Influences of changing inorganic nitrogen concentration on accumulation and degradation of organic components in indigenous microalgae cultivated with secondary effluent.

Climatic changes due to emission of greenhouse gases are a global concern. These emissions occur by combustion of fossil fuels whose drought is near in which case renewable energy is the only alternative. Microalgae are promising sources of sustainable bioenergy production, and utilisation of wastewater as cultures is recommended for economical production cost.

Biochemical response of indigenous microalgal consortia to variations in nitrogen concentration of treated effluent.

Cultivation conditions influence microalgal cellular components, such as lipid accumulation under nutrient depletion, high light irradiation and salinity stress. In this study, indigenous microalgal consortia were cultivated in batch mode using an actual treated effluent. The temporal response of cellular components to the variations in nitrogen concentration and influence of light irradiation on the response were investigated.

Hsp90 prevents interaction between CHIP and HERG proteins to facilitate maturation of wild-type and mutant HERG proteins.

Aims: We examined the role of Hsp90 in expression and maturation of wild-type (WT) and mutant ether-a-go-go related gene (HERG) proteins by using Hsp90 inhibitors, geldanamycin (GA) and radicicol, and Hsp90 overexpression.

Methods And Results: The proteins were expressed in HEK293 cells or collected from HL-1 mouse cardiomyocytes, and analysed by western blotting, immunoprecipitation, immunofluorescence, and whole-cell patch-clamp techniques. GA and radicicol suppressed maturation of HERG-FLAG proteins and increased their immature forms.

AMP deaminase 3 plays a critical role in remote reperfusion lung injury.

Remote reperfusion lung injury following skeletal muscle ischemia and reperfusion accounts for high morbidity and mortality. AMP deaminase (AMPD), a key enzyme for nucleotide cycle, has been implicated in the regulation of this phenomenon. However, the function of Ampd2 and Ampd3 subtype has not been elucidated in remote reperfusion rodent lung injury.

Involvement of microRNAs in regulation of osteoblastic differentiation in mouse induced pluripotent stem cells.

Unlabelled: BACKGOROUND: MicroRNAs (miRNAs), which regulate biological processes by annealing to the 3'-untranslated region (3'-UTR) of mRNAs to reduce protein synthesis, have been the subject of recent attention as a key regulatory factor in cell differentiation. The effects of some miRNAs during osteoblastic differentiation have been investigated in mesenchymal stem cells, however they still remains to be determined in pluripotent stem cells.

Methodology/principal Findings: Bone morphogenic proteins (BMPs) are potent activators of osteoblastic differentiation.

Reactive oxygen species and NADPH oxidase 4 induced by transforming growth factor β1 are the therapeutic targets of polyenylphosphatidylcholine in the suppression of human hepatic stellate cell activation.

Objective And Design: To clarify the molecular mechanism of polyenylphosphatidylcholine (PPC), we examined the involvement of reactive oxygen species (ROS) and NADPH oxidase 4 (Nox4) in human hepatic stellate cells (HSCs).

Material: Using human LX-2 HSC cells, we examined the effects of PPC on expression of α-smooth muscle actin (α-SMA) and collagen 1, generation of ROS, Nox4 expression, p38 activation and cell proliferation, induced by transforming growth factor β1 (TGFβ1).

Results: PPC suppressed ROS which are induced by TGFβ1, phosphorylation of p38MAPK, and expression levels of α-SMA and collagen 1 in a dose-dependent manner.

c-Jun N-terminal kinase activation by oxidative stress suppresses retinoid signaling through proteasomal degradation of retinoic acid receptor α protein in hepatic cells.

We previously reported that impaired retinoid signaling causes hepatocellular carcinoma (HCC) through oxidative stress. However, the interaction between oxidative stress and retinoid signaling has not been fully understood. To address this issue, the effects of hydrogen peroxide on the transcriptional activity of RAR/RXR heterodimers, RARα and RXRα proteins and intracellular signaling pathways were examined.

Iron state in association with retinoid metabolism in non-alcoholic fatty liver disease.

Aim:   We have recently reported that hyperdynamic state of retinoid metabolism, which may lead to the shortage of retinoid, is observed in patients with non-alcoholic fatty liver disease (NAFLD). Hepatic iron overload, which causes production of reactive oxygen species (ROS), is also frequently seen in NAFLD patients. The aim of the study is to examine iron state and retinoid metabolic state simultaneously, and to clarify the relationship between two disorders.

Genetic analysis of expression profile involved in retinoid metabolism in non-alcoholic fatty liver disease.

Aim: The patients with non-alcoholic fatty liver disease (NAFLD) have been reported to be at greater risk for progression to chronic liver disease including liver cirrhosis (LC). To examine the mechanisms for the progression of NAFLD, a genetic analysis of hepatic expression profile in retinoid metabolism in NAFLD was performed since the loss of retinoid signaling is associated with the progression of liver disease via reactive oxygen species (ROS) generation.

Methods: Fifty-one genes, which are associated with retinoid metabolism and action, were examined in thirty six subjects including 17 patients with simple steatosis, 11 with non-alcoholic steatohepatitis (NASH) and eight controls were examined by real-time reverse transcriptase polymerase chain reaction.

A close association of abnormal iron metabolism with steatosis in the mice fed a choline-deficient diet.

Hepatic iron overload has been frequently observed in the liver of patients with chronic liver diseases. In this study, the effect of hepatic fatty acid accumulation on the iron metabolism was investigated. Mice fed a choline-deficient diet developed severe steatosis associated with increased total amount of non-heme iron in the liver.

Stabilizing effects of eicosapentaenoic acid on Kv1.5 channel protein expressed in mammalian cells.

We investigated the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the stability of Kv1.5 channel protein. The expression and function of Kv1.

Involvement of thioredoxin-binding protein 2 in the antitumor activity of CD437.

The present authors previously reported that a synthetic retinoid, CD437, induces endoplasmic reticulum stress-mediated apoptosis in ovarian adenocarcinoma cells in spite of no response to natural retinoids. However, the precise mechanism of its proapoptotic action has not been fully determined. The present study herein demonstrates that apoptosis induction of ovarian adenocarcinoma SKOV3 cells by CD437 involves the upregulation of thioredoxin-binding protein 2 (TBP2) by a mechanism that is dependent on the intracellular calcium concentration.

Suppressive effects of retinoids on iron-induced oxidative stress in the liver.

Background & Aims: We previously reported that impaired retinoid signaling in the liver causes steatohepatitis and hepatocellular carcinoma. Recently, oxidative stress induced by hepatic iron overload has emerged as an important factor for the progression of liver disease in patients with chronic hepatitis C, alcoholic liver disease, and nonalcoholic steatohepatitis. In this study, the relationship between retinoid signaling and iron metabolism in the liver was investigated.

Hepatic differentiation of human bone marrow-derived mesenchymal stem cells by tetracycline-regulated hepatocyte nuclear factor 3beta.

Unlabelled: Human bone marrow-derived mesenchymal stem cells (BM-MSCs) are expected to be a potential source of cells for transplantation. Although recent reports have shown that isolated MSCs can differentiate into hepatocytes, the efficiency of differentiation is insufficient for therapeutic application. To circumvent this problem, it is necessary to understand the mechanisms of hepatic differentiation of human BM-MSCs.

Functional stabilization of Kv1.5 protein by Hsp70 in mammalian cell lines.

The aim of this study was to elucidate the mechanisms for regulations of cardiac Kv1.5 channel expression. We particularly focused on the role of heat shock proteins (Hsps).

Synthetic retinoid CD437 induces mitochondria-mediated apoptosis in hepatocellular carcinoma cells.

Retinoids play an important role in the regulation of cell growth and death. Synthetic retinoid CD437 reportedly induces apoptosis in various cancer cell lines. However, the mechanism of inducing apoptosis in hepatocellular carcinoma (HCC) cells by this agent remains to be clarified.

CD437 induces apoptosis in ovarian adenocarcinoma cells via ER stress signaling.

A synthetic retinoid, CD437, has been shown to exert potent anti-tumor activity against various types of cancer cell lines, regardless of their sensitivities to natural retinoids. We herein demonstrate that CD437 induces endoplasmic reticulum (ER) stress, including the up-regulation of CHOP, BIP and GADD34 mRNA through ER stress transducer (PERK and IRE1alpha) activation in an ovarian adenocarcinoma cell line, SKOV3. It was also shown that CD437 induced the CHOP and GADD34 expressions in another four ovarian adenocarcinoma cell lines, indicating that CD437 functions as an ER stress inducer in these cell lines.

Significance of urinary excretion of 8-hydroxy-2'-deoxyguanosine in healthy subjects and liver disease patients.

Background/aims: Although the importance of reactive oxygen species (ROS) in the pathogenesis of various diseases is stressed, clinical significance of the markers reflecting DNA oxidation such as 8-hydroxy-2'-deoxyguanosine (8-OHdG) remains to be clarified.

Methodology: To examine clinical usefulness of 8-OHdG in healthy individuals in comparison with liver disease patients, urinary excretion of 8-OHdG was measured in 336 healthy individuals and 110 patients with liver disease.

Results: In healthy persons, the 8-OHdG excretion was increased in an age-dependent manner.

A role of Wnt/beta-catenin signals in hepatic fate specification of human umbilical cord blood-derived mesenchymal stem cells.

Human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) are expected to be an excellent source of cells for transplantation. In addition, the stem cell plasticity of human UCBMSCs, which can transdifferentiate into hepatocytes, has been reported. However, the mechanisms involved remain to be clarified.

The vIL-10 gene of the Epstein-Barr virus (EBV) is conserved in a stable manner except for a few point mutations in various EBV isolates.

A gene of the Epstein-Barr virus (EBV), BamHI-C fragment rightward reading frame 1 (BCRF1), codes viral interleukin-10 (vIL-10), which is a close homolog to human IL-10. EBV strain variations are known at EBV latent membrane protein 1 (LMP1), and the distinct forms of LMP1 have been identified. In order to further elucidate the variations of EBV strains, the BCRF1 (vIL-10) gene was analyzed using PCR-direct sequencing in African Burkitt's lymphoma (BL) cell lines Raji, P3HR-1, EB1 and Daudi, Japanese BL cell line Akata, lymphoblastoid cell line OB and 22 wild EBV isolates from eight gastric carcinoma tissues and 14 throat washes.

Hepatic differentiation of human bone marrow-derived UE7T-13 cells: Effects of cytokines and CCN family gene expression.

Aim: Bone marrow-derived mesenchymal stem cells (MSC) are expected to be an excellent source of cells for transplantation. We aimed to study the culture conditions and involved genes to differentiate MSC into hepatocytes.

Methods: The culture conditions to induce the efficient differentiation of human bone marrow-derived UE7T-13 cells were examined using cytokines, hormones, 5-azacytidine and type IV collagen.

Regulation of hepatic oval cell proliferation by adenoviral mediated hepatocyte growth factor gene transfer and signal transduction inhibitors.

Background/aims: To rescue patients with severe liver injury, it is critical to develop the efficient regulatory system of hepatic stem cell proliferation in vitro. Our aims are to examine whether combination of adenovirus-mediated hepatocyte growth factor (HGF) gene transfer with signal transduction inhibitors can regulate cell proliferation of oval cells.

Methodology: We examined the effects of treatment with adenoviral mediated HGF gene transfer and signal transduction inhibitors including LY294002, rapamycin and U0126 on proliferation OC/CDE22 hepatic oval cells and expression of signal transduction molecules.

Remote reperfusion lung injury is associated with AMP deaminase 3 activation and attenuated by inosine monophosphate.

Background: Remote reperfusion lung injury occurs in patients with vascular occlusion and surgical procedures. Inosine monophosphate (IMP) produced by adenosine monophosphate deaminase (AMPD) 3 is involved in the remote reperfusion injury. The purpose of the present study was to identify whether IMP administration attenuated the remote reperfusion lung injury in a skeletal muscle ischemia-reperfusion model.

An antioxidant effect by acyclic retinoid suppresses liver tumor in mice.

The mechanisms of prevention of the development of liver cancer by NIK-333, an acyclic retinoid (ACR), were investigated. The transgenic mice expressing the dominant negative form of retinoic acid receptor alpha (RARE mice), that produce reactive oxygen species and lead to development of liver tumor were used. The effect of NIK-333 on hepatocarcinogenesis in RARE mice was studied.