Implantable endovascular devices such as bare metal, drug eluting, and bioresorbable stents have transformed interventional care by providing continuous structural and mechanical support to many peripheral, neural, and coronary arteries affected by blockage. Although effective in achieving immediate restoration of blood flow, the long-term re-endothelialization and inflammation induced by mechanical stents are difficult to diagnose or treat. Here we present nanomaterial designs and integration strategies for the bioresorbable electronic stent with drug-infused functionalized nanoparticles to enable flow sensing, temperature monitoring, data storage, wireless power/data transmission, inflammation suppression, localized drug delivery, and hyperthermia therapy. In vivo and ex vivo animal experiments as well as in vitro cell studies demonstrate the previously unrecognized potential for bioresorbable electronic implants coupled with bioinert therapeutic nanoparticles in the endovascular system.
BackgroundKaempferol, a kind of flavonol, has been reported to possess various osteogenic biological activities, such as inhibiting bone resorption of osteoclasts and promoting the differentiation and mineralization of preosteoblasts. However, the precise cellular mechanism of action of kaempferol in osteogenesis is elusive.Autophagy is a major intracellular degradation system, which plays an important role in cell growth, survival, differentiation and homeostasis in mammals. Recent studies showed that autophagy appeared to be involved in the degradation of osteoclasts, osteoblasts and osteocytes, potentially pointing to a new pathogenic mechanism of bone homeostasis and bone marrow disease. The potential correlation between autophagy, osteogenesis and flavonoids is unclear.MethodsThe present study verified that kaempferol promoted osteogenic differentiation and mineralization and that it elevated osteogenic gene expression based on alkaline phosphatase (ALP) activity, alizarin red staining and quantitative PCR. And then we found that kaempferol induced autophagy by acridine orange (AO) and monodansylcadaverine (MDC) staining and autophagy-related protein expression. The correlation between kaempferol-induced autophagy and the osteogenic process was confirmed by the autophagy inhibitor 3-methyladenine (3-MA).ResultsKaempferol promoted the proliferation, differentiation and mineralization of osteoblasts at a concentration of 10 μM. Kaempferol showed cytotoxic properties at concentrations above 50 μM. Concentrations above 10 μM decreased ALP activity, whereas those up to 10 μM increased ALP activity. Kaempferol at concentrations up to 10 μM also increased the expression of the osteoblast- activated factors RUNX-2, osterix, BMP-2 and collagen I according to RT-PCR analyses. 10 μM or less, the higher of the concentration and over time, kaempferol promoted the activity of osteoblasts. Kaempferol induced autophagy. It also increased the expression of the autophagy-related factors beclin-1, SQSTM1/p62 and the conversion of LC3-II from LC3-I. The application of 3-MA decreased the activity of ALP and the autophagy induced by kaempferol. In the RT-PCR analysis, the expression of RUNX-2, osterix, BMP-2 and collagen I was decreased.ConclusionThe present study showed that kaempferol stimulated the osteogenic differentiation of cultured osteoblasts by inducing autophagy.
OSCC is the most common malignant cancer of the head and neck. EMT is an essential cellular process critical to the morphogenesis and homeostasis of solid tissues. It is also involved in the initial stage of cancer metastasis and invasion in which cells lose epithelial characteristics. While cancer therapy protocols such as surgery, radiation, and chemotherapy are effective and useful, the drug tolerance and toxicity of OSCC patients remain a problem. Resveratrol is mainly produced in red grape skin and exhibits anti-oxidative, anti-inflammatory, anti-proliferative, and anti-cancer properties. This study was undertaken to investigate the underlying mechanisms giving rise to the induction of apoptosis by resveratrol in the human tongue squamous cell carcinoma cell line. Resveratrol treatment resulted in a time- and dose-dependent decrease in cell viability and increased the apoptotic cell ratio in CAL-27, SCC15, and SCC25 cells. Resveratrol treatment of CAL-27 cells showed that several lines of apoptotic manifestation and decreased cell migration, invasion, and EMT-inducing transcription factor. Taken together, our findings demonstrate the inhibitory effect of resveratrol in human OSCC cells via the mitochondrial pathway and that resveratrol is able to inhibit cell invasion and migration by inhibiting the EMT-inducing transcription factors.
From the above results, the expression of OPG, RANKL, and RANK during the osseointegration of the dental titanium implant was observed within bone tissue. The application of the LLL influenced the expression of OPG, RANKL, and RANK, and resulted in the expansion of metabolic bone activity and increased the activity of bone tissue cells.
The aim of this study was to examine the effect of low-level laser therapy (LLLT) on the cell viability and the expression of hypoxia-inducible factor-1s (HIF-1s), bone morphogenic protein-2 (BMP-2), osteocalcin, type I collagen, transforming growth factor-β1 (TGF-β1), and Akt in hypoxic-cultured human osteoblasts. Human fetal osteoblast cells (cell line 1.19) were cultured under 1 % oxygen tension for 72 h. Cell cultures were divided into two groups. At the experimental side, low-level laser (808 nm, GaAlAs diode) was applied at 0, 24, and 48 h. After irradiation, each cell culture was incubated 24 h more under hypoxia. Total energy was 1.2, 2.4, and 3.6 J/cm(2), respectively. Non-irradiated cultures served as controls. Comparisons between the two groups were analyzed by t test; a p value <0.05 was considered statistically significant. Hypoxia resulted in a decrease in the expression of type I collagen, osteocalcin, and TGF-β1 (p < 0.001, p < 0.001, and p < 0.01, respectively). Cell viability and BMP-2 expression were not decreased by hypoxic condition. On the other hand, LLLT on hypoxic-cultured osteoblast promoted the expression of BMP-2, osteocalcin, and TGF-β1 (p < 0.05, p < 0.01, and p < 0.001, respectively). Cell proliferation was also increased time-dependently. However, hypoxia decreased in type I collagen expression (p < 0.001), and LLLT did not affect type I collagen expression in hypoxic-cultured osteoblasts. Furthermore, LLLT inhibited HIF-1 and Akt expression in hypoxic conditioned osteoblasts. We concluded that LLLT induces the expression of BMP-2, osteocalcin, and TGF- β1 in 1 % hypoxic-cultured human osteoblasts.
Kaempferol, a flavonoid compound, is derived from the rhizome of Kaempferia galanga L., which is used in traditional medicine in Asia. Autophagy has pleiotropic functions that are involved in cell growth, survival, nutrient supply under starvation, defense against pathogens, and antigen presentation. There are many studies dealing with the inhibitory effects of natural flavonoids in bone resorption. However, no studies have explained the relationship between the autophagic and inhibitory processes of osteoclastogenesis by natural flavonoids. The present study was undertaken to investigate the inhibitory effects of osteoclastogenesis through the autophagy inhibition process stimulated by kaempferol in murin macrophage (RAW 264.7) cells. The cytotoxic effect of Kaempferol was investigated by MTT assay. The osteoclast differentiation and autophagic process were confirmed via tartrate-resistant acid phosphatase (TRAP) staining, pit formation assay, western blot, and real-time PCR. Kaempferol controlled the expression of autophagy-related factors and in particular, it strongly inhibited the expression of p62/SQSTM1. In the western blot and real time-PCR analysis, when autophagy was suppressed with the application of 3-Methyladenine (3-MA) only, osteoclast and apoptosis related factors were not significantly affected. However, we found that after cells were treated with kaempferol, these factors inhibited autophagy and activated apoptosis. Therefore, we presume that kaempferol-inhibited autophagy activated apoptosis by degradation of p62/SQSTM1. Further study of the p62/SQSTM1 gene as a target in the autophagy mechanism, may help to delineate the potential role of kaempferol in the treatment of bone metabolism disorders.
ObjectivesThe purpose of this study is to analyze clinical impact factors on the survival rate, and to acquire basic clinical data for the diagnosis of oral cancer, for a determination of the treatment plan with long-term survival in oral cancer patients.Materials and MethodsThrough a retrospective review of the medical records, the factors for long-term survival rate were analyzed. Thirty-seven patients, among patient database with oral cancer treated in the Department of Oral and Maxillofacial Surgery at Pusan National University Hospital within a period from March 1998 to March 2008, were selected within the study criteria and were followed-up for more than 5 years. The analyzed factors were gender, age, drinking, smoking, primary tumor site, type of cancer, TNM stage, recurrence of affected region, and metastasis of cervical lymph node. The 5-year survival rate on the impact factors was calculated statistically using the Kaplan-Meier method.ResultsBy classification of clinical TNM at the 1st visit, there were 11 (29.7%) cases for stage I, 11 (29.7%) cases for stage II, 3 (8.1%) cases for stage III, and 12 (32.5%) cases for stage IV. The 5-year survival rate of total oral cancer patients after the operation were 75.7%, pathological TNM stage related 5-year survival rate were as follows: stage I 90.0%, stage II 81.8%, stage III 100% and stage IV 45.5%; in which the survival rate difference by each stage was significantly observed. The recurrence of cervical lymph node was the significant impact factor for the survival rate, because only 30.0% the survival rate in recurrent cases existed. During the follow-up, there were 15 (40.5%) patients with confirmed recurrence, and the 5-year survival rate of these patients was decreased as 46.7%.ConclusionThe classification of clinical and pathological TNM stage, local recurrence after surgery, and metastasis of cervical lymph node after surgery were analyzed as the 3 most significant factors.
A multisized piezoelectric microcantilever biosensor array with scaling down in two dimensions is presented as a multifunctional resonant cantilever-based sensor platform. The multisized microcantilever array allowed simultaneous sensing of the surface stress as well as mass. The adsorption-induced surface stress and resulting spring constant change were analyzed in the multisized microcantilever array, and a mass sensitivity in the femtogram regime was demonstrated. The array sensor was used to immobilize human IgG on its cantilever surface, suggesting that the dynamic and simultaneous analysis of both adsorption-induced mass and the surface stress is feasible.
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