Prevalence and clinical features of interstitial lung disease in patients with psoriasis.

Background: Despite the autoimmune nature of psoriasis, the potential association between psoriasis and interstitial lung disease (ILD) remains underexplored. This study aimed to investigate the frequency and clinical features of ILD in patients with psoriasis and propose a new conceptual framework of "ILD associated with psoriasis".

Methods: A retrospective analysis of 117 patients with psoriasis was conducted, excluding those without chest imaging prior to methotrexate or biologic use and those with other comorbidities leading to ILD.

Staphylococcus aureus-specific skin resident memory T cells protect against bacteria colonization but exacerbate atopic dermatitis-like flares in mice.

Background: The contribution of Staphylococcus aureus to the exacerbation of atopic dermatitis (AD) is widely documented, but its role as a primary trigger of AD skin symptoms remains poorly explored.

Objectives: This study sought to reappraise the main bacterial factors and underlying immune mechanisms by which S aureus triggers AD-like inflammation.

Methods: This study capitalized on a preclinical model, in which different clinical isolates were applied in the absence of any prior experimental skin injury.

B-cell immune dysregulation with low soluble CD22 levels in refractory seronegative myasthenia gravis.

Myasthenia gravis (MG), primarily caused by acetylcholine receptor (AChR) autoantibodies, is a chronic autoimmune disorder causing severe muscle weakness and fatigability. In particular, seronegative MG constitutes 10%-15% of MG cases and presents diagnostic challenges especially in early-onset female patients who often show severe disease and resistance to immunosuppressive therapy. Furthermore, the immunopathology of seronegative MG remains unclear.

Inflammatory loops in the epithelial-immune microenvironment of the skin and skin appendages in chronic inflammatory diseases.

The epithelial-immune microenvironment (EIME) of epithelial tissues has five common elements: (1) microbial flora, (2) barrier, (3) epithelial cells, (4) immune cells, and (5) peripheral nerve endings. EIME provides both constant defense and situation-specific protective responses through three-layered mechanisms comprising barriers, innate immunity, and acquired immunity. The skin is one of the largest organs in the host defense system.

Alopecia areata: What's new in the epidemiology, comorbidities, and pathogenesis?

Background: Alopecia areata (AA) is a common, acquired, and nonscarring type of hair loss that affects people of every generation and is intractable in severe and relapsing cases. Patients with AA, especially those with greater scalp involvement, have poor health-related quality-of-life scores.

Purpose: Following our previous review article in the April 2017 issue of the Journal of Dermatological Science, we aim to provide a pair of review articles on recent progress in multidisciplinary approaches to AA.

Endoscopic-assisted Surgical Removal of Infected Interosseous Wires 40 Years After Mandibular Surgery.

We demonstrate a highly reliable minimally invasive treatment for removal of residual wire from the mandible. The patient was a 55-year-old Japanese man who was referred to our department for a fistula in his submental area. The patient had undergone open reduction and fixation with wires for mandibular fractures (left parasymphysis, right angle fracture) more than 40 years prior and mandibular tooth extraction and drainage 6 months prior.

Single-cell analysis of human skin identifies CD14+ type 3 dendritic cells co-producing IL1B and IL23A in psoriasis.

Inflammatory skin diseases including atopic dermatitis (AD) and psoriasis (PSO) are underpinned by dendritic cell (DC)-mediated T cell responses. Currently, the heterogeneous human cutaneous DC population is incompletely characterized, and its contribution to these diseases remains unclear. Here, we performed index-sorted single-cell flow cytometry and RNA sequencing of lesional and nonlesional AD and PSO skin to identify macrophages and all DC subsets, including the newly described mature LAMP3+BIRC3+ DCs enriched in immunoregulatory molecules (mregDC) and CD14+ DC3.

Net Effects of NETs: New Concepts.

It is challenging to investigate neutrophil extracellular traps (NETs) and bacterial colonization in vivo. Bitschar et al. (2020) oppose an existing paradigm regarding neutrophils in host defense and propose that neutrophils increase Staphylococcus aureus skin colonization through NETs, not by trapping microbes but via indirect mechanisms.

Discovery of a novel B-cell lymphoma 6 (BCL6)-corepressor interaction inhibitor by utilizing structure-based drug design.

B-cell lymphoma 6 (BCL6) is a transcriptional repressor that can form complexes with corepressors via protein-protein interactions (PPIs). The complexes of BCL6 and corepressors play an important role in the formation of germinal centers (GCs), and differentiation and proliferation of lymphocytes. Therefore, BCL6-corepressor interaction inhibitors would be drug candidates for managing autoimmune diseases and cancer.

Mechanisms of inhibitory action of TRK-130 (Naltalimide), a μ-opioid receptor partial agonist, on the micturition reflex.

Purpose: To clarify the mechanism of inhibitory action of TRK-130 (Naltalimide), a unique µ-opioid receptor partial agonist, on the micturition reflex.

Methods: The effect of TRK-130 on isovolumetric rhythmic bladder contractions (RBCs) was examined in guinea pigs, the effect of which was clarified by co-treatment with naloxone or in spinal cord transection. The effect of TRK-130 on urodynamic parameters was also observed in guinea pigs.

Design of cyclic RGD-conjugated Aib-containing amphipathic helical peptides for targeted delivery of small interfering RNA.

To achieve the targeted delivery of siRNA, five conjugates of Aib-containing amphipathic helical peptides with mono-, di-, and trivalent cRGDfC [cyclo(-Arg-Gly-Asp-d-Phe-Cys-)], which is known to bind to αVβ3 integrin, at several positions of the amphipathic helical peptide were designed and synthesized. Among the five conjugates, the monovalent cRGDfC conjugating at position 20 of the amino acid sequence of the helical peptide through the formation of a disulfide bond (PI) and the divalent cRGDfC conjugating at positions 2 and 14 of the amino acid sequence of the helical peptide through the formation of disulfide bonds (PIII) significantly enhanced the delivery of fluorescence-labeled siRNA into A549 cells as the peptide/siRNA complex formed by electrostatic interaction. The cellular uptake of the PI/siRNA complex was mediated by both endocytic and non-endocytic pathways, whereas that of the PIII/siRNA complex was enabled by endocytosis.

Activation of peripheral KCNQ channels attenuates inflammatory pain.

Background: Refractory chronic pain dramatically reduces the quality of life of patients. Existing drugs cannot fully achieve effective chronic pain control because of their lower efficacy and/or accompanying side effects. Voltage-gated potassium channels (KCNQ) openers have demonstrated their analgesic effect in preclinical and clinical studies, and are thus considered to be a potential therapeutic target as analgesics.

A channelopathy contributes to cerebellar dysfunction in a model of multiple sclerosis.

Objective: Cerebellar dysfunction in multiple sclerosis (MS) contributes significantly to disability, is relatively refractory to symptomatic therapy, and often progresses despite treatment with disease-modifying agents. We previously observed that sodium channel Nav1.8, whose expression is normally restricted to the peripheral nervous system, is present in cerebellar Purkinje neurons in a mouse model of MS (experimental autoimmune encephalomyelitis [EAE]) and in humans with MS.

High-frequency stimulation in the ventral posterolateral thalamus reverses electrophysiologic changes and hyperalgesia in a rat model of peripheral neuropathic pain.

Chronic neuropathic pain is associated with long-term changes at multiple levels of the neuroaxis, including in the brain, where electrical stimulation has been used to manage severe pain conditions. However, the clinical outcome of deep brain stimulation is often mixed, and the mechanisms are poorly understood. By means of electrophysiologic methods, we sought to characterize the changes in neuronal activity in the ventral posterolateral nucleus of the thalamus (VPL) in a rat model of peripheral neuropathic pain, and to reverse these changes with low-voltage, high-frequency stimulation (HFS) in the VPL.

Ear pain and its treatment in hypobaric chamber training in the Japan Air Self-Defense Force.

Background: We have documented that ear pain is the most prevalent physiologic incident during hypobaric chamber training in the Japan Air Self-Defense Force. Ear pain may increase also in flight in the future because it is closely related to allergic rhinitis. Therefore, it is very important to know the characteristic of ear pain and the efficacy of its treatment.

Allergic rhinitis and ear pain in flight.

Background: Ear pain is the most common physiologic incident in hypobaric chamber training in the Japan Air Self-Defense Force, and the incidence of ear pain has been gradually increasing. There has been a concomitant increase in the incidence of allergic rhinitis in Japan. We hypothesized that the increased incidence of ear pain may be due to the increased incidence of eustachian tube dysfunction associated with allergic rhinitis.

Synthesis of (R)-(+)-tanikolide through stereospecific C-H insertion reaction of dichlorocarbene with optically active secondary alcohol derivatives.

Stereospecific alpha C-H insertion reaction of protected chiral 1,2-glycols, (S)-1,2-isopropylidenedioxytridecane (3) and ethyl (S)-4,5-isopropylidenedioxy-pentanoate (4), prepared from (R)-glyceraldehyde acetonide (2), with dichlorocarbene generated from CHCl(3)/50% NaOH/cetyltrimethylammonium chloride (as ptc.) took place with complete retention of configuration to provide (S)-4-dichloromethyl-2,2-dimethyl-4-undecyl-1,3-dioxolane (5) and ethyl (S)-3-(4-dichloromethyl-2,2-dimethyl-1,3-dioxolan-4-yl)-propanoate (8), respectively. The ester (8) was transformed to 5 by elongation of the side chain.