1.Protective effect of loganin and morroniside on HUVEC injury induced by advanced glycation end products
Hongsheng SHEN ; Huiqin XU ; Chunhong LU ; Guoying DAI ; Kang XU ; Xing LYU ; Yuping CHEN ; Yunhao WU
Chinese Pharmacological Bulletin 2016;32(8):1063-1067
Aim To observe the protective mechanism of loganinand morroniside ( active components in Cornus officinalis) on HUVEC injury induced by advanced glycation end products ( AGEs ) .Methods HUVECs were cultured in vitro and divided into control group , model group ( AGEs group ) , loganin group , morroni-side group and aminoguanidine group ( set as positive control).After being incubated with loganin and mor-roniside( final concentrations were 100,10,1 μmol?L-1 ) for 1 h, HUVECs were stimulated by AGEs of 200 mg? L-1 for 24 h.Then, the cell viability was measured by using MTT method .The supernatant was extracted and the levels of NO ,ET-1,MCP-1,VCAM-1 were measured by the corresponding kits .Receptors of advanced glycation end products ( RAGE ) and NF-κB in HUVEC were detected by Western blot .Results Loganin and morroniside could inhibit HUVEC injury induced by AGEs .In model group ,the contents of ET-1,MCP-1,VCAM-1 increased(P<0.01),the content of NO decreased ( P <0.01 ) and the expression of RAGE and NF-κB increased(P<0.01); however,lo-ganin and morronside could reduce the ET-1,MCP-1, VCAM-1contents,increase the NO content and down-regulate the expression of RAGE and NF-κB to differ-ent extents .Conclusion Loganin and morroniside could ameliorate HUVEC injury , and its mechanism may be related to inhibit inflammation , the improve-ment of endothelial cell function , and the decrease of the expression of RAGE .
2.Effects of 5-fluorouracil with 1-methyl tryptophan on myeloid-derived suppressor cells in gastric cancer bearing 615 mice
Gai WANG ; Huiqin SHEN ; Xirun WU ; Xiaoli LIU ; Guiyun KANG ; Zheping LI ; Qi WANG
Chinese Journal of General Surgery 2014;29(6):464-466
Objective To investigate the effect of 1-MT in combination with 5-FU on the number of myeloid-derived supressor cells (MDSC) in gastric carcinoma beating mice.Methods By using the lipofectamine TM 2000,the eukaryotic expression plasmid pcDNA3.1-IDO and empty vector pcDNA3.1 (+) were transfected in a MFC cell line.Animal model of gastric cancer bearing 615 mice were established to give respectively normal saline (NS),1-MT,5-FU and 1-MT + 5-FU therapy.Flow cytometry and immunofluorescence were used to analyze MDSC expression in tumor tissue.Result (1) The expression of MDSC was detected in transplanted tumor.(2)The expression of MDSC in gastric cancer beating 615 mice (49.8% ± 1.1%) was higher than the normal group (1.2% ± 0.3%) (P < 0.05).(3) Compared with normal group the MDSC expression in 1-MT + 5-FU group (18.5 % ± 0.5 %) decreased significantly (P < 0.05).Conclusions Combining 1-MT with 5-FU can reduce the number of MDSC in gastric cancer bearing 615 mice,improving tumor microenvironment.
3.Study on the relationship between apoptosis modulator Fas/ FasL and sFas in peripheral blood lytnphoeytes and KD
Yazhen DI ; Haiyan QIU ; Jianping ZHANG ; Guogui KANG ; Huiqin CHEN ; Ruosong ZHANG ; Chao LI ; Yihong FENG ; Jianying ZHAO
Chinese Journal of Rheumatology 2008;12(9):635-637
Objective To explore the effect of Fas, Fas ligand (FasL), soluble Fas (sFas) and their clinical significance in KD. Methods The expression of Fas, FasL in peripheral blood lymphocytes (PBLC) were detected with flow cytometery at acute and remission stages in patients with KD; and the serums Fas was detected by double antibody sandwich ELISA in the patients with KD at acute and remission stage, meanwhile erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) were also tested. Results The expression of Fas, FasL in PBLC in patients with KD at acute stage was (14.2±0.5)% and (1.61±0.09)% respectively , which were significantly lower than those at remission stage [(15.7±0.5)%, (1.95±0.09)% respectively (P<0.05 and P<0.01)]. The expression of Fas in PBLC in the patients with KD at acute and remission stage was both significantly lower than that in normal control group (20.8±0.5)% (P<0.01 both);The expression of FasL in PBLC in patients with KD at acute and remission stage was both significantly lower than that in normal control group (20.8±0.5)% (P<0.01 both); the serum sFas in patients with KD at acute and remission stage was (1906±55)μg/L and (1622±52)μg/L respectively , which was significantly higher than that in normal control group (1151±51)μg/L (P<0.01 both); the serum sFas at acute stage was obviously higher than that at remission stage (P<0.01); there was positive correlation between sFas and ESR, CRP (P<0.01 both). Conclusion There are abnormal expressions of Fas/FasL in PBLC and sFas in patients with KD. Fas/FasL is lower and sFas is higher than that of the controls. The abnormal expression of Fas/ FasL in lymphocytes and the apoptosis triggered by sFas are probably involved in the immunological aberrance and pathogenesis of KD. sFas may be used as a marker to evaluate the disease activity and therapeutic efficacy.
4.Detailed resume of RNA m6A demethylases.
Dandan SHEN ; Bo WANG ; Ya GAO ; Lijuan ZHAO ; Yaping BI ; Jinge ZHANG ; Ning WANG ; Huiqin KANG ; Jingru PANG ; Ying LIU ; Luping PANG ; Zhe-Sheng CHEN ; Yi-Chao ZHENG ; Hong-Min LIU
Acta Pharmaceutica Sinica B 2022;12(5):2193-2205
N6-Methyladenosine (m6A) is the most abundant internal modification in eukaryotic mRNA, playing critical role in various bioprocesses. Like other epigenetic modifications, m6A modification can be catalyzed by the methyltransferase complex and erased dynamically to maintain cells homeostasis. Up to now, only two m6A demethylases have been reported, fat mass and obesity-associated protein (FTO) and alkylation protein AlkB homolog 5 (ALKBH5), involving in a wide range of mRNA biological progress, including mRNA shearing, export, metabolism and stability. Furthermore, they participate in many significantly biological signaling pathway, and contribute to the progress and development of cancer along with other diseases. In this review, we focus on the studies about structure, inhibitors development and biological function of FTO and ALKBH5.