The small molecule peroxiredoxin mimetics restore growth factor signalings and reverse vascular remodeling.

Epidithio-diketopiperazine (ETP) compound is the family of natural fungal metabolites that are known to exert diverse biological effects, such as immunosuppression and anti-cancer activity, in higher animals. However, an enzyme-like catalytic activity or function of the ETP derivatives has not been reported. Here, we report the generation of novel thiol peroxidase mimetics that possess peroxide-reducing activity through strategic derivatization of the core ETP ring structure.

A two-year dataset of energy, environment, and system operations for an ultra-low energy office building.

This paper describes a two-year high-fidelity dataset for an ultra-low energy office building and living laboratory called HouseZero. The building integrates multiple low-energy technologies, such as natural ventilation with automatic windows, ground source heat pump, and thermally activated building systems. The building's performance is continuously monitored with an extensive sensor network.

Blood flow patterns switch VEGFR2 activity through differential S-nitrosylation and S-oxidation.

Vascular endothelial growth factor receptor-2 (VEGFR2) plays a key role in maintaining vascular endothelial homeostasis. Here, we show that blood flows determine activation and inactivation of VEGFR2 through selective cysteine modifications. VEGFR2 activation is regulated by reversible oxidation at Cys residue.

A small molecule compound that inhibits blue light-induced retinal damage via activation of autophagy.

Dry age-related macular degeneration (AMD) is a type of disease that causes visual impairment due to changes in the macula located in the center of the retina. The accumulation of drusen under the retina is also a characteristic of dry AMD. In this study, we identified a compound (JS-017) that can potentially degrade N-retinylidene-N-retinylethanolamine (A2E), one of the components of lipofuscin, using fluorescence-based screening, which measures A2E degradation in human retinal pigment epithelial cells.

Intensity Modulated High Dose Rate (HDR) Brachytherapy Using Patient Specific 3D Metal Printed Applicators: Proof of Concept.

Purpose: In high-dose-rate (HDR) brachytherapy, an anisotropic dose distribution may be desirable for achieving a higher therapeutic index, particularly when the anatomy imposes challenges. Several methods to deliver intensity-modulated brachytherapy (IMBT) have been proposed in the literature, however practical implementation is lacking due to issues of increased delivery times and complicated delivery mechanisms. This study presents the novel approach of designing a patient-specific inner shape of an applicator with 3D metal printing for IMBT using an inverse plan optimization model.

Assessment of dose perturbations for metal stent in photon and proton radiotherapy plans for hepatocellular carcinoma.

Background: The present study aimed to investigate the dosimetric impact of metal stent for photon and proton treatment plans in hepatocellular carcinoma.

Methods: With computed tomography data of a water-equivalent solid phantom, dose perturbation caused by a metal stent included in the photon and proton treatment of hepatocellular carcinoma was evaluated by comparing Eclipse and RayStation treatment planning system (TPS) to a Monte Carlo (MC) based dose calculator. Photon and proton plans were created with anterior-posterior/posterior-anterior (AP/PA) fields using a 6 MV beam and AP/PA fields of a wobbling beam using 150 MeV and a 10 cm ridge filter.

Evaluation of the dosimetric and radiobiological parameters in four radiotherapy regimens for synchronous bilateral breast cancer.

This study is to investigate the optimal treatment option for synchronous bilateral breast cancer (SBBC) by comparing dosimetric and radiobiological parameters of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans using single and dual isocenters. Twenty patients with SBBC without lymph node involvement were selected retrospectively. Four treatment plans were generated for each patient using the Eclipse treatment planning system (Varian Medical System, Palo Alto, CA, USA) following two delivery techniques with two isocenter conditions-IMRT using a single isocenter (IMRT_Iso1), VMAT using a single isocenter (VMAT_Iso1), IMRT using dual isocenters (IMRT_Iso2), and VMAT using dual isocenters (VMAT_Iso2).

PI3Kγ stimulates a high molecular weight form of myosin light chain kinase to promote myeloid cell adhesion and tumor inflammation.

Myeloid cells play key roles in cancer immune suppression and tumor progression. In response to tumor derived factors, circulating monocytes and granulocytes extravasate into the tumor parenchyma where they stimulate angiogenesis, immune suppression and tumor progression. Chemokines, cytokines and interleukins stimulate PI3Kγ-mediated Rap1 activation, leading to conformational changes in integrin α4β1 that promote myeloid cell extravasation and tumor inflammation Here we show that PI3Kγ activates a high molecular weight form of myosin light chain kinase, MLCK210, that promotes myosin-dependent Rap1 GTP loading, leading to integrin α4β1 activation.

Heat shock protein 60 couples an oxidative stress-responsive p38/MK2 signaling and NF-κB survival machinery in cancer cells.

Mitochondria communicate with other cellular compartments via the secretion of protein factors. Here, we report an unexpected messenger role for heat shock protein 60 (HSP60) as a mitochondrial-releasing protein factor that couples stress-sensing signaling and cell survival machineries. We show that mild oxidative stress predominantly activates the p38/MK2 complex, which phosphorylates mitochondrial fission factor 1 (MFF1) at the S155 site.

RIP3-Dependent Accumulation of Mitochondrial Superoxide Anions in TNF-α-Induced Necroptosis.

Excessive production of reactive oxygen species (ROS) is a key phenomenon in tumor necrosis factor (TNF)-α-induced cell death. However, the role of ROS in necroptosis remains mostly elusive. In this study, we show that TNF-α induces the mitochondrial accumulation of superoxide anions, not HO, in cancer cells undergoing necroptosis.

Association between circulating bile acid alterations and nonalcoholic steatohepatitis independent of obesity and diabetes mellitus.

Background And Aims: Bile acid (BA) dysregulation is related to not only metabolic diseases but also nonalcoholic fatty liver disease (NAFLD). We investigated whether circulating BA levels are altered according to the histological severity of NAFLD independent of metabolic derangements.

Methods: Global metabolic profiling and targeted BA analysis using sera collected from biopsy-proven no-NAFLD (n = 67), nonalcoholic fatty liver (NAFL) (n = 99), and nonalcoholic steatohepatitis (NASH, n = 75) subjects were performed sequentially.

Glutathione peroxidase-1 regulates ASK1-dependent apoptosis via interaction with TRAF2 in RIPK3-negative cancer cells.

Glutathione peroxidase (GPx) is a selenocysteine-containing peroxidase enzyme that defends mammalian cells against oxidative stress, but the role of GPx signaling is poorly characterized. Here, we show that GPx type 1 (GPx1) plays a key regulatory role in the apoptosis signaling pathway. The absence of GPx1 augmented TNF-α-induced apoptosis in various RIPK3-negative cancer cells by markedly elevating the level of cytosolic HO, which is derived from mitochondria.

Evaluation of a new foetal shielding device for pregnant brain tumour patients.

Background: The present study aimed to propose a new foetal shielding device for pregnant cancer patients to reduce the foetal dose associated with treatment techniques using multiple gantry angles, such as intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT).

Methods: Three shielding structures were designed to minimise the scattered and leaked radiation from various gantry angles and radiation scattering within the patient. The base-plate part that can be placed on the treatment couch was designed to reduce the scattered and leaked radiation generated at gantry angles located near 180°.

GPx-1-encoded adenoviral vector attenuates dopaminergic impairments induced by methamphetamine in GPx-1 knockout mice through modulation of NF-κB transcription factor.

We suggested that selenium-dependent glutathione peroxidase (GPx) plays a protective role against methamphetamine (MA)-induced dopaminergic toxicity. We focused on GPx-1, a major selenium-dependent enzyme and constructed a GPx-1 gene-encoded adenoviral vector (Ad-GPx-1) to delineate the role of GPx-1 in MA-induced dopaminergic neurotoxicity. Exposure to Ad-GPx-1 significantly induced GPx activity and GPx-1 protein levels in GPx-1-knockout (GPx-1-KO) mice.

Development of Dosimetric Verification System for Patient-Specific Quality Assurance of High-Dose-Rate Brachytherapy.

The aim of this study was to develop a dosimetric verification system (DVS) using a solid phantom for patient-specific quality assurance (QA) of high-dose-rate brachytherapy (HDR-BT). The proposed DVS consists of three parts: dose measurement, dose calculation, and analysis. All the dose measurements were performed using EBT3 film and a solid phantom.

CHIP and BAP1 Act in Concert to Regulate INO80 Ubiquitination and Stability for DNA Replication.

The INO80 chromatin remodeling complex has roles in many essential cellular processes, including DNA replication. However, the mechanisms that regulate INO80 in these processes remain largely unknown. We previously reported that the stability of Ino80, the catalytic ATPase subunit of INO80, is regulated by the ubiquitin proteasome system and that BRCA1-associated protein-1 (BAP1), a nuclear deubiquitinase with tumor suppressor activity, stabilizes Ino80 via deubiquitination and promotes replication fork progression.

Four-dimensional inverse-geometry computed tomography: a preliminary study.

This study introduces and evaluates respiratory-correlated four-dimensional (4D) inverse geometry computed tomography (IGCT). The projection data of the IGCT were acquired in a single gantry rotation over 120 s. Three virtual phantoms-static Defrise, 4D Shepp-Logan, and 4D extended cardiac-torso (XCAT)-were used to obtain projection data for the IGCT and cone-beam computed tomography (CBCT).

Dose Super-Resolution in Prostate Volumetric Modulated Arc Therapy Using Cascaded Deep Learning Networks.

Purpose: This study proposes a cascaded network model for generating high-resolution doses (i.e., a 1 mm grid) from low-resolution doses (i.

An adenoviral vector encoded with the GPx-1 gene attenuates memory impairments induced by β-amyloid (1-42) in GPx-1 KO mice via activation of M1 mAChR-mediated signalling.

In the present study, we examined whether glutathione peroxidase-1 (GPx-1), a major HO scavenger in the brain, affects memory deficits induced by Aβ (1-42) in mice. Treatment with 400 pmol/5 μl Aβ (1-42) (i.c.

SEZ6L2 Is an Important Regulator of Drug-Resistant Cells and Tumor Spheroid Cells in Lung Adenocarcinoma.

Many lung cancer deaths result from relapses in distant organs, such as the brain or bones, after standard chemotherapy. For cancer cells to spread to other organs, they must survive as circulating tumor cells (CTCs) in blood vessels. Thus, reducing distant recurrence after chemotherapy requires simultaneously inhibiting drug resistance and CTC survival.

Glutathione Peroxidase-1 Knockout Facilitates Memory Impairment Induced by β-Amyloid (1-42) in Mice via Inhibition of PKC βII-Mediated ERK Signaling; Application with Glutathione Peroxidase-1 Gene-Encoded Adenovirus Vector.

A growing body evidence suggests that selenium (Se) deficiency is associated with an increased risk of developing Alzheimer's disease (AD). Se-dependent glutathione peroxidase-1 (GPx-1) of a major antioxidant enzyme, and the most abundant isoform of GPx in the brain. In the present study, we investigated whether GPx-1 is protective against memory impairments induced by beta-amyloid (Aβ) (1-42) in mice.

Phosphorylation of OCT4 Serine 236 Inhibits Germ Cell Tumor Growth by Inducing Differentiation.

Octamer-binding transcription factor 4 (Oct4) plays an important role in maintaining pluripotency in embryonic stem cells and is closely related to the malignancies of various cancers. Although posttranslational modifications of Oct4 have been widely studied, most of these have not yet been fully characterized, especially in cancer. In this study, we investigated the role of phosphorylation of serine 236 of OCT4 [OCT4 (S236)] in human germ cell tumors (GCTs).

Circulating lipidomic alterations in obese and non-obese subjects with non-alcoholic fatty liver disease.

Background: Non-alcoholic fatty liver disease (NAFLD) affects obese and non-obese individuals. However, mechanisms underlying non-obese non-alcoholic steatohepatitis (NASH) remain unclear.

Aims: To attempt to identify metabolic perturbations associated with non-obese and obese NAFLD using a lipidomics approach.

Peroxidasin is essential for endothelial cell survival and growth signaling by sulfilimine crosslink-dependent matrix assembly.

Peroxidasin (PXDN) has been reported to crosslink the C-terminal non-collagenous domains of collagen IV (Col IV) by forming covalent sulfilimine bond. Here, we explored the physiological role of PXDN and its mechanism of action in endothelial cell survival and growth. Silencing of PXDN using siRNAs decreased cell proliferation without increase of the number of detached cells and decreased cell viability under serum-starved condition with increased fragmented nuclei and caspase 3/7 activity.