Search results for "PAI"
showing 10 items of 10553 documents
Gene therapy for chondral and osteochondral regeneration: is the future now?
2017
Gene therapy might represent a promising strategy for chondral and osteochondral defects repair by balancing the management of temporary joint mechanical incompetence with altered metabolic and inflammatory homeostasis. This review analysed preclinical and clinical studies on gene therapy for the repair of articular cartilage defects performed over the last 10 years, focussing on expression vectors (non-viral and viral), type of genes delivered and gene therapy procedures (direct or indirect). Plasmids (non-viral expression vectors) and adenovirus (viral vectors) were the most employed vectors in preclinical studies. Genes delivered encoded mainly for growth factors, followed by transcripti…
Taxonomic clarification of three taxa of Iberian geomitrids, Helix montserratensis Hidalgo, 1870 and subspecies (Gastropoda, Pulmonata), based on mor…
2017
Revisión taxonómica de tres taxones de geomítridos ibéricos, Helix montserratensis Hidalgo, 1870, y subespecies (Gastropoda, Pulmonata), basada en datos morfo–anatómicos Helix montserratensis (actualmente Xerocrassa montserratensis) es un geomítrido ibérico descrito por Hidalgo en 1870 en Montserrat (Barcelona, España). Sobre la base de varios caracteres conquiológicos, se describieron dos taxones muy similares, como variedades de este taxón: Helix montserratensis betulonensis y otro menos nombrado, Helix montserratensis delicatula. Estas variedades, sobre todo betulonensis, se han considerado subespecies de X. montserratensis, aunque algunos autores las consideran especies diferentes, basá…
CHK1 inhibitor sensitizes resistant colorectal cancer stem cells to nortopsentin
2021
Summary Limited therapeutic options are available for advanced colorectal cancer (CRC). Herein, we report that exposure to a neo-synthetic bis(indolyl)thiazole alkaloid analog, nortopsentin 234 (NORA234), leads to an initial reduction of proliferative and clonogenic potential of CRC sphere cells (CR-CSphCs), followed by an adaptive response selecting the CR-CSphC-resistant compartment. Cells spared by the treatment with NORA234 express high levels of CD44v6, associated with a constitutive activation of Wnt pathway. In CR-CSphC-based organoids, NORA234 causes a genotoxic stress paralleled by G2-M cell cycle arrest and activation of CHK1, driving the DNA damage repair of CR-CSphCs, regardless…
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…
Bioenergetic Failure in Rat Oligodendrocyte Progenitor Cells Treated with Cerebrospinal Fluid Derived from Multiple Sclerosis Patients
2017
In relapsing-remitting multiple sclerosis (RRMS) subtype, the patient's brain itself is capable of repairing the damage, remyelinating the axon and recovering the neurological function. Cerebrospinal fluid (CSF) is in close proximity with brain parenchyma and contains a host of proteins and other molecules, which influence the cellular physiology, that may balance damage and repair of neurons and glial cells. The purpose of this study was to determine the pathophysiological mechanisms underpinning myelin repair in distinct clinical forms of MS and neuromyelitis optica (NMO) patients by studying the effect of diseased CSF on glucose metabolism and ATP synthesis. A cellular model with primary…
Cardiac Glycoside Glucoevatromonoside Induces Cancer Type-Specific Cell Death.
2018
Cardiac glycosides (CGs) are natural compounds used traditionally to treat congestive heart diseases. Recent investigations repositioned CGs as potential anticancer agents. To discover novel cytotoxic CG scaffolds, we selected the cardenolide glucoevatromonoside (GEV) out of 46 CGs for its low nanomolar anti-lung cancer activity. GEV presented reduced toxicity toward non-cancerous cell types (lung MRC-5 and PBMC) and high-affinity binding to the Na+/K+-ATPase α subunit, assessed by computational docking. GEV-induced cell death was caspase-independent, as investigated by a multiparametric approach, and culminates in severe morphological alterations in A549 cells, monitored by transmission el…
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…
Evaluation of Long-Time Decoction-Detoxicated Hei-Shun-Pian (Processed Aconitum carmichaeli Debeaux Lateral Root With Peel) for Its Acute Toxicity an…
2020
Background As a degenerative joint disease with severe cartilage destruction and pain, osteoarthritis (OA) has no satisfactory therapy to date. In traditional Chinese medicine (TCM), Aconitum carmichaeli Debeaux derived Hei-shun-pian (Hsp) has been developed for joint pain treatment. However, it causes adverse events in OA patients. Long-time decoction has been traditionally applied to reduce the aconite toxicity of Hsp and other aconite herbs, but its detoxifying effect is uncertain. Methods Hsp was extracted with dilute decoction times (30, 60, and 120 min) and evaluated by toxicological, chemical, pharmacological assays. Acute toxicity assay and chemical analysis were employed to determi…
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…