Association of lysophosphatidic acid molecules with liver fibrosis: different roles indicated.

Lysophosphatidic acid is composed of lysophosphatidic acid (LPA) molecules with varied chemical forms. The present cross-sectional study was conducted to investigate the associations of various LPA molecules with liver fibrosis. Forty-six patients affected by various types of liver disease who underwent an ultrasound-guided liver biopsy were recruited for this study. Liver fibrosis was evaluated using histological grading, as well as shear wave velocity (Vs) and serum level of type IV collagen 7S (T4c7s). Serum levels of LPA molecules were determined using liquid-chromatography tandem mass-spectrometry (LC-MSMS). Total LPA showed a significant positive association with fibrosis severity evaluated based on histological grading, Vs, and T4c7s used as parameters, following adjustment for other confounding factors, including disease type, age, gender, body mass index, and high-sensitivity C-reactive protein. This association was replicated when 16:0-LPA was substituted for total LPA. In contrast, when 20:4-LPA was substituted for total LPA, no significant association with liver fibrosis was observed. In conclusion, the degree of association varied among the different LPA molecule chemical forms, suggesting different pathophysiological roles of individual LPA molecules, although total LPA concentration was shown to be associated with liver fibrosis.

[Fostering Pharmacists to Succeed in a Drastically Changing Society].

In 2006, Japan's pharmaceutical science education was revised to a 6-year enrollment course, placing greater emphasis on cultivating practical clinical ability. Quality Assurance (QA) measures have been implemented including offering education based on a model core curriculum and third-party assessments. In August 2021, Ministry of Education, Culture, Sports, Science and Technology (MEXT) launched an investigative commission to review the above. For QA, the commission summarized a comprehensive report in August 2022 for items including: modality of selecting entrants; revising enrollment limits; securing education management; information disclosure; corresponding to pharmaceutical education assessments. For revising the model core curriculum, the commission is reviewing correspondence to: demographic changes due to decreasing birthrates, an ageing population, changes in the structure of diseases; rising and emerging infectious diseases; utilizing Big Data and artificial intelligence (AI). As Japan's ageing population is forecast to peak in 2040s, pharmacists must be fostered to provide safe and quality medicine towards a drastically changing future. Medical care is provided through the collaboration of various professions. In such changing demographics, team medicine is crucial to provide quality medical care. Moreover, towards all medical professions sharing the same vision, revisions to the model core curricula for medical and dental education are also being reviewed. The commission is now reviewing detailed curricula to foster pharmacists with competencies to: comprehensively assess patients and ordinary citizens; utilize information science and technology; professionalism. Towards securing quality pharmaceutical education, pharmaceutical departments at universities must also organize and implement an educational curriculum based on the Model Core Curriculum for Pharmaceutical Education. This paper will introduce the investigative commission's review.

Analysis of the time-dependent changes of phospholipids in the brain regions of a mouse model of Alzheimer's disease.

Phospholipid levels are reported to be decreased in Alzheimer's disease (AD). For a better understanding, we investigated the time-dependent changes of phospholipids species in a mouse model of AD. The levels of phospholipids in the hippocampus and prefrontal cortex of wild-type and APP-Tg (J20) mice were measured by LC-ESI-MS/MS. Compared to wild-type, total phosphatidylcholine (PC), phosphatidylethanolamine (PE), and lysophosphatidylcholine (LPC) were Increased at 3 months but decreased at 6 months in the cortex of J20 mice. Total lysophosphatidylethanolamine (LPE) was decreased both at 3 and 6 months. PC was decreased and LPC was increased at 6 months, resulting in an increased LPC/PC ratio in the hippocampus of J20 mice. At species levels, PCA analysis could discriminate wild-type and J20 based on PC and LPC distribution at 6 months. At 6 months, several highly abundant PC including PC (16:0/16:0), PC (16:0/18:0), PC (16:0/18:1), and PC (18:0/18:1) were decreased in the cortex and hippocampus of J20. Conversely, LPC species including LPC 16:0, LPC 18:1, and LPC 20:4 were increased especially in the hippocampal area. Increased activation of phospholipid-metabolizing enzyme cPLA2 was seen in the hippocampus and cortex of J20 mice at 9 months. On the other hand, ROS levels started to increase as early as 3 months. Compared to 3 months, ROS levels were higher at 6 months in J20 mice. Thus, we demonstrated here a time- and area-dependent alteration of phospholipid composition during the early stage of AD, which could be important in understanding the pathological process.

Myristic acid selectively augments ß-tubulin levels in C2C12 myotubes via diacylglycerol kinase δ.

Effective amelioration of type II diabetes requires therapies that increase both glucose uptake activity per cell and skeletal muscle mass. Myristic acid (14:0) increases diacylglycerol kinase (DGK) δ protein levels and enhances glucose uptake in myotubes in a DGKδ-dependent manner. However, it is still unclear whether myristic acid treatment affects skeletal muscle mass. In this study, we found that myristic acid treatment increased the protein level of ß-tubulin, which constitutes microtubules and is closely related to muscle mass, in C2C12 myotubes but not in the proliferation stage in C2C12 myoblasts. However, lauric (12:0), palmitic (16:0) and oleic (18:1) acids failed to affect DGKδ and ß-tubulin protein levels in C2C12 myotubes. Moreover, knockdown of DGKδ by siRNA significantly inhibited the increased protein level of ß-tubulin in the presence of myristic acid, suggesting that the increase in ß-tubulin protein by myristic acid depends on DGKδ. These results indicate that myristic acid selectively affects ß-tubulin protein levels in C2C12 myotubes via DGKδ, suggesting that this fatty acid improves skeletal muscle mass in addition to increasing glucose uptake activity per cell.

Rapid identification of plasmalogen molecular species using targeted multiplexed selected reaction monitoring mass spectrometry.

Plasmalogens (Pls) levels are reported to be altered in several neurological and metabolic diseases. Identification of sn-1 fatty alcohols and sn-2 fatty acids of different Pls species is necessary to determine the roles and mechanisms of action of Pls in different diseases. Previously, full-scan tandem mass spectrometry (MS/MS) was used for this purpose but is not effective for low-abundance Pls species. Recently, multiplexed selected reaction monitoring MS (SRM/MS) was found to be more selective and sensitive than conventional full-scan MS/MS for the identification of low-abundance compounds. In the present study, we developed a liquid chromatography (LC)-targeted multiplexed SRM/MS system for the identification and quantification of different Pls choline (Pls-PC) and Pls ethanolamine (Pls-PE) species. We determined five precursor-product ion transitions to identify sn-1 and sn-2 fragments of each Pls species. Consequently, sn-1 and sn-2 fatty acyl chains of 22 Pls-PC and 55 Pls-PE species were identified in mouse brain samples. Among them, some species had C20:0 and C20:1 fatty alcohols at the sn-1 position. For quantification of Pls species in mouse brain samples, a single SRM transition was employed. Thus, our results suggest that the LC-targeted multiplexed SRM/MS system is very sensitive for the identification and quantification of low-abundance lipids such as Pls, and is thus expected to make a significant contribution to basic and clinical research in this field in the future.

Time-Dependent Analysis of Plasmalogens in the Hippocampus of an Alzheimer's Disease Mouse Model: A Role of Ethanolamine Plasmalogen.

Plasmalogens are alkenyl-acyl glycerophospholipids and decreased in post-mortem Alzheimer's disease (AD) brains. The aim of this study is to investigate the time-dependent changes of plasmalogens in the hippocampus of an AD model mouse (J20). Plasmalogen levels at 3, 6, 9, 12 and 15 months were analyzed by liquid-chromatography-targeted-multiplexed-selected-reaction-monitoring-tandem-mass-spectrometry (LC-SRM/MS). Reactive oxygen species (ROS) levels were evaluated using dichlorofluorescein diacetate (DCF-DA). Plasmalogen synthesizing enzyme glycerone-phosphate O-acyltransferase (GNPAT) and late endosome marker Rab7 levels were quantified by Western blotting. GNPAT localization, changes of neuronal and glial cell numbers were evaluated by immunostaining. Compared to wild-type mice (WT), total plasmalogen-ethanolamine, but not plasmalogen-choline levels, were increased at 9 months and subsequently decreased at 15 months in J20 mice. A principal component analysis of plasmalogen-ethanolamine species could separate WT and J20 mice both at 9 and 15 months. Both GNPAT and Rab7 protein were increased in J20 mice at 9 months, whereas GNPAT was decreased at 15 months. ROS levels were increased in J20 mice except for 9 months. Our results suggest that increased plasmalogen-ethanolamine could counteract ROS levels and contribute to the phagocytosis process in J20 mice at 9 months. Such results might indicate a transient protective response of plasmalogen-ethanolamine in AD conditions.

The Roles of Diacylglycerol Kinase α in Cancer Cell Proliferation and Apoptosis.

Diacylglycerol (DG) kinase (DGK) phosphorylates DG to generate phosphatidic acid (PA). The α isozyme is activated by Ca2+ through its EF-hand motifs and tyrosine phosphorylation. DGKα is highly expressed in several refractory cancer cells including melanoma, hepatocellular carcinoma, and glioblastoma cells. In melanoma cells, DGKα is an antiapoptotic factor that activates nuclear factor-κB (NF-κB) through the atypical protein kinase C (PKC) ζ-mediated phosphorylation of NF-κB. DGKα acts as an enhancer of proliferative activity through the Raf-MEK-ERK pathway and consequently exacerbates hepatocellular carcinoma progression. In glioblastoma and melanoma cells, DGKα attenuates apoptosis by enhancing the phosphodiesterase (PDE)-4A1-mammalian target of the rapamycin pathway. As PA activates PKCζ, Raf, and PDE, it is likely that PA generated by DGKα plays an important role in the proliferation/antiapoptosis of cancer cells. In addition to cancer cells, DGKα is highly abundant in T cells and induces a nonresponsive state (anergy), which represents the main mechanism by which advanced cancers escape immune action. In T cells, DGKα attenuates the activity of Ras-guanyl nucleotide-releasing protein, which is activated by DG and avoids anergy through DG consumption. Therefore, a DGKα-specific inhibitor is expected to be a dual effective anticancer treatment that inhibits cancer cell proliferation and simultaneously enhances T cell functions. Moreover, the inhibition of DGKα synergistically enhances the anticancer effects of programmed cell death-1/programmed cell death ligand 1 blockade. Taken together, DGKα inhibition provides a promising new treatment strategy for refractory cancers.

Diacylglycerol kinase η regulates C2C12 myoblast proliferation through the mTOR signaling pathway.

Diacylglycerol kinase (DGK) phosphorylates diacylglycerol to produce phosphatidic acid (PA). The η isozyme of DGK is abundantly expressed in C2C12 myoblasts. However, the role of DGKη in skeletal muscle cells remains unknown. In the present study, we showed that DGKη was downregulated at an early stage of myogenic differentiation. The knockdown of DGKη by siRNAs significantly inhibited C2C12 myoblast proliferation but did not inhibit differentiation. Moreover, the suppression of DGKη expression decreased the expression levels of mammalian target of rapamycin (mTOR), which is a key regulator of cell proliferation, and fatty acid synthase (FASN), which catalyzes the de novo synthesis of fatty acids for cell proliferation and is transcriptionally regulated via mTOR signaling. Furthermore, the knockdown of mTOR or raptor, which is a component of mTOR complex 1 (mTORC1), decreased the amount of FASN. These results indicate that DGKη regulates myoblast proliferation through the mTOR (mTORC1)-FASN pathway. Interestingly, the knockdown of mTOR reduced the expression levels of DGKη, implying mutual regulation between DGKη and mTOR. In DGKη-knockdown myoblasts, C30-C36-PA species, mTOR activators, were decreased, suggesting that the modulation of mTOR activity through these PA species also plays an important role in myoblast proliferation.

1-Stearoyl-2-docosahexaenoyl-phosphatidic acid interacts with and activates Praja-1, the E3 ubiquitin ligase acting on the serotonin transporter in the brain.

Serotonin transporter (SERT) is involved in serotonergic system regulation and in the pathophysiology/therapeutics of serotonin-/SERT-related diseases such as obsessive-compulsive disorder, depression, autism, and schizophrenia. We recently revealed that diacylglycerol (DG) kinase (DGK) δ induces ubiquitination/degradation of SERT in a DGK activity-dependent manner through Praja-1 E3 ubiquitin-protein ligase. However, it is still unclear how Praja-1 activity is regulated by DGKδ. Here, we reveal that 1-stearoyl-2-docosahexaenoyl (18:0/22:6)-phosphatidic acid (PA) and 18:0/22:6-DG are simultaneously decreased and accumulated, respectively, in the DGKδ-knockout mouse brain, indicating that DGKδ selectively phosphorylates 18:0/22:6-DG to generate 18:0/22:6-PA. Moreover, we find that 18:0/22:6-PA selectively binds to Praja-1 and enhances its activity. These results strongly suggest that 18:0/22:6-PA generated by DGKδ activates Praja-1 to degrade SERT in the brain.

Diacylglycerol kinase δ and sphingomyelin synthase-related protein functionally interact via their sterile α motif domains.

The δ isozyme of diacylglycerol kinase (DGKδ) plays critical roles in lipid signaling by converting diacylglycerol (DG) to phosphatidic acid (PA). We previously demonstrated that DGKδ preferably phosphorylates palmitic acid (16:0)- and/or palmitoleic acid (16:1)-containing DG molecular species, but not arachidonic acid (20:4)-containing DG species, which are recognized as DGK substrates derived from phosphatidylinositol turnover, in high glucose-stimulated myoblasts. However, little is known about the origin of these DG molecular species. DGKδ and two DG-generating enzymes, sphingomyelin synthase (SMS) 1 and SMS-related protein (SMSr), contain a sterile α motif domain (SAMD). In this study, we found that SMSr-SAMD, but not SMS1-SAMD, co-immunoprecipitates with DGKδ-SAMD. Full-length DGKδ co-precipitated with full-length SMSr more strongly than with SMS1. However, SAMD-deleted variants of SMSr and DGKδ interacted only weakly with full-length DGKδ and SMSr, respectively. These results strongly suggested that DGKδ interacts with SMSr through their respective SAMDs. To determine the functional outcomes of the relationship between DGKδ and SMSr, we used LC-MS/MS to investigate whether overexpression of DGKδ and/or SMSr in COS-7 cells alters the levels of PA species. We found that SMSr overexpression significantly enhances the production of 16:0- or 16:1-containing PA species such as 14:0/16:0-, 16:0/16:0-, 16:0/18:1-, and/or 16:1/18:1-PA in DGKδ-overexpressing COS-7 cells. Moreover, SMSr enhanced DGKδ activity via their SAMDs in vitro Taken together, these results strongly suggest that SMSr is a candidate DG-providing enzyme upstream of DGKδ and that the two enzymes represent a new pathway independent of phosphatidylinositol turnover.

Creatine kinase muscle type specifically interacts with saturated fatty acid- and/or monounsaturated fatty acid-containing phosphatidic acids.

Diacylglycerol kinase (DGK) δ, which is a key enzyme in the pathogenesis of type 2 diabetes (T2D), preferentially generates saturated fatty acid (SFA)- and/or monounsaturated fatty acid (MUFA)-containing phosphatidic acids (PAs) such as 16:0/16:0-PA and 16:0/18:1-PA, but not polyunsaturated fatty acid (PUFA)-containing PAs, in glucose-stimulated myoblast cells. Here, we searched for the target proteins of 16:0/16:0-PA in the mouse skeletal muscle and identified an energy metabolizing enzyme, creatine kinase muscle type (CKM), which is correlated with T2D. CKM bound to 16:0/16:0-PA with the highest affinity (dissociation constant: 2.0 µM) among all the PA-binding proteins reported thus far. Intriguingly, CKM preferentially interacted with SFA- and/or MUFA-containing PAs, but not with PUFA-containing PAs. Notably, CKM exclusively interacted with PA, whereas the protein did not bind to other lipids such as diacylglycerol, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol (3,4,5)-trisphosphate and cardiolipin. Taken together, these results demonstrate that CKM is a very unique PA-binding protein that possesses exceedingly high affinity for PA, exceptional preference for SFA/MUFA-PA and extremely high specificity to PA and suggest that SFA/MUFA-PAs produced by DGKδ are novel regulators of CKM function.

Myristic acid specifically stabilizes diacylglycerol kinase δ protein in C2C12 skeletal muscle cells.

Decreased levels of the δ isozyme of diacylglycerol kinase (DGK) in skeletal muscle attenuate glucose uptake and, consequently, are critical for the pathogenesis of type 2 diabetes. We recently found that free myristic acid (14:0), but not free palmitic acid (16:0), increased the DGKδ protein levels and enhanced glucose uptake in C2C12 myotube cells. However, it has been unclear how myristic acid regulates the level of DGKδ2 protein. In the present study, we characterized the myristic acid-dependent increase of DGKδ protein. A cycloheximide chase assay demonstrated that myristic acid, but not palmitic acid, markedly stabilized DGKδ protein. Moreover, other DGK isozymes, DGKη and ζ, as well as glucose uptake-related proteins, such as protein kinase C (PKC) α, PKCζ, Akt and glycogen synthase kinase 3ß, failed to be stabilized by myristic acid. Furthermore, DGKδ was not stabilized in cultured hepatocellular carcinoma cells, pancreas carcinoma cells or neuroblastoma cells, and only a moderate stabilizing effect was observed in embryonic kidney cells. A proteasome inhibitor and a lysosome inhibitor, MG132 and chloroquine, respectively, partly inhibited DGKδ degradation, suggesting that myristic acid prevents, at least in part, the degradation of DGKδ by the ubiquitin-proteasome system and the autophagy-lysosome pathway. Overall, these results strongly suggest that myristic acid attenuates DGKδ protein degradation in skeletal muscle cells and that this attenuation is fatty acid-, protein- and cell line-specific. These new findings provide novel insights into the molecular mechanisms of the pathogenesis of type 2 diabetes mellitus.

Diacylglycerol kinase ß induces filopodium formation via its C1, catalytic and carboxy-terminal domains and interacts with the Rac1-GTPase-activating protein, ß2-chimaerin.

The ß-isoform of diacylglycerol kinase (DGK) localizes predominantly to neurons and induces neurite outgrowth and spine formation. However, the detailed molecular mechanisms underlying the functions of DGKß remain elusive. During the course of studies on other DGK isozymes, we unexpectedly found that the overexpression of wild-type DGKß in COS-7 cells markedly induced filopodium formation. Because filopodium formation is closely related to neurite outgrowth and spine formation, we constructed various DGKß mutants and compared their abilities to induce filopodium formation in order to elucidate the structure-function relationships of DGKß. We found that the C-terminal, C1 and catalytic domains and catalytic activity were indispensable for filopodium formation, but the recoverin homology domain and EF-hand motifs were not. Moreover, the extent of plasma membrane localization and F-actin colocalization were positively correlated with filopodium formation. Intriguingly, DGKß selectively interacted and colocalized at the plasma membrane with a Rac1-GTPase-activating protein, ß2-chimaerin, which is an inducer of filopodia; it also interacted, to lesser extent, with α2-chimaerin, but not with α1- or ß1-chimaerin. Moreover, DGKß enhanced the plasma membrane localization of ß2-chimaerin. These results suggest that DGKß plays an important role in neurite outgrowth and spine formation in neurons via its ability to induce filopodium formation.

Diacylglycerol kinase δ controls down-regulation of cyclin D1 for C2C12 myogenic differentiation.

Diacylglycerol kinase (DGK) is a lipid-metabolizing enzyme that phosphorylates diacylglycerol (DG) to produce phosphatidic acid (PA). DGKδ is highly expressed in the skeletal muscle, and a decrease in DGKδ expression increases the severity of type 2 diabetes. However, the role of DGKδ in myogenic differentiation is still unknown. The present study demonstrated that DGKδ expression was down-regulated in the early stage of C2C12 myogenic differentiation almost concurrently with a decrease in cyclin D1 expression. The knockdown of DGKδ by DGKδ-specific siRNAs significantly increased the levels of cyclin D1 expression at 48 h after C2C12 myogenic differentiation. In contrast, at the same time, the knockdown of DGKδ decreased the levels of myogenin expression and the number of myosin heavy chain (MHC)-positive cells. These results indicate that DGKδ regulates the early differentiation of C2C12 myoblasts via controlling the down-regulation of cyclin D1 expression. Moreover, the suppression of DGKδ expression increased the phosphorylation levels of conventional and novel protein kinase Cs (cnPKCs). Furthermore, DGKδ suppression increased the levels of cyclin D1 and phospho-cnPKCs even at the first 24 h of myogenic differentiation. These results suggest that DGKδ controls the down-regulation of cyclin D1 expression by attenuating the PKC signaling pathway for C2C12 myogenic differentiation.

Where do substrates of diacylglycerol kinases come from? Diacylglycerol kinases utilize diacylglycerol species supplied from phosphatidylinositol turnover-independent pathways.

Diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DG) to produce phosphatidic acid (PA). Mammalian DGK comprises ten isozymes (α-κ) and regulates a wide variety of physiological and pathological events, such as cancer, type II diabetes, neuronal disorders and immune responses. DG and PA consist of various molecular species that have different acyl chains at the sn-1 and sn-2 positions, and consequently, mammalian cells contain at least 50 structurally distinct DG/PA species. Because DGK is one of the components of phosphatidylinositol (PI) turnover, the generally accepted dogma is that all DGK isozymes utilize 18:0/20:4-DG derived from PI turnover. We recently established a specific liquid chromatography-mass spectrometry method to analyze which PA species were generated by DGK isozymes in a cell stimulation-dependent manner. Interestingly, we determined that DGKδ, which is closely related to the pathogenesis of type II diabetes, preferentially utilized 14:0/16:0-, 14:0/16:1-, 16:0/16:0-, 16:0/16:1-, 16:0/18:0- and 16:0/18:1-DG species (X:Y = the total number of carbon atoms: the total number of double bonds) supplied from the phosphatidylcholine-specific phospholipase C pathway, but not 18:0/20:4-DG, in high glucose-stimulated C2C12 myoblasts. Moreover, DGKα mainly consumed 14:0/16:0-, 16:0/18:1-, 18:0/18:1- and 18:1/18:1-DG species during cell proliferation in AKI melanoma cells. Furthermore, we found that 16:0/16:0-PA was specifically produced by DGKζ in Neuro-2a cells during retinoic acid- and serum starvation-induced neuronal differentiation. These results indicate that DGK isozymes utilize a variety of DG molecular species derived from PI turnover-independent pathways as substrates in different stimuli and cells. DGK isozymes phosphorylate various DG species to generate various PA species. It was revealed that the modes of activation of conventional and novel protein kinase isoforms by DG molecular species varied considerably. However, PA species-selective binding proteins have not been found to date. Therefore, we next attempted to identify PA species-selective binding proteins from the mouse brain and identified α-synuclein, which has causal links to Parkinson's disease. Intriguingly, we determined that among phospholipids, including several PA species (16:0/16:0-PA, 16:0/18:1-PA, 18:1/18:1-PA, 18:0/18:0-PA and 18:0/20:4-PA); 18:1/18:1-PA was the most strongly bound PA to α-synuclein. Moreover, 18:1/18:1-PA strongly enhanced secondary structural changes from the random coil form to the α-helix form and generated a multimeric and proteinase K-resistant α-synuclein protein. In contrast with the dogma described above, our recent studies strongly suggest that PI turnover-derived DG species and also various DG species derived from PI turnover-independent pathways are utilized by DGK isozymes. DG species supplied from distinct pathways may be utilized by DGK isozymes based on different stimuli present in different types of cells, and individual PA molecular species would have specific targets and exert their own physiological functions.

A potential contribution of tenascin-X to blood vessel formation in peripheral nerves.

Tenascin-X (TNX), an extracellular matrix protein, is abundantly expressed in peripheral nerves. However, the physiological role of TNX in peripheral nerves remains unknown. In this study, we found that actin levels in sciatic nerves of TNX-deficient mice were markedly decreased. Since actin was highly expressed in endothelial cells in wild-type sciatic nerves, we assessed morphological alterations of blood vessels in TNX-null sciatic nerves. The density of blood vessels was significantly decreased and the size of blood vessels was larger than those in wild-type sciatic nerves. Immunofluorescence showed that TNX was expressed by Schwann cells and fibroblasts in sciatic nerves. The results suggest that TNX secreted from Schwann cells and/or fibroblasts is involved in blood vessel formation in peripheral nerves.

The prevalence and risk factor control associated with noncommunicable diseases in China, Japan, and Korea.

BACKGROUND: Noncommunicable disease (NCD) has become the leading cause of mortality and disease burden worldwide. METHODS: A cross-sectional survey was carried out to investigate the prevalence of NCDs and risk factor control on dietary behaviors and dietary intake in China, Japan, and Korea. RESULTS: There were significant differences among the three countries on the prevalence of hypertension (24.5% in China, 17.6% in Korea, and 15.2% in Japan), diabetes (8.9% in China, 5.7% in Korea, and 4.8% in Japan), hyperlipidemia (13.1% in China, 9.2% in Korea, and 6.9% in Japan), and angina pectoris (3.6% in China, 1.7% in Korea, and 1.5% in Japan). The prevalence rate of hypertension, diabetes, hyperlipidemia, and angina pectoris was highest in China and lowest in Japan. However, 82.2%, 48.4%, and 64.4% of Chinese, Koreans, and Japanese presented good dietary behavior, respectively. Multivariable logistic regression analysis found that sex, age, and marital status were predictors of good dietary behavior. In addition, in comparison with subjects without hypertension, diabetes, or hyperlipidemia, subjects with hypertension, diabetes, or hyperlipidemia significantly improved their dietary behaviors and controlled their intake of salt, sugar, and oil. CONCLUSIONS: The prevalence of NCDs and trends in major modifiable risk factor control in China, Korea, and Japan remain troubling. Public efforts to introduce healthy lifestyle changes and systematic NCDs prevention programs are necessary to reduce the epidemic of NCDs in these three Asian countries.

Perceptions of Factors Impacting Longevity among Hawai'i Older Adults.

With increased life expectancy, people need more education about healthy aging. This paper examines older adult perceptions regarding various factors impacting longevity, including genetics, lifestyle, and the environment. Data were collected from 733 Hawai'i adults age 50 years and older (39% Caucasian, 27% Japanese, 19% Native Hawaiian and Pacific Islander (NHOPI), 9% Chinese, and 7% Filipino) through randomized telephone interviews. Participants were asked to rate a variety of factors as having "great impact," "some impact," or "no impact" on lifespan. Regardless of ethnicity, more than half of the participants felt that eating habits, exercise, health information, health care, and the environment had great impact on lifespan. Less than half felt that economic status and community had great impact. Compared to the all ethnic groups, Filipino respondents were significantly less likely to feel that smoking (44%, compared with an average across all race/ethnicities of 64%) and stress (48%, average 62%) had great impact. Chinese participants were more likely to feel that drinking alcohol (64%) had great impact (average 38%). Filipinos and Chinese were more likely to perceive that working conditions have great impact (65% and 56%, respectively; average 45%), and NHOPI and Filipinos were more likely to perceive the natural environment as having great impact (59% and 54%, respectively; average 46%). Findings suggest that cultural values and experiences may shape older adults' perceptions of factors associated with lifespan, providing guidance for health professionals on how to tailor health messages to older adults in different ethnic groups.

Behavioral and pharmacological phenotypes of brain-specific diacylglycerol kinase δ-knockout mice.

Diacylglycerol kinase (DGK) is a lipid-metabolizing enzyme that phosphorylates diacylglycerol to produce phosphatidic acid. Previously, we reported that the δ isozyme of DGK was abundantly expressed in the mouse brain. However, the functions of DGKδ in the brain are still unclear. Because conventional DGKδ-knockout (KO) mice die within 24h after birth, we have generated brain-specific conditional DGKδ-KO mice to circumvent the lethality. In the novel object recognition test, the number of contacts in the DGKδ-KO mice to novel and familiar objects was greatly increased compared to the control mice, indicating that the DGKδ-KO mice showed irrational contacts with objects such as compulsive checking. In the marble burying test, which is used for analyzing obsessive-compulsive disorder (OCD)-like phenotypes, the DGKδ-KO mice buried more marbles than the control mice. Additionally, these phenotypes were significantly alleviated by the administration of an OCD remedy, fluoxetine. These results indicate that the DGKδ-KO mice showed OCD-like behaviors. Moreover, the number of long axon/neurites increased in both DGKδ-KO primary cortical neurons and DGKδ-knockdown neuroblastoma Neuro-2a cells compared to control cells. Conversely, overexpression of DGKδ decreased the number of long axon/neurites of Neuro-2a cells. Taken together, these results strongly suggest that a deficiency of DGKδ induces OCD-like behavior through enhancing axon/neurite outgrowth.

Distinct 1-monoacylglycerol and 2-monoacylglycerol kinase activities of diacylglycerol kinase isozymes.

Diacylglycerol kinase (DGK) consists of ten isozymes and is involved in a wide variety of patho-physiological events. However, the enzymological properties of DGKs have not been fully understood. In this study, we performed a comprehensive analysis on the 1-monoacylglycerol kinase (MGK) and 2-MGK activities of ten DGK isozymes. We revealed that type I (α, ß and γ), type II (δ, η and κ) and type III (ε) DGKs have 7.9-19.2% 2-MGK activity compared to their DGK activities, whereas their 1-MGK activities were <3.0%. Both the 1-MGK and 2-MGK activities of the type IV DGKs (ζ and ι) were <1% relative to their DGK activities. Intriguingly, type V DGKθ has approximately 6% 1-MGK activity and <2% 2-MGK activity compared to its DGK activity. Purified DGKθ exhibited the same results, indicating that its 1-MGK activity is intrinsic. Therefore, DGK isozymes are categorized into three types with respect to their 1-MGK and 2-MGK activities: those having (1) 2-MGK activity relatively stronger than their 1-MGK activity (types I-III), (2) only negligible 1-MGK and 2-MGK activities (type IV), and (3) 1-MGK activity stronger than its 2-MGK activity (type V). The 1-MGK activity of DGKθ and the 2-MGK activity of DGKα were stronger than those of the acylglycerol kinase reported as 1-MGK and 2-MGK to date. The presence or absence of 1-MGK and 2-MGK activities may be essential to the patho-physiological functions of each DGK isozyme.