Effect and mechanism of adrenomedullin on apoptosis of renal tubular epithelial cell in rats induced by renal ischemia reperfusion injury

Objective To investigate the effect and mechanism of adrenomedullin ( AM ) on apoptosis of renal tubular epithelial cell in rats induced by renal ischemia reperfusion injury. Methods Thirty-two Wistar rats were randomly divided into 4 groups: control group,IRI group, empty plasmid group and AM group. One week after re-

Molecular mechanisms of TRAIL-induced apoptosis of cancer cells

Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) is a recently identified member of the tumor necrosis factor (TNF) family[1]. Numerous studies indicate that TRAIL can induce apoptosis of cancer cells but not of normal cells, pointing to the possibility of developing TRAIL into a cancer drug[2-4]. This review will summary the molecular mechanisms of TRAIL-induced apoptosis and discuss the questions to be resolved in this field.

Antineoplastic mechanism of Octreotide action in human hepatoma

Objectives To investigate whether apoptosis can be induced by Octreotide in human hepatoma cells in vitro and elucidate the antineoplastic mechanism of Octreotide in hepatoma.Methods A cultured human hepatoma cell line,BEL-7402,was exposed to Octreotide and apoptosis was evaluated by cytochemical staining(Hochesst 33258),transmission electron microscopy,agarose gel electrophoresis and flow cytometry(FCM).Results After exposure to 0.2 μg/ml Octreotide,apoptosis with nuclear chromatin condensation as well as fragmentation,cell shrinkage and the formation of apoptotic bodies was observed using cytochemical staining and transmission electron microscopy.A DNA ladder in agarose gel electrophoresis was also displayed.FCM showed that the apoptotic cell number rose with an increase in the concentration of Octreotide(0- 2 iμg/ml).There was a positive correlation between Octreotide concentration and apoptotic rate in BEL-7402 cells(r=0.809,P＜0.05).Conclusion Apoptosis in human hepatoma cells can be induced by Octreotide,which may be related to the mechanism of antineoplastic action of Octreotide in hepatoma.

Effects of tensile forces on serum deprivation-induced osteoblast apoptosis： expression analysis of caspases, Bcl-2, and Bax

Background Apoptosis is involved in the adaptive responses of bone to mechanical loading. The purpose of this study was to investigate the effects of tensile forces on osteoblast apoptosis and the related mechanism by analyzing the expression of caspases, Bcl-2, and Bax. Methods Primary osteoblasts were harvested from neonatal rat calvaria and were subjected to cyclic tensile forces for 72 hours using Flexcell 4000 strain unit in Minimum Essential Medium （MEM） with 10% fetal calf serum （FCS） or with serum deprivation. Apoptosis was tested by flow cytometry using annexin V/PI staining. Caspase-3 activity was analyzed via Elisa. The gene expression of caspase-8, -9, Bcl-2, and Bax was quantified by reverse transcription （RT）-PCR. Results In 10% FCS condition, no significant difference in cell apoptosis was found between the stretched and non-stretched osteoblast cultures. Serum withdrawal resulted in higher apoptosis rate in the osteoblasts with increased caspase-3 activity, and elevated expression of caspase-9 and Bax. Six-percent elongation of stretch attenuated the cell apoptosis induced by serum starvation, concurrent with a decrease in caspase-3 activity, a decline of caspase-8 expression, and an elevation of Bcl-2 level. On the contrary, 12% elongation of stretch increased caspase-3 activity and promoted the apoptosis with an elevated expression of caspase-8 and Bax. No significant change of caspase-9 expression was identified upon force application. Conclusions These results suggested that tensile forces regulate cell apoptosis of primary rat osteoblasts through caspase-3 and caspase-8 signaling cascade. Light forces rescue the cells from serum deprivation-induced apoptosis by elevating Bcl-2 expression, while heavy forces promote the apoptotic insult by inducing Bax expression.

A versatile Pt-Ce6 nanoplatform as catalase nanozyme and NIR-Ⅱ photothermal agent for enhanced PDT/PTT tumor therapy

The hypoxic nature of solid tumors has severely negative effects on oxygen-based photodynamic therapy.In this study,we used porous Pt nanoparticles as a catalase(CAT)nanozyme,the second near-infrared(NIR-Ⅱ)region photothermal transition agents(PTAs),and carriers of photosensitizer chlorin e6(Ce6)to synthesize a composite nanosystem Pt-Ce6.In this system,Pt-Ce6 can continuously and stably decompose H2O2 into oxygen,thereby alleviating tumor hypoxia and improving the effect of photodynamic therapy(PDT).With 650 nm illumination,the reactive oxygen species(ROS)produced by Ce6 will decrease the mitochondrial membrane potential(MMP,ΔΨm)to release cytochrome c(Cyt-c)from the mitochondria into the cytoplasm,eventually leading to mitochondrial-mediated cellular apoptosis during the PDT process.In addition,Pt-Ce6 has good photothermal stability and high photothermal conversion efficiency(52.62%)in the NIR-II region.In U14 tumor-bearing mice,Pt-Ce6 completely suppressed tumor growth and recurrence under laser irradiation.Thus the nanocomposite shows excellent PDT/photothermal therapy(PTT)synergistic performance in vitro and in vivo.