Induction of interleukin 21 receptor expression via enhanced intracellular metabolism in B cells and its relevance to the disease activity in systemic lupus erythematosus.

Objective: To elucidate the association between the changes in intracellular metabolism in the early stage of B cell activation and systemic lupus erythematosus (SLE) pathogenesis.

Methods: CD19 or CD19CD27 (naïve) cells from the peripheral blood of healthy controls and lupus patients were cultured under different stimuli. The changes in intracellular metabolism and signalling pathways in these cells were evaluated.

The abundance of regulatory T cell subsets is associated with the clinical outcomes of sarcoidosis.

Objectives: Some patients with sarcoidosis achieve spontaneous remission, whereas others repeatedly experience relapse. We examined differences in the clinical course of active sarcoidosis according to peripheral blood immunophenotypes before treatment.

Methods: This retrospective study compared peripheral blood immunophenotypes between patients with active sarcoidosis (n=28) and healthy control subjects (n=10).

Predictors of the effectiveness to first-line CTLA4-Ig in patients with rheumatoid arthritis: the FIRST registry.

Objectives: This study aimed to elucidate which bio-naïve patients with rheumatoid arthritis (RA) are suitable for treatment with CTLA4-Ig.

Methods: This study enrolled 953 patients with RA who were administered their first biological disease-modifying antirheumatic drug (CTLA4-Ig, n = 328; tumour necrosis factor inhibitor [TNFi], n = 625) from July 2013 to August 2022. The primary outcome was the Clinical Disease Activity Index (CDAI) remission rate at week 24 in each group, adjusted using Propensity Score-based Inverse Probability of Treatment Weighting (PS-IPTW).

Efficacy, safety, and optimal intervention of belimumab for proliferative lupus nephritis patients in real-world settings: LOOPS registry.

Objectives: This study investigated the efficacy, safety, and predictive factors of belimumab (BEL) in induction therapy for patients with proliferative lupus nephritis (LN) in real-world settings.

Methods: Patients with biopsy-proven ISN/RPS class III or IV LN, with or without coexisting class V LN, who underwent standard of care (SoC), glucocorticoid (GC), and either mycophenolate mofetil or cyclophosphamide treatments were included. Participants were treated with SoC (SoC group, n = 32) or BEL and SoC (BEL+SoC group, n = 30).

Long-term safety and efficacy of anti-TNF multivalent VHH antibodies ozoralizumab in patients with rheumatoid arthritis.

Objectives: This study aimed to evaluate the long-term safety and efficacy profiles of ozoralizumab in patients with rheumatoid arthritis (RA) from the OHZORA, NATSUZORA and HOSHIZORA trials.

Methods: This study conducted an integrated analysis of the three trials. Patients who completed the OHZORA trial with concomitant treatment of ozoralizumab and methotrexate (MTX) or the NATSUZORA trial without MTX were eligible to participate in the long-term extension HOSHIZORA trial.

Efficacy and Safety of Biologics in Polymyalgia Rheumatica: A Retrospective Study.

Introduction: The study aimed to determine the efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) in the treatment of polymyalgia rheumatica (PMR) complicated by rheumatoid arthritis (RA).

Methods: Patients with PMR which could be classified as RA and who were treated with bDMARDs were included in the analysis. The primary endpoint was the clinical Polymyalgia Rheumatica Activity Score (Clin-PMR-AS) after 26 weeks of treatment, and the secondary endpoint was adverse events during the observation period.

Oxygenation and Carbon Dioxide Rebreathing of a Well-fitting Non-rebreathing EcoLite™ Mask with a Reservoir: A Single-center Prospective Observational Study in Healthy Volunteers.

Background: The fitting of oxygen mask affects the performance of it such as oxygenation or CO₂ elimination. The intersurgical EcoLite™ adult high-concentration oxygen mask (EcoLite with a reservoir, Intersurgical, UK) was developed to give well-fitting. The purpose of this study is to evaluate the performance of EcoLite with a reservoir compared to the conventional mask.

Comparison of anti-IL-6 receptor and JAK inhibitors in patients with rheumatoid arthritis from the real-world practice FIRST study.

Objectives: A molecular-targeted drug that is suitable as the second choice for patients with rheumatoid arthritis (RA) who show an inadequate response to the first biological disease-modifying antirheumatic drug (bDMARD) is unknown. This study aimed to analyze the efficacy and safety of interleukin-6 receptor (IL-6Ri) and Janus kinase inhibitors (JAKis), often selected as molecular-targeted drugs for second or subsequent treatments.

Methods: The efficacy and safety of JAKis and IL-6Ri were compared using propensity score-based inverse probability of treatment weighting (PS-IPTW) using propensity scores after 26 weeks of therapy in patients with RA.

Exclusion of sulfide:quinone oxidoreductase from mitochondria causes Leigh-like disease in mice by impairing sulfide metabolism.

Leigh syndrome is the most common inherited mitochondrial disease in children and is often fatal within the first few years of life. In 2020, mutations in the gene encoding sulfide:quinone oxidoreductase (SQOR), a mitochondrial protein, were identified as a cause of Leigh syndrome. Here, we report that mice with a mutation in the gene encoding SQOR (SqorΔN/ΔN mice), which prevented SQOR from entering mitochondria, had clinical and pathological manifestations of Leigh syndrome.

CT informs detection and treatment options in rheumatoid arthritis complicated by pulmonary non-tuberculous mycobacterial disease from the FIRST registry.

Objective: To investigate the early detection of pulmonary non-tuberculous mycobacterial (PNTM) disease by CT before the initiation of molecular-targeted therapeutic drugs in patients with rheumatoid arthritis (RA) and the efficacy and safety of combined treatment with antibiotics.

Methods: Patients with RA underwent chest CT before the introduction of molecular-targeted therapies in the Further Improvement of Rheumatoid arthritis Treatment registry. The primary endpoint was the number of patients who were detected by CT as having PNTM disease, complicating RA.

Understanding the effects of ethanol on the liposome bilayer structure using microfluidic-based time-resolved small-angle X-ray scattering and molecular dynamics simulations.

Lipid nanoparticles (LNPs) are essential carrier particles in drug delivery systems, particularly in ribonucleic acid delivery. In preparing lipid-based nanoparticles, microfluidic-based ethanol injection may produce precisely size-controlled nanoparticles. Ethanol is critical in LNP formation and post-treatment processes and affects liposome size, structure, lamellarity, and drug-loading efficiency.

Isolation of Cationic η-Allenylnickel(II) Key Intermediate Complexes: Origins of Enantioselectivity and Regioselectivity in Nickel(0)-Catalyzed Asymmetric Propargylic Substitutions.

Herein, we report the synthesis and isolation of cationic η-allenylnickel(II) complexes that bear -BINAP as a bidentate ligand for the first time via MeSiOTf-promoted C-O bond cleavage of propargylic -butyl carbonate. In contrast, in the presence of the monodentate phosphine ligand PEt, treatment of propargylic -butyl carbonate with Ni(cod) resulted in a gradual C-O bond cleavage leading to η-allenylnickel(II) complexes, i.e.

Light-controllable cell-membrane disturbance for intracellular delivery.

Highly polar and charged molecules, such as oligonucleotides, face significant barriers in crossing the cell membrane to access the cytoplasm. To address this problem, we developed a light-triggered twistable tetraphenylethene (TPE) derivative, TPE-C-N, to facilitate the intracellular delivery of charged molecules through an endocytosis-independent pathway. The central double bond of TPE in TPE-C-N is planar in the ground state but becomes twisted in the excited state.

pSPICA Force Field Extended for Proteins and Peptides.

Many coarse-grained (CG) molecular dynamics (MD) studies have been performed to investigate biological processes involving proteins and lipids. CG force fields (FFs) in these MD studies often use implicit or nonpolar water models to reduce computational costs. CG-MD using water models cannot properly describe electrostatic screening effects owing to the hydration of ionic segments and thus cannot appropriately describe molecular events involving water channels and pores through lipid membranes.

Improved Protein Model in SPICA Force Field.

The previous version of the SPICA coarse-grained (CG) force field (FF) protein model focused primarily on membrane proteins and successfully reproduced the dimerization free energies of several transmembrane helices and the stable structures of various membrane protein assemblies. However, that model had limited accuracy when applied to other proteins, such as intrinsically disordered proteins (IDPs) and peripheral proteins, because the dimensions of the IDPs in an aqueous solution were too compact, and protein binding on the lipid membrane surface was overstabilized. To improve the accuracy of the SPICA FF model for the simulation of such systems, in this study, we introduce protein secondary structure-dependent nonbonded interaction parameters to the backbone segments and reoptimize almost all nonbonded parameters for amino acids.

Extracting immunological and clinical heterogeneity across autoimmune rheumatic diseases by cohort-wide immunophenotyping.

Objective: Extracting immunological and clinical heterogeneity across autoimmune rheumatic diseases (AIRDs) is essential towards personalised medicine.

Methods: We conducted large-scale and cohort-wide immunophenotyping of 46 peripheral immune cells using Human Immunology Protocol of comprehensive 8-colour flow cytometric analysis. Dataset consisted of >1000 Japanese patients of 11 AIRDs with deep clinical information registered at the FLOW study, including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).

Generation-Dependent Retention Rates and Reasons for Discontinuation of Molecular Targeted Therapies in Patients with Rheumatoid Arthritis: From FIRST Registry.

Introduction: The study aimed to optimize medical care for elderly patients with rheumatoid arthritis (RA) by examining the 3-year continuation rate of different molecular targeted therapies across age groups in Japan, which has a significant elderly population.

Methods: The study included patients with RA who started molecular targeted therapies between 2013 and 2019 and divided them into three age groups. The primary outcome was to assess the 3-year continuation rate of each drug and analyze reasons for treatment discontinuation using inverse probability of treatment weighting.