Mouse Type-I Interferon-Mannosylated Albumin Fusion Protein for the Treatment of Chronic Hepatitis.

Although a lot of effort has been put into creating drugs and combination therapies against chronic hepatitis, no effective treatment has been established. Type-I interferon is a promising therapeutic for chronic hepatitis due to its excellent anti-inflammatory effects through interferon receptors on hepatic macrophages. To develop a type-I IFN equipped with the ability to target hepatic macrophages through the macrophage mannose receptor, the present study designed a mouse type-I interferon-mannosylated albumin fusion protein using site-specific mutagenesis and albumin fusion technology.

Morphological and Proteomic Analyses of Soybean Seedling Interaction Mechanism Affected by Fiber Crosslinked with Zinc-Oxide Nanoparticles.

Nanoparticles (NPs) enhance soybean growth; however, their precise mechanism is not clearly understood. To develop a more effective method using NPs for the enhancement of soybean growth, fiber crosslinked with zinc oxide (ZnO) NPs was prepared. The solution of ZnO NPs with 200 nm promoted soybean growth at the concentration of 10 ppm, while fibers crosslinked with ZnO NPs promoted growth at a 1 ppm concentration.

α-Acid Glycoprotein Enhances the Immunosuppressive and Protumor Functions of Tumor-Associated Macrophages.

Blood levels of acute-phase protein α-acid glycoprotein (AGP, orosmucoid) increase in patients with cancer. Although AGP is produced from hepatocytes following stimulation by immune cell-derived cytokines under conditions of inflammation and tumorigenesis, the functions of AGP in tumorigenesis and tumor progression remain unknown. In the present study, we revealed that AGP contributes directly to tumor development by induction of programmed death ligand 1 (PD-L1) expression and IL6 production in macrophages.

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Nonproliferative and Proliferative Lesions of the Dog.

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions) Project (www.toxpath.org/inhand.

Immune Checkpoint Inhibitor Can Reduce HCV-RNA without Liver Damage.

Recently, immune checkpoint inhibitors (iCIs) have been used to treat cancers. Once some of the iCIs for the treatment of hepatocellular carcinoma (HCC) are certified in clinical trials, they are likely be administered to HCC patients with hepatitis C virus (HCV). However, the immunopathogenesis of HCV after the administration of iCIs has not been clarified.

[Cutting Edge of Hepatic Artery Infusion Chemotherapy for Hepatocellular Carcinoma].

Recently, the choices of treatments for hepatocellular carcinoma(HCC)were increasing since the several molecular targeting agents(MTA)were approved for treatment of advanced HCC patients. On the other hand, the transarterial chemoembolization( TACE)and hepatic artery infusion chemotherapy(HAIC)have been improved by various kinds of methods. The liver resection, radiofrequency ablation(RFA)and microwave coagulation(MWA)might achieve complete cure.

The reduction of miR146b-5p in monocytes and T cells could contribute to the immunopathogenesis of hepatitis C virus infection.

It has been reported that various kinds of miRNAs could affect the pathogenesis of hepatitis C virus infection. Recently, our group reported that deep-sequencing analysis was useful to detect disease-specific miRNAs. The aim of this study is to identify the HCV-specific miRNAs that could contribute to the immunopathogenesis of HCV by using clinical samples and in vitro analysis.

Hepatitis C virus infection could affect the pathogenesis of ischemic heart diseases in northern Japan.

Aims: Previously, our group reported that lymphotropic hepatitis C virus (HCV) could induce various kinds of immune dysfunctions. The immune dysfunctions could cause vascular disease by inducing cryoglobulinemia. It has been reported that ischemic heart diseases might be caused by HCV.

Complete Atrioventricular Block Associated with Pembrolizumab-induced Acute Myocarditis: The Need for Close Cardiac Monitoring.

Pembrolizumab, a humanized monoclonal IgG4 antibody directed against programmed death-1, is an immune checkpoint inhibitor that has been introduced for the treatment of non-small-cell lung cancer. However, immune checkpoint inhibitors may cause severe immune-related adverse events. We herein present a case of lung cancer with complete atrioventricular block associated with acute myocarditis, which developed 16 days after the administration of pembrolizumab.

Accumulation of Mott cells in the spleen in a CB6F1-Tg rasH2 mouse.

Mott cells are a variant form of plasma cells in humans and laboratory animals. This report describes the morphological characteristics of Mott cells observed in a 33-week-old female CB6F1-Tg rasH2 mouse. Microscopically, a large number of round cells with abundant eosinophilic globules, which were variable in size, were observed in the spleen and were densely distributed in the red pulp adjacent to the marginal zone.

Adipose progenitor cells reside among the mature adipocytes: morphological research using an organotypic culture system.

The precise localization and biological characteristics of the adipose progenitor cells are still a focus of debate. In this study, the localization of the adipose progenitor cells was determined using an organotypic culture system of adipose tissue slices. The tissue slices of subcutaneous white adipose tissue from rats were placed on a porous membrane and cultured at the interface between air and the culture medium for up to 5 days with or without adipogenic stimulation.

A case of metastatic adrenocortical carcinoma diagnosed with steroidogenic factor-1 in a sprague-dawley rat.

This report describes the morphological and immunohistochemical characteristics of an adrenocortical carcinoma with distant metastasis in a Sprague-Dawley rat. Macroscopically, a single large mass was observed in the adrenal gland, and multiple nodules were noted in the lung, liver and thyroid. Histologically, the adrenal tumor consisted of a solid growth of eosinophilic round cells with nuclear atypia.

Expression of steroidogenic factor 1 and pituitary specific transcription factor 1 in rat pituitary adenomas.

The protein expressions of steroidogenic factor l (SF-l) and pituitary-specific transcription factor 1 (Pit-1) were investigated immunohistochemically for 53 spontaneous pituitary adenomas of the pars distalis from male Crl:CD(SD) rats. Luteinizing hormone (LH)-positive/prolactin (PRL)-negative and LH-negative/PRL-positive adenomas showed that the expression of SF-1 and Pit-1 was exclusively related to the immunoreactivity of LH and PRL, respectively. All double-positive adenomas (positive for both LH and PRL) were positive for Pit-1 and were supposed to be derived from PRL cells, although some of them also showed SF-1 immunoreactivity.

Energy management by enhanced glycolysis in G1-phase in human colon cancer cells in vitro and in vivo.

Unlabelled: Activation of aerobic glycolysis in cancer cells is well known as the Warburg effect, although its relation to cell- cycle progression remains unknown. In this study, human colon cancer cells were labeled with a cell-cycle phase-dependent fluorescent marker Fucci to distinguish cells in G1-phase and those in S + G2/M phases. Fucci-labeled cells served as splenic xenograft transplants in super-immunodeficient NOG mice and exhibited multiple metastases in the livers, frozen sections of which were analyzed by semiquantitative microscopic imaging mass spectrometry.

Retinol supplements antiviral action of interferon in patients with chronic hepatitis C: a prospective pilot study.

Sustained virologic response with peg-interferon and ribavirin combination therapy for 48 weeks is still inadequate. Our study examined whether short-term administration of retinol clinically influences the anti-viral activity of interferon early during interferon and ribavirin combination therapy. The control group received 6 MIU of interferon alpha-2b every day for two weeks and then 3 times a week for 22 weeks intramuscularly plus 600 mg or 800 mg per day of ribavirin orally for 24 weeks.

Interactions of multiple gas-transducing systems: hallmarks and uncertainties of CO, NO, and H2S gas biology.

The diverse physiological actions of the "biologic gases," O2, CO, NO, and H2S, have attracted much interest. Initially viewed as toxic substances, CO, NO, and H2S play important roles as signaling molecules. The multiplicity of gas actions and gas targets and the difficulty in measuring local gas concentrations obscures detailed mechanisms whereby gases exert their actions, and many questions remain unanswered.

HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity.

Many cancer cells are characterized by increased glycolysis and decreased respiration, even under aerobic conditions. The molecular mechanisms underlying this metabolic reprogramming are unclear. Here we show that hypoxia-inducible factor 1 (HIF-1) negatively regulates mitochondrial biogenesis and O(2) consumption in renal carcinoma cells lacking the von Hippel-Lindau tumor suppressor (VHL).

HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells.

O(2) is the ultimate electron acceptor for mitochondrial respiration, a process catalyzed by cytochrome c oxidase (COX). In yeast, COX subunit composition is regulated by COX5a and COX5b gene transcription in response to high and low O(2), respectively. Here we demonstrate that in mammalian cells, expression of the COX4-1 and COX4-2 isoforms is O(2) regulated.

Induction of hypoxia-inducible factor 1 activity by muscarinic acetylcholine receptor signaling.

Hypoxia-inducible factor-1 (HIF-1) is a master regulator of cellular adaptive responses to hypoxia. Levels of the HIF-1alpha subunit increase under hypoxic conditions. Exposure of cells to growth factors, prostaglandin, and certain nitric oxide donors also induces HIF-1alpha expression under non-hypoxic conditions.

Defective balancing ability and hyperactivity in the CLX (circling behavior linked to the X-chromosome) mutant rat.

We have reported that the recently described circling behavior rat (CLX) is a hereditary mutant controlled by a single sex-linked recessive gene (gene symbol: clx). This mutant shows intermittent circle walking and/or running and head tossing with the neck twisted. The abnormal behavior begins to appear around weaning and continues throughout life.

Vascular endothelial growth factor gene expression in colon cancer cells exposed to prostaglandin E2 is mediated by hypoxia-inducible factor 1.

Prostaglandin E(2) (PGE(2)) has been implicated as an inducer of angiogenesis in human colon cancer. Here, we demonstrate that PGE(2) exposure induces the expression of vascular endothelial growth factor (VEGF) mRNA in HCT116 human colon carcinoma cells that is mediated by the transcriptional activator hypoxia-inducible factor 1 (HIF-1). PGE(2) exposure induces the phosphorylation of extracellular signal-regulated kinase (ERK) and AKT.

9-cis retinoic acid enhances the antiviral effect of interferon on hepatitis C virus replication through increased expression of type I interferon receptor.

The concentration of type I interferon receptor (IFN-Rc) in the liver is a crucial factor in determining the efficacy of interferon (IFN) therapy in patients with chronic hepatitis C. Retinoic acids (RAs) can enhance the expression of type I IFN-Rc expression. The aim of this study was to investigate whether RAs increase the anti-hepatitis C virus (HCV) effect of IFN through an increase in IFN-Rc.

New behavioral mutant rat exhibiting circling behavior (clx) controlled by a sex-linked recessive gene.

A male rat showing intermittent circling behavior was discovered among the Jcl:Wistar rats in our laboratories, and among its backcross offspring individuals showing the same behavior were found. The abnormalities in these animals were characterized by intermittent circling behavior (walking and/or running in circles) and head tossing with the neck twisted. No abnormalities were observed in fertility, delivery or pup mortality.