Search results for " PAI."
showing 10 items of 3604 documents
Dying with or because of invasive fungal infection? The role of immunity exhaustion on patient outcome
2016
De Rosa et al. considered clinical scores, biomarkers and their combination as useful aids for an early antifungal treatment and advocated the adoption of de-escalation therapy in an antifungal stewardship approach as a possible key for a better management of these patients. Authors considered the high burden of invasive fungal infections in terms of patient outcomes and costs and focused on current strategies for their optimization.
Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy
2016
Peripheral or central nerve injury is a frequent cause of chronic pain and the mechanisms are not fully understood. Using newly generated transgenic mice we show that progranulin overexpression in sensory neurons attenuates neuropathic pain after sciatic nerve injury and accelerates nerve healing. A yeast-2-hybrid screen revealed putative interactions of progranulin with autophagy-related proteins, ATG12 and ATG4b. This was supported by colocalization and proteomic studies showing regulations of ATG13 and ATG4b and other members of the autophagy network, lysosomal proteins and proteins involved in endocytosis. The association of progranulin with the autophagic pathway was functionally confi…
Acute surgical abdomen during the COVID‑19 pandemic: Clinical and therapeutic challenges
2021
The present study investigated the effects of the COVID-19 pandemic on the clinical presentation and therapeutic management of acute surgical abdomen. A retrospective study of emergency hospitalizations with a diagnosis of acute surgical abdomen between April and July 2020 vs. a similar period in 2019 was performed. The observation sheets and the operating protocols were analyzed. Between April and July 2020, 50 cases of acute surgical abdomen were hospitalized and treated, compared to 43 cases in the same period last year. The main types of pathology in both groups included: Occlusions (60%, respectively 44.2% in 2019) and peritonitis (32%, respectively 41.8% in 2019). There was an increas…
New insights into the mechanism of action of pyrazolo[1,2-a]benzo[1,2,3,4]tetrazin-3-one derivatives endowed with anticancer potential
2018
Due to the scarce biological profile, the pyrazolo[1,2-a]benzo[1,2,3,4]tetrazine-3-one scaffold (PBT) has been recently explored as promising core for potential anticancer candidates. Several suitably decorated derivatives (PBTs) exhibited antiproliferative activity in the low-micromolar range associated with apoptosis induction and cell cycle arrest on S phase. Herein, we selected the most active derivatives and submitted them to further biological explorations to deepen the mechanism of action. At first, a DNA targeting is approached by means of flow Linear Dichroism experiments so as to evaluate how small planar molecules might interact with DNA, including the interference with the catal…
Human Dental Pulp Stem Cells Exhibit Different Biological Behaviours in Response to Commercial Bleaching Products
2018
The purpose of this study was to evaluate the diffusion capacity and the biological effects of different bleaching products on human dental pulp stem cells (hDPSCs). The bleaching gel was applied for 90, 30 or 15 min to enamel/dentine discs that adapted in an artificial chamber. The diffusion of hydrogen peroxide (HP) was analysed by fluorometry and the diffusion products were applied to hDPSCs. Cell viability, cell migration and cell morphology assays were performed using the eluates of diffusion products. Finally, cell apoptosis and the expression of mesenchymal stem cell markers were analysed by flow cytometry. Statistical analysis was performed using analysis of variance and Kruskal&nda…
Targeting Voltage-Dependent Calcium Channels with Pregabalin Exerts a Direct Neuroprotective Effect in an Animal Model of Multiple Sclerosis
2018
Background/aims Multiple sclerosis (MS) is a prototypical autoimmune central nervous system (CNS) disease. Particularly progressive forms of MS (PMS) show significant neuroaxonal damage as consequence of demyelination and neuronal hyperexcitation. Immuno-modulatory treatment strategies are beneficial in relapsing MS (RMS), but mostly fail in PMS. Pregabalin (Lyrica®) is prescribed to MS patients to treat neuropathic pain. Mechanistically, it targets voltage-dependent Ca2+ channels and reduces harmful neuronal hyperexcitation in mouse epilepsy models. Studies suggest that GABA analogues like pregabalin exert neuroprotective effects in animal models of ischemia and trauma. Methods We tested t…
A swift, easy and cheap protocol to evaluate the tooth bleaching in vitro
2018
Background: This study aims to develop a protocol that optimizes in vitro dental bleaching procedures in a cheap, fast and accessible manner. Material and Methods: 18 bovine incisors were cut and polished in enamel/dentin and submitted to staining in coffee solution during 72 hours. After the standardization and staining of the enamel surfaces, three groups (n = 6) were formed to receive three different gels, WHITENESS (commercial gel); H 2 O 2 - 5% (manipulated gel); CAR - BOPOL GEL (manipulated gel and without H 2 O 2 ). The color of the enamel surfaces was evaluated using digital images, obtained with digital camera and controlled luminosity, before and after staining, as well as after e…
Curcumin downregulates expression of opioid-related nociceptin receptor gene (OPRL1) in isolated neuroglia cells.
2018
Abstract Background: Curcumin (CC) exerts polyvalent pharmacological actions and multi-target effects, including pain relief and anti-nociceptive activity. In combination with Boswellia serrata extract (BS), curcumin shows greater efficacy in knee osteoarthritis management, presumably due to synergistic interaction of the ingredients. Aim: To elucidate the molecular mechanisms underlying the analgesic activity of curcumin and its synergistic interaction with BS. Methods: We performed gene expression profiling by transcriptome-wide mRNA sequencing in human T98G neuroglia cells treated with CC (Curamed), BS, and the combination of CC and BS (CC-BS; Curamin), followed by interactive pathways a…
Contribution of allelic imbalance to colorectal cancer
2018
Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (AI) landscape in 1699 colorectal cancers, 256 of which have been whole-genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible AI targets based on previous knowledge. Unbiased CRISPR-Cas9 knockout and activation screens identified in total 79 genes within AI peaks regulating cell growth. Genetic and functional data implicate loss of TP53 as a sufficient driver of AI. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point muta…
Correlation between micro-hardness and mineral content in healthy human enamel
2016
Background Enamel is the hardest and the stiffest tissue in the human body. The enamel undergoes multidirectional stresses, withstands multimillion chewing cycles, all while protecting the internal dentin and pulp from damage due to mechanical overload and exposure to the harsh chemical environment of the mouth. Raman spectroscopy allows to study enamel mineral content in a non-destructive and site-specific way. While Raman spectroscopy has been applied in other studies to assess tooth mineralization, there are no studies that examine the relationship between micro-hardness and mineral content of the untreated enamel. An understanding of this relationship is extremely important in a clinica…