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Skin aging is a multifaceted process influenced by genetic, environmental, and immunological factors, resulting in visible changes such as wrinkles, pigmentation, and alterations in skin texture. Despite its high relevance, there is a paucity of large-scale studies focusing on visible age-related changes in facial skin among Japanese populations, particularly by region. This study aims to address these gaps by examining age- and sex-specific skin changes in a large cohort of 2,543 Japanese subjects using advanced skin imaging techniques. The study included subjects aged 17–71 years who provided informed consent. The imaging system captures facial images using standard light, UV light, and two types of polarized light, applying deep learning techniques to analyze various skin parameters. Statistical analysis was performed to evaluate correlations between age, gender, and skin characteristics. Results indicated significant correlations between age and skin color across all domains, with large pores on the nose showing the highest correlation with age. Sebum and porphyrin levels exhibited a decreasing trend with age, though correlation coefficients were low. Cheek gloss, both in area and color, showed relatively high correlation coefficients. Pigmentation-related items, such as spots and melanin, demonstrated significant age correlations, particularly in areas like the corners of the eyes, under the eyes, and cheeks. Wrinkles and fine wrinkles correlated with age in various regions, though not on the forehead. The findings highlight the importance of understanding regional and demographic variations in skin aging to develop effective anti-aging treatments.

Abstract Background Psoriasis is a chronic skin inflammatory disease characterized by epidermal proliferation and inflammatory cell infiltration. AXL is a tyrosine kinase receptor that promotes cell proliferation and invasion in cancer cells, and its expression is elevated in multiple tumors. However, less is known about its expression and function in inflammatory diseases. Objectives The aim of this study is to examine AXL expression in psoriasis and investigate the biological function of AXL under psoriatic conditions. Results AXL mRNA expression was decreased in psoriatic skin compared to healthy skin, and an inverse correlation with neutrophil‐to‐lymphocyte ratio and platelet‐to‐lymphocyte ratio was observed. Immunohistochemical staining of psoriatic skin revealed decreased AXL expression of the epidermis and an increased number of AXL‐positive dendritic cells in the dermis. Stimulation of epidermal keratinocytes with antimicrobial peptide LL37, but not with IL‐17A, resulted in decreased AXL expression. Knockdown of AXL in epidermal keratinocytes did not affect cell proliferation or expression of psoriasis‐associated cytokines and chemokines. Conclusion Decreased epidermal AXL expression and increased infiltration of AXL‐expressing dendritic cells were revealed in psoriasis.

IntroductionAs a form of precision medicine, this study aimed to investigate the specific patient population that would derive the greatest benefit from tildrakizumab, as well as the mechanism of action and efficacy of tildrakizumab in reducing the occurrence of psoriatic arthritis (PsA).MethodsTo achieve this, a multi-center, prospective cohort study was conducted, involving a population of 246 psoriasis patients who had not received any systemic therapy or topical finger therapy between January 2020 and April 2023. Two independent clinicians, who were blinded to the study, analyzed nailfold capillary (NFC) abnormalities, such as nailfold bleeding (NFB) and enlarged capillaries, as well as the incidence of new PsA. Additionally, the factors that determined the response of psoriasis after seven months of tildrakizumab treatment were examined. The study also examined the quantity and role of regulatory T cells (Tregs) and T helper 17 cells both pre- and post-treatment.ResultsThe severity of psoriasis, as measured by the Psoriasis Area and Severity Index (PASI), was found to be more pronounced in the tildrakizumab group (n=20) in comparison to the topical group (n=226). At 7 months after tildrakizumab treatment, multivariate analysis showed that those 65 years and older had a significantly better response to treatment in those achieved PASI clear or PASI 2 or less (Likelihood ratio (LR) 16.15, p

Comprehensive autoantibody evaluation is essential for the management of autoimmune disorders. However, conventional methods suffer from poor sensitivity, low throughput, or limited availability. Here, using a proteome-wide human cDNA library, we developed a novel multiplex protein assay (autoantibody array assay; A-Cube) covering 65 antigens of 43 autoantibodies that are associated with systemic sclerosis (SSc) and polymyositis/dermatomyositis (PM/DM). The performance of A-Cube was validated against immunoprecipitation and established enzyme-linked immunosorbent assay. Further, through an evaluation of serum samples from 357 SSc and 172 PM/DM patients, A-Cube meticulously illustrated a diverse autoantibody landscape in these diseases. The wide coverage and high sensitivity of A-Cube also allowed the overlap and correlation analysis between multiple autoantibodies. Lastly, reviewing the cases with distinct autoantibody profiles by A-Cube underscored the importance of thorough autoantibody detection. Together, these data highlighted the utility of A-Cube as well as the clinical relevance of autoantibody profiles in SSc and PM/DM.

Introduction: Artificial placenta therapy (APT) is an experimental life support system to improve outcomes for extremely preterm infants (EPI) less than 1,000 g by obviating the need for pulmonary gas exchange. There are presently no long-term survival data for EPI supported with APT. To address this, we aimed to maintain 95d-GA (GA; term-150d) sheep fetuses for up to 2 weeks using our APT system.Methods: Pregnant ewes (n = 6) carrying singleton fetuses underwent surgical delivery at 95d GA. Fetuses were adapted to APT and maintained for up to 2 weeks with constant monitoring of key physiological parameters and extensive time-course blood and urine sampling, and ultrasound assessments. Six age-matched in-utero fetuses served as controls. Data were tested for group differences with ANOVA.Results: Six APT Group fetuses (100%) were adapted to APT successfully. The mean BW at the initiation of APT was 656 ± 42 g. Mean survival was 250 ± 72 h (Max 336 h) with systemic circulation and key physiological parameters maintained mostly within normal ranges. APT fetuses had active movements and urine output constantly exceeded infusion volume over the experiment. At delivery, there were no differences in BW (with edema in three APT group animals), brain weight, or femur length between APT and in-utero Control animals. Organ weights and humerus lengths were significantly reduced in the APT group (p < 0.05). Albumin, IGF-1, and phosphorus were significantly decreased in the APT group (p < 0.05). No cases of positive blood culture were detected.Conclusion: We report the longest use of APT to maintain extremely preterm fetuses to date. Fetal systemic circulation was maintained without infection, but growth was abnormal. This achievement suggests a need to focus not only on cardiovascular stability and health but also on the optimization of fetal growth and organ development. This new challenge will need to be overcome prior to the clinical translation of this technology.

Abstract Background Cutaneous T‐cell lymphomas (CTCLs) often have skin dryness and skin barrier dysfunctions, which are also seen in atopic dermatitis (AD). Expression of keratinocyte proline‐rich protein (KPRP) was decreased in the epidermis of AD, which led to barrier defects and further allergic inflammation. Objectives The aim of this study was to analyze KPRP expression in CTCL. Materials & Methods Skin samples of CTCL and healthy control were collected, and KPRP mRNA expression in the skin tissue was analyzed. We also performed immunohistochemistry of KPRP protein. Results Keratinocyte proline‐rich protein (KPRP) mRNA expression was decreased compared with normal skin. KPRP expression was positively correlated with that of filaggrin and loricrin, and it was negatively correlated with serum interleukin‐2 receptor levels. Immunohistochemistry staining showed that KPRP was detected in upper part of granular layer of epidermis in normal skin and in early‐stage CTCL, but rarely detected in the advanced‐stage CTCL. Conclusion In conclusion, we revealed the decrease in KPRP expression in CTCL.

Abstract Objectives Although the prognosis of Sézary syndrome (SS) is highly unfavorable, the prognostic factors have not been fully understood. In this study, we tried to investigate the prognostic factors in Japanese SS patients for the first time. Methods We performed a retrospective cohort study of 19 SS patients who visited our hospital between January 1, 1999, and December 31, 2019. The collected clinical findings were age, gender, performance status (PS), and TNMB staging at diagnosis. TNMB staging was determined according to the International Society for Cutaneous Lymphomas and the cutaneous task force of the European Organization of Research and Treatment of Cancer criteria. The collected hematological findings were serum levels of soluble IL‐2 receptor (sIL‐2R), lactate dehydrogenase (LDH), thymus and activation‐regulated chemokine (TARC), and immunoglobulin E (IgE), Sézary cell count, Sézary cell ratio among white blood cells, and eosinophil count in peripheral blood at diagnosis. Results We analyzed the correlations between overall survival and various clinical and hematological findings. In the log‐rank test, PS1‐3, N2‐3 stage, higher serum levels of LDH (≥355 IU/L), sIL‐2R (≥1729 U/ml) and TARC (≥19,867 pg/ml), and higher Sézary cell count (≥7480/μl) and Sézary cell ratio among white blood cells (≥52%) at diagnosis were associated with decreased overall survival. Conclusions This is the first report evaluating prognostic factors in Asian SS patients. This study may contribute to selecting the treatment strategy and improving survival and quality of life of Asian SS patients.

Abstract Linear childhood discoid lupus erythematosus (DLE) is a rare variant of DLE with a linear distribution that preferentially occurs on the face and scalp of children. We report a rare case of linear childhood DLE on the Blaschko's line of his left upper arm of a 7‐year‐old Japanese boy with 4‐year history of the disease. He was positive for anti‐single‐stranded DNA antibodies, but still showed no systemic symptoms during the 3‐year follow‐up period. We reviewed previous reports on linear childhood DLE and found that patients with nonfacial/nonscalp skin lesions are significantly more likely to be positive for autoantibodies.

Bullous pemphigoid (BP) is an autoimmune disease characterized by autoantibody-mediated activation of immune cells and subepidermal blister formation. Excess amounts of extracellular DNA are produced in BP, however, it remains unclear how extracellular DNA contributes to BP pathogenesis. Here we show a possible mechanism by which interleukin (IL)-26 binds to extracellular DNA released from neutrophils and eosinophils to support DNA sensing. Patients with BP exhibited high circulating levels of IL-26, forming IL-26–DNA complexes in the upper dermis and inside the blisters. IL-26–DNA complexes played a dual role in regulating local immunity and blister formation. First, they enhanced the production of inflammatory cytokines in monocytes and neutrophils. Second, and importantly, the complexes augmented the production and activity of proteases from co-cultured monocytes and neutrophils, which induced BP180 cleavage in keratinocytes and dermal-epidermal separation in a modified human cryosection model. Collectively, we propose a model in which IL-26 and extracellular DNA synergistically act on immune cells to enhance autoantibody-driven local immune responses and protease-mediated fragility of dermal-epidermal junction in BP.

Abstract Antimelanoma differentiation‐associated gene 5 antibody (anti‐MDA5 Ab)‐positive dermatomyositis frequently develops life‐threatening rapidly progressive interstitial lung disease (RP‐ILD). The longitudinal dynamics of antibody titers reflects treatment responses, and negative conversion of anti‐MDA5 Ab leads to the prevention of RP‐ILD relapse. Case 1 finally achieved negative conversion of anti‐MDA5 Ab after 18‐month immunosuppressive therapy despite early diagnosis from skin manifestations. Case 2 showed re‐elevation of anti‐MDA5 Ab after tacrolimus discontinuation; immediate restart of tacrolimus recovered it without relapse. These cases suggest that anti‐MDA5 Ab monitoring is essential to determine therapeutic strategy in dermatomyositis patients with RP‐ILD during both initial and maintenance phases.

Systemic sclerosis (SSc) is a rare intractable systemic disease that causes fibrosis and vasculopathy against a background of autoimmune abnormalities. Although the etiology is not yet fully understood, the type of autoantibodies detected in SSc is closely associated with disease severity and prognosis, supporting that those autoimmune abnormalities play an important role in the pathogenesis of SSc. Although the direct pathogenicity of autoantibodies found in SSc is unknown, many previous studies have shown that B cells are involved in the development of SSc through a variety of functions. Furthermore, a number of clinical studies have been conducted in which B-cell depletion therapy has been tried for SSc, and many of these studies have found B-cell depletion therapy to be effective for SSc. However, the involvement of B cells in pathogenesis is complex, as they not only promote inflammation but also play an inhibitory role. This article outlines the role of B cells in the development of SSc, including the latest research.

BackgroundAdvance care planning (ACP) is a widely advocated strategy to improve outcomes at end-of-life care for patients suffering from heart failure (HF). However, finding the right time to start ACP is challenging for healthcare providers because it is often a sensitive issue for patients with HF and their families. We interviewed patients with cardiovascular diseases regarding ACP readiness and investigated the relationship between the ACP desire and multiple clinical prognostic parameters.MethodEighty-one patients (average age 81.8 ± 10.3 years old, 42 men, 62 cases of HF) who introduced cardiac rehabilitation were inquired about previous ACP experience, a desire for ACP, understanding of their cardiovascular diseases, and lifestyle-associated questionnaires. Multiple logistic regression analyses were employed to identify the clinical parameters associated with ACP desire. Patients who desired ACP were also asked about their preferences for medical care at the end-of-life.ResultsNine patients (11.1%) had previous experience with ACP, and 28 (34.6%) preferred to implement ACP. Patients who did not want to implement ACP were 54.3%. Patients with HF showed a higher acceptance rate of ACP (odds ratio [OR] 5.56, p = 0.015). Interestingly, patients harboring skeletal muscle frailty showed lower ACP acceptance, while patients with non-frailty rather positively wanted to implement ACP. Two types of prognosis evaluation scales, such as the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) risk score and the Japanese Version of Supportive and Palliative Care Indicators Tool (SPICT-JP), identified 31 patients (38.3%) needing ACP; however, 19 (61.3%) did not want ACP. The wish not to attempt resuscitation and life-prolonging treatment at the end-of-life reached approximately 70% among patients who requested ACP.ConclusionsAlthough patients with HF tended to be ready for implementing ACP, the presence of skeletal muscle frailty was negatively associated with ACP preference. Indeed, patients who should be considered ACP were not carried out and did not desire it. Earlier introduction of ACP into patients before having skeletal muscle frailty may be considered.

Autoantibodies are found in various pathological conditions such as autoimmune diseases, infectious diseases, and malignant tumors. However their clinical implications have not yet been fully elucidated. Herein, we conducted proteome-wide autoantibody screening and quantification with wet protein arrays consisting of proteins synthesized from proteome-wide human cDNA library (HuPEX) maintaining their three-dimensional structure. A total of 565 autoantibodies were identified from the sera of three representative inflammatory disorders (systemic sclerosis, psoriasis, and cutaneous arteritis). Each autoantibody level either positively or negatively correlated with serum levels of C-reactive protein, the best-recognized indicator of inflammation. In particular, we discovered total levels of a subset of autoantibodies correlates with the severity of clinical symptoms. From the sera of malignant melanoma, 488 autoantibodies were detected. Notably, patients with metastases had increased overall autoantibody production compared to those with tumors limiting to the primary site. Collectively, proteome-wide screening of autoantibodies using the in vitro proteome can reveal the “autoantibody landscape” of human subjects and may provide novel clinical biomarkers.

Neutrophil extracellular traps (NETs) are web-like structures consisting of decondensed chromatin DNA and contents of granules, such as myeloperoxidase (MPO) and neutrophil elastase (NE). NETs are usually released from neutrophils undergoing NETosis, a neutrophil-specific cell death mode characterized by the collapse and disappearance of cell membranes and nuclear envelopes. It is well known that production of reactive oxygen species (ROS) triggers NETosis and NET formation. However, details of intracellular signaling downstream of ROS production during NETosis and NET formation remains uncertain. Here, we demonstrated that the peroxidation of phospholipids plays a critical role in NETosis and NET formation induced by phorbol 12-myristate13-acetate (PMA) or immune complex in vitro and by lipopolysaccharide (LPS) in vivo. This phospholipid peroxidation is mediated by the enzymatic activity of MPO. On the other hand, NE, which was previously reported to be released from granules to cytosol by MPO during NET formation, is not required for either the peroxidation of phospholipids or the execution of NETosis, but contributes to chromatin decondensation and nuclear swelling independently of MPO-mediated oxidized phospholipids. Analysis of isolated nuclei clearly demonstrated that oxidized phospholipids and NE differently yet synergistically execute chromatin decondensation and nuclear swelling, and the subsequent release of nuclear contents. These findings indicate the dual roles of MPO in NETosis and NET formation, and provide new insight into the molecular mechanism of these phenomena.

Abstract B cells are generally considered to regulate immune responses positively because they differentiate into plasma cells and produce antigen‐specific antibodies. However, specific B‐cell subsets have been reported to regulate immune responses negatively and have been termed regulatory B cells. Accumulating evidence has shown that regulatory B cells play an important role in a variety of inflammatory and autoimmune diseases. Among several regulatory B‐cell subsets, IL‐10–producing regulatory B cells are the most widely investigated. This review focused on the role of regulatory B cells in autoimmune and inflammatory skin diseases. The frequency of IL‐10–producing B cells in the peripheral blood from patients with systemic sclerosis was decreased compared to healthy controls. In addition, the function of regulatory B cells was impaired in patients with systemic sclerosis. As for systemic lupus erythematosus, the frequency of regulatory B cells was increased in the peripheral blood, while their regulatory function was impaired. In inflammatory skin diseases including psoriasis and atopic dermatitis, the number of IL‐10–producing B cells was decreased compared to healthy controls. Similarly, patients with cutaneous T‐cell lymphoma showed decreased number of IL‐10–producing B cells. Taken together, regulatory B cells would play important roles in suppressing the disease onset, whose dysfunction might lead to worsening the disease symptoms. Revealing the mechanisms of human regulatory B cells in skin diseases could lead to the development of novel therapies targeting regulatory B cells.

This work presents a case study on fieldwork in a group home for the elderly with dementia using a teleoperated robot called Telenoid. We compared Telenoid-mediated and face-to-face conditions with three residents with Alzheimer's disease (AD). The result indicates that two of the three residents with moderate AD showed a positive reaction to Telenoid. Both became less nervous while communicating with Telenoid from the time they were first introduced to it. Moreover, they started to use more body gestures in the face-to-face condition and more physical interactions in the Telenoid-mediated condition. In this work, we present all the results and discuss the possibilities of using Telenoid as a tool to provide opportunities for seniors to communicate over the long term.

Comprehensive autoantibody evaluation is essential for the management of autoimmune disorders. However, conventional methods suffer from poor sensitivity, low throughput, or limited availability. Here, using a proteome-wide human cDNA library, we developed a novel multiplex protein assay (autoantibody array assay; A-Cube) covering 65 antigens of 43 autoantibodies that are associated with systemic sclerosis (SSc) and polymyositis/dermatomyositis (PM/DM). The performance of A-Cube was validated against immunoprecipitation and established enzyme-linked immunosorbent assay. Further, through an evaluation of serum samples from 357 SSc and 172 PM/DM patients, A-Cube meticulously illustrated a diverse autoantibody landscape in these diseases. The wide coverage and high sensitivity of A-Cube also allowed the overlap and correlation analysis between multiple autoantibodies. Lastly, reviewing the cases with distinct autoantibody profiles by A-Cube underscored the importance of thorough autoantibody detection. Together, these data highlighted the utility of A-Cube as well as the clinical relevance of autoantibody profiles in SSc and PM/DM. [ABSTRACT FROM AUTHOR]

This work presents a case study on fieldwork in a group home for the elderly with dementia using a teleoperated robot called Telenoid. We compared Telenoid-mediated and face-to-face conditions with three residents with Alzheimer's disease (AD). The result indicates that two of the three residents with moderate AD showed a positive reaction to Telenoid. Both became less nervous while communicating with Telenoid from the time they were first introduced to it. Moreover, they started to use more body gestures in the face-to-face condition and more physical interactions in the Telenoid-mediated condition. In this work, we present all the results and discuss the possibilities of using Telenoid as a tool to provide opportunities for seniors to communicate over the long term. [ABSTRACT FROM AUTHOR]