Browsing by Author "Sousa, Daniela"
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- Epigenetic and transcriptional modulator potential of epigallocatechin-3-gallate and genistein on fetal hemoglobin reactivators genesPublication . Ribeiro, Edna; Delgadinho, Mariana; Matos, Elisabete; Santos, Raquel; Sousa, Daniela; Galante, Heloísa; Brito, MiguelBackground: β-hemoglobinopathies is one of the most common recessive genetic diseases worldwide, with limited treatments available, particularly in developed countries where the prevalence is higher. Pharmacological reactivation of Fetal Hemoglobin (HbF) is a promising therapeutic strategy. However, approximately 25% of the patients do not respond to Hydroxyurea (HU), the first and most commonly used HbF inducing agent approved by the FDA. Objective: Here, we performed an in vitro assessment of transcriptional effects induced by natural bioactive compounds, namely Epigallocatechin-3-gallate (EGCG) and Genistein (GN) in globin genes (HBA1, HBB, HBG1, and HBG2) in HbF regulators/silencer genes (KLF1, BCL11A, MYB, and BGLT3) and in epigenetic regulator genes (DNMT1, DNMT3A, DNMT3B, HDAC1, HDAC2, HDAC3, and HDAC8). Moreover, we evaluated EGCG in vivo effects on hematological parameters of healthy volunteers. Methods: K562 cells were exposed for 72 and 96 h to GN and EGCG at 100, 250, and 500 ng/ml. Cell proliferation and viability were measured, and transcriptional levels were evaluated by qRT-PCR. For in vivo assay, complete blood count was determined by flow cytometry and HbF through HPLC in 30 healthy individuals before and after 225 mg EGCG ingestion per day during a 90-day period. Results: Both compounds impact cellular metabolism and proliferation with no cytotoxic effects. Divergent GN and EGCG effects in globin and BGLT3 expression levels suggest the involvement of divergent signaling pathways. As for the epigenetic potential, EGCG particularly affects HDAC2 and HDAC8 transcription, whereas GN significantly affects expression patterns of methylation and acetylation modulators. HU appears to have time divergent effects, with a greater impact in methylation at 72 h (overregulates DNTM3A) while affecting acetylation mostly at 96 h (downregulates HDAC1 and HDAC8). Additionally, in vivo, EGCG demonstrated a modulator effect in hematopoiesis and HbF induction. Conclusion: Our results advocate EGCG and GN with HbF pharmacological reactivation potential and sustain further research as new alternative approaches for β-hemoglobinopathies therapies.
- Hybrid wireless network with SDN and legacy devices in ad-hoc environmentsPublication . Sousa, Daniela; Sargento, Susana; Luís, MiguelOn temporary events, like concerts or emergency scenarios, where a communication infrastructure may not be sufficient or even present, networks can be built in a spontaneous way with the available network elements and radio access technologies, to support proper communication and data access. However, these ad-hoc networks, without a centralized view, can be inefficient when compared to a detached centralized control approach like in Software Defined Networks (SDNs). Moreover, SDNs can bring several advantages to these environments, such as adaptability and performance increase, despite not supporting wireless interfaces. However, in these scenarios, not all nodes are able to support SDN. This paper proposes a Spontaneous Heterogeneous Wireless Software Defined Network with a hybrid approach that is able to opportunistically use all available elements that may compose the network, regardless of whether they are legacy or SDN nodes. The proposed approach is tested in several scenarios with a different ratio of legacy to SDN nodes. We conclude that the network is able to work with hybrid nodes, and that when more Hybrid SDN (H-SDN) devices are used to forward packets, the network performance increases or is maintained when compared to a pure ad-hoc solution.
- O potencial da epigalocatequina-3-galato na reativação da expressão da y-globina e indução da hemoglobina fetalPublication . Sousa, Daniela; Matos, Elisabete; Delgadinho, Mariana; Ribeiro, Edna; Mateus, Vanessa; Silva, Inês; Brito, MiguelAs hemoglobinopatias estão entre as doenças genéticas mais comuns em todo o mundo, particularmente a doença falciforme (DF) e a β talassemia e são causadas por defeitos na estrutura da hemoglobina ou na expressão dos genes da globina durante a transição de hemoglobina fetal HbF pela hemoglobina adulta HbA. Novas abordagens terapêuticas estão a ser desenvolvidas para irem além do tratamento paliativo que impõe altos custos aos sistemas de saúde. Desta forma, uma terapia alternativa mais acessível e promissora é a indução farmacológica de HbF. A elevação da síntese da cadeia γ-globina fetal equilibra o excesso da cadeia α globina pela formação de HbF modulando a anemia severa nos pacientes com β talassemia maior e inibindo diretamente a polimerização da hemoglobina falciforme em pacientes com DF. A hidroxiureia (HU) é o único medicamento aprovado pela FDA para o tratamento de pacientes com DF e com β talassemia intermédia. No entanto, este fármaco inibe a replicação do ADN e a possibilidade de ser mutagénico e carcinogénico limita o seu uso clínico. Por este motivo, o desenvolvimento de novos compostos indutores de HbF com alta eficiência e menor toxicidade, estão a ser investigados. Os compostos biológicos da dieta, como a epigalocatequina galato (EGCG) estão associados a efeitos benéficos para a saúde devido aos seus efeitos anti inflamatórios e antioxidantes. A EGCG é a catequina mais abundante no chá verde e a sua propriedade anti inflamatória desempenha um papel crucial na regulação da expressão e transcrição relativa de genes. O objetivo deste projeto foi avaliar o potencial da EGCG, na reativação da expressão do gene da γ-globina e, deste modo, na indução de HbF.
- Potencial da genisteína na reativação da expressão do gene da γ-globulina e indução da hemoglobina fetalPublication . Matos, Elisabete; Sousa, Daniela; Delgadinho, Mariana; Mateus, Vanessa; Silva, Inês; Ribeiro, Edna; Brito, MiguelProject goals: Identification of novel agents with higher HbF inducing activity and lower cytotoxicity accessible in low-income countries, has been one of the major challenges over the past few years. A naturally occurring isoflavone found in plant products ( lentils, and chickpeas). Potent inhibitor of the PTK and topoisomerase II G 2 /M cell cycle arrest) regulates MAPK pathways (p 38 MAPK and ERK 1 /ERK 2. Antioxidant, antineoplastic, antihelmintic antiangiogenic, and immunosuppressive properties. Structurally similar to estrogen (estradiol 17 β). Potential to mimic, enhance, or impair the estradiol biosynthesis pathway with high reported binding selectivity for ER β isoform.
- A simulation environment for software defined wireless networks with legacy devicesPublication . Sousa, Daniela; Sargento, Susana; Luís, MiguelThe adoption of Software Defined Networks (SDNs) in a Mobile ad-hoc network (MANET) could present several benefits, such as adaptability and performance increase. However, to assess this possibility, a simulation tool may be necessary to test new protocols and solutions in a large combination of scenarios and traffic patterns, without the need of real equipment. Unfortunately, few tools are available for wireless SDNs, and none have the ability to also support MANETs with multiple radio access technologies. While NS-3 has the ability to simulate heterogeneous MANETs, it does not support wireless OpenFlow capable devices or wireless OpenFlow channels. In this work we present a simulation environment that, besides creating an ad-hoc data plane, enables the possibility of creating wireless hybrid SDN devices capable of connecting to legacy devices, alongside with an LTE OpenFlow channel connected to an external SDN Controller (RYU). Results show that the simulation environment supports large networks with both legacy and SDN devices, although these will bear an effective running time higher than their simulation time. Moreover, when comparing to an OLSR-only network, the proposed network (with a basic path search metric) has the same or higher performance.