A comprehensive patient-specific prediction model for temporomandibular joint osteoarthritis progression.

Temporomandibular joint osteoarthritis (TMJ OA) is a prevalent degenerative disease characterized by chronic pain and impaired jaw function. The complexity of TMJ OA has hindered the development of prognostic tools, posing a significant challenge in timely, patient-specific management. Addressing this gap, our research employs a comprehensive, multidimensional approach to advance TMJ OA prognostication. We conducted a prospective study with 106 subjects, 74 of whom were followed up after 2 to 3 y of conservative treatment. Central to our methodology is the development of an innovative, open-source predictive modeling framework, the Ensemble via Hierarchical Predictions through Nested cross-validation tool (EHPN). This framework synergistically integrates 18 feature selection, statistical, and machine learning methods to yield an accuracy of 0.87, with an area under the ROC curve of 0.72 and an F1 score of 0.82. Our study, beyond technical advancements, emphasizes the global impact of TMJ OA, recognizing its unique demographic occurrence. We highlight key factors influencing TMJ OA progression. Using SHAP analysis, we identified personalized prognostic predictors: lower values of headache, lower back pain, restless sleep, condyle high gray level-GL-run emphasis, articular fossa GL nonuniformity, and long-run low GL emphasis; and higher values of superior joint space, mouth opening, saliva Vascular-endothelium-growth-factor, Matrix-metalloproteinase-7, serum Epithelial-neutrophil-activating-peptide, and age indicate recovery likelihood. Our multidimensional and multimodal EHPN tool enhances clinicians' decision-making, offering a transformative translational infrastructure. The EHPN model stands as a significant contribution to precision medicine, offering a paradigm shift in the management of temporomandibular disorders and potentially influencing broader applications in personalized healthcare.

Particle-based hematite crystallization is invariant to initial particle morphology.

SignificanceMany crystallization processes occurring in nature produce highly ordered hierarchical architectures. Their formation cannot be explained using classical models of monomer-by-monomer growth. One of the possible pathways involves crystallization through the attachment of oriented nanocrystals. Thus, it requires detailed understanding of the mechanism of particle dynamics that leads to their precise crystallographic alignment along specific faces. In this study, we discover a particle-morphology-independent oriented attachment mechanism for hematite nanocrystals. Independent of crystal morphology, particles always align along the [001] direction driven by aligning interactions between (001) faces and repulsive interactions between other pairs of hematite faces. These results highlight that strong face specificity along one crystallographic direction can render oriented attachment to be independent of initial particle morphology.

Ti─O─C Bonding at 2D Heterointerfaces of 3D Composites for Fast Sodium Ion Storage at High Mass Loading Level.

3D composite electrodes have shown extraordinary promise as high mass loading electrode materials for sodium ion batteries (SIBs). However, they usually show poor rate performance due to the sluggish Na+ kinetics at the heterointerfaces of the composites. Here, a 3D MXene-reduced holey graphene oxide (MXene-RHGO) composite electrode with Ti─O─C bonding at 2D heterointerfaces of MXene and RHGO is developed. Density functional theory (DFT) calculations reveal the built-in electric fields (BIEFs) are enhanced by the formation of bridged interfacial Ti─O─C bonding, that lead to not only faster diffusion of Na+ at the heterointerfaces but also faster adsorption and migration of Na+ on the MXene surfaces. As a result, the 3D composite electrodes show impressive properties for fast Na+ storage. Under high current density of 10 mA cm-2, the 3D MXene-RHGO composite electrodes with high mass loading of 10 mg cm-2 achieve a strikingly high and stable areal capacity of 3 mAh cm-2, which is same as commercial LIBs and greatly exceeds that of most reported SIBs electrode materials. The work shows that rationally designed bonding at the heterointerfaces represents an effective strategy for promoting high mass loading 3D composites electrode materials forward toward practical SIBs applications.

Modulating Electronic Structure of Iridium Single-Atom Anchored on 3D Fe-Doped ß-Ni(OH)2 Catalyst with Nanopyramid Array Structure for Enhanced Oxygen Evolution Reaction.

Developing high-performance electrocatalysts for oxygen evolution reaction (OER) is crucial in the pursuit of clean and sustainable hydrogen energy, yet still challenging. Herein, a spontaneous redox strategy is reported to achieve iridium single-atoms anchored on hierarchical nanosheet-based porous Fe doped ß-Ni(OH)2 pyramid array electrodes (SAs Ir/Fe-ß-Ni(OH)2 ), which exhibits high OER performance with a low overpotential of 175 mV at 10 mA cm-2 and a remarkable OER current density in alkaline electrolyte, surpassing Fe-ß-Ni(OH)2 /NF and IrO2 by 31 and 38 times at 1.43 V versus RHE, respectively. OER catalytic mechanism demonstrates that the conversion of * OH→* O and the active lattice O content can be significantly improved due to the modulation effect of the Ir single atoms on the local electronic structure and the redox behavior of FeNi (oxy) hydroxide true active species. This work provides a promising insight into understanding the OER enhancement mechanism for Ir single-atoms modified FeNi-hydroxide systems.

Identification of therapeutic targets in osteoarthritis by combining heterogeneous transcriptional datasets, drug-induced expression profiles, and known drug-target interactions.

BACKGROUND: Osteoarthritis (OA) is a multifactorial, hypertrophic, and degenerative condition involving the whole joint and affecting a high percentage of middle-aged people. It is due to a combination of factors, although the pivotal mechanisms underlying the disease are still obscure. Moreover, current treatments are still poorly effective, and patients experience a painful and degenerative disease course. METHODS: We used an integrative approach that led us to extract a consensus signature from a meta-analysis of three different OA cohorts. We performed a network-based drug prioritization to detect the most relevant drugs targeting these genes and validated in vitro the most promising candidates. We also proposed a risk score based on a minimal set of genes to predict the OA clinical stage from RNA-Seq data. RESULTS: We derived a consensus signature of 44 genes that we validated on an independent dataset. Using network analysis, we identified Resveratrol, Tenoxicam, Benzbromarone, Pirinixic Acid, and Mesalazine as putative drugs of interest for therapeutics in OA for anti-inflammatory properties. We also derived a list of seven gene-targets validated with functional RT-qPCR assays, confirming the in silico predictions. Finally, we identified a predictive subset of genes composed of DNER, TNFSF11, THBS3, LOXL3, TSPAN2, DYSF, ASPN and HTRA1 to compute the patient's risk score. We validated this risk score on an independent dataset with a high AUC (0.875) and compared it with the same approach computed using the entire consensus signature (AUC 0.922). CONCLUSIONS: The consensus signature highlights crucial mechanisms for disease progression. Moreover, these genes were associated with several candidate drugs that could represent potential innovative therapeutics. Furthermore, the patient's risk scores can be used in clinical settings.

Exploring different models of pain phenotypes and their association with pain worsening in people with early knee osteoarthritis: The MOST cohort study.

OBJECTIVE: To determine i) pain phenotypes (PP) in people with early-stage knee osteoarthritis (EKOA); ii) the longitudinal association between the phenotypes and pain worsening at two years. DESIGN: We studied participants with EKOA from the Multicenter Osteoarthritis Study defined as pain intensity ≤3/10, Kellgren and Lawrence grade ≤2, intermittent pain none to sometimes, and no constant pain. Two models of PP were explored. Model A included pressure pain thresholds, temporal summation, conditioned pain modulation, pain catastrophizing, sleep quality, depression, and widespread pain (WSP). In Model B, gait characteristics, quadriceps strength, comorbidities, and magnetic resonance imaging features were added to Model A. Latent Class Analysis was used to create phenotypes, and logistic regression was used to determine their association with pain worsening. RESULTS: 750 individuals (60% females), mean age [standard deviation (SD)]: 60.3 (9.4) were included in Model A and 333 individuals (60% females), mean age (SD): 59.4 (8.1) in Model B. 3-class and 4-class solutions were chosen for Model A and Model B. In Model A, the most "severe" phenotype was dominated by psychosocial factors, WSP, and measures of nervous system sensitization. Similarly in Model B, the Model A phenotype plus gait variables, quadriceps strength, and comorbidities were dominant. Surprisingly, none of the phenotypes in either model had a significant relationship with pain worsening. CONCLUSION: Phenotypes based upon various factors thought to be important for the pain experience were identified in those with EKOA but were not significantly related to pain worsening. These phenotypes require validation with clinically relevant endpoints.

Associations between anterior knee pain and 2-year patellofemoral cartilage worsening: The MOST study.

OBJECTIVE: Anterior knee pain (AKP) is associated with patellofemoral osteoarthritis (PFOA), but longitudinal studies are lacking. If AKP precedes PFOA, it may create an opportunity to identify and intervene earlier in the disease process. The purpose of this study was to examine the longitudinal relation of AKP to worsening patellofemoral (PF) cartilage over two years. DESIGN: Participants were recruited from the Multicenter Osteoarthritis Study, a longitudinal study of individuals with or at risk for knee osteoarthritis (OA). Exclusion criteria included bilateral knee replacements, arthritis other than OA, and radiographic PFOA. At baseline, participants completed a knee pain map questionnaire and underwent knee magnetic resonance imaging (MRI). Imaging was repeated at 2-year follow-up. Exposure was presence of frequent AKP. Outcome was worsening cartilage damage in the PF joint defined as increase in MRI Osteoarthritis Knee Score from baseline to 2 years. Log-binomial models were used to calculate risk ratios (RR). RESULTS: One knee from 1083 participants (age 56.7 ± 6.6 years; body mass index 28.0 ± 4.9 kg/m2) was included. Frequent AKP and frequent isolated AKP were present at baseline in 14.5% and 3.6%, respectively. Frequent AKP was associated with an increased risk (RR: 1.78, 95% confidence interval: 1.21, 2.62) of 2-year worsening cartilage damage in the lateral PF compartment. No association was found between frequent AKP and worsening in the medial PF joint. CONCLUSION: Frequent AKP at baseline was associated with worsening cartilage damage in the lateral PF joint over 2 years.

Constructing a clinical radiographic knee osteoarthritis database using artificial intelligence tools with limited human labor: A proof of principle.

OBJECTIVE: To create a scalable and feasible retrospective consecutive knee osteoarthritis (OA) radiographic database with limited human labor using commercial and custom-built artificial intelligence (AI) tools. METHODS: We applied four AI tools, two commercially available and two custom-built tools, to analyze 6 years of clinical consecutive knee radiographs from patients aged 35-79 at the University of Copenhagen Hospital, Bispebjerg-Frederiksberg Hospital, Denmark. The tools provided Kellgren-Lawrence (KL) grades, joint space widths, patella osteophyte detection, radiographic view detection, knee joint implant detection, and radiographic marker detection. RESULTS: In total, 25,778 knee radiographs from 8575 patients were included in the database after excluding inapplicable radiographs, and 92.5% of the knees had a complete OA dataset. Using the four AI tools, we saved about 800 hours of radiologist reading time and only manually reviewed 16.0% of the images in the database. CONCLUSIONS: This study shows that clinical knee OA databases can be built using AI with limited human reading time for uniform grading and measurements. The concept is scalable temporally and across geographic regions and could help diversify further OA research by efficiently including radiographic knee OA data from different populations globally. We can prevent data dredging and overfitting OA theories on existing trite cohorts by including various gene pools and continuous expansion of new clinical cohorts. Furthermore, the suggested tools and applied approaches provide an ability to retest previous hypotheses and test new hypotheses on real-life clinical data with current disease prevalence and trends.

Identification of CD64 as a marker for the destructive potential of synovitis in osteoarthritis.

OBJECTIVES: OA is characterized by cartilage degeneration and persistent pain. The majority of OA patients present with synovitis, which is associated with increased cartilage damage. Activated synovial macrophages are key contributors to joint destruction. Therefore, a marker that reflects the activation of these cells could be a valuable tool to characterize the destructive potential of synovitis and benefit monitoring of OA. Here, we aimed to investigate the use of CD64 (FcγRI) as a marker to characterize the damaging potential of synovitis in OA. METHODS: Synovial biopsies were obtained from end-stage OA patients that underwent joint replacement surgery. CD64 protein expression and localization was evaluated using immunohistochemistry and immunofluorescence and quantified using flow cytometry. qPCR was performed to measure the expression of FCGR1 and OA-related genes in synovial biopsies, and in primary chondrocytes and primary fibroblasts stimulated with OA conditioned medium (OAS-CM). RESULTS: Our data exposed a wide range of CD64 expression in OA synovium and showed positive correlations between FCGR1 and S100A8, S100A9, IL1B, IL6 and MMP1/2/3/9/13 expression. CD64 protein correlated with MMP1, MMP3, MMP9, MMP13 and S100A9. Furthermore, we observed that synovial CD64 protein levels in source tissue for OAS-CM significantly associated with the OAS-CM-induced expression of MMP1, MMP3 and especially ADAMTS4 in cultured fibroblasts, but not chondrocytes. CONCLUSION: Together, these results indicate that synovial CD64 expression is associated with the expression of proteolytic enzymes and inflammatory markers related to structural damage in OA. CD64 therefore holds promise as marker to characterize the damaging potential of synovitis.

Association between knee magnetic resonance imaging markers and knee symptoms over 6-9 years in young adults.

OBJECTIVES: To describe associations between MRI markers with knee symptoms in young adults. METHODS: Knee symptoms were assessed using the WOMAC scale during the Childhood Determinants of Adult Health Knee Cartilage study (CDAH-knee; 2008-2010) and at the 6- to 9-year follow-up (CDAH-3; 2014-2019). Knee MRI scans obtained at baseline were assessed for morphological markers (cartilage volume, cartilage thickness, subchondral bone area) and structural abnormalities [cartilage defects and bone marrow lesions (BMLs)]. Univariable and multivariable (age, sex, BMI adjusted) zero-inflated Poisson (ZIP) regression models were used for analysis. RESULTS: The participants' mean age in CDAH-knee and CDAH-3 were 34.95 (s.d. 2.72) and 43.27 (s.d. 3.28) years, with 49% and 48% females, respectively. Cross-sectionally, there was a weak but significant negative association between medial femorotibial compartment (MFTC) [ratio of the mean (RoM) 0.99971084 (95% CI 0.9995525, 0.99986921), P < 0.001], lateral femorotibial compartment (LFTC) [RoM 0.99982602 (95% CI 0.99969915, 0.9999529), P = 0.007] and patellar cartilage volume [RoM 0.99981722 (95% CI 0.99965326, 0.9999811), P = 0.029] with knee symptoms. Similarly, there was a negative association between patellar cartilage volume [RoM 0.99975523 (95% CI 0.99961427, 0.99989621), P = 0.014], MFTC cartilage thickness [RoM 0.72090775 (95% CI 0.59481806, 0.87372596), P = 0.001] and knee symptoms assessed after 6-9 years. The total bone area was negatively associated with knee symptoms at baseline [RoM 0.9210485 (95% CI 0.8939677, 0.9489496), P < 0.001] and 6-9 years [RoM 0.9588811 (95% CI 0.9313379, 0.9872388), P = 0.005]. The cartilage defects and BMLs were associated with greater knee symptoms at baseline and 6-9 years. CONCLUSION: BMLs and cartilage defects were positively associated with knee symptoms, whereas cartilage volume and thickness at MFTC and total bone area were weakly and negatively associated with knee symptoms. These results suggest that the quantitative and semiquantitative MRI markers can be explored as a marker of clinical progression of OA in young adults.

Trends for opioid prescribing and the impact of the COVID-19 pandemic in patients with rheumatic and musculoskeletal diseases between 2006 and 2021.

OBJECTIVE: To investigate opioid prescribing trends and assess the impact of the COVID-19 pandemic on opioid prescribing in rheumatic and musculoskeletal diseases (RMDs). METHODS: Adult patients with RA, PsA, axial spondyloarthritis (AxSpA), SLE, OA and FM with opioid prescriptions between 1 January 2006 and 31 August 2021 without cancer in UK primary care were included. Age- and gender-standardized yearly rates of new and prevalent opioid users were calculated between 2006 and 2021. For prevalent users, monthly measures of mean morphine milligram equivalents (MME)/day were calculated between 2006 and 2021. To assess the impact of the pandemic, we fitted regression models to the monthly number of prevalent opioid users between January 2015 and August 2021. The time coefficient reflects the trend pre-pandemic and the interaction term coefficient represents the change in the trend during the pandemic. RESULTS: The study included 1 313 519 RMD patients. New opioid users for RA, PsA and FM increased from 2.6, 1.0 and 3.4/10 000 persons in 2006 to 4.5, 1.8 and 8.7, respectively, in 2018 or 2019. This was followed by a fall to 2.4, 1.2 and 5.9, respectively, in 2021. Prevalent opioid users for all RMDs increased from 2006 but plateaued or dropped beyond 2018, with a 4.5-fold increase in FM between 2006 and 2021. In this period, MME/day increased for all RMDs, with the highest for FM (≥35). During COVID-19 lockdowns, RA, PsA and FM showed significant changes in the trend of prevalent opioid users. The trend for FM increased pre-pandemic and started decreasing during the pandemic. CONCLUSION: The plateauing or decreasing trend of opioid users for RMDs after 2018 may reflect the efforts to tackle rising opioid prescribing in the UK. The pandemic led to fewer people on opioids for most RMDs, providing reassurance that there was no sudden increase in opioid prescribing during the pandemic.

High-fat diet causes endothelial dysfunction in the mouse ophthalmic artery.

Obesity is a significant health concern that leads to impaired vascular function and subsequent abnormalities in various organs. The impact of obesity on ocular blood vessels, however, remains largely unclear. In this study, we examined the hypothesis that obesity induced by high-fat diet produces vascular endothelial dysfunction in the ophthalmic artery. Mice were subjected to a high-fat diet for 20 weeks, while age-matched controls were maintained on a standard diet. Reactivity of isolated ophthalmic artery segments was assessed in vitro. Reactive oxygen species (ROS) were quantified in cryosections by dihydroethidium (DHE) staining. Redox gene expression was determined in ophthalmic artery explants by real-time PCR. Furthermore, the expression of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), the receptor for advanced glycation end products (RAGE), and of the lectin-like oxidized low-density-lipoprotein receptor-1 (LOX-1) was determined in cryosections using immunofluorescence microscopy. Ophthalmic artery segments from mice on a high-fat diet exhibited impaired vasodilation responses to the endothelium-dependent vasodilator acetylcholine, while endothelium-independent responses to nitroprusside remained preserved. DHE staining intensity in the vascular wall was notably stronger in mice on a high-fat diet. Messenger RNA expression for NOX2 was elevated in the ophthalmic artery of mice subjected to high fat diet. Likewise, immunostainings revealed increased expression of NOX2 and of RAGE, but not of LOX-1. These findings suggest that a high-fat diet triggers endothelial dysfunction by inducing oxidative stress in the ophthalmic artery via involvement of RAGE and NOX2.

Effect of Osteoporosis Treatments on Osteoarthritis Progression in Postmenopausal Women: A Review of the Literature.

PURPOSE OF REVIEW: The purpose of this literature review was to determine if medications used to treat osteoporosis are also effective for treating osteoarthritis (OA). RECENT FINDINGS: A total of 40 relevant articles were identified. Studies were categorized into those (1) discussing estrogen and selective estrogen receptor modulators (SERMs), (2) bisphosphonates, (3) parathyroid hormone (PTH) analogs, and (4) denosumab, and (5) prior review articles. A large amount of evidence suggests that estrogen and SERMs are effective at reducing OA symptoms and disease progression. Evidence suggests that bisphosphonates, the most common medications used to treat osteoporosis, can reduce OA symptoms and disease progression. In vivo studies suggest that PTH analogs may improve the cartilage destruction associated with OA; however, few human trials have examined its use for OA. Denosumab is approved to treat osteoporosis, bone metastases, and certain types of breast cancer, but little study has been done with respect to its effect on OA. The current evidence indicates that medications used to treat osteoporosis are also effective for treating OA. Estrogen, SERMs, and bisphosphonates have the most potential as OA therapies. Less is known regarding the effectiveness of PTH analogs and denosumab in OA, and more research is needed.

Oleanolic acid attenuates hydrogen peroxide-induced apoptosis of IPEC-J2 cells through suppressing c-Jun and MAPK pathway.

Oleanolic acid (OA) is a natural triterpenoid with therapeutic potential for a multitude of diseases. However, the precise mechanism by which OA influences stress-induced apoptosis of intestinal epithelial cells remains elusive. Therefore, the effect of OA on intestinal diseases under stressful conditions and its possible mechanisms have been investigated. In a hydrogen peroxide (H2 O2 )-induced oxidative stress model, OA attenuated H2 O2 -induced apoptosis in a concentration-dependent manner. To investigate the underlying mechanisms, the gene expression profile of OA on IPEC-J2 cells was analyzed using an RNA sequencing system. Results from gene ontology and Kyoto encyclopedia of genes and genomes analysis confirmed that OA may mitigate the cytotoxic effects of H2 O2 by downregulating gene expression through the MAPK signaling pathway. Furthermore, Quantitative real-time polymerase chain reaction results validated the differentially expressed genes data. Western blot analysis further demonstrated that OA effectively suppressed the expression level of c-Jun protein induced by H2 O2 in IPEC-J2 cells. Collectively, our results indicate that OA pretreatment significantly attenuated H2 O2 -induced apoptosis in intestinal epithelial cells through suppressing c-Jun and MAPK pathway.

Gold nanoparticles exhibit anti-osteoarthritic effects via modulating interaction of the "microbiota-gut-joint" axis.

Osteoarthritis (OA) is a common degenerative joint disease that can cause severe pain, motor dysfunction, and even disability. A growing body of research indicates that gut microbiota and their associated metabolites are key players in maintaining bone health and in the progression of OA. Short-chain fatty acids (SCFAs) are a series of active metabolites that widely participate in bone homeostasis. Gold nanoparticles (GNPs) with outstanding anti-bacterial and anti-inflammatory properties, have been demonstrated to ameliorate excessive bone loss during the progression of osteoporosis (OP) and rheumatoid arthritis (RA). However, the protective effects of GNPs on OA progression are not clear. Here, we observed that GNPs significantly alleviated anterior cruciate ligament transection (ACLT)-induced OA in a gut microbiota-dependent manner. 16S rDNA gene sequencing showed that GNPs changed gut microbial diversity and structure, which manifested as an increase in the abundance of Akkermansia and Lactobacillus. Additionally, GNPs increased levels of SCFAs (such as butyric acid), which could have improved bone destruction by reducing the inflammatory response. Notably, GNPs modulated the dynamic balance of M1/M2 macrophages, and increased the serum levels of anti-inflammatory cytokines such as IL-10. To sum up, our study indicated that GNPs exhibited anti-osteoarthritis effects via modulating the interaction of "microbiota-gut-joint" axis, which might provide promising therapeutic strategies for OA.

MicroRNA-mediated Krüppel-like factor 4 upregulation induces alternatively activated macrophage-associated marker and chemokine transcription in 4,4'-methylene diphenyl diisocyanate exposed macrophages.

1. Occupational exposure to 4,4'-methylene diphenyl diisocyanate (MDI) is associated with occupational asthma (OA) development. Alveolar macrophage-induced recruitment of immune cells to the lung microenvironment plays an important role during asthma pathogenesis. Previous studies identified that MDI/MDI-glutathione (GSH)-exposure downregulates endogenous hsa-miR-206-3p/hsa-miR-381-3p. Our prior report shows that alternatively activated (M2) macrophage-associated markers/chemokines are induced by MDI/MDI-GSH-mediated Krüppel-Like Factor 4 (KLF4) upregulation in macrophages and stimulates immune cell chemotaxis. However, the underlying molecular mechanism(s) by which MDI/MDI-GSH upregulates KLF4 remain unclear.2. Following MDI-GSH exposure, microRNA(miR)-inhibitors/mimics or plasmid transfection, endogenous hsa-miR-206-3p/hsa-miR-381-3p, KLF4, or M2 macrophage-associated markers (CD206, TGM2), and chemokines (CCL17, CCL22, CCL24) were measured by either RT-qPCR, western blot, or luciferase assay.3. MDI-GSH exposure downregulates hsa-miR-206-3p/hsa-miR-381-3p by 1.46- to 9.75-fold whereas upregulates KLF4 by 1.68- to 1.99-fold, respectively. In silico analysis predicts binding between hsa-miR-206-3p/hsa-miR-381-3p and KLF4. Gain- and loss-of-function, luciferase reporter assays and RNA-induced silencing complex-immunoprecipitation (RISC-IP) studies confirm the posttranscriptional regulatory roles of hsa-miR-206-3p/hsa-miR-381-3p and KLF4 in macrophages. Furthermore, hsa-miR-206-3p/hsa-miR-381-3p regulate the expression of M2 macrophage-associated markers and chemokines via KLF4.4. In conclusion, hsa-miR-206-3p/hsa-miR-381-3p play a major role in regulation of MDI/MDI-GSH-induced M2 macrophage-associated markers and chemokines by targeting the KLF4 transcript, and KLF4-mediated regulation in macrophages.

Proteomics Profiling of Human Synovial Fluid Suggests Increased Protein Interplay in Early-Osteoarthritis (OA) That Is Lost in Late-Stage OA.

The underlying molecular mechanisms in osteoarthritis (OA) development are largely unknown. This study explores the proteome and the pairwise interplay of proteins in synovial fluid from patients with late-stage knee OA (arthroplasty), early knee OA (arthroscopy due to degenerative meniscal tear), and from deceased controls without knee OA. Synovial fluid samples were analyzed using state-of-the-art mass spectrometry with data-independent acquisition. The differential expression of the proteins detected was clustered and evaluated with data mining strategies and a multilevel model. Group-specific slopes of associations were estimated between expressions of each pair of identified proteins to assess the co-expression (i.e., interplay) between the proteins in each group. More proteins were increased in early-OA versus controls than late-stage OA versus controls. For most of these proteins, the fold changes between late-stage OA versus controls and early-stage OA versus controls were remarkably similar suggesting potential involvement in the OA process. Further, for the first time, this study illustrated distinct patterns in protein co-expression suggesting that the interplay between the protein machinery is increased in early-OA and lost in late-stage OA. Further efforts should focus on earlier stages of the disease than previously considered.

Barriers and facilitators to implementation of an exercise and education programme for osteoarthritis: a qualitative study using the consolidated framework for implementation research.

Targeted efforts to better understand the barriers and facilitators of stakeholders and healthcare settings to implementation of exercise and education self-management programmes for osteoarthritis (OA) are needed. This study aimed to explore the barriers and facilitators to the implementation of Good Life with osteoArthritis in Denmark (GLA:D), a supervised group guideline-based OA programme, across Irish public and private healthcare settings. Interviews with 10 physiotherapists (PTs; 8 public) and 9 people with hip and knee OA (PwOA; 4 public) were coded by the Consolidated Framework for Implementation Research (CFIR) constructs in a case memo (summary, rationale, quotes). The strong positive/negative implementation determinants were identified collaboratively by rating the valence and strength of CFIR constructs on implementation. Across public and private settings, PTs and PwOA strongly perceived GLA:D Ireland as evidence-based, with easily accessible education and modifiable marketing/training materials that meet participants' needs, improve skills/confidence and address exercise beliefs/expectations. Despite difficulties in scheduling sessions (e.g., work/caring responsibilities), PTs in public and private settings perceived advantages to implementation over current clinical practice (e.g., shortens waiting lists). Only PTs in public settings reported limited availability of internal/external funding, inappropriate space, marketing/training tools, and inadequate staffing. Across public and private settings, PwOA reported adaptability, appropriate space/equipment and coaching/supervision, autonomy, and social support as facilitators. Flexible training and tailored education for stakeholders and healthcare settings on guideline-based OA management may promote implementation. Additional support on organising (e.g., scheduling clinical time), planning (e.g., securing appropriate space, marketing/training tools), and funding (e.g., accessing dedicated internal/external grants) may strengthen implementation across public settings.

Metabolic syndrome increases osteoarthritis risk: findings from the UK Biobank prospective cohort study.

OBJECTIVE: The association between Metabolic Syndrome (MetS), its components, and the risk of osteoarthritis (OA) has been a topic of conflicting evidence in different studies. The aim of this present study is to investigate the association between MetS, its components, and the risk of OA using data from the UK Biobank. METHODS: A prospective cohort study was conducted in the UK Biobank to assess the risk of osteoarthritis (OA) related to MetS. MetS was defined according to the criteria set by the International Diabetes Federation (IDF). Additionally, lifestyle factors, medications, and the inflammatory marker C-reactive protein (CRP) were included in the model. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). The cumulative risk of OA was analyzed using Kaplan-Meier curves and log-rank tests. To explore potential nonlinear associations between MetS components and OA risk, a restricted cubic splines (RCS) model was employed. In addition, the polygenic risk score (PRS) of OA was calculated to characterize individual genetic risk. RESULTS: A total of 45,581 cases of OA were identified among 370,311 participants, with a median follow-up time of 12.48 years. The study found that individuals with MetS had a 15% higher risk of developing OA (HR = 1.15, 95%CI:1.12-1.19). Additionally, central obesity was associated with a 58% increased risk of OA (HR = 1.58, 95%CI:1.5-1.66), while hyperglycemia was linked to a 13% higher risk (HR = 1.13, 95%CI:1.1-1.15). Dyslipidemia, specifically in triglycerides (HR = 1.07, 95%CI:1.05-1.09) and high-density lipoprotein (HR = 1.05, 95%CI:1.02-1.07), was also found to be slightly associated with OA risk. When stratified by PRS, those in the high PRS group had a significantly higher risk of OA compared to those with a low PRS, whereas no interaction was found between MetS and PRS on OA risks. Furthermore, the presence of MetS significantly increased the risk of OA by up to 35% in individuals with elevated CRP levels (HR = 1.35, 95% CI:1.3-1.4). CONCLUSION: MetS and its components have been found to be associated with an increased risk of OA, particularly in individuals with elevated levels of CRP. These findings highlight the significance of managing MetS as a preventive and intervention measure for OA.

Transcriptomics Analysis of the Immune Effects of Okadaic Acid on Caco-2 Cells.

Okadaic Acid, a type of diarrhetic shellfish poison, is widely distributed and harmful, causing symptoms such as diarrhea, vomiting, and more in humans. Recent studies have demonstrated that OA can lead to various toxicities such as cytotoxicity, neurotoxicity, embryotoxicity, and hepatotoxicity. In order to investigate the immunotoxicity of OA on intestinal cells, a transcriptome analysis was conducted to compare the differences in the Caco-2 cell transcriptional group before and after administration. The CCK-8 experiment demonstrated that OA had a detrimental effect on the activity of Caco-2 cells, with an IC50 value of 33.98 nM. Transcriptome data revealed changes in immune-related genes between the experimental and control groups, including inflammatory factors, heat shock proteins, and zinc finger proteins. The analysis of the results suggests that OA can induce the production of inflammatory factors and apoptosis in cells, and may also affect cell ferroptosis. These findings indicate that OA has a significant impact on intestinal immunity, providing valuable insights for the study of immune toxicity associated with OA.