Publications by authors named "Hiroaki Iwata"

The Hashimoto Research Group for Comprehensive Research of Gene Mutation-related Rare and Intractable Diseases of the Skin is a contributor to the Project for Research on Intractable Diseases of the Ministry of Health, Labor, and Welfare (MHLW) of Japan. Our research group performs clinical research on 23 rare intractable genetic skin diseases that are classified into eight disease groups. Among the 23 diseases, 17 are mainly studied by our research group, and 6 diseases are studied in collaboration with other research groups.

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The process of developing new drugs in the pharmaceutical industry is both time-consuming and costly, making efficiency crucial. Recent advances in hardware and computational methods have led to the widespread application of computational science approaches in drug discovery. These approaches, including artificial intelligence and molecular simulations, span from target identification to pharmacokinetics research, aiming to reduce the likelihood of failure and present lower costs.

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The pharmaceutical industry has increasingly adopted model-informed drug discovery and development (MID3) to enhance productivity in drug discovery and development. Quantitative systems pharmacology (QSP), which integrates drug action mechanisms and disease complexities to predict clinical endpoints and biomarkers is central to MID3. QSP modeling has proven successful in metabolic and cardiovascular diseases and has expanded into oncology, immunotherapy, and infectious diseases.

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  • Mechanical irritation during skincare can harm the skin barrier in older adults, highlighting the need for proper skin assessments, though no validated methods have been available.
  • A study created a nomogram to predict skin barrier dysfunction in Japanese patients aged 65 and older, based on data from a randomized controlled trial, using a mechanical irritation test on their volar forearms.
  • The final nomogram includes factors like chronic kidney disease and body mass index, and it effectively identifies those at risk, aiming to enhance skincare strategies and reduce skin disorders among this population.
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  • An 89-year-old woman from Japan had a skin condition that made her skin very red and scaly.
  • Doctors found some unusual changes in her skin cells and discovered she had mutations in two specific genes (IL36RN and CARD14).
  • She later developed small, round spots on her skin that looked normal, but tests showed these spots might be different from her red, scaly skin despite having the same gene mutations.
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  • Bullous pemphigoid is an autoimmune skin disease caused by antibodies against type XVII collagen, leading to blister formation and inflammation in the skin.
  • Researchers created specific CD4 T cell lines that recognize the collagen and tested their effects by transferring them into specially designed mice that only express human COL17.
  • The study found that certain T cell lines caused symptoms similar to bullous pemphigoid, and high levels of IL-5 cytokine were linked to this effect; blocking IL-5 reduced the skin damage and antibody production.
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ROS are involved in the pathogenesis of bullous pemphigoid (BP), but this involvement has not been fully elucidated. In this study, to further elucidate the pathogenic role of ROS in BP, we examined the results of the diacron-reactive oxygen metabolite test and the biological antioxidant potential test for 16 patients with BP who visited our hospital before being treated with systemic corticosteroids. In the patients with BP, the average diacron-reactive oxygen metabolite levels, expressed in Carratelli units, were significantly reduced at 1 month of treatment (from 335.

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Bullous pemphigoid (BP), an autoimmune subepidermal blistering disease, shows tense blisters associated with urticarial erythema. Tissue-bound Immunoglobulin G (IgG) at the basement membrane zone (BMZ) detected by direct immunofluorescence (DIF) is strong evidence for a diagnosis of BP. The sensitivity of DIF is higher in complement component 3 (C3) than in IgG, but the reason for this different sensitivity is not fully understood.

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The combination of the cancer mitochondrial metabolic inhibitor CPI-613 and hydroxychloroquine has tumor-suppressive effects on clear cell sarcoma, which shares pathobiological properties with melanoma. Therefore, we intended to examine the effects of a combination of CPI-613 and hydroxychloroquine on the growth of melanoma cells in the present study. However, cell death was not induced in melanoma cells.

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  • - Mitochondrial toxicity is important in drug development as it is linked to various toxicities like hepatotoxicity, prompting the need for early screening tools to predict such toxicity based on chemical structures.
  • - Current predictive models usually give a simple yes/no result without identifying specific substructures causing toxicity; thus, an AI model was developed using a graph neural network to predict and visualize these structural alerts.
  • - By addressing dataset imbalances and using techniques like bagging and the integrated gradient method, the new AI model achieved high predictive accuracy (F1 score of 0.839) and can visualize elements within chemical structures that indicate mitochondrial toxicity.
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Scanning electron microscopy (SEM) images are the most widely used tool for evaluating particle morphology; however, quantitative evaluation using SEM images is time-consuming and often neglected. In this study, we aimed to extract features related to particle morphology of pharmaceutical excipients from SEM images using a convolutional neural network (CNN). SEM images of 67 excipients were acquired and used as models.

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Granuloma annulare (GA) is characterized by palisading granuloma, which is histopathologically distinguished by histiocytes arrayed in a palisade configuration encircling insoluble entities associated with degenerated collagen fibrils. The present case demonstrated multiple cutaneous papules showing palisading granuloma in a patient with SLE. A 39-year-old woman has been taking oral prednisolone daily, hydroxychloroquine sulfate, and belimumab for systemic lupus erythematosus (SLE).

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  • Molecular generation plays a vital role in drug discovery, materials science, and chemical research by speeding up the identification of new drug candidates, creating custom materials, and increasing our knowledge of molecular diversity.
  • Researchers have developed a novel molecular generative model that merges graph-based deep neural networks with reinforcement learning to efficiently discover molecules with specific desired properties.
  • This model not only demonstrates its effectiveness by exploring new areas of chemical space but also holds great promise for transforming scientific innovation in drug development and materials creation.
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  • * The main treatment for AIGA is steroid pulse therapy, although the number of treatment courses needed for improvement isn’t well established.
  • * A study of 28 AIGA patients over the past decade found that those with larger areas of anhidrosis require more steroid therapy courses for improvement.
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