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Hypoxia plays an important role in tumor phenotype and progression and alters glycolysis, with changes in signaling pathways that develop in response to hypoxia. In this study, the effects of oxygen (normoxia/hypoxia) and of glucose levels on the glucose metabolism was investigated in MCF-7 cancer cells. Under either normoxia or hypoxia conditions, the cells were exposed to glucose at different concentrations (0, 5.5, 15 or 55 mM) for either 3, 6, 12, 24 or 48 h. In all groups, cell viability, levels of key enzymes reflecting glycolytic metabolism in cell lysates, glucose consumed in the medium and extracellular lactate levels and wound closure percentages were determined. In hypoxic cells, intracellular consumption of glucose, and extracellular lactate levels due to increased glucose concentration were observed to be higher (compared to normoxia) and as a result of prolonged exposure to hypoxia, cells were observed to develop resistance to the prolonged exposure to hypoxia. The number of glycolytic enzymes obtained at different levels proved that cells had different potential capacities and changing mechanisms for the metabolic needs of the cell depending on the glucose amount in the medium and time in adapting to the oxygen tension. This study showed that there was an important interaction between hypoxia and glucose metabolism in general, and it was concluded that metabolic processes activated by hypoxia could offer new therapeutic targets.Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling, which exists in both pulmonary arteries and pulmonary veins. Pulmonary vascular remodeling stems from excessive proliferation of pulmonary vascular myocytes. Platelet-derived growth factor-BB (PDGF-BB) is a vital vascular regulator whose level increases in PH human lungs. Although the mechanisms by which pulmonary arterial smooth muscle cells respond to PDGF-BB have been studied extensively, the effects of PDGF-BB on pulmonary venous smooth muscle cells (PVSMCs) remain unknown. We herein examined the involvement of calcium sensing receptor (CaSR) in PDGF-BB-induced PVSMCs proliferation under hypoxic conditions. In PVSMCs isolated from rat intrapulmonary veins, PDGF-BB increased the cell number and DNA synthesis under normoxic and hypoxic conditions, which was accompanied by upregulated CaSR expression. The influences of PDGF-BB on proliferation and CaSR expression in hypoxic PVSMCs were greater than that in normoxic PVSMCs. In hypoxic PVSMCs superfused with Ca2+-free solution, restoration of extracellular Ca2+ induced an increase of [Ca2+]i, which was significantly smaller than that in PDGF-BB-treated hypoxic PVSMCs. Calcium folinate manufacturer The positive CaSR modulator spermine enhanced, whereas the negative CaSR modulator NPS2143 attenuated, the extracellular Ca2+-induced [Ca2+]i increase in PDGF-BB-treated hypoxic PVSMCs. Furthermore, the spermine enhanced, whereas the NPS2143 inhibited, PDGF-BB-induced proliferation in hypoxic PVSMCs. Silencing CaSR with siRNA attenuated the extracellular Ca2+-induced [Ca2+]i increase in PDGF-BB-treated hypoxic PVSMCs and inhibited PDGF-BB-induced proliferation in hypoxic PVSMCs. In conclusion, these results demonstrated that CaSR mediating PDGF-BB-induced excessive PVSMCs proliferation is an important mechanism involved in the initiation and progression of PVSMCs proliferation under hypoxic conditions.The study intends to investigate the regulation of syndecan-1 in human uterine leiomyoma cells. Human syndecan-1 levels were detected by Western blot in uterus leimyoma's tissue. The efficacy of syndecan-1 silencing on the cell proliferation, metalloproteinases and extracellular matrix were determined through Cell Counting Kit (CCK8) assay and Western blot assay, respectively. We compared the respective and combined effect of mifepristone and syndecan-1 on cell proliferation and the expression of metalloproteinases and extracellular matrix (ECM) in human uterine leiomyoma cells. The inhibitory effects of Syndecan-1 silencing on proliferation, ECM and Matrix Metalloproteinase (MMP) were observed in human uterine leiomyoma cells. Furthermore, syndecan-1 inhibition enhanced the effects of mifepristone against uterine leiomyoma cell proliferation. The expression of MMPs and ECM components in human uterine leiomyoma cells was decreased dramatically after syndecan-1 silencing, which was promoted after mifepristone treatment. Altogether, syndecan-1 silencing enhanced the efficacy of mifepristone on the uterine leiomyoma cell proliferation and ECM formation. Therefore, targeting syndecan-1 represents a novel therapeutic strategy to treat uterine leiomyoma.Dioscorea opposita Thunb has the effect of anti-osteoporosis, but whether its active ingredient diosgenin (DIO) has an anti-osteoporosis effect is unknown. The purpose of this study is to investigate the effect of DIO on the proliferation and differentiation of MG-63 cells. MG-63 cells were treated with different concentrations of DIO (0.001, 0.01, 0.1 and 1 μM) or 20 mM Wnt/β-catenin signaling agonist-LiCl, and then their cell cycle and viability were analyzed by flow cytometry and 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), respectively. To investigate osteoblast differentiation, alizarin red staining and ultraviolet spectrophotometer were used to determine the number of calcified nodules and the activity of alkaline phosphatase (ALP), respectively. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting were used to detect the expressions of proliferation-related, osteogenic-related and Wnt/β-catenin signal pathway-related factors. After the cells were treated with low-concentration (0.001 or 0.01 μM) DIO, cell viability was significantly increased and the proportion of cells in S phase was increased. In addition, low-concentration DIO could significantly increase the expression of Ki67, proliferating cell nuclear antigen (PCNA), osteopontin (OPN), and osteocalcin (BGP), promote osteoblast differentiation, and suppress the expression of β-catenin, Runx2 and cyclinD1. However, high concentrations of DIO showed the opposite effect. Low-concentration DIO obviously reversed the effect of LiCl on decreasing the number of calcified nodules and inhibiting the expression of OPN and BGP in cells. Low-concentration DIO might promote the proliferation and differentiation of MG-63 cell by inhibiting the Wnt/β-catenin signal pathway.
Website: https://www.selleckchem.com/products/calcium-folinate.html
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