Intranasal administration of trehalose reduces α-synuclein oligomers and accelerates α-synuclein aggregation.

Abnormal α-synuclein (αSyn), including an oligomeric form of αSyn, accumulates and causes neuronal dysfunction in the brains of patients with multiple system atrophy. Neuroprotective drugs that target abnormal αSyn aggregation have not been developed for the treatment of multiple system atrophy. In addition, treating diseases at an early stage is crucial to halting the progress of neuronal damage in neurodegeneration.

Characteristics of sphingomyelin metabolism in the MCF7 and BT474 radiotherapy‑resistant HER2‑positive breast cancer cell lines.

Breast cancer is the most common cancer globally in terms of incidence. This cancer is classified into subtypes based on histological or immunological characteristics. HER2-positive cases account for 15-25% of breast cancer cases, and one of the first events in breast carcinogenesis is HER2 upregulation.

Exploring predictive molecules of acute adverse events in response to volumetric‑modulated arc therapy for prostate cancer using urinary metabolites.

Volumetric-modulated arc therapy (VMAT) is a radiotherapy technique used to treat patients with localized prostate cancer, which is frequently associated with acute adverse events (AEs) that can affect subsequent treatment. Notably, the radiation dose of VMAT can be tailored to each patient. In the present study, a retrospective analysis was performed to predict acute AEs in response to a therapeutic high radiation dose rate based on urinary metabolomic molecules, which are easily collected as noninvasive biosamples.

Overexpression of carbonyl reductase 1 in ovarian cancer cells suppresses proliferation and activates the eIF2 signaling pathway.

High expression of carbonyl reductase 1 (CBR1) protein in ovarian cancer cells inhibits tumor growth and metastasis. However, the underlying mechanism is unknown. To investigate the mechanism by which CBR1 suppresses tumor growth, the present study generated ovarian cancer cells that constitutively overexpress human CBR1 (hCBR1) protein.

Purification and Characterization of α-Mannosidase from Onion, .

α-Mannosidase (ALMAN) extracted from onion () was purified by column chromatography such as hydrophobic and gel filtration. ALMAN is an acidic α-mannosidase that exhibits maximum activity against NP-α-Man at pH 4.0-5.

Dairy consumption, bone turnover biomarkers, and osteo sono assessment index in Japanese adults: A cross-sectional analysis of data from the Iwaki Health Promotion Project.

Purpose: Dairy foods are nutritional sources of calcium, phosphorus, protein, and other nutrients that improve bone health. However, the effects of dairy consumption on bone biomarkers in the Japanese population remain unclear. This study explored the association between dairy consumption and bone biomarkers in Japanese adults.

Emerging Role of GCN1 in Disease and Homeostasis.

GCN1 is recognized as a factor that is essential for the activation of GCN2, which is a sensor of amino acid starvation. This function is evolutionarily conserved from yeast to higher eukaryotes. However, recent studies have revealed non-canonical functions of GCN1 that are independent of GCN2, such as its participation in cell proliferation, apoptosis, and the immune response, beyond the borders of species.

Proteomics and secreted lipidomics of mouse-derived bone marrow cells exposed to a lethal level of ionizing radiation.

High doses of ionizing radiation (IR) exposure can lead to the development of severe acute radiation syndrome with bone marrow failure. Defining risk factors that predict adverse events is a critical mission to guide patient selection for personalized treatment protocols. Since non-hematopoietic stem cells act as feeder cells in the niche and their secreted lipids may regulate hematopoietic stem cells, we focused on non-hematopoietic stem cells and aimed to discover biomarkers that can assess radiation exposure from their secreted lipids.

Oxidative Modification Status of Human Serum Albumin Caused by Chronic Low-Dose Radiation Exposure in Mamuju, Sulawesi, Indonesia.

The recently discovered high-level natural background radiation area (HBRA) of Mamuju in Indonesia provides a unique opportunity to study the biological effects of chronic low-dose radiation exposure on a human population. The mean total effective dose in the HBRA was approximately 69.6 mSv y (range: 47.

Multiomics and artificial intelligence enabled peripheral blood-based prediction of amnestic mild cognitive impairment.

Background: Since dementia is preventable with early interventions, biomarkers that assist in diagnosing early stages of dementia, such as mild cognitive impairment (MCI), are urgently needed.

Methods: Multiomics analysis of amnestic MCI (aMCI) peripheral blood (n = 25) was performed covering the transcriptome, microRNA, proteome, and metabolome. Validation analysis for microRNAs was conducted in an independent cohort (n = 12).

Development of transgenic mice overexpressing mouse carbonyl reductase 1.

Background: Carbonyl reductase 1 (CBR1) is a nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductase with broad substrate specificity. CBR1 catalyzes the reduction of numerous carbonyl compounds, including quinones, prostaglandins, menadione, and multiple xenobiotics, while also participating in various cellular processes, such as carcinogenesis, apoptosis, signal transduction, and drug resistance. In this study, we aimed to generate transgenic mice overexpressing mouse Cbr1 (mCbr1), characterize the mCbr1 expression in different organs, and identify changes in protein expression patterns.

Serum Proteomic and Oxidative Modification Profiling in Mice Exposed to Total Body X-Irradiation.

The details of the dose-dependent response of serum proteins exposed to ionizing radiation, especially the oxidative modification response in amino acid sequences of albumin, the most abundant protein, are unknown. Thus, a proteomic analysis of the serum components from mice exposed to total body X-irradiation (TBI) ranging from 0.5 Gy to 3.

Sulforaphane Increase Mitochondrial Biogenesis-Related Gene Expression in the Hippocampus and Suppresses Age-Related Cognitive Decline in Mice.

Sulforaphane (SFN) is a potent activator of the transcriptional factor, Nuclear Factor Erythroid 2 (NF-E2)-Related factor 2 (NRF2). SFN and its precursor, glucoraphanin (sulforaphane glucosinolate, SGS), have been shown to ameliorate cognitive function in clinical trials and studies. However, the effects of SGS on age-related cognitive decline in Senescence-Accelerated Mouse Prone 8 (SAMP8) is unknown.

Heterogeneity of metabolic adaptive capacity affects the prognosis among pancreatic ductal adenocarcinomas.

Background: Evolutionary cancer has a supply mechanism to satisfy higher energy demands even in poor-nutrient conditions. Metabolic reprogramming is essential to supply sufficient energy. The relationship between metabolic reprogramming and the clinical course of pancreatic ductal adenocarcinoma (PDAC) remains unclear.

Detection of biological responses to low-dose radiation in humans.

It has been considered difficult to detect the biological effects of low-dose radiation exposure below approximately 100 mSv in humans. Serum proteomic analysis and oxidative modification profiling were conducted with blood samples collected from residents of a newly discovered high-level natural background radiation area (annual effective dose approximately 50 mSv y) and normal-level area (1.22 mSv y) in Mamuju, Indonesia, where many people have been living for generations.

Inducible Systemic Deletion in Mice Leads to Transient Body Weight Loss upon Tamoxifen Treatment Associated with Decrease of Fat and Liver Glycogen Storage.

GCN1 is an evolutionarily-conserved ribosome-binding protein that mediates the amino acid starvation response as well as the ribotoxic stress response. We previously demonstrated that mutant mice lacking the GCN2-binding domain suffer from growth retardation and postnatal lethality via GCN2-independent mechanisms, while -null mice die early in embryonic development. In this study, we explored the role of GCN1 in adult mice by generating tamoxifen-inducible conditional knockout (CKO) mice.

Capillary Electrophoresis Mass Spectrometry-Based Metabolomics of Plasma Samples from Healthy Subjects in a Cross-Sectional Japanese Population Study.

For large-scale metabolomics, such as in cohort studies, normalization protocols using quality control (QC) samples have been established when using data from gas chromatography and liquid chromatography coupled to mass spectrometry. However, normalization protocols have not been established for capillary electrophoresis-mass spectrometry metabolomics. In this study, we performed metabolome analysis of 314 human plasma samples using capillary electrophoresis-mass spectrometry.

Essential hyaluronan structure for binding with hyaluronan-binding protein (HABP) determined by glycotechnological approach.

Hyaluronan specifically binds to aggrecan globular domain 1, which is often referred to as just hyaluronan binding protein (HABP), however, the hyaluronan carbohydrate structure recognized by HABP had not been studied in detail. The aim of the present study was to investigate the important structure of hyaluronan for binding to HABP. We prepared hybrid oligosaccharides from hyaluronan and chondroitin, with or without modification of the reducing or non-reducing terminus, as tools to determine the preferred structure of hyaluronan for binding to the HABP by a competitive ELISA-like method.

HER2-positive breast cancer that resists therapeutic drugs and ionizing radiation releases sphingomyelin-based molecules to circulating blood serum.

Breast cancer is the second most common cancer in the world based on incidence, reaching more than 2 million new cases in 2018, while continuing to increase. Invasive ductal carcinoma is the most common type of this cancer, making up approximately 70-80% of all breast cancer diagnoses. In particular, the type of breast cancer overexpressing human epidermal growth factor receptor 2 (HER2) has potential of strong proliferation, migration and invasion and early treatment is necessary.

Proteomic changes by radio-mitigative thrombopoietin receptor agonist romiplostim in the blood of mice exposed to lethal total-body irradiation.

Purpose: The thrombopoietin receptor agonist romiplostim (RP) is a therapeutic agent for immune thrombocytopenia that can achieve complete survival in mice exposed to a lethal dose of ionizing radiation. The estimated mechanism of the radio-protective/mitigative effects of RP has been proposed; however, the detailed mechanism of action remains unclear. This study aimed to elucidate the mechanism of the radio-protective/mitigative effects of RP, the fluctuation of protein in the blood was analyzed by proteomics.

Blockade of PAR-1 Signaling Attenuates Cardiac Hypertrophy and Fibrosis in Renin-Overexpressing Hypertensive Mice.

Background Although PAR-1 (protease-activated receptor-1) exerts important functions in the pathophysiology of the cardiovascular system, the role of PAR-1 signaling in heart failure development remains largely unknown. We tested the hypothesis that PAR-1 signaling inhibition has protective effects on the progression of cardiac remodeling induced by chronic renin-angiotensin system activation using renin-overexpressing hypertensive (Ren-Tg) mice. Methods and Results We treated 12- to 16-week-old male wild-type (WT) mice and Ren-Tg mice with continuous subcutaneous infusion of the PAR-1 antagonist SCH79797 or vehicle for 4 weeks.