498 research outputs found
Multiple Haemangiomas, Diaphragmatic Eventration and Beckwith-Wiedemann Syndrome: An Unusual Association
A 6-month-old girl with Beckwith-Wiedemann syndrome, multiple haemangiomas (axillary, laryngeal, pulmonary and hepatic) and diaphragmatic eventration was reported. All tumours responded to treatment with propranolol. The surgical correction of diaphragmatic eventration was crucial to a better outcome
SHOC2 scaffold protein modulates daunorubicin-induced cell death through p53 modulation in lymphoid leukemia cells
SHOC2 scaffold protein has been mainly related to oncogenic ERK signaling through the RAS-SHOC2-PP1 phosphatase complex. In leukemic cells however, SHOC2 upregulation has been previously related to an increased 5-year event-free survival of pediatric pre-B acute lymphoid leukemia, suggesting that SHOC2 could be a potential prognostic marker. To address such paradoxical function, our study investigated how SHOC2 impact leukemic cells drug response. Our transcriptome analysis has shown that SHOC2 can modulate the DNA-damage mediated by p53. Notably, upon genetic inhibition of SHOC2 we observed a significant impairment of p53 expression, which in turn, leads to the blockage of key apoptotic molecules. To confirm the specificity of DNA-damage related modulation, several anti-leukemic drugs has been tested and we did confirm that the proposed mechanism impairs cell death upon daunorubicin-induced DNA damage of human lymphoid cells. In conclusion, our study uncovers new insights into SHOC2 function and reveals that this scaffold protein may be essential to activate a novel mechanism of p53-induced cell death in pre-B lymphoid cells
Some arachnidan peptides with potential medical application
The search for new active drugs that can alleviate or cure different diseases is a constant challenge to researchers in the biological area and to the pharmaceutical industry. Historically, research has focused on the study of substances from plants. More recently, however, animal venoms have been attracting attention and studies have been successful in addressing treatment of accidents. Furthermore, venoms and their toxins have been considered good tools for prospecting for new active drugs or models for new therapeutic drugs. In this review, we discuss some possibilities of using different toxins, especially those from arachnid venoms, which have shown some potential application in diseases involving pain, hypertension, epilepsy and erectile dysfunction. A new generation of drugs is likely to emerge from peptides, including those found in animal venoms
Cyclodextrin modulation of gallic acid in vitro antibacterial activity
The substitution of large spectrum antibiotics for natural bioactive molecules (especially polyphenolics) for the treatment of wound infections has come into prominence in the pharmaceutical industry. However, the use of such molecules depends on their stability during environmental stress and on their ability to reach the action site without losing biological properties. The application of cyclodextrins as a vehicle for polyphenolics protection has been documented and appears to enhance the properties of bioactive molecules. Therefore, the encapsulation of gallic acid, an antibacterial agent with low stability, by -cyclodextrin, (2-hydroxy) propyl--cyclodextrin and methyl--cyclodextrin, was investigated. Encapsulation by -cyclodextrin was confirmed for pH 3 and 5, with similar stability parameters. The (2-hydroxy) propyl--cyclodextrin and methyl--cyclodextrin interactions with gallic acid were only confirmed at pH 3. Among the three cyclodextrins, better gallic acid encapsulation were observed for (2-hydroxy) propyl--cyclodextrin, followed by -cyclodextrin and methyl--cyclodextrin. The effect of cyclodextrin encapsulation on the gallic acid antibacterial activity was also analysed. The antibacterial activity of the inclusion complexes was investigated here for the first time. According to the results, encapsulation of gallic acid by (2-hydroxy) propyl--cyclodextrin seems to be a viable option for the treatment of skin and soft tissue infections, since this inclusion complex has good stability and antibacterial activity.The authors are grateful for the FCT Strategic Project PEst-OE/EQB/LA0023/2013 and the Project "BioHealth-Biotechnology and Bioengineering approaches to improve health quality", Ref. NORTE-07-0124-FEDER-000027, co-funded by the "Programa Operacional Regional do Norte" (ON.2-O Novo Norte), QREN, FEDER. The authors also acknowledge the project "Consolidating Research Expertise and Resources on Cellular and Molecular Biotechnology at CEB/IBB", Ref. FCOMP-01-0124-FEDER-027462. This work is, also, funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE and National Funds through FCT-Foundation for Science and Technology under the project PEst-C/CTM/UI0264/2011. Additionally, the authors would like to thank the FCT for the grant for E. Pinho (SFRH/BD/62665/2009)
Antibacterial activity and mode of action of selected glucosinolate hydrolysis products against bacterial pathogens
Plants contain numerous components that are important sources of new bioactive molecules with antimicrobial properties. Isothiocyanates (ITCs) are plant secondary metabolites found in cruciferous vegetables that are arising as promising antimicrobial agents in food industry. The aim of this study was to assess the antibacterial activity of two isothiocyanates (ITCs), allylisothiocyanate (AITC) and 2-phenylethylisothiocyanate (PEITC) against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Listeria monocytogenes. The antibacterial mode of action was also characterized by the assessment of different physiological indices: membrane integrity, intracellular potassium release, physicochemical surface properties and surface charge. The minimum inhibitory concentration (MIC) of AITC and PEITC was 100 g/mL for all bacteria. The minimum bactericidal concentration (MBC) of the ITCs was at least 10 times higher than the MIC. Both AITC and PEITC changed the membrane properties of the bacteria decreasing their surface charge and compromising the integrity of the cytoplasmatic membrane with consequent potassium leakage and propidium iodide uptake. The surface hydrophobicity was also non-specifically altered (E. coli and L. monocytogenes become less hydrophilic; P. aeruginosa and S. aureus become more hydrophilic). This study shows that AITC and PEITC have strong antimicrobial potential against the bacteria tested, through the disruption of the bacterial cell membranes. Moreover, phytochemicals are highlighted as a valuable sustainable source of new bioactive products.This work was supported by the Operational Programme for Competitiveness Factors - COMPETE and by the Portuguese Foundation for Science and Technology through Project Phytodisinfectants - PTDC/DTP-SAP/1078/2012 (COMPETE: FCOMP-01-0124-FEDER-028765), the PhD grant awarded to Ana Abreu (SFRH/BD/84393/2012), and the post-doctoral grants awarded to Anabela Borges (SFRH/BPD/98684/2013) and Lucia C. Simoes (SFRH/BPD/81982/2011). Also, this work was undertaken as part of the European Research Project SUSCLEAN (Contract no FP7-KBBE-2011-5, project number: 287514) and the COST Action FA1202. The authors are solely responsible for this work. It does not represent the opinion of the European Community, and the Community is not responsible for any use that might be made of data appearing herein
Snail1 factor behaves as a therapeutic target in renal fibrosis.
Kidney fibrosis is a devastating disease that leads to organ failure, and no
specific treatment is available to preserve organ function. In fibrosis,
myofibroblasts accumulate in the interstitium leading to massive
deposition of extracellular matrix and organ disfunction. The origin of
myofibroblasts is multiple and the contribution of renal epithelial cells
after undergoing epithelial-to-mesenchymal transition (EMT) is still
debated. In a model unable to reactivate the EMT inducer Snail1 upon
damage, we show that Snail1 is required in renal epithelial cells for the
development of fibrosis. Damage-mediated Snail1 reactivation induces a
partial EMT that relays fibrotic and inflammatory signals to the interstitium
through the activation of TGF-β and NF-B pathways. Snail1-induced
fibrosis can be reverted in vivo and inhibiting Snail1 in a model of
obstructive nephropathy highly ameliorates fibrosis. These results
reconcile conflicting data on the role of EMT in renal fibrosis and provide
avenues for the design of antifibrotic therapies.pre-print8435 K
Fatores associados à participação de idosos em atividades educativas grupais
Estudo que objetivou caracterizar os idosos e a sua participação em atividades educativas grupais, verificar os fatores sociodemográficos e de saúde associados à não participação. O inquérito transversal foi realizado com 2.142 idosos. Utilizouse análise descritiva, teste t-Student e regressão logÃstica (p < 0,05). A maioria, em ambos os grupos, era do sexo feminino, 60├70 anos, casados e com renda de um salário mÃnimo. Os idosos participativos apresentaram, predominantemente, 1├4 anos de estudo e os não participativos, 4├8. As morbidades mais referidas pelos idosos que participavam de atividades educativas foram hipertensão arterial e problemas de visão. Entre os não participativos, prevaleceram os problemas de visão e problemas de coluna. Em ambos os grupos, o maior percentual foi para 1├3 incapacidades. A faixa etária de 80 anos e mais esteve associada à maior chance de não participação nas atividades. Faz-se necessário planejar ações que favoreçam a participação, contribuindo para o acompanhamento das suas condições de saúde.
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