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991.
Despite studies on the use of human embryonic stem cell (hESC) derivatives to treat ischemic diseases, there are technical safety issues that have yet to be resolved. Herein, we sought to develop a method for using secreted angiogenic factors from hESC-derived endothelial cell derivatives (hESC-ECs), while avoiding direct cell incorporation, to reduce tumorigenesis or unidentified side effects of injected cells in vivo. Multicellular aggregation of hESC-ECs (MA-hESC-ECs) increases survivability, and encapsulation in Matrigel (EnMA-hESC-ECs) blocks the cells' in vivo migration. To examine the therapeutic effects of EnMA-hESC-ECs, we implanted both forms of hESC-ECs in a mouse model of hindlimb ischemia. Treatment with EnMA-hESC-ECs suppressed limb loss and tissue damage with no noticeable side effects, such as tumorigenesis or teratoma formation, and the Matrigel implant could be easily removed after the procedure. Thus, MA and the encapsulation system are effective techniques for utilizing humoral factors secreted by hESC derivatives that aid in the survivability and safety. We expect these results to contribute to the thriving stem cell field by improving the bioavailability of hESC derivatives for regenerative medicine. 相似文献
992.
In the recent decade, numerous lignan derivatives isolated from plants have been proven to have the potential as an anti-cancer substance. On the search for anti-cancer compounds from Korean medicinal plants, the methanolic extract from the trunk of Tilia amurensis Rupr. (Tiliaceae) was found to have significant cytotoxicity against A549 (lung carcinoma), SK-OV-3 (ovary malignant ascites), SK-MEL-2 (skin melanoma), and HCT-15 (colon adenocarcinoma) in our screening test. Hence, a bioassay-guided fractionation and chemical investigation of the methanolic extract resulted in the isolation and identification of 10 lignan derivatives (1–10) including two new lignan glycosides named tiliamurosides A (1) and B (2). The structures of these new compounds were determined by spectroscopic methods, namely 1D and 2D nuclear magnetic resonance (NMR) techniques, high resolution mass spectrometry (HRMS), circular dichroism (CD) data, and chemical methods. Tiliamuroside B (2) and schizandriside (3) showed significant cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines with inhibitory concentration (IC50) values of 3.26–8.89 μM. Moreover, (−)-syringaresinol (8) and (−)-pinoresinol 4-O-β-d-glucopyranoside (10) significantly inhibited nitric oxide (NO) production in murine microglia BV-2 with IC50 values of 15.05 and 34.35 μM, respectively. 相似文献
993.
Ko-Woon Choi Sung Hee Um Jong-Hwan Kwak Hye-Jin Park Kyung-Ho Kim Eun-Yi Moon Soon-Tae Kwon Suhkneung Pyo 《Food and chemical toxicology》2012
Atherosclerosis is a chronic inflammatory disease associated with increased expression of adhesion molecules in vascular smooth muscle cells (VSMCs). The objective of this study was to examine the in vitro effects of extract from aerial Bulbil of Dioscorea batatas Decne (Db-Ex) on the ability to suppress the expression of adhesion molecules induced by TNF-α. We also identified bioactive components from a methanol extract. VSMCs pre-exposed to Db-Ex (10–100 μg/ml) were stimulated with TNF-α (10 ng/ml). Preincubation of VSMCs for 2 h with Db-Ex dose-dependently inhibited TNF-α-induced adhesion of THP-1 monocytic cells and mRNA and protein expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Db-Ex treatment decreased ROS production and the amount of phosphorylated form of p38, ERK, JNK and Akt in TNF-α-stimulated cells, suggesting that Db-Ex inhibits adhesion molecule expression possibly through MAPK and Akt regulation. Db-Ex also suppressed TNF-α-activation NK-κB. This effect was mediated through degradation of IκBα and nuclear translocation of the p65 subunit of NF-κB. These results suggest that Db-Ex inhibits monocyte adhesion and the TNF-α-mediated induction of adhesion molecules in VSMC by downregulating the MAPK/Akt/NF-κB signaling pathway, which may explain the ability of Db-Ex to suppress inflammation within the atherosclerotic lesion. 相似文献
994.
Joong-Sun Kim Seung-Bum Ryoo Kyu Heo Joong-Gook Kim Tae-Gen Son Changjong Moon Kwangmo Yang 《Food and chemical toxicology》2012
Gastrointestinal injury is a major cause of death following exposure to high levels of radiation, and no effective treatments are currently available. In this study, we examined the capacity of granulocyte colony-stimulating factor (G-CSF) to mitigate intestinal injury in, and improve survival of, C3H/HeN mice given a lethal dose (12 Gy) of radiation to the abdomen. G-CSF (100 μg/kg body weight) was injected subcutaneously daily for 3 days after irradiation and shown to improve survival and intestinal morphology at 3.5 days compared with saline-injected controls. The morphological features improved by G-CSF included crypt number and depth, villous length, and the length of basal lamina of 10 enterocytes. G-CSF also normalized the levels of circulating tumor necrosis factor alpha and attenuated the loss of peripheral neutrophils, caused by radiation-induced myelosuppression. In conclusion, our results suggest that G-CSF enhanced the survival of irradiated mice and minimized the effects of radiation on gastrointestinal injury. 相似文献
995.
996.
Cho HJ Ku WS Termsarasab U Yoon I Chung CW Moon HT Kim DD 《International journal of pharmaceutics》2012,423(2):153-160
To achieve rapid onset of action and improved bioavailability of udenafil, a microemulsion system was developed for its intranasal delivery. Phase behavior, particle size, transmission electron microscope (TEM) images, and the drug solubilization capacity of the microemulsion were investigated. A single isotropic region was found in pseudo-ternary phase diagrams developed at various ratios with CapMul MCM L8 as an oil, Labrasol as a surfactant, and Transcutol or its mixture with ethanol (1:0.25, v/v) as a cosurfactant. Optimized microemulsion formulations with a mean diameter of 120-154 nm achieved enhanced solubility of udenafil (>10 mg/ml) compared with its aqueous solubility (0.02 mg/ml). An in vitro permeation study was performed in human nasal epithelial (HNE) cell monolayers cultured by the air-liquid interface (ALI) method, and the permeated amounts of udenafil increased up to 3.41-fold versus that of pure udenafil. According to the results of an in vivo pharmacokinetic study in rats, intranasal administration of udenafil-loaded microemulsion had a shorter Tmax value (1 min) compared with oral administration and improved bioavailability (85.71%) compared with oral and intranasal (solution) administration. The microemulsion system developed for intranasal administration may be a promising delivery system of udenafil, with a rapid onset of action and improved bioavailability. 相似文献
997.
998.
Nephrotoxicity occurs when kidney-specific detoxification and excretion do not work properly due to the damage or destruction of kidney function by exogenous or endogenous toxicants. Exposure to drugs often results in toxicity in kidney which represents the major control system maintaining homeostasis of body and thus is especially susceptible to xenobiotics. Understanding the toxic mechanisms for nephrotoxicity provides useful information on the development of drugs with therapeutic benefi ts with reduced side effects. Mechanisms for drug-induced nephrotoxicity include changes in glomerular hemodynamics, tubular cell toxicity, inflammation, crystal nephropathy, rhabdomyolysis, and thrombotic microangiopathy. Biomarkers have been identifi ed for the assessment of nephrotoxicity. The discovery and development of novel biomarkers that can diagnose kidney damage earlier and more accurately are needed for effective prevention of drug-induced nephrotoxicity. Although some of them fail to confer specificity and sensitivity, several promising candidates of biomarkers were recently proved for assessment of nephrotoxicity. In this review, we summarize mechanisms of drug-induced nephrotoxicity and present the list of drugs that cause nephrotoxicity and biomarkers that can be used for early assessment of nephrotoxicity. 相似文献
999.
Cheon YH Kim MJ Kang MG Kim HJ Lee SS Kim CY Jeon DH Kim YE Lee GW 《Yonsei medical journal》2011,52(4):695-698
Erlotinib is accepted as a standard second-line chemotherapeutic agent in patients with non-small cell lung cancer who are refractory or resistant to first-line platinum- based chemotherapy. There has been no previous report of bowel perforation with or without gastrointestinal metastases related to erlotinib in patients with non-small cell lung cancer. The exact mechanism of bowel perforation in patients who received erlotinib remains unclear. In this report, we report the first case of enterocutaneous fistula in a female patient with metastatic non-small cell lung cancer 9 months, following medication with erlotinib as second-line chemotherapy. 相似文献
1000.