Growing evidence supporting the use of mesenchymal stem cell therapies in multiple sclerosis: a systematic review

Background: Multiple sclerosis (MS) typically arises in early/middle adulthood and is characterized by a progressive disability of the central nervous system (CNS). Currently approved therapies do not promote tissue repair or stop disease progression. Emerging data demonstrate that stem cells present a great potential in regenerative medicine and, consequently, have also been widely investigated as a potential treatment for MS. Therefore, the aim of this study was to conduct a systematic review to inquire into the safety, tolerability, and efficacy of mesenchymal stem cells (MSCs) therapies in MS. Methods: Three electronic databases (Web of Science, PubMed, and Cochrane) were searched from April until June 2019. Clinical trials or case reports with information related to the effects of MSC therapies in MS patients were considered for this review. Results: 10 manuscripts were selected, namely 7 uncontrolled clinical trials, 2 randomized controlled clinical trials, and 1 case report. The overall quality of the studies was considered good. Besides minor adverse events (AEs), it was reported one case of encephalopathy with seizures and two cases of iatrogenic meningitis, which were not related to the treatment, but with the administration route. The analyses of the expanded disability status scale (EDSS) in the uncontrolled clinical trials demonstrated that 48 patients improved, 39 maintained and 16 worsened their clinical condition. Regarding the randomized studies, one did not show statistically significant variations in the mean EDSS score and in the other the mean EDSS score was statistically significantly lower for the experimental group. The case report also showed an improvement in the EDSS score. Conclusions: MSCs transplantation proved to be a safe and tolerable therapy. Their potential therapeutic benefits were also validated. However, larger placebo controlled blinded clinical trials will be required to establish the long term safety and efficacy profile of these therapies for MS. Their translation into the clinical practice can provide a new hope for the patients of this highly debilitating disease

Development of dioctadecyldimethylammonium bromide/monoolein liposomes for gene delivery

The artificial introduction of nucleic acids (NA) into mammalian cells (transfection) has become, in recent years, a well-established procedure in basic and applied research, which allowed the study of gene function and regulation. The advances in this area have made possible the use of these methods for gene-based medicines, which constitute alternative therapeutic approaches. One of the most prominent methods is lipofection that uses cationic liposome/NA complexes (a.k.a. lipoplexes) for the complexation, transport and release of therapeutic sequences into target cells. Although yielding lower transfection efficiencies compared with viral gene delivery, lipofection vectors are much safer for medical applications because no significant mutational or toxicological risk exist. Dioctadecyldimethylammonium Bromide (DODAB)/Monoolein (MO) liposomes have recently been described as a new promising alternative to common transfection reagents, due to the pioneering application of MO as helper lipid in lipoplex formulations. In this chapter, we will review the effect of MO on the physicochemical properties of DODAB/MO liposomes and pDNA/DODAB/MO lipoplexes. How lipoplex properties may affect the interaction with different extracellular components and their cell uptake and trafficking will be discussed. The importance of lipoplex biocompatibility towards efficient gene therapy will also be approached presenting pDNA/DODAB/MO system as a lipoplex model, supporting the use of MO as new helper lipid in lipofection.FCTCOMPETEThis work was supported by FCT research project PTDC/QUI/69795/2006, which is cofunded by the program COMPETE from QREN with co-participation from the European Community fund FEDER; CFUM [PEst-C/FIS/UI0607/2011]; CBMA [Pest C/BIA/UI4050/2011]; J.P.N. Silva holds a PhD Grant (SFRH/BD/46968/2008); A. C.N. Oliveira holds a PhD grant (SFRH/BD/68588/2010)

Novel benzopsoralen analogues : synthesis, biological activity and molecular docking studies

New benzopsoralen analogues were synthesized and their inhibitory effect on the growth of tumourtumour cell lines (MDA MB231 and TCC-SUP) was evaluated. The in vitro antitumour activity of the new benzopsoralen analogues was discussed in terms of structure–activity relationship. Molecular docking studies with human-CYP2A6 enzymes were also carried out with the synthesized compounds to evaluate the potential of these molecules to interact with the haem group of the enzymes. The results demonstrated that the compounds that are able to interact with the iron ion of the haem cofactor and at the same time with active site Asn297 are those that have better anti-proliferative activity.To the Foundation for the Science and Technology (FCT, Portugal) for financial support to the NMR Portuguese network (PTNMR, Bruker Avance III 400-Univ. Minho). FCT and FEDER (European Fund for Regional Development)-COMPETE-QREN-EU for financial support to the Chemistry Research Centre, CQ/UM [PEst-C/QUI/UI0686/2011 (FCOMP-01-0124-FEDER-022716)], to REQUIMTE (PEst-C/EQB/LA0006/2011), to the Centre of Biological Engineering (PEst-OE/EQB/LA0023/2013) and the PhD grant to C.S.F. (SFRH/BD/48636/2008). The authors also acknowledge the Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP, Porto, Portugal) for kindly providing the breast cancer cell lines used in this work

Synthesis of novel psoralen analogues derived from 7-hydroxy-4-methylcoumarin

Fundação para a Ciência e a Tecnologia (FCT) FEDER (European Fund for Regional Development)-COMPETE-QREN-EU FCOMP-01-0124-FEDER-022716FEDER (European Fund for Regional Development)-COMPETE-QREN-EU FCOMP-01-0124-FEDER-02271

Synthesis of novel psoralen analogues and their in vitro antitumor activity

New tetracyclic benzofurocoumarin (benzopsoralen) analogues were synthesized and their inhibitory effect on the growth of tumor cell lines was evaluated. The human tumor cell lines used were MDA MB231 (breast adenocarcinoma), HeLa (cervix adenocarcinoma) and TCC-SUP (bladder transitional cell carcinoma). The in vitro antitumor activity of the new benzopsoralens was discussed in terms of structure–activity relationship. Molecular docking studies with human-CYP2A6 enzymes were also carried out with the synthesized compounds in order to evaluate the potential of these compounds to interact with the heme group of the enzymes. The results have demonstrated that the linear compounds have the most pronounced activity against tumor cell lines and this might be related to the better accessibility that these compounds have to the active site in relation to the angular ones that have shown in the majority of the cases multiple binding poses in the active site of CYP2A6.To the Foundation for the Science and Technology (FCT, Portugal) for financial support to the NMR portuguese network (PTNMR, Bruker Avance III 400-Univ. Minho). FCT and FEDER (European Fund for Regional Development)-COMPETE-QREN-EU for financial support to the Research Centre, CQ/UM [PEst-C/QUI/UI0686/2011 (FCOMP-01-0124-FEDER-022716)], (Pest-C/EQB/LA0006/2011) and the PhD grant to C.S.F. (SFRH/BD/48636/2008). The authors also acknowledge the Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP, Porto, Portugal) for kindly providing the breast cancer cell line used in this work

Mathematical modelling of convective drying of Galega kale

info:eu-repo/semantics/publishedVersio

Synthesis of novel benzofurocoumarin analogues and their anti-proliferative effect on human cancer cell lines

The synthesis of five new tetracyclic benzofurocoumarin (benzopsoralen) analogues is described. Their inhibitory effects on the growth of three human tumour cell lines (MDA MB 231 (breast adenocarcinoma), HeLa (cervix adenocarcinoma) and TCC-SUP (bladder transitional cell carcinoma)) were evaluated, and discussed in terms of structure–activity relationship.FCT and FEDER, for National NMR Network (Bruker Avance II 400), REEQ/630/QUI/2005 (LC/MS instrument) and the PhD grant (SFRH/BD/48636/2008)

Synthesis of novel psoralen analogues and in vitro antitumor activity

Psoralens are natural products present in several plant families that are extremely toxic to a wide variety of prokaryotic and eukaryotic organisms. They are potentially active in diseases such as vitiligo, psoriasis, and several types of cancer. Following our interest on this type of compounds 1 four new psoralen analogues were prepared, 1a-1c and 1e. To synthesize 1a (R = H) the method of Harayama and Ishii was used where the cinnamate was obtained by the Wittig reaction followed by ring closure. Condensation of 1-formyl-2-hydroxycarbazole with diethyl malonate gave 1b which by basic hydrolysis yielded compound 1c. Compound 1d was prepared before.2 Condensation of the 2-hydroxycarbazole with ethyl acetoacetate gave 1e. The products were characterized by elemental analysis, 1H and 13C NMR. Moreover, the anti-proliferative effect of compounds 1a-1e on human cancer cell lines (MDA-MB 231, HeLa and TCCSUP) was evaluated. Results suggest that these psoralen analogues possess a potent cytotoxic effect against the cell lines studied. Computational and molecular docking studies are being carried out.Fundação para a Ciência e a Tecnologia (FCT)(PEst-C/QUI/UI0686/2011), FEDER-COMPET

DODAB:MO versus novel liposomes for protein delivery: comparing toxicity and encapsulation efficiency

UID/BIA/04050/2019, funded by national funds through the FCT IP, and project FUN2CYT: Harnessing the potential for biomedical applications of pleiotropic cytokines LIF and oncostatin M (PTDC/BTM-MAT/30568/2017, POCI-01-0145-FEDER-030568) supported by POCI through FEDER and FCT IPinfo:eu-repo/semantics/publishedVersio