Bowel obstruction due to post-sclerotherapy inflammation and hemorrhage in a mesenteric lymphatic malformation: a case report

Bisphenol S and high-fat diet drive structural and inflammatory remodeling of the colon in C57Bl/6 male mice.

Dietary N-acetylneuraminic acid maintains intestinal homeostasis and protects against aging- and inflammation-associated colonic dysfunction.

Ginsenoside Rb1 downregulates proinflammatory cytokines expression via the Tlr2/Tlr4 signaling pathway in mice with experimental autoimmune myocarditis.

The 2022 global Mpox outbreak was characterised byprominent cutaneous and mucocutaneous findings, often with significant associated pain, that posed uniquechallenges for clinicians. To date, there are no known effective treatments that reduce time to lesion resolution. Although clade IIb Mpox is generally milder than endemic forms, this outbreak was notable for localized lesions to head, genital or perianal skin as a result of direct inoculation, often with co-infection of other sexually transmitted infections. Bacterial superinfection is among the most common complications of Mpox infection, and can increase the risk of long-term scarring. Complications and more severe illness are more frequent in patients with advanced HIV and low CD4 + T cell count. Excellent supportive care for the diverse cutaneous lesions of Mpox is critical to reducethe risk of complications and long-term sequelae of infection. The identification of therapeutics that lead to rapidlesion resolution and reduce local pain and inflammation associated with infection could further improve outcomes.

Acute "in vivo" LPS causes an early presynaptic C1q and C3 accumulation and increases the "prunability" of cortical synaptosomes.

Connecting the dots: Gouty arthritis, clonal haematopoiesis and myeloid activation, in a unified inflammation model for atherosclerosis progression.

Peripheral nerve stimulation offers a promising alternative to pharmacological treatments for chronic pain, and recent advances in direct current stimulation enable selective inhibition of nociceptive activity. However, the safety of direct current delivery systems, particularly soft, metal-free nerve cuffs, remains poorly characterized under pathological conditions. This study evaluated the safety and biocompatibility of a silicone tripolar cuff for ionic direct current delivery in naïve rats and rodent models of neuropathic (spared nerve injury) and inflammatory (complete Freund's adjuvant) pain. The cuff was implanted around the sciatic nerve and evaluated through behavioral testing (von Frey and Hargreaves), magnetic resonance imaging, and immunohistochemistry of the sciatic nerve, dorsal root ganglia, and spinal cord. In naïve cohorts, both short- and long-term implantation did not alter behavior outcomes, and neither disease model showed worsening of pain sensitivity. Across implanted groups, markers associated with immune activation and fibrotic encapsulation were upregulated. Notably, only the implanted spared nerve injury cohort exhibited additional pathological changes, including T cell infiltration in the sciatic nerve and dorsal root ganglia, elevated satellite glial and astrocytic responses, and significant interaction between injury and implantation. Demyelination and C-fiber loss were observed in spared nerve injury cohort irrespective of cuff placement, consistent with baseline injury-driven pathology. These findings indicate that the soft, metal-free cuff is well tolerated in healthy and inflammatory pain conditions but may exacerbate local inflammation and tissue changes when implanted near nerve injury. This supports its potential use in chronic pain management when implantation is distal to local injury site. PERSPECTIVE: This study provides the first comprehensive safety assessment of a soft, metal-free nerve cuff for iDC delivery in healthy and pathological pain models. This work advances iDC as a potential treatment for chronic pain, and helps identify pathological conditions in which invasive cuff implantation could exacerbate existing nerve injury.

Isoliquiritigenin restores bone homeostasis in osteoporotic rats by enhancing BMSCs osteogenesis via ERK1/2-mTOR-HIF-1α-glycolytic axis and suppressing inflammation.

Selenium-albumin corona rinse ameliorates diabetic periodontitis by inhibiting inflammation, anti-bacterial and improving osteogenesis via activating TrxR1/ROS/β-catenin anti-oxidation cascade.

Coronary inflammation: Identification, clinical impact and possible therapeutical solutions.

Intradermal application of lipopolysaccharide (LPS), a Toll-like receptor 4 agonist, induces a local inflammatory response and is used as a human challenge model to evaluate the pharmacodynamics of investigational medicinal products. While currently applied in a single, parallel-group setting, alternative within-subject designs involving repeated LPS challenges at different skin sites and spaced across multiple timepoints would enable within-subject comparisons, potentially reducing inter-individual variability in pharmacodynamic assessments. We aimed to determine whether intradermal LPS challenges at different sites on the back, with 14-day intervals, would be an optimal design for clinical pharmacology studies. Eight healthy volunteers received seven 5-ng intradermal LPS injections: six on the back on Days 1, 15 and 29 (two per day) and one on the volar forearm on Day 1. Local inflammation was assessed via non-invasive imaging (skin perfusion and erythema) and suction blister fluid (cytokines and leukocytes) at 10- and 24 h post-injection. Systemic responses were evaluated through blood cytokine and leukocyte levels. Repeated intradermal LPS challenges were well tolerated. Skin perfusion, erythema and local cytokine and chemokine levels were similar across challenges. However, on subsequent challenge days there were shifts in vascular responses and counts of classical monocyte, and other leukocytes in blister fluid were reduced at 10 h on Day 15 compared to Day 1. The results indicate that following Day 1 intradermal LPS challenges, a subtle immune adaptation may occur, potentially limiting the model's reliability for cellular endpoint-focused within-subject pharmacological investigations.

Ureteral stents are among the most frequently used devices in urology, yet their high susceptibility to biofilm and encrustation continues to evade current surface-coating strategies. The development of emerging coatings faces significant challenges due to the complex physiological environment of the urinary tract, featuring high salinity, continuous shear stress, fluctuating pH, and microbial contamination. Here, we report an effective anti-fouling and anti-encrustation surface-engineering strategy by developing a coating from intrinsically disordered protein condensates of fused in sarcoma (FUS) protein (IDPFUS) and applying it to ureteral stents via a polydopamine-assisted two-step modified method. The IDPFUS-modified surface exhibited markedly enhanced hydrophilicity and demonstrated strong resistance to nonspecific protein adsorption, urinary tract infection-related bacteria adhesion, and ureteral epithelial cell attachment, significantly outperforming the benchmark polyethylene glycol (PEG) coating. In a rat model of infection-induced urolithiasis, the IDPFUS coating reduced stent encrustation by over 80% compared to clinical polyurethane and Percuflex™ stents, and markedly mitigated local tissue inflammation. Mechanistically, IDPFUS is thought to form a hydrating, densely entangled network through coacervation, which can help minimize surface contamination. This dynamic network could also inhibit stone nucleation near the stent surfaces by regulating local pH and ionic strength through charge neutralization and non-ionic interactions. These findings address the long-standing challenge of biofilm and encrustation on urinary implants by leveraging the integrated capabilities of IDPFUS condensate, including strong hydration, fouling resistance, and dynamic buffering, highlighting its translational potential for use in complex biofluids. STATEMENT OF SIGNIFICANCE: Ureteral stent encrustation remains a major clinical problem that is inadequately addressed by current hydrophilic coatings in the challenging urinary environment. This work introduces a bioinspired anti-encrustation coating made from intrinsically disordered proteins that forms highly hydrated, tightly tangled networks. Unlike conventional materials, this protein-based layer can spontaneously coacervate and locally regulate pH and ionic strength, preventing the initial attachment of proteins, bacteria and cells, while reducing stone formation. By demonstrating over 80% reduction of infection-induced encrustation compared with clinical stents, this study establishes intrinsically disordered proteins as a promising class of functional biomaterials with broad potential for improving urinary implants and other medical devices exposed to harsh biological environments.

Colorectal cancer remains a major global health burden and an area of urgent unmet medical need. Immunotherapy has shown limited success in colorectal cancer as most patients present with an immune-excluded, "cold" tumor microenvironment (TME). In this study, we report a dual-modality approach to treating colorectal cancer by combining the tumor necrosis factor (TNF)-based fusion protein directed to the extradomain B (EDB) of fibronectin, L19-TNF, which induces localized intratumoral inflammation and facilitates T-cell infiltration, with a CD3-based bispecific T-cell engager (TCE) targeting carcinoembryonic antigen (CEA), which mediates antigen-specific cytotoxicity. Together, these agents aim to remodel the TME, convert "cold" tumors into inflamed "hot" lesions, and broaden the therapeutic reach of immunotherapy in colorectal cancer. Immunohistochemistry confirmed coexpression of CEA and EDB across microsatellite-stable and -instable tumors. In vitro, L19-TNF in combination with a CEAxCD3 TCE significantly enhanced tumor cell killing and CD8+ T-cell proliferation. In vivo, the combination induced complete tumor regression in most animals, prolonged survival, and conferred durable protection against tumor rechallenge. Furthermore, mechanistic analyses revealed enhanced TCE extravasation, upregulated intercellular adhesion molecule 1 expression, and increased CD8+ T-cell infiltration, indicating vascular modulation and remodeling of the TME toward an inflamed "hot" phenotype. These findings confirm that targeted delivery of TNF to the TME can effectively enhance the activity of immunotherapeutic agents, such as T cell-redirecting therapies, in challenging tumor settings.

Raillietiella orientalis (Ro) is a parasitic pentastome with a rapidly expanding geographic and herpetofaunal host range in the southeastern USA since its introduction, probably with the invasive Burmese python (Python bivittatus). However, little is known about the health impacts of Ro infection in native USA host species. Pygmy rattlesnakes (Sistrurus miliarius), small pit vipers native to the southeastern USA, were among the first documented naïve hosts of Ro in Florida, USA. Between December 2018 and February 2019, 17 free-ranging S. miliarius from central Florida were evaluated for Ro pentastomiasis and comorbidities. Necropsy revealed Ro pentastomiasis in eight (47%) rattlesnakes confirmed by morphologic and molecular methods. Pygmy rattlesnakes harbored more Ro pentastomes (mean) than documented in Burmese pythons in southern Florida; moreover, the mean length of mature female Ro in S. miliarius was greater than in pythons, suggesting altered host-parasite interactions in this naïve host. Microscopically, localized inflammation and parasitic hematin deposition were associated with Ro in respiratory and coelomic tissues. All 17 snakes (100%) had both fungal dermatitis consistent with ophidiomycosis and mixed endoparasitism; other findings included two (12%) snakes with ferlaviral pneumonia and one (6%) with gastric cryptosporidiosis. This study shows that although lesions directly attributable to Ro in S. miliarius were mild, mixed-pathogen coinfections were common, highlighting the need for further study of potential host health and fitness impacts in native Florida snakes.

Peripheral inflammation is known to enhance pain sensitivity through nociceptive pathways, but its impact on large-diameter myelinated fibers, which mediate touch and proprioception, is less understood. Here, we examined the temporal dynamics of large fiber (Aα/β) excitability in a mouse model of Complete Freund's Adjuvant (CFA)-induced hind paw inflammation, integrating behavioral, electrophysiological, proteomic, and immune analyses. CFA induced a biphasic modulation of large fiber function, with early hypoexcitability on day 1 followed by hyperexcitability on day 7, temporally aligned with thermal hypersensitivity. Proteomic analysis of sciatic nerve tissue on day 7 revealed upregulation of immune-related proteins, including CD45, providing proteomic evidence of local nerve inflammation. Systemic cytokines and paw skin thrombin activity showed transient elevations at early time points. In vitro, lipopolysaccharide-stimulated Schwannoma-derived cells modulated thrombin activity and altered expression of complement- and inflammation-associated genes. These findings demonstrate that peripheral inflammation dynamically modulates large fiber excitability alongside intrinsic neural and systemic immune responses, highlighting the importance of considering multi-level neuro-immune interactions in models of peripheral nerve function.

Sjögren's disease (SjD) causes localized and systemic inflammation and autoantibody production against intracellular proteins such as TRIM21/Ro52 (tripartite motif-containing protein 21). TRIM21, an E3 ubiquitin ligase, binds antibody Fc domains on opsonized pathogens that have escaped extracellular immunity and entered the cytosol. TRIM21 then ubiquitinates these pathogens, driving their proteasomal degradation. How TRIM21 becomes an autoantigen remains unclear. We show that TRIM21 is released upon lytic cell death (pyroptosis or necroptosis) but not apoptosis. Although many cytosolic proteins are released by dead cells, liberated TRIM21 is distinct: Its high antibody affinity enables binding to Fc domains of circulating immunoglobulins, forming large immune complexes (ICs). These ICs increase in SjD, where anti-TRIM21 autoantibodies interact with released TRIM21 via Fc and F(ab')2. TRIM21 ICs are taken up by macrophages, which drive proinflammatory responses, antigen presentation, and metabolic changes in high interferon environments. Thus, TRIM21 may perpetuate inflammation and autoantigen presentation, resulting in high immunogenicity.

Implant-associated infections present a major clinical challenge, as orthopedic implants are required to both suppress bacterial infection and support subsequent bone regeneration. Herein, a mechanically adaptive auxetic titanium scaffold integrated with a lattice-modulated piezocatalytic coating is developed for infected bone repair. A titanium scaffold with a negative Poisson's ratio structure demonstrates uniform stress distribution under compression. It prolongs fluid residence time by creating complex flow paths, which is favorable for interaction with surrounding bone tissue. Additionally, a potassium sodium niobate (KNN) piezoelectric coating with strontium (Sr) incorporated as a lattice dopant is constructed on the scaffold surface. Strontium doping restructures the electromechanical landscape of KNN, amplifying its piezoelectric response and piezocatalytic reactivity, which underpins potent antibacterial efficacy. Concurrently, the osteogenic bioactivity imparted by Sr enables robust osseointegration and bone regeneration. In a rabbit femoral condyle infected bone defect repairment, the piezo-coated auxetic scaffold achieves suppression of local infection and inflammation after 1 week of ultrasound treatment. Subsequently, enhanced osseointegration and bone regeneration are observed, accompanied by improved hindlimb strength and motor coordination. This work establishes a multifunctional implant paradigm that couples mechanical adaptation with lattice-modulated piezocatalysis, enabling synergistic infection eradication and bone regeneration.

Multi-omics analyses reveal a rhamnogalacturonan I (RG-I) from Polygonum aviculare ameliorates nephrolithiasis through regulation of the gut-kidney axis.

Chronic diabetic wounds complicated by biofilm infections resist healing because persistent bacterial colonization coexists with microenvironmental imbalances, including oxidative stress and inflammation. Conventional pharmacotherapy and wound care are limited by impaired local perfusion, which hinders both effective biofilm eradication and reversal of the pathological wound microenvironment. We developed an ultrasound-activated core-shell microneedle platform (CCA&Lut@MN) that combines sonodynamic gas cascade antimicrobial therapy with a ROS-responsive microenvironment modulation strategy. Upon ultrasonic stimulation, L-arginine-modified copper-cysteine nanoparticles (CCA) in the microneedle shell generate reactive oxygen species (ROS) and catalyze NO release from L-Arg, producing synergistic oxidative and nitrative stress that yields rapid bactericidal activity and effective biofilm eradication. The microneedle core consists of an ROS-responsive PVA-HP-luteolin hydrogel that degrades in response to elevated ROS in the microenvironment, releasing luteolin. Luteolin scavenges excess ROS and promotes macrophage polarization to the M2 phenotype, thereby enhancing angiogenesis and cell migration. In a diabetic rat wound model infected with MRSA, CCA&Lut@MN markedly reduced wound bacterial load, alleviated local inflammation and improved blood supply, and thereby accelerated wound healing. This microneedle platform produces synergistic antibacterial effects via sonodynamic therapy (SDT)-gas cascade reactions, modulates the pathological microenvironment, and improves local blood supply, offering a promising strategy for treating complex and refractory wounds.