Targeting Angiotensin Ii Type-1 Receptor (at(1)r) Inhibits The Harmful Phenotype Of Plasmodium-specific Cd8(+) T Cells During Blood-stage Malaria

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CD8(+) T-cell response is critical in the pathogenesis of cerebral malaria during blood-stage. Our group and other have been shown that angiotensin II (Ang II) and its receptor AT(1) (AT(1)R), a key effector axis of renin-angiotensin system (RAS), have immune regulatory effects on T cells. Previously, we showed that inhibition of AT(1)R signaling protects mice against the lethal disease induced by Plasmodium berghei ANKA infection However, most of the Ang II/AT(1)R actions were characterized by using only pharmacological approaches, the effects of which may not always be due to a specific receptor blockade. In addition, the mechanisms of action of the AT(1)R in inducing the pathogenic activity of Plasmodium-specific CD8(+) T cells during blood-stage were not determined. Here, we examined how angiotensin II/AT1R axis promotes the harmful response of Plasmodium-specific CD8(+) T-cell during blood-stage by using genetic and pharmacological approaches. We evaluated the response of wild-type (WT) and AT1R(-/-) Plasmodium-specific CD8(+) T cells in mice infected with a transgenic PbA lineage expressing ovalbumin; and in parallel infected mice receiving WT Plasmodium-specific CD8(+) T cells were treated with losartan (AT(1)R antagonist) or captopril (ACE inhibitor). Both, AT(1)R(-/-) OT-I cells and WT OT-I cells from losartan- or captopril-treated mice showed lower expansion, reduced IL-2 production and IL-2R? expression, lower activation (lower expression of CD69, CD44 and CD160) and lower exhaustion profiles. AT(1)R-/- OT-I cells also exhibit lower expression of the integrin LFA-1 and the chemokine receptors CCR5 and CXCR3, known to play a key role in the development of cerebral malaria. Moreover, AT1R(-/-) OT-I cells produce lower amounts of IFN-gamma and TNF-alpha and show lower degranulation upon restimulation. In conclusion, our results show the pivotal mechanisms of AT(1)R-induced harmful phenotype of Plasmodium-specific CD8(+) T cells during blood-stage malaria.7Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [57.3695/2008-3, 57.3767/2008-4, 471771/2013-9, 456997/2014-8]Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro [E-26/110.551/2010, 111681/2013, E-26/102.170/2013, E-26/201.197/2014]Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Effect of sodium dichloroacetate as single agent or in combination with cisplatin in normal and human cervical cancer cell lines

Purpose: To evaluate the synergistic cytotoxicity of sodium dichloroacetate (DCA) in combination with cisplatin (CIS) against human cervical cancer cell lines. Methods: Cervical cancer SiHa and HeLa cells and normal cells (Hek-293, Vero, peripheral blood mononuclear and human erythrocytes) were treated in vitro with DCA and CIS individually or their combination. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method while hemolytic activity was evaluated from the released hemoglobin. Halfmaximal inhibitory concentration (IC50) of DCA or CIS was obtained. Results: The combination of DCA + CIS decreased the cell viability of SiHa, Hek-293, Vero, and PBMC cells, but not of Hela cells (p < 0.05). Furthermore, the individual treatments alone or in combination did not cause significant hemolysis (p < 0.05). Conclusion: The combination of DCA + CIS increases the damage caused by CIS alone on SiHa cells. It also decreases the cell viability of Hek-293 and Vero without affecting peripheral blood mononuclear and human erythrocyte integrity. The results suggest that the combination of DCA and CIS can induce synergistic antitumor effect in different types of cancer cell lines. However, further studies are required to determine the biological effects of the combination of DCA and CIS in vivo. Keywords: Cervical cancer, Sodium dichloroacetate, Cisplatin, Viability, Hemolysi

Seleção de fungos produtores de β-D-frutosiltransferase por fermentação em estado sólido

A enzima β-D-frutosiltransferase é responsável pela síntese de FOS (frutooligossacarídeos) a partir de sacarose por reação de transfrutosilação é produzida por diferentes micro-organismos, principalmente por fungos filamentosos. O objetivo deste trabalho foi selecionar a melhor linhagem fúngica produtora da -D-frutosiltransferase por fermentação em estado sólido, bem como o método de extração. A fermentação em estado sólido utilizando o substrato farelo de trigo umedecido com solução de sacarose atingindo 70% de umidade na concentração de esporos de 107 no tempo de 96 horas de crescimento. Todas as linhagens manipuladas apresentaram atividade hidrolítica, no entanto apenas uma linhagem não demonstrou atividade transfrutosilação. O isolado SIS 14 que pertence ao gênero Aspergillus sp. destacou-se pelos maiores valores em atividade no método de extração utilizando água destilada, apresentando 300,90 U/mL na atividade de transfrutosilação e na atividade hidrolítica de 155,74 U/mL. Contudo, pode-se perceber que dos solventes estudados a água destilada foi melhor obtendo o valor em atividade de transfrutosilação, como também a linhagem SIS 14 é promissora para a produção da β-D-frutosiltransferase

Fresh-cut melon quality during storage: an NMR study of water transverse relaxation time

Molecular mobility is a fundamental parameter which reflects the dynamic properties of food components and contributes to food degradation reactions comprehension. Fresh-cut fruits have become an important food market segment. However, processing of fruits promotes faster its physiological deterioration, biochemical changes and microbial degradation. The purpose of this work was to use NMR methodology as a tool to evaluate fresh-cut fruit quality, during storage at refrigerated conditions. The fresh-cut melon transverse relaxation time (T2) was measured for a period of 7 days of storage at 5 °C. The relationship between the obtained values, microstructure and quality parameters was investigated. In general, results show the existence of one class of water fluidity in the system, the one present in cells after processing. T2, a measure of this fluidity, is affected by the processing and storage time. Also, it is possible to find a close relationships between T2 and quality parameters of total colour difference (TCD), firmness and aw. As T2 increases TCD also increases, while firmness and aw decrease. These results highlight the usefulness of NMR methodology application in food science.Author Joana F. Fundo acknowledges Fundacao para a Ciencia e a Tecnologia (grant SFRH/BD/62176/2009). The authors acknowledge the Portuguese NMR Network and Strategic Project PEst-C/CTM/LA0025/2013-14. This work was supported by National Funds from FCT through project PEst-OE/EQB/LA0016/201

GC- and UHPLC-MS Profiles as a Tool to Valorizate the Red Alga Asparagopsis armata

Conference Report XVI International Symposium on Marine Natural Products | XI European Conference on Marine Natural Products, 1-5 September 2019, Peniche, Portugal.Asparagopsis armata is considered a biological invader and this red alga is in the last few years one of the worst nightmares for Azores coast biodiversity. So efforts to find an economically valuable application are welcome. In this context biological evaluations of its extracts, such as anti-aging, antioxidant and anticholinesterasic activities, were recently presented [1,2]. Naturally, the knowledge of this species chemical composition is utmost importance not only to find some valuable utilization but also to discovery its mechanisms of defence that can explain its invasive behaviour. In our effort to contribute to this problem solution we establish the GC-MS and UHPLC-MS profiles of both the non-polar and polar extracts. The main compounds in the lipophilic extract were palmitic acid and 1-monopalmitin and brominated compounds dominate both extracts. The detailed results will be presented and discussed in the presentation.info:eu-repo/semantics/publishedVersio

Optimal design of THEDES based on Perillyl Alcohol and Ibuprofen

Therapeutic deep eutectic systems (THEDES) have dramatically expanded their popularity in the pharmaceutical field due to their ability to increase active pharmaceutical ingredients (APIs) bioavailability. However, their biological performance has not yet been carefully scrutinized. Herein, THEDES based on the binary mixture of perillyl alcohol (POH) and ibuprofen (IBU) were prepared using different molar ratios. Our comprehensive strategy includes the characterization of their thermal and structural behavior to identify the molar ratios that successfully form deep eutectic systems. The in vitro solubility of the different systems prepared has demonstrated that, unlike other reported examples, the presence of the terpene did not affect the solubility of the anti-inflammatory agent in a physiological simulated media. The biological performance of the systems was studied in terms of their antimicrobial activity against a wide panel of microorganisms. The examined THEDES showed relevant antimicrobial activity against all tested microbial strains, with the exception of P. aeruginosa. A synergistic effect from the combination of POH and IBU as a eutectic system was verified. Furthermore, the cytotoxic profile of these eutectic systems towards colorectal cancer (CRC) in vitro cell models was also evaluated. The results provide the indication that the cell viability varies in a dose-dependent manner, with a selective THEDES action towards CRC cells. With tunable bioactivities in a ratio-dependent manner, THEDES enhanced the antimicrobial and anticancer properties, representing a possible alternative to conventional therapies. Therefore, this study provides foreseeable indications about the utility of THEDES based on POH and IBU as strong candidates for novel active pharmaceutical systems.Foundation for Science and Technology (FCT), through project PTDC/BBB-490 EBB/1676/2014–Des.Zyme, Light2Skin-PTDC/CTM-CTM/29813/2017 and ERC-2016-CoG 725034 (ERC Consolidator Grant Des.solve). E.S. would also like to acknowledge the financial support by the FCT through the doctoral grant with reference number SFHR/BD/143902/2019. J.M.S. would also like to acknowledge the financial support by the FCT through the post-doctoral grant with reference number SFRH/BPD/116779/201

Compounds identified on hexane and dichloromethane extracts of Salicornia ramosissima

3rd Portuguese Meeting on Medicinal Chemistry and 1st Portuguese-Spanish-Brazilian Meeting on Medicinal Chemistry, Aveiro, 28-30 Novembro 2012.Salicornia ramosissima J. Woods (common purple glasswort) is an annual halophyte, widely distributed in the salt marsh of Ria de Aveiro (Portugal), that belongs to the Salicornia L. genus (Chenopodiaceae).[4] Although phytochemical studies genus on this genus report the presence of compounds which are well-recognized for their biological activities, such as flavonoids, chromones and alkaloids,[3] too little is known about secondary metabolites on purple glasswort. In our previous work we were able to isolate and identify ethyl o-hydroxycinnamate, (E)-fatty alcohol ferulic acid and scopoletin from the dichloromethane extract of S. ramosissima aerial parts. The structure and spectroscopic characterization of some secondary metabolites isolated from dichloromethane crude extract also will be presented and discussed.Thanks are due to the University of Aveiro, Fundação para a Ciência e a Tecnologia (FCT) and FEDER for funding the Organic Chemistry Research Unit (project PEst-C/QUI/UI0062/2011) and Portuguese National NMR Network (RNRMN)