Connexin 43 Modulation in Human Chondrocytes, Osteoblasts and Cartilage Explants: Implications for Inflammatory Joint Disorders.

Connexin 43 (Cx43) is crucial for the development and homeostasis of the musculoskeletal system, where it plays multifaceted roles, including intercellular communication, transcriptional regulation and influencing osteogenesis and chondrogenesis. Here, we investigated Cx43 modulation mediated by inflammatory stimuli involved in osteoarthritis, i.e.

Cartilage responses to inflammatory stimuli and adipose stem/stromal cell-derived conditioned medium: Results from an ex vivo model.

Introduction: Osteoarthritis (OA), a chronic inflammatory joint disorder, still lacks effective therapeutic interventions. Consequently, the development of convenient experimental models is crucial. Recently, research has focused on the plasticity of Mesenchymal Stem/stromal Cells, particularly adipose-derived ones (ASCs), in halting OA progression.

A call for caution when using network methods to study multimorbidity: an illustration using data from the Canadian Longitudinal Study on Aging.

Objectives: To examine the impact of two key choices when conducting a network analysis (clustering methods and measure of association) on the number and type of multimorbidity clusters.

Study Design And Setting: Using cross-sectional self-reported data on 24 diseases from 30,097 community-living adults aged 45-85 from the Canadian Longitudinal Study on Aging, we conducted network analyses using 5 clustering methods and 11 association measures commonly used in multimorbidity studies. We compared the similarity among clusters using the adjusted Rand index (ARI); an ARI of 0 is equivalent to the diseases being randomly assigned to clusters, and 1 indicates perfect agreement.

FGF23 Expression Is a Promising Immunohistochemical Diagnostic Marker for Undifferentiated Pleomorphic Sarcoma of Bone (UPSb).

Undifferentiated pleomorphic sarcoma of bone (UPSb) is a rare primary bone sarcoma that lacks a specific line of differentiation. Distinguishing between UPSb and other malignant bone sarcomas, including dedifferentiated chondrosarcoma and osteosarcoma, is challenging due to their overlapping features. We have previously identified that UPSb tumours have elevated mRNA levels of Fibroblast Growth Factor 23 () transcripts compared to other sarcomas including osteosarcoma.

Financial Toxicity and Health-Related Quality of Life Profile of Patients With Hematologic Malignancies Treated in a Universal Health Care System.

Purpose: We investigated the association of financial toxicity (FT) with the health-related quality of life (HRQoL) profile of patients with hematologic malignancies treated in a universal health care system.

Methods: We did a secondary analysis of six multicenter studies enrolling patients with hematologic malignancies. FT was evaluated using the financial difficulties item of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30).

Boosting the therapeutic potential of cell secretome against osteoarthritis: Comparison of cytokine-based priming strategies.

The secretome, or conditioned medium (CM), from Mesenchymal Stem/stromal Cells (MSCs) has recently emerged as a promising cell-free therapeutic against osteoarthritis (OA), capable of promoting cartilage regeneration and immunoregulation. Priming MSCs with 10 ng/ml tumor necrosis factor α (TNFα) and/or 10 ng/ml interleukin 1β (IL-1β) aims at mimicking the pathological milieu of OA joints in order to target their secretion towards a pathology-tailored phenotype. Here we compare the composition of the CM obtained after 24 or 72 h from untreated and cytokine-treated adipose-derived MSCs (ASCs).

An Exploration of Methods to Resolve Inconsistent Self-Reporting of Chronic Conditions and Impact on Multimorbidity in the Canadian Longitudinal Study on Aging.

Objectives: To quantify inconsistent self-reporting of chronic conditions between the baseline (2011-2015) and first follow-up surveys (2015-2018) in the Canadian Longitudinal Study on Aging (CLSA), and to explore methods to resolve inconsistent responses and impact on multimorbidity.

Methods: Community-dwelling adults aged 45-85 years in the baseline and first follow-up surveys were included ( = 45,184). At each survey, participants self-reported whether they ever had a physician diagnosis of 35 chronic conditions.

Cognitive dysfunction and impaired neuroplasticity following repeated exposure to the synthetic cannabinoid JWH-018 in male mice.

Background And Purpose: Psychotic disorders have been reported in long-term users of synthetic cannabinoids. This study aims at investigating the long-lasting effects of repeated JWH-018 exposure.

Experimental Approach: Male CD-1 mice were injected with vehicle, JWH-018 (6 mg·kg ), the CB -antagonist NESS-0327 (1 mg·kg ) or co-administration of NESS-0327 and JWH-018, every day for 7 days.

Optimizing Catalytic Depolymerization of Lignin in Ethanol with a Day-Clustered Box-Behnken Design.

Lignin is a potential resource for biobased aromatics with applications in the field of fuel additives, resins, and bioplastics. Via a catalytic depolymerization process using supercritical ethanol and a mixed metal oxide catalyst (CuMgAlO), lignin can be converted into a lignin oil, containing phenolic monomers that are intermediates to the mentioned applications. Herein, we evaluated the viability of this lignin conversion technology through a stage-gate scale-up methodology.

Serum starvation affects mitochondrial metabolism of adipose-derived stem/stromal cells.

Background Aims: A large part of mesenchymal stromal cell (MSC) regenerative and immunomodulatory action is mediated by paracrine signaling. Hence, an increasing body of evidence acknowledges the potential of MSC secretome in a variety of preclinical and clinical scenarios. Mid-term serum deprivation is a common approach in the pipeline of MSC secretome production.

Short- and long-term outcomes after endarterectomy with autologous patching in endurance athletes with iliac artery endofibrosis.

Objective: Endurance athletes such as cyclists may develop intermittent claudication owing to iliac artery endofibrosis after long-lasting extreme hemodynamic challenges. This study investigated short-term (<1.5 years) and long-term (>5 years) satisfaction and safety after a surgical endarterectomy and autologous patching.

Determinants of information needs in patients with coronary artery disease receiving cardiac rehabilitation: a prospective observational study.

Objectives: Knowledge on information needs in cardiac rehabilitation (CR) patients is scarce. This study investigates determinants of information needs in patients with coronary artery disease (CAD).

Design: Prospective observational study.

Significant association between FGFR1 mutation frequency and age in central giant cell granuloma.

Central giant cell granulomas (CGCG) are rare intraosseous osteolytic lesions of uncertain aetiology. Despite the benign nature of this neoplasia, the lesions can rapidly grow and become large, painful, invasive, and destructive. The identification of molecular drivers could help in the selection of targeted therapies for specific cases.

Surgical shortening of lengthened iliac arteries in endurance athletes: Short-term and long-term satisfaction.

Objective: Endurance athletes are prone to develop flow limitations in iliac arteries (FLIA). Especially in cyclists and ice speed skaters, excessive hemodynamic loading coupled with hip hyperflexion may cause kinking in lengthened iliac arteries necessitating surgical correction. This study investigated the short-term (≤1.

Polythiophene-mediated light modulation of membrane potential and calcium signalling in human adipose-derived stem/stromal cells.

Recent progress in the fields of regenerative medicine and tissue engineering has been strongly fostered both by the investigation of crucial cues, able to trigger the regeneration of damaged tissues, and by the development of functional materials, capable of selectively (re-)activating relevant physiological pathways. In parallel to the successful realization of biochemical cues and the optimization of delivery protocols, the use of biophysical stimuli has been emerging as an alternative, highly effective strategy. Techniques based on electrical, magnetic and mechanical stimulation have been reported to efficiently direct differentiation of stem cells and modulate cell physiology at different developmental stages.

Lipidomics of Cell Secretome Combined with the Study of Selected Bioactive Lipids in an In Vitro Model of Osteoarthritis.

Analytical advancements in lipidomics have enabled large-scale investigations of lipid biology. Herein, we focused on four bioactive lipid families, namely polyunsaturated fatty acids, eicosanoids, endocannabinoids, and N-acylethanolamines, and their involvement in the mesenchymal stem cells (MSC)-related inflammatory scenario. Since MSC secretome may represent a valid therapeutic alternative, here, the complete secretome and its vesicular component from adipose- and bone marrow-derived MSC and dermal fibroblasts were characterized by targeted mass spectrometry lipidomics.

Human Osteochondral Explants as an Ex Vivo Model of Osteoarthritis for the Assessment of a Novel Class of Orthobiologics.

Osteoarthritis (OA) is a highly prevalent joint disease still lacking effective treatments. Its multifactorial etiology hampers the development of relevant preclinical models to evaluate innovative therapeutic solutions. In the last decade, the potential of Mesenchymal Stem Cell (MSC) secretome, or conditioned medium (CM), has emerged as an alternative to cell therapy.

Dynamics of Connexin 43 Down Modulation in Human Articular Chondrocytes Stimulated by Tumor Necrosis Factor Alpha.

Connexin 43 (Cx43) exerts pivotal functions in articular chondrocytes (CH). It is involved in the communication among cells and between cells and the extracellular environment, and it contributes to the maintenance of the correct cell phenotype. The pro-inflammatory cytokine TNFα induces a reduction in Cx43 expression in CH.

Short- and long-term results of operative iliac artery release in endurance athletes.

Objective: Endurance athletes can develop intermittent claudication due to sports-related flow limitations of the iliac artery (FLIA) caused by arterial kinking. In the present study, we investigated the short- and long-term efficacy of an operative release for iliac artery kinking.

Methods: Between 1996 and 2015, all patients with a diagnosis of FLIA due to iliac artery kinking without substantial arterial stenosis (<15%) or an excessive arterial length (vessel length to straight ratio, <1.

Predictors of non-participation in a cardiac telerehabilitation programme: a prospective analysis.

Aims: Current cardiac telerehabilitation (CTR) interventions are insufficiently tailored to the preferences and competences of individual patients, which raises the question whether their implementation will increase overall participation and adherence to cardiac rehabilitation (CR). However, research on patient-specific factors that influence participation and adoption of CTR interventions is scarce. The aim of this study was to evaluate which patient-related characteristics influence participation in a novel CTR intervention in patients with coronary artery disease.

Towards Secretome Standardization: Identifying Key Ingredients of MSC-Derived Therapeutic Cocktail.

The therapeutic potential of the conditioned medium (CM) derived from MSCs (mesenchymal stem/stromal cells) in disparate medical fields, from immunology to orthopedics, has been widely suggested by and evidences. Prior to MSC-CM use in clinical applications, appropriate quality controls are needed in order to assess its reproducibility. Here, we evaluated different CM characteristics, including general features and precise protein and lipid concentrations, in 3 representative samples from adipose-derived MSCs (ASCs).

Raman Fingerprint of Extracellular Vesicles and Conditioned Media for the Reproducibility Assessment of Cell-Free Therapeutics.

Extracellular Vesicles (EVs) and Conditioned Medium (CM) are promising cell-free approaches to repair damaged and diseased tissues for regenerative rehabilitation purposes. They both entail several advantages, mostly in terms of safety and handling, compared to the cell-based treatment. Despite the growing interest in both EVs and CM preparations, in the light of a clinical translation, a number of aspects still need to be addressed mainly because of limits in the reproducibility and reliability of the proposed protocols.

Improved One-Class Modeling of High-Dimensional Metabolomics Data via Eigenvalue-Shrinkage.

One-class modelling is a useful approach in metabolomics for the untargeted detection of abnormal metabolite profiles, when information from a set of reference observations is available to model "normal" or baseline metabolite profiles. Such outlying profiles are typically identified by comparing the distance between an observation and the reference class to a critical limit. Often, multivariate distance measures such as the Mahalanobis distance (MD) or principal component-based measures are used.

Secretome of human adipose-derived mesenchymal stem cell relieves pain and neuroinflammation independently of the route of administration in experimental osteoarthritis.

Objective: Treatment of pain associated with osteoarthritis (OA) is unsatisfactory and innovative approaches are needed. The secretome from human adipose-derived mesenchymal stem cells (hASC-Conditioned Medium, CM) has been successfully used to relieve painful symptoms in models of chronic pain. The aim of this study was to explore the efficacy of the hASC-CM to control pain and neuroinflammation in an animal model of OA.

Bioactive Lipids in MSCs Biology: State of the Art and Role in Inflammation.

Lipidomics is a lipid-targeted metabolomics approach that aims to the comprehensive analysis of lipids in biological systems in order to highlight the specific functions of lipid species in health and disease. Lipids play pivotal roles as they are major structural components of the cellular membranes and energy storage molecules but also, as most recently shown, they act as functional and regulatory components of intra- and intercellular signaling. Herein, emphasis is given to the recently highlighted roles of specific bioactive lipids species, as polyunsaturated fatty acids (PUFA)-derived mediators (generally known as eicosanoids), endocannabinoids (eCBs), and lysophospholipids (LPLs), and their involvement in the mesenchymal stem cells (MSCs)-related inflammatory scenario.