PMID- 33634985
OWN - NLM
STAT- MEDLINE
DCOM- 20211223
LR  - 20240330
IS  - 2001-1326 (Print)
IS  - 2001-1326 (Electronic)
IS  - 2001-1326 (Linking)
VI  - 11
IP  - 2
DP  - 2021 Feb
TI  - CCL4-mediated targeting of spleen tyrosine kinase (Syk) inhibitor using 
      nanoparticles alleviates inflammatory bowel disease.
PG  - e339
LID - 10.1002/ctm2.339 [doi]
LID - e339
AB  - Inflammatory bowel disease (IBD) has emerged a global disease and the ascending 
      incidence and prevalence is accompanied by elevated morbidity, mortality, and 
      substantial healthcare system costs. However, the current typical 
      one-size-fits-all therapeutic approach is suboptimal for a substantial proportion 
      of patients due to the variability in the course of IBD and a considerable number 
      of patients do not have positive response to the clinically approved drugs, so 
      there is still a great, unmet demand for novel alternative therapeutic 
      approaches. Spleen tyrosine kinase (Syk), a cytoplasmic nonreceptor protein 
      tyrosine kinase, plays crucial roles in signal transduction and there are 
      emerging data implicating that Syk participates in pathogenesis of several gut 
      disorders, such as IBD. In this study, we observed the Syk expression in IBD 
      patients and explored the effects of therapeutic Syk inhibition using 
      small-molecule Syk inhibitor piceatannol in bone marrow-derived macrophages 
      (BMDMs). In addition, due to the poor bioavailability and pharmacokinetics of 
      small-molecule tyrosine kinase inhibitors and superiority of targeting 
      nanoparticles-based drug delivery system, we herein prepared 
      piceatannol-encapsulated poly(lactic-co-glycolic acid) nanoparticles that 
      conjugated with chemokine C-C motif ligand 4 (P-NPs-C) and studied its 
      therapeutic effects in vitro in BMDMs and in vivo in experimental colitis model. 
      Our results indicated that in addition to alleviating colitis, oral 
      administration of P-NPs-C promoted the restoration of intestinal barrier function 
      and improved intestinal microflora dysbiosis, which represents a promising 
      treatment for IBD.
CI  - (c) 2021 The Authors. Clinical and Translational Medicine published by John Wiley & 
      Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
FAU - Gong, Wenbin
AU  - Gong W
AD  - School of Medicine, Southeast University, Research Institute of General Surgery, 
      Jinling Hospital, Nanjing, China.
AD  - Research Institute of General Surgery, Jinling Hospital, Nanjing, China.
FAU - Yu, Jiafei
AU  - Yu J
AD  - Research Institute of General Surgery, Jinling Hospital, Nanjing, China.
FAU - Zheng, Tao
AU  - Zheng T
AD  - Research Institute of General Surgery, Jinling Hospital, Nanjing, China.
FAU - Liu, Peizhao
AU  - Liu P
AD  - Research Institute of General Surgery, Jinling Hospital, Nanjing, China.
FAU - Zhao, Fan
AU  - Zhao F
AD  - Research Institute of General Surgery, Jinling Hospital, Nanjing, China.
FAU - Liu, Juanhan
AU  - Liu J
AD  - Research Institute of General Surgery, Jinling Hospital, Nanjing, China.
FAU - Hong, Zhiwu
AU  - Hong Z
AD  - Research Institute of General Surgery, Jinling Hospital, Nanjing, China.
FAU - Ren, Huajian
AU  - Ren H
AD  - Research Institute of General Surgery, Jinling Hospital, Nanjing, China.
FAU - Gu, Guosheng
AU  - Gu G
AD  - Research Institute of General Surgery, Jinling Hospital, Nanjing, China.
FAU - Wang, Gefei
AU  - Wang G
AD  - Research Institute of General Surgery, Jinling Hospital, Nanjing, China.
FAU - Wu, Xiuwen
AU  - Wu X
AD  - Research Institute of General Surgery, Jinling Hospital, Nanjing, China.
FAU - Zhao, Yun
AU  - Zhao Y
AD  - Department of General Surgery, BenQ Medical Center, The Affiliated BenQ Hospital 
      of Nanjing Medical University, Nanjing, China.
FAU - Ren, Jianan
AU  - Ren J
AUID- ORCID: 0000-0002-4697-4762
AD  - School of Medicine, Southeast University, Research Institute of General Surgery, 
      Jinling Hospital, Nanjing, China.
AD  - Research Institute of General Surgery, Jinling Hospital, Nanjing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Transl Med
JT  - Clinical and translational medicine
JID - 101597971
RN  - 0 (Chemokine CCL4)
RN  - 0 (Ligands)
RN  - 0 (Nanoparticle Drug Delivery System)
RN  - 0 (Stilbenes)
RN  - 6KS3LS0D4F (3,3',4,5'-tetrahydroxystilbene)
RN  - EC 2.7.10.2 (SYK protein, human)
RN  - EC 2.7.10.2 (Syk Kinase)
MH  - Animals
MH  - Caco-2 Cells
MH  - Chemokine CCL4/*metabolism
MH  - Disease Models, Animal
MH  - Humans
MH  - Inflammatory Bowel Diseases/*drug therapy
MH  - Intestinal Mucosa/drug effects/metabolism
MH  - Ligands
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nanoparticle Drug Delivery System/*therapeutic use
MH  - Stilbenes/administration & dosage/*therapeutic use
MH  - Syk Kinase/*antagonists & inhibitors
MH  - THP-1 Cells
PMC - PMC7888545
OTO - NOTNLM
OT  - CCL4
OT  - Syk
OT  - inflammatory bowel disease
OT  - piceatannol
COIS- The authors declare no conflict of interest.
EDAT- 2021/02/27 06:00
MHDA- 2021/02/27 06:01
PMCR- 2021/02/17
CRDT- 2021/02/26 08:38
PHST- 2020/12/02 00:00 [received]
PHST- 2021/02/01 00:00 [revised]
PHST- 2021/02/07 00:00 [accepted]
PHST- 2021/02/26 08:38 [entrez]
PHST- 2021/02/27 06:00 [pubmed]
PHST- 2021/02/27 06:01 [medline]
PHST- 2021/02/17 00:00 [pmc-release]
AID - CTM2339 [pii]
AID - 10.1002/ctm2.339 [doi]
PST - ppublish
SO  - Clin Transl Med. 2021 Feb;11(2):e339. doi: 10.1002/ctm2.339.