Efficacy of Mesenchymal Stem Cells in Suppression of Hepatocarcinorigenesis in Rats: Possible Role of Wnt Signaling

<p>Abstract</p> <p>Background</p> <p>The present study was conducted to evaluate the tumor suppressive effects of bone marrow derived mesenchymal stem cells (MSCs) in an experimental hepatocellular carcinoma (HCC) model in rats and to investigate the possible role of Wnt signaling in hepato-carcinogenesis.</p> <p>Methods</p> <p>Ninety rats were included in the study and were divided equally into: Control group, rats which received MSCs only, rats which received MSCs vehicle only, HCC group induced by diethylnitroseamine (DENA) and CCl_<b>4</b>, rats which received MSCs after HCC induction, rats which received MSCs before HCC induction. Histopathological examination and gene expression of Wnt signaling target genes by real time, reverse transcription-polymerase chain reaction (RT-PCR) in rat liver tissue, in addition to serum levels of ALT, AST and alpha fetoprotein were performed in all groups.</p> <p>Results</p> <p>Histopathological examination of liver tissue from animals which received DENA-CCl₄only, revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules type II with foci of large and small cell dysplasia. Administration of MSCs into rats after induction of experimental HCC improved the histopathological picture which showed minimal liver cell damage, reversible changes, areas of cell drop out filled with stem cells. Gene expression in rat liver tissue demonstrated that MSCs downregulated <it>β-catenin</it>, proliferating cell nuclear antigen (<it>PCNA</it>), <it>cyclin D </it>and <it>survivin </it>genes expression in liver tissues after HCC induction. Amelioration of the liver status after administration of MSCs has been inferred by the significant decrease of ALT, AST and Alpha fetoprotein serum levels. Administration of MSCs before HCC induction did not show any tumor suppressive or protective effect.</p> <p>Conclusions</p> <p>Administration of MSCs in chemically induced HCC has tumor suppressive effects as evidenced by down regulation of Wnt signaling target genes concerned with antiapoptosis, mitogenesis, cell proliferation and cell cycle regulation, with subsequent amelioration of liver histopathological picture and liver function.</p

Effect of novel water soluble curcumin derivative on experimental type- 1 diabetes mellitus (short term study)

Abstract Background Diabetes mellitus type 1 is an autoimmune disorder caused by lymphocytic infiltration and beta cells destruction. Curcumin has been identified as a potent inducer of heme-oxygenase-1 (HO-1), a redoxsensitive inducible protein that provides protection against various forms of stress. A novel water soluble curcumin derivative (NCD) has been developed to overcome low in vivo bioavailability of curcumin. The aim of the present work is to evaluate the anti diabetic effects of the “NCD” and its effects on diabetes-induced ROS generation and lipid peroxidation in experimental type- 1 diabetes mellitus. We also examine whether the up regulation of HO-1 accompanied by increased HO activity mediates these antidiabetic and anti oxidant actions. Materials and methods Rats were divided into control group, control group receiving curcumin derivative, diabetic group, diabetic group receiving curcumin derivative and diabetic group receiving curcumin derivative and HO inhibitor ZnPP. Type-1 diabetes was induced by intraperitoneal injection of streptozotocin. Curcumin derivative was given orally for 45 days. At the planned sacrification time (after 45 days), fasting blood samples were withdrawn for estimation of plasma glucose, plasma insulin and lipid profile . Animals were sacrificed; pancreas, aorta and liver were excised for the heme oxygenase - 1 expression, activity and malondialdehyde estimation. Results NCD supplementation to diabetic rats significantly lowered the plasma glucose by 27.5% and increased plasma insulin by 66.67%. On the other hand, the mean plasma glucose level in the control group showed no significant difference compared to the control group receiving the oral NCD whereas, NCD supplementation to the control rats significantly increased the plasma insulin by 47.13% compared to the control. NCD decreased total cholesterol, triglycerides, LDL cholesterol and increased HDL cholesterol levels. Also, it decreased lipid peroxides (malondialdehyde) in the pancreas, aorta and liver. Conclusion The (NCD) by its small dose possesses antidiabetic actions and that heme oxygenase induction seems to play an important role in its anti-diabetic effects. NCD also improves the lipid profile and oxidative status directly, proved by decreasing lipid peroxides (malondialdehyde) in pancreas, liver & aorta. The new water soluble curcumin derivative still retains the essential potencies of natural curcumin.</p

Simulation-aided occupant-centric building design: A critical review of tools, methods, and applications

Occupants are active participants in their built environment, affecting its performance while simultaneously being affected by its design and indoor environmental conditions. With recent advances in computer modeling, simulation tools, and analysis techniques, topics such as human-building interactions and occupant behavior have gained significant interest in the literature given their premise of improving building design processes and operating strategies. In practice, the focus of occupant-centric literature has been mostly geared towards the latter (i.e., operation), leaving the implications on building design practices underexplored. This paper fills the gap by providing a critical review of existing studies applying computer-based modeling and simulation to guide occupant-centric building design. The reviewed papers are organized along four main themes, namely occupant-centric: (i) metrics of building performance, (ii) modeling and simulation approaches, (iii) design methods and applications, and (iv) supporting practices and mechanisms. Important barriers are identified for a more effective application of occupant-centric building design practices, including the limited consideration of metrics beyond energy efficiency (e.g., occupant well-being and space planning), the limited implementation and validation of the proposed methods, and the lack of integration of occupant behavior modeling in existing building performance simulation tools. Future research directions are discussed, covering large-scale international data collection efforts to move from generic assumptions about occupant behavior to specific/localized knowledge, improved metrics of measuring building performance, and improved industry practices, such as building codes, to promote an occupant-in-the-loop approach to the building design process

Water Quality Observations in the Marine Aquaculture Complex of the Deeba Triangle, Lake Manzala, Egyptian Mediterranean Coast

Coastal aquaculture is faced with extreme variation in water quality. The Deeba Triangle on Lake Manzala is the largest marine coastal aquaculture-producing area on the Egyptian Mediterranean. Samples from 16 ponds were taken during four seasons (2014–2015), to investigate the variation of 12 water quality parameters at that region. We tested the hypothesis that there is no spatial or temporal variation in water quality of the fish ponds. Fish ponds were statistically clustered into three groups (p = 0.0005) coincident with their geographical location. Hypersaline and transparent waters characterized the western ponds; higher dissolved oxygen and higher nutrients characterized the central region. These spatial differences were principally due to variations in salinity and nutrients of the water sources used for irrigation of the ponds and to differences in the aeration management styles. Strong seasonality was seen in water temperature (following air temperature), nutrients, and turbidity (following the seasonal cycles of various water sources from the Lake Manzala and the seasonality of the petrochemical plants effluents close to these ponds). We conclude that municipal effluents significantly affected, spatially and temporally, the quality of the irrigation water used for coastal aquaculture purposes, which consequently might affect fish yield