In vitro and in vivo characteristics of frozen/thawed neonatal pig split-skin strips: A novel biologically active dressing for areas of severe, acute or chronic skin loss

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Role of p75 Neurotrophin Receptor in the Neurotoxicity by β-amyloid Peptides and Synergistic Effect of Inflammatory Cytokines

The neurodegenerative changes in Alzheimer's disease (AD) are elicited by the accumulation of β-amyloid peptides (Aβ), which damage neurons either directly by interacting with components of the cell surface to trigger cell death signaling or indirectly by activating astrocytes and microglia to produce inflammatory mediators. It has been recently proposed that the p75 neurotrophin receptor (p75NTR) is responsible for neuronal damage by interacting with Aβ. By using neuroblastoma cell clones lacking the expression of all neurotrophin receptors or engineered to express full-length or various truncated forms of p75NTR, we could show that p75NTR is involved in the direct signaling of cell death by Aβ via the function of its death domain. This signaling leads to the activation of caspases-8 and -3, the production of reactive oxygen intermediates and the induction of an oxidative stress. We also found that the direct and indirect (inflammatory) mechanisms of neuronal damage by Aβ could act synergistically. In fact, TNF-α and IL-1β, cytokines produced by Aβ-activated microglia, could potentiate the neurotoxic action of Aβ mediated by p75NTR signaling. Together, our results indicate that neurons expressing p75NTR, mostly if expressing also proinflammatory cytokine receptors, might be preferential targets of the cytotoxic action of Aβ in AD

Comano's (Trentino) thermal water interferes with interleukin-6 production and secretion and with cytokeratin-16 expression by cultured human psoriatic keratinocytes: Further potential mechanisms of its anti-psoriatic action

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Survey of the main causal agents of fusarium head blight of durum wheat around Bologna, northern Italy

Several Fusarium species and Microdochium nivale are involved in fusarium head blight (FHB), which in Italy has been constantly present on wheat since 1995. This study was carried out from 1995 to 2007 on FHB-infected durum wheat heads collected in the Bologna countryside, Emilia-Romagna, northern Italy. The most frequent Fusarium species found were: Fusarium graminearum (32.1%), F. culmorum (25.2%) and F. poae (17.8%), while F. avenaceum and M. nivale occurred discontinuously. Other Fusarium species were also found, but only sporadically. It is important to identify and characterize the main species involved in the FHB syndrome for this will help us to establish control strategies that will contain the disease and the content of mycotoxins in food and animal feed

Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients

Sampling seeds in storage facilities: hunting for Fusarium infection

Fusarium graminearum is one of the most studied fungal pathogens in the world. A great number of scientific publications are available that describe morphology, physiology, toxicology and genome of this species. On the other hand, F. poae is less widely studied but its importance as toxigenic fungus has been recently recognized. In Italy, F. poae is rapidly becoming one of the most widespread Fusarium species on small seeds cereals heads. Soft wheat is often colonised by these species. So far, Fusarium Head Blight (FHB) symptoms have been always investigated on soft wheat heads or on seeds collected in the field during harvesting. This poses a problem, as the seed industry and the national seed certification services would be interested to know the percentage of infection of seeds stored into facilities after processing and how infection is distributed inside seed lots. In order to study these aspects, we performed a mycological screening on soft wheat seed samples collected inside a facility, sampling directly from bags intended for seed trading. Sampling was performed during the years 2013 and 2014. The screening, carried out on Potato Dextrose Agar (PDA), was limited to organic soft wheat coming from Northern and Central Italy. Putative F. graminearum and F. poae colonies were selected and single spores purified and confirmed through microscope observations and through a molecular identification. Seed samples resulted to be infected at a very low level. Though some lack of homogeneity was observed among the lots, this was sufficiently small to allow statistical studies

Calcium-sensing receptor (CaSR) in human brain's pathophysiology: roles in late-onset Alzheimer's disease (LOAD)

Although the calcium-sensing receptor (CaSR) is expressed by all types of nerve cells in widespread areas of the human central nervous system (CNS), so far its roles in brain pathophysiology remain largely unknown. Here, we review the available evidence concerning the stages of development of sporadic late-onset Alzheimer's disease (LOAD) and the roles therein played by CaSR signaling. As the brain ages, its ability to dispose of dangerous synapse-targeting soluble amyloid \u3b2-(1-42) (sA\u3b242) oligomers released from normal neuronal activity declines. As their levels slowly rise, these oligomers increasingly target and eliminate synapses and prevent synapse formation, thereby eroding the foundations of memory formation and cognitive functions. In this initial stage, neurons, even though synaptically impaired, remain alive. Concurrently, sA\u3b242 oligomers by binding to CaSR on human astrocytes induce via mitogen activated protein kinase (MAPK) activity the release of huge amounts nitric oxide (NO), which by itself and after conversion to peroxynitrite (ONOO-) damages neighboring neurons. When the sA oligomers increasingly aggregate into fibrillar plaques, they attract and activate microglial macrophages that, while trying to clear the plaques, produce via A CaSR signaling several proinflammatory cytokines and reactive oxygen species (ROS). Notably, the microglial cytokines, like sA oligomers, induce human astrocytes to make large amounts of NO and hence ONOO- via CaSR signal-dependent MAPK activity. The microglial cytokines-activated astrocytes might also produce their own sA, which would combine with neuron- and microglia-released sA\u3b242 to increase the fibrillar burden and promote the further production of reactive oxygen species (ROS), NO/ONOO-, and proinflammatory cytokines to efficiently kill both normal and functionally impaired (undead) neurons. But, on a somewhat positive note, we speculate that the astrocytes' CaSR-stimulated MAPK activities might also induce vascular endothelial growth factor (VEGF) expression and production. This might in turn enhance neuronal stem cells neurogenesis at least in the subgranular zone (SGZ) of the hippocampal dentate gyrus.Peer reviewed: YesNRC publication: Ye

Emerging concepts of how beta-amyloid proteins and pro-inflammatory cytokines might collaborate to produce an Alzheimer Brain Molecular Medicine Reports (review).

NRC publication: Ye