Sitagliptin attenuates endothelial dysfunction independent of its blood glucose controlling effect

Xin-Miao Chang,Fei Xiao,Qi Pan,Xiao-Xia Wang,Li-Xin Guo 대한생리학회-대한약리학회 2021 The Korean Journal of Physiology & Pharmacology Vol.25 No.5

Although the contributions of sitagliptin to endothelial dysfunction in diabetes mellitus were previously reported, the mechanisms still undefined. Autophagy plays an important role in the development of diabetes mellitus, but its role in diabetic macrovascular complications is unclear. This study aims to observe the effect of sitagliptin on macrovascular endothelium in diabetes and explore the role of autophagy in this process. Diabetic rats were induced through administration of high-fat diet and intraperitoneal injection of streptozotocin. Then diabetic rats were treated with or without sitagliptin for 12 weeks. Endothelial damage and autophagy were measured. Human umbilical vein endothelial cells were cultured either in normal glucose or in high glucose medium and intervened with different concentrations of sitagliptin. Rapamycin was used to induce autophagy. Cell viability, apoptosis and autophagy were detected. The expressions of proteins in c-Jun N-terminal kinase (JNK)-Bcl-2-Beclin-1 pathway were measured. Sitagliptin attenuated injuries of endothelium in vivo and in vitro. The expression of microtubuleassociated protein 1 light chain 3 II (LC3II) and beclin-1 were increased in aortas of diabetic rats and cells cultured with high-glucose, while sitagliptin inhibited the over-expression of LC3II and beclin-1. In vitro pre-treatment with sitagliptin decreased rapamycin-induced autophagy. However, after pretreatment with rapamycin, the protective effect of sitagliptin on endothelial cells was abolished. Further studies revealed sitagliptin increased the expression of Bcl-2, while inhibited the expression of JNK in vivo. Sitagliptin attenuates injuries of vascular endothelial cells caused by high glucose through inhibiting over-activated autophagy. JNK-Bcl-2-Beclin-1 pathway may be involved in this process.

FoxM1 as a Novel Therapeutic Target for Cancer Drug Therapy

Xu, Xin-Sen,Miao, Run-Chen,Wan, Yong,Zhang, Ling-Qiang,Qu, Kai,Liu, Chang Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.1

Background: Current cancer therapy mainly focuses on identifying novel targets crucial for tumorigenesis. The FoxM1 is of preference as an anticancer target, due to its significance in execution of mitosis, cell cycle progression, as well as other signal pathways leading to tumorigenesis. FoxM1 is partially regulated by oncoproteins or tumor suppressors, which are often mutated, lost, or overexpressed in human cancer. Since sustaining proliferating signaling is an important hallmark of cancer, FoxM1 is overexpressed in a series of human malignancies. Alarge-scale gene expression analysis also identified FoxM1 as a differentially-expressed gene in most solid tumors. Furthermore, overexpressed FoxM1 is correlated with the prognosis of cancer patients, as verified in a series of malignancies by Cox regression analysis. Thus, extensive studies have been conducted to explore the roles of FoxM1 in tumorigenesis, making it an attractive target for anticancer therapy. Several antitumor drugs have been reported to target or inhibit FoxM1 expression in different cancers, and down-regulation of FoxM1 also abrogates drug resistance in some cancer cell lines, highlighting a promising future for FoxM1 application in the clinic.

Model Based on Alkaline Phosphatase and Gamma-Glutamyltransferase for Gallbladder Cancer Prognosis

Xu, Xin-Sen,Miao, Run-Chen,Zhang, Ling-Qiang,Wang, Rui-Tao,Qu, Kai,Pang, Qing,Liu, Chang Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Purpose: To evaluate the prognostic value of alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) in gallbladder cancer (GBC). Materials and Methods: Serum ALP and GGT levels and clinicopathological parameters were retrospectively evaluated in 199 GBC patients. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off values of ALP and GGT. Then, associations with overall survival were assessed by multivariate analysis. Based on the significant factors, a prognostic score model was established. Results: By ROC curve analysis, $ALP{\geq}210U/L$ and $GGT{\geq}43U/L$ were considered elevated. Overall survival for patients with elevated ALP and GGT was significantly worse than for patients within the normal range. Multivariate analysis showed that the elevated ALP, GGT and tumor stage were independent prognostic factors. Giving each positive factor a score of 1, we established a preoperative prognostic score model. Varied outcomes would be significantly distinguished by the different score groups. By further ROC curve analysis, the simple score showed great superiority compared with the widely used TNM staging, each of the ALP or GGT alone, or traditional tumor markers such as CEA, AFP, CA125 and CA199. Conclusions: Elevated ALP and GGT levels were risk predictors in GBC patients. Our prognostic model provides infomration on varied outcomes of patients from different score groups.

Ultrasonic Synthesis of Au/AgCl Hybrid Cubes and Their Evolution Under Electron Beam Irradiation

Hongliang Cao,Xiaoli Miao,Mengqin Zhu,Chang Li,Feifei Wei,Xin Chen 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2015 NANO Vol.10 No.6

The utilization of ultrasound offers a facile tool for the synthesis of Au/AgCl hybrid particles. We have obtained the architectures of Au nanoparticles on AgCl sub-micrometer cubes by simply ultrasonic irradiating their precursors in ethylene glycol (EG). The formation process of Au/AgCl hybrid particles in the reaction solution has been studied based on the optical absorption spectra and the scanning electron microscope (SEM) images of the particles obtained at different ultrasonic irradiation stages. The dynamic changes of Au/AgCl hybrid particles under electron beam irradiation have been investigated in both SEM and in situ liquid cell transmission electron microscope (TEM). Hollow Au/AgCl hybrid particle structures have been obtained under the electron beam irradiation in liquid, with the cuboid contour shape preserved.

Characteristics and Impact Factors of Renal Threshold for Glucose Excretion in Patients with Type 2 Diabetes Mellitus

Xiao-Dan Yue,Jing-Yu Wang,Xin-Rong Zhang,Ju-Hong Yang,Chun-Yan Shan,Miao-Yan Zheng,Hui-Zhu Ren,Yi Zhang,Shao-Hua Yang,Zhen-Hong Guo,Bai Chang,Bao-Cheng Chang 대한의학회 2017 Journal of Korean medical science Vol.32 No.4

Sodium glucose co-transporter 2 (SGLT-2) inhibitors are newly developed but promising medicine for type 2 diabetes. However, patients with a different renal threshold for glucose excretion (RTG) may have a different reaction to this medicine. Therefore, the objective of this study was to investigate the characteristics of RTG and its impact factors in patients with type 2 diabetes mellitus (T2DM). The clinical and laboratory data of 36 healthy individuals and 168 in-hospital patients with T2DM were collected and analyzed, RTG was calculated using blood glucose (BG) measured by dynamic BG monitoring, urinary glucose excretion (UGE) and estimated glomerular filtration rate (eGFR). The characteristics of RTG were investigated. The risk factors for high RTG were analyzed using non-conditional logistic regression analysis. Our results found that RTG of the T2DM group was higher than that of the healthy individuals (P < 0.05); and 22.22% from the healthy individuals group but 58.33% from the T2DM group had high RTG. Age, duration of diabetes, body mass index (BMI), and homeostasis model assessment insulin resistance index (HOMA-IR) were independently associated with high RTG (P < 0.05). Further stratified analysis revealed that RTG in T2DM patients increased with age, duration of diabetes, and BMI. In conclusion, RTG is increased in patients with T2DM, especially in those with longer diabetic duration, higher BMI, and those who are older. Therefore, these patients may be more sensitive to SGLT-2 inhibitors.