担当区分：筆頭著者,　最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Bba Advances  

Background: Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) has been recognized as a marker of lymphatic vessels; however, recent studies have reported that LYVE-1 is expressed in diverse cell types and functionally contributes to organ repair. Herein, we examined the expression pattern of LYVE-1 in acute respiratory distress syndrome (ARDS) model mice. Methods: Acute lung injury (ALI) was induced by intratracheal administration of lipopolysaccharide (LPS) in mice. The expression and localization of LYVE-1 during the inflammatory and resolution phases were assessed by immunohistochemistry and western blot analysis. We also assessed the extent of lung injury following pharmacological inhibition of LYVE-1. Results: During the inflammatory phase of lung injury, 6 h after LPS treatment, a marked decrease in LYVE-1 expression was observed, accompanied by the accumulation of hyaluronan in the tissue. During the repair process at 12 and 24 h, LYVE-1 expression transiently increased beyond baseline levels before returning to a steady state. Notably, LYVE-1-positive M2 macrophages were detected during the resolution phase. Furthermore, LYVE-1 inhibition exacerbated the severity of lung injury and resulted in poor prognosis. Conclusion: LYVE-1 exhibits dynamic expression during lung inflammation and repair, not only in lung tissues but also in M2-like macrophages. Therefore, LYVE-1 may serve as a target for future pharmacological interventions in ALI.

DOI： 10.1016/j.bbadva.2026.100202

Web of Science

Scopus

PubMed

記述言語：英語   出版者・発行元：(一社)日本炎症・再生医学会  

記述言語：英語   出版者・発行元：Inflammation and Regeneration  

Background: Sepsis-induced myocardial dysfunction (SIMD) is a prevalent complication among septic patients, significantly worsening patient prognosis and elevating the mortality rate. Connexin 43 (Cx43), a pivotal cardiac gap junction protein, maintains cardiac function, and its disarrangement is closely linked to cardiac diseases. However, the role of Cx43 localization changes in SIMD remains unclear. Amphiregulin (AREG) was recently reported to promote the recovery of Cx43 disarrangements. This research aimed to explore the role of Cx43 in SIMD and the preventive potential of AREG. Methods: A mouse model of SIMD was induced using lipopolysaccharide (LPS) and treated with AREG. Cardiac function and electrical conduction were assessed using echocardiography and an electrocardiogram. Inflammatory responses, Cx43 regulation, and related signaling pathways were further investigated in serum and cardiac tissues. Relevant signal pathway analysis was investigated in cultured cardiomyocytes. Results: LPS administration significantly reduced cardiac ejection fraction and left ventricular fractional shortening, which were accompanied by disorganization, fragmentation, and lateralization of Cx43 at 6 h. These pathological alterations were associated with increased phosphorylation of p^S368-Cx43, mediated by p38 activation. AREG pretreatment improved cardiac function and QRS interval, and preserved Cx43 localization at intercellular discs, along with p^S368-Cx43 phosphorylation with reduction of p38 inhibition. Myocardial cell studies confirmed that AREG inhibited p38 phosphorylation, independent of AKT, in LPS-induced cardiac dysfunction. Conclusion: This study highlights the role of Cx43 phosphorylation in SIMD and demonstrates the preventive potential of AREG in SIMD, which is associated with a reduction in p38 activation and a decrease in the phosphorylation level of p^S368-Cx43. These findings may provide a novel therapeutic target for SIMD.

DOI： 10.1186/s41232-026-00410-y

Web of Science

Scopus

PubMed

記述言語：英語   出版者・発行元：Shock  

Background: Histidine-rich glycoprotein (HRG), a potential prognostic factor in sepsis, lacks clarity regarding its relevance in septic-induced shock, disseminated intravascular coagulation (DIC), and acute respiratory distress syndrome (ARDS) pathogenesis. This study investigated the association between HRG concentrations and these critical conditions. Methods: Blood samples were collected from 53 critically ill patients on days 1, 3, 5, and 7 after ICU admission at the Kyushu University Hospital. Daily clinical and laboratory data were recorded, and patient survival was assessed 28 days after ICU admission. Results: Serum HRG concentrations were significantly reduced on days 3, 5, and 7 in patients with septic shock and DIC but not in those with ARDS. While initial HRG levels on day one were not correlated with survival, nonsurvivors displayed decreased HRG levels, notably on days 3, 5, and 7 post-ICU admissions. The HRG levels remained stable in survivors. A progressive decrease was associated with higher mortality rates, particularly on days 5 and 7. On day 5, an HRG level with a cutoff of 25.5 μg/mL showed a sensitivity of 0.77 and a specificity of 0.75, indicating significantly lower survival rates (log-rank test, P < 0.05). Conclusion: HRG presents a potential intervention for critically ill sepsis patients, providing a novel strategy to enhance outcomes. Further research is needed to explore the therapeutic potential of HRG in sepsis management.

DOI： 10.1097/SHK.0000000000002406

Web of Science

Scopus

PubMed

記述言語：日本語   出版者・発行元：(一社)日本熱傷学会  

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：英語  

記述言語：英語  

ICLSコースを学生、研修医対象に院外病院と連携し開催した。