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1.
PLoS One ; 15(10): e0240883, 2020.
Article in English | MEDLINE | ID: mdl-33064766

ABSTRACT

It has been reported that supplementing certain amino acids has therapeutic effects on ulcerative colitis (UC). We intend to explore whether citrulline (Cit) supplementation has protective effects on UC. Fifteen male Wistar rats were divided into normal control group (NC group), UC group and UC+Cit group, with five rats in each group. The UC model was established by TNBS/ethanol method. Rats in UC+Cit group were intragastrically administered with Cit for 7 consecutive days after modeling. All rats were sacrificed after 7 days. Blood samples were collected to detect the number of monocytes. Colon tissues were taken for HE staining. Immunohistochemistry staining for CD68 and p-STAT3 were performed to detect the infiltration of monocytes and the phosphorylation of STAT3 in colon tissues. The concentrations of MCP-1, IL-6 and IL-17A and the protein expression of p-STAT3 in colon tissues were measured by ELISA and western blot methods, respectively. The body weight of UC group rats decreased significantly after 7 days (p<0.05). However, the weight loss of UC+Cit group rats was not statistically significant (p>0.05). The number of peripheral blood monocytes in UC+Cit group was significantly lower than that in UC group (p<0.05), and the infiltration of CD68-positive monocytes in the colon tissue of UC+Cit group was significantly reduced than that in UC group. The concentrations of MCP-1, IL-6 and IL-17A and the expression of p-STAT3 in colon tissues of UC+Cit group rats were significantly lower than those in UC group (both p<0.05). Our study suggests that Cit supplementation may be a potential therapy for UC.


Subject(s)
Citrulline/therapeutic use , Colitis, Ulcerative/drug therapy , Protective Agents/therapeutic use , Animals , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Body Weight , Colitis, Ulcerative/pathology , Colon/metabolism , Colon/pathology , Dietary Supplements , Disease Models, Animal , Interleukin-17/metabolism , Interleukin-6/metabolism , Male , Monocytes/cytology , Monocytes/immunology , Monocytes/metabolism , Phosphorylation , Rats , Rats, Wistar , STAT3 Transcription Factor/metabolism
2.
Biosci Rep ; 37(2)2017 04 30.
Article in English | MEDLINE | ID: mdl-28108674

ABSTRACT

The present study aimed to investigate the effects of miR-338 on morphine tolerance through the targeting of CXC chemokine receptor-4 (CXCR4) in a rat model of bone cancer pain (BCP). Sprague-Dawley (SD) rats were obtained and divided into model saline (n=10), model morphine (n=50), normal saline (n=10) and normal morphine (healthy rats, n=10) groups. After BCP rat model establishment, the remaining SD rats (n=40) in the model saline group were assigned into pLV-THM-miR-338, pLV-THM-anti-miR-338, CXCR4 shRNA, blank and PBS groups. Luciferase reporter gene assay was used for luciferase activity. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to detect the miR-338 and CXCR4 mRNA and protein expression. The model saline group showed increased mRNA and protein expressions of CXCR4 but decreased miR-338 compared with the model saline group, and the model morphine group had increased mRNA and protein expressions of CXCR4 but decreased miR-338 compared with the model saline group. The mRNA and protein expressions of miR-338 in the pLV-THM-miR-338 group increased remarkably while those of the pLV-THM-anti-miR-338 group decreased significantly compared with the CXCR4 shRNA, blank and PBS groups. The pLV-THM-miR-338, pLV-THM-anti-miR-338, CXCR4 shRNA and CXCR4 mRNA groups all had lower mRNA and protein expressions of CXCR4 than those in the blank and PBS groups. miR-338 exerts significant influence in the inhibition of morphine tolerance by suppressing CXCR4 in BCP.


Subject(s)
Bone Neoplasms/genetics , Cancer Pain/genetics , Drug Tolerance/genetics , MicroRNAs/genetics , Morphine/pharmacology , Receptors, CXCR4/genetics , Animals , Behavior, Animal/physiology , Blotting, Western , Bone Neoplasms/metabolism , Bone Neoplasms/physiopathology , Cancer Pain/metabolism , Cancer Pain/physiopathology , Disease Models, Animal , Female , Gene Expression Regulation, Neoplastic , Microscopy, Fluorescence , RNA Interference , Rats, Sprague-Dawley , Receptors, CXCR4/metabolism , Reverse Transcriptase Polymerase Chain Reaction
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