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Akkermansia muciniphila and Parabacteroides distasonis synergistically protect ...

Gaifem, Joana; Mendes-Frias, Ana; Wolter, Mathis; Steimle, Alex; Garzón, Maria Jose; Ubeda, Carles; Nobre, Clarisse; González, Abigail; Pinho, Salomé S.

The contribution of the gut microbiome to the balance between homeostasis and inflammation is widely known. Nevertheless, the etiology of inflammatory bowel disease, which is known to be influenced by genetics, immune response, and environmental cues, remains unclear. Unlocking novel players involved in the dictation of a protective gut, namely, in the microbiota component, is therefore crucial to develop novel...


Cisplatin-resistant urothelial bladder cancer cells undergo metabolic reprogram...

Afonso, Julieta Alexandra Pereira; Matos, Ana Catarina Barbosa; Silvestre, Ricardo Jorge Leal; Pereira-Vieira, Joana; Gonçalves, Samuel Martins

Advanced urothelial bladder cancer (UBC) patients are tagged by a dismal prognosis and high mortality rates, mostly due to their poor response to standard-of-care platinum-based therapy. Mediators of chemoresistance are not fully elucidated. This work aimed to study the metabolic profile of advanced UBC, in the context of cisplatin resistance. Three isogenic pairs of parental cell lines (T24, HT1376 and KU1919)...


Analysis of salivary levels of IL-1β, IL17A, OPG and RANK-L in periodontitis us...

Relvas, Marta; Silvestre, Ricardo Jorge Leal; Gonçalves, Maria; Cabral, Cristina; Frias, Ana Isabel Mendes; Monteiro, Luís; Viana da Costa, Alexandra

Periodontitis is a chronic disease with a high overall prevalence. It involves a complex interplay between the immune-inflammatory pathways and biofilm changes, leading to periodontal attachment loss. The aims of this study were (i) to assess whether the salivary IL-1β, IL-17A, RANK-L and OPG levels have the potential to discriminate between the mild and severe periodontitis conditions; and (ii) to enable diagn...


Immune tumor microenvironment in ovarian cancer ascites

Almeida-Nunes, Diana Luísa; Frias, Ana Isabel Mendes; Silvestre, Ricardo Jorge Leal; Dinis-Oliveira, Ricardo Jorge; Ricardo, Sara

Ovarian cancer (OC) has a specific type of metastasis, via transcoelomic, and most of the patients are diagnosed at advanced stages with multiple tumors spread within the peritoneal cavity. The role of Malignant Ascites (MA) is to serve as a transporter of tumor cells from the primary location to the peritoneal wall or to the surface of the peritoneal organs. MA comprise cellular components with tumor and non-t...


Methods for the analysis of transcriptome dynamics

Rodrigues, Daniela F.; Costa, Vera M.; Silvestre, Ricardo Jorge Leal; Bastos, Maria L.; Carvalho, Félix

The transcriptome is the complete set of transcripts in a cell or tissue and includes ribosomal RNA (rRNA), messenger RNA (mRNA), transfer RNA (tRNA), and regulatory noncoding RNA. At steady-state, the transcriptome results from a compensatory variation of the transcription and decay rate to maintain the RNA concentration constant. RNA transcription constitutes the first stage in gene expression, and thus is a ...


PTX3 Polymorphisms Influence Cytomegalovirus Reactivation After Stem-Cell Trans...

Campos, Cláudia F.; Leite, Luís; Pereira, Paulo; Vaz, Carlos Pinho; Branca, Rosa; Campilho, Fernando; Freitas, Fátima; Ligeiro, Dário; Marques, António

Background: Reactivation of latent human cytomegalovirus (CMV) in patients undergoing allogeneic stem-cell transplantation (HSCT) predisposes to several clinical complications and is therefore a major cause of morbidity and mortality. Although pentraxin-3 (PTX3) has been previously described to bind both human and murine CMV and mediate several host antiviral mechanisms, whether genetic variation in the PTX3 lo...


Definition of the anti-inflammatory oligosaccharides derived from the galactosa...

Gressler, Markus; Heddergott, Christoph; N'Go, Inés C.; Renga, Giorgia; Oikonomou, Vasilis; Moretti, Silvia; Coddeville, Bernadette; Gaifem, Joana

Galactosaminogalactan (GAG) is an insoluble aminosugar polymer produced by Aspergillus fumigatus and has anti-inflammatory properties. Here, the minimum glycosidic sequences required for the induction of IL-1Ra by peripheral blood mononuclear cells (PBMCs) was investigated. Using chemical degradation of native GAG to isolate soluble oligomers, we have found that the de-N-acetylation of galactosamine residues an...


The impact of IL-10 dynamic modulation on host immune response against visceral...

Mesquita, Inês Morais; Ferreira, Carolina; Barbosa, Ana Margarida; Ferreira, Catarina Machado; Moreira, Diana; Carvalho, Agostinho; Cunha, Cristina

Leishmaniasis is a vector-borne disease caused by protozoan parasites from the genus Leishmania. The most severe form of disease is visceral leishmaniasis (VL), which is fatal if left untreated. It has been demonstrated that interleukin (IL)-10, is associated with disease progression and susceptibility. In this work, we took advantage of a transgenic mouse model that expresses high levels of IL-10 upon zinc sul...


More than just exosomes: distinct Leishmania infantum extracellular products po...

Pérez-Cabezas, Begoña; Santarém, Nuno; Cecílio, Pedro; Silva, Cátia; Silvestre, Ricardo Jorge Leal; Catita, José A. M.; Cordeiro da Silva, Anabela

The use of secretion pathways for effector molecule delivery by microorganisms is a trademark of pathogenesis. Leishmania extracellular vesicles (EVs) were shown to have significant immunomodulatory potential. Still, they will act in conjunction with other released parasite-derived products that might modify the EVs effects. Notwithstanding, the immunomodulatory properties of these non-vesicular components and ...


The anti-caspase inhibitor Q-VD-OPH prevents AIDS disease progression in SIV-in...

Laforge, Mireille; Silvestre, Ricardo Jorge Leal; Rodrigues, Vasco; Garibal, Julie; Campillo-Gimenez, Laure; Mouhamad, Shahul; Monceaux, Valérie

Apoptosis has been proposed as a key mechanism responsible for CD4+ T cell depletion and immune dysfunction during HIV infection. We demonstrated that Q-VD-OPH, a caspase inhibitor, inhibits spontaneous and activation-induced death of T cells from SIV-infected rhesus macaques (RMs). When administered during the acute phase of infection, Q-VD-OPH was associated with (a) reduced levels of T cell death, (b) preser...


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