IntroductionWe have assessed the utility of autologous mesenchymal stem cell (MSC) peripheral vein infusion as a possible therapeutic modality for patients with end-stage liver diseases.MethodsForty patients with post-hepatitis C virus (HCV) end-stage liver disease were randomized into two groups: Group 1 (GI): 20 patients who received granulocyte colony-stimulating factor (G-CSF) for 5 days followed by autologous MSCs peripheral-vein infusion and group 2 (GII): 20 patients who received regular liver-supportive treatment only (control group).ResultsIn MSC-infused patients (GI), 54% showed near normalization of liver enzymes and improvement in liver synthetic function. Significant changes were reported in albumin (P = 0.000), bilirubin (P = 0.002), increased international normalized ratio (INR) (P = 0.017), prothrombin concentration (P = 0.029) and alanine transaminase (ALT) levels (P = 0.029), with stabilization of clinical and biochemical status in 13% of cases. None of the patients in GII showed any significant improvement. Hepatic fibrosis was assessed in GI by detection of procollagen IIIC peptide level (PIIICP) and procollagen III N peptide level (PIIINP). The pretreatment values of s-PIIICP and s-PIIINP were 9.4 ± 4.2 and 440 ± 189, respectively, with a decrease to 8.1 ± 2.6 and 388 ± 102, respectively, 3 months after MSC therapy. However, the difference was statistically nonsignificant (P = 0.7). A significant correlation coefficient was reported after 3 months between the s-PIIINP and prothrombin concentration (P = -0.5) and between s-PIIICP and ascites (P = 0.550).ConclusionsFirst, autologous MSC infusion into a peripheral vein is as effective as the previously reported intrahepatic infusion. Second, MSCs have a supportive role in the treatment of end-stage liver disease, with satisfactory tolerability and beneficial effects on liver synthetic functions and hepatic fibrosis. Third, IV infusion of MSCs after G-CSF mobilization improves s-albumin within the first 2 weeks and prothrombin concentration and alanine Taransaminase after 1 month. According to the data from this current study and those previously reported by our group, we recommend further studies on patients’ infusion with pure CD133 and CD34 followed by IV infusion of in vitro-differentiated MSCs within 1 week and another infusion after 3 months.Trial registrationClinicalTrials.gov NCT01729221. Registered 17 November 2012.

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A simple and rapid method for morphine detection is described based on PEDOT electrode in the presence of SDS. The electrochemistry of morphine is investigated by CV, LSV and SWV. The effect of common interferences on the current response of morphine namely AA and UA is studied. The electrode is applied to the selective determination of morphine in urine samples in the linear ranges 0.3-8 mmol L À1 and 10-60 mmol L À1 , with low detection limits of 50 and 68 nmol L À1, respectively and recovery of 96.4 %. The application of PEDOT is realized in determination of morphine in tablets successfully.

A promising electrochemical sensor was developed using poly(3,4-ethylene dioxythiophene) modified platinum electrode in the presence of sodium dodecyl sulphate (SDS). This sensor is sensitive for the determination of catecholamine compounds, namely dopamine, epinephrine, L-norepinephrine, and L-DOPA, as well as serotonin (ST) in the presence of interference molecules such as uric acid, ascorbic acid (AA), and glucose. The presence of SDS in the medium plays a key role in the electrostatic attraction of these compounds toward the polymeric surface and causes repulsion toward the interfering ones. Cyclic voltammetry, linear sweep voltammetry, ultraviolet-visible (UV-vis), nuclear magnetic resonance and electrochemical impedance spectroscopy were used to verify the behavior of the studied compounds in micellar media. In the presence of an anionic surfactant, the presence of large excess of AA and glucose did not interfere with the voltammetric responses of catecholamine and ST. The linear response was obtained for serotonin in the range of 0.05-10 lmol l À1 and 20-100 lmol l À1 with correlation coefficients of 0.997 and 0.998 and detection limits 48 and 71 nmol l À1 , respectively. The utility of this modified electrode was demonstrated for the determination of ST in human urine.There is considerable interest in developing electrochemical techniques for measurement of catecholamines such as epinephrine (E), norepinephrine (NE), dopamine (DA), and serotonin (ST), which are important neurotransmitters in mammalian species. 1 DA is widely distributed in the brain tissues for message transfer in mammalian central nervous system. The deficiency of DA can result in some neurological disorders such as schizophrenia and Parkinson's disease. 2-4 ST is also distributed in the brain and plays a crucial role in emotional system together with other neurotransmitters. Uric acid (UA) is the primary end product of purine metabolism. Abnormal levels of UA are symptoms of several diseases such as hyperuricaemia, gout, and Lesch-Nyan disease. 5 Thus, detecting and determining the concentrations of catecholamines in the presence of interfering species is an important goal in electrochemical analysis. Much attention has been given to the design and development of novel materials coated on electrode surfaces with improved molecular recognition capabilities. 6-9 The determination of monoamine neurotransmitters have been carried out by using spectrophotometery, 10 fluorescence, 11 chemical luminescence, 12 pseudopolarography, 13 voltammetry, 14 capillary electrophoresis, 15 and sensors based on enzymatic amplification. 16 High performance liquid chromatography (HPLC) with electrochemical detection is most often used for the analysis of catecholamines and their metabolites. 1,16-18 The detection of neurotransmitters and their metabolites by electrochemical methods have attracted great interests because of their simplicity, rapidness, high sensitivity, and the ability of sensing neurotransmitters in living organisms and in vivo real time an...

MicroRNAs regulate the expression of many genes and subsequently control various cellular processes, such as the immune response to viral infections mediated by type I interferon (IFN). In this study, the expression pattern of two interferon-related microRNAs, miR-146a and miR-155, was examined in healthy and HCV-genotype-4-infected peripheral blood mononuclear cells (PBMCs) using qRT-PCR. In contrast to other viral infections, the expression pattern was similar in both healthy and infected PBMCs. This could be attributed to attenuation of IFN pathway by HCV, which was assessed by investigating the expression of MxA, an interferon-stimulated gene, that showed lower expression in HCV-infected PBMCs. To determine the site of interference of HCV in the IFN pathway, expression of both microRNAs was examined following stimulation of PBMCs with IFN-α2a, an activator of the JAK/STAT pathway as well as with imiquimod, a toll-like receptor-7 (TLR-7) agonist that promotes interferon release. IFN stimulation induced the expression of miR-146a and miR-155 in HCV-infected and healthy PBMCs. Stimulation with imiquimod led to a down-regulation of both microRNAs in infected PBMCs, while it increased their expression in healthy PBMCs, indicating that HCV might interfere with miR-146a and miR-155 expression at sites upstream of interferon release, specifically in the TLR-7 pathway. The pattern of expression of both miR-146a and miR-155 was very similar with a strong positive correlation, but showed no correlation to the patients’ clinical or histopathological parameters or response to treatment. In conclusion, HCV infection might repress the induction of miR-146a and miR-155 by interfering with TLR-7 signaling.