Uniaxial Tensile Properties of Atherosclerotic Carotid Artery After Mobilization of Pushing on Qiao-Gong: A Safety Study Using an Animal Model of Carotid Atherosclerosis.

OBJECTIVES: This study aimed to preliminarily explore the effects of the soft tissue mobilization of pushing on Qiao-Gong (MPQ) on biomechanical properties of the carotid artery using an animal model of carotid atherosclerosis (CAS). METHODS: Fifty rabbits were randomly divided into 4 groups: animals with CAS treated with MPQ (CAS-MPQ [n = 15]); animals with CAS treated without MPQ (CAS [n = 15]); normal animals treated with MPQ (normal-MPQ [n = 10]); and a blank control group (n = 10). The MPQ procedure consisted of soft tissue mobilization of the Qiao-Gong acupoint on the front edge of the sternocleidomastoid muscle applied from top to bottom, by flat pushing with the thumb repeatedly for 20 times. Disease in the CAS models was induced by carotid artery balloon injury combined with a high-fat diet for 12 weeks. At the end of modeling, carotid color Doppler ultrasonography examination was performed to confirm which animal models were successfully induced with CAS, excluding model rabbits without typical CAS at the same time. Then, MPQ was applied on rabbits in the CAS-MPQ and the normal-MPQ groups for 3 weeks. By contrast, rabbits in the other 2 groups were fed normally without MPQ. Uniaxial failure tests were later performed on carotid arteries in all 4 groups, and at the end of the study, a 2-way factorial analysis of variance of the results was conducted. RESULTS: (1) At the end of modeling, 10 rabbits in the CAS-MPQ group and 9 in the CAS group were included with typical carotid atherosclerotic characteristics. (2) Young's elastic modulus of the rabbit carotid artery increased more significantly in the CAS-MPQ group than the CAS group. (3) Compared with normal rabbit carotid arteries, atherosclerotic carotid arteries had lower levels of ultimate stress and ultimate strain but higher levels of ultimate load. CONCLUSIONS: The uniaxial tensile mechanical properties of the rabbit atherosclerotic carotid artery were impaired after MPQ.

Thioridazine upregulates programmed cell death 4 to induce apoptosis in nasopharyngeal carcinoma through the PI3K/Akt signalling pathway.

Thioridazine (THZ) has been identified as a potential regulator of tumour progression, and programmed cell death 4 (PDCD4) has been reported as a novel tumour suppressor. This study aimed to investigate the link between PDCD4 and THZ in the regulation of nasopharyngeal cancer (NPC) cell proliferation. The effect of THZ on NPC cells was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays. Then, the involvement of apoptosis and cell cycle in the THZ-mediated regulation of cell viability was assessed by flow cytometry. Related mRNAs and proteins were subsequently examined by real-time PCR and western blot, respectively. After transfection with the PDCD4-siRNA, pGC-FU-GFP-PDCD4 vector and phosphoinositide 3-kinase (PI3K) inhibitor Ly294002, we investigated the antagonistic effects of THZ and PDCD4 on NPC-related protein expression. MTT assays showed that THZ treatment suppressed cell viability. THZ-treated cells were arrested at the G1/G0 phase and showed a significantly increased apoptotic fraction. Furthermore, PDCD4-siRNA antagonized THZ treatment and promoted NPC cell proliferation. Western blot analysis showed that PDCD4 overexpression or PI3K inhibition by LY294002 significantly reduced the expression of phospho-PI3K, phospho-Akt, phospho-mammalian target of rapamycin and phospho-p70s6k, but not their total protein levels. In conclusion, our findings show that THZ and PDCD4 exert antagonistic effects on NPC cell proliferation, probably through the PI3K/Akt pathway. Moreover, these results provide an insight into the mechanism by which THZ targets PDCD4 in NPC cell lines and suggest that the ectopic expression of PDCD4 is a potential therapeutic strategy.