Evidence map›Paper›PMID 30801519›Full record

ArticleTransplantation2019

Inhibition of Cyclin-dependent Kinase 2 Signaling Prevents Liver Ischemia and Reperfusion Injury.

Jin Xu, Zhengze Xue, Cheng Zhang, Yuan Liu, Ronald W Busuttil, Jiamin Zhang, Jerzy W Kupiec-Weglinski, Haofeng Ji

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Transplantation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.8field-weighted citation impact, top 35% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. Inflammatory response to the ischaemia-reperfusion insult in the liver after major tissue trauma.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2022
    Review
  4. Review
  5. Review
  6. Frontiers in immunology · 2021
    Article
  7. Article
  8. Article
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 2 countries.

Jin XuDivision of Liver and Pancreas Transplantation, Department of Surgery, Dumont-UCLA Transplant Center, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA.
Zhengze XueDivision of Liver and Pancreas Transplantation, Department of Surgery, Dumont-UCLA Transplant Center, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA.
Cheng ZhangDivision of Liver and Pancreas Transplantation, Department of Surgery, Dumont-UCLA Transplant Center, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA.
Yuan LiuDivision of Liver and Pancreas Transplantation, Department of Surgery, Dumont-UCLA Transplant Center, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA.
Ronald W BusuttilDivision of Liver and Pancreas Transplantation, Department of Surgery, Dumont-UCLA Transplant Center, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA.
Jiamin ZhangDepartment of Surgery, People's Hospital of Jinhua, Jinhua, Zhejiang, China.
Jerzy W Kupiec-WeglinskiDivision of Liver and Pancreas Transplantation, Department of Surgery, Dumont-UCLA Transplant Center, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA.
Haofeng JiDivision of Liver and Pancreas Transplantation, Department of Surgery, Dumont-UCLA Transplant Center, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA.
University of California, Los Angeles · US

Funding

Regulation of Innate Immune Responses by Alloimmunity in Liver Ischemia-Reperfusion InjuryP01AI120944 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Fady M Kaldas · 2017 to 2026
$20.0M
NRF2 - SIRT1 SIGNALING AXIS IN LIVER TRANSPLANT REJUVENATIONR01DK062357 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KUPIEC-WEGLINSKI, JERZY W · 2003 to 2025
$8.4M
Tim Costimulation in Liver Transplant Ischemia InjuryR01DK102110 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KUPIEC-WEGLINSKI, JERZY W · 2015 to 2019
$1.7M
TIM-3 Negative Costimulation Signaling at the Innate-Adaptive Immune interface in Liver Transplant Ischemia-Reperfusion InjuryR01DK107533 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KUPIEC-WEGLINSKI, JERZY W · 2016 to 2020
$1.7M
Ischemia / Reperfusion Injury Mediated TIM-3+CD4+ T Cell Exhaustion In Liver TransplantR21AI138165 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JI, HAOFENG · 2018 to 2019
$428k
PACAP Mediated Neural Regulation of Hepatic Inflammation in Orthotopic Liver TransplantationR21AI122155 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JI, HAOFENG · 2016 to 2017
$424k
NIAID NIH HHS P01 AI120944NIAID NIH HHS R21 AI122155NIAID NIH HHS R21 AI138165NIDDK NIH HHS R01 DK062357NIDDK NIH HHS R01 DK102110NIDDK NIH HHS R01 DK107533
6 · The paper itself

Abstract

backgroundLiver ischemia and reperfusion injury (IRI) is a major complication of liver transplant, hepatectomy, and hemorrhagic shock. The cyclin-dependent kinase 2 (CDK2) acts as a pivotal regulator of cell cycle and proliferation.

methodsThis study evaluated the modulation and therapeutic potential of CDK2 inhibition in a mouse model of partial liver warm IRI.

resultsLiver IR-triggered intrinsic CDK2 expression, peaking by 0.5 hour of reperfusion and maintaining a high-level throughout 1 to 24 hours. Roscovitine, a specific CDK2 inhibitor, prevented liver IR-mediated damage with abolished serum alanine aminotransferase levels and reserved liver pathology. CDK2 inhibition-mediated liver protection was accompanied by decreased macrophage/neutrophil infiltration, diminished hepatocyte apoptosis, abolished toll like receptor 4 signaling and downstream gene inductions (C-X-C motif ligand-10, Tumor necrosis factor-α, interleukin-1β, and interleukin-6), yet augmented interleukin-10 expression. In vitro, CDK2 inhibition by Roscovitine suppressed macrophage TLR4 activation and further depressed downstream inflammatory signaling (myeloid differentiation factor 88, interferon regulatory transcription factor 3, p38, c-Jun N-terminal kinase, and extracellular-regulated kinase).

conclusionsOur novel findings revealed the critical role of CDK2 in hepatic cytoprotection and homeostasis against liver IRI. As CDK2 inhibition regulated local immune response and prevented hepatocyte death, this study provided the evidence for new treatment approaches to combat IRI in liver transplant.

Indexed as

AnimalsApoptosisCyclin-Dependent Kinase 2LiverMacrophagesMaleMAP Kinase Signaling SystemMiceMice, Inbred C57BLNeutrophil InfiltrationReperfusion InjurySignal TransductionToll-Like Receptor 4Cyclin-Dependent Kinase 2Tlr4 protein, mouseToll-Like Receptor 4

Identifiers

PMID30801519
PMCPMC6433525
OpenAlexW2919992868

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.