A aterosclerose é uma doença cardiovascular (DCV) que afeta 4 em cada 1.000 pessoas, e é caracterizada por lesões arteriais inflamatórias que evoluem com o desenvolvimento da doença. Está envolvida neste processo uma alta produção de citocinas pró-inflamatórias cuja expressão é mediada pela ativação do fator de transcrição nuclear kappa B (NF-B), responsável por desencadear processos de proliferação celular e migração de células musculares lisas nas regiões de lesões arteriais, contribuindo para o agravamento da doença. Estudos de nosso laboratório mostraram que prostaglandinas ciclopentenônicas (CP-PGs), que são anti-inflamatórias, revertem as lesões ateromatosas em modelos animais, num processo que depende da indução de proteínas de choque térmico - HSP (do inglês Heat Shock Protein) por estas CP-PGs. HSPs impedem a desnaturação de proteínas intracelulares e “desligam” o fator nuclear NF-B, que é um dos principais envolvidos na doença inflamatória vascular da aterosclerose. Por isso, decidimos investigar o efeito direto da expressão de HSPs via choque térmico, no processo inflamatório da aterosclerose, pelo método de “hot tub” realizado semanalmente em camundongos machos nocaute para o receptor de LDL (KO-LDLr), em dieta hiperlipídica e hipercolesterolêmica. Para avaliar estes efeitos os animais foram semanalmente (num período de oito semanas) submetidos a um banho térmico elevando a temperatura corporal para 41,5°C por 15 min. Os resultados demonstraram que, na aorta torácica, o choque térmico aumentou a expressão da HSP70 em cerca de 50% o que foi acompanhado de aumento de 100% na expressão do fator de choque térmico – HSF e dramática queda na ativação do fator NF-kB (75%). Em paralelo, o choque térmico reduziu em mais de 50% a deposição de lípides na parede da aorta e na gordura epididimal e a lipoperoxidação em cerca de 40%. As análises com ultrassonografia Doppler demonstraram que o choque térmico melhorou o fluxo sanguíneo, reduziu a espessura da parede aórtica e melhorou a performance cardíaca. O tratamento também melhorou o status glicêmico (redução de glicemia de jejum e aumento de sensibilidade à insulina) além de reduzir significativamente os valores de colesterol total e LDL, aumentando a proporção de HDL. Os mecanismos envolvidos nestes efeitos benéficos do tratamento com choque térmico encontram-se em estudo em nosso laboratório. / Atherosclerosis is a cardiovascular disease (CVD) that affects four in every 1,000 people, and is characterized by inflammatory arterial lesions which evolve with the development of the disease. It is involved in this process a high production of proinflammatory cytokines whose expression is mediated by the activation of nuclear transcription factor kappa B (NF-B), responsible for triggering the processes of cell proliferation and migration of smooth muscle cells into the arterial lesions, thus contributing to the worsening of the disease. Studies of our laboratory have shown that cyclopentenone prostaglandins (CP-PGs), which are anti-inflammatory, revert atherosclerotic lesions in animal models in a process that depends on the induction of heat shock proteins - HSPs by these CP-PGs. HSPs prevent denaturation of intracellular proteins and "turn off" nuclear factor NF-B, which is a major player involved in the inflammatory vascular disease that accompanies atherosclerosis. Therefore, we decided to investigate the effect of the direct expression of HSPs via heat shock, on the inflammatory process of atherosclerosis, by the "hot tub" method performed weekly in male mice knockout for the LDL receptor (LDLr-KO) under a high fat and hypercholesterolemic diet. To assess these effects, the animals were weekly subjected to a thermal bath (for a period of eight weeks) by raising the body temperature to 41.5 ° C for 15 min. The results demonstrated that in the thoracic aorta, the heat shock increased HSP70 expression approximately 50%, which was accompanied by an increase of 100% in the expression of heat shock factor - HSF and a dramatic decrease in the activation of nuclear factor NF-kB (75%). In parallel, heat shock decreased by more than 50% lipid deposition in the aortic wall and in the epididymal fat, and lipid peroxidation by about 40%. Ultrasound with Doppler analysis showed that heat shock improved blood flow, reduced thickness of the aortic wall and improved cardiac performance. The treatment also improved the glycemic status (reduction of fasting blood glucose and increased insulin sensitivity) and significantly lower levels of total and LDL cholesterol and by increasing the rates of HDL. The mechanisms involved in these beneficial effects of treatment with heat shock are under investigation in our laboratory.

A aterosclerose é uma doença cardiovascular (DCV) que afeta 4 em cada 1.000 pessoas, e é caracterizada por lesões arteriais inflamatórias que evoluem com o desenvolvimento da doença. Está envolvida neste processo uma alta produção de citocinas pró-inflamatórias cuja expressão é mediada pela ativação do fator de transcrição nuclear kappa B (NF-B), responsável por desencadear processos de proliferação celular e migração de células musculares lisas nas regiões de lesões arteriais, contribuindo para o agravamento da doença. Estudos de nosso laboratório mostraram que prostaglandinas ciclopentenônicas (CP-PGs), que são anti-inflamatórias, revertem as lesões ateromatosas em modelos animais, num processo que depende da indução de proteínas de choque térmico - HSP (do inglês Heat Shock Protein) por estas CP-PGs. HSPs impedem a desnaturação de proteínas intracelulares e “desligam” o fator nuclear NF-B, que é um dos principais envolvidos na doença inflamatória vascular da aterosclerose. Por isso, decidimos investigar o efeito direto da expressão de HSPs via choque térmico, no processo inflamatório da aterosclerose, pelo método de “hot tub” realizado semanalmente em camundongos machos nocaute para o receptor de LDL (KO-LDLr), em dieta hiperlipídica e hipercolesterolêmica. Para avaliar estes efeitos os animais foram semanalmente (num período de oito semanas) submetidos a um banho térmico elevando a temperatura corporal para 41,5°C por 15 min. Os resultados demonstraram que, na aorta torácica, o choque térmico aumentou a expressão da HSP70 em cerca de 50% o que foi acompanhado de aumento de 100% na expressão do fator de choque térmico – HSF e dramática queda na ativação do fator NF-kB (75%). Em paralelo, o choque térmico reduziu em mais de 50% a deposição de lípides na parede da aorta e na gordura epididimal e a lipoperoxidação em cerca de 40%. As análises com ultrassonografia Doppler demonstraram que o choque térmico melhorou o fluxo sanguíneo, reduziu a espessura da parede aórtica e melhorou a performance cardíaca. O tratamento também melhorou o status glicêmico (redução de glicemia de jejum e aumento de sensibilidade à insulina) além de reduzir significativamente os valores de colesterol total e LDL, aumentando a proporção de HDL. Os mecanismos envolvidos nestes efeitos benéficos do tratamento com choque térmico encontram-se em estudo em nosso laboratório. / Atherosclerosis is a cardiovascular disease (CVD) that affects four in every 1,000 people, and is characterized by inflammatory arterial lesions which evolve with the development of the disease. It is involved in this process a high production of proinflammatory cytokines whose expression is mediated by the activation of nuclear transcription factor kappa B (NF-B), responsible for triggering the processes of cell proliferation and migration of smooth muscle cells into the arterial lesions, thus contributing to the worsening of the disease. Studies of our laboratory have shown that cyclopentenone prostaglandins (CP-PGs), which are anti-inflammatory, revert atherosclerotic lesions in animal models in a process that depends on the induction of heat shock proteins - HSPs by these CP-PGs. HSPs prevent denaturation of intracellular proteins and "turn off" nuclear factor NF-B, which is a major player involved in the inflammatory vascular disease that accompanies atherosclerosis. Therefore, we decided to investigate the effect of the direct expression of HSPs via heat shock, on the inflammatory process of atherosclerosis, by the "hot tub" method performed weekly in male mice knockout for the LDL receptor (LDLr-KO) under a high fat and hypercholesterolemic diet. To assess these effects, the animals were weekly subjected to a thermal bath (for a period of eight weeks) by raising the body temperature to 41.5 ° C for 15 min. The results demonstrated that in the thoracic aorta, the heat shock increased HSP70 expression approximately 50%, which was accompanied by an increase of 100% in the expression of heat shock factor - HSF and a dramatic decrease in the activation of nuclear factor NF-kB (75%). In parallel, heat shock decreased by more than 50% lipid deposition in the aortic wall and in the epididymal fat, and lipid peroxidation by about 40%. Ultrasound with Doppler analysis showed that heat shock improved blood flow, reduced thickness of the aortic wall and improved cardiac performance. The treatment also improved the glycemic status (reduction of fasting blood glucose and increased insulin sensitivity) and significantly lower levels of total and LDL cholesterol and by increasing the rates of HDL. The mechanisms involved in these beneficial effects of treatment with heat shock are under investigation in our laboratory.

A aterosclerose é uma doença cardiovascular (DCV) que afeta 4 em cada 1.000 pessoas, e é caracterizada por lesões arteriais inflamatórias que evoluem com o desenvolvimento da doença. Está envolvida neste processo uma alta produção de citocinas pró-inflamatórias cuja expressão é mediada pela ativação do fator de transcrição nuclear kappa B (NF-B), responsável por desencadear processos de proliferação celular e migração de células musculares lisas nas regiões de lesões arteriais, contribuindo para o agravamento da doença. Estudos de nosso laboratório mostraram que prostaglandinas ciclopentenônicas (CP-PGs), que são anti-inflamatórias, revertem as lesões ateromatosas em modelos animais, num processo que depende da indução de proteínas de choque térmico - HSP (do inglês Heat Shock Protein) por estas CP-PGs. HSPs impedem a desnaturação de proteínas intracelulares e “desligam” o fator nuclear NF-B, que é um dos principais envolvidos na doença inflamatória vascular da aterosclerose. Por isso, decidimos investigar o efeito direto da expressão de HSPs via choque térmico, no processo inflamatório da aterosclerose, pelo método de “hot tub” realizado semanalmente em camundongos machos nocaute para o receptor de LDL (KO-LDLr), em dieta hiperlipídica e hipercolesterolêmica. Para avaliar estes efeitos os animais foram semanalmente (num período de oito semanas) submetidos a um banho térmico elevando a temperatura corporal para 41,5°C por 15 min. Os resultados demonstraram que, na aorta torácica, o choque térmico aumentou a expressão da HSP70 em cerca de 50% o que foi acompanhado de aumento de 100% na expressão do fator de choque térmico – HSF e dramática queda na ativação do fator NF-kB (75%). Em paralelo, o choque térmico reduziu em mais de 50% a deposição de lípides na parede da aorta e na gordura epididimal e a lipoperoxidação em cerca de 40%. As análises com ultrassonografia Doppler demonstraram que o choque térmico melhorou o fluxo sanguíneo, reduziu a espessura da parede aórtica e melhorou a performance cardíaca. O tratamento também melhorou o status glicêmico (redução de glicemia de jejum e aumento de sensibilidade à insulina) além de reduzir significativamente os valores de colesterol total e LDL, aumentando a proporção de HDL. Os mecanismos envolvidos nestes efeitos benéficos do tratamento com choque térmico encontram-se em estudo em nosso laboratório. / Atherosclerosis is a cardiovascular disease (CVD) that affects four in every 1,000 people, and is characterized by inflammatory arterial lesions which evolve with the development of the disease. It is involved in this process a high production of proinflammatory cytokines whose expression is mediated by the activation of nuclear transcription factor kappa B (NF-B), responsible for triggering the processes of cell proliferation and migration of smooth muscle cells into the arterial lesions, thus contributing to the worsening of the disease. Studies of our laboratory have shown that cyclopentenone prostaglandins (CP-PGs), which are anti-inflammatory, revert atherosclerotic lesions in animal models in a process that depends on the induction of heat shock proteins - HSPs by these CP-PGs. HSPs prevent denaturation of intracellular proteins and "turn off" nuclear factor NF-B, which is a major player involved in the inflammatory vascular disease that accompanies atherosclerosis. Therefore, we decided to investigate the effect of the direct expression of HSPs via heat shock, on the inflammatory process of atherosclerosis, by the "hot tub" method performed weekly in male mice knockout for the LDL receptor (LDLr-KO) under a high fat and hypercholesterolemic diet. To assess these effects, the animals were weekly subjected to a thermal bath (for a period of eight weeks) by raising the body temperature to 41.5 ° C for 15 min. The results demonstrated that in the thoracic aorta, the heat shock increased HSP70 expression approximately 50%, which was accompanied by an increase of 100% in the expression of heat shock factor - HSF and a dramatic decrease in the activation of nuclear factor NF-kB (75%). In parallel, heat shock decreased by more than 50% lipid deposition in the aortic wall and in the epididymal fat, and lipid peroxidation by about 40%. Ultrasound with Doppler analysis showed that heat shock improved blood flow, reduced thickness of the aortic wall and improved cardiac performance. The treatment also improved the glycemic status (reduction of fasting blood glucose and increased insulin sensitivity) and significantly lower levels of total and LDL cholesterol and by increasing the rates of HDL. The mechanisms involved in these beneficial effects of treatment with heat shock are under investigation in our laboratory.

No description available.

MSc (Microbiology) / Department of Microbiology / See the attached abstract below

No description available.

No description available.

Les quantum dots (QDs) sont des cristaux semi-conducteurs de dimensions nanométriques. Ils peuvent être employés comme des marqueurs photosensibles du métabolisme cellulaire et peuvent être utiles dans différents domaines notamment en médecine mais il s’est rapidement avéré nécessaire de démontrer leur innocuité avant leur utilisation à grande échelle et leur diffusion dans l’environnement. Nous proposons un projet de thèse de doctorat sur le thème : La génotoxicité des quantum dots et le rôle du stress oxydant, implications sur l’environnement et la santé humaine. Il s’organise suivant trois axes: L’étude in vitro des propriétés génotoxiques et mutagènes des QDs Les QDs induisent des lésions primaires de l’ADN sur cellules CHO-K1 par le test des comètes qui sont associées à un stress oxydant. Ils sont plus actifs après irradiation par le spectre solaire. Ils induisent des mutations chromosomiques. L’étude in vivo des propriétés génotoxiques et mutagènes des QDs Les QDs induisent une augmentation significative des lésions de l'ADN chez le rat qui varie selon l’organe considéré (foie, rein, poumon, cerveau et testicule). Ils induisent une augmentation significative et une réponse dose-dépendante des micronoyaux indiquant nettement leur pouvoir clastogène/aneugène. Aucune variation significative des variables biochimiques mesurées n’est apparue. La mise en évidence de leurs effets sur l’environnement L'exposition aux QDs et au CdCl2 a entraîné une augmentation significative des lésions de l'ADN chez E. fetida et N. diversicolor. / Quantum dots (QDs) are semiconductor nanocrystals which can be employed as sensitive biomarkers of cellular metabolism and thus show their usefulness in various fields, including medicine and it soon became necessary to prove their safety before their widespread use and their distribution in the environment. The thesis project targeted on: Genotoxicity of quantum dots and the role of oxidative stress implications for the environment and human health. This study was organized in three main parts The in vitro study of the genotoxic and mutagenic properties of QDs QDs induced primary DNA lesions in CHO-K1 cells using the comet assay and were associated with oxidative stress. We demonstrated that the QDs were more active after irradiation by the solar spectrum. We showed the ability of QDs to induce chromosomal mutations. The main mechanism was probably that of the production of free radicals. The in vivo study of the genotoxic and mutagenic properties of QDs The comet assay shows that QDs induced an overall significant increase in DNA lesions of different organs (liver, kidneys, lungs, brain and testes). However, each organ had a specific susceptibility. QDs induced a significant increase in a dose-dependent manner of micronuclei. These results clearly indicated the in vivo clastogenic / aneugenic properties of QDs. No significant variation in the measured biochemical variables. The evidence of their effects on the environment Evaluation of genotoxicity was performed on coelomocytes of E. fetida and N. diversicolor resulting in a significant increase in DNA damage.

No description available.

The cyanobacterial neurotoxin β-N-methylamino-L-alanine (BMAA), a non-protein amino acid, first attracted attention in correlation to reports of high incidence of the unusual neurological disease amyotrophic lateral sclerosis/Parkinsonism-dementia (ALS/PDC) among the people of Guam in the South Pacific Ocean. Experimental studies have revealed that BMAA causes neuronal cell death. The neurotoxin is suggested to act via excitotoxicity through interaction with glutamatergic receptors. More importantly, BMAA is suggested to misincorporate in the synthesis of proteins, and contribute to protein misfolding and/or deleterious aggregation, which are hallmarks of several neurodegenerative disorders. A selective uptake of BMAA in the rat neonatal hippocampus can interfere with brain development, causing learning and memory impairments in adult rats. The aim of the present study was to investigate the effects of BMAA in human neuroblastoma SH-SY5Y cells. These cells were exposed to BMAA (10 μM, 50 μM, 100 μM or 500 μM) for 72 hours, and the expression of five selected proteins, including heat shock protein-27 (HSP-27), lysosomal associated membrane protein-1 (LAMP-1), CCAAT-enhancer-binding protein homologous protein (CHOP), Golgi associated plant pathogenesis related protein-2 (GLIPR-2), and glucose regulated protein-78 (GRP-78). They were carried out with immunohistochemistry (IHC). Results revealed an increased expression of all selected proteins, which indicates an uptake and shows the effects of BMAA in the cell cultures. Taken together, BMAA caused cellular stress, including endoplasmic reticulum (ER) stress that is correlated with HSP-27, LAMP-1, CHOP, GLIPR-2, and GRP-78. Further studies are needed in order to support the results. The experiments require being repeated using the same biomarkers as well as a combination of them with other biomarkers to elucidate the effects of BMAA.