Repositório Colecção: ICVS - articlesICVS - articleshttps://hdl.handle.net/1822/10302024-03-28T14:55:28Z2024-03-28T14:55:28ZCOX-2 inhibitor delivery system aiming intestinal inflammatory disordersOliveira, A.Rodrigues, L.C.Soares da Costa, D.Fernandes, E. M.Reis, R. L.Neves, N. M.Leão, P.Martins, Albinohttps://hdl.handle.net/1822/885222024-02-23T17:55:56Z2024-02-05T18:36:38ZTítulo: COX-2 inhibitor delivery system aiming intestinal inflammatory disorders
Autor: Oliveira, A.; Rodrigues, L.C.; Soares da Costa, D.; Fernandes, E. M.; Reis, R. L.; Neves, N. M.; Leão, P.; Martins, Albino
Resumo: Selective COX-2 inhibitors such as etoricoxib (ETX) are potentially indicated for the treatment of intestinal inflammatory disorders. However, their systemic administration provokes some off-site secondary effects, decreasing the desirable local effectiveness. To circumvent such limitations, herein an ETX delivery system based on electrospun fibrous meshes (eFMs) was proposed. ETX at different concentrations (1, 2, and 3 mg mL−1) was loaded into eFMs, which not affect the morphology and the mechanical properties of this drug delivery system (DDS). The ETX showed a burst release within the first 12 h, followed by a faster release until 36 h, gradually decreasing over time. Importantly, the ETX studied concentrations were not toxic to human colonic cells (i.e. epithelial and fibroblast). Moreover, the DDS loading the highest concentration of ETX, when tested with stimulated human macrophages, promoted a reduction of PGE2, IL-8 and TNF-α secretion. Therefore, the proposed DDS may constitute a safe and efficient treatment of colorectal diseases promoted by inflammatory disorders associated with COX-2.
<b>Tipo</b>: article2024-02-05T18:36:38ZConstitutive deficiency of the neurogenic hippocampal modulator AP2γ promotes anxiety-like behavior and cumulative memory deficits in mice from juvenile to adult periodsLoureiro-Campos, EduardoMateus-Pinheiro, AntónioPatrício, PatríciaCunha, Carina Isabel SoaresSilva, JoanaSardinha, Vanessa Alexandra MoraisPinheiro, Bárbara Filipa MendesSilveira-Rosa, TiagoDomingues, Ana Verónica MendesRodrigues, Ana JoãoOliveira, JoãoSousa, NunoAlves, Nuno Dinis Lopes OliveiraPinto, Luísahttps://hdl.handle.net/1822/872052023-12-20T15:42:02Z2023-11-09T16:45:36ZTítulo: Constitutive deficiency of the neurogenic hippocampal modulator AP2γ promotes anxiety-like behavior and cumulative memory deficits in mice from juvenile to adult periods
Autor: Loureiro-Campos, Eduardo; Mateus-Pinheiro, António; Patrício, Patrícia; Cunha, Carina Isabel Soares; Silva, Joana; Sardinha, Vanessa Alexandra Morais; Pinheiro, Bárbara Filipa Mendes; Silveira-Rosa, Tiago; Domingues, Ana Verónica Mendes; Rodrigues, Ana João; Oliveira, João; Sousa, Nuno; Alves, Nuno Dinis Lopes Oliveira; Pinto, Luísa
Resumo: The transcription factor activating protein two gamma (AP2γ) is an important regulator of neurogenesis both during embryonic development as well as in the postnatal brain, but
its role for neurophysiology and behavior at distinct postnatal periods is still unclear. In this work,
we explored the neurogenic, behavioral, and functional impact of a constitutive and heterozygous
AP2γ deletion in mice from early postnatal development until adulthood. AP2γ deficiency promotes
downregulation of hippocampal glutamatergic neurogenesis, altering the ontogeny of emotional
and memory behaviors associated with hippocampus formation. The impairments induced by AP2γ
constitutive deletion since early development leads to an anxious-like phenotype and memory
impairments as early as the juvenile phase. These behavioral impairments either persist from the
juvenile phase to adulthood or emerge in adult mice with deficits in behavioral flexibility and object
location recognition. Collectively, we observed a progressive and cumulative impact of constitutive AP2γ deficiency on the hippocampal glutamatergic neurogenic process, as well as alterations
on limbic-cortical connectivity, together with functional behavioral impairments. The results herein
presented demonstrate the modulatory role exerted by the AP2γ transcription factor and the relevance of hippocampal neurogenesis in the development of emotional states and memory processes.
<b>Tipo</b>: article2023-11-09T16:45:36ZThe yeast protein kinase Sch9 functions as a central nutrient-responsive hub that calibrates metabolic and stress-related responsesCaligaris, MarcoMarques, Maria Belém Sousa SampaioHatakeyama, RikoPillet, BenjaminLudovico, PaulaDe Virgilio, ClaudioWinderickx, JorisNicastro, Raffaelehttps://hdl.handle.net/1822/870822023-10-25T17:07:31Z2023-10-25T10:44:01ZTítulo: The yeast protein kinase Sch9 functions as a central nutrient-responsive hub that calibrates metabolic and stress-related responses
Autor: Caligaris, Marco; Marques, Maria Belém Sousa Sampaio; Hatakeyama, Riko; Pillet, Benjamin; Ludovico, Paula; De Virgilio, Claudio; Winderickx, Joris; Nicastro, Raffaele
Resumo: Yeast cells are equipped with different nutrient signaling pathways that enable them to sense the availability of various nutrients and adjust metabolism and growth accordingly. These pathways are part of an intricate network since most of them are cross-regulated and subject to feedback regulation at different levels. In yeast, a central role is played by Sch9, a protein kinase that functions as a proximal effector of the conserved growth-regulatory TORC1 complex to mediate information on the availability of free amino acids. However, recent studies established that Sch9 is more than a TORC1-effector as its activity is tuned by several other kinases. This allows Sch9 to function as an integrator that aligns different input signals to achieve accuracy in metabolic responses and stress-related molecular adaptations. In this review, we highlight the latest findings on the structure and regulation of Sch9, as well as its role as a nutrient-responsive hub that impacts on growth and longevity of yeast cells. Given that most key players impinging on Sch9 are well-conserved, we also discuss how studies on Sch9 can be instrumental to further elucidate mechanisms underpinning healthy aging in mammalians.
<b>Tipo</b>: article2023-10-25T10:44:01ZExploring the diversity of visceral, subcutaneous and perivascular adipose tissue in a vascular surgery populationFerreira, JoanaAfonso, Julieta Alexandra PereiraCarneiro, Alexandre LimaVila, IsabelCunha, CristinaRoque, SusanaSilva, CristinaMesquita, AmílcarCotter, JorgeCorreia-Neves, MMansilha, ArmandoLongatto, AdhemarCunha, Pedrohttps://hdl.handle.net/1822/869862023-10-19T20:04:24Z2023-10-19T09:12:26ZTítulo: Exploring the diversity of visceral, subcutaneous and perivascular adipose tissue in a vascular surgery population
Autor: Ferreira, Joana; Afonso, Julieta Alexandra Pereira; Carneiro, Alexandre Lima; Vila, Isabel; Cunha, Cristina; Roque, Susana; Silva, Cristina; Mesquita, Amílcar; Cotter, Jorge; Correia-Neves, M; Mansilha, Armando; Longatto, Adhemar; Cunha, Pedro
Resumo: The prevalence of obesity has doubled, with a concomitant increase in cardiovascular disease. This study aimed to compare the characteristics of visceral, subcutaneous and peri-aortic adipose tissue determined with computed tomography (CT) scans and to correlate them with cardiovascular risk factors, anthropometric measures and medication. An observational and prospective study was conducted, and 177 subjects were included. Peri-aortic adipose tissue had the highest density, while the subcutaneous adipose tissue had the lowest. The density of subcutaneous adipose tissue differs from the density of visceral (p = 0.00) and peri-aortic adipose tissue (p = 0.00). Smokers/ex-smokers had a lower area (p = 0.00) and density (p = 0.02) of subcutaneous adipose tissue. Multiple linear regression analysis showed that sex was a predictor of subcutaneous adipose tissue area (β = −0.27, t = −3.12, p = 0.00) but smoking habits were not. After controlling for sex, we found that the association between smokers/ex-smokers and area of subcutaneous adipose tissue was lost, but the association with density persisted. Patients with hypertension had a higher visceral adipose tissue area, and this relationship was maintained even after adjusting for gender. Peri-aortic adipose tissue is similar to visceral and distinct from subcutaneous adipose tissue. Cardiovascular risk factors have different influences in distinct adipose compartments.
<b>Tipo</b>: article2023-10-19T09:12:26ZGenetic ablation of inositol 1,4,5-Trisphosphate receptor type 2 (IP3R2) fails to modify disease progression in a mouse model of Spinocerebellar Ataxia type 3Garcia, Daniela Raquel CunhaFernandes, Daniela MonteiroCorreia, Joana SofiaCarvalho, Andreia Alexandra NevesFerreira, Ana Catarina Coutinho VilaçaGomes, Sónia Isabel Nunes GuerraViana, João Filipe OliveiraOliveira, João F.Castro, Andreia Cristiana TeixeiraMaciel, P.Silva, Sara Carina Duartehttps://hdl.handle.net/1822/869702023-10-18T20:09:40Z2023-10-18T09:40:53ZTítulo: Genetic ablation of inositol 1,4,5-Trisphosphate receptor type 2 (IP3R2) fails to modify disease progression in a mouse model of Spinocerebellar Ataxia type 3
Autor: Garcia, Daniela Raquel Cunha; Fernandes, Daniela Monteiro; Correia, Joana Sofia; Carvalho, Andreia Alexandra Neves; Ferreira, Ana Catarina Coutinho Vilaça; Gomes, Sónia Isabel Nunes Guerra; Viana, João Filipe Oliveira; Oliveira, João F.; Castro, Andreia Cristiana Teixeira; Maciel, P.; Silva, Sara Carina Duarte
Resumo: Spinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disease caused by an abnormal polyglutamine expansion within the ataxin-3 protein (ATXN3). This leads to neurodegeneration of specific brain and spinal cord regions, resulting in a progressive loss of motor function. Despite neuronal death, non-neuronal cells, including astrocytes, are also involved in SCA3 pathogenesis. Astrogliosis is a common pathological feature in SCA3 patients and animal models of the disease. However, the contribution of astrocytes to SCA3 is not clearly defined. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant IP3R in mediating astrocyte somatic calcium signals, and genetically ablation of IP3R2 has been widely used to study astrocyte function. Here, we aimed to investigate the relevance of IP3R2 in the onset and progression of SCA3. For this, we tested whether IP3R2 depletion and the consecutive suppression of global astrocytic calcium signalling would lead to marked changes in the behavioral phenotype of a SCA3 mouse model, the CMVMJD135 transgenic line. This was achieved by crossing IP3R2 null mice with the CMVMJD135 mouse model and performing a longitudinal behavioral characterization of these mice using well-established motor-related function tests. Our results demonstrate that IP3R2 deletion in astrocytes does not modify SCA3 progression.
<b>Tipo</b>: article2023-10-18T09:40:53Z