A 3D-printable device allowing fast and reproducible longitudinal preparation of mouse intestines

Accurate and reproducible analysis of murine small and large intestinal tissue is key for preclinical models involving intestinal pathology.Currently,there is no easily ac-cessible,standardized method that allows researchers of different skill levels to con-sistently dissect intestines in a time-efficient manner.Here,we describe the design and use of the 3D-printed“Mouse Intestinal Slicing Tool”(MIST),which can be used to longitudinally dissect murine intestines for further analysis.We benchmarked the MIST against a commonly used procedure involving scissors to make a longitudinal cut along the intestines.Use of the MIST halved the time per mouse to prepare the intestines and outperformed alternative methods in smoothness of the cutting edge and overall reproducibility.By sharing the plans for printing the MIST,we hope to contribute a uniformly applicable method for saving time and increasing consistency in studies of the mouse gastrointestinal tract.

Immunological mechanisms and therapeutic targets of fatty liver diseases

Alcoholic liver disease(ALD)and nonalcoholic fatty liver disease(NAFLD)are the two major types of chronic liver disease worldwide.Inflammatory processes play key roles in the pathogeneses of fatty liver diseases,and continuous inflammation promotes the progression of alcoholic steatohepatitis(ASH)and nonalcoholic steatohepatitis(NASH).Although both ALD and NAFLD are closely related to inflammation,their respective developmental mechanisms differ to some extent.Here,we review the roles of multiple immunological mechanisms and therapeutic targets related to the inflammation associated with fatty liver diseases and the differences in the progression of ASH and NASH.Multiple cell types in the liver,including macrophages,neutrophils,other immune cell types and hepatocytes,are involved in fatty liver disease inflammation.In addition,microRNAs(miRNAs),extracellular vesicles(EVs),and complement also contribute to the inflammatory process,as does intertissue crosstalk between the liver and the intestine,adipose tissue,and the nervous system.We point out that inflammation also plays important roles in promoting liver repair and controlling bacterial infections.Understanding the complex regulatory process of disrupted homeostasis during the development of fatty liver diseases may lead to the development of improved targeted therapeutic intervention strategies.

Type I interferon signaling facilitates resolution of acute liver injury by priming macrophage polarization

Due to their broad functional plasticity,myeloid cells contribute to both liver injury and recovery during acetaminophen overdose-induced acute liver injury(APAP-ALI).A comprehensive understanding of cellular diversity and intercellular crosstalk is essential to elucidate the mechanisms and to develop therapeutic strategies for APAP-ALI treatment.Here,we identified the function of IFN-I in the myeloid compartment during APAP-ALI.Utilizing single-cell RNA sequencing,we characterized the cellular atlas and dynamic progression of liver CD11b+cells post APAP-ALI in WT and STAT2 T403A mice,which was further validated by immunofluorescence staining,bulk RNA-seq,and functional experiments in vitro and in vivo.We identified IFN-I-dependent transcriptional programs in a three-way communication pathway that involved IFN-I synthesis in intermediate restorative macrophages,leading to CSF-1 production in aging neutrophils that ultimately enabled Trem2+restorative macrophage maturation,contributing to efficient liver repair.Overall,we uncovered the heterogeneity of hepatic myeloid cells in APAP-ALI at single-cell resolution and the therapeutic potential of IFN-I in the treatment of APAP-ALI.

Hospital readmission following transjugular intrahepatic portosystemic shunt:a 14-year single-center experience

Background:Placement of a transjugular intrahepatic portosystemic shunt(TIPS)is a relatively common procedure used to treat complications of portal hypertension.However,only limited data exist regarding the hospital-readmission rate after TIPS placement and no studies have addressed the causes of hospital readmission.We therefore sought to identify the 30-day hospital-readmission rate after TIPS placement at our institution and to determine potential causes and predictors of readmission.Methods:We reviewed our electronic medical-records system at our institution between 2004 and 2017 to identify patients who had undergone primary TIPS placement with polytetrafluoroethylene-covered stents and to determine the 30-day readmission rate among these patients.A series of univariable logistic-regression models were fit to assess potential predictors of 30-day readmission.Results:A total of 566 patients were included in the analysis.The 30-day readmission rate after TIPS placement was 36%.The most common causes for readmission were confusion(48%),infection(15%),bleeding(11%),and fluid overload(7%).A higher Model for End-Stage Liver Disease(MELD)score corresponded with a higher rate of readmission(odds ratio associated with each 1-unit increase in MELD score:1.06;95%confidence interval:1.02–1.09;P=0.001).Other potential predictors,including indication for TIPS placement,were not significantly associated with a higher readmission rate.Conclusions:The 30-day readmission rate after TIPS placement with covered stents is high,with nearly half of these readmissions due to hepatic encephalopathy—a known complication of TIPS placement.Novel interventions to help reduce the TIPS readmission rate should be prioritized in future research.