| 1. |
- Ruiz-Romero, Cristina, et al.
(författare)
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Mining the Proteome Associated with Rheumatic and Autoimmune Diseases
- 2019
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 18:12, s. 4231-4239
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Tidskriftsartikel (refereegranskat)abstract
- A steady increase in the incidence of osteoarthritis and other rheumatic diseases has been observed in recent decades, including autoimmune conditions such as rheumatoid arthritis, spondyloarthropathies, systemic lupus erythematosus, systemic sclerosis, and Sjogren's syndrome. Rheumatic and autoimmune diseases (RADs) are characterized by the inflammation of joints, muscles, or other connective tissues. In addition to often experiencing debilitating mobility and pain, RAD patients are also at a higher risk of suffering comorbidities such as cardiovascular or infectious events. Given the socioeconomic impact of RADs, broad research efforts have been dedicated to these diseases worldwide. In the present work, we applied literature mining platforms to identify "popular" proteins closely related to RADs. The platform is based on publicly available literature. The results not only will enable the systematic prioritization of candidates to perform targeted proteomics studies but also may lead to a greater insight into the key pathogenic processes of these disorders.
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| 2. |
- Almet, Axel A., et al.
(författare)
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A Roadmap for a Consensus Human Skin Cell Atlas and Single-Cell Data Standardization
- 2023
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Ingår i: Journal of Investigative Dermatology. - : Elsevier. - 0022-202X .- 1523-1747. ; 143:9, s. 1667-1677
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Forskningsöversikt (refereegranskat)abstract
- Single-cell technologies have become essential to driving discovery in both basic and translational investigative dermatology. Despite the multitude of available datasets, a central reference atlas of normal human skin, which can serve as a reference resource for skin cell types, cell states, and their molecular signatures, is still lacking. For any such atlas to receive broad acceptance, participation by many investigators during atlas construction is an essential prerequisite. As part of the Human Cell Atlas project, we have assembled a Skin Biological Network to build a consensus Human Skin Cell Atlas and outline a roadmap toward that goal. We define the drivers of skin diversity to be considered when selecting sequencing datasets for the atlas and list practical hurdles during skin sampling that can result in data gaps and impede comprehensive representation and technical considerations for tissue processing and computational analysis, the accounting for which should minimize biases in cell type enrichments and exclusions and decrease batch effects. By outlining our goals for Atlas 1.0, we discuss how it will uncover new aspects of skin biology.
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| 3. |
- Mason, Deborah, et al.
(författare)
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Prevention of posttraumatic osteoarthritis at the time of injury : Where are we now, and where are we going?
- 2021
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Ingår i: Journal of Orthopaedic Research. - : Wiley. - 0736-0266 .- 1554-527X. ; 39:6, s. 1152-1163
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Forskningsöversikt (refereegranskat)abstract
- This overview of progress made in preventing post-traumatic osteoarthritis (PTOA) was delivered in a workshop at the Orthopaedics Research Society Annual Conference in 2019. As joint trauma is a major risk factor for OA, defining the molecular changes within the joint at the time of injury may enable the targeting of biological processes to prevent later disease. Animal models have been used to test therapeutic targets to prevent PTOA. A review of drug treatments for PTOA in rodents and rabbits between 2016 and 2018 revealed 11 systemic interventions, 5 repeated intra-articular or topical interventions, and 5 short-term intra-articular interventions, which reduced total Osteoarthritis Research Society International scores by 30%–50%, 20%–70%, and 0%–40%, respectively. Standardized study design, reporting of effect size, and quality metrics, alongside a “whole joint” approach to assessing efficacy, would improve the translation of promising new drugs. A roadblock to translating preclinical discoveries has been the lack of guidelines on the design and conduct of human trials to prevent PTOA. An international workshop addressing this in 2016 considered inclusion criteria and study design, and advocated the use of experimental medicine studies to triage candidate treatments and the development of early biological and imaging biomarkers. Human trials for the prevention of PTOA have tested anakinra after anterior cruciate ligament rupture and dexamethasone after radiocarpal injury. PTOA offers a unique opportunity for defining early mechanisms of OA to target therapeutically. Progress in trial design and high-quality preclinical research, and allegiance with patients, regulatory bodies, and the pharmaceutical industry, will advance this field.
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| 4. |
- Tan, Khooi Y, et al.
(författare)
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Decoupling geometrical and chemical cues directing epidermal stem cell fate on polymer brush-based cell micro-patterns
- 2013
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Ingår i: Integrative Biology. - : RSC Publishing. - 1757-9694 .- 1757-9708. ; 5:6, s. 899-910
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Tidskriftsartikel (refereegranskat)abstract
- The intricacy of the different parameters involved in cell adhesion to biomaterials and fate decision (e.g. proliferation, differentiation, apoptosis) makes the decoupling of the respective effects of surface properties, extra-cellular matrix protein adsorption and ultimately cell behaviour difficult. This work presents a micro-patterned polymer brush platform to control the adsorption of extra-cellular matrix (ECM) proteins to well defined micron-size areas and consequently control cell adhesion, spreading and shape independently of other chemical and physical surface properties. Protein patterns can be readily generated with brushes presenting a range of hydrophilicity and surface charge density. The surface properties of the selected brushes are fully characterised using a combination of FTIR, XPS, ellipsometry, atomic force microscopy, water contact goniometry, dynamic light scattering and ζ-potential measurements. Interactions of proteins relevant to cell patterning and culture with these brushes are studied by surface plasmon resonance, dynamic light scattering, ellipsometry and immuno-fluorescence microscopy. Finally this platform is used in an assay investigating the relative contributions of matrix geometry and surface chemistry on epidermal stem cell differentiation. It is found that moderate hydrophobicity does not impact stem cell commitment, whereas strongly negative surface potential increases the incidence of differentiation. This correlates with a marked decrease in the formation of focal adhesions (but not cell spreading).
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| 5. |
- Whittaker, Jackie L., et al.
(författare)
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Toward designing human intervention studies to prevent osteoarthritis after knee injury : A report from an interdisciplinary OARSI 2023 workshop
- 2024
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Ingår i: Osteoarthritis and Cartilage Open. - 2665-9131. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The global impact of osteoarthritis is growing. Currently no disease modifying osteoarthritis drugs/therapies exist, increasing the need for preventative strategies. Knee injuries have a high prevalence, distinct onset, and strong independent association with post-traumatic osteoarthritis (PTOA). Numerous groups are embarking upon research that will culminate in clinical trials to assess the effect of interventions to prevent knee PTOA despite challenges and lack of consensus about trial design in this population. Our objectives were to improve awareness of knee PTOA prevention trial design and discuss state-of-the art methods to address the unique opportunities and challenges of these studies. Design: An international interdisciplinary group developed a workshop, hosted at the 2023 Osteoarthritis Research Society International Congress. Here we summarize the workshop content and outputs, with the goal of moving the field of PTOA prevention trial design forward. Results: Workshop highlights included discussions about target population (considering risk, homogeneity, and possibility of modifying osteoarthritis outcome); target treatment (considering delivery, timing, feasibility and effectiveness); comparators (usual care, placebo), and primary symptomatic outcomes considering surrogates and the importance of knee function and symptoms other than pain to this population. Conclusions: Opportunities to test multimodal PTOA prevention interventions across preclinical models and clinical trials exist. As improving symptomatic outcomes aligns with patient and regulator priorities, co-primary symptomatic (single or aggregate/multidimensional outcome considering function and symptoms beyond pain) and structural/physiological outcomes may be appropriate for these trials. To ensure PTOA prevention trials are relevant and acceptable to all stakeholders, future research should address critical knowledge gaps and challenges.
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