Unraveling the biological potential of skin fibroblast: responses to TNF-α, highlighting intracellular signaling pathways and secretome.

Objective: In this study, we examined the molecular response of human skin fibroblasts to an inflammatory cytokine to evaluate their suitability as models for immunopathology research.

Methods: Skin fibroblasts were stimulated with tumour necrosis factor (TNF)-α, and the transcriptome was profiled via RNA-Seq. The differentially expressed genes were screened to predict immunological pathways and interactions.

Mapping the diagnostic odyssey of congenital disorders of glycosylation (CDG): insights from the community.

Background: Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases with heterogeneous presentations, leading to substantial diagnostic challenges, which are poorly understood. Therefore, this study aims to elucidate this diagnostic journey by examining families' and professionals' experiences.

Results And Discussion: A questionnaire was designed for CDG families and professionals, garnering 160 and 35 responses, respectively.

A community-centric model for conference co-creation: the world conference on CDG for patients, families and professionals.

Background: Patient and public co-creation and involvement in health initiatives have been witnessing great expansion in recent years. From healthcare to research settings, collaborative approaches are becoming increasingly prevalent and diverse, especially in the field of rare diseases which faces complex challenges. Conference development and implementation, however, have been primarily guided by passive, information-sharing models.

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.

Congenital disorders of glycosylation (CDG): state of the art in 2022.

Congenital disorders of glycosylation (CDG) are a complex and heterogeneous family of rare metabolic diseases. With a clinical history that dates back over 40 years, it was the recent multi-omics advances that mainly contributed to the fast-paced and encouraging developments in the field. However, much remains to be understood, with targeted therapies' discovery and approval being the most urgent unmet need.

Sialyl Lewis and Cytokeratin Crosstalk in Triple Negative Breast Cancer.

Triple-negative breast cancer (TNBC) encompasses multiple entities and is generally highly aggressive and metastatic. We aimed to determine the clinical and biological relevance of Sialyl-Lewis X and A (sLe)-a fucosylated glycan involved in metastasis-in TNBC. Here, we studied tissues from 50 TNBC patients, transcripts from a TNBC dataset from The Cancer Genome Atlas (TCGA) database, and a primary breast cancer cell line.

A Community-Based Participatory Framework to Co-Develop Patient Education Materials (PEMs) for Rare Diseases: A Model Transferable across Diseases.

At least 50% of chronic disease patients don't follow their care plans, leading to lower health outcomes and higher medical costs. Providing Patient Education Materials (PEMs) to individuals living with a disease can help to overcome these problems. PEMs are especially beneficial for people suffering from multisystemic and underrecognized diseases, such as rare diseases.

A Participatory Framework for Plain Language Clinical Management Guideline Development.

Background: Clinical management guidelines (CMGs) are decision support tools for patient care used by professionals, patients, and family caregivers. Since clinical experts develop numerous CMGs, their technical language hinders comprehension and access by nonmedical stakeholders. Additionally, the views of affected individuals and their families are often not incorporated into treatment guidelines.

Stakeholders' views on drug development: the congenital disorders of glycosylation community perspective.

Background: Congenital disorders of glycosylation (CDG) are a large family of rare genetic diseases for which therapies are virtually nonexistent. However, CDG therapeutic research has been expanding, thanks to the continuous efforts of the CDG medical/scientific and patient communities. Hence, CDG drug development is a popular research topic.

A Community-Led Approach as a Guide to Overcome Challenges for Therapy Research in Congenital Disorders of Glycosylation.

Congenital Disorders of Glycosylation (CDG) are a large family of rare genetic diseases for which effective therapies are almost nonexistent. To better understand the reasons behind this, to analyze ongoing therapy research and development (R&D) for CDG, and to provide future guidance, a community-led mixed methods approach was organized during the 4th World Conference on CDG for Families and Professionals. In the quantitative phase, electronic surveys pointed to the prioritization of six therapeutic R&D tools, namely biobanks, registries, biomarkers, disease models, natural history studies, and clinical trials.

Patient-reported outcomes and quality of life in PMM2-CDG.

Patient-reported outcomes (PROs) measure important aspects of disease burden, however they have received limited attention in the care of patients with Congenital Disorders of Glycosylation (CDG). We evaluated the PROs and correlation between clinical disease severity scoring and reported quality of life (QoL) in a PMM2-CDG patient cohort. Twenty-five patients with diagnosis of PMM2-CDG were enrolled as part of the Frontiers in Congenital Disorders of Glycosylation Consortium (FCDGC) natural history study.

The road to successful people-centric research in rare diseases: the web-based case study of the Immunology and Congenital Disorders of Glycosylation questionnaire (ImmunoCDGQ).

Background: Congenital Disorders of Glycosylation (CDG) are a complex family of rare metabolic diseases. Robust clinical data collection faces many hurdles, preventing full CDG biological and clinical comprehension. Web-based platforms offer privileged opportunities for biomedical data gathering, and participant recruitment, particularly in rare diseases.

International consensus guidelines for phosphoglucomutase 1 deficiency (PGM1-CDG): Diagnosis, follow-up, and management.

Phosphoglucomutase 1 (PGM1) deficiency is a rare genetic disorder that affects glycogen metabolism, glycolysis, and protein glycosylation. Previously known as GSD XIV, it was recently reclassified as a congenital disorder of glycosylation, PGM1-CDG. PGM1-CDG usually manifests as a multisystem disease.

New Insights into Immunological Involvement in Congenital Disorders of Glycosylation (CDG) from a People-Centric Approach.

Congenital disorders of glycosylation (CDG) are rare diseases with variable phenotypes and severity. Immunological involvement remains a largely uncharted topic in CDG, mainly due to lack of robust data. To better characterize immune-related manifestations' prevalence, relevance, and quality-of-life (QoL) impact, we developed electronic questionnaires targeting (1) CDG patients and (2) the general "healthy" population.

Artificial Intelligence (AI) in Rare Diseases: Is the Future Brighter?

The amount of data collected and managed in (bio)medicine is ever-increasing. Thus, there is a need to rapidly and efficiently collect, analyze, and characterize all this information. Artificial intelligence (AI), with an emphasis on deep learning, holds great promise in this area and is already being successfully applied to basic research, diagnosis, drug discovery, and clinical trials.

CDG and immune response: From bedside to bench and back.

Glycosylation is an essential biological process that adds structural and functional diversity to cells and molecules, participating in physiological processes such as immunity. The immune response is driven and modulated by protein-attached glycans that mediate cell-cell interactions, pathogen recognition and cell activation. Therefore, abnormal glycosylation can be associated with deranged immune responses.

Keeping an eye on congenital disorders of O-glycosylation: A systematic literature review.

Congenital disorders of glycosylation (CDG) are a rapidly growing family comprising >100 genetic diseases. Some 25 CDG are pure O-glycosylation defects. Even among this CDG subgroup, phenotypic diversity is broad, ranging from mild to severe poly-organ/system dysfunction.

International clinical guidelines for the management of phosphomannomutase 2-congenital disorders of glycosylation: Diagnosis, treatment and follow up.

Phosphomannomutase 2 (PMM2-CDG) is the most common congenital disorder of N-glycosylation and is caused by a deficient PMM2 activity. The clinical presentation and the onset of PMM2-CDG vary among affected individuals ranging from a severe antenatal presentation with multisystem involvement to mild adulthood presentation limited to minor neurological involvement. Management of affected patients requires a multidisciplinary approach.

Patient and observer reported outcome measures to evaluate health-related quality of life in inherited metabolic diseases: a scoping review.

Background: Health-related Quality of Life (HrQoL) is a multidimensional measure, which has gained clinical and social relevance. Implementation of a patient-centred approach to both clinical research and care settings, has increased the recognition of patient and/or observer reported outcome measures (PROMs or ObsROMs) as informative and reliable tools for HrQoL assessment. Inherited Metabolic Diseases (IMDs) are a group of heterogeneous conditions with phenotypes ranging from mild to severe and mostly lacking effective therapies.

CDG Therapies: From Bench to Bedside.

Congenital disorders of glycosylation (CDG) are a group of genetic disorders that affect protein and lipid glycosylation and glycosylphosphatidylinositol synthesis. More than 100 different disorders have been reported and the number is rapidly increasing. Since glycosylation is an essential post-translational process, patients present a large range of symptoms and variable phenotypes, from very mild to extremely severe.

Inhibition of fucosylation in human invasive ductal carcinoma reduces E-selectin ligand expression, cell proliferation, and ERK1/2 and p38 MAPK activation.

Breast cancer tissue overexpresses fucosylated glycans, such as sialyl-Lewis X/A (sLe ), and α-1,3/4-fucosyltransferases (FUTs) in relation to increased disease progression and metastasis. These glycans in tumor circulating cells mediate binding to vascular E-selectin, initiating tumor extravasation. However, their role in breast carcinogenesis is still unknown.