Aβ treatment increased the surface area of BV-2 cells, which acquired a flat and polygonal morphology.

Mediterranean Diet and Neurodegenerative Diseases: The Neglected Role of Nutrition in the Modulation of the Endocannabinoid System.

Neurodegenerative disorders are a widespread cause of morbidity and mortality worldwide, characterized by neuroinflammation, oxidative stress and neuronal depletion. The broad-spectrum neuroprotective activity of the Mediterranean diet is widely documented, but it is not yet known whether its nutritional and caloric balance can induce a modulation of the endocannabinoid system. In recent decades, many studies have shown how endocannabinoid tone enhancement may be a promising new therapeutic strategy to counteract the main hallmarks of neurodegeneration.

Therapeutic Opportunities for Food Supplements in Neurodegenerative Disease and Depression.

Emerging evidence is showing nutrition as a crucial factor in the high prevalence and incidence of neurodegenerative mental disorders. Preventive interventions on neuroinflammation seem to be able to interfere with neurodegeneration. Supplementation of essential nutrients, such as long-chain-polyunsaturated fatty acids, vitamin E and mineral elements, may minimize inflammation, enhancing antioxidative defense, and lowering the risk and incidence of age-related diseases, such as cardiovascular diseases and neurodegenerative diseases.

Pulmonary toxicants and fibrosis: innate and adaptive immune mechanisms.

Pulmonary fibrosis is characterized by destruction and remodeling of the lung due to an accumulation of collagen and other extracellular matrix components in the tissue. This results in progressive irreversible decreases in lung capacity, impaired gas exchange and eventually, hypoxemia. A number of inhaled and systemic toxicants including bleomycin, silica, asbestos, nanoparticles, mustard vesicants, nitrofurantoin, amiodarone, and ionizing radiation have been identified.

Immunohistochemical detection of IL-17 and IL-23 improves the identification of patients with a possible diagnosis of Sjogren's syndrome.

Objectives: The diagnosis of primary Sjogren's syndrome (pSS) continues to be difficult and several patients keep symptomatic for years with different diagnoses before confirmation of pSS. Since the IL-23-IL-17 axis is involved in the etiopathogenesis of pSS we evaluated by immunohistochemistry and morphometric methods the presence of IL-17 as well as IL-23 within minor salivary glands (MSG) obtained from patients with uncertain diagnosis of pSS.

Materials And Methods: 42 patients, with symptoms attributable to pSS, and 8 patients used as a control, were enrolled for the study.

Nutraceuticals as potential therapeutics for vesicant-induced pulmonary fibrosis.

Exposure to vesicants, including sulfur mustard and nitrogen mustard, causes damage to the epithelia of the respiratory tract and the lung. With time, this progresses to chronic disease, most notably, pulmonary fibrosis. The pathogenic process involves persistent inflammation and the release of cytotoxic oxidants, cytokines, chemokines, and profibrotic growth factors, which leads to the collapse of lung architecture, with fibrotic involution of the lung parenchyma.

Blueberry Counteracts BV-2 Microglia Morphological and Functional Switch after LPS Challenge.

Microglia, the innate immune cells of the CNS, respond to brain injury by activating and modifying their morphology. Our study arises from the great interest that has been focused on blueberry (BB) for the antioxidant and pharmacological properties displayed by its components. We analyzed the influence of hydroalcoholic BB extract in resting or lipopolysaccharide (LPS)-stimulated microglia BV-2 cells.

The role of diet in preventing and reducing cognitive decline.

Purpose Of Review: This review summarises the most recent evidence regarding the effects of diet in preventing and reducing age-related cognitive decline and neurodegenerative diseases.

Recent Findings: Recent evidence indicates that nutraceuticals and whole diet approaches may protect against the development of age-related cognitive decline and pathological neurodegeneration. The neuroprotective effects are diverse depending on the nutrient employed and may involve a reduction of neuroinflammation, an activation of the endogenous antioxidant defence system and a modulation of the gut microbiota structure and function.

Ketone Bodies Promote Amyloid-β Clearance in a Human in Vitro Blood-Brain Barrier Model.

Alzheimer's disease (AD) is characterized by the abnormal accumulation of amyloid-β (Aβ) peptides in the brain. The pathological process has not yet been clarified, although dysfunctional transport of Aβ across the blood-brain barrier (BBB) appears to be integral to disease development. At present, no effective therapeutic treatment against AD exists, and the adoption of a ketogenic diet (KD) or ketone body (KB) supplements have been investigated as potential new therapeutic approaches.

Role of extracellular vesicles in cell-cell communication and inflammation following exposure to pulmonary toxicants.

Extracellular vesicles (EVs) have emerged as key regulators of cell-cell communication during inflammatory responses to lung injury induced by diverse pulmonary toxicants including cigarette smoke, air pollutants, hyperoxia, acids, and endotoxin. Many lung cell types, including epithelial cells and endothelial cells, as well as infiltrating macrophages generate EVs. EVs appear to function by transporting cargo to recipient cells that, in most instances, promote their inflammatory activity.

Blueberry-Based Meals for Obese Patients with Metabolic Syndrome: A Multidisciplinary Metabolomic Pilot Study.

A pilot study was carried out on five obese/overweight patients suffering from metabolic syndrome, with the aim to evaluate postprandial effects of high fat/high glycemic load meals enriched by blueberries. Postprandial urine samples were analyzed by H-NMR spectroscopy after 2 and 4 h from ingestion to identify potential markers of blueberry intake. Significant decrease of methylamines, acetoacetate, acetone and succinate, known indicators of type 2 diabetes mellitus, were observed after the intake of meals enriched with blueberries.

Platelet Lysate-Derived Neuropeptide y Influences Migration and Angiogenesis of Human Adipose Tissue-Derived Stromal Cells.

Neuropeptide Y (NPY), a powerful neurotransmitter of the central nervous system, is a key regulator of angiogenesis and biology of adipose depots. Intriguingly, its peripheral vascular and angiogenic powerful activity is strictly associated to platelets, which are source of clinical hemoderivates, such as platelet lysate (PL), routinely employed in several clinical applications as wound healing, and to preserve ex vivo the progenitor properties of the adipose stromal cells pool. So far, the presence of NPY in PL and its biological effects on the adipose stromal cell fraction (ASCs) have never been investigated.

Oxidative Stress Induces HSP90 Upregulation on the Surface of Primary Human Endothelial Cells: Role of the Antioxidant 7,8-Dihydroxy-4-methylcoumarin in Preventing HSP90 Exposure to the Immune System.

We have previously demonstrated that human heat shock protein 90 (HSP90), an intracellular self protein, is the target of cellular and humoral autoimmune responses in patients with carotid atherosclerosis. In this study, we evaluated whether oxidative stress, a feature of atherosclerotic plaque, alters HSP90 expression in endothelial cells, thus inducing surface localization of this molecule and whether the antioxidant compound 7,8-dihydroxy-4-methylcoumarin (7,8-DHMC) is able to prevent oxidative stress-induced alterations of HSP90 localization. By the use of flow cytometry, immunofluorescence, enzyme-linked immunosorbent assay, and semiquantitative reverse-transcription polymerase chain reaction, we demonstrated that exposure of human umbilical vein endothelial cells (HUVEC) to the prooxidant compound HO upregulated HSP90 surface expression and reduced its secretion without altering HSP90 gene expression and intracytoplasmic protein levels.

Anti-Oxidant and Anti-Inflammatory Activity of Ketogenic Diet: New Perspectives for Neuroprotection in Alzheimer's Disease.

The ketogenic diet, originally developed for the treatment of epilepsy in non-responder children, is spreading to be used in the treatment of many diseases, including Alzheimer’s disease. The main activity of the ketogenic diet has been related to improved mitochondrial function and decreased oxidative stress. B-Hydroxybutyrate, the most studied ketone body, has been shown to reduce the production of reactive oxygen species (ROS), improving mitochondrial respiration: it stimulates the cellular endogenous antioxidant system with the activation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2), it modulates the ratio between the oxidized and reduced forms of nicotinamide adenine dinucleotide (NAD⁺/NADH) and it increases the efficiency of electron transport chain through the expression of uncoupling proteins.

MDCT of the liver in obese patients: evaluation of a different method to optimize iodine dose.

Purpose: To prospectively compare two different approaches for estimating the amount of intravenous contrast media (CM) needed for multiphasic MDCT of the liver in obese patients.

Materials And Methods: This single-center, HIPAA-compliant prospective study was approved by our Institutional Review Board. Ninety-six patients (55 men, 41 women), with a total of 42 hypovascular liver lesions, underwent MDCT of the liver.

Wounds Difficult to Heal: An Effective Treatment Strategy.

Objective: Treatment of wounds difficult to heal concerns 50% of the elderly population in Italy and is therefore a relevant social burden. The present study shows how the treatment with autologous leuco-platelets reduces the healing time of wounds improving the functional recovery.

Patients And Methods: Patients (n=100) with ulcers of the legs were divided in two groups: 1) 50 patients treated with conventional therapies; 2) 50 patients treated with autologous leuco-platelet concentrate (LPC) and hyaluronic acid (HIAFF, Hyalofill-F® ) as a scaffold.