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Zeyu Wu Tingting Wang Yonghong Song Yang Lu Tianyun Chen Pengpeng Chen 《Journal of liposome research》2019,29(2):133-141
The purpose of this study was to optimize the preparation conditions of podophyllotoxin liposomes (PPT-Lips), and to investigate their effects on PC3 cells. PPT-Lips were prepared by using a thin-film dispersion method. In order to achieve maximum drug encapsulation efficiency (EE), the process and formulation variables were optimized by response surface methodology (RSM). The optimum preparation conditions were cholesterol to lecithin ratio of 3.6:40 (w/w), lipid to drug ratio of 15.8:1 (w/w), and the ultrasonic intensity of 35% (total power of 400?W). The experimental EE of PPT-Lips was 90.425%, which was consistent with the theoretically predicted value. The characterization studies showed that PPT-Lips were well-dispersible spherical particles with an average size of 106?nm and a zeta potential of –10.1?mV. A gradual and time-dependent pattern of PPT from liposomes was found in in vitro drug release with a cumulative release amount up to 70.3% in 24?h. Results of cell viability experiments on PC3 cells demonstrated that PPT-Lips exhibited more effective anticancer activity in comparison with free PPT. Therefore, PPT-Lips represent an efficient and promising drug delivery system for PPT. 相似文献
43.
Yanan Li Yu Yan Fang Liu Luguang Wang Fumin Feng Yonghong Xiao 《Journal of cellular biochemistry》2019,120(2):1685-1693
We previously showed that changes in calcium concentrations were related to cell apoptosis in vitro. The endoplasmic reticulum (ER) is the main component of calcium storage and signal transduction, and disrupting the balance of intracellular Ca2+ can cause endoplasmic reticulum stress (ERS). In this process, the ER releases stored Ca 2+ into the cytoplasm and activates calpain-2. To further investigate the effect of calpain in hepatic stellate cells (HSCs), in the current study, we examine the effect of N-acetyl-leu-leu-norleucinal (ALLN) on apoptosis resulting from calcium ionophore A23187–induced ERS. Our findings indicate that calpain inhibition reduces calcium ionophore A23187–induced apoptosis of HSCs and decreases the expression of ER stress proteins that may be related to the calpain/caspase signaling pathway. 相似文献
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Shigang Qiao Lei Hong Yongming Zhu Jun Zha An Wang Jia Qiu Wei Li Chen Wang Jianzhong An Huiling Zhang 《Cell death & disease》2022,13(2)
Receptor-interacting protein kinase 1 (RIPK1) and 3 (RIPK3) are critical regulators of programmed necrosis or necroptosis. However, the role of the RIPK1/RIPK3 signaling pathway in myocardial fibrosis and related diabetic cardiomyopathy is still unclear. We hypothesized that RIPK1/RIPK3 activation mediated myocardial fibrosis by impairing the autophagic flux. To this end, we established in vitro and in vivo models of type 2 diabetes mellitus with high glucose fat (HGF) medium and diet respectively. HGF induced myocardial fibrosis, and impaired cardiac diastolic and systolic function by activating the RIPK1/RIPK3 pathway, which increased the expression of autophagic related proteins such as LC3-II, P62 and active-cathepsin D. Inhibition of RIPK1 or RIPK3 alleviated HGF-induced death and fibrosis of cardiac fibroblasts by restoring the impaired autophagic flux. The autophagy blocker neutralized the effects of the RIPK1 inhibitor necrostatin-1 (Nec-1) and RIPK3 inhibitor GSK872 (GSK). RIPK1/RIPK3 inhibition respectively decreased the levels of RIPK3/p-RIPK3 and RIPK1/p-RIPK1. P62 forms a complex with RIPK1-RIPK3 and promotes the binding of RIPK1 and RIPK3, silencing of RIPK1 decreased the association of RIPK1 with P62 and the binding of P62 to LC3. Furthermore, inhibition of both kinases in combination with a low dose of Nec-1 and GSK in the HGF-treated fibroblasts significantly decreased cell death and fibrosis, and restored the autophagic flux. In the diabetic rat model, Nec-1 (1.65 mg/kg) treatment for 4 months markedly alleviated myocardial fibrosis, downregulated autophagic related proteins, and improved cardiac systolic and diastolic function. In conclusion, HGF induces myocardial fibrosis and cardiac dysfunction by activating the RIPK1-RIPK3 pathway and by impairing the autophagic flux, which is obviated by the pharmacological and genetic inhibition of RIPK1/RIPK3.Subject terms: Necroptosis, Diabetes complications 相似文献
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A human genetic disorder, Tangier disease, has been linked recently to mutations in ATP-binding cassette protein A1 (ABCA1). In addition to its function in apoprotein A-I-mediated lipid removal, ABCA1 was also shown to be a phosphatidylserine (PS) translocase that facilitates PS exofacial flipping. This PS translocation is crucial for the plasma membrane to produce protrusions enabling the engulfment of apoptotic cells. In this report, we show that ABCA1 also plays a role in endocytosis. Receptor-mediated endocytosis, probed by both transferrin and low density lipoprotein, is up-regulated by more than 50% in homozygous Tangier fibroblasts in comparison with controls. Fluid-phase uptake is increased similarly. We also demonstrate that bulk membrane flow, including lipid endocytosis and exocytosis, is accelerated greatly in Tangier cells. Moreover, endocytosis is similarly enhanced in normal fibroblasts when ABCA1 function is inhibited by glyburide, whereas glyburide has no effect on endocytosis in Tangier cells. In addition, we demonstrate a decreased annexin V binding in Tangier fibroblasts as compared with controls, supporting the notion that PS transmembrane distribution is indeed defective in the presence of ABCA1 mutations. Furthermore, adding a PS analog to the exofacial leaflet of the plasma membrane normalizes endocytosis in Tangier cells. Taken together, these data demonstrate that ABCA1 plays an important role in endocytosis. We speculate that this is related to the PS translocase function of ABCA1. A loss of functional ABCA1, as in the case of Tangier cells, enhances membrane inward bending and facilitates endocytosis. 相似文献
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BACKGROUND AND AIMS: Stem respiration of trees is a major, but poorly assessed component of the carbon balance of forests, and important for geo-chemistry. Measurements are required under naturally changing seasonal conditions in different years. Therefore, intra- and inter-annual carbon fluxes of stems in forests were measured continuously from April to November in three consecutive years. METHODS: Stem respiratory CO2 fluxes of 50-year-old Scots pine (Pinus sylvestris) trees were continuously measured with a CO2 analyser, and, concomitantly, stem circumference, stem and air temperature and other environmental factors and photosynthesis, were also measured automatically. KEY RESULTS: There were diurnal, seasonal and inter-annual changes in stem respiration, which peaked at 1600 h during the day and was highest in July. The temperature coefficient of stem respiration (Q10) was greater during the growing season than when growth was slow or had stopped, and more sensitive to temperature in the growing season. The annual Q10 remained relatively constant at about 2 over the three years, while respiration at a reference temperature of 15 degrees C (R15) was higher in the growing than in the non-growing season (1.09 compared with 0.78 micromol m(-2) stem surface s(-1)), but was similar between the years. Maintenance respiration was 76 %, 82 % and 80 % of the total respiration of 17.46, 17.26 and 19.35 mol m2 stem surface in 2001, 2002 and 2003, respectively. The annual total stem respiration of the stand per unit ground area was 75.97 gC m(-2) in 2001 and 74.28 gC m(-2) in 2002. CONCLUSIONS: Stem respiration is an important component in the annual carbon balance of a Scots pine stand, contributing 9 % to total carbon loss from the ecosystem and consuming about 8 % of the carbon of the ecosystem gross primary production. Stem (or air) temperature was the most important predictor of stem carbon flux. The magnitude of stem respiration is modified by photosynthesis and tree growth. Solar radiation indirectly affects stem respiration through its effect on photosynthesis. 相似文献
49.
Green BT Lyte M Chen C Xie Y Casey MA Kulkarni-Narla A Vulchanova L Brown DR 《American journal of physiology. Gastrointestinal and liver physiology》2004,287(6):G1238-G1246
Enteric neurotransmitters can modulate the biodefensive functions of the intestinal mucosa, but their role in mucosal interactions with enteropathogens is not well defined. Here we tested the hypothesis that norepinephrine (NE) modulates interactions between enterohemorrhagic Escherichia coli O157:H7 (EHEC) and the colonic epithelium. Mucosal sheets from porcine distal colon were mounted in Ussing chambers. Drugs and an inoculum of either Shiga toxin-negative or -positive EHEC were added to the contraluminal and luminal bathing medium, respectively. After 90 min, adherent bacteria were quantified by an adherence assay and by immunohistochemical methods; short-circuit current (I(sc)) was measured continuously to assess changes in active ion transport. NE-treated tissues exhibited concentration-dependent increases in I(sc) and EHEC adherence. NE did not alter adherence of a rodent-adapted, noninfectious E. coli strain or two porcine-adapted non-O157 E. coli strains. The actions of NE on EHEC adherence but not I(sc) were prevented by the alpha-adrenergic antagonist yohimbine and the PKA activator Sp-8-bromoadenosine-3',5'-cyclic monophosphorothioate. Like NE, the PKA inhibitor Rp-8-bromoadenosine-3',5'-cyclic monophosphorothioate or indirectly acting sympathomimetic agents increased EHEC adherence. Nerve fibers immunoreactive for the NE-synthesizing enzymes tyrosine hydroxylase and dopamine beta-hydroxylase appeared to innervate the colonic epithelium. EHEC-like immunoreactivity on the colonic surface had the appearance of bacterial microcolonies and increased after NE treatment by a phentolamine-sensitive mechanism. Through interactions with alpha(2)-adrenergic receptors, NE appears to increase EHEC adherence to the colonic mucosa. Changes in sympathetic neural outflow may alter intestinal susceptibility to infection. 相似文献
50.
Mixotrophic cultivation of <Emphasis Type="Italic">Platymonas subcordiformis</Emphasis> 总被引:4,自引:0,他引:4
Jingli Xie Yuanxing Zhang Yuanguang Li Yonghong Wang 《Journal of applied phycology》2001,13(4):343-347
The effects of glucose concentration and irradiance on mixotrophiccultivation of Platymonas subcordiformis were investigated in flaskcultures. The optimal glucose concentration was 24 g L-1, andirradiance was 95 mol photon m-2 s-1. Based on theoptimization of culture conditions and a modified SK(IA) medium, themaximum biomass was 3.68 g L-1 after 14 days, which was about6 times that in autotrophic culture, and the specific growth rate reached0.62 d-1, twice that in autotrophic culture. Using the optimalconditions established in flasks, mixotrophic culture in a 5.0-Lphotobioreactor was achieved, and the yield after 8 days was 3.30 gL-1. 相似文献