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Objective:To investigate the effect of ubiquitin binding enzyme 2T (UBE2T) on the radiosensitivity of lung adenocarcinoma and unravel its possible mechanism.Methods:A total of 45 patients pathologically diagnosed with different stages of lung adenocarcinoma and treated with radiotherapy in the Second Affiliated Hospital of Zunyi Medical University from March, 2019 to December, 2021 were enrolled, and the efficacy was evaluated according to response evaluation criteria in solid tumors (RECIST1.1). All patients were divided into radiosensitive group ( n=25) and radioresistant group ( n=20). Radiosensitive group was complete remission (CR)+partial remission (PR), and radioresistant group was stable disease (SD) + progression disease (PD). Immunohistochemistry (IHC) was used to calculate the score based on the staining intensity and the number of positive cells. Chi-square test was combined to analyze the correlation between the expression level of UBE2T in paraffin specimens of lung adenocarcinoma patients and the radiosensitivity of patients. Lentivirus UBE2T-interfered (UBE2Tsh) A549 and UBE2T-overexpressed SPC-A-1 lung adenocarcinoma cells and their respective controls were constructed for irradiation and colony formation assay. The survivor fraction curve was fitted by single-hit multi-target model. The DNA double-strand break (DSB) marker γH2AX foci were detected by immunofluorescence (IF). The expression levels of UBE2T, γH 2AX and Rad51 proteins were detected by Western blot. Cell cycle and apoptosis rate of A549 were determined by flow cytometry. Binary variables were statistically analyzed by Fisher's exact probability method and measurement data were assessed by t-test. Results:High-expression level of UBE2T was correlated with the radiosensitivity of lung adenocarcinoma patients ( P<0.05). UBE2Tsh improved the radiosensitivity of A549 lung adenocarcinoma cells, and the sensitizing enhancement ratio (SER) was 1.795. UBE2T overexpression decreased the radiosensitivity of SPC-A-1 lung adenocarcinoma cells with an SER of 0.293. γH2AX foci number per cell were significantly increased in UBE2Tsh A549 cells after irradiation ( P<0.01) . Compared with the control group, the expression level of γH2AX protein was up-regulated ( P<0.01)and that of Rad51 protein was down-regulated in UBE2Tsh A549 cells after radiation ( P<0.001). Compared with the control group, the expression level of γH2AX protein was down-regulated ( P<0.05) and that of Rad51 protein was up-regulated in UBE2T overexpressed SPC-A-1 cells ( P<0.001). The proportion of UBE2Tsh A549 cells in G 2 phase was decreased ( P<0.01) and cell apoptosis was increased ( P<0.001). Conclusions:UBE2T might promote the radioresistance of lung adenocarcinoma cells by enhancing DNA DSB repair induced by radiotherapy, inducing cell cycle G 2 phase arrest, and reducing cell apoptosis.
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[Objective] To describe a case of a rare,novel mutation causing recurrent chorioamniotic membrane separation in a Chinese family with combined next-generation sequencing (NGS) and Sanger sequencing.[Methods] For the affected fetus,potential mutation were detected by the conbinedcombined next-generation sequencing (NGS) and Sanger sequencing.And the prenatal diagnosis were identified by Sanger sequencing.[Results] A frameshifting mutation c.1389_1390delAG (inherited from mother),and a missense mutationc.1006 G ＞ C (inherited from mother) have been identified in the affected fetus (the second pregnancy).The prenatal diagnosis of the third fetus turns out to be a carrier,the mutation was inherited from father.[Conclusions] We describe a novel mutation in gene ZMPSTE24,which was considered with mandibuloacral dysplasia with type B,and that may be the cousecoursecausing of recurrent chorioamniotic membrane separation.This rare mutation constitutes an additional heterogeneous defect causing chorioamniotic membrane separation.And the conbinedcombined next-generation sequencing (NGS) and Sanger sequencing allows high resolution characterization of novel mutions that are not readily detected by present methods.
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AIM:To investigate the effects of grape polyphenol ( GP) on caerulein-induced acute pancreatitis (AP) in mice.METHODS:Two-month-old female mice of ICR strains (n=21) were randomly divided into 3 groups:normal control ( NC) group, AP group, and GP-treated AP group.Before AP induction, the mice in GP-treated AP group were continuously administrated with 1.5 g/kg GP aqueous solution by gavage for 7 d, while those in NC group and AP group were treated with saline as a vehicle control.On the 7th day, the mice in AP group and GP-treated AP group were in-traperitoneally injected with caerulein (50μg/kg) in 1 h interval for 7 serial injections in total.The mice in NC group were treated with saline according to the same procedure in experimental group.All the mice were sacrificed 24 h after AP induc-tion, and the pancreatic tissues and lung tissues were harvested for further investigation of the pathological changes, macro-phages infiltration, myeloperoxidase ( MPO ) activity and expression of inflammatory and oxidative stress factors.RE-SULTS:Compared with AP group, the mice in GP-treated AP group showed milder morphological changes and lower path-ological scores, including the scores of edema, inflammation and vacuolization (P<0.05), but the necrosis scores and to-tal scores showed no statistical difference between these 2 groups.Besides, the mice in GP-treated AP group had fewer macrophage infiltration, lower lung MPO activity (P<0.01), and lower expression of inflammatory factors, tumor necrosis factor α(TNF-α)and monocyte chemotactic protein 1 (MCP-1) (P<0.05), and oxidative stress factors, superoxide dis-mutase (SOD)-1, SOD-2 and NADPH oxidase 2 (NOX-2) (P<0.01).CONCLUSION:Grape polyphenol has remark-able protective effect on pancreatic tissues of mice with caerulein-induced acute pancreatitis, and the mechanisms may be related to down-regulation of inflammatory and oxidative stress factors.
