Ubiquitin-specific peptidase 11 selectively interacts with and deubiquitination-dependently stabilizes diacylglycerol kinase δ to maintain cellular glucose uptake.

Diacylglycerol kinase δ (DGKδ) phosphorylates diacylglycerol and converts it into phosphatidic acid. DGKδ contributes to glucose uptake as one of its cellular functions. However, detail mechanisms underlying the regulation of DGKδ protein stability remain unelucidated.

The acetylglucosaminyltransferase GnT-Ⅲ regulates erythroid differentiation through ERK/MAPK signaling.

Differentiation therapy is an alternative strategy used in treating chronic myelogenous leukemia to induce the differentiation of immature or cancerous cells toward mature cells and inhibit tumor cell proliferation. We aimed to explore N-glycans' roles in erythroid differentiation using the sodium butyrate (NaBu)-induced model of K562 cells (WT/NaBu cells). Here, using lectin blot, flow cytometry, real-time PCR, and mass spectrometry analyses, we demonstrated that the mRNA levels of N-acetylglucosaminyltransferase Ⅲ ((encoded by the MGAT3 gene) and its product (bisected N-glycans) were significantly increased during erythroid differentiation.

Effects of multimorbidity and polypharmacy on physical function in community-dwelling older adults: A 3-year prospective cohort study from the SONIC.

Background: We prospectively examined the effect of baseline multimorbidity and polypharmacy on the physical function of community-dwelling older adults over a three-year period.

Methods: The analysis included 1,401 older adults (51.5 % women) who participated in both wave 1 and wave 2 (3-year follow-up) of the Septuagenarians, Octogenarians, and Nonagenarians Investigation with Centenarians (SONIC) study.

Changes in the amount of nucleotide sugars in aged mouse tissues.

Aging affects tissue glycan profiles, which may alter cellular functions and increase the risk of age-related diseases. Glycans are biosynthesized by glycosyltransferases using the corresponding nucleotide sugar, and the availability of nucleotide sugars affects glycosylation efficiency. However, the effects of aging on nucleotide sugar profiles and contents are yet to be elucidated.

Potential role of lipophagy impairment for anticancer effects of glycolysis-suppressed pancreatic ductal adenocarcinoma cells.

Although increased aerobic glycolysis is common in various cancers, pancreatic ductal adenocarcinoma (PDAC) cells can survive a state of glycolysis suppression. We aimed to identify potential therapeutic targets in glycolysis-suppressed PDAC cells. By screening anticancer metabolic compounds, we identified SP-2509, an inhibitor of lysine-specific histone demethylase 1A (LSD1), which dramatically decreased the growth of PDAC PANC-1 cells and showed an anti-tumoral effect in tumor-bearing mice.

Tocotrienols Prevent the Decline of Learning Ability in High-Fat, High-Sucrose Diet-Fed C57BL/6 Mice.

Obesity has been increasing worldwide and is well-known as a risk factor for cognitive decline. It has been reported that oxidative stress in the brain is deeply involved in cognitive dysfunction in rodent models. While there are many studies on oxidation in the liver and adipose tissue of obese mice, the relationship between obesity-induced cognitive dysfunction and brain oxidation has not been elucidated.

Distinguishing two distinct types of salivary extracellular vesicles: a potential tool for understanding their pathophysiological roles.

Extracellular vesicles (EVs), which are found in almost all cells and human body fluids, are currently being studied as a source of pathophysiological information. Previously, we demonstrated that at least two types of EVs can be isolated from human whole saliva (WS) using enzymatic activity of dipeptidyl peptidase IV (DPP IV) as a marker for differentiating the EV subsets. In the present study, EV fractions, termed EV-I 20 k-ppt and EV-II 100 k-ppt, were prepared by a combination of size-exclusion chromatography of improved condition and sequential centrifugation.

Axonal distribution of mitochondria maintains neuronal autophagy during aging via eIF2β.

Neuronal aging and neurodegenerative diseases are accompanied by proteostasis collapse, while cellular factors that trigger it are not identified. Impaired mitochondrial transport in the axon is another feature of aging and neurodegenerative diseases. Using , we found that genetic depletion of axonal mitochondria causes dysregulation of protein degradation.

Association Between Serum GDF15 Concentration and Total Mortality in Community-Dwelling Japanese Older Populations: The Involvement of Renal Dysfunction.

Background: Serum growth differentiation factor 15 (GDF15) is associated with age-related adverse outcomes. However, renal function has not been thoroughly evaluated in studies addressing the association between GDF15 and mortality. We aimed to clarify whether GDF15 is associated with total mortality after carefully controlling renal function markers.

Saturated fatty acid- and/or monounsaturated fatty acid-containing phosphatidic acids selectively interact with heat shock protein 27.

Diacylglycerol kinase (DGK) α, which is a key enzyme in the progression of cancer and, in contrast, in T-cell activity attenuation, preferentially produces saturated fatty acid (SFA)- and/or monounsaturated fatty acid (MUFA)-containing phosphatidic acids (PAs), such as 16:0/16:0-, 16:0/18:0-, and 16:1/16:1-PA, in melanoma cells. In the present study, we searched for the target proteins of 16:0/16:0-PA in melanoma cells and identified heat shock protein (HSP) 27, which acts as a molecular chaperone and contributes to cancer progression. HSP27 more strongly interacted with PA than other phospholipids, including phosphatidylcholine, phosphatidylserine, phosphatidylglycerol, cardiolipin, phosphatidylinositol, phosphatidylinositol 4-monophosphate, and phosphatidylinositol 4,5-bisphosphate.

A characteristic N-glycopeptide signature associated with diabetic cognitive impairment identified in a longitudinal cohort study.

Background: Identifying a biomarker for the decline in cognitive function in patients with diabetes is important. Therefore, we aimed to identify the N-glycopeptides on plasma proteins associated with diabetic cognitive impairment in participants in a longitudinal study using N-glycoproteomics.

Methods: We used samples from the 3-year SONIC (Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians) longitudinal cohort study of older Japanese people in the general population.

A chemical probe for proteomic analysis and visualization of intracellular localization of lysine-succinylated proteins.

Protein acylation is a vital post-translational modification that regulates various protein functions. In particular, protein succinylation has attracted significant attention because of its potential relationship with various biological events and diseases. In this report, we establish a new method for the comprehensive detection and analysis of potentially succinylated proteins using a chemical tagging technology.

Mechanistic insights into cancer drug resistance through optogenetic PI3K signaling hyperactivation.

Hyperactivation of phosphatidylinositol 3-kinase (PI3K) signaling is a prominent feature in cancer cells. However, the mechanism underlying malignant behaviors in the state remains unknown. Here, we describe a mechanism of cancer drug resistance through the protein synthesis pathway, downstream of PI3K signaling.

Changes in the Genotypic Characteristics of Community-Acquired Methicillin-Resistant Staphylococcus aureus Collected in 244 Medical Facilities in Japan between 2010 and 2018: a Nationwide Surveillance.

Although community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged worldwide, no nationwide CA-MRSA surveillance has been conducted in Japan to determine the changes in its molecular characteristics over time. We aimed to characterize the molecular epidemiology of Panton-Valentine leucocidin (PVL)-positive CA-MRSA strains collected from across Japan in the past decade. We isolated 1,770 MRSA strains from the skin and pus samples of outpatients of 244 medical facilities in 31 prefectures between 2010 and 2018 (2010, 2012, 2014, 2016, and 2018).

The seasonality, steroid use, and lower ratio of neutrophil to lymphocyte associated with bacteremia of Listeria monocytogenes in Japan from 2010 to 2019: a case-control study.

Background: Despite having a high mortality rate, Asian studies about the characteristics of adult listeriosis are limited. We investigated the incidence of listeriosis per admissions, associated factors, and rate of mortality in listeriosis, compared with non-listeriosis.

Methods: We recorded the incidence of listeriosis per 10,000 admissions and conducted a case-control study from January 1, 2010, to December 31, 2019, at Tokyo Medical University Hospital (TMUH) in Japan.

Diagnostic potential of serum extracellular vesicles expressing prostate-specific membrane antigen in urologic malignancies.

We aimed to develop a sandwich ELISA to detect prostate-specific membrane antigen (PSMA) on small extracellular vesicles (EVs) using T-cell immunoglobulin domain and mucin domain-containing protein 4 (Tim4) as a capture molecule for EVs and to evaluate its diagnostic potential in urologic malignancies. First, we optimized the conditions for sandwich ELISA measuring the PSMA level on EVs captured from serum by Tim4 and found that the use of highly-purified EVs released from Tim4 that had captured EVs in serum reduced the background. Second, we confirmed its validity by studying mouse xenograft model for prostate cancer (PC).

Proteome analysis demonstrates involvement of endoplasmic reticulum stress response in human myocardium with subclinical left ventricular diastolic dysfunction.

Aim: Heart failure is increasing in Japan, in particular that with preserved ejection fraction (HFpEF) prevalent in older-aged patients. The purpose of this study was to investigate the pathophysiology during the early stage of left ventricular (LV) diastolic dysfunction by the quantitative proteome analysis of human myocardium.

Methods: Among 331 post-mortem autopsy patients, we selected 23 patients (aged 79 ± 9.

Proteomic analysis of extracellular vesicles identified PI3K pathway as a potential therapeutic target for cabazitaxel-resistant prostate cancer.

Background: Cabazitaxel (CBZ) is now widely used for prostate cancer (PC) patients resistant to docetaxel (DOC), however, most patients eventually acquire resistance. It will, therefore, be of great benefit to discover novel therapeutic target for the resistance. We aimed to identify candidate therapeutic targets for CBZ-resistance by proteomic analysis of extracellular vesicles (EVs) isolated from serum of DOC-resistant PC patients who later developed CBZ-resistance as well as those harvested from culture medium of DOC- and CBZ-resistant PC cell lines.

Profiling of Serum Extracellular Vesicles Reveals as a Potential Biomarker for Advanced Renal Cell Carcinoma.

Aim: To identify novel diagnostic markers for renal cell carcinoma (RCC), we analyzed miRNAs in serum extracellular vesicles (EVs).

Materials And Methods: EVs were purified from serum of healthy controls and patients with localized and advanced RCC using T-cell immunoglobulin domain and mucin domain-containing protein 4 conjugated to magnetic beads. miRNA profiling of EVs was conducted by microarray analysis.

Imipenem plus Fosfomycin as Salvage Therapy for Vertebral Osteomyelitis.

We applied combination antibiotic therapy to treat vertebral osteomyelitis and a psoas abscess caused by glycopeptide-intermediate (MIC, 2 μg/ml) and daptomycin-nonsusceptible (>2 μg/ml) methicillin-resistant The Etest synergy test showed the largest synergistic effects for imipenem/cilastatin and fosfomycin. Whole-gene sequencing showed amino acid changes in SA0802, SA1193 (), and SA1531 (). Four weeks of combination treatment using imipenem/cilastatin (1.

DJ-1 is indispensable for the S-nitrosylation of Parkin, which maintains function of mitochondria.

The DJ-1 gene, a causative gene for familial Parkinson's disease (PD), has been reported to have various functions, including transcriptional regulation, antioxidant response, and chaperone and protease functions; however, the molecular mechanism associated with the pathogenesis of PD remains elusive. To further explore the molecular function of DJ-1 in the pathogenesis of PD, we compared protein expression profiles in brain tissues from wild-type and DJ-1-deficient mice. Two-dimensional difference gel electrophoresis analysis and subsequent analysis using data mining methods revealed alterations in the expression of molecules associated with energy production.