The spread of Carpophilus truncatus is on the razor's edge between an outbreak and a pest invasion.

In 2019, in southern Italy (Campania) there was an outbreak of a sap beetle infesting stored walnut fruits. A monitoring activity started to assess the spread and impact of the pest in walnut orchards and in warehouses, and an integrative characterization led to identify the beetle as Carpophilus truncatus. This species has been in Europe for a long time, rare and harmless until recently.

CT-based radiomics for prediction of therapeutic response to Everolimus in metastatic neuroendocrine tumors.

Aim: To test radiomic approach in patients with metastatic neuroendocrine tumors (NETs) treated with Everolimus, with the aim to predict progression-free survival (PFS) and death.

Materials And Methods: Twenty-five patients with metastatic neuroendocrine tumors, 15/25 pancreatic (60%), 9/25 ileal (36%), 1/25 lung (4%), were retrospectively enrolled between August 2013 and December 2020. All patients underwent contrast-enhanced CT before starting Everolimus, histological diagnosis, tumor grading, PFS, overall survival (OS), death, and clinical data collected.

An Integrative Study on spp. (Diptera: Cecidomyiidae), Causing Flower Galls on Lamiaceae, with Description, Phenology, and Associated Fungi of Two New Species.

An integrative study on some species of was carried out. Two species of gall midges from Italy, sp. nov.

Up-regulation of PCSK6 by lipid oxidation products: A possible role in atherosclerosis.

Atherosclerosis is a degenerative disease characterized by lesions that develop in the wall of large- and medium-sized arteries due to the accumulation of low-density lipoproteins (LDLs) in the intima. A growing bulk of evidence suggests that cholesterol oxidation products, known as oxysterols, and the aldehyde 4-hydroxy-2-nonenal (HNE), the major pro-atherogenic components of oxidized LDLs, significantly contribute to atherosclerotic plaque progression and destabilization, with eventual plaque rupture. The involvement of certain members of the protein convertase subtilisin/kexin proteases (PCSKs) in atherosclerosis has been recently hypothesized.

Up-regulation of COX-2 and mPGES-1 by 27-hydroxycholesterol and 4-hydroxynonenal: A crucial role in atherosclerotic plaque instability.

Atherosclerosis is currently understood to be mainly the consequence of a complicated inflammatory process at the different stages of plaque development. Among the several inflammatory molecules involved, up-regulation of the functional cyclooxygenase 2/membrane-bound prostaglandin E synthase 1 (COX-2/mPGES-1) axis plays a key role in plaque development. Excessive production of oxidized lipids, following low-density lipoprotein (LDL) oxidation, is a characteristic feature of atherosclerosis.

A silver lining for 24-hydroxycholesterol in Alzheimer's disease: The involvement of the neuroprotective enzyme sirtuin 1.

It is now established that cholesterol oxidation products (oxysterols) are involved in several events underlying Alzheimer's disease (AD) pathogenesis. Of note, certain oxysterols cause neuron dysfunction and degeneration but, recently, some of them have been shown also to have neuroprotective effects. The present study, which aimed to understand the potential effects of 24-hydroxycholesterol (24-OH) against the intraneuronal accumulation of hyperphosphorylated tau protein, stressed these latter effects.

The role of autophagy in survival response induced by 27-hydroxycholesterol in human promonocytic cells.

Autophagy has been shown to be stimulated in advanced atherosclerotic plaques by metabolic stress, inflammation and oxidized lipids. The lack of published studies addressing the potential stimulation of pro-survival autophagy by oxysterols, a family of cholesterol oxidation products, has prompted our study. Thus, the goal of the current study is to elucidate the molecular mechanism of the autophagy induced by 27-hydroxycholesterol (27-OH), that is one of the most abundant oxysterols in advanced atherosclerotic lesions, and to assess whether the pro-oxidant effect of the oxysterol is involved in the given response.

Oxysterols and 4-hydroxy-2-nonenal contribute to atherosclerotic plaque destabilization.

A growing bulk of evidence suggests that cholesterol oxidation products, known as oxysterols, and 4-hydroxy-2-nonenal (HNE), the major proatherogenic components of oxidized low density lipoproteins (oxLDLs), significantly contribute to atherosclerotic plaque progression and destabilization, with eventual plaque rupture. These oxidized lipids are involved in various key steps of this complex process, mainly thanks to their ability to induce inflammation, oxidative stress, and apoptosis. This review summarizes the current knowledge of the effects induced by these compounds on vascular cells, after their accumulation in the arterial wall and in the atherosclerotic plaque.

Changes in brain oxysterols at different stages of Alzheimer's disease: Their involvement in neuroinflammation.

Alzheimer's disease (AD) is a gradually debilitating disease that leads to dementia. The molecular mechanisms underlying AD are still not clear, and at present no reliable biomarkers are available for the early diagnosis. In the last several years, together with oxidative stress and neuroinflammation, altered cholesterol metabolism in the brain has become increasingly implicated in AD progression.

Nrf2 antioxidant defense is involved in survival signaling elicited by 27-hydroxycholesterol in human promonocytic cells.

Cholesterol oxidation products such as oxysterols are considered critical factors in the atherosclerotic plaque formation since they induce oxidative stress, inflammation and apoptotic cell death. 27-hydroxycholesterol (27-OH) is one of the most represented oxysterols in atherosclerotic lesions. We recently showed that relatively low concentrations of 27-OH generated a strong survival signaling through an early and transient increase of cellular ROS level, that enhanced MEK-ERK/PI3K-Akt phosphorylation, in turn responsible of a sustained quenching of ROS production.

The role of oxysterols in vascular ageing.

The ageing endothelium progressively loses its remarkable and crucial ability to maintain homeostasis of the vasculature, as it acquires a proinflammatory phenotype. Cellular and structural changes gradually accumulate in the blood vessels, and markedly in artery walls. Most changes in aged arteries are comparable to those occurring during the atherogenic process, the latter being more marked: pro-oxidant and proinflammatory molecules, mainly deriving from or triggered by oxidized low density lipoproteins (oxLDLs), are undoubtedly a major driving force of this process.

Modulation of cell signaling pathways by oxysterols in age-related human diseases.

Cholesterol oxidation products, named oxysterols, may derive from the diet or originate endogenously by autoxidative nonenzymatic modification of cholesterol as well as through enxymatic pathways involved in lipid metabolism and maintenance of cholesterol homeostasis. Oxysterols have been shown to exert several in vitro and in vivo biochemical activities of both physiologic and pathologic relevance and they appear to be implicated in the pathogenesis of various age-related chronic diseases, including atherosclerosis and Alzheimer's disease (AD), where hypercholesterolemia represents a primary risk factor, and a redox state impairment and inflammation seem to play a central role. Our recent studies show that, in cells of the macrophage lineage or in human neuronal cells (differentiated or not), respectively in the contest of atherosclerosis or AD, oxysterols can initiate specific signal transduction pathways that are relevant to the development of these diseases.

Oxidized cholesterol as the driving force behind the development of Alzheimer's disease.

Alzheimer's disease (AD), the most common neurodegenerative disorder associated with dementia, is typified by the pathological accumulation of amyloid Aβ peptides and neurofibrillary tangles (NFT) within the brain. Considerable evidence indicates that many events contribute to AD progression, including oxidative stress, inflammation, and altered cholesterol metabolism. The brain's high lipid content makes it particularly vulnerable to oxidative species, with the consequent enhancement of lipid peroxidation and cholesterol oxidation, and the subsequent formation of end products, mainly 4-hydroxynonenal and oxysterols, respectively from the two processes.

Postprandial Dysmetabolism and Oxidative Stress in Type 2 Diabetes: Pathogenetic Mechanisms and Therapeutic Strategies.

Postprandial dysmetabolism in type 2 diabetes (T2D) is known to impact the progression and evolution of this complex disease process. However, the underlying pathogenetic mechanisms still require full elucidation to provide guidance for disease prevention and treatment. This review focuses on the marked redox changes and inflammatory stimuli provoked by the spike in blood glucose and lipids in T2D individuals after meals.

Relation between TLR4/NF-κB signaling pathway activation by 27-hydroxycholesterol and 4-hydroxynonenal, and atherosclerotic plaque instability.

It is now thought that atherosclerosis, although due to increased plasma lipids, is mainly the consequence of a complicated inflammatory process, with immune responses at the different stages of plaque development. Increasing evidence points to a significant role of Toll-like receptor 4 (TLR4), a key player in innate immunity, in the pathogenesis of atherosclerosis. This study aimed to determine the effects on TLR4 activation of two reactive oxidized lipids carried by oxidized low-density lipoproteins, the oxysterol 27-hydroxycholesterol (27-OH) and the aldehyde 4-hydroxynonenal (HNE), both of which accumulate in atherosclerotic plaques and play a key role in the pathogenesis of atherosclerosis.

The role of p38 MAPK in the induction of intestinal inflammation by dietary oxysterols: modulation by wine phenolics.

Dietary oxysterols are cholesterol auto-oxidation products widely present in cholesterol-rich foods. They are thought to affect the intestinal barrier function, playing a role in gut inflammation. This study has characterized specific cell signals that are up-regulated in differentiated CaCo-2 colonic epithelial cells by a mixture of oxysterols representative of a hyper-cholesterolemic diet.

Survival signaling elicited by 27-hydroxycholesterol through the combined modulation of cellular redox state and ERK/Akt phosphorylation.

The oxysterol 27-hydroxycholesterol (27-OH) is increasingly considered to be involved in a variety of pathophysiological processes, having been shown to modulate cell proliferation and metabolism, and also to exert proinflammatory and proapoptotic effects. This study aimed to elucidate the molecular pathways whereby 27-OH may generate survival signals in cells of the macrophage lineage, and to clarify whether its known prooxidant effect is involved in that process. A net up-regulation of survival signaling, involving the extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/Akt phosphorylation pathways, was observed in U937 promonocytic cells cultivated over time in the presence of a low micromolar concentration of the oxysterol.

Loading into nanoparticles improves quercetin's efficacy in preventing neuroinflammation induced by oxysterols.

Chronic inflammatory events appear to play a fundamental role in Alzheimer's disease (AD)-related neuropathological changes, and to result in neuronal dysfunction and death. The inflammatory responses observed in the AD brain include activation and proliferation of glial cells, together with up-regulation of inflammatory mediators and of free radicals. Along with glial cells, neurons themselves can also react and contribute to neuroinflammatory changes in the AD brain, by serving as sources of inflammatory mediators.

Up-regulation of β-amyloidogenesis in neuron-like human cells by both 24- and 27-hydroxycholesterol: protective effect of N-acetyl-cysteine.

An abnormal accumulation of cholesterol oxidation products in the brain of patients with Alzheimer's disease (AD) would further link an impaired cholesterol metabolism in the pathogenesis of the disease. The first evidence stemming from the content of oxysterols in autopsy samples from AD and normal brains points to an increase in both 27-hydroxycholesterol (27-OH) and 24-hydroxycholesterol (24-OH) in the frontal cortex of AD brains, with a trend that appears related to the disease severity. The challenge of differentiated SK-N-BE human neuroblastoma cells with patho-physiologically relevant amounts of 27-OH and 24-OH showed that both oxysterols induce a net synthesis of Aβ1-42 by up-regulating expression levels of amyloid precursor protein and β-secretase, as well as the β-secretase activity.

Metalloproteinases and metalloproteinase inhibitors in age-related diseases.

Degradation of the extracellular matrix is an important feature of embryonic development, morphogenesis, angiogenesis, tissue repair and remodeling. It is precisely regulated under physiological conditions, but when dysregulated it becomes a cause of many diseases, including atherosclerosis, osteoarthritis, diabetic vascular complications, and neurodegeneration. Various types of proteinases are implicated in extracellular matrix degradation, but the major enzymes are considered to be metalloproteinases such as matrix metalloproteinases (MMPs) and disintegrin and metalloproteinase domain (ADAMs) that include ADAMs with a thrombospondin domain (ADAMTS).

Phenolic compounds present in Sardinian wine extracts protect against the production of inflammatory cytokines induced by oxysterols in CaCo-2 human enterocyte-like cells.

Cholesterol auto-oxidation products, namely oxysterols, are widely present in cholesterol-rich foods. They are thought to potentially interfere with homeostasis of the human digestive tract, playing a role in intestinal mucosal damage. This report concerns the marked up-regulation in differentiated CaCo-2 colonic epithelial cells of two key inflammatory interleukins, IL-6 and IL-8, caused by a mixture of oxysterols representative of a high cholesterol diet.

Molecular signaling involved in oxysterol-induced β₁-integrin over-expression in human macrophages.

The hypercholesterolemia-atherosclerosis association is now established; hypercholesterolemia may induce vascular-cell activation, subsequently increasing expression of adhesion molecules, cytokines, chemokines, growth factors, and other key inflammatory molecules. Among inflammatory molecules expressed by vascular cells, integrins play a critical role in regulating macrophage activation and migration to the site of inflammation, by mediating cell-cell and cell-extracellular matrix interactions. The main lipid oxidation products present in oxidized LDL that may be responsible for inflammatory processes in atherogenesis, are cholesterol oxidation products, known as oxysterols.

Evidence of cell damage induced by major components of a diet-compatible mixture of oxysterols in human colon cancer CaCo-2 cell line.

Cholesterol oxidation products, termed oxysterols, have been shown to be more reactive than unoxidized cholesterol, possessing marked pro-inflammatory and cytotoxic effects in a number of cells and tissues. Oxysterols, absorbed with the diet as products of cholesterol auto-oxidation, have recently been suggested to potentially interfere with homeostasis of the mucosal intestinal epithelium, by promoting and sustaining irreversible damage. However, the treatment of colon cancer cells with a diet-compatible mixture of oxysterols does not elicit the same responses than individual components added to the cells at the same concentrations at which they are present in the mixture.

Potentiation of amyloid-β peptide neurotoxicity in human dental-pulp neuron-like cells by the membrane lipid peroxidation product 4-hydroxynonenal.

Lipid peroxidation is generally considered as primarily implicated in the pathogenesis of Alzheimer's disease (AD); one of its more reactive end products, 4-hydroxynonenal (HNE), has been shown to cause neuron dysfunction and degeneration. HNE production in the brain is stimulated by the amyloid-β peptide (Aβ), whose excessive accumulation in specific brain areas is a hallmark of AD. Conversely, Aβ production is up-regulated by this multifunctional aldehyde.

The link between altered cholesterol metabolism and Alzheimer's disease.

Alzheimer's disease (AD), the most common form of dementia, is characterized by the progressive loss of neurons and synapses, and by extracellular deposits of amyloid-β (Aβ) as senile plaques, Aβ deposits in the cerebral blood vessels, and intracellular inclusions of hyperphosphorylated tau in the form of neurofibrillary tangles. Several mechanisms contribute to AD development and progression, and increasing epidemiological and molecular evidence suggests a key role of cholesterol in its initiation and progression. Altered cholesterol metabolism and hypercholesterolemia appear to play fundamental roles in amyloid plaque formation and tau hyperphosphorylation.