Inhibition of hepatic stellate cells by bone marrow-derived mesenchymal stem cells in hepatic fibrosis

Background/AimsTherapies involving bone-marrow-derived mesenchymal stem cells (BM-MSCs) have considerable potential in the management of hepatic disease. BM-MSCs have been investigated in regenerative medicine due to their ability to secrete various growth factors and cytokines that regress hepatic fibrosis and enhance hepatocyte functionality. The aim of this study was to determine the antifibrosis effect of BM-MSCs on activated hepatic stellate cells (HSCs) and the mechanism underlying how BM-MSCs modulate the function of activated HSCs.MethodsWe used HSCs in both direct and indirect co-culture systems with BM-MSCs to evaluate the antifibrosis effect of BM-MSCs. The cell viability and apoptosis were evaluated by a direct co-culture system of activated HSCs with BM-MSCs. The activations of both HSCs alone and HSCs with BM-MSCs in the direct co-culture system were observed by immunocytochemistry for alpha-smooth muscle actin (α-SMA). The levels of growth factors and cytokines were evaluated by an indirect co-culture system of activated HSCs with BM-MSCs.ResultsThe BM-MSCs in the direct co-culture system significantly decreased the production of α-SMA and the viability of activated HSCs, whereas they induced the apoptosis of activated HSCs. The BM-MSCs in the indirect co-culture system decreased the production of transforming growth factor-β1 and interleukin (IL)-6, whereas they increased the production of hepatocyte growth factor and IL-10. These results confirmed that the juxtacrine and paracrine effects of BM-MSCs can inhibit the proliferative, fibrogenic function of activated HSCs and have the potential to reverse the fibrotic process by inhibiting the production of α-SMA and inducing the apoptosis of HSCs.ConclusionsThese results have demonstrated that BM-MSCs may exert an antifibrosis effect by modulating the function of activated HSCs

Replication of the genetic effects of IFN regulatory factor 5 (IRF5) on systemic lupus erythematosus in a Korean population

Recently, two studies provided convincing evidence that IFN regulatory factor 5 (IRF5) gene polymorphisms are significantly associated with systemic lupus erythematosus (SLE) in several white populations. To replicate the association with SLE in an Asian population, we examined the genetic effects in our SLE cohort from a Korean population. A total of 1,565 subjects, composed of 593 cases and 972 controls, were genotyped using the TaqMan® (Applied Biosystems, Foster City, CA, USA) method. The genetic effects of polymorphisms on the risk of SLE were evaluated using χ2 tests and a Mantel–Haenszel meta-analysis. Statistical analysis revealed results in the Korean population were similar to the previous reports from white populations. The rs2004640 T allele had a higher frequency in SLE cases (0.385) than controls (0.321; odds ratio (OR) = 1.32, P = 0.0003). In combined analysis, including all seven independent cohorts from the three studies so far, robust and consistent associations of the rs2004640 T allele with SLE were observed. The estimate of risk was OR = 1.44 (range, 1.34–1.55), with an overall P = 1.85 × 10-23 for the rs2004640 T allele. The haplotype (rs2004640T–rs2280714T) involved in both the alternative splice donor site and the elevated expression of IRF5 also had a highly significant association with SLE (pooled, P = 2.11 × 10-16). Our results indicate that the genetic effect on the risk of SLE mediated by IRF5 variants can be generally accepted in both white and Asian populations

Curative Effects of Thiacremonone against Acetaminophen-Induced Acute Hepatic Failure via Inhibition of Proinflammatory Cytokines Production and Infiltration of Cytotoxic Immune Cells and Kupffer Cells

High doses of acetaminophen (APAP; N-acetyl-p-aminophenol) cause severe hepatotoxicity after metabolic activation by cytochrome P450 2E1. This study was undertaken to examine the preventive effects of thiacremonone, a compound extracted from garlic, on APAP-induced acute hepatic failure in male C57BL/6J. Mice received with 500 mg/kg APAP after a 7-day pretreatment with thiacremonone (10–50 mg/kg). Thiacremonone inhibited the APAP-induced serum ALT and AST levels in a dose-dependent manner, and markedly reduced the restricted area of necrosis and inflammation by administration of APAP. Thiacremonone also inhibited the APAP-induced depletion of intracellular GSH, induction of nitric oxide, and lipid peroxidation as well as expression of P450 2E1. After APAP injection, the numbers of Kupffer cells, natural killer cells, and cytotoxic T cells were elevated, but the elevated cell numbers in the liver were reduced in thiacremonone pretreated mice. The expression levels of I-309, M-CSF, MIG, MIP-1α, MIP-1β, IL-7, and IL-17 were increased by APAP treatment, which were inhibited in thiacremonone pretreated mice. These data indicate that thiacremonone could be a useful agent for the treatment of drug-induced hepatic failure and that the reduction of cytotoxic immune cells as well as proinflammatory cytokine production may be critical for the prevention of APAP-induced acute liver toxicity

Immobilization of Lead in Contaminated Firing Range Soil Using Biochar

Soybean stover-derived biochar was used to immobilize lead (Pb) in military firing range soil at a mass application rate of 0 to 20 wt.% and a curing period of 7 days. The toxicity characteristic leaching procedure (TCLP) was performed to evaluate the effectiveness of the treatment. The mechanism responsible for Pb immobilization in military firing range soil was evaluated by scanning electron microscopy-energy dispersive x-ray spectroscopy (SEM-EDX) and x-ray absorption fine structure (XAFS) spectroscopy analyses. The treatment results showed that TCLP Pb leachability decreased with increasing biochar content. A reduction of over 90 % in Pb leachability was achieved upon treatment with 20 wt.% soybean stover-derived biochar. SEM-EDX, elemental dot mapping and XAFS results in conjunction with TCLP leachability revealed that effective Pb immobilization was probably associated with the pozzolanic reaction products, chloropyromorphite and Pb-phosphate. The results of this study demonstrated that soybean stover-derived biochar was effective in immobilizing Pb in contaminated firing range soil

High Shear Stress at the Surface of Enhancing Plaque in the Systolic Phase is Related to the Symptom Presentation of Severe M1 Stenosis

The computational fluid dynamics methods for the limited flow rate and the small dimensions of an intracranial artery stenosis may help demonstrate the stroke mechanism in intracranial atherosclerosis. We have modeled the high wall shear stress (WSS) in a severe M1 stenosis. The high WSS in the systolic phase of the cardiac cycle was well-correlated with a thick fibrous cap atheroma with enhancement, as was determined using high-resolution plaque imaging techniques in a severe stenosis of the middle cerebral artery

Conical Ground Helical Antenna with Feed-Through Insulator for High-Power Microwave Applications

In this paper, a novel helical antenna for high-power microwave is proposed. The proposed antenna is intended to demonstrate improved power handling capacity without any deterioration in matching characteristics, gain, and axial ratio. The proposed antenna with a long helix structure is investigated in order to achieve high gain and a relatively wide impedance bandwidth. By increasing the distance between the helix and the ground plane, an improved power handling capacity is obtained, and the impedance matching problem caused by the proposed method is addressed with the use of a feed-through insulator. In addition, a conical-shaped ground is used to compensate for the gain reduction by increasing the distance between the helix and the ground plane. As a result, the proposed antenna exhibits a gain exceeding 11 dBi and an axial ratio of less than 2 dB within the frequency range of 0.86–1.09 GHz. In addition, its power handling capacity exceeds 50 MW for a 0.7-ns input pulse length in air conditions

Novel Swine-Origin Influenza A (H1N1) Viral Encephalitis

The World Health Organization declared that a new strain of novel swine-origin influenza A (H1N1) virus was responsible for the pandemic infection in June 2009. We report a case of encephalitis diagnosed as the H1N1 virus infection. We describe a 17-year-old patient who had a seizure attack, diagnosed with a H1N1 virus infection via real time reverse-transcriptase polymerase chain reaction (RT-PCR). The H1N1 virus infection can be causative of the encephalitis, as with other influenza virus infections. Careful monitoring is essential for reducing complications