ABSTRACT
Chemotherapy resistance is the main cause of poor prognosis in patients with advanced esophageal squamous cell carcinoma (ESCC). Pyroptosis is one of the anti-tumor mechanisms by chemotherapy drugs. Studies have shown that DEP-domain containing mTOR-interacting protein (DEPTOR) is correlated with sorafenib and gefitnib resistance, which is discovered as a naturally negative regulator of mammalian/mechanistic target of rapamicin (mTOR). In this study, DEPTOR knockdown (shDEPTOR) lentivirus was used to establish the stable DEPTOR knockdown ESCC cell lines. The results showed that knockdown of DEPTOR reduced chemosensitivity to cisplatin in ESCC cells in vitro. The lower expression of DEPTOR caused less extensive morphological characteristics of pyroptosis than that was observed in sh-con cells with the treatment of cisplain. Further studies showed that knockdown of DEPTOR induced downregulation of Caspase-1 expression and reduction of Caspase-1 activation, thereby inhibiting the activation of the classical pathway of pyroptosis. This paper demonstrates that DEPTOR can improve cisplatin chemosensitivity in ESCC cells via inducing Caspase-1-mediated pyroptosis.
ABSTRACT
Total flavonoids of Humulus lupulus [TFHL] were prepared using ethanol extraction, liquid-liquid partition and purification with polyamide resin. Different dose of TFHL were orally administered to normal and hyperuricemic mice for 7 days. The xanthine oxidase [XOD] inhibitory activity and hypouricemic effects of TFHL on potassium oxonate-induced hyperuricemic mice were examined. The TFHL showed very potent XOD inhibitory activity with IC[50]=66.8 micro g/mL. At a single oral dose of 100mg/kg TFHL, the serum uric acid levels of hyperuricemic mice significantly decreased [P<0.01] compared with a hyperuricemic control group, and the XOD activity was inhibited by 22%. Moreover, TFHL has a protective role against potassium oxonate-induced renal damage in mice. The results suggested that TFHL could be used as a promising drug or ingredient for treatment of hyperuricemia and gout
ABSTRACT
Objectives To investigate the correlation between transcutaneous oxygen partial pressure (TcPO2) and nerve conduction determination (NC) in type 2 diabetic patients. Methods From January to July in 2012, 381 age-matched type 2 diabetic patients were enrolled in the Xi'nan Hospital of Third Military Medical University. These patients were divided into 4 groups depending on the results of NCS and symptoms of diabetic peripheral neuropathy (DPN), among which there were 129 with abnormal NCS but no DPN symptoms as group 1, 50 with DPN symptoms and normal NCS as group 2, 122 with both abnormal NCS and DPN symptoms as group 3 and 80 without abnormal NCS nor any DPN symptoms as group 4. Groups 1 and 3 served as DPN group, while groups 2 and 4 were respectively named as possible DPN group and non-DPN group. The differences of 33 indexes of TcPO2 in erect and recumbent positions, correlation between TcPO2 values and differences in erect and recumbent positions between groups, and the correlation between TcPO2 values and various NCS parameters were analyzed. Results The values of TcPO2 in erect position and recumbent position in DPN and possible DPN group were lower, while the difference between them was higher than that (erect-recumbent position difference) in non-DPN group (P<0.05). The value of erect position TcPO2 was correlated with all the 26 parameters of NCS including the velocity of median nerve conduction, distal latency, amplitude of compound muscle action potential (P<0.05); the value of recumbent position TcPO2 was also correlated with almost all parameters except the shortest latency of F wave; the erect-recumbent position difference was correlated with 11 out of the above 26 parameters (P<0.05). Conclusion There is a good correlation between TcPO2 and NCS, which suggests that TcPO2 can serve as a potential and effective method for detecting DPN at early stage.