1.Effects of intraperitoneal injection of 5-HT2A receptor antagonist MDL11939 on acute and chronic pain in mice
Siting HUANG ; Ningning JI ; Lei DU ; Gongliang ZHANG ; Yongmei ZHANG
Chinese Pharmacological Bulletin 2017;33(2):223-226,227
Aim To investigate the effects and signifi-cance of 5-HT2A receptor antagonist MDL1 1 939 on a-mice.Methods Kunming male mice were suffered a-cute acetic acid visceral pain,acute incision pain and CCI neuropathic pain.After each animal model was es-tablished,MDL1 1 939 was injected intraperitoneally. The writhing reaction was used to assess acute acetic acid visceral pain,while the thermal withdrawal laten-cy (TWL)was used to evaluate the acute incision pain and CCI neuropathic pain.Results Compared with the control group,MDL1 1 939 (0.25,0.5,1 .0 mg· kg -1 ,i.p.)relieved acetic acid visceral pain signifi-cantly in a dose-dependent manner in mice,as re-vealed by the significant reduction of the number of twisting.In acute incision pain and CCI neuropathic pain,MDL1 1 939 (0.5 mg·kg -1 ,i.p.)significantly increased TWL level.Conclusion 5-HT2A receptor antagonist MDL1 1 939 has analgesic effects on visceral pain,acute pain and neuropathic pain,which might be a novel therapeutic target to treat different pain in clini-cal situations.
2.Characterization of swine leukocyte antigen class I genes and homology analysis of the similarity to HLA in GGTA1 -/- Wuzhishan minipigs
Yingdi JIANG ; Guomin ZENG ; Ningning SHI ; Xirui LI ; Huili JI ; Dengke PAN ; Shuangbao GUN
Acta Laboratorium Animalis Scientia Sinica 2016;24(4):375-380
Objective This study was aimed to characterize the swine leukocyte antigen( SLA) class I genes of GGTA1 -/ - Wuzhishan minipigs and compare their similarity to human leukocyte antigen( HLA) . It has important implica?tions for understanding the cellular rejection in xenotransplantation. Methods Specimens of ear tissue from six founding GGTA1 -/ - Wuzhishan minipigs were collected, and the SLA class I genes (SLA?1, SLA?3, SLA?2) were amplified by RT?PCR. Purified products were cloned into pEASY?T1 vectors and sequenced, followed by BLAST alignment and using bioin? formatc analysis to characterize the SLA class I genes and compare with the similarity to HLA. Results A total of six al?leles were detected, among them alleles were previously reported (SLA?1?0703,SLA?2?1102, SLA?3?0401, SLA?3?0403), and the other were novel (SLA?1?0401wz01, SLA?2?11wz01). The homology between alleles of SLA class I genes in Wuzhishan minipigs and HLA was from 70?5% to 72?1%. The homology analysis of critical amino acid residues on HLA binding with human CD8 + molecules showed that SLA?1?0401wz01, SLA?1?0703, SLA?2?11wz01, SLA?2?1102 and SLA?3?0401 occurred mutant at amino acid positions 225 and 228 ( T→S,T→M) , whereas the other loci were highly conserved. There was a high homology at amino acid level between SLA?2?11wz01, SLA?2?1102 and HLA class I genes which are NK cell KIRs binding sites. Conclusions The amino acid sequences of SLA class I genes of GGTA1 -/ -Wuzhishan minipigs have a high homology to HLA. From the point of view of cell?mediated xenograft rejection, the amino acid sequences of SLA class I genes of GGTA1 -/ - Wuzhishan minipigs have a high homology to HLA, therefore, Wzhishan minipigs may become a good potential donor for pig?human xenotransplantation.
3.Activation of small conductance Ca2+ activated K+ channelin spinal cord could inhibit morphine-induced hyperalgesia in mice
Junsheng ZHU ; Gongliang ZHANG ; Lei DU ; Ningning JI ; Siting HUANG ; Yongmei ZHANG ; Rong HUA
Chinese Pharmacological Bulletin 2017;33(4):547-551
Aim To explore the effect of activated SK channels(small conductance Ca2+-activated K+ channels) on morphine-induced hyperalgesia in the spinal cord in mice.Methods Adult C57BL6/N male mice were chosen to establish the model of morphine-hyperalgesia.The changes of tail withdrawal latency(TWL), mechanical withdrawal threshold(MWT) and the threshold of visceral pain were observed after intrathecal 1-EBIO, the agonist of SK channels.Results Compared with the control group, TWL, MWT and the threshold of visceral pain were decreased after morphine injection.After intrathecal 1-EBIO, the TWL, MWT and visceral pain threshold were increased.The level of spinal membrane SK2 expression in morphine-treated mice was decreased compared with that of control group.After intrathecal 1-EBIO, the level of spinal membrane SK2 expression was increased.Conclusion SK channels in the spinal cord are involved in morphine-induced hyperalgesia in mice.
4.Effect of continuous incision infusion different concentration of ropivacaine for postoperative analgesia after radical mastectomy
Ming XIA ; Hui LI ; Jianhua TONG ; Ningning JI ; Wen QI ; Manlin DUAN ; Shaohua WANG ; Jianguo XU
The Journal of Clinical Anesthesiology 2017;33(1):19-21
Objective To observe the effect of continuous incision infusion different concentra-tion of ropivacaine for postoperative analgesia after radical mastectomy.Methods One hundred pa-tients under radical mastectomy,aged 40-70 years,ASA Ⅰ or Ⅱ,were randomly divided into four groups (n =25 each):0.2% (group R1),0.3% (group R2),0.4% (group R3)ropivacaine incision continued infiltration group and patient-controlled intravenous analgesia (group PCIA)as control group.VAS pain scores,sedation Ramsay score and side effects were recorded at each time point in rest and turning over 90°,2 h (T1 ),4 h (T2 ),8 h (T3 ),12 h (T4 ),24 h (T5 ),48 h (T6 )after the operation.Results VAS scores in group R1 at T1-T6 in rest and turn over 90°were significantly high-er than that of group PCIA (P <0.05).There were no significant differences among the group PCIA, group R2 and group R3.Sedation score in PCIA group was significantly higher than that in the other three groups (P <0.05),and the adverse reactions,such as nausea and vomiting,in group PCIA (2 cases)were more serious than that in the other groups (0 cases ).There were no significant differences among the other groups.Conclusion Ropivacaine plays an effective role in infiltration an-algesia when its concentration reaches 0.3% subcutaneous after radical mastectomy.
5.Expression of interleukin-18 and interleuldn-18 receptor a chain of the peripheral white blood cells in immune thrombocytopeula
Qian WANG ; Fengxia ZHAN ; Ningning SHAN ; Ming HOU ; Xiaojing YANG ; Nan LU ; Hongchun WANG ; Xiaolin ZHANG ; Xuebin JI ; Chunyan JI
Chinese Journal of Internal Medicine 2010;49(4):316-319
Objective To detect the expression of interleukin (IL)-18 of the peripheral blood cells and IL-18 receptor α chain(IL-18Rα) on the surface of CD_3~+ cells in patients newly diagnosed as immune thrombocytopenia (ITP) before medication and to explore the roles of IL-18 and IL-18Rα in the development of ITP. Methods Eighteen out-patients or inpatients with acute ITP accepting treatment in Qilu Hospital were enrolled in this study and 15 matching healthy subjects were taken as control. Plasma IL-18 level was detected with enzyme linked immunosorbent assay (ELISA), the expression of IL-18Rα on CD_3~+ lymphocytes and total lymphoeytes were measured with flow cytometry; T-bet and GATA-3 mRNA were measured with reverse transcriptase polymcrase chain reaction (RT-PCR). Results The expression of IL-18 in acute ITP plasma was (468. 57 ± 141.62) ng/L and IL-18Rα on the surface of CD_3~+ cells and lymphocytes were (8.50 ±3. 16)% and (9. 16±2.98)% respectively. The levels of IL-18 and IL-18Rα were increased in active ITP patients as compared with those in the controls (P <0. 05). The levels of IL-18 mRNA (0. 12 ±0. 02) and T-bet mRNA (0. 07 ±0. 02) were significantly increased in patients with active ITP as compared with those in the controls (P <0.05), while GATA-3 mRNA (0.0039±0.0014) were significantly decreased in patients with active ITP (P < 0. 05). The balance between T-bet and GATA-3 was significantly disturbed in ITP. Conclusions Through the variation of the levels of gene and protein, our study showed that IL-18 and IL-18Rα might upregulate the expression of Th1-cytokines in ITP patients. It is also suggested that IL-18 has potential association with the development of ITP. Especially, it may provide a new treatment method for ITP by regulating the ratio of T-bet and GATA-3 and resuming the balance of Th1/ Th2.
6.The outcomes of brachytherapy combined with external beam radiotherapy and hormonal therapy for local high-risk or intermediated-risk prostate cancer
Weigang YAN ; Zhi'en ZHOU ; Yi ZHOU ; Hanzhong LI ; Zhigang JI ; Fuquan ZHANG ; Jie QIU ; Mei XU ; Ningning LI ;
Chinese Journal of Urology 2017;38(6):442-447
Objective To evaluate the outcomes and complications of permanent brachytherapy combined with external beam radiotherapy and hormonal therapy for local high-risk or intermediated-risk prostate cancer.Methods There were 354 men with local high-risk or intermediated-risk prostate cancer were reviewed,including 111 men with local intermediated-risk prostate cancer and 243 men with local highrisk prostate cancer.The age of the patients were 48 to 84 years old (mean age 72.4 years old).The preoperative PSA levels were in a range of 3.8 to 99.8ng/ml (mean 29.6 g/ml) and the preoperative Gleason scores were 4 to 9 (mean 6.8).The prostate volume were 13.7 to 65.0 ml (mean 30.5 ml).All the patients were treated with brachytherapy combined with hormonal therapy,including 69 patients received additional external beam radiotherapy.All patients were followed up for biochemical progression-free survival (bPFS),distant disease free survival (DDFS),overall survival (OS),cause-specific survival (CSS) rate and complications.Results Among 354 cases,174 cases underwent brachytherapy after the diagnosis of prostate cancer,and 157 cases underwent brachytherapy after maximal androgen blockade (MAB) treatmentfor 3 months,while the other 23 patients with large prostate underwent brachytherapy after MAB treatment for 6 months.All 354 cases were treated with MAB after brachytherapy.One hundred and eleven cases in intermediated-risk group were treated with MAB for 6 months and 243 cases in high-risk group were treated with MAB for 6 months to 3 years.Another 69 patients received adjuvant external radiotherapy.All cases were followed up for 9 to 128 months (mean 91 months),including 135 cases having biochemical recurrence,and 63 cases having distant metastasis.There were 81 cases died,including 24 cases died of prostate cancer.The overall bPFS,DDFS,OS and CSS were 61.9%,82.2%,77.1% and 93.2% respectively.There were significant difference in the survival rate between the high-risk group and the intermediated-risk group(P < 0.001).The incidence of urinary retention and long term urethral stricture were 6.8% and 1.7%,respectively.No serious complications occurred.Conclusion Permanent brachytherapy combined with external beam radiotherapy and hormonal therapy treating local high-risk or intermediated-risk prostate cancer can be effective with few complications.
7.Treatment with 3-Bromo-4,5-Dihydroxybenzaldehyde Improves Cardiac Function by Inhibiting Macrophage Infiltration in Mice
Ningning JI ; Honghong LOU ; Xinyan GONG ; Ting FU ; Shimao NI
Korean Circulation Journal 2018;48(10):933-943
BACKGROUND AND OBJECTIVES: Appropriate inflammatory response is necessary for cardiac repairing after acute myocardial infarction (MI). Three-Bromo-4,5-dihydroxybenzaldehyde (BDB) is a potent antioxidant and natural bromophenol compound derived from red algae. Although BDB has been shown to have an anti-inflammatory effect, it remains unclear whether BDB affects cardiac remolding after MI. The aim of this study was to investigate the potential role of BDB on cardiac function recovery after MI in mice. METHODS: Mice were intraperitoneally injected with BDB (100 mg/kg) or vehicle control respectively 1 hour before MI and then treated every other day. Cardiac function was monitored by transthoracic echocardiography at day 7 after MI. The survival of mice was observed for 2 weeks and hematoxylin and eosin (H&E) staining was used to determine the infarct size. Macrophages infiltration was examined by immunofluorescence staining. Enzyme-linked immunosorbent assay (ELISA) was used to test the production of cytokines associated with macrophages. The phosphorylation status of nuclear factor (NF)-κB was determined by western blot. RESULTS: BDB administration dramatically improved cardiac function recovery, and decreased mortality and infarcted size after MI. Treatment with BDB reduced CD68+ macrophages, M1 and M2 macrophages infiltration post-MI, and suppressed the secretion of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, monocyte chemoattractant protein (MCP)-1, and IL-6 in the injured hearts. Furthermore, BDB inhibited the phosphorylation of NF-κB in the infarcted hearts. CONCLUSIONS: These data demonstrate, for the first time, that BDB treatment facilitated cardiac healing by suppressing pro-inflammatory cytokine secretion, and indicate that BDB may serve as a therapeutic agent for acute MI.
Animals
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Blotting, Western
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Cytokines
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Echocardiography
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Enzyme-Linked Immunosorbent Assay
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Eosine Yellowish-(YS)
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Fluorescent Antibody Technique
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Heart
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Hematoxylin
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Interleukin-6
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Interleukins
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Macrophages
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Mice
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Monocytes
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Mortality
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Myocardial Infarction
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Phosphorylation
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Recovery of Function
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Rhodophyta
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Tumor Necrosis Factor-alpha
8.Effect of dexmedetomidine on proliferation, migration and invasion of human gastric cancer SGC-7901 cells
Jianhua TONG ; Ningning JI ; Manlin DUAN ; Zhiqiang ZHOU ; Ming XIA ; Jianguo XU
The Journal of Clinical Anesthesiology 2017;33(11):1096-1098
Objective To observe different behavior of proliferation,migration and invasion of SGC-7901 cells when exposured to dexrnedetomidine of different concentrations.Methods Human gastric cancer cells SGC-7901 were inoculated on culture plate for 24 h,then were randomly divided into 5 groups:control group (group C),dexmedetomidine 312.5μg/ml group (group D1),dexme detomidine 625μg/ml group (group D2),dexmedetomidine 1 250 μg/ml group (group D3),dexmedetomidine 2 500 μg/ml group (group D4).Each group was medicated and incubated for 48 h,then the cell proliferation,migration and invasion immediately were detected by CCK-8 and Transwell.Results SGC-7901 cell viability of groups D1,D2,D3 和 D4 had no significant difference compared with that of group C.The invasion ability and migration ability of SGC-7901 cells in groups D1,D2,D3 and D4 were significantly higher than those in group C (P < 0.05 or P < 0.01).Conclusion Dexmedetomidine can promote migration and invasion of SGC-7901 cells.
9.Effects of ropivacaine on proliferation,apoptosis and cell cycle of MDA-MB-231 cells
Ningning JI ; Ming XIA ; Jingyu HUA ; Lei DU ; Yongmei ZHANG
The Journal of Practical Medicine 2017;33(21):3527-3530
Objective To investigate the effects of ropivacaine on proliferation,apoptosis and cell cycle of MDA-MB-231 Cells. Methods The cultured MDA-MB-231 cells were treated with different concentrations of ropivacaine. The proliferation of MDA-MB-231 cells was detected by MTT method. Cell apoptosis and cell cycle were detected by Annexin V-FITC/PI and flow cytometry. Results After ropivacaine administration,MDA-MB-231 cells proliferation inhibition ratio increased significantly.Annexin V-FITC/PI and flow cytometry showed ropiva-caine had no significant effects on cell apoptosis and cell cycle.Conclusion Ropivacaine can inhibit the prolifera-tion of MDA-MB-231 cells,but can′t induce apoptosis and block cell cycle.
10.Treatment with 3-Bromo-4,5-Dihydroxybenzaldehyde Improves Cardiac Function by Inhibiting Macrophage Infiltration in Mice
Ningning JI ; Honghong LOU ; Xinyan GONG ; Ting FU ; Shimao NI
Korean Circulation Journal 2018;48(10):933-943
BACKGROUND AND OBJECTIVES:
Appropriate inflammatory response is necessary for cardiac repairing after acute myocardial infarction (MI). Three-Bromo-4,5-dihydroxybenzaldehyde (BDB) is a potent antioxidant and natural bromophenol compound derived from red algae. Although BDB has been shown to have an anti-inflammatory effect, it remains unclear whether BDB affects cardiac remolding after MI. The aim of this study was to investigate the potential role of BDB on cardiac function recovery after MI in mice.
METHODS:
Mice were intraperitoneally injected with BDB (100 mg/kg) or vehicle control respectively 1 hour before MI and then treated every other day. Cardiac function was monitored by transthoracic echocardiography at day 7 after MI. The survival of mice was observed for 2 weeks and hematoxylin and eosin (H&E) staining was used to determine the infarct size. Macrophages infiltration was examined by immunofluorescence staining. Enzyme-linked immunosorbent assay (ELISA) was used to test the production of cytokines associated with macrophages. The phosphorylation status of nuclear factor (NF)-κB was determined by western blot.
RESULTS:
BDB administration dramatically improved cardiac function recovery, and decreased mortality and infarcted size after MI. Treatment with BDB reduced CD68+ macrophages, M1 and M2 macrophages infiltration post-MI, and suppressed the secretion of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, monocyte chemoattractant protein (MCP)-1, and IL-6 in the injured hearts. Furthermore, BDB inhibited the phosphorylation of NF-κB in the infarcted hearts.
CONCLUSIONS
These data demonstrate, for the first time, that BDB treatment facilitated cardiac healing by suppressing pro-inflammatory cytokine secretion, and indicate that BDB may serve as a therapeutic agent for acute MI.