1.Effect of Vitamin D Supplementation in Early Pregnancy on High-risk Women with Gestational Diabetes Mellitus
Yuzhen ZHANG ; Zhirui CAO ; Qiaoting CUI
Journal of Medical Research 2023;52(12):61-64
Objective To investigate the effect of vitamin D supplementation in early pregnancy on the incidence and glucose metab-olism of high-risk women with gestational diabetes mellitus.Methods Pregnant women who had regular prenatal examination in Hefei First People's Hospital from December 2019 to May 2022 with serum 25(OH)D level<30ng/ml,expected date of delivery ≥ 35 years or pre-pregnancy body mass index(BMI)≥24kg/m2were selected.They were randomly divided into intervention group(86 cases)and control group(94 cases).The intervention group,took 1200IU/d vitamin D3 capsules orally from the first trimester of pregnancy to the second trimester of pregnancy[the date of oral glucose tolerance test(OGTT)examination for pregnant women];the control group was not given vitamin D3 capsules,and pregnant women with vitamin D deficiency or insufficient were recommended to take vitamin D3 cap-sules or calcium tablets containing vitamin D.Results The levels of vitamin D in the first and second trimester of pregnancy were 12.986± 5.654ng/ml and 31.277±9.856ng/ml in the intervention group,and the difference was statistically significant(P<0.001).The inci-dence of gestational diabetes mellitus in control group and intervention group was 24.5%and 20.9%,and the difference was not statisti-cally significant(P>0.05).There were no significant difference in fasting blood glucose,fasting insulin,1h blood glucose,2h blood glucose and homeostasis model assessment insulin resistance index(HOMR-IR)between the intervention group and the control group in the second trimester of pregnancy(P>0.05).Conclusion Vitamin D supplementation in early pregnancy can only significantly improve the level of vitamin D in pregnant women,and almost make it reach sufficient state,but has no obvious effect on the risk of gestational dia-betes mellitus and glucose metabolism.
2.Static balance and limits of stability in patients with cervical vertigo
Wei LUO ; Zhirui HUANG ; Zhixian CAO ; Zhen HUANG ; Yu MIN ; Tao ZHONG
Chinese Journal of Rehabilitation Theory and Practice 2022;28(2):165-169
Objective To analyze the characteristics of static balance and limits of stability (LOS) in patients with cervical vertigo (CV). Methods From January, 2020 to August, 2021, 30 CV patients in our hospital (vertigo group) and 30 healthy people (control group) were selected and tested with PRO-KIN system, under the conditions of eyes open and closed. The standard deviation of the vertical and horizontal amplitude, the mean of vertical and horizontal sway velocities, the area of the movement, the length of the movement, and LOS at eight directions, The Romberg ratios of the area and the length were caculated. Results All the indicators of the static balance were higher under eyes closed than under eyes open in both groups (|Z| > 2.138, P < 0.05); whether under the eyes open or closed, the static balance indicators were higher in the vertigo group than in the control group (|Z| > 2.004, P < 0.05), except for the mean of horizontal sway velocities (|Z| < 1.026, P > 0.05). The LOS and total LOS completion percentage in the front (upper right, right above, upper left) were lower in the vertigo group than in the control group (|Z| > 2.240, P < 0.05). Conclusion The static balance abilities decrease for CV patients, and the balance control depends on visual compensation. The range of LOS reduces, means a higher risk of falling.
3.Study on the Effects and Its Mechanism of Sinapine Thiocyanate on the Proliferation ,Epithelial Mesenchymal Transition and Metastasis of Human Cutaneous Squamous Cell Carcinoma SCL- 1 Cells
Yushen SU ; Zhirui ZENG ; Dongyun RONG ; Ye WANG ; Dan LI ; Shanshan TANG ; Tao WANG ; Xuemei LONG ; Yu CAO
China Pharmacy 2021;32(8):952-960
OBJECTIVE:To stud y the effects of sinapine thiocyanate (ST) on the proliferation ,epithelial mesenchymal transformation(EMT)and metastasis of human cutaneous squamous cell carcinoma SCL- 1 cells,and to investigate its possible mechanism. METHODS :Human cutaneous squamous cell carcinoma SCL- 1 cells were divided into blank control group (0.1% DMSO) and ST different concentration groups (5,10,20 μmol/L). CCK- 8 assay,5-ethynyl-2′-deoxyuridine(EDU)test, scratch test and Transwell chamber invasion test were adopted to test the proliferation ,migration and invasion ability. The expression of N-cadherin and E-cadherin were detected by Western blot and immunofluorescence assay . Other SCL- 1 cells were collected and divided into blank control group (0.1% DMSO),ST group (20 μmol/L),ST+NSC228155 group [ 20 μmol/L ST+100 μmol/L NSC228155(EGFR agonist )] and ST+SC 79 group [ 20 μmol/L ST+20 μmol/L SC79(PI3K/Akt agonist )]. The proliferation ,migration and invasion ability of SCL- 1 cells in each group were detected by CCK- 8 assay,scratch test and Transwell chamber invasion assay. The expression of epidermal growth factor receptor (EGFR),phosphatidylinositol 3 kinase(PI3K),phosphorylated phosphatidylinositol 3 kinase(p-PI3k),protein kinase B (Akt)and phosphorylated protein Akt (p-Akt)protein of cells in blank control group and ST different concentration groups(5,10,20 μmol/L)were determined by Western blot assay so as to validate the relationship between ST effect and EGFR/ PI3K/Akt signaling pathway. SCL- 1 cells and human normal skin fibroblasts cell WS 1 were divided into blank control group (0.1% DMSO),ST group (20 μmol//L),ZD1839 group(positive control ,20 μmol//L,EGFR inhibitor )and LY 294002 group(positive control,20 μmol//L,PI3K/Akt inhibitor ). CCK- 8 assay was used to detect the cell proliferation in order to evaluate the cells cytotoxicity of ST. RESULTS :Compared with blank control group ,the proliferation ,migration and invasion ability of SCL- 1 cells were significantly decreased in 5,10,20 μmol/L ST groups(P<0.05). Western blot and immunofluorescence assay showed that the expression of N-cadherin in SCL- 1 cells were decreased significantly in 5,10,20 μmol/L ST groups(P<0.05),while the protein expression of E-cadherin was increased significantly (P<0.05);the protein expressions of EGFR ,p-PI3K and p-Akt were significantly decreased (P<0.05). Compared with ST group ,the proliferation ,migration and invasion ability of SCL- 1 cells were increased significantly in ST + NSC 228155 group and ST + SC 79 group (P<0.05). Compared with blank control group ,the proliferation ability of WS 1 cells had no significant change in ST group ,while the proliferation ability of SCL- 1 cells was decreased significantly (P<0.05);the proliferation ability of the two kinds of cells were decreased significantly in ZD 1839 group and LY 294002 group(P<0.05). Compared with ST group ,the proliferation ability of WS 1 cells was decreased significantly in ZD1839 group and LY 294002 group(P<0.05),but there was no significant difference in the proliferation ability of SCL- 1 cells (P>0.05). CONCLUSIONS :ST may inhibit the proliferation ,EMT and metastasis of SCL- 1 cells through inhibiting the activation of EGFR/PI 3K/Akt signaling pathway ,and its side effects are few.
4.Pharmacological inhibition of BAP1 recruits HERC2 to competitively dissociate BRCA1-BARD1, suppresses DNA repair and sensitizes CRC to radiotherapy.
Xin YUE ; Tingyu LIU ; Xuecen WANG ; Weijian WU ; Gesi WEN ; Yang YI ; Jiaxin WU ; Ziyang WANG ; Weixiang ZHAN ; Ruirui WU ; Yuan MENG ; Zhirui CAO ; Liyuan LE ; Wenyan QIU ; Xiaoyue ZHANG ; Zhenyu LI ; Yong CHEN ; Guohui WAN ; Xianzhang BU ; Zhenwei PENG ; Ran-Yi LIU
Acta Pharmaceutica Sinica B 2023;13(8):3382-3399
Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.