1.Adonesine A1 receptor and megalin defect in diabetic mice with early kidney disease
Dongli TIAN ; Xiaoxiao SHI ; Jing WANG ; Xiaoyan PENG ; Lubin XU ; Yubing WEN ; Limeng CHEN
Chinese Journal of Nephrology 2017;33(2):120-125
Objective To observe the effect of adenosine A1 receptor (A1AR) on the megalin defect in type 1 diabetic mice with early kidney disease.Methods 7-8 week-old,baseline body weight and fasting blood glucose matched wild type (WT) C57BL/6J mice were selected,and randomly divided into two groups:control group (n=6) and WT DM group (n=6).In the same way,male A1AR knock-out C57BL/6J mice were selected as A1AR-/-DM group (n=6).DM model was established by intraperitoneal injection of streptozocin.The blood glucose (BG),body weight (BW),kidney weight (KW),24 h proteinuria (24hUP) and albumin creatine ratio (ACR) were measured at 4 weeks.The renal pathological lesion was observed and the expression of megalin in proximal tubules was examined by immunohistochemistry.The expression of caspase-1,IL-18 and A1AR were detected by Western blotting.Results At 4th week,compared with WT control mice,the BG,BW,KW and 24hUP of WT DM mice were increased significantly (n=6,P < 0.01),with the pathological glomerular enlargement,mesangial cell proliferation,extracellular matrix accumulation and renal tubule hypertrophy being observed.Immunohistochemistry revealed decreased expression of megalin,an important multiligand protein receptor on the brush border of proximal tubular epithelial cells in WT DM mice,which was correlated with 24hUP (r=-0.645,P < 0.01).Compared with the control mice,the expressions of caspase-1,IL-18 and A1AR were significantly increased in WT DM mice (P < 0.05).For A1AR-/-DM mice,more serious pathological lesion and megalin defect,together with increasing of casapase-1 and heavier proteinuria were observed than those in WT DM mice.Conclusion A1AR may play a protective role in megalin expression of diabetic mice with early kidney disease,in which the mechanism may be associated with caspase-1 related pyroptosis pathway.The details need further exploration.
2.Role of tumor-derived exosomes in tumor metastasis
Haiyan DONG ; Xiaoyan PANG ; Lei DOU ; Fengxin LI ; Dongli TIAN ; Yi ZHANG
Journal of International Oncology 2018;45(7):427-431
Tumor-derived exosomes (TEXs) are small membrane vesicles secreted by tumor cells.They contain various proteins and RNA which make they serve as functional mediators in cell interaction.TEXs can alter the components of extracellular matrix and induces epithelial-mesenchymal transition of tumor cells,which enhance the invasiveness of tumor cells.TEXs regulate immunity through multiple pathways,allowing circulating tumor cells to escape immune surveillance.TEXs promote pre-metastatic microenvironment in target organ before metastasis and induce angiogenesis after circulating tumor cells colonization.Understanding the role and mechanism of TEXs in this process can effectively block relevant signaling pathways which may provide new targeted therapies for clinic.
3.Clinical Significance of Endometrial Abnormalities in Patients with Breast Cancer after Oral Administration of Tamoxifen
Dongli TIAN ; Fengxin LI ; Lei DENG ; Feiran SONG ; Xiaoyan PANG ; Yi ZHANG
Journal of China Medical University 2019;48(1):62-65
Objective To analyze the clinical significance of endometrial abnormalities in patients with breast cancer after oral administration of tamoxifen, and to determine the risk factors for endometrial malignancy. Methods We collected data from 135 patients with breast cancer who underwent surgery for endometrial abnormalities after oral administration of tamoxifen at the Department of Gynecology from September 2011 to December 2017. According to the pathological results obtained, the patients were divided into groups A (benign endometrial lesion) and B (precancerous and malignant endometrial lesion). The relationships between endometrial malignancy and factors including age, menopausal status, body mass index, endometrial thickness, abnormal uterine bleeding, oral dose of tamoxifen, duration of oral medication, and complications (hypertension and diabetes) were compared between the groups. Results There were 124 patients in group A and 11 patients in group B. The difference in the incidence of abnormal uterine bleeding, which was a risk factor for endometrial malignancy, was significant different between the groups (P < 0.05). Conclusion Physicians should pay close attention to abnormal uterine bleeding in patients taking tamoxifen after surgery for breast cancer. Hysteroscopy should be used to confirm the nature of lesions, and patients without symptoms should be followed up.
4.Clinical Progress in Negative-Pressure Endometrial Sampler for Endometrial Cancer Screening
Fengxin LI ; Dongli TIAN ; Xiaoyan PANG ; Lei DOU ; Yi ZHANG
Journal of China Medical University 2019;48(1):78-81
Endometrial cancer is a common malignancy of the female reproductive system. Despite improvement in living standards, the incidence of endometrial cancer is increasing due to the lack of effective screening. Early detection of endometrial cancer and precancerous lesions can significantly improve prognosis and survival. At present, China lacks a method for screening endometrial lesions comparable to that for cervical cancer screening. A recently introduced endometrial sampler has the advantages of simple operation, low cost, and minimal trauma, and is gradually being accepted for clinical screening of endometrial cancer and precancerous lesions in other countries.This study aims to explore current screening methods for endometrial cancer and precancerous lesions and the clinical application of an endometrial sampler for screening.
5.Effect of lncRNA SNHG6 targeting miR-485-3p on proliferation and radiotherapy sensitivity of cervical cancer SiHa cells
Dongli ZHANG ; Guixia SUN ; Jun TIAN ; Juncai LIU
Chinese Journal of Radiation Oncology 2022;31(9):828-833
Objective:To investigate the effect of lncRNA SNHG6 on the proliferation and radiotherapy sensitivity of cervical cancer SiHa cells and its potential mechanism.Methods:The expression levels of lncRNA SNHG6 and miR-485-3p in cervical cancer tissues, paracancer tissues, SiHa cells and SiHa cells exposed to X-ray were detected. The relationship between lncRNA SNHG6 and miR-485-3p was analyzed. After overexpression or knockdown of SNHG6 and miR-485-3p, cell proliferation ability, number of invasion and apoptosis rate were determined by MTT, Transwell chamber assay and flow cytometry, respectively. The effect of miR-485-3p on the Wnt/β-catenin pathway and the effect of XAV939 on SiHa cell proliferation and radiation sensitivity were analyzed.Results:lncRNA SNHG6 was highly expressed in cervical cancer tissues and SiHa cells, whereas was lowly expressed in X-ray irradiated SiHa cells. miR-485-3p was lowly expressed in cervical cancer tissues and SiHa cells, whereas was highly expressed in X-ray irradiated SiHa cells. lncRNA SNHG6 targeted miR-485-3p. Down-regulation of lncRNA SNHG6 expression inhibited cell proliferation and invasion, and enhanced its sensitivity to X-ray radiotherapy, while miR-485-3p inhibitor transfected cells exerted the opposite effect. The up-regulation of lncRNA SNHG6 promoted the proliferation and invasion of SiHa cells through miR-485-3p, and reduced the sensitivity of radiotherapy. Down-regulation of miR-485-3p activated the Wnt/β-catenin pathway, promoted cell proliferation and invasion of SiHa, and reduced its radiation sensitivity to X-ray.Conclusion:Overexpression of lncRNA SNHG6 targeting miR-485-3p activates the Wnt/β-catenin pathway to regulate the proliferation and radiotherapy sensitivity of SiHa cells.