Accepted

Pain, a complex subjective experience, is common in care home residents. Despite advances in pain management, optimal pain control remains a challenge. In this updated systematic review, we examined effectiveness of interventions for treating chronic pain in care home residents.

Enhancer of zeste homolog 2 (EZH2) has been noted to contribute to the pathogenesis of autoimmune diseases. This study sought to investigate the mechanism of EZH2 in osteoclast (OCL) and osteoblast (OBL) differentiation (OCLD/OBLD) and bone destruction in RA. The animal model of collagen-induced arthritis (CIA) was established, followed by arthritis index (AI) scoring and histological staining, and measurements of inflammatory cytokines levels. The number of OCLs was detected via Tartrate-resistant acid phosphatase (TRAP) staining, and levels of OBL markers were determined by Western blot analysis. Trimethylated histone H3 at lysine 27 (H3K27me3) expression and its enrichment in the Ndrg2 promoter were detected. Collaborative experiments were performed with GSK-J1 or sh-Ndrg2 in CIA mice with EZH2 knockdown. EZH2 was upregulated while Ndrg2 was downregulated in knee joint tissues of CIA mice. Silencing EZH2 reduced AI scores, pathological injury of the knee joint, levels of inflammatory cytokines, and TRAP-positive cells, and increased protein levels of RUNX2 and BMP2. EZH2 promoted H3K27me3 level in the Ndrg2 promoter to inhibit Ndrg2 transcription. H3K27me3 upregulation or Ndrg2 downregulation reversed the role of silencing EZH2 in bone destruction. Overall, EZH2 repressed OBLD and promoted OCLD to aggravate bone destruction in CIA mice through H3K27me3/Ndrg2.

We predicted that chronic pain patients have a more negative stress mindset and a lower level of social identification than people without chronic pain and that this, in turn, influences well-being through less adaptive coping. 1240 participants (465 chronic pain patients; 775 people in the control group) completed a cross-sectional online-survey. Chronic pain patients had a more negative stress mindset and a lower level of social identification than people without chronic pain. However, a positive stress mindset was linked to better well-being and fewer depressive symptoms, through the use of the adaptive coping behaviors positive reframing and active coping. A higher level of social identification did not impact well-being or depression through the use of instrumental and emotional support coping, but through the more frequent use of positive reframing and active coping. For chronic pain therapy, we propose including modules that foster social identification and a positive stress mindset.

Low back pain is the most common health problem with a prevalence of over 80% worldwide and an estimated annual cost of $100 billion in the United States. Intervertebral disc degeneration accounts for a major cause of low back pain. However, there is still a lack of safe and effective treatment to tackle this devastating condition. In this study, we synthesized four functionalized trimetallic nitride endohedral metallofullerenes (carboxyl-f-ScN@C, carboxyl-f-GdN@C, amino-f-ScN@C, and amino-f-GdN@C) and characterized them with X-ray photoelectron spectroscopy, matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and UV-vis. Via electron paramagnetic resonance, all four metallofullerene derivatives possessed dose-dependent radical scavenging capabilities (hydroxyl radicals and superoxide anions), with the most promising radical scavenging properties shown in the amine functionalized C metallofullerenes. Both amino-f-ScN@C and amino-f-GdN@C at 1 μM significantly reduced lipopolysaccharide induced reactive oxygen species production and mRNA expressions of pro-inflammatory mediators (, , , and ) in macrophages without apparent cytotoxicity through regulating activity of p38 MAPK, p65, and nuclear translocation of NF-κB. Furthermore, in an established mouse model of lumbar radiculopathy, amino-f-ScN@C and amino-f-GdN@C effectively alleviated ipsilateral mechanical hyperalgesia for up to 2 weeks. In dorsal root ganglia explant culture, we also showed that amino-f-ScN@C and amino-f-GdN@C ameliorated TNF-α elicited neuroinflammation. In summary, we presented results for a potent radical scavenging, anti-inflammatory and analgesic nanoparticle, amino-functionalized eighty-carbon metallofullerenes and . Our study provides important assets for developing pleiotropic treatment strategies to tackle the inflammation, a significant pathological hallmark in the intervertebral disc degeneration and associated pain.

Atopic dermatitis (AD) is a chronic, heterogenous, inflammatory skin disorder associated with a high skin-related health burden, typically starting in childhood and often persisting into adulthood. AD is characterized by a wide range of clinical phenotypes, reflecting multiple underlying pathophysiological mechanisms and interactions between genetics, immune system dysregulation, and environmental factors. In this review, we describe the diverse cellular and molecular mechanisms involved in AD, including the critical role of T cell-driven inflammation, primarily via T helper (Th) 2- and Th17-derived cytokines, many of which are mediated by the Janus kinase (JAK) signaling pathway. These local inflammatory processes interact with sensory neuronal pathways, contributing to the clinical manifestations of AD, including itch, pain, and sleep disturbance. The recent elucidation of the molecular pathways involved in AD has allowed treatment strategies to evolve from broad-acting systemic immunosuppressive therapies to more targeted agents, including JAK inhibitors and cytokine-specific biologic agents. Evidence from the clinical development of these targeted therapies has reinforced and expanded our understanding of the pathophysiological mechanisms underlying AD and holds promise for individualized treatment strategies tailored to specific AD subtypes.