Genetic Association of Juvenile Idiopathic Arthritis With Adult Rheumatic Disease.

Importance: Patients with juvenile idiopathic arthritis (JIA) may develop adult rheumatic diseases later in life, and prolonged or recurrent disease activity is often associated with substantial disability; therefore, it is important to identify patients with JIA at high risk of developing adult rheumatic diseases and provide specialized attention and preventive care to them.

Objective: To elucidate the full extent of the genetic association of JIA with adult rheumatic diseases, to improve treatment strategies and patient outcomes for patients at high risk of developing long-term rheumatic diseases.

Design, Setting, And Participants: In this genetic association study of 4 disease genome-wide association study (GWAS) cohorts from 2013 to 2024 (JIA, rheumatoid arthritis [RA], systemic lupus erythematosus [SLE], and systemic sclerosis [SSc]), patients in the JIA cohort were recruited from the US, Australia, and Norway (with a UK cohort included in the meta-analyzed cohort), while patients in the other 3 cohorts were recruited from US and Western European countries.

Rat Models in Post-Traumatic Stress Disorder Research: Strengths, Limitations, and Implications for Translational Studies.

Post-Traumatic Stress Disorder (PTSD) is a multifaceted psychiatric disorder triggered by traumatic events, leading to prolonged psychological distress and varied symptoms. Rat models have been extensively used to explore the biological, behavioral, and neurochemical underpinnings of PTSD. This review critically examines the strengths and limitations of commonly used rat models, such as single prolonged stress (SPS), stress-re-stress (S-R), and predator-based paradigms, in replicating human PTSD pathology.

Favorable long-term outcomes of autoimmune nodopathy with mycophenolate mofetil.

Autoimmune nodopathy (AN) is a rare immune-mediated neuropathy characterized by autoantibodies against nodal or paranodal proteins. Patients with AN generally respond poorly to immunoglobulin therapy, and as a newly defined condition, there are currently no established treatment guidelines. Although rituximab shows potential as a therapeutic option, its high cost, limited availability, and the need for infusion monitoring hinder its use as a first-line treatment in many countries.

Microcystin-LR induces neuronal damage through mitophagy defects resulted from the downregulated transcription of Scd2 by directly targeting IGF-1R.

Microcystin-LR (MC-LR), a prevalent cyanotoxin present in hazardous cyanobacterial blooms, is recognized as a neurotoxic environmental pollutant that induces brain damage and neurobehavioral deficits. However, the mechanisms underlying MC-LR-induced neurotoxicity remain unclear. This study aims to elucidate the role of mitophagy in MC-LR-induced neurotoxicity both in vitro and in vivo.

Regulation of pathway choice in DNA repair after double-strand breaks.

DNA damage signaling is a highly coordinated cellular process which is required for the removal of DNA lesions. Amongst the different types of DNA damage, double-strand breaks (DSBs) are the most harmful type of lesion that attenuates cellular proliferation. DSBs are repaired by two major pathways-homologous recombination (HR), and non-homologous end-joining (NHEJ) and in some cases by microhomology-mediated end-joining (MMEJ).

MS4A superfamily molecules in tumors, Alzheimer's and autoimmune diseases.

MS4A (membrane-spanning 4-domain, subfamily A) molecules are categorized into tetraspanins, which possess four-transmembrane structures. To date, eighteen MS4A members have been identified in humans, whereas twenty-three different molecules have been identified in mice. MS4A proteins are selectively expressed on the surfaces of various immune cells, such as B cells (MS4A1), mast cells (MS4A2), macrophages (MS4A4A), Foxp3CD4 regulatory T cells (MS4A4B), and type 3 innate lymphoid cells (TMEM176A and TMEM176B).

Impact of repeat human leukocyte antigen mismatches on kidney graft survival: A contemporary Collaborative Transplant Study analysis.

Repeat human leukocyte antigen (HLA) mismatches (RMM) have been historically associated with an increased risk of graft loss after repeat kidney transplantation, in particular HLA-DR RMM in sensitized recipients. As routine use of sensitive assays can at present prevent the transplantation of RMM in hosts with donor-specific antibodies, we hypothesized that RMM would no longer be associated with graft loss. We performed a registry analysis of the Collaborative Transplant Study database including 6711 patients who received a second kidney transplant (KT) between 2010 and 2021, with at least 1 HLA-A, HLA-B, or HLA-DR mismatch.

Enhanced engraftment of human haematopoietic stem cells via mechanical remodelling mediated by the corticotropin-releasing hormone.

The engraftment of haematopoietic stem and progenitor cells (HSPCs), particularly in cord-blood transplants, remains challenging. Here we report the role of the corticotropin-releasing hormone (CRH) in enhancing the homing and engraftment of human-cord-blood HSPCs in bone marrow through mechanical remodelling. By using microfluidics, intravital two-photon imaging and long-term-engraftment assays, we show that treatment with CRH substantially enhances HSPC adhesion, motility and mechanical remodelling, ultimately leading to improved bone-marrow homing and engraftment in immunodeficient mice.

Inter-chromosomal transcription hubs shape the 3D genome architecture of African trypanosomes.

The eukaryotic nucleus exhibits a highly organized 3D genome architecture, with RNA transcription and processing confined to specific nuclear structures. While intra-chromosomal interactions, such as promoter-enhancer dynamics, are well-studied, the role of inter-chromosomal interactions remains poorly understood. Investigating these interactions in mammalian cells is challenging due to large genome sizes and the need for deep sequencing.

Influence of Newborns' Sex on Minor and Trace Element Concentrations in Human Milk During Early Lactation.

This study aimed to investigate the influence of newborns' sex on the concentrations of minor and trace elements in the human milk of lactating mothers during early lactation. The elemental analysis focused on calcium (Ca), potassium (K), sodium (Na), and chlorine (Cl) as minor elements and iodine (I), aluminum (Al), bromine (Br), and rubidium (Rb) as trace elements. Breast milk samples were collected from 75 lactating mothers in Tehran, Iran, during the early feeding stage.

Structured Polymers Enable the Sustained Delivery of Glucocorticoids within the Intra-Articular Space.

Intra-articular glucocorticoid injections are effective in controlling inflammation and pain in arthritides but restricted by short duration of action and risk of joint degeneration. Controlled drug release using biocompatible hydrogels offers a unique solution, but limitations of in situ gelation restrict their application. Gellan sheared hydrogels (GSHs) retain the advantages of hydrogels, however their unique microstructures lend themselves to intra-articular application - capable of shear thinning under force but restructuring at rest to enhance residence.

InTraSeq: A Multimodal Assay that Uncovers New Single-Cell Biology and Regulatory Mechanisms.

Single-cell RNA sequencing (scRNA-seq) has revolutionized cell biology by enabling the profiling of transcriptomes at a single-cell resolution, leading to important discoveries that have advanced our understanding of cellular and tissue heterogeneity, developmental trajectories, and disease progression. Despite these important advances, scRNA-seq is limited to measuring the transcriptome providing a partial view of cellular function. To address this limitation, multimodal scRNA-seq assays have emerged, allowing for the simultaneous measurement of RNA expression and protein.

Ubiquitin-Conjugating Enzyme Ubc13 in Macrophages Suppresses Lung Tumor Progression Through Inhibiting PD-L1 Expression.

Tumor cell-intrinsic ubiquitin-conjugating enzyme Ubc13 promotes tumorigenesis, yet how Ubc13 in immune cell compartments regulates tumor progression remains elusive. Here, we show that myeloid-specific deletion of Ubc13 (Ubc13Lyz2) leads to accelerated transplanted lung tumor growth in mice. Compared with their littermate controls, tumor-bearing Ubc13Lyz2 mice had lower proliferation and effector function of CD8 T lymphocytes, accompanied by increased infiltration of myeloid-derived suppressor cells within the tumor microenvironment.

Dura immunity configures leptomeningeal metastasis immunosuppression for cerebrospinal fluid barrier invasion.

The cerebrospinal fluid (CSF) border accommodates diverse immune cells that permit peripheral cell immunosurveillance. However, the intricate interactions between CSF immune cells and infiltrating cancer cells remain poorly understood. Here we use fate mapping, longitudinal time-lapse imaging and multiomics technologies to investigate the precise origin, cellular crosstalk and molecular landscape of macrophages that contribute to leptomeningeal metastasis (LM) progression.

Traumatic brain Injury: Comprehensive overview from pathophysiology to Mesenchymal stem Cell-Based therapies.

Traumatic brain injury (TBI) is a disastrous phenomenon which is considered to cause high mortality and morbidity rate. Regarding the importance of TBI due to its prevalence and its effects on the brain and other organs, finding new therapeutic methods and improvement of conventional therapies seems to be vital. TBI involves a complex physiological mechanism, with inflammation being a key component among various contributing factors.

Protocol for isolating extracellular vesicles from alveolar macrophages phagocytosing MRSA in vitro cell culture models.

Extracellular vesicles (EVs) play a crucial role in delivering bioactive cargo in infectious diseases. Here, we present a protocol for isolating EVs from alveolar macrophages (AMs) that phagocytose methicillin-resistant Staphylococcus aureus (MRSA) in vitro cell culture models. We describe steps for bacterial preparation; infection of AMs with MRSA; and isolation, purification, and characterization of EVs.

Basement membranes' role in immune cell recruitment to the central nervous system.

Basement membranes form part of the extracellular matrix (ECM), which is the structural basis for all tissue. Basement membranes are cell-adherent sheets found between cells and vascular endothelia, including those of the central nervous system (CNS). There is exceptional regional specialisation of these structures, both in tissue organisation and regulation of tissue-specific cellular processes.

Effect of synthesis strategies on morphology and antibacterial properties and photocatalytic activity of graphitic carbon nitride (g-CN).

Different morphologies of graphitic carbon nitride (g-CN), including bulk g-CN(B-CN), ultrathin nanosheet g-CN(N-CN), and porous g-CN(P-CN) were synthesized through a facile one-step approach. They were then employed as efficient photocatalysts under visible light to degrade methylene blue and deactivate() and() bacteria. The synthesized powders were characterized using various industry standard techniques and field emission scanning electron microscopy (SEM) analysis successfully represented the various morphologies of g-CN.

Polymorphisms within genes encoding Ikaros family proteins IKZF1 and IKZF3 in multiple myeloma patients treated with thalidomide.

Background: Multiple myeloma (MM) is a hematological malignancy characterized by the presence of abnormal plasma cells. It is associated with anemia, bone lesions and renal dysfunction. Immunomodulatory drugs (IMiDs) are commonly used in MM treatment.

Persistent Epstein-Barr Virus Infection of Epithelial Cells Leads to APOBEC3C Expression and Induces Mitochondrial DNA Mutations.

Upon infection with the virus, cells increase the expression of cytidine deaminase APOBEC3 family genes. This leads to the accumulation of C-to-T mutations in the replicating viral genome and suppresses viral propagation. In contrast, herpesviruses, including Epstein-Barr virus (EBV), express genes that counteract APOBEC3 during lytic infection.

Investigating the link between Helicobacter pylori infection and psoriatic disease: an immunological study.

Helicobacter pylori (Hp) has been postulated as an infectious trigger of psoriatic disease, namely psoriasis (Ps) and psoriatic arthritis (PsA), but meticulous antibody (ab) reactivity against all dominant and subdominant Hp antigens in demographically matched PsA and Ps patients and healthy controls has not been performed so far. IgG anti-Hp ab testing was performed by combining immunoblotting and line assays in 263 serum samples from 89 patients with PsA, 114 patients with Ps, and 60 demographically matched healthy controls (HCs). Anti-Hp positivity did not differ between PsA, Ps, and HCs (P > 0.