The only presently viable treatment for end-stage liver disease is whole organ transplantation. However, there are insufficient livers available. The aim of the present study is to provide autologous bone marrowderived stem cells as a potential therapeutic for patients with end-stage cirrhosis. This is a retrospective chart review of autologous stem cell treatment in 48 patients, 36 with chronic end-stage hepatitis C-induced liver disease and 12 with end-stage autoimmune liver disease. For all patients, granulocyte colony-stimulating factor was administered to mobilize their hematopoietic stem cells. Following leukapheresis, CD34 + stem cells were isolated, amplified, and partially differentiated in culture, then reinjected into each subject via their hepatic artery or portal vein. Treatment was generally well tolerated with the expected moderate but transient bone pain from G-CSF in less than half of the patients. Three patients had serious treatment-related complications, and only 20.8% of these end-stage liver disease patients died during 12 months of follow up. For all patients there was a statistically significant decrease in ascites. There was clinical and biochemical improvement in a large percentage of patients who received the transplantation. In the viral group, there were marked changes in albumin (p = 0.0003), bilirubin (p = 0.04), INR (p = 0.0003), and ALT levels (p = 0.02). In the autoimmune group, values also improved significantly for albumin (p = 0.001), bilirubin (p = 0.002), INR (p = .0005), and ALT levels (p = 0.003). These results suggest that autologous CD34 + stem cell transplantation may be safely administered and appears to offer some therapeutic benefit to patients with both viral and autoimmune-induced end-stage liver disease.
In this study, hybrid carbon dots-plasmonic nanostructures including carbon dots/polyethyleneimine/gold (C-dots/PEI/Au), and carbon dots/polyethyleneimine/silver (C-dots/PEI/Ag) have been prepared using a microwave irradiation method. The prepared hybrid nanostructures have been characterized via optical spectroscopy, high resolution transmission electron microscopy (HRTEM), and X-ray diffraction (XRD).A remarkable enhancement in the optical parameters, such as absorptivity and quantum yield (QY), has been observed for the hybrid nanostructure compared to pure carbon dots. This plasmonic enhancement was more pronounced in the presence of silver (C-dots/PEI/Ag nanohybrid) than that of gold (C-dots/PEI/Au nanohybrid). This is referred to the low intrinsic loss and the degree of the overlap between the absorption spectra of silver nanoparticles and carbon dots. Furthermore, the biocompatibility assay and cellular response on epithelial kidney (Vero) normal cell has been investigated.The results showed that the optimal dose of treatment is about $200 mg ml À1 using both C-dots/PEI/Au or C-dots/PEI/Ag, nano-hybrids could be used safely in diagnostic bioimaging applications.
To evaluate the cytotoxic effect of chitosan nanoparticles (CS-NPs) on an in vitro human liver cancer cell model (HepG2) and their possible application as a drug delivery system, we synthesized water-soluble CS-NPs, investigated their properties and extensively evaluated their cytotoxic activity on the cellular and molecular levels. A human liver cancer cell line was used as a model of human liver cancer. The CS-NPs were characterized using transmission electron microscopy, Fourier transform infrared spectroscopy, and zeta analysis. The cytotoxic effects of the CS-NPs on HepG2 cells were monitored by sulforhodamine B colorimetric assays for cytotoxicity screening and flow cytometric analysis. Molecular investigations including DNA fragmentation and the expression of some apoptotic genes on the transcriptional RNA level were conducted. Treatment of HepG2 with different concentrations of 150 nm diameter CS-NPs did not show alteration of cell morphology after 24 h of cell exposure. Also, when cells were treated with 100 μg ml −1 of CS-NPs, 12% of them were killed and IC 50 reached 239 μg ml −1 after 48 h of cell exposure. Flow cytometry evaluation of the CS-NPs revealed mild accumulation in the G2/M phase followed by cellular DNA fragmentation after 48 h of cell exposure. Extensive evaluation of the cytotoxic effect of the CS-NPs showed messenger RNA (mRNA) apoptotic gene expression (p53, Bak, Caspase3) after 24 h of cell exposure with no expression of the mRNA of the caspase 3 gene after 48 h of cell exposure, suggesting the involvement of an intrinsic apoptotic caspase-independent pathway by increasing the exposure time of 100 μg ml −1 of the CS-NPs. The engineered CS-NPs were controlled to a 150 nm size and charges of 40 mV and a concentration of 100 μg ml −1 revealed a genotoxic effect on HepG2 after 48 h of cell exposure through intrinsic apoptotic caspase-independent mechanisms. Further quantitative analysis on the molecular and protein levels is still required to confirm the impact of chitosan size and time on genotoxic effect before reaching a final conclusion and starting its biomedical application.
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