Gold nanoparticles (AuNPs) with antitumorigenic effects obstruct the initiation, development and progression of tumors via the regulation of various processes, such as proliferation and apoptosis. However, the effects of AuNPs on breast cancer metastasis have not been well studied, and their response to 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulation remains unclear. Therefore, we synthesized resveratrol-capped gold nanoparticles (Rev-AuNPs) using green nanotechnology and investigated their potential anti-invasive properties in human breast cancer cells in response to TPA stimulation. The Rev-AuNPs formed spherical nanoparticles of 22.28±2.98 nm in diameter. Next, we found that non-cytotoxic concentrations of Rev-AuNPs significantly suppressed the TPA-induced migration and invasion abilities of breast cancer cells. Rev-AuNPs suppressed TPA-induced enzymatic activity and the expression of matrix metalloproteinase (MMP)-9 and cyclooxygenase-2 (COX-2). Furthermore, Rev-AuNP treatment remarkably downregulated TPA-induced nuclear translocation and transcriptional activation of nuclear transcription factor-κB (NF-κB) and activator protein-1 (AP-1). Rev-AuNPs reduced the phosphorylation of phosphoinositide 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase (ERK)1/2 signaling, but did not affect the phosphorylation of Jun N-terminal kinase (JNK) or p38 MAPK in the TPA-stimulated breast cancer cells. Notably, Rev-AuNPs generally showed better anti-invasive activity than resveratrol without cytotoxicity. The inhibitory effect of Rev-AuNPs on MMP-9, COX-2, NF-κB, AP-1, PI3K/Akt and ERK activation was stronger than that of resveratrol for the same concentrations. We also demonstrated that Rev-AuNPs induced heme oxygenase-1 (HO-1) expression and that the inhibition of MMP-9 and COX-2 expression and MMP-9 enzymatic activity of Rev-AuNPs were abrogated by siRNA knockdown of HO-1 expression. Our findings revealed that the anti-invasive effects of Rev-AuNPs in response to TPA-stimulation were mediated by the suppression of MMP-9, COX-2, NF-κB, AP-1, PI3K/Akt and ERK and/or the activation of HO-1 signaling cascades. This novel finding emphasizes the pharmacological ability of Rev-AuNPs to treat breast cancer metastasis.
Acellular scaffolds, possessing an intact three-dimensional extracellular matrix (ECM) architecture and biochemical components, are promising for regeneration of complex organs, such as the kidney. We have successfully developed a porcine renal acellular scaffold and analyzed its physical/biochemical characteristics, biocompatibility, and kidney reconstructive potential. Segmented porcine kidney cortexes were treated with either 1% (v/v) Triton X-100 (Triton) or sodium dodecyl sulfate (SDS). Scanning electron microscopy showed both treatments preserved native tissue architecture, including porosity and composition. Swelling behavior was higher in the Triton-treated compared with the SDS-treated scaffold. Maximum compressive strength was lower in the Triton-treated compared with the SDS-treated scaffold. Attenuated total reflective-infrared spectroscopy showed the presence of amide II (-NH) in both scaffolds. Furthermore, richer ECM protein and growth factor contents were observed in the Triton-treated compared with SDS-treated scaffold. Primary human kidney cell adherence, viability, and proliferation were enhanced on the Triton-treated scaffold compared with SDS-treated scaffold. Following murine in vivo implantation, tumorigenecity was absent for both scaffolds after 8 weeks and in the Triton-treated scaffold only, glomeruli-like structure formation and neovascularity were observed. We identified 1% Triton X-100 as a more suitable decellularizing agent for porcine renal ECM scaffolds prior to kidney regeneration.
Oxidative stress-induced cellular senescence is an important contributor to the pathogenesis of age-related macular degeneration (AMD). Characteristics of premature cellular senescence include a loss of proliferation, change in cell shape, irreversible cell cycle arrest, and elevated senescence-associated β-galactosidase (SA-β-gal) activity. It was hypothesized that lutein may have anti-senescence potential and may be useful as a treatment for AMD. In the present study, premature cellular senescence was induced in ARPE-19 cells via treatment with H 2 O 2 and the effects of lutein application were confirmed by observing cell morphology, lysosome contents, reactive oxygen species (ROS) generation and SA-β-gal activity, and cell cycle progression. The protein expression was also analyzed via western blotting in order to identify the affected signaling pathways. The results revealed that H 2 O 2 treatment induced premature cellular senescence in ARPE-19 cells, as evidenced by an increased production of ROS and SA-β-gal, altered lysosome contents, changed cellular morphology and arrested cell cycle progression. However, when treated with lutein, ARPE-19 cells were effectively protected from these H 2 O 2 -induced effects. Western blot analysis revealed that lutein induced the expression of heme oxygenase-1, NAD(P)H quinone dehydrogenase 1, sirtuin (SIRT)-1, and SIRT3. Together, the results indicated that lutein protects cells from cellular senescence induced by oxidative stress; therefore, it may be able to suppress the progression of AMD. In addition, our increased understanding of the pathways through which lutein acts is useful for the development of novel therapies for the treatment of oxidative stress-associated retinal disease.Abbreviations: WST-1, water-soluble tetrazolium salt-1;CM-H 2 DCFDA, chloromethyl derivative of 2' ,7'-dichlorodihydrofluorescein diacetate; ROS, reactive oxygen species; SA-β-gal, senescence-associated β-galatosidase; PI, Propidium iodide; HO-1, heme oxygenase-1; NQO1, NAD(P)H quinone dehydrogenase 1; Nrf2, nuclear factor erythroid 2-related factor 2; SIRT1, sirtuin-1; SIRT3, sirtuin-3
Purpose:The purpose of this study was to compare reported physical symptoms, hope and family support of cancer patients between general hospitals and long-term care hospitals. Methods: Subjects were 175 patients diagnosed with cancers from two general hospitals and six long-term care hospitals located in G city. Subjects completed a questionnaire with questions about general characteristics and questions about the disease, physical symptoms, hope and family support. Data was collected from February to April and the data were analyzed using an independent t-test and one-way ANOVA. Results: The subjects in long-term care hospitals showed higher percentage in pain, nausea, fatigue, sleep disorder, and change in appearance. There was a significant difference in family support between two groups. A significant positive correlation was found between hope and family support in subjects in general and long-term care hospitals. Conclusion: Significant differences were found in some physical symptoms and family support between cancer patients in general hospitals and long-term care hospitals. Thus, nurses in long-term care hospitals need provide care suitable for the characteristics of cancer patients in long-term care hospitals.
The most promising treatment for stress urinary incontinence can be a cell therapy. We suggest human amniotic fluid stem cells (hAFSCs) as an alternative cell source. We established the optimum in vitro protocol for the differentiation from hAFSCs into muscle progenitors. These progenitors were transplanted into the injured urethral sphincter and their therapeutic effect was analyzed. For the development of an efficient differentiation system in vitro, we examined a commercial medium, co-culture and conditioned medium (CM) systems. After being treated with CM, hAFSCs were effectively developed into a muscle lineage. The progenitors were integrated into the host urethral sphincter and the host cell differentiation was stimulated in vivo. Urodynamic analysis showed significant increase of leak point pressure and closing pressure. Immunohistochemistry revealed the regeneration of circular muscle mass with normal appearance. Molecular analysis observed the expression of a larger number of target markers. In the immunogenicity analysis, the progenitor group had a scant CD8 lymphocyte. In tumorigenicity, the progenitors showed no teratoma formation. These results suggest that hAFSCs can effectively be differentiated into muscle progenitors in CM and that the hAFSC-derived muscle progenitors are an accessible cell source for the regeneration of injured urethral sphincter.
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