1.Negative regulation on allograft immune response induced with up-regulated expression of IDO mediated by 3,4-DAA
Junling HUANG ; Jiongbo LIAO ; Kun SHAO ; Xianghui WANG ; Da XU ; Peijun ZHOU
Chinese Journal of Organ Transplantation 2013;34(10):620-624
Objective To investigate role of N-(30,40-dimethoxycinnamonyl) anthranilic acid (3,4-DAA) in mediating the negative immune regulation by indoleamine 2,3-dioxygenase in mice skin transplantation.Method The mice skin transplant model was established.T lymphocytes were isolated from mice splenocytes,and serum was collected.ELISA was applied to detect the IL-2 and IFN-γ concentrations in culture supernates of mice spleen lymphocytes and serum.Flow cytometry was applied to examine the phenotypes of T lymphocytes and RT-PCR to analyze the IDO mRNA transcription.Results T lymphocyte proliferation was significantly decreased by 3,4-DAA and the concentrations of IL-2 and IFN-γ were apparently decreased in 3,4-DAA group as compared with those in control group.The percentages of CD3 +,CD4 + and CD8 + T lymphocytes were lower,and the percentage of CD4 + CD25 + T lymphocytes was higher in 3,4-DAA disposal group than in control group,but there was no significant difference.IDO mRNA expression showed obvious increase in 3,4-DAA group as compared with control group.Conclusion 3,4-DAA can up-regulate the IDO expression to induce the increasing metabolism of tryptophan,subsequently inhibiting T cell proliferation and showing specific property of negative immune regulation.
2.Comparison of the effect of oral megestrol acetate with or without levonorgestrel-intrauterine system on fertility-preserving treatment in patients with early-stage endometrial cancer: a prospective, open-label, randomized controlled phase II trial (ClinicalTrials.gov NCT03241914)
Zhiying XU ; Bingyi YANG ; Jun GUAN ; Weiwei SHAN ; Jiongbo LIAO ; Wenyu SHAO ; Xiaojun CHEN
Journal of Gynecologic Oncology 2023;34(1):e32-
Objective:
To evaluate the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) plus oral megestrol acetate (MA) as fertility-preserving treatment in patients with early-stage endometrial cancer (EEC).
Methods:
In this single-center, phase II study with open-label, randomized and controlled design, young patients (18–45 years) diagnosed with primary EEC were screened, who strongly required fertility-preserving treatment. Patients were randomly assigned (1:1) into MA group (160 mg oral daily) or MA (160 mg oral daily) plus LNG-IUS group. Pathologic evaluation on endometrium retrieved by hysteroscopy was performed every 3 months. The primary endpoint was complete response (CR) rate within 16 weeks of treatment. The secondary endpoints were CR rate within 32 weeks of treatment, adverse events, recurrent and pregnancy rate.
Results:
Between July 2017 and June 2020, 63 patients were enrolled and randomly assigned. Totally 56 patients (26 in MA group; 28 in MA + LNG-IUS group) were included into primary-endpoint analyses. The median follow-up was 31.6 months (range, 3.1–94.0). No significant difference in 16-week CR rate were found between MA and MA + LNG-IUS groups (19.2% vs. 25.0%, p=0.610; odds ratio=1.40; 95% confidence interval=0.38–5.12), while the 32-week CR rates were also similar (57.1% and 61.5%, p=0.743), accordingly. More women in MA + LNG-IUS group experienced vaginal hemorrhage (46.4% vs. 16.1%; p=0.012) compared with MA group. No intergroup difference was found regarding recurrence or pregnancy rate.
Conclusion
Compared with MA alone, the addition of LNG-IUS may not improve the early CR rate for EEC, and may produce more adverse events instead.
3.Repair Effect and Mechanism of Taohong Siwu Decoction on Rotator Cuff Injury in Rabbits
Zhonghua XU ; Jiongbo XU ; Wenwu QIAN ; Yunduan QUE ; Qiuping WANG ; Jianfa CHEN
China Pharmacy 2021;32(24):2975-2979
OBJECTIVE:To study the repa ir effect and mechanism of Taohong siwu decoction on rotator cuff injury in rabbits. METHODS:New Zealand rabbits were randomly divided into blank control group ,model group ,Taohong siwu decoction low-dose,medium-dose and high-dose groups (2.75,5.5,11 g/kg),and Taohong siwu decoction+LY 294002 group [ 5.5 g/kg Taohong siwu decoction+ 6.4 μg/kg LY294002(pathway inhibitor )],with 11 rabbits in each group. Except for blank control group , other groups underwent right subscapularis muscle detachment to establish rotator cuff injury model. After modeling ,blank control group and model group were given normal saline intragastrically ;Taohong siwu decoction groups were given relevant medicine intragastrically;Taohong siwu decoction+LY 294002 group was given Taohong siwu decoction intragastrically ,and then injected with LY 294002 at the ear edge ,once a day ,for 12 weeks. After last intragastric administration (injection),the pathological changes of tendon-bone interface was observed ;the levels of TNF-α,IL-10 and IL- 6 in serum were detected ;mRNA and protein expressions of PI 3K,Akt and mTOR in tendon-bone interface were detected ;the expression of autophagy related protein (Beclin1, LC3Ⅱ)were detected. RESULTS :Compared with blank control group ,the tendon-bone interface was uneven and the intima was swollen in model group. Serum levels of TNF-α and IL-6,mRNA and protein expressions of PI 3K,Akt and mTOR in tendon-bone interface were increased significantly (P<0.05 or P<0.01),while the level of IL- 10 and protein expression of Beclin 1 and LC 3Ⅱ were decreased significantly (P<0.01). Compared with model group ,the tendon-bone interface of rabbits in Taohong siwu decoction low-dose and medium-dose groups still had certain intimal damage ,while the tendon-bone interface of rabbits in high-dose group was smooth and flat without an obvious intimal tear ;the levels of most indexes in serum and tendon-bone interface of rabbits were significantly reversed in each dose group (P<0.05 or P<0.01). Swollen tendon-bone interface and obvious intimal tear were obse rved in Taohong siwu decoction + LY group;compared with model group ,there w as no significant difference in above indexes of serum and tendon-bone interface (P>0.05). CONCLUSIONS :Taohong siwu decoction may repair the rotator cuff injury of rabbits ,the mechanism of which may be associated with inhibiting PI3K/Akt/mTOR signaling pathway,activating autophagy and inhibiting inflammatory response.