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Chronic obstructive pulmonary disease (COPD) is a progressive disease that is characterized by chronic airway inflammation. A Japanese herbal medicine, hochuekkito (TJ-41), is prominently used for chronic inflammatory diseases in Japan. This study aimed to analyze the anti-inflammatory effect of TJ-41 in vivo and its underlying mechanisms. We created a COPD mouse model using intratracheal administration of porcine pancreatic elastase and lipopolysaccharide (LPS) and analyzed them with and without TJ-41 administration. A TJ-41-containing diet reduced inflammatory cell infiltration of the lungs in the acute and chronic phases and body weight loss in the acute phase. In vitro experiments revealed that TJ-41 treatment suppressed the LPS-induced inflammatory cytokines in BEAS-2B cells. Furthermore, TJ-41 administration activated the AMP-activated protein kinase (AMPK) pathway and inhibited the mechanistic target of the rapamycin (mTOR) pathway, both in cellular and mouse experiments. We concluded that TJ-41 administration reduced airway inflammation in the COPD mouse model, which might be regulated by the activated AMPK pathway, and inhibited the mTOR pathway., (© 2024. The Author(s).)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients frequently show physical dysfunction due to loss of muscle mass. This study aimed to clarify the reliability and validity of ultrasound in evaluating muscle mass and to analyze the patterns of change in muscle mass before and after allo-HSCT. We conducted a prospective observational study using data from 68 patients who had undergone their first allo-HSCT. We evaluated the thickness of the quadriceps, biceps, and suprahyoid muscle. Three individual evaluators underwent this examination for each muscle before transplantation and on days 30, 90, and 180 after allo-HSCT. Inter-rater reliability was calculated using the interclass correlation (ICC), and the level of correlation between muscle mass measured by ultrasound and psoas muscle mass assessed using computed tomography (CT) was assessed using Pearson correlation. ICC values ranged from 0.897 to 0.977 in the measurement. The correlation scores were 0.730, 0.546 and 0.579 between psoas muscle and the biceps, quadriceps, and suprahyoid muscle. The thickness of the biceps and quadriceps muscle were both significantly decreased after allo-HSCT from baseline. These results showed that the ultrasound technique was a reliable tool for evaluating muscle mass and detecting changes in muscle mass following allo-HSCT., (© 2022. The Author(s).)

Spirometry is a standard method for assessing lung function. However, its use is challenging in some patients, and it has limitations such as risk of infection and inability to assess regional chest wall motion. A three-dimensional motion capture system using the one-pitch phase analysis (MCO) method can facilitate high precision measurement of moving objects in real-time in a non-contacting manner. In this study, the MCO method was applied to examine thoraco-abdominal (TA) wall motion for assessing pulmonary function. We recruited 48 male participants, and all underwent spirometry and chest wall motion measurement with the MCO method. A significant positive correlation was observed between the vital capacity (Spearman's ρ = 0.68, p < 0.0001), forced vital capacity (Spearman's ρ = 0.62, p < 0.0001), and tidal volume (Spearman's ρ = 0.61, p < 0.0001) of spirometry and the counterpart parameters of MCO method. Moreover, the MCO method could detect regional rib cage and abdomen compartment contributions and could assess TA asynchrony, indicating almost complete synchronous movement (phase angle for each compartment: - 5.05° to 3.86°). These findings suggest that this technique could examine chest wall motion, and may be effective in analyzing chest wall volume changes and pulmonary function., (© 2021. The Author(s).)

Approximately 60-70% of EWSR1-negative small blue round cell sarcomas harbour a rearrangement of CIC, most commonly CIC-DUX 4 . CIC-DUX 4 sarcoma (CDS) is an aggressive and often fatal high-grade sarcoma appearing predominantly in children and young adults. Although cell lines and their xenograft models are essential tools for basic research and development of antitumour drugs, few cell lines currently exist for CDS. We successfully established a novel human CDS cell line designated Kitra-SRS and developed orthotopic tumour xenografts in nude mice. The CIC-DUX 4 fusion gene in Kitra-SRS cells was generated by t(12;19) complex chromosomal rearrangements with an insertion of a chromosome segment including a DUX 4 pseudogene component. Kitra-SRS xenografts were histologically similar to the original tumour and exhibited metastatic potential to the lungs. Kitra-SRS cells displayed autocrine activation of the insulin-like growth factor 1 (IGF-1)/IGF-1 receptor (IGF-1R) pathway. Accordingly, treatment with the IGF-1R inhibitor, linsitinib, attenuated Kitra-SRS cell growth and IGF-1-induced activation of IGF-1R/AKT signalling both in vitro and in vivo. Furthermore, upon screening 1134 FDA-approved drugs, the responses of Kitra-SRS cells to anticancer drugs appeared to reflect those of the primary tumour. Our model will be a useful modality for investigating the molecular pathology and therapy of CDS.

Period circadian clock (Per) genes Per1 and Per2 have essential roles in circadian oscillation. In this study, we identified a new role of Per1-Per2 cooperation, and its mechanism, using our new experimental methods. Under constant light conditions, the period length of Per1 and Per2 knockout mice depended on the copy number ratio of Per1:Per2. We then established a light-emitting diode-based lighting system that can generate any pattern of light intensity. Under gradually changing light in the absence of phase shift with different periods, both Per1((-/-)) and Per2((-/-)) mice were entrained to a broader range of period length than wild-type mice. To analyse Per1-Per2 cooperative roles at the cell culture level, we established a Per2 knockout-rescue system, which can detect period shortening in a familial advanced sleep phase syndrome (FASPS) mutant. Upon introduction of the Per1 coding region in this system, we saw period shortening. In conclusion, short period-associated protein Per1 and long period-associated Per2 cooperated to rigidly confine the circadian period to "circa" 24-h. These results suggest that the rigid circadian rhythm maintained through the cooperation of Per1-Per2 could negatively impact modern society, in which the use of artificial lighting is ubiquitous, and result in circadian disorders, including delirium.