1,720,984 research outputs found
PBL (Psoralens + Blue light): how blue light activates furocoumarin derivatives triggering tumor cell apoptosis
No full textBACKGROUND. Furocoumarins are natural and synthetic compounds with high chemotherapeutic potency under UVA irradiation. To improve their activity and avoid severe side effects likely mainly related to the formation of interstrand crosslinks (XLs) with DNA pyrimidine bases, a variety of derivatives, hopefully monofunctionals, have been synthesized. Although angelicins, due to their angular geometry, do not generally form XLs, some of them, i.e. (TMA), can crosslink folded DNA upon UVA. The UVA photobiological effects of furocoumarins are mainly related to their capacity to photoreact with DNA. Furthermore, furocoumarins produce ROS that impair cellular functions through lipid peroxidation, oxidation of guanine and strand breaks in nucleic acids, oxidation of proteins and inactivation of enzymes.
To photoactivate 8- MOP and 4,6,4'-trimetylangelicin (TMA) towards human prostate (DU145 PCa) and bladder (T24) cancer cell lines, a new approach based on less toxic and more penetrating visible radiation (BL, 420 nm) is presented.
RESULTS. TMA and 8-MOP show high antiproliferative activity towards cancer cells, through induction of apoptosis. Besides ROS generation (less efficient under BL than UVA), the proapoptotic effect seems related to the activation of p38 and inhibition of p44/42 phosphorylation. Interestingly, the decrease of β nuclear-catenin is coupled with dropping of CD44-positive cells. The strong photocytotoxicity of TMA and 8-MOP can be related to the kind and number of DNA lesions. Under BL, no mutagenic crosslinks, no photocleavage nor photooxidative lesions are detected on isolated DNA by TMA treatment, but only MAs form. However, formation of XLs still remains for 8-MOP under BL but in a lower amount than UVA.
CONCLUSIONS. Overall, our results indicate that 8-MOP, and particularly TMA, can be efficiently activated by BL and may be considered good compounds for targeted phototherapy of prostate and bladder cancers and possibly for other solid tumors
PBL (PSORALENS + BLUE LIGHT): BLUE LIGHT ACTIVATES 8-MOP AND TMA TRIGGERING PROSTATE (DU145) AND VESICAL (T24) TUMOR CELL APOPTOSIS AND DEATH
No full textBACKGROUND. Psoralens and angelicins (furocoumarins) are natural and synthetic compounds with high antiproliferative potency under UVA irradiation mainly used for the treatment of skin diseases (PUVA therapy) or immunological disorders in extracorporeal photopheresis (ECP). To improve their activity against psoriasis or vitiligo and avoid severe side effects mainly related to the formation of interstrand crosslinks (XLs) with DNA pyrimidine bases, a variety of derivatives, hopefully monofunctional, have been synthesized. Although angelicins, due to their angular geometry, do not generally form XLs, some of them, i.e. (TMA), can crosslink folded DNA upon UVA. Furthermore, furocoumarins produce ROS that impair cellular functions through lipid peroxidation, oxidation of guanine and strand breaks in nucleic acids, oxidation of proteins and inactivation of enzymes.
To photoactivate 8- MOP and 4,6,4'-trimetylangelicin (TMA) towards human prostate (DU145 PCa) and bladder (T24) cancer cell lines, a new approach based on less toxic and more penetrating visible radiation (BL, 420 nm) is proposed.
RESULTS. TMA and 8-MOP showed high antiproliferative activity towards both cancer cell lines, through induction of apoptosis. Besides ROS generation (less efficient under BL than UVA), the proapoptotic effect seemed related to the activation of p38 and inhibition of p44/42 phosphorylation. Moreover, no phosphorylation of the histone H2AX, nuclear β -catenin and GSK3β occurred. Moreover, Cyclin D1, c-Myc and CD44v6 expression were reduced through inhibition of the Wnt pathway. Overall, DU145 cells appeared more sensitive to PBL than T24, showing a specificity of the test compounds towards different tumor cell lines. The strong photocytotoxicity of TMA and 8-MOP can be related to the kind and number of DNA lesions. Under BL, no mutagenic crosslinks, no photocleavage nor photooxidative lesions were detected on isolated DNA by TMA phototreatment, but only MAs can form. However, generation of XLs still remained for 8-MOP under BL but in a lower amount than under UVA.
CONCLUSIONS. Overall, our results indicate that 8-MOP, and particularly TMA, can be efficiently activated by BL and may be considered good candidates for targeted PBL of prostate and bladder cancers and possibly for other solid tumors
Angiogenic response induced by acellular brain scaffolds grafted onto the embryo chorioallantoic membrane. BRAIN RESEARCH
No full text
Gut acellular matrix for the in vitro study of Enteric Nervous System cells
Full text linkEnteric nervous system (ENS) cells respond to the intestinal extracellular matrix (ECM) signals changing their proliferation rate, migration and differentiation. In this study, we explored in vitro the adaptive response of primary ENS cell cultures to the stimulation of gut acellular matrix (AM) defining the gene expression profile of neuronal functionality markers. Scanning electron microscopy was used to detect the acquisition of specific morphological features.
Intestinal AM was prepared using an enzyme-detergent treatment. Primary rat enteric cells were isolated from the myenteric plexus of postnatal rats using an enzymatic method and seeded on intestinal AM in the presence of exogenous neurotrophic factors. The morphological properties and the expression of specific differentiation markers were evaluated by Scanning Electron Microscopy (SEM) and wholemount fluorescent staining. In order to verify the synergic activity of soluble factors and AM, the gene expression of neurotransmitter receptors was evaluated by qPCR in ENS cells cultured in SM conditions in the presence or not of AM.
The development of interconnected ganglion-like structures and the expression of neurotransmitter receptors suggested that gut matrix engineered with ENS cells could be useful for medical applications of regenerative medicine or for the in vitro assessment of tridimensional culture system of ENS
4,6,4′-trimethylangelicin photoactivated by blue light might represent an interesting option for photochemotherapy of non-invasive bladder carcinoma: An in vitro study on T24 cells
Full text linkPhotodynamic therapy (PDT) is frequently used to treat non-muscle invasive bladder cancer due its low toxicity and high selectivity. Since recurrence often occurs, alternative approaches and/or designs of combined therapies to improve PDT effectiveness are needed. This work aimed to evaluate the cytotoxicity of 4,6,4′-trimethylangelicin (TMA) photoactivated by blue light (BL) on human bladder cancer T24 cells and investigate the mechanisms underlying its biological effects. TMA/BL exerted antiproliferative activity through the induction of apoptosis without genotoxicity, as demonstrated by the expression levels of phospho-H2AX, an indicator of DNA double-stranded breaks. It also modulated the Wnt canonical signal pathway by increasing the phospho-β-catenin and decreasing the nuclear levels of β-catenin. The inhibition of this pathway was due to the modulation of the GSK3β phosphorylation state (Tyr 216) that induces a proteasomal degradation of β- catenin. Indeed, a partial recovery of nuclear β-catenin expression and reduction of its phosphorylated form after treatment with LiCl were detected. As demonstrated by RT-PCR and cytofluorimetric analysis, TMA/BL also decreased the expression of CD44v6, a marker of cancer stem cells. Taken together, our data suggest that TMA photoactivated by BL may represent an interesting option for the photochemotherapy of noninvasive bladder carcinomas, since this treatment is able to inhibit key pathways for tumour growth and progression in the absence of genotoxic effects
GENDER AS PREDISPOSING FACTOR TO LIVER REGENERATION BY HEPATIC PROGENITOR CELLS PROLIFERATION AND STELLATE CELL ACTIVATION IN A MURINE MODEL OF ACUTE LIVER INJURY
No full textGoing Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Growth and Differentiation of Circulating Stem Cells After Extensive Ex Vivo Expansion
Full text linkBackground:: Stem cell therapy is gaining momentum as an effective treatment strategy for degenerative diseases. Adult stem cells isolated from various sources (i.e., cord blood, bone marrow, adipose tissue) are being considered as a realistic option due to their well-documented therapeutic potentials. Our previous studies standardized a method to isolate circulating multipotent cells (CMCs) that are able to sustain long term in vitro culture and differentiate towards mesodermal lineages. Methods:: In this work, long-term cultures of CMCs were stimulated to study in vitro neuronal and myogenic differentiation. After induction, cells were analysed at different time points. Morphological studies were performed by scanning electron microscopy and specific neuronal and myogenic marker expression were evaluated using RT-PCR, flow cytometry and western blot. For myogenic plasticity study, CMCs were transplanted into in vivo model of chemically-induced muscle damage. Results:: After neurogenic induction, CMCs showed characteristic dendrite-like morphology and expressed specific neuronal markers both at mRNA and protein level. The calcium flux activity of CMCs under stimulation with potassium chloride and the secretion of noradrenalin confirmed their ability to acquire a functional phenotype. In parallel, the myogenic potential of CMCs was confirmed by their ability to form syncytium-like structures in vitro and express myogenic markers both at early and late phases of differentiation. Interestingly, in a rat model of bupivacaine-induced muscle damage, CMCs integrated within the host tissue taking part in tissue repair. Conclusion:: Overall, collected data demonstrated long-term cultured CMCs retain proliferative and differentiative potentials suggesting to be a good candidate for cell therapy
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