PMID- 32933722
OWN - NLM
STAT- MEDLINE
DCOM- 20210609
LR  - 20210609
IS  - 1532-3072 (Electronic)
IS  - 0040-8166 (Linking)
VI  - 66
DP  - 2020 Oct
TI  - Liraglutide in combination with human umbilical cord mesenchymal stem cell could 
      improve liver lesions by modulating TLR4/NF-kB inflammatory pathway and oxidative 
      stress in T2DM/NAFLD rats.
PG  - 101382
LID - S0040-8166(20)30079-3 [pii]
LID - 10.1016/j.tice.2020.101382 [doi]
AB  - Studies have shown that liraglutide, or human umbilical cord mesenchymal stem 
      cell (hUC-MSCs) can improve non-alcoholic fatty liver disease (NAFLD). However 
      there have been no studies on the combination of the two used to treat NAFLD. 
      This study aimed to explore the therapeutic effects of combination of liraglutide 
      and hUC-MSCs on liver injury in rats with type 2 diabetes mellitus (T2DM) and 
      NAFLD, and further investigate their mechanisms. Sprague Dawley rats fed by a 
      high fat and high sucrose diet were randomly divided into 5 groups, including NC 
      group, T2DM/NAFLD group, liraglutide group (treated with liraglutide, 200 mug/kg, 
      twice daily for 8 weeks), hUC-MSCs group (treated with hUC-MSCs at the first and 
      fifth weeks), liraglutid＋hUC-MSCs group (treated with liraglutide and hUC-MSCs). 
      Liver tissue was procured for histological examination, real-time qRT-PCR and 
      Western blot analysis. After treatment, liraglutide and hUC-MSCs reduced serum 
      ALT and AST levels, alleviate liver inflammation and improved liver 
      histopathology. The expressions of inflammatory cytokines, TLR4 and NF-kappaB in 
      serum and liver were significantly inhibited, particularly in the combination 
      treatment group. Eight weeks after liraglutide or hUC-MSCs administration, FBG, 
      HbA1c, HOMA-IR, ALT, AST, Liver wet eight and hepatic TLR4, NF-kappaB, IL-6, TNF-alpha, 
      8-OHdG mRNA and proteins were significantly decreased, and the levels of SOD 
      expression were significantly increased in three treatment groups compared with 
      T2DM/NAFLD group. This study suggests that liraglutide in combination with 
      hUC-MSCs could significantly improve glycolipid metabolism, insulin resistance 
      and liver injury in T2DM/NAFLD rats. Its mechanism may be related to the 
      down-regulation of the TLR4/NF-kappaB inflammatory pathway and improvement in 
      oxidative stress.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Xu, Xiangjin
AU  - Xu X
AD  - 900 Hospital of the Joint Logistics Team, Fuzong Clinical Medical College of 
      Fujian Medical University, Fuzhou 365000, Fujian, China.
FAU - Wang, Wenqing
AU  - Wang W
AD  - The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, 
      China.
FAU - Lin, Lu
AU  - Lin L
AD  - 900 Hospital of the Joint Logistics Team, Fuzong Clinical Medical College of 
      Fujian Medical University, Fuzhou 365000, Fujian, China.
FAU - Chen, Pin
AU  - Chen P
AD  - 900 Hospital of the Joint Logistics Team, Fuzong Clinical Medical College of 
      Fujian Medical University, Fuzhou 365000, Fujian, China. Electronic address: 
      chenpin@21cn.com.
LA  - eng
PT  - Journal Article
DEP - 20200512
PL  - Scotland
TA  - Tissue Cell
JT  - Tissue & cell
JID - 0214745
RN  - 0 (Cytokines)
RN  - 0 (NF-kappa B)
RN  - 0 (Toll-Like Receptor 4)
RN  - 839I73S42A (Liraglutide)
RN  - 88847-89-6 (8-Hydroxy-2'-Deoxyguanosine)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - 8-Hydroxy-2'-Deoxyguanosine/metabolism
MH  - Animals
MH  - Combined Modality Therapy
MH  - Cytokines/blood/genetics
MH  - Diabetes Mellitus, Type 2/blood/*complications
MH  - Humans
MH  - Inflammation/*pathology
MH  - Liraglutide/*pharmacology
MH  - Liver/pathology/ultrastructure
MH  - Liver Neoplasms/blood/pathology/*therapy
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*cytology/drug effects
MH  - NF-kappa B/genetics/*metabolism
MH  - Non-alcoholic Fatty Liver Disease/blood/*complications
MH  - *Oxidative Stress/drug effects
MH  - Rats, Sprague-Dawley
MH  - Superoxide Dismutase/genetics/metabolism
MH  - Toll-Like Receptor 4/genetics/*metabolism
MH  - Umbilical Cord/cytology
OTO - NOTNLM
OT  - Human umbilical cord mesenchymal stem cell
OT  - Liraglutide
OT  - Non-alcoholic fatty liver disease
OT  - Oxidative stress
OT  - TLR4/NF-kappaB
OT  - Type 2 diabetes mellitus
EDAT- 2020/09/17 06:00
MHDA- 2021/06/10 06:00
CRDT- 2020/09/16 05:30
PHST- 2020/02/12 00:00 [received]
PHST- 2020/05/08 00:00 [revised]
PHST- 2020/05/08 00:00 [accepted]
PHST- 2020/09/16 05:30 [entrez]
PHST- 2020/09/17 06:00 [pubmed]
PHST- 2021/06/10 06:00 [medline]
AID - S0040-8166(20)30079-3 [pii]
AID - 10.1016/j.tice.2020.101382 [doi]
PST - ppublish
SO  - Tissue Cell. 2020 Oct;66:101382. doi: 10.1016/j.tice.2020.101382. Epub 2020 May 
      12.