A5020759539- Organ Transplantation Techniques and Outcomes
- Liver Disease and Transplantation
- Liver Disease Diagnosis and Treatment
- Renal Transplantation Outcomes and Treatments
- Heme Oxygenase-1 and Carbon Monoxide
- Liver physiology and pathology
- Transplantation: Methods and Outcomes
- Macrophage Migration Inhibitory Factor
- High Altitude and Hypoxia
- Inflammasome and immune disorders
- Neonatal Health and Biochemistry
- Eicosanoids and Hypertension Pharmacology
- Dietary Effects on Health
- Biochemical effects in animals
- Diet and metabolism studies
- MicroRNA in disease regulation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune Response and Inflammation
- Advanced Glycation End Products research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Anesthesia and Neurotoxicity Research
- Pneumocystis jirovecii pneumonia detection and treatment
- Organ Donation and Transplantation
- Genomics, phytochemicals, and oxidative stress
- Galectins and Cancer Biology
Kyoto University
2015-2025
University of California, Los Angeles
2018-2024
Kitano Hospital
2015-2018
Kagawa University
2015
Asahi General Hospital
2010
Ischemia-reperfusion injury (IRI) is believed to contribute graft dysfunction after liver transplantation (LT). However, studies on IRI and the impact of early allograft (EAD) in grafts are limited. Histological was graded 506 from patients who had undergone LT classified based severity (no, minimal, mild, moderate, severe). Of grafts, 87.4% (no: 12.6%, minimal: 38.1%, mild: 35.4%, moderate: 13.0%, severe: 0.8%). correlated with incidence EAD survival at 6 months. Longer cold/warm ischemia...
Macrophages polarize into heterogeneous proinflammatory M1 and antiinflammatory M2 subtypes. Heme oxygenase 1 (HO-1) protects against inflammatory processes such as ischemia-reperfusion injury (IRI), organ transplantation, atherosclerosis. To test our hypothesis that HO-1 regulates macrophage polarization IRI, we generated myeloid-specific HO-1–knockout (mHO-1–KO) –transgenic (mHO-1–Tg) mice, with deletion or overexpression of HO-1, in various populations. Bone marrow–derived macrophages...
Significance Long-term fasting for more than 24 h has been reported to ameliorate liver ischemia and reperfusion injury (IRI). However, it is difficult apply long-term human preoperative management, the underlying molecular mechanisms remain unclear. Our present research demonstrates that 12-h remarkably ameliorates IRI. The induces up-regulation of FOXO1 by raising level acetylated histone β-hydroxybutyric acid, followed antioxidative enzyme autophagy activity, improves IRI through...
Although modifications of gut microbiota with antibiotics (Abx) influence mouse skin and cardiac allografts, its role in orthotopic liver transplantation (OLT) remains unknown. We aimed to determine whether how recipient Abx pretreatment may affect hepatic ischemia-reperfusion injury (IRI) OLT outcomes. Mice (C57BL/6) or without treatment (10 days) were transplanted allogeneic (BALB/c) cold-stored (18 hours) livers, followed by blood sampling (6 hours). divided 264 human recipients on the...
Although Ikaros (IKZF1) is a well-established transcriptional regulator in leukocyte lymphopoiesis and differentiation, its role myeloid innate immune responses remains unclear. Sirtuin 1 (SIRT1) histone/protein deacetylase involved cellular senescence, inflammation, stress resistance. Whether SIRT1 signaling essential cell activation uncertain, while the molecular communication between SIRT1, two major regulators, has not been studied.We undertook functional studies to interrogate...
Neutrophils, the largest innate immune cell population in humans, are primary proinflammatory sentinel ischemia-reperfusion injury (IRI) mechanism orthotopic liver transplantation (OLT). Carcinoembryonic antigen-related adhesion molecule 1 (CEACAM1, CC1, or CD66a) is essential neutrophil activation and serves as a checkpoint regulator of immune-driven IRI cascade OLT. Although CC1 alternative splicing generates two functionally distinct short long cytoplasmic isoforms, their role remains...
Many pediatric patients who receive a living-donor liver transplant undergo withdrawal of immunosuppression (IS). For them, the high incidence long-term progressive graft fibrosis is particular concern.We conducted cross-sectional study including 81 underwent IS after at Kyoto University Hospital and whose serum samples pathological data could be obtained during analysis period. We examined association donor-specific anti-human leukocyte antigen (HLA) antibody (DSA) angiotensin II type 1...
To investigate the influence of donor age on recipient outcome after living-donor partial liver transplantation (LDLT).Donor is a well-known prognostic factor in deceased transplantation; however, its role LDLT remains unclear.We retrospectively analyzed 315 consecutive cases primary adult-to-adult our center between April 2006 and March 2014. Recipients were divided into 5 groups according to age: D-20s (n = 60); D-30s 72); D-40s 57); D-50s 94); D-60s 32). The survival association with...
Although cold preservation remains the gold standard in organ transplantation, stress–induced cellular injury is a significant problem clinical orthotopic liver transplantation (OLT). Because recent study showed that stress activates ferroptosis, form of regulated cell death, we investigated whether and how ferroptosis determines OLT outcomes mice humans. Treatment with inhibitor (ferrostatin-1) during reduced lipid peroxidation (malondialdehyde; MDA), primarily sinusoidal endothelial cells...
Liver ischemia reperfusion injury (IRI) is an important problem in liver transplantation. Thrombomodulin (TM), effective drug for disseminated intravascular coagulation, also known to exhibit anti-inflammatory effect through binding the high-mobility group box 1 protein (HMGB-1) as a proinflammatory mediator. We examined of recombinant human TM (rTM) on partial warm hepatic IRI model wild-type (WT) and toll-like receptor 4 (TLR-4) KO mice focusing HMGB-1/TLR-4 axis. As vitro experiments,...
Although CEACAM1 (CC1) glycoprotein resides at the interface of immune liver injury and metabolic homeostasis, its role in orthotopic transplantation (OLT) remains elusive. We aimed to determine whether/how signaling may affect hepatic ischemia-reperfusion (IRI) OLT outcomes. In mouse, donor CC1 null mutation augmented IRI-OLT (CC1-KO→WT) by enhancing ROS expression HMGB1 translocation during cold storage, data supported vitro studies where flush from CC1-deficient livers enhanced macrophage...
Although alternative splicing (AS) drives transcriptional responses and cellular adaptation to environmental stresses, its contributions in organ transplantation have not been appreciated. We shown that carcinoembryonic antigen–related cell adhesion molecule (Ceacam1; CD66a ), a transmembrane biliary glycoprotein expressed epithelial, endothelial, immune cells, determines donor liver transplant quality. Here, we studied how AS of Ceacam1 affects ischemia-reperfusion injury (IRI) mouse human...
The current drastic shortage of donor organs has led to acceptance extended-criteria donors for transplantation, despite higher risk primary nonfunction. Here, we report the impact subnormothermic machine perfusion (SMP) preservation on protection >50% macrosteatotic livers. Dietary hepatic steatosis was induced in Wistar rats via 2-day fasting and subsequent 3-day re-feeding with a fat-free, carbohydrate-rich diet. This protocol induces 50-60% macrovesicular steatosis, which should be...
Carcinoembryonic antigen-related cell adhesion molecule 1 (CC1) acts through homophilic and heterophilic interactions with T immunoglobulin domain mucin domain-containing protein 3 (TIM-3), which regulates innate immune activation in orthotopic liver transplantation (OLT). We investigated whether cluster of differentiation (CD) 4
Abstract Sirtuin 1 (SIRT1) is a histone/protein deacetylase in the cellular response to inflammatory, metabolic, and oxidative stressors. We previously reported that myeloid SIRT1 regulates inflamed liver’s canonical pyroptosis cell death pathway. However, whether/how hepatocyte engaged programmed cold-stressed liver remains uncertain. Here, we undertook translational studies human mouse orthotopic transplantation (OLT) interrogate significance of hepatocyte-specific cold-stored donor livers...
Background. A major discrepancy between clinical and most experimental settings of liver ischemia-reperfusion injury (IRI) is the allogenicity. Methods. In current study, we first established a murine model allogeneic orthotopic transplantation with extended cold ischemia time (18 h). Roles CD4 T cells in pathogenesis IRI allografts were determined using depleting anti-CD4 antibody. The relevance as marker was analyzed retrospectively 55 transplant patients. Results. depletion both donors...
Preconditioning by brief ischemia protects not only the concerned organ but also other distant organs against subsequent lethal damage; this is called remote ischemic preconditioning (RIPC). This study was designed to investigate impact of intestinal RIPC on hepatic ischemia/reperfusion injury (IRI) with a special interest in heme oxygenase 1 (HO-1) induction second window protection (SWOP). Male Wistar rats were randomly assigned 2 groups: an group or sham group. Before IRI, either RIPC,...
Intestinal microbiota is thought to play an important role in hepatic ischemia/reperfusion injury (IRI) after liver transplantation (LT). Rifaximin, a nonabsorbable antibiotic used treat encephalopathy, exhibits antibacterial activity within the gut. We report first study examining impact of pre‐LT rifaximin use on reducing IRI and inflammatory cell infiltration LT. This retrospective single‐center included adult LT recipients from January 2013 through June 2016. Patients were divided into 2...
Galectin-9 (Gal-9) has gained attention as a multifaceted player in adaptive and innate immunity. To elucidate the role of Gal-9, we used mouse model partial liver ischemia/reperfusion injury (IRI) with wild type (WT) Gal-9 knockout (KO) mice well recombinant galectin-9 (reGal-9) protein. We found that expression was enhanced endogenously especially by hepatocytes Kupffer cells during warm IRI for liver, which causes massive destruction tissue. released into extracellular space highest...
Abstract Although Duchenne muscular dystrophy (DMD) primarily affects muscle tissues, the alterations to systemic metabolism manifested in DMD patients contribute severe phenotype of this fatal disorder. We propose that microRNA-378a (miR-378) alters carbohydrate and lipid dystrophic mdx mice. In our study, we utilized double knockout animals which lacked both dystrophin miR-378 ( /miR-378 −/− ). RNA sequencing liver identified 561 194 differentially expressed genes distinguished versus...
Liver fibrosis is a common pathway leading to cirrhosis. Cilostazol, clinically available oral phosphodiesterase-3 inhibitor, has been shown have antifibrotic potential in experimental non-alcoholic fatty liver disease. However, the detailed mechanisms of effect and its efficacy different model remain elusive.Male C57BL/6J mice were assigned five groups: fed normal diet (groups 1 2); 0.1% or 0.3% cilostazol-containing 3 4, respectively); 0.125% clopidogrel-containing (group 5). Two weeks...
By documenting potent antioxidative and anti-inflammatory functions, preclinical studies encourage heme oxygenase-1 (HO-1)-inducing regimens in clinical orthotopic liver transplantation (OLT). We aimed to determine the importance of recipient-derived HO-1 murine human OLTs. Hepatic biopsies from 51 OLT patients were screened for expression (Western blots) prior put-in (basal) post reperfusion (stressed) correlated with hepatocellular function. In parallel, livers proficient mice (WT;...