Cyclopropenes for the Stepwise Synthesis of 1,2,4,5-Tetraarylbenzenes via 1,4-Cyclohexadienes.

This paper describes a synthetic approach to the synthesis of 1,2,4,5-tetraarylbenzene derivatives from cyclopropenes. The Lewis acid-mediated dimerization of cyclopropenes gives tricyclo[3.1.

Growth Factor Midkine Aggravates Pulmonary Arterial Hypertension via Surface Nucleolin.

Pulmonary arterial hypertension (PAH) is a progressive fatal disease caused by pulmonary arterial remodeling. Midkine regulates cell proliferation and migration, and it is induced by hypoxia, but its roles in pulmonary arterial remodeling remain unclear. Serum midkine levels were significantly increased in PAH patients compared with control patients.

Thymidylate synthase inhibitor raltitrexed can induce high levels of DNA damage in MYCN-amplified neuroblastoma cells.

MYCN gene amplification is consistently associated with poor prognosis in patients with neuroblastoma, a pediatric tumor arising from the sympathetic nervous system. Conventional anticancer drugs, such as alkylating agents and platinum compounds, have been used for the treatment of high-risk patients with MYCN-amplified neuroblastoma, whereas molecule-targeting drugs have not yet been approved. Therefore, the development of a safe and effective therapeutic approach is highly desired.

Neurocan, an extracellular chondroitin sulfate proteoglycan, stimulates neuroblastoma cells to promote malignant phenotypes.

Neurocan (NCAN), a secreted chondroitin sulfate proteoglycan, is one of the major inhibitory molecules for axon regeneration in nervous injury. However, its role in cancer is not clear. Here we observed that high NCAN expression was closely associated with the unfavorable outcome of neuroblastoma (NB).

PRC2-Mediated Transcriptomic Alterations at the Embryonic Stage Govern Tumorigenesis and Clinical Outcome in MYCN-Driven Neuroblastoma.

Pediatric cancers such as neuroblastoma are thought to involve a dysregulation of embryonic development. However, it has been difficult to identify the critical events that trigger tumorigenesis and differentiate them from normal development. In this study, we report the establishment of a spheroid culture method that enriches early-stage tumor cells from TH-MYCN mice, a preclinical model of neuroblastoma.

Temporally and Spatially Regulated Expression of the Linker Histone H1fx During Mouse Development.

The linker histone H1fx is the least characterized member of the H1 family. To investigate the developmental changes of H1fx, we performed an immunohistochemical analysis of its expression pattern from embryos to adult mice. We found that H1fx was highly expressed during gastrulation, and was positive in all embryonic germ layers between E8.

SGO1 is involved in the DNA damage response in MYCN-amplified neuroblastoma cells.

Shugoshin 1 (SGO1) is required for accurate chromosome segregation during mitosis and meiosis; however, its other functions, especially at interphase, are not clearly understood. Here, we found that downregulation of SGO1 caused a synergistic phenotype in cells overexpressing MYCN. Downregulation of SGO1 impaired proliferation and induced DNA damage followed by a senescence-like phenotype only in MYCN-overexpressing neuroblastoma cells.

Midkine Deteriorates Cardiac Remodeling via Epidermal Growth Factor Receptor Signaling in Chronic Kidney Disease.

In chronic kidney disease, activation of the epidermal growth factor receptor (EGFR) leads to cardiac hypertrophy, which affects morbidity and mortality. In patients with renal insufficiency and heart failure, the expression of midkine, a heparin-binding growth factor, is increased. Therefore, we investigated the association between midkine and EGFR in the induction of cardiac hypertrophy and dysfunction in chronic kidney disease.

Hydrocortisone enhances the barrier properties of HBMEC/ciβ, a brain microvascular endothelial cell line, through mesenchymal-to-endothelial transition-like effects.

Background: Because in vitro blood-brain barrier (BBB) models are important tools for studying brain diseases and drug development, we recently established a new line of conditionally immortalized human brain microvascular endothelial cells (HBMEC/ciβ) for use in such models. Since one of the most important functional features of the BBB is its strong intercellular adhesion, in this study, we aimed at improving HBMEC/ciβ barrier properties by means of culture media modifications, thus enhancing their use for future BBB studies. In addition, we simultaneously attempted to obtain insights on related mechanistic properties.

NeuroD1 promotes neuroblastoma cell growth by inducing the expression of ALK.

Neuroblastoma is derived from the sympathetic neuronal lineage of neural crest cells, and is the most frequently observed of the extracranial pediatric solid tumors. The neuronal differentiation factor, NeuroD1, has previously been shown to promote cell motility in neuroblastoma by suppressing the expression of Slit2. Here we report that NeuroD1 is also involved in the proliferation of neuroblastoma cells, including human cell lines and primary tumorspheres cultured from the tumor tissues of model mice.

Nucleolar protein PES1 is a marker of neuroblastoma outcome and is associated with neuroblastoma differentiation.

Neuroblastoma (NB) is a childhood malignant tumor that arises from precursor cells of the sympathetic nervous system. Spontaneous regression is a phenomenon unique to NBs and is caused by differentiation of tumor cells. PES1 is a multifunctional protein with roles in both neural development and ribosome biogenesis.

Inactivation of SMC2 shows a synergistic lethal response in MYCN-amplified neuroblastoma cells.

The condensin complex is required for chromosome condensation during mitosis; however, the role of this complex during interphase is unclear. Neuroblastoma is the most common extracranial solid tumor of childhood, and it is often lethal. In human neuroblastoma, MYCN gene amplification is correlated with poor prognosis.

A new tumorsphere culture condition restores potentials of self-renewal and metastasis of primary neuroblastoma in a mouse neuroblastoma model.

Tumorsphere culture enriches and expands tumor cells, thus providing important resources for cancer studies. However, as compared with metastatic tissues, primary tumors in the nervous system rarely give rise to long-surviving tumorspheres, thereby seriously limiting studies on these cancers. This might be due to the limited self-renewal capability of tumor cells and/or to inappropriate culture conditions.

ALK is a MYCN target gene and regulates cell migration and invasion in neuroblastoma.

Human anaplastic lymphoma kinase (ALK) has been identified as an oncogene that is mutated or amplified in NBLs. To obtain a better understanding of the molecular events associated with ALK in the pathogenesis of NBL, it is necessary to clarify how ALK gene contributes to NBL progression. In the present study, we found that ALK expression was significantly high in NBL clinical samples with amplified MYCN (n = 126, P < 0.

Therapeutic potential of midkine in cardiovascular disease.

Unlabelled: Ischaemic heart disease, stroke and their pathological consequences are life-threatening conditions that account for about half of deaths in developed countries. Pathology of these diseases includes cell death due to ischaemia/reperfusion injury, vascular stenosis and cardiac remodelling. The growth factor midkine plays a pivotal role in these events.

Functional analysis of purine nucleoside phosphorylase as a key enzyme in ribavirin metabolism.

Ribavirin is a purine nucleoside analogue that possesses potent anti-hepatitis C virus activity, and it has long been considered likely that ribavirin undergoes a first-pass metabolism at the small intestine. Although purine nucleoside phosphorylase (PNP) is assumed to be involved in this metabolism, this has not been conclusively demonstrated. Furthermore, no pharmacogenomic studies related to PNP-mediated ribavirin phosphorolysis have previously been conducted.

The heparin-binding growth factor midkine: the biological activities and candidate receptors.

The heparin-binding growth factor midkine (MK) comprises a family with pleiotrophin/heparin-binding growth-associated molecule. The biological phenomena in which MK is involved can be categorized into five areas: (i) cancer, (ii) inflammation/immunity, (iii) blood pressure, (iv) development and (v) tissue protection. The phenotypes are clear in vivo, but the mechanisms by which MK exerts these actions are not fully understood.

Midkine promotes neuroblastoma through Notch2 signaling.

Midkine is a heparin-binding growth factor highly expressed in various cancers, including neuroblastoma, the most common extracranial pediatric solid tumor. Prognosis of patients with neuroblastoma in which MYCN is amplified remains particularly poor. In this study, we used a MYCN transgenic model for neuroblastoma in which midkine is highly expressed in precancerous lesions of sympathetic ganglia.

Establishment of a new conditionally immortalized cell line from human brain microvascular endothelial cells: a promising tool for human blood-brain barrier studies.

The blood-brain barrier (BBB) is formed by brain microvascular endothelial cells (BMEC) working together with astrocytes and pericytes, in which tight junctions and various transporters strictly regulate the penetration of diverse compounds into the brain. Clarification of the molecular machinery that provides such regulation using in vitro BBB models has provided important insights into the roles of the BBB in central nervous system (CNS) disorders and CNS drug development. In this study, we succeeded in establishing a new cell line, hereinafter referred to as human BMEC/conditionally immortalized, clone β (HBMEC/ciβ), as part of our ongoing efforts to develop an in vitro human BBB model.

Midkine inhibits inducible regulatory T cell differentiation by suppressing the development of tolerogenic dendritic cells.

Midkine (MK), a heparin-binding growth factor, reportedly contributes to inflammatory diseases, including Crohn's disease and rheumatoid arthritis. We previously showed that MK aggravates experimental autoimmune encephalomyelitis (EAE) by decreasing regulatory CD4(+)CD25(+)Foxp3(+) T cells (Tregs), a population that regulates the development of autoimmune responses, although the precise mechanism remains uncertain. In this article, we show that MK produced in inflammatory conditions suppresses the development of tolerogenic dendritic cells (DCregs), which drive the development of inducible Treg.

CD48 as a novel molecular target for antibody therapy in multiple myeloma.

Monoclonal antibody (mAb) drugs are desirable for the improvement of multiple myeloma (MM) treatment. In this study, we found for the first time that CD48 was highly expressed on MM plasma cells. In 22 out of 24 MM patients, CD48 was expressed on more than 90% of MM plasma cells at significantly higher levels than it was on normal lymphocytes and monocytes.

Effect of manufacturing methods of AgCl/Al2O3 catalyst on selective catalytic reduction of NO(x).

The AgCl/Al2O3 catalyst has potential for use in the selective catalytic reduction (SCR) of NO(x). A compound hydrocarbon, following oxygenation is used as a type of reducing agent. In this experiment, the AgCl/Al2O3 catalyst was produced by four different methods, and the differences among their reduction catalysis of NO(x) were compared.

Influence of coating method on catalyst activity of AgCl/Al2O3/SUS304 composite plate.

The γ-Al203 and AgCl/Al203 catalyst powder were coated on a stainless steel substrate by dip coating and electrophoretic deposition method. And AgCl/Al203 catalyst was produced by three kinds of methods, and the difference between the NOx reduction catalysis of the coated sample was compared. XRD and SEM were used to study the crystalline structure and cross-section of the coatings.

The neuronal differentiation factor NeuroD1 downregulates the neuronal repellent factor Slit2 expression and promotes cell motility and tumor formation of neuroblastoma.

The basic helix-loop-helix transcription factor NeuroD1 has been implicated in the neurogenesis and early differentiation of pancreatic endocrine cells. However, its function in relation to cancer has been poorly examined. In this study, we found that NeuroD1 is involved in the tumorigenesis of neuroblastoma.

DRR1 is expressed in the developing nervous system and downregulated during neuroblastoma carcinogenesis.

Down-regulated in renal cell carcinoma 1 (DRR1) is mapped at 3p21.1, and is a candidate tumor suppressor gene. However, its biological roles have yet to be elucidated.