Biomarkers in Genitourinary Cancers, Volume I

project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy - i4HB.Genitourinary cancers are known as significant causes of mortality worldwide. This heterogeneous group includes, among others, the most common cancer in men, prostate cancer, the most common form of kidney cancer, renal cell carcinoma (RCC), and the 10th most common cancer, bladder cancer. These entities present biological diversity with various histological subtypes and a poor prognosis when metastatic. There has been considerable progress in treating patients with genitourinary cancers due to the improved understanding of their pathological mechanisms and the identification of meaningful biomarkers. The treatment progress has led to a fundamental paradigm shift in treatments. For example, our current understanding of the immunogenicity of these tumours has improved tremendously. Thanks to that, today, immunotherapy is a reliable strategy to improve the outcomes of patients with metastatic urothelial carcinoma, renal cell carcinoma, and prostate cancer. However, there is still a critical need to enrich our understanding of additional molecular mechanisms. Along with the mechanisms, there is an urgent requirement to identify novel biomarkers to progress the diagnosis and prognosis of genitourinary cancers and their treatment. Biomarkers have become a significant focus of research, primarily on how they can help predict response to systemic therapy, identify treatment resistance, and avoid toxicities. Biomarkers that reveal the mutated tumour suppressor genes, the altered signalling pathways and the aberrantly expressed molecules help select potentially responsive patients to a given therapy. In this way, biomarkers improve outcomes and reduce costs related to ineffective treatments, and, most importantly, they significantly upsurge patients’ quality of life. This Research Topic named Biomarkers in Genitourinary Cancers includes an interesting and up to date palette of publications from prominent research and clinical groups focused on identifying significant and emerging prognostic and predictive biomarkers. These biomarkers encompass non-coding RNA, serum proteins, gene expression, and glycans, among other entities identified in patients’ cohorts, samples and in the increasing number of public databases.publishersversionpublishe

Registered human trials addressing environmental and occupational toxicant exposures: Scoping review of immunological markers and protective strategies

Exposure to pollution is a worldwide societal challenge participating in the etiology and progression of different diseases. However, the scarce information hinders our understanding of the actual level of human exposure and its specific effects. Inadequate and excessive immune responses underlie diverse chronic diseases. Yet, it is unclear which and how toxicant exposures affect the immune system functions. There is a multiplicity of immunological outcomes and biomarkers being studied in human trials related to exposure to different toxicants but still without clear evidence of their value as biomarkers of exposure or effect. The main aim of this study was to collect scientific evidence and identify relevant immunological biomarkers used at the clinical level for toxicant exposures. We used the platform clinical trials.gov as a database tool. First, we performed a search combining research items related to toxicants and immunological parameters. The resulting117 clinical trials were examined for immune-related outcomes and specific biomarkers evaluated in subjects exposed to occupational and environmental toxicants. After categorization, relevant immunological outcomes and biomarkers were identified related to systemic and airway inflammation, modulation of immune cells, allergy and autoimmunity. In general, the immune markers related to inflammation are more frequently investigated for exposure to pollutants, namely IL-6, C-reactive protein (CRP) and nitric oxide (NO). Nevertheless, the data also indicated that prospective biomarkers of effect are gaining ground and a guiding representation of the established and novel biomarkers is suggested for upcoming trials. Finally, potential protective strategies to mitigate the adverse effects of specific toxicants are underlined for future studies.info:eu-repo/semantics/publishedVersio

Concerted Regulation of Glycosylation Factors Sustains Tissue Identity and Function

Funding Information: This work was financed by national funds from Fundação para a Ciência e Tecnologia (FCT), in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB. Moreover, this research was funded by: PTDC/MED-ONC/28660/2017 from Fundação para a Ciência e Tecnologia (FCT) to A.R.G. A.R.G is recipient of Researcher Grant CEECIND/02699/2017 from FCT. R.F. is recipient of a research grant (SFRH/BD/124326/2016) from FCT, Portugal; European Union’s Horizon 2020 research and innovation program under the EJP RD COFUND-EJP N° 825575, EJPRD/0001/2020. This work had also the support of INCD funded by FCT and FEDER under the project 22153-01/SAICT/2016. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Publisher Copyright: © 2022 by the authors.Glycosylation is a fundamental cellular process affecting human development and health. Complex machinery establishes the glycan structures whose heterogeneity provides greater structural diversity than other post-translational modifications. Although known to present spatial and temporal diversity, the evolution of glycosylation and its role at the tissue-specific level is poorly understood. In this study, we combined genome and transcriptome profiles of healthy and diseased tissues to uncover novel insights into the complex role of glycosylation in humans. We constructed a catalogue of human glycosylation factors, including transferases, hydrolases and other genes directly involved in glycosylation. These were categorized as involved in N-, O- and lipid-linked glycosylation, glypiation, and glycosaminoglycan synthesis. Our data showed that these glycosylation factors constitute an ancient family of genes, where evolutionary constraints suppressed large gene duplications, except for genes involved in O-linked and lipid glycosylation. The transcriptome profiles of 30 healthy human tissues revealed tissue-specific expression patterns preserved across mammals. In addition, clusters of tightly co-expressed genes suggest a glycosylation code underlying tissue identity. Interestingly, several glycosylation factors showed tissue-specific profiles varying with age, suggesting a role in ageing-related disorders. In cancer, our analysis revealed that glycosylation factors are highly perturbed, at the genome and transcriptome levels, with a strong predominance of copy number alterations. Moreover, glycosylation factor dysregulation was associated with distinct cellular compositions of the tumor microenvironment, reinforcing the impact of glycosylation in modulating the immune system. Overall, this work provides genome-wide evidence that the glycosylation machinery is tightly regulated in healthy tissues and impaired in ageing and tumorigenesis, unveiling novel potential roles as prognostic biomarkers or therapeutic targets.publishersversionpublishe

Os factores genéticos da asma Asthma genetic factors

A asma brônquica é uma doença inflamatória crónica das vias aéreas, de prevalência crescente, particularmente na infância, sendo considerado um importante problema de saúde pública. É reconhecidamente uma doença de transmissão familiar, sendo um desafio a descrição e potencial identificação dos genes envolvidos na sua génese. Pretende-se com o presente artigo de revisão explicitar exaustivamente os genes associados a esta patologia, bem como esclarecer os métodos laboratoriais que permitem a sua identificação.Asthma is a chronic inflammatory airways disease, with a rising prevalence, particularly in childhood, and is considered an important Public Health problem. It’s familial transmission is recognised, while the description and identification of the genes implicated in this disease are a challenge. In this revision paper the authors give a comprehensive explanation of the associated genes as well as the laboratorial methods that allow their identification

Os factores genéticos da asma

Resumo: A asma brônquica é uma doença inflamatória crónica das vias aéreas, de prevalência crescente, particularmente na infância, sendo considerado um importante problema de saúde pública.É reconhecidamente uma doença de transmissão familiar, sendo um desafio a descrição e potencial identificação dos genes envolvidos na sua génese.Pretende-se com o presente artigo de revisão explicitar exaustivamente os genes associados a esta patologia, bem como esclarecer os métodos laboratoriais que permitem a sua identificação. Abstract: Asthma is a chronic inflammatory airways disease, with a rising prevalence, particularly in childhood, and is considered an important Public Health problem.It's familial transmission is recognised, while the description and identification of the genes implicated in this disease are a challenge.In this revision paper the authors give a comprehensive explanation of the associated genes as well as the laboratorial methods that allow their identification. Palavras-chave: Asma, susceptibilidade genética, genome wide screen, estudos de associação, farmacogenética, Key-words: Asthma, genetic susceptibility, genome wide screen, association studies, pharmacogenetic

Normas GRI como suporte na elaboração de relatórios de sustentabilidade: estudo de caso da Comunidade Intermunicipal das Terras de Trás-os-Montes

O presente estudo tem como objetivo compreender como e porquê usar as Normas Global Reporting Initiative (GRI) como suporte na elaboração de Relatórios de Sustentabilidade na Comunidade Intermunicipal das Terras de Trás-os-Montes (CIM-TTM). Recentemente, a consciencialização das entidades e dos stakeholders acerca dos impactos das organizações na sociedade e no meio ambiente tem vindo a ganhar relevância. No processo de tomada de decisão, a divulgação de informação é um fator imprescindível, ou seja, quanto mais transparentes forem as organizações, melhores decisões são tomadas, na medida em que essas mesmas decisões têm na sua génese informação útil, fiável, completa, atualizada, compreensível e comparável, permitindo avaliar com precisão os benefícios e os riscos que uma determinada entidade tem subjacente. Esta informação pode ser financeira ou não financeira. Uma das formas de reportar informação não financeira é através da elaboração de relatórios de sustentabilidade. Para tal, podem ser utilizados diversos sistemas que suportam a divulgação de práticas de responsabilidade social, sendo uma dessas formas a utilização das Normas GRI que permitem reportar os impactos económicos, ambientais e sociais, aumentando assim a responsabilidade e a transparência das entidades acerca da sua contribuição para o desenvolvimento sustentável (e.g., Guthrie & Farneti, 2008; Lamprinidi & Kubo, 2008; Muñoz et al., 2020). Considerando que a elaboração de relatórios de sustentabilidade por parte das entidades públicas é facultativa, pelo que cabe a estas entidades a sua elaboração e publicação (Hutchinson et al., 2019), entendemos ser pertinente explorar esta temática no Setor Público e, posteriormente, a um nível mais concreto, na Administração Local. Para o efeito, identificamos como estudo de caso a CIM-TTM, sendo os dados recolhidos através de documentos e por observação direta, e o tratamento das evidências foi feito através da análise de conteúdo. Resultados Esperados | Deste trabalho resultou uma proposta de Relatório de Sustentabilidade para a CIM-TTM que pretende contribuir para a literatura do Setor Público, em geral, e, mais especificamente, para a CIM-TTM, no sentido de potenciar a sua aplicação noutras Comunidades Intermunicipais, funcionando assim como um mecanismo impulsionador. Para além disso, importa referir que nenhuma Comunidade Intermunicipal elaborou ainda este tipo de relatório.info:eu-repo/semantics/publishedVersio

Dendritic Cells: a Spot on Sialic Acid

Glycans decorating cell surface and secreted proteins and lipids occupy the juncture where critical host-host and host-pathogen interactions occur. The role of glycan epitopes in cell-cell and cell-pathogen adhesive events is already well-established, and cell surface glycan structures change rapidly in response to stimulus and inflammatory cues. Despite the wide acceptance that glycans are centrally implicated in immunity, exactly how glycan changes contribute to the overall immune response remains poorly defined.The terminal position of the glycan chains are usually occupied by sialic acids. And sialic acid-modified structures form the key fundamental determinants for a number of receptors with known involvement in cellular adhesiveness and cell trafficking, such as the Selectins and the Siglec families of carbohydrate recognizing receptors.On dendritic cells (DC), sialic acid-modified structures are involved in all their functions and their expression changes along differentiation and activation with important functional implications. DCs preside over the transition from innate to the adaptive immune repertoires, and no other cell has the relevance of role in antigen screening, uptake and presentation to ultimately trigger the adaptive immune response. This review focuses on the developmental regulation of DC surface sialic acids and how manipulation of DC surface sialic acids can affect immune-critical DC functions by altering antigen endocytosis, pathogen and tumor cell recognition, cell recruitment, and capacity for T cell priming. The existing evidence points to a potential of DC surface sialylation as a therapeutic target to improve and diversify DC-based therapies.<br/

Revisiting the immunopathology of congenital disorders of glycosylation: an updated review

Glycosylation is a critical post-translational modification that plays a pivotal role in several biological processes, such as the immune response. Alterations in glycosylation can modulate the course of various pathologies, such as the case of congenital disorders of glycosylation (CDG), a group of more than 160 rare and complex genetic diseases. Although the link between glycosylation and immune dysfunction has already been recognized, the immune involvement in most CDG remains largely unexplored and poorly understood. In this study, we provide an update on the immune dysfunction and clinical manifestations of the 12 CDG with major immune involvement, organized into 6 categories of inborn errors of immunity according to the International Union of Immunological Societies (IUIS). The immune involvement in phosphomannomutase 2 (PMM2)-CDG - the most frequent CDG - was comprehensively reviewed, highlighting a higher prevalence of immune issues during infancy and childhood and in R141H-bearing genotypes. Finally, using PMM2-CDG as a model, we point to links between abnormal glycosylation patterns in host cells and possibly favored interactions with microorganisms that may explain the higher susceptibility to infection. Further characterizing immunopathology and unusual host-pathogen adhesion in CDG can not only improve immunological standards of care but also pave the way for innovative preventive measures and targeted glycan-based therapies that may improve quality of life for people living with CDG