Emerging evidence suggests that systemic inflammation may play a critical role in neurological disorders. Recent studies have shown the connection between inflammatory bowel diseases (IBD) and neurological disorders, revealing a bidirectional relationship through the gut-brain axis.Immunotherapies, such as Treg cells infusion, have been proposed for IBD. However, the role of adaptive immune cells in IBD-induced neuroinflammation remains unclear. In this study, we established an animal model for IBD in mice with severe combined immune-deficient (SCID), an adaptive immune deficiency, to investigate the role of adaptive immune cells in IBD-induced neuroinflammation. Mice were fed 1%, 3%, or 5% dextran sulfate sodium (DSS) for 5 days. We measured body weight, colon length, disease activity index (DAI), and crypt damage. Pro-inflammatory cytokines were measured in the colon, while microglial morphology, neuronal count, and inflammatory cytokines were analyzed in the brain. In the 3% DSS group, colitis symptoms appeared at day 7, with reduced colon length and increased crypt damage showing colitis-like symptoms. By day 21, colon length and crypt damage persisted, while DAI showed recovery. Although colonic inflammation peaked at day 7, no significant increase in inflammatory cytokines or microglial hyperactivation was observed in the brain. By day 21, neuroinflammation was detected, albeit with a slight delay, in the absence of adaptive immune cells. The colitis-induced neuroinflammation model provides insights into the fundamental immune mechanisms of the gut-brain axis and may contribute to developing immune cell therapies for IBD-induced neuroinflammation.

Emerging evidence suggests that systemic inflammation may play a critical role in neurological disorders. Recent studies have shown the connection between inflammatory bowel diseases (IBD) and neurological disorders, revealing a bidirectional relationship through the gut-brain axis.Immunotherapies, such as Treg cells infusion, have been proposed for IBD. However, the role of adaptive immune cells in IBD-induced neuroinflammation remains unclear. In this study, we established an animal model for IBD in mice with severe combined immune-deficient (SCID), an adaptive immune deficiency, to investigate the role of adaptive immune cells in IBD-induced neuroinflammation. Mice were fed 1%, 3%, or 5% dextran sulfate sodium (DSS) for 5 days. We measured body weight, colon length, disease activity index (DAI), and crypt damage. Pro-inflammatory cytokines were measured in the colon, while microglial morphology, neuronal count, and inflammatory cytokines were analyzed in the brain. In the 3% DSS group, colitis symptoms appeared at day 7, with reduced colon length and increased crypt damage showing colitis-like symptoms. By day 21, colon length and crypt damage persisted, while DAI showed recovery. Although colonic inflammation peaked at day 7, no significant increase in inflammatory cytokines or microglial hyperactivation was observed in the brain. By day 21, neuroinflammation was detected, albeit with a slight delay, in the absence of adaptive immune cells. The colitis-induced neuroinflammation model provides insights into the fundamental immune mechanisms of the gut-brain axis and may contribute to developing immune cell therapies for IBD-induced neuroinflammation.

Emerging evidence suggests that systemic inflammation may play a critical role in neurological disorders. Recent studies have shown the connection between inflammatory bowel diseases (IBD) and neurological disorders, revealing a bidirectional relationship through the gut-brain axis.Immunotherapies, such as Treg cells infusion, have been proposed for IBD. However, the role of adaptive immune cells in IBD-induced neuroinflammation remains unclear. In this study, we established an animal model for IBD in mice with severe combined immune-deficient (SCID), an adaptive immune deficiency, to investigate the role of adaptive immune cells in IBD-induced neuroinflammation. Mice were fed 1%, 3%, or 5% dextran sulfate sodium (DSS) for 5 days. We measured body weight, colon length, disease activity index (DAI), and crypt damage. Pro-inflammatory cytokines were measured in the colon, while microglial morphology, neuronal count, and inflammatory cytokines were analyzed in the brain. In the 3% DSS group, colitis symptoms appeared at day 7, with reduced colon length and increased crypt damage showing colitis-like symptoms. By day 21, colon length and crypt damage persisted, while DAI showed recovery. Although colonic inflammation peaked at day 7, no significant increase in inflammatory cytokines or microglial hyperactivation was observed in the brain. By day 21, neuroinflammation was detected, albeit with a slight delay, in the absence of adaptive immune cells. The colitis-induced neuroinflammation model provides insights into the fundamental immune mechanisms of the gut-brain axis and may contribute to developing immune cell therapies for IBD-induced neuroinflammation.

Emerging evidence suggests that systemic inflammation may play a critical role in neurological disorders. Recent studies have shown the connection between inflammatory bowel diseases (IBD) and neurological disorders, revealing a bidirectional relationship through the gut-brain axis.Immunotherapies, such as Treg cells infusion, have been proposed for IBD. However, the role of adaptive immune cells in IBD-induced neuroinflammation remains unclear. In this study, we established an animal model for IBD in mice with severe combined immune-deficient (SCID), an adaptive immune deficiency, to investigate the role of adaptive immune cells in IBD-induced neuroinflammation. Mice were fed 1%, 3%, or 5% dextran sulfate sodium (DSS) for 5 days. We measured body weight, colon length, disease activity index (DAI), and crypt damage. Pro-inflammatory cytokines were measured in the colon, while microglial morphology, neuronal count, and inflammatory cytokines were analyzed in the brain. In the 3% DSS group, colitis symptoms appeared at day 7, with reduced colon length and increased crypt damage showing colitis-like symptoms. By day 21, colon length and crypt damage persisted, while DAI showed recovery. Although colonic inflammation peaked at day 7, no significant increase in inflammatory cytokines or microglial hyperactivation was observed in the brain. By day 21, neuroinflammation was detected, albeit with a slight delay, in the absence of adaptive immune cells. The colitis-induced neuroinflammation model provides insights into the fundamental immune mechanisms of the gut-brain axis and may contribute to developing immune cell therapies for IBD-induced neuroinflammation.

The evaluation of respiratory chemical substances has been mostly performed in animal tests (OECD TG 403, TG 412, TG 413, etc.). However, there have been ongoing discussions about the limited use of these inhalation toxicity tests due to differences in the anatomical structure of the respiratory tract, difficulty in exposure, laborious processes, and ethical reasons. Alternative animal testing methods that mimic in vivo testing are required. Therefore, in this study, we established a co-culture system composed of differentiated epithelial cells under an air-liquid interface (ALI) system in the apical part and fibroblasts in the basal part. This system was designed to mimic the wound-healing mechanism in the respiratory system. In addition, we developed a multi-analysis system that simultaneously performs toxicological and functional evaluations. Several individual assays were used sequentially in a multi-analysis model for pulmonary toxicity. Briefly, cytokine analysis, histology, and cilia motility were measured in the apical part, and cell migration and gel contraction assay were performed by exposing MRC-5 cells to the basal culture. First, human airway epithelial cells from bronchial (hAECB) were cultured under air-liquid interface (ALI) system conditions and validated pseudostratified epithelium by detecting differentiation-related epithelial markers using Transepithelial Electrical Resistance (TEER) measurement, Hematoxylin and Eosin (H&E) staining, and immunocytochemistry (ICC) staining. Afterward, the co-culture cells exposed to Transforming growth factor-beta 1 (TGF-β1), a key mediator of pulmonary fibrosis, induced significant toxicological responses such as cytotoxicity, cell migration, and gel contraction, which are wound-healing markers. In addition, cilia motility in epithelial cells was significantly decreased compared to control. Therefore, the multi-analysis model with a 3D epithelial-fibroblast co-culture system is expected to be useful in predicting pulmonary toxicity as a simple and efficient high-throughput screening method and as an alternative to animal testing.

Purpose: This study compared the diagnostic performance of quantitative ultrasonography (QUS) with that of conventional ultrasonography (US) in assessing hepatic steatosis among individuals undergoing health screening using magnetic resonance imaging–derived proton density fat fraction (MRI-PDFF) as the reference standard. Methods: This single-center prospective study enrolled 427 participants who underwent abdominal MRI and US. Measurements included the attenuation coefficient in tissue attenuation imaging (TAI) and the scatter-distribution coefficient in tissue scatter-distribution imaging (TSI). The correlation between QUS and MRI-PDFF was evaluated. The diagnostic capabilities of QUS, conventional B-mode US, and their combined models for detecting hepatic fat content of ≥5% (MRI-PDFF ≥5%) and ≥10% (MRI-PDFF ≥10%) were compared by analyzing the areas under the receiver operating characteristic curves. Additionally, clinical risk factors influencing the diagnostic performance of QUS were identified using multivariate linear regression analyses. Results: TAI and TSI were strongly correlated with MRI-PDFF (r=0.759 and r=0.802, respectively; both P<0.001) and demonstrated good diagnostic performance in detecting and grading hepatic steatosis. The combination of QUS and B-mode US resulted in the highest areas under the ROC curve (AUCs) (0.947 and 0.975 for detecting hepatic fat content of ≥5% and ≥10%, respectively; both P<0.05), compared to TAI, TSI, or B-mode US alone (AUCs: 0.887, 0.910, 0.878 for ≥5% and 0.951, 0.922, 0.875 for ≥10%, respectively). The independent determinants of QUS included skinliver capsule distance (β=7.134), hepatic fibrosis (β=4.808), alanine aminotransferase (β=0.202), triglyceride levels (β=0.027), and diabetes mellitus (β=3.710). Conclusion QUS is a useful and effective screening tool for detecting and grading hepatic steatosis during health checkups.

Purpose: This study compared the diagnostic performance of quantitative ultrasonography (QUS) with that of conventional ultrasonography (US) in assessing hepatic steatosis among individuals undergoing health screening using magnetic resonance imaging–derived proton density fat fraction (MRI-PDFF) as the reference standard. Methods: This single-center prospective study enrolled 427 participants who underwent abdominal MRI and US. Measurements included the attenuation coefficient in tissue attenuation imaging (TAI) and the scatter-distribution coefficient in tissue scatter-distribution imaging (TSI). The correlation between QUS and MRI-PDFF was evaluated. The diagnostic capabilities of QUS, conventional B-mode US, and their combined models for detecting hepatic fat content of ≥5% (MRI-PDFF ≥5%) and ≥10% (MRI-PDFF ≥10%) were compared by analyzing the areas under the receiver operating characteristic curves. Additionally, clinical risk factors influencing the diagnostic performance of QUS were identified using multivariate linear regression analyses. Results: TAI and TSI were strongly correlated with MRI-PDFF (r=0.759 and r=0.802, respectively; both P<0.001) and demonstrated good diagnostic performance in detecting and grading hepatic steatosis. The combination of QUS and B-mode US resulted in the highest areas under the ROC curve (AUCs) (0.947 and 0.975 for detecting hepatic fat content of ≥5% and ≥10%, respectively; both P<0.05), compared to TAI, TSI, or B-mode US alone (AUCs: 0.887, 0.910, 0.878 for ≥5% and 0.951, 0.922, 0.875 for ≥10%, respectively). The independent determinants of QUS included skinliver capsule distance (β=7.134), hepatic fibrosis (β=4.808), alanine aminotransferase (β=0.202), triglyceride levels (β=0.027), and diabetes mellitus (β=3.710). Conclusion QUS is a useful and effective screening tool for detecting and grading hepatic steatosis during health checkups.