In vitro and in silico evaluation of the schistosomicidal activity of eugenol derivatives using biochemical, molecular, and morphological tools

Background Eugenol shows both antibacterial and antiparasitic activities, suggesting that it might be evaluated as an option for the treatment of praziquantel-resistant schistosome. Methods The in vitro activities of three eugenol derivatives (FB1, FB4 and FB9) on adult worms from Schistosoma mansoni were examined by fluorescence and scanning electron microscopy to analyze effects on the excretory system and integument damage, respectively. Biochemical tests with verapamil (a calcium channel antagonist) and ouabain (a Na+/K+-ATPase pump inhibitor) were used to characterize eugenol derivative interactions with calcium channels and the Na+/K+-ATPase, while in silico analysis identified potential Na+/K+-ATPase binding sites. Results The compounds showed effective doses (ED50) of 0.324 mM (FB1), 0.167 mM (FB4), and 0.340 mM (FB9). In addition, FB4 (0.322 mM), which showed the lowest ED50, ED90 and ED100 (p < 0.05), caused the most damage to the excretory system and integument, according to both fluorescence and scanning electron microscopy analysis. The death of adult worms was delayed by ouabain treatment plus FB1 (192 versus 72 hours) and FB9 (192 versus 168 hours), but the response to FB4 was the same in the presence or absence of ouabain. Besides, no changes were noted when all of the eugenol derivatives were combined with verapamil. Moreover, FB1 and FB9 inhibited Na+/K+-ATPase activity according to in silico analysis but FB4 did not show a time-dependent relationship and may act on targets other than the parasite Na+/K+-ATPase. Conclusion Eugenol derivatives, mainly FB4 when compared to FB1 and FB9, seem to act more effectively on the integument of adult S. mansoni worms.(AU)

Mesenchymal stem cells promote augmented response of endogenous neural stem cells in spinal cord injury of rats / Células-tronco mesenquimais ampliam a resposta de células-tronco neurais endógenas no trauma da medula espinhal em ratos

Traumatic spinal cord injury results in severe neurological deficits, mostly irreversible. The cell therapy represents a strategy for treatment particularly with the use of stem cells with satisfactory results in several experimental models. The aim of the study was to compare the treatment of spinal cord injury (SCI) with and without mesenchymal stem cells (MSC), to investigate whether MSCs migrate and/or remain at the site of injury, and to analyze the effects of MSCs on inflammation, astrocytic reactivity and activation of endogenous stem cells. Three hours after SCI, animals received bone marrow-derived MSCs (1×107 in 1mL PBS, IV). Animals were euthanized 24 hours, 7 and 21 days post-injury. The MSC were not present in the site of the lesion and the immunofluorescent evaluation showed significant attenuation of inflammatory response with reduction in macrophages labeled with anti-CD68 antibody (ED1), decreased immunoreactivity of astrocytes (GFAP+) and greater activation of endogenous stem cells (nestin+) in the treated groups. Therefore, cell transplantation have a positive effect on recovery from traumatic spinal cord injury possibly due to the potential of MSCs to attenuate the immune response.(AU)

A lesão medular resulta em déficits neurológicos graves, a maioria irreversíveis. A terapia celular representa uma estratégia para o tratamento, especialmente com a utilização de células-tronco, com resultados satisfatórios em vários modelos experimentais. O objetivo do estudo foi comparar o tratamento de lesões da medula espinal (SCI), com e sem o uso de células-tronco mesenquimais (MSC), para investigar se as MSCs migram e/ou permanecem no local de lesão, e para analisar os efeitos de MSCs sobre a inflamação, reatividade astrocitária e ativação das células-tronco endógenas. Três horas depois da SCI, os animais receberam as MSC derivadas da medula óssea (1 × 107 em 1 mL de PBS, IV). Os animais foram sacrificados 24 horas, 7 e 21 dias pós-lesão. As MSC não estavam presentes no local da lesão e a avaliação por imunofluorescência demonstrou atenuação significativa da resposta inflamatória com redução em macrófagos marcados com anticorpo anti CD68 (ED1), diminuição da imunorreatividade de astrócitos (GFAP +) e maior ativação das células-tronco endógenas (nestin+) nos grupos tratados. Assim, o transplante de células teve efeito positivo sobre a recuperação de lesão traumática da medula espinal, possivelmente devido ao potencial das MSCs para atenuar a resposta imunológica.(AU)

Mesenchymal stem cells promote augmented response of endogenous neural stem cells in spinal cord injury of rats / Células-tronco mesenquimais ampliam a resposta de células-tronco neurais endógenas no trauma da medula espinhal em ratos

Traumatic spinal cord injury results in severe neurological deficits, mostly irreversible. The cell therapy represents a strategy for treatment particularly with the use of stem cells with satisfactory results in several experimental models. The aim of the study was to compare the treatment of spinal cord injury (SCI) with and without mesenchymal stem cells (MSC), to investigate whether MSCs migrate and/or remain at the site of injury, and to analyze the effects of MSCs on inflammation, astrocytic reactivity and activation of endogenous stem cells. Three hours after SCI, animals received bone marrow-derived MSCs (1×107 in 1mL PBS, IV). Animals were euthanized 24 hours, 7 and 21 days post-injury. The MSC were not present in the site of the lesion and the immunofluorescent evaluation showed significant attenuation of inflammatory response with reduction in macrophages labeled with anti-CD68 antibody (ED1), decreased immunoreactivity of astrocytes (GFAP+) and greater activation of endogenous stem cells (nestin+) in the treated groups. Therefore, cell transplantation have a positive effect on recovery from traumatic spinal cord injury possibly due to the potential of MSCs to attenuate the immune response.

A lesão medular resulta em déficits neurológicos graves, a maioria irreversíveis. A terapia celular representa uma estratégia para o tratamento, especialmente com a utilização de células-tronco, com resultados satisfatórios em vários modelos experimentais. O objetivo do estudo foi comparar o tratamento de lesões da medula espinal (SCI), com e sem o uso de células-tronco mesenquimais (MSC), para investigar se as MSCs migram e/ou permanecem no local de lesão, e para analisar os efeitos de MSCs sobre a inflamação, reatividade astrocitária e ativação das células-tronco endógenas. Três horas depois da SCI, os animais receberam as MSC derivadas da medula óssea (1 × 107 em 1 mL de PBS, IV). Os animais foram sacrificados 24 horas, 7 e 21 dias pós-lesão. As MSC não estavam presentes no local da lesão e a avaliação por imunofluorescência demonstrou atenuação significativa da resposta inflamatória com redução em macrófagos marcados com anticorpo anti CD68 (ED1), diminuição da imunorreatividade de astrócitos (GFAP +) e maior ativação das células-tronco endógenas (nestin+) nos grupos tratados. Assim, o transplante de células teve efeito positivo sobre a recuperação de lesão traumática da medula espinal, possivelmente devido ao potencial das MSCs para atenuar a resposta imunológica.