1.The protective effect and mechanism of icarisideⅡ in a rat model of radiation cystitis
Jilei SUN ; Yongde XU ; Zhitao WEI ; Yang LIU ; Shukun LIU ; Mingxing WANG ; Yong YANG
Chinese Journal of Urology 2022;43(12):929-935
Objective:To investigate the protective effect and mechanism of Icaritin Ⅱ (ICAⅡ) on bladder in radiation cystitis model.Methods:A total of 18 10-week-old male SD rats were selected from July 2021 to March 2022 and divided into control group, model group and treatment group by random number table method, with 6 cases in each group. Model group and treatment group were given a single dose of 20 Gy X-ray irradiation in the pelvic area. 24 h after irradiation, the treatment group was given ICAⅡ 4.5 mg/(kg·d) gavage, while the control group and model group were given the same volume of solvent (10% anhydrous ethanol, 20% isopropyl alcohol, 30% polyethylene glycol and 40% deionized water) gavage for 4 consecutive weeks. Drug eluting for 1 week. The bladder volume and leakage point pressure of the three groups of rats were measured by multi-conducting physiological apparatus, and the bladder function was evaluated. HE staining, Masson staining, ELISA, TUNEL staining and western blotting were performed on the bladder samples of the three groups of rats. The pathological changes (thickness of bladder mucosa, ratio of smooth muscle to collagen fiber), oxidative stress level (superoxide dismutase SOD, malondialdehyde), apoptosis rate, protein levels of inflammatory factors (IL-6, NF-kB) and anti-oxidative stress signaling pathway factors (Nrf2, HO-1) of the three groups of rats were compared.Results:After 4 weeks of modeling, in the model group, the bladder volume [(1.01±0.12)ml vs. (1.58±0.21)ml, P=0.001], the bladder leakage point pressure [(38.79±4.12) cmH 2O (1 cmH2O=0.098 kPa)vs.(60.59±3.81) cmH 2O, P=0.001], the ratio of smooth muscle of bladder wall to collagen fiber [1.78±0.17 vs.3.15±0.57, P=0.001], SOD[(6.31±0.73) U/mg vs.(14.67±1.04) U/mg, P=0.001] were lower than the control group, and the differences were statistically significant. In the model group, the thickness of bladder mucosa [(47.33±1.78)μm vs.(20.83±2.33)μm, =, P=0.001], malondialdehyde [(1.01±0.13) nmol/mg vs.(0.49±0.03) nmol/mg, P=0.001], IL-6 (0.87±0.11 vs. 0.33±0.10, P=0.001), NF-kB (0.71±0.14 vs. 0.29±0.07, P=0.001), apoptosis rate [(11.60±3.04)% vs. (3.91±1.40)%, P=0.007] was higher than the control group, and the differences were statistically significant. In the treatment group, the bladder volume [(1.27±0.13)ml, P=0.030], bladder leakage point pressure [(47.83±2.50)cmH 2O, P=0.004], smooth muscle to collagen fiber ratio (2.78±0.68, P=0.015), SOD[(10.48±0.85) U/mg, Compared with model group, bladder mucosa thickness [(31.94±3.20)μm, P=0.001], malondialdehyde [(0.64±0.09) nmol/mg, P=0.001], IL-6 (0.69±0.11, P=0.035), NF-kB (0.45±0.06, P=0.002) and apoptosis rate [(6.05±0.60)%, P=0.030] were lower than those in model group. The protein expression level of Nrf2 in model group (0.73±0.08 vs. 0.58±0.11, P=0.023) was higher than that in control group, but there was no significant difference in the protein expression level of downstream antioxidant factor HO-1 (0.50±0.14 vs. 0.35±0.06, P=0.060). Nrf2 protein expression level (0.88±0.03, P=0.027) and HO-1 expression level (0.68±0.07, P=0.026) in treatment group were higher than those in model group. Conclusion:ICAⅡ can reduce radiation cystitis injury, and its mechanism may be related to anti-oxidative stress and reducing inflammation.
2.Application of core-shell structured nanofibers in oral tissue regeneration
Tong YIN ; Jilei YANG ; Yourui LI ; Zhuoran LIU ; Ming JIANG
Chinese Journal of Tissue Engineering Research 2024;28(5):766-770
BACKGROUND:The combination of good biomechanical properties,controlled drug release and multi-functionality of core-shell structured nanofibers is receiving more and more attention,which also makes them promising for a wide range of applications in the field of oral tissue regeneration. OBJECTIVE:To summarize the preparation,drug loading and release mechanisms of core-shell structured nanofibers and their application in the regenerative repair of oral tissues. METHODS:A computer search of the literature collected in CNKI and PubMed from January 2000 to November 2022 was applied,and the search terms in English and Chinese were"electrospinning,core-shell structures,drug delivery systems,jaw bone regeneration,cartilage regeneration,periodontal tissue regeneration". RESULTS AND CONCLUSION:(1)There are various methods for the preparation of core-shell structured nanofibers,but the coaxial and emulsion methods of electrostatic spinning have unique advantages such as simple operation,diverse material selection and good biocompatibility.(2)Core-shell structured nanofibers can be used as bacteriostatic agents,carriers of different types of drugs,and scaffolds for cell adhesion,providing new therapeutic options for oral tissue regeneration.(3)Controlled degradation and drug release rate of core-shell structured nanofibers can better adapt to the healing process of oral tissue defect repair and achieve ideal tissue regeneration.
3.miR-125a-5p promotes the resistance to gefitinib in non-small cell lung carcinoma cells by targetingAPAF1
LI Yanming ; HAO Yanbing ; YANG Jilei ; LI Chuangui ; CHEN Wansheng ; SUN Zhongzhe ; RONG Yu
Chinese Journal of Cancer Biotherapy 2020;27(6):622-628
[Abstract] Objective:ToinvestigatetheroleofmiR-125a-5pininducingthegefitinib(Gef)-resistance of non-small cell lung carcinoma (NSCLC) cells and its possible mechanism. Methods: Human NSCLC drug-resistant cell line A549/GR and NSCLC cell line A549 were chosen for this study. miR-125a-5p mimic, miR-125a-5p inhibitor, pcDNA3.1-APAF1 and empty vector pcDNA3.1 were transfected into A549/GR cells. The expression level of miR-125a-5p in cell lines was detected by qPCR. MTT, Transwell and Flow cytometry were used to detect the effects of Gef on proliferation, migration and apoptosis of cell lines, respectively. The targeting relationship between miR-125a-5p and APAF1 (apoptotic peptidase activating factor 1) was verified by Dual-luciferase reporter gene system. In addition, the expression of APAF1 protein in A549/GR cells was detected by Western blotting. The expression levels of caspase-3 and caspase-9 were assessed by colorimetry. Results: Expression level of miR-125a-5p was upregulated significantly in Gefresistant A549/GR cells (P<0.01). AndtheinfluencesofGefonA549/GRcellswereenhancedby knockdown of miR-125a-5p, including inhibiting cell proliferation and migration (all P<0.05) and inducing apoptosis (P<0.01). Dual luciferase reporter gene assay confirmed that miR-125a-5p targeted APAF1 and negatively regulated its expression. Furthermore, by targetedly downregulating APAF1, miR-125a-5p alleviated the inhibition of proliferation and migration (all P<0.05) and promotion of apoptosis (P<0.05) of A549/GR cells caused by Gef, and attenuated Gef-induced upregulation of apoptosis-related proteins caspase-3 and caspase-9 (all P<0.05). Conclusion: miR-125a-5p promotes Gef-resistance of A549/GR cells, and the underlying mechanisms are promotion of proliferation, migration and inhibition of apoptosis of non-small cell lung cancer cells by targetingAPAF1.