NFAT activation by FKBP52 promotes cancer cell proliferation by suppressing p53.

FK506-binding protein 52 (FKBP52) is a member of the FKBP family of proline isomerases. FKBP52 is up-regulated in various cancers and functions as a positive regulator of steroid hormone receptors. Depletion of FKBP52 is known to inhibit cell proliferation; however, the detailed mechanism remains poorly understood.

Evaluating the Effectiveness and Clinical Outcomes of Endovascular Aneurysm Repair-First Approach for Ruptured Abdominal Aortic Aneurysm in Japan.

Purpose: To verify the validity of an endovascular aneurysm repair (EVAR)-first strategy for treating patients with ruptured abdominal aortic aneurysm (rAAA) in Japan.

Materials And Methods: This study was conducted on 2 groups of patients with rAAA who underwent surgical treatment at 3 hospitals in the Kanagawa Prefecture, Japan, between January 2007 and September 2016. The open surgical treatment group comprised patients with rAAA who underwent open surgical treatment before January 2012; their data were retrospectively collected from their medical records.

Long-Term Outcomes of a Japanese Prospective Multicenter Registry Using a Heparin-Bonded Expanded Polytetrafluoroethylene Graft for Above-the-Knee Femoropopliteal Bypasses.

Background: Despite the widespread use of PROPATEN, a bioactive heparin-bonded expanded polytetrafluoroethylene graft, in bypass surgery, there are only a few reports of long-term results. We evaluated the long-term results of PROPATENuse for above-knee femoropopliteal bypass (AKFPB).

Methods And Results: After PROPATEN-based AKFPB, patients were prospectively registered at 20 Japanese institutions between July 2014 and October 2017 to evaluate long-term results.

A Dual Cobalt and Photoredox Catalysis for Hydrohalogenation of Alkenes.

We demonstrate hydrohalogenation of aliphatic alkenes with collidine·HX salts through dual photoredox/cobalt catalysis. The dual catalysis enables conversion of a proton and a halide anion from collidine·HX salt to a nucleophilic hydrogen radical equivalent and an electrophilic halogen radical equivalent and delivery of them to an alkene moiety. This protocol allows for introduction of fluorine, chlorine, bromine, or iodine atom to alkene, producing highly functionalized alkyl halides.

Serial longitudinal changes of coronary calcified plaques with clear outer borders under intensive lipid management: insights from optical coherence tomography.

Percutaneous coronary intervention (PCI) for calcified lesions is one of the most challenging procedures related to worse clinical outcomes. To stabilize vulnerable plaques, intensive lipid management is recommended; however, the serial changes of calcified plaques under intensive lipid management are unknown. A total of 31 patients (mean age, 63 ± 10 years; men, 29 patients) who underwent PCI with intensive lipid management were retrospectively studied.

PP2A inhibitor SET promotes mTORC1 and Bmi1 signaling through Akt activation and maintains the colony-formation ability of cancer cells.

Protein phosphatase 2A (PP2A) is an essential tumor suppressor, with its activity often hindered in cancer cells by endogenous PP2A inhibitory proteins like SE translocation (SET). SET/PP2A axis plays a pivotal role in the colony-formation ability of cancer cells and the stabilization of c-Myc and E2F1 proteins implicated in this process. However, in osteosarcoma cell line HOS, SET knock-down (KD) suppresses the colony-formation ability without affecting c-Myc and E2F1.

AMP-activated protein kinase (AMPK) suppresses Ibaraki virus propagation.

The Ibaraki virus (IBAV) causes Ibaraki disease in cattle. Our previous studies have shown that IBAV uses macropinocytosis to enter the host cell and exit from the endosome to the cytosol in response to endosomal acidification. To further explore the mechanism of IBAV infection and replication, we examined the effect of inhibitors of mitochondrial oxidative phosphorylation, carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and antimycin A, on IBAV propagation.

Dephosphorylation of NFAT by Calcineurin inhibits Skp2-mediated degradation.

The transcription factor NFAT plays key roles in multiple biological activities, such as immune responses, tissue development and malignant transformation. NFAT is dephosphorylated by calcineurin, which is activated by intracellular calcium levels, and translocated into the nucleus, resulting in transcriptional activation. Calcineurin dephosphorylates various target proteins and regulates their functions.

Incidence, Predictors, and Outcome Associated With Ventricular Tachycardia or Fibrillation in Patients Undergoing Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction.

Background: The characteristics and clinical outcomes associated with sustained ventricular tachycardia and fibrillation (VT/VF) in Japanese acute myocardial infarction (AMI) patients remain unknown.

Methods and results: Consecutive AMI patients (n=1,941) transferred to the Hirosaki University Hospital and treated with primary percutaneous coronary intervention (PCI) within 12 h of onset were retrospectively studied. The incidence of VT/VF during hospitalization was 8.

IgG and insulin enhance endocytosis in THP-1 cells via activation of phosphatidylinositol 3-kinase (PI3K).

Extracellular substances, including membrane-impermeable nutrients, are taken up by cells via endocytosis. Endocytosis is also an important pathway for antigen uptake by antigen-presenting cells such as monocytes, macrophages, dendritic cells, and B cells. In this study, we investigated the regulatory mechanism of endocytosis in THP-1 cells, a monocytic leukemia cell line.

Assessment of soil-soil solution distribution coefficients of global fallout Np and Pu in Japanese upland soils.

Neptunium-237 and Pu are important radionuclides in the safety assessment related to geological disposal of radioactive waste because of the possibility of long-term exposure to humans. Mobilities of these radionuclides in the environment are of particular importance for their radiation dose evaluation; therefore, in this study, we have made the assessment of the soil-soil solution distribution coefficient (K, L/kg) using global fallout Np and Pu in Japanese upland soils. The K values were determined by extracting these radionuclides from 24 soil samples using a laboratory batch method.

Mechanistic/mammalian target of rapamycin complex 1 (mTORC1) signaling is involved in phagocytosis activation during THP-1 cell differentiation.

Mechanistic/mammalian target of rapamycin complex 1 (mTORC1) is a serine/threonine kinase that plays a major role in cell metabolism. Although mTORC1 inhibitors are known to exert immunosuppressive effects, their effects on immune cells are not fully understood. In the present study, we examined the involvement of mTORC1 in the differentiation and functions of macrophages using THP-1 cells, which are derived from human monocytic leukemia and differentiate into macrophage-like cells upon treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA).

Age-related alterations in protein phosphatase 2A methylation levels in brains of cynomolgus monkeys: a pilot study.

The abnormal activity of PP2A, a dominant member of type 2A serine/threonine protein phosphatase, has been implicated in the development of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). PP2A is a holoenzyme, and protein methylation of the catalytic subunit, PP2Ac, alters the complex composition. A decrease in PP2Ac methylation levels has been reported in AD and DLB.

Dephosphorylation of the EGFR protein by calcineurin at serine 1046/1047 enhances its stability.

The epidermal growth factor receptor (EGFR) is highly expressed or abnormally activated in several types of cancers, such as lung and colorectal cancers. Inhibitors that suppress the tyrosine kinase activity of EGFR have been used in the treatment of lung cancer. However, resistance to these inhibitors has become an issue in cancer treatment, and the development of new therapies that inhibit EGFR is desired.

Nuclear-targeted 4E-BP1 is dephosphorylated, induces nuclear translocation of eIF4E, and alters mRNA translation.

Mechanistic target of rapamycin complex 1 (mTORC1) phosphorylates and inhibits eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1). This leads to the release of eIF4E from 4E-BP1 and the initiation of eIF4E-dependent mRNA translation. In this study, we examined the expression of a 4E-BP1-based reporter (mTORC1 activity reporter; TORCAR) with various localization signal tags to clarify the relationship between the localization of 4E-BP1 and its phosphorylation.

Approaches to the definition of potentially exposed groups and potentially exposed populations of biota in the context of solid radioactive waste.

A methodology for addressing the biosphere in safety assessments for solid radioactive waste disposal was developed through theme 1 of the IAEA coordinated research project on BIOsphere Modelling and ASSessment (BIOMASS) that ran from 1996 to 2001. This methodology provided guidance on how the biosphere can be addressed in safety assessments for disposal of solid radioactive waste. Since the methodology was developed, it has proven useful and has been widely referenced in assessments in a diversity of contexts encompassing both near-surface and deep geological disposal of solid radioactive waste.

Soil-soil solution distribution coefficients of global fallout Pu and Np in Japanese paddy soils.

Pu and Np are long-lived radionuclides that emit alpha rays, and once released into the environment, they are present there for a long period of time. Therefore,Pu and Np are important radionuclides in the safety assessment related to geological disposal of radioactive waste because of the possibility of long-term exposure to humans. Mobilities of these radionuclides in the environment are of particular interest; therefore, in this study, we have made the first-time determination of the soil-soil solution distribution coefficient (K, L/kg) using global fallout Pu and Np in soil.

Partial glycosylation of the Ibaraki virus NS3 protein is sufficient to support virus propagation.

Ibaraki virus (IBAV) causes Ibaraki disease. We have previously shown that IBAV NS3 protein is highly glycosylated and that tunicamycin, an inhibitor of N-linked glycosylation, suppressed NS3 glycosylation and viral propagation. Since tunicamycin is known to cause endoplasmic reticulum (ER) stress, we explored the effects of ER stress and NS3 glycosylation on IBAV infection using tunicamycin and thapsigargin.

Less Carcinogenic Chlorinated Estrogens Applicable to Hormone Replacement Therapy.

Human estrogens prescribed for hormone replacement therapy (HRT) are known to be potent carcinogens. To find safer estrogens, several chlorinated estrogens were synthesized and their carcinogenic potential were determined. A pellet containing either 2-chloro-17β-estradiol (2-ClE) or 4-chloro-17β-estradiol (4-ClE) was implanted subcutaneously for 52 weeks into August Copenhagen Irish (ACI) rats, a preferred animal model for human breast cancer.

Diltiazem Inhibits Coronary Spasm via Inhibition of Cav1.2Phosphorylation and Protein Kinase C Activation in a Mouse Model of Coronary Spastic Angina.

Calcium antagonists are used for coronary spastic angina (CSA) treatment. We previously identified a phospholipase C (PLC) -δ1 gene variant that results in enhanced PLC activity in patients with CSA and developed a CSA animal model by generating vascular smooth muscle cell-specific human variant PLC-δ1 overexpression (PLC-TG) mice. In this study, we investigated the molecular mechanism of CSA using the PLC-TG mice and the inhibitory effect of a calcium antagonist, diltiazem hydrochloride (DL).