Musculoskeletal manifestations of acute pancreatitis are uncommon and are most frequently described as pancreatic panniculitis or pancreatic panniculitis-polyarthritis (PPP) syndrome. Diffuse inflammatory myositis with fascial involvement is exceedingly rare and may mimic cellulitis, pyomyositis, septic arthritis, necrotizing fasciitis, or deep venous thrombosis, leading to diagnostic uncertainty and potentially unnecessary surgical intervention. A 44-year-old man presented with severe epigastric pain radiating to the back for 15 days, followed by fever and rapidly progressive painful swelling of the left thigh, knee, and leg. Serum lipase was elevated (867 U/L). Contrast-enhanced computed tomography (CECT) demonstrated acute necrotizing pancreatitis with <30% pancreatic necrosis, multiple acute necrotic collections, a modified CT severity index (MCTSI) of 8/10, and partial thrombosis of the splenic, superior mesenteric, and portal veins. Venous Doppler excluded deep venous thrombosis. Magnetic resonance imaging (MRI) of the thigh and knee revealed diffuse multicompartment inflammatory myositis, extensive fascial fluid tracking, diffuse subcutaneous panniculitis, and mild knee joint effusion without osteomyelitis or drainable abscess. Knee ultrasonography showed quadriceps edema with mild suprapatellar effusion. Synovial fluid analysis demonstrated a leukocyte count of only 250 cells/mm[3], while blood and urine cultures remained sterile. Based on the clinicoradiological findings and exclusion of infection, a diagnosis of pancreatic enzyme-mediated lower limb myositis, fasciitis, panniculitis, and sterile reactive synovitis was made. The patient was treated conservatively with supportive care for acute pancreatitis, therapeutic anticoagulation for splanchnic venous thrombosis, analgesia, nutritional support, and physiotherapy, resulting in progressive clinical recovery without surgical intervention. This case expands the recognized musculoskeletal spectrum of acute pancreatitis by demonstrating extensive MRI-confirmed myositis, fasciitis, panniculitis, and sterile synovitis occurring concurrently with necrotizing pancreatitis and splanchnic venous thrombosis. Recognition of this rare entity is essential because it closely mimics soft tissue infection but responds to treatment directed at the underlying pancreatic disease. Multimodality imaging and careful exclusion of infective etiologies are critical to establishing the diagnosis and avoiding unnecessary operative management.

Hydrogel dressings that can simultaneously curb infection and dampen inflammation are particularly attractive for accelerating multidrug-resistant bacteria-infected wound healing. However, clinical translation of many reported hydrogels is often constrained by multi-component formulations, complicated preparation procedures, and insufficient sprayability, which limit conformal coverage on irregular wound beds. Polyitaconate possesses intrinsic antibacterial and anti-inflammatory activities, yet its weak antioxidative properties and lack of thermogelling properties limit its utility in infected wound healing. In this study, we develop a curcumin-modified polyitaconate-based hydrogel (FPIC) that integrates antibacterial, anti-inflammatory, and antioxidant properties. FPIC hydrogel exhibits thermoresponsive gelation, injectability, sprayability, and shear-thinning properties, allowing convenient close contact with complex wound geometries. FPIC hydrogel inhibits bacterial growth, moderates excessive inflammatory responses, and eliminates reactive oxygen species while promoting angiogenesis, thereby facilitating the shift from the inflammatory phase to the proliferative phase of healing. Moreover, FPIC hydrogel enhances collagen deposition, speeds re-epithelialization, and supports balanced tissue remodeling, enabling improved skin regeneration with a lower propensity for fibrosis. These findings establish FPIC hydrogel as a multifunctional and highly bioactive polyitaconate-based hydrogel dressing with strong promise for treating infection- and inflammation-associated wounds and advancing toward clinical use.

Despite decades of intensive investigation, rheumatoid arthritis (RA) remains a therapeutic challenge, primarily attributed to its intricate pathological microenvironment and poorly elucidated etiology. However, mitochondrial dysfunction and abnormal activation of the cGAS-STING signaling pathway play a key role in RA. Herein, we report mitochondria targeted biomimetic nanovesicles (SS31-CB@MM-FNVs/CLT) for the targeted therapy of RA. SS31-CB@MM-FNVs/CLT is constructed by macrophage membrane fusion nanovesicles, which are encapsulated with celastrol (CLT) and functionalized with the chitosan-bilirubin (CS-BR) conjugate and SS-31 peptide. SS31-CB@MM-FNVs/CLT bypasses immune surveillance and prolongs circulatory persistence through macrophage membrane fusion, targets macrophage mitochondria by CS and SS-31 peptide decoration, and scavenges reactive oxygen species (ROS), activates autophagy, and repolarizes macrophages from the M1 to M2 subtypes through the synergistic effects of bilirubin, celastrol, and the nanoplatform. In general, SS31-CB@MM-FNVs/CLT exhibits therapeutic efficacy in vitro and in vivo by scavenging ROS, inhibiting the STING pathway, and enhancing autophagy, thereby regulating macrophage polarization. Taken together, this biomimetic nanoplatform provides a promising basis for safer and more potent therapeutic interventions.

Inflammatory arthritis is a chronic immune disorder characterized by synovial inflammation, pain, and progressive joint destruction, yet most current therapies focus on the regulation of a single pathological process or symptom. In the present work, we report the establishment of self-assembled strontium-caffeic acid nanoparticles (CA-Sr NPs) through metal-polyphenol coordination, which function as an integrated neuro-immune-bone modulator for inflammatory arthritis therapy. By coupling redox catalysis with TRPV1-associated Ca2+ antagonism and Sr2+-enabled osteoregulation, CA-Sr NPs exhibit combined effects of sustained reactive oxygen species scavenging and enhanced regulation of the Ca2+-permeable TRPV1 channel on macrophages and dorsal root ganglion (DRG) neurons, thus repolarizing macrophages from M1 to M2 phenotype and suppressing the pathological Ca2+ influx and neuronal hyperexcitability, respectively. Meanwhile, CA-Sr NPs promote osteoblast activity while inhibiting osteoclast differentiation. In the Complete Freund's Adjuvant-induced murine arthritis model, CA-Sr NPs markedly alleviated multiple inflammatory arthritis symptoms, including joint swelling, pain, and bone erosion. Collectively, this study highlights highly promising therapeutic potentials of CA-Sr NPs for inflammatory arthritis management and broadens the scope of metal-phenolic nanocatalysts toward treating neuro-immune-bone disorders.

The terminal differentiation of osteoblasts into osteocytes, the most abundant cell type in cortical bone, is critical for skeletal homeostasis. Osteocyte loss is a hallmark of bone aging and fragility, yet the mechanisms regulating osteocyte formation and survival are poorly understood. We show that inactivation of fibroblast growth factor receptor 1 (Fgfr1) in the mature osteoblast lineage results in extensive osteocyte death, identifying FGFR1 signaling as essential for osteocyte viability and bone integrity. Lineage tracing and analysis of endogenous and induced appositional bone formation revealed that newly embedded osteocytes fail to survive without FGFR1. These osteocytes exhibited ectopic expression of osteocalcin and podoplanin within sclerostin-positive, TUNEL-reactive lacunae, along with defective dendrite formation and disruption of the local lacunocanalicular network. RNA sequencing of cortical bone demonstrated reduced expression of extracellular matrix (ECM) genes and neuronal regulatory genes, while histological and ultrastructural analyses showed disorganized collagen fibrils, diminished osteoid, and abnormal mineralization. In vitro, FGF signaling in Ocy454 cells regulated gene programs involved in development, axon guidance, and bone ECM organization, highlighting a dual function for FGF signaling in which it controls both matrix-dependent and intrinsic cell differentiation mechanisms during the osteoblast-to-osteocyte transition. We propose that FGFR1 deficiency causes ECM disorganization and impaired dendrite formation, disrupting osteocyte communication with neighboring bone and vascular cells, ultimately leading to cell death. These findings establish FGFR signaling as a critical regulator of osteocyte differentiation, viability of bone-embedded osteocytes, and bone homeostasis.

Emerging evidence links reactive oxygen species modulator 1 (ROMO1), a key mitochondrial ROS regulator, to rheumatoid arthritis (RA) pathogenesis. However, its exact mechanism remains elusive given the conflicting evidence about its specific function. We used a four-level integrative framework combining multi-omics data and literature‑supported mechanistic inference. At the genetic level, Mendelian randomization (MR) was performed to explore potential causal relationships between ROMO1, IL2RA, HLA-DR, MIF, and RA risk, followed by differential expression analysis and machine learning-based feature selection to identify key mROS genes. The temporal expression dynamics of ROMO1 were assessed in RA progression. At the cellular and tissue levels, we integrated single-cell RNA sequencing and spatial transcriptomics to map cell-type-specific expression and synovial localization of ROMO1-related immune cells and pathways. Finally, our multi-omics findings were contextualized with literature-supported mechanistic inference. (1) MR results were consistent with a potential protective effect of ROMO1 on RA (OR = 0.52) and its potential regulation of risk factors IL2RA (OR = 0.46) and HLA-DR (OR = 0.40). Conversely, IL2RA (OR = 1.42), HLA-DR (OR = 1.88), and MIF (OR = 1.17) were positively associated with RA risk. Additionally, ROMO1 was identified as a top candidate diagnostic predictor with stage-specific dynamics: downregulated in the early but upregulated in the late/remission stages. (2) Single-cell RNA sequencing showed ROMO1's cell-specific expression in CD14+ HLA-DR+ CD74+ monocytes and CD4+ IL2RA+ T cells. Cell communication analysis further suggested that these cells may participate in MIF pathway regulation. Spatial transcriptomics subsequently identified that ROMO1-related cells localized to synovial pathological regions, with MIF pathway changes correlated with RA progression. (3) Finally, literature-supported mechanistic inference suggests that ROMO1 may modulate mROS levels to promote anti-inflammatory M2 macrophage polarization, which could theoretically contribute to reduced systemic inflammation and the alleviation of multi-organ decline in RA. This integrated multi-omics investigation, supported by literature-based mechanistic inference, suggests ROMO1 as a stage-dependent biomarker candidate and potential immune regulator in RA.

Rheumatoid arthritis (RA) is a chronic autoimmune systemic inflammatory condition that significantly damages bone and cartilage, leading to severe joint deformities. Matrix metalloproteinase(s) (MMP-9) plays a significant role in both the pathogenesis and management of RA, and its status as a biomarker and a target for inhibition is important in understanding and treating the disease. This work aims to examine the interactions between the molecules of MMP-9 and bioactive compounds derived from marine algae using molecular docking and absorption, distribution, metabolism, excretion, and toxicity investigations. Docking results were assessed using Glide gscore, the top 5 compounds (6,6-Bieckol, Dieckol, Lophocladine B, Sargachromanol E, and Porphyran) docked against protein receptors were chosen. The selected compounds had binding affinities that varied from -8.523 to -6.327 kcal/mol, and the selected compounds also had undergone absorption, distribution, metabolism, excretion, and toxicity analysis. Density functional theory analysis was conducted against finalized compound, Lophocladine B, with HOMO-LUMO gaps of 4.235 and 5.275 eV, respectively, confirming electronic stability and binding-relevant reactive sites consistent with its predicted MMP-9 inhibition. It was discovered that only Lophocladine B met the selection criteria, so this compound was subjected to molecular dynamics simulations for stability analysis. Moreover, the docking studies were supported by redocking validation of the native inhibitor, heavy-atom root mean square deviation, benchmarking with a known inhibitor, and molecular dynamics simulations along with a replication run. The results of the study imply that these substances might ultimately be employed to treat rheumatoid arthritis. Although this study only included computer validations, in vitro investigations are needed to convert these potential inhibitors into medicinal products.

Postoperative infection is a rare but serious complication following anterior cruciate ligament reconstruction (ACLR). This review integrates current epidemiological trends, risk factors, and novel diagnostic and therapeutic approaches reported in the existing literature. The estimated incidence of septic arthritis (SA) after ACLR typically ranges from 0.14% to 2.6%. Male sex, smoking, hamstring autograft use, diabetes mellitus, and elevated body mass index (BMI) were identified as risk factors in earlier studies. Intraoperative presoaking of the graft in vancomycin, known as the 'vancomycin wrap' technique, has reduced infection rates and improved prophylactic practice. Diagnosis relies on patient history, physical assessment, and laboratory findings, including synovial fluid analysis and C-reactive protein (CRP). Management often involves urgent arthroscopic debridement and individualized antibiotic treatment, with the primary aim of preserving the ACL graft. Although graft retention is successful in many cases, persistent infection may require graft removal, which is associated with poorer outcomes.

Chronic, low-grade systemic inflammation is a polygenic trait captured with the INFLA-score, a composite of C-reactive protein, platelet count, leukocyte count, and granulocyte-to-lymphocyte ratio. We derived a polygenic risk score from the INFLA-score (iPRS) in a multi-ancestry population from the UK Biobank (n=421,368), then evaluated and used it in a phenome-wide association study among participants in the All of Us Research Program (AoU). The multi-ancestry iPRS was tested for association with the INFLA-score in AoU (N=4,833 with biomarker data) via linear regression, adjusting for age, sex, and genetically-determined principal components (PCs) and with 2,821 phecodeX-defined phenotypes in AoU (N=265,068) via logistic regression, adjusting for sex, age, EHR length, race, ethnicity and PCs. The iPRS predicted the INFLA-score (R-squared=0.026, beta=0.980, p<2x10[-16]) and was associated with 47 phenotypes (Bonferroni-corrected p<0.05). The strongest associations were with blood-related phenotypes: elevated white blood cell count (OR=1.19, p=3.85x10[-66]), thrombocytopenia (OR=0.86, p=5.70x10[-44]), platelet defects (OR=0.86, p=2.47x10[-43]), neutropenia (OR= 0.86, p=5.52x10[-18]), myeloproliferative disorder (OR= 1.2, p=2.77x10[-15]). Others included celiac disease (OR=0.713, p=2.98x10[-46]), ankylosing spondylitis (OR=1.4, p=1.33 x 10[-17]), hypertension (OR=1.04, p=4.56x10[-15]), rheumatoid arthritis (OR=1.09, p=1.02x10[-13]), hematuria (OR=1.05, p=1.96x10[-10]). Removing major-histocompatibility-complex SNPs abolished associations with known autoimmune diseases, while all other associations remained. We replicated 17 (42.5%) of 40 significant phenotypes available in the Vanderbilt University Medical Center's BioVU. Our findings demonstrate that systemic inflammation can be predicted using the iPRS across multiple ancestries, and the iPRS is associated with numerous clinical endpoints. This multi-ancestry iPRS may have future utility in stratifying risk for inflammation-driven conditions across diverse populations.