A guiding role of the Arabidopsis circadian clock in cell differentiation revealed by time-series single-cell RNA sequencing

Circadian rhythms and progression of cell differentiation are closely coupled in multicellular organisms. However, whether establishment of circadian rhythms regulates cell differentiation or vice versa has not been elucidated due to technical limitations. Here, we exploit high cell fate plasticity of plant cells to perform single-cell RNA sequencing during the entire process of cell differentiation. By analyzing reconstructed actual time series of the differentiation processes at single-cell resolution using a method we developed (PeakMatch), we find that the expression profile of clock genes is changed prior to cell differentiation, including induction of the clock gene LUX ARRYTHMO (LUX). ChIP sequencing analysis reveals that LUX induction in early differentiating cells directly targets genes involved in cell-cycle progression to regulate cell differentiation. Taken together, these results not only reveal a guiding role of the plant circadian clock in cell differentiation but also provide an approach for time-series analysis at single-cell resolution

The changes in treatment strategies in ABOi living donor liver transplantation for acute liver failure

Introduction. Living donor liver transplantation (LDLT) using ABO-incompatible (ABOi) graft for acute liver failure (ALF) is a developing treatment modality. Methods. We reviewed the changes in our treatment strategies in applying ABOi LDLT for FH over our fourteen years of experience. Results. Five patients with ALF received LDLT in adults using ABOi grafts, with different but gradually renewed protocols. The etiologies for acute liver failure included autoimmune hepatitis (n=3) and unknown (n=2). The desensitization protocol for ABOi barrier included Case #1 ; local infusion (portal vein)+plasma exchange (PE), Case #2 ; local infusion (hepatic artery)+rituximab+PE, Case #3 and #4 ; rituximab+PE, and Case #5 ; rituximab+PE under high-flow continuous hemodiafiltration. Local infusion was abandoned since Case #3, because Case #1 had portal vein thrombosis resulting in graft necrosis and Case #2 had hepatic artery dissection. The patients (Case #2 and #3), who received rituximab within 7 days before LDLT, experienced antibody-mediated rejection. Thus, the most recent protocol for ABOi-LDLT is that rituximab is given 2 weeks before LDLT, followed by high-flow continuous hemodiafiltration to obstacle hepatic encephalopathy until LDLT. The four patients except Case #1 are doing well with good graft function over 3.8±3.7 years. Conclusion. Rituximab-based ABOi-LDLT, most-recently under high-flow hemodiafiltration for treating encephalopathy, is a feasible option for applying LDLT for ALF

Serum Wisteria Floribunda Agglutinin-Positive Mac-2 Binding Protein Values Predict the Development of Hepatocellular Carcinoma among Patients with Chronic Hepatitis C after Sustained Virological Response

Measurement of Wisteria floribundaagglutinin-positive human Mac-2 binding protein (WFA+-M2BP) in serum was recently shown to be a noninvasive method to assess liver fibrosis. The aim of this study was to evaluate the utility of serum WFA+-M2BP values to predict the development of hepatocellular carcinoma (HCC) in patients who achieved a sustained virological response (SVR) by interferon treatment. For this purpose, we retrospectively analyzed 238 patients with SVR who were treated with interferon in our department. Serum WFA+-M2BP values were measured at pre-treatment (pre-Tx), post-treatment (24 weeks after completion of interferon; post-Tx), the time of HCC diagnosis, and the last clinical visit. Of 238 patients with SVR, HCC developed in 16 (6.8%) patients. The average follow-up period was 9.1 years. The cumulative incidence of HCC was 3.4% at 5 years and 7.5% at 10 years. The median pre-Tx and post-Tx WFA+-M2BP values were 1.69 (range: 0.28 to 12.04 cutoff index (COI)) and 0.80 (range: 0.17 to 5.29 COI), respectively. The WFA+-M2BP values decreased significantly after SVR (P 60 years), sex (male), pre-Tx platelet count ( 2.0 COI) were associated with the development of HCC after SVR. Conclusion: Post-Tx WFA+-M2BP (> 2.0 COI) is associated with the risk for development of HCC among patients with SVR. The WFA+-M2BP values could be a new predictor for HCC after SVR

Hepatic stellate cells secrete WFA+-M2BP; its role in biological interactions with Kupffer cells

Background and aims: Hepatic stellate cells (HSCs) play a central role in hepatic fibrosis, and are regulated by Kupffer cells (KCs). Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA(+) -M2BP) was recently identified as a serum marker for hepatic fibrosis. Although WFA(+) -M2BP was identified as a ligand of Mac-2, the function of WFA(+) -M2BP in hepatic fibrosis remains unclear. Methods: Liver specimens were obtained from five patients with cirrhosis, five with chronic hepatitis, and five without hepatic fibrosis. WFA(+) -M2BP kinetics were evaluated histologically and in subpopulations of liver cells such as HSCs, Kupffer cells, endothelial cells, biliary epithelial cells, and hepatocytes in in vitro culture. The function of WFA(+) -M2BP in activated HSCs was evaluated using immunoblot analysis. Results: Numbers of WFA(+) -M2BP-positive cells in liver tissues increased with fibrosis stage. There were significant differences in WFA(+) -M2BP levels between fibrosis stages F0 and F1-2 (P = 0.012), and between fibrosis stages F1-2 and F3-4 (P < 0.001). HSCs were the source of WFA(+) -M2BP secretion in in vitro cultures of liver cells, as determined by sandwich ELISA. Cells of the human HSC line LX-2 also secreted WFA(+) -M2BP. Histologically, tissue sections showed that WFA(+) -M2BP was located in Mac-2 expressing KCs. In vitro assays showed exogenous WFA(+) -M2BP stimulation enhanced Mac-2 expression in KCs, and that HSCs co-cultured with KCs increased α-SMA expression. Finally, Mac-2-depleted KCs with siRNA had reduced α-SMA expression following coculture with HSCs. Conclusions: WFA(+) -M2BP from HSCs induces Mac-2 expression in KCs, which in turn activates HSCs to be fibrogenic. Hepatic stellate cells secreting WFA+‐M2BP: Its role in biological interactions... | Request PDF. Available from: https://www.researchgate.net/publication/311898414_Hepatic_stellate_cells_secreting_WFA-M2BP_Its_role_in_biological_interactions_with_Kupffer_cells [accessed Jan 17 2018]

Ascending Aortic Calcification as a Potential Predictor for Low Bone Mineral Density: A Pilot Study

Background. Identifying the factors related to low bone mineral density (BMD) can have significant implications for preventing hip fractures. The correlation between ascending aortic calcification and BMD has never been reported. Therefore, the purpose of the current study is to confirm the hypothesis that ascending aortic calcification can be used as a predictive factor for low BMD and to find a radiographic sign to show it. Method. Plain film and computed tomography (CT) images of the thorax were obtained from 91 patients with hip fractures. Using the images, the calcification line of the ascending aorta adjacent to the aortic arch was evaluated. A prominent calcification line confirmed by both plain film and CT was classified as +2. A line which was ambiguous on plain film but confirmed by CT was classified as +1. Cases with no calcification were categorized as 0 (control). We compared the classified score with the BMD and calculated the kappa coefficient to measure intraobserver reliabilities for this radiographic finding. Results. Twenty-eight patients showed a +2 line, twenty-four patients showed a +1 line, and thirty-nine patients showed 0 lines. The median BMD of each group was 0.37 for the +2 line, 0.45 for the +1 line, and 0.51 for the 0 line. The BMD for the +2 group was significantly lower than the others. The kappa coefficient was approximately 0.6 (p<0.01). Conclusion. The imaging finding of calcification of the ascending aorta might be considered as a potential surrogate marker of low BMD. In such subjects, BMD might be ordered for the confirmation of diagnosis of osteoporosis. Mini-Abstract. The Aortic Arch Tail Sign, a calcification line on the ascending aorta, was relevant to low BMD in the current study. BMD can be ordered for the confirmation of diagnosis of osteoporosis in a subject incidentally found to have ascending aorta calcification on X-ray or CT

Normothermic Regional Perfusion Can Improve Both Utilization and Outcomes in DCD Liver, Kidney, and Pancreas Transplantation

Background. Normothermic regional perfusion (NRP) has gained widespread adoption in multiple European countries. The aim of this study was to examine the influence of thoracoabdominal-NRP (TA-NRP) on the utilization and outcomes of liver, kidney, and pancreas transplantation in the United States. Methods. Using the US national registry data between 2020 and 2021, donation after circulatory death (DCD) donors were separated into 2 groups: DCD with TA-NRP and without TA-NRP. There were 5234 DCD donors; among them 34 donors were with TA-NRP. After 1:4 propensity score matching, the utilization rates were compared between DCD with and without TA-NRP. Results. Although the utilization rates of kidney and pancreas were comparable (P = 0.71 and P = 0.06, 94.1% versus 95.6% and 8.8% versus 2.2%, respectively), that of liver in DCD with TA-NRP was significantly higher (P < 0.001; 70.6% versus 39.0%). Among 24 liver transplantations, 62 kidney transplantations, and 3 pancreas transplantations from DCD with TA-NRP, there were 2 liver grafts and 1 kidney graft that failed within 1 y after transplantation. Conclusions. TA-NRP in the United States significantly increased the utilization rate of abdominal organs from DCD donors with comparable outcomes after transplantation. Increasing use of NRP may expand the donor pool without compromising transplant outcomes

Association of gut microbiota with portal vein pressure in patients with liver cirrhosis undergoing living donor liver transplantation

Abstract Background and Aim Many recent studies have shown a relationship between various systemic diseases and the gut microbiota (GM), with the gut–liver axis receiving particular attention. In contrast, no report has comprehensively shown the effects of GM on the pathophysiology of patients undergoing living donor liver transplantation (LDLT). Method We enrolled 16 recipients who underwent LDLT for liver cirrhosis, and 17 donors constituted the reference group. We examined the differences in GM between recipients and donors. We also examined the relationships between GM, short‐chain fatty acids, and portal vein pressure (PVP) in recipients. Results There was no significant difference in alpha‐diversity between the recipients and donors, but there was variation in beta‐diversity among the recipients. The abundance of the phylum Bacteroidetes was significantly higher in recipients than in donors (P = 0.016), and it was positively correlated with PVP (r = 0.511, P = 0.043). Propionic acid, which is a component of short‐chain fatty acids, was positively correlated with PVP (r = 0.544, P = 0.0295), the phylum Bacteroidetes (r = 0.677, P = 0.004), and total bilirubin concentration (r = 0.501, P = 0.048). Propionic acid was negatively correlated with serum albumin concentration (r = −0.482, P = 0.043). Conclusion Our findings suggest relationships between fecal Bacteroidetes levels, propionic acid concentrations, and PVP in patients with liver cirrhosis undergoing LDLT

Surgery-related disseminated intravascular coagulation predicts postoperative complications

Abstract Purpose The rate of postoperative morbidity, including infectious complications, is still high after major hepatobiliary pancreatic (HBP) surgery. Although surgery-related disseminated intravascular coagulation (DIC) occurs in some cases, its significance has not been elucidated in HBP surgery. This study aimed to evaluate the influence of surgery-related DIC on the complication severity after HBP surgery. Methods We analyzed the records of 100 patients with hepatectomy in two or more segments, hepatectomy with biliary tract reconstruction, and pancreaticoduodenectomy. The baseline characteristics and complications were compared between patients with and without surgery-related DIC on postoperative day 1 (POD1) after HBP surgery between 2010 and 2018. Complication severity was assessed using the Comprehensive Complication Index (CCI). Results The DIC group (surgery-related DIC on POD1) had predictive factors, such as larger bleeding volume and higher liver enzyme levels. The DIC group exhibited significantly elevated rates of surgical site infection, sepsis, prolonged intensive care unit stay, more frequent blood transfusions, and higher CCI. Furthermore, compared with and without adjustment of DIC, odds ratio (OR) of AST level and operation time for  the risk of high CCI decreased (OR of AST level: 1.25 to 1.19 and OR of operation time: 1.30 to 1.23) and the significant differences had vanished. Conclusions Surgery-related DIC on POD1 could be a partial mediator between AST level, operation time and higher CCI. The prevention or proper management of surgery-related DIC on POD1 can be an important target to reduce the severity of postoperative complications