Association between Dietary Diversity Score and Metabolic Syndrome in Korean Adults: A Community-Based Prospective Cohort Study.

Dietary diversity is recognized as a key indicator of dietary quality and is known to affect the burden of non-communicable diseases. This study examined the gender-stratified association between dietary diversity score (DDS) and risk of metabolic syndrome (MetS) in 5468 adults aged 40−69 years during a 12-year follow-up of the Korean Genome and Epidemiology Study (KoGES). DDS was calculated according to the consumption of the five food groups based on the Dietary Reference Intakes (DRIs) for Koreans. The Cox proportional hazard model was used to evaluate MetS risk according to DDS. A higher DDS was negatively associated with the consumption of grains but positively associated with the consumption of fruits and non-salted vegetables. Furthermore, participants with a higher DDS showed higher consumption of fish and milk. Prospectively, a higher DDS was significantly associated with a lower risk of MetS in men (HR: 0.76, 95% CI: 0.63−0.92, p < 0.01). In all participants, a higher DDS was inversely associated with the incidence of abdominal obesity (men, HR: 0.76, 95% CI: 0.62−0.93, p < 0.01; women, HR: 0.79, 95% CI: 0.67−0.94, p < 0.01). Furthermore, men with a higher DDS had a lower risk of hypertriglyceridemia (HR: 0.83, 95% CI: 0.71−0.97, p < 0.05). These findings suggested that eating a more varied diet might have favorable effects on preventing MetS in Korean adults.

Association between Seafood Intake and Cardiovascular Disease in South Korean Adults: A Community-Based Prospective Cohort Study.

Cardiovascular disease (CVD) is the most common non-communicable diseases causing 18.6 million deaths worldwide. Several studies have revealed that seafood consumption has a protective effect against CVD. This study investigated the correlation between CVD and seafood intake based on a 10-year follow-up of the Korean Genome and Epidemiology Study (KoGES). The study population, which included 6565 adults age, 55.65 (±8.68), was divided into seafood intake-based tertiles. CVD included myocardial infarction, coronary artery disease, congestive heart failure, cerebrovascular disease, and peripheral vascular disease. At baseline, participants with low seafood intake also had low eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intakes. Prospectively, hazard ratios (HRs) with 95% confidence intervals (CIs) for CVD were analyzed using Cox proportional hazards regression models. Seafood intake exhibited a significantly inverse relationship with the cumulative CVD incidence over 10 years regardless of sex (women: log-rank test p < 0.001 and men: log-rank test p < 0.0401). The longitudinal association of low seafood intake with the CVD risk was significantly stronger in female participants after adjusting for confounding variables (HR (95% confidence interval (CI)) = 0.718 (0.519−0.993) p-trend = 0.043). These results suggested that seafood consumption potentially ameliorates CVD risk in middle-aged adults.

Automated brain volumetric program measuring regional brain atrophy in diagnosis of mild cognitive impairment and Alzheimer's disease dementia.

A quantitative analysis of brain volume can assist in the diagnosis of Alzheimer's disease (AD) which is ususally accompanied by brain atrophy. With an automated analysis program Quick Brain Volumetry (QBraVo) developed for volumetric measurements, we measured regional volumes and ratios to evaluate their performance in discriminating AD dementia (ADD) and mild cognitive impairment (MCI) patients from normal controls (NC). Validation of QBraVo was based on intra-rater and inter-rater reliability with a manual measurement. The regional volumes and ratios to total intracranial volume (TIV) and to total brain volume (TBV) or total cerebrospinal fluid volume (TCV) were compared among subjects. The regional volume to total cerebellar volume ratio named Standardized Atrophy Volume Ratio (SAVR) was calculated to compare brain atrophy. Diagnostic performances to distinguish among NC, MCI, and ADD were compared between MMSE, SAVR, and the predictive model. In total, 56 NCs, 44 MCI, and 45 ADD patients were enrolled. The average run time of QBraVo was 5 min 36 seconds. Intra-rater reliability was 0.999. Inter-rater reliability was high for TBV, TCV, and TIV (R = 0.97, 0.89 and 0.93, respectively). The medial temporal SAVR showed the highest performance for discriminating ADD from NC (AUC = 0.808, diagnostic accuracy = 80.2%). The predictive model using both MMSE and medial temporal SAVR improved the diagnostic performance for MCI in NC (AUC = 0.844, diagnostic accuracy = 79%). Our results demonstrated QBraVo is a fast and accurate method to measure brain volume. The regional volume calculated as SAVR could help to diagnose ADD and MCI and increase diagnostic accuracy for MCI.

LPIN1 Induces Gefitinib Resistance in EGFR Inhibitor-Resistant Non-Small Cell Lung Cancer Cells.

Drug resistance limits the efficacy of targeted therapies, including tyrosine kinase inhibitors (TKIs); however, a substantial portion of the drug resistance mechanisms remains unexplained. In this study, we identified LPIN1 as a key factor that regulates gefitinib resistance in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) cells. Unlike TKI-sensitive HCC827 cells, gefitinib treatment induced LPIN1 expression and increased diacylglycerol concentration in TKI-resistant H1650 cells, followed by the activation of protein kinase C delta and nuclear factor kappa B (NF-κB) in an LPIN1-dependent manner, resulting in cancer cell survival. Additionally, LPIN1 increased the production of lipid droplets, which play an important role in TKI drug resistance. All results were recapitulated in a patient-derived EGFR-mutant NSCLC cell line. In in vivo tumorigenesis assay, we identified that both shRNA-mediated depletion and pharmaceutical inhibition of LPIN1 clearly reduced tumor growth and confirmed that gefitinib treatment induced LPIN1 expression and LPIN1-dependent NF-κB activation (an increase in p-IκBα level) in tumor tissues. These results suggest an effective strategy of co-treating TKIs and LPIN1 inhibitors to prevent TKI resistance in NSCLC patients.

Evolution of magnetic resonance imaging features in cerebral parenchyma from prolonged focal status epilepticus: a case study.

It has rarely been documented that permanent alteration of cerebral structures occurs by focal status epilepticus (FSE). We report the case of a 16-year-old boy with FSE in whom serial T1-weighted magnetic resonance volumetry and conventional magnetic resonance imaging were useful for investigating an evolving pattern of morphological changes during and after the FSE, including cortical laminar necrosis (CLN), increased T2 signal intensities, and marked regional atrophy on the corresponding areas. Despite cessation of FSE after adequate medication (combination therapy including clobazam of 1 mg/kg/day), further significant cerebral atrophy was detected at the limited regions where discrete CLN had occurred during the FSE.

PKM2 Regulates HSP90-Mediated Stability of the IGF-1R Precursor Protein and Promotes Cancer Cell Survival during Hypoxia.

Insulin-like growth factor-1 receptor (IGF-1R), an important factor in promoting cancer cell growth and survival, is commonly upregulated in cancer cells. However, amplification of the IGF1R gene is extremely rare in tumors. Here, we have provided insights into the mechanisms underlying the regulation of IGF-1R protein expression. We found that PKM2 serves as a non-metabolic protein that binds to and increases IGF-1R protein expression by promoting the interaction between IGF-1R and heat-shock protein 90 (HSP90). PKM2 depletion decreases HSP90 binding to IGF-1R precursor, thereby reducing IGF-1R precursor stability and the basal level of mature IGF-1R. Consequently, PKM2 knockdown inhibits the activation of AKT, the key downstream effector of IGF-1R signaling, and increases apoptotic cancer cell death during hypoxia. Notably, we clinically verified the PKM2-regulated expression of IGF-1R through immunohistochemical staining in a tissue microarray of 112 lung cancer patients, demonstrating a significant positive correlation (r = 0.5208, p < 0.0001) between PKM2 and IGF-1R expression. Together, the results of a previous report demonstrated that AKT mediates PKM2 phosphorylation at serine-202; these results suggest that IGF-1R signaling and PKM2 mutually regulate each other to facilitate cell growth and survival, particularly under hypoxic conditions, in solid tumors with dysregulated IGF-1R expression.

CD9 induces cellular senescence and aggravates atherosclerotic plaque formation.

CD9, a 24 kDa tetraspanin membrane protein, is known to regulate cell adhesion and migration, cancer progression and metastasis, immune and allergic responses, and viral infection. CD9 is upregulated in senescent endothelial cells, neointima hyperplasia, and atherosclerotic plaques. However, its role in cellular senescence and atherosclerosis remains undefined. We investigated the potential mechanism for CD9-mediated cellular senescence and its role in atherosclerotic plaque formation. CD9 knockdown in senescent human umbilical vein endothelial cells significantly rescued senescence phenotypes, while CD9 upregulation in young cells accelerated senescence. CD9 regulated cellular senescence through a phosphatidylinositide 3 kinase-AKT-mTOR-p53 signal pathway. CD9 expression increased in arterial tissues from humans and rats with age, and in atherosclerotic plaques in humans and mice. Anti-mouse CD9 antibody noticeably prevented the formation of atherosclerotic lesions in ApoE-/- mice and Ldlr-/- mice. Furthermore, CD9 ablation in ApoE-/- mice decreased atherosclerotic lesions in aorta and aortic sinus. These results suggest that CD9 plays critical roles in endothelial cell senescence and consequently the pathogenesis of atherosclerosis, implying that CD9 is a novel target for prevention and treatment of vascular aging and atherosclerosis.

Study on the Relevance of Metabolic Syndrome and Incidence of Gastric Cancer in Korea.

(1) Background: This study aimed to determine the relevance between stages of metabolic syndrome (MS) progression and the incidence of gastric cancer utilizing a big data cohort for the national health checkup. (2) Methods: There were 7,785,098 study subjects, and three stages of metabolic syndrome were categorized using the health checkup results from 2009. Incidence of gastric cancer was traced and observed from the date of the health insurance benefit claim in 2009 until 31 December, 2016, and Cox hazard-proportional regression was performed to determine the risk of gastric cancer incidence based on the stage of progression for metabolic syndrome. (3) Results: Hazard ratio (HR) incidence rate for the MS group was 2.31 times higher than the normal group (95% CI 2.22⁻2.40) after adjustment (Model 4). The HR incidence rate of gastric cancer for the pre-MS group was 1.08 times higher (95% CI 1.04⁻1.12) than the normal group, while the HR incidence rate of gastric cancer for the MS group was 1.26 times higher (95% CI 1.2⁻1.32). (4) Conclusions: Causal relevance observed in this study between metabolic syndrome and incidence of gastric cancer was high. Promotion and education for active responses in the general population and establishment of appropriate metabolic syndrome management systems to prevent gastric cancer are needed.

Lactate Activates the E2F Pathway to Promote Cell Motility by Up-Regulating Microtubule Modulating Genes.

Excess lactate production due to enhanced aerobic glycolysis is characteristic of malignant cancers, which is also intimately associated with poor cancer prognoses. Although tumor-associated lactate contributes to all major steps in carcinogenesis, its action mechanism remains obscure. To understand the molecular mechanism of the lactate-induced tumor metastatic process, we identified an array of lactate-responsive genes via transcriptome analysis of a metformin-induced hyper-glycolytic liver cancer model. Gene set enrichment analysis suggested E2F-RB pathway as the dominant regulator of the lactate-induced gene expression. We experimentally verified that lactate indeed activates E2F-mediated transcription by promoting E2F1 protein accumulation through a posttranscriptional mechanism. Literature-based analysis of target pathways potentially modulated by 136 top-ranked genes indicated that genes functioning in cell-cell or cell-matrix communications dominate the lactate-induced gene expression. Especially, those regulating microtubule functions, including a group of kinesin family members, were significantly up-regulated in lactate- and E2F1-dependent manners. Depletion of E2F1 or kinesins (KIF2C, KIF18B, KIF20A) led to deformation of microtubule structures, impairing cell motility as much as the deficit in lactate production. These results indicate that E2F pathway activation by tumor-associated lactate and subsequent transcriptional activation of microtubule functions play crucial roles in tumor metastasis, providing mechanistic clues to cell motility-directed anti-cancer strategies.

Pulse wave response characteristics for thickness and hardness of the cover layer in pulse sensors to measure radial artery pulse.

BACKGROUND: Piezo-resistive pressure sensors are widely used for measuring pulse waves of the radial artery. Pulse sensors are generally fabricated with a cover layer because pressure sensors without a cover layer are fragile when they come into direct contact with the skin near the radial artery. However, no study has evaluated the dynamic pulse wave response of pulse sensors depending on the thickness and hardness of the cover layer. This study analyzed the dynamic pulse wave response according to the thickness and hardness of the cover layer and suggests an appropriate thickness and hardness for the design of pulse sensors with semiconductor device-based pressure sensors. METHODS: Pulse sensors with 6 different cover layers with various thicknesses (0.8 mm, 1 mm, 2 mm) and hardnesses (Shore type A; 30, 43, 49, 71) were fabricated. Experiments for evaluating the dynamic pulse responses of the fabricated sensors were performed using a pulse simulator to transmit the same pulse wave to each of the sensors. To evaluate the dynamic responses of the fabricated pulse sensors, experiments with the pulse sensors were conducted using a simulator that artificially generated a constant pulse wave. The pulse wave simulator consisted of a motorized cam device that generated the artificial radial pulse waveform by adjusting the stroke of the cylindrical air pump and an air tube that conveyed the pulse to the artificial wrist. RESULTS: The amplitude of the measured pulse pressure decreased with increasing thickness and hardness of the cover layer. Normalized waveform analysis showed that the thickness rather than the hardness of the cover layer contributed more to waveform distortion. Analysis of the channel distribution of the pulse sensor with respect to the applied constant dynamic pressure showed that the material of the cover layer had a large effect. CONCLUSIONS: In this study, in-line array pulse sensors with various cover layers were fabricated, the dynamic pulse wave responses according to the thickness and the hardness of the cover layer were analyzed, and an appropriate thickness and hardness for the cover layer were suggested. The dynamic pulse wave responses of pulse sensors revealed in this study will contribute to the fabrication of improved pulse sensors and pulse wave analyses.

RNF25 promotes gefitinib resistance in EGFR-mutant NSCLC cells by inducing NF-κB-mediated ERK reactivation.

Non-small cell lung cancer (NSCLC) patients with EGFR mutations initially respond well to EGFR tyrosine kinase inhibitors (TKIs) but eventually exhibit acquired or innate resistance to the therapies typically due to gene mutations, such as EGFR T790M mutation or a second mutation in the downstream pathways of EGFR. Importantly, a significant portion of NSCLC patients shows TKI resistance without any known mechanisms, calling more comprehensive studies to reveal the underlying mechanisms. Here, we investigated a synthetic lethality with gefitinib using a genome-wide RNAi screen in TKI-resistant EGFR-mutant NSCLC cells, and identified RNF25 as a novel factor related to gefitinib resistance. Depletion of RNF25 expression substantially sensitized NSCLC cells to gefitinib treatment, while forced expression of RNF25 augmented gefitinib resistance in sensitive cells. We demonstrated that RNF25 mediates NF-κB activation in gefitinib-treated cells, which, in turn, induces reactivation of ERK signal to cause the drug resistance. We identified that the ERK reactivation occurs via the function of cytokines, such as IL-6, whose expression is transcriptionally induced in a gefitinib-dependent manner by RNF25-mediated NF-κB signals. These results suggest that RNF25 plays an essential role in gefitinib resistance of NSCLC by mediating cross-talk between NF-κB and ERK pathways, and provide a novel target for the combination therapy to overcome TKI resistance of NSCLC.

Regulation of hypoxia responses by flavin adenine dinucleotide-dependent modulation of HIF-1α protein stability.

Oxygen deprivation induces a range of cellular adaptive responses that enable to drive cancer progression. Here, we report that lysine-specific demethylase 1 (LSD1) upregulates hypoxia responses by demethylating RACK1 protein, a component of hypoxia-inducible factor (HIF) ubiquitination machinery, and consequently suppressing the oxygen-independent degradation of HIF-1α. This ability of LSD1 is attenuated during prolonged hypoxia, with a decrease in the cellular level of flavin adenine dinucleotide (FAD), a metabolic cofactor of LSD1, causing HIF-1α downregulation in later stages of hypoxia. Exogenously provided FAD restores HIF-1α stability, indicating a rate-limiting role for FAD in LSD1-mediated HIF-1α regulation. Transcriptomic analyses of patient tissues show that the HIF-1 signature is highly correlated with the expression of LSD1 target genes as well as the enzymes of FAD biosynthetic pathway in triple-negative breast cancers, reflecting the significance of FAD-dependent LSD1 activity in cancer progression. Together, our findings provide a new insight into HIF-mediated hypoxia response regulation by coupling the FAD dependence of LSD1 activity to the regulation of HIF-1α stability.

Hippocampal and entorhinal structures in subjective memory impairment: a combined MRI volumetric and DTI study.

BACKGROUND: Subjective memory impairment (SMI) is common among older adults. Increasing evidence suggests that SMI is a risk factor for future cognitive decline, as well as for mild cognitive impairment and dementia. Medial temporal lobe structures, including the hippocampus and entorhinal cortex, are affected in the early stages of Alzheimer's disease. The current study examined the gray matter (GM) volume and microstructural changes of hippocampal and entorhinal regions in individuals with SMI, compared with elderly control participants without memory complaints. METHODS: A total of 45 participants (mean age: 70.31 ± 6.07 years) took part in the study, including 18 participants with SMI and 27 elderly controls without memory complaints. We compared the GM volume and diffusion tensor imaging (DTI) measures in the hippocampal and entorhinal regions between SMI and control groups. RESULTS: Individuals with SMI had lower entorhinal cortical volumes than control participants, but no differences in hippocampal volume were found between groups. In addition, SMI patients exhibited DTI changes (lower fractional anisotropy (FA) and higher mean diffusivity in SMI) in the hippocampal body and entorhinal white matter compared with controls. Combining entorhinal cortical volume and FA in the hippocampal body improved the accuracy of classification between SMI and control groups. CONCLUSIONS: These findings suggest that the entorhinal region exhibits macrostructural as well as microstructural changes in individuals with SMI, whereas the hippocampus exhibits only microstructural alterations.

Simultaneous determination of imperatorin and its metabolite xanthotoxol in rat plasma and urine by LC-MS/MS and its application to pharmacokinetic studies.

An accurate, precise, selective, and sensitive liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of imperatorin (IMP) and its metabolite, xanthotoxol (XAN), in rat plasma and urine samples. The analytes, along with psoralen as an internal standard, were determined by multiple reaction monitoring (MRM) operated in the positive electrospray ionization (ESI) mode. Chromatographic separation was performed on an Acquity UPLC BEH C18 column (50mm×2.1mm, 1.7µm) with a mobile phase consisting of 0.1% formic acid solution and 0.1% formic acid in methanol at a flow rate of 0.3mL/min. The run time was 6min per sample and the injection volume was 5µL. The method had a lower limit of quantification (LLOQ) of 0.25ng/mL for IMP in plasma and urine, and 1ng/mL for XAN in urine. The linear calibration curves were fitted over the range of 0.25-1000ng/mL for IMP in plasma, 0.25-1000ng/mL for IMP in urine, and 1-1000ng/mL for XAN in urine, with correlation coefficients greater than 0.995. The inter- and intra-day accuracies (relative error, RE%) were between -8.5% and 3.5%, and the precisions (relative standard deviation, RSD%) were less than 10.0% for all quality control samples (QCs). The analytes were extracted from rat plasma and urine samples using a liquid-liquid extraction method with the extraction recovery in the range of 60.3-79.1%. A good stability of the analytes was observed in all the analysis procedures. The method was successfully validated and applied to determine the pharmacokinetics of IMP in rat plasma and, for the first time, the metabolite kinetics of IMP to XAN in rat urine after IMP administration.

Anti-inflammatory effect of tricin isolated from Alopecurus aequalis Sobol. on the LPS-induced inflammatory response in RAW 264.7 cells.

The aim of this study was to identify major anti-inflammatory compounds in Alopecurus aequalis Sobol. (A. aequalis). The ethanol extract and the hexane-, dichloromethane-, ethyl acetate- and n-butanol-soluble fractions derived from A. aequalis were evaluated in order to determine their inhibitory effects on nitric oxide (NO) production in RAW 264.7 cells stimulated with lipopolysaccharide (LPS). The ethanol extract decreased NO production in a dose-dependent manner without any evidence of cytotoxicity at a concentration range of 0-200 µg/ml. The ethyl acetate soluble fraction was the most potent among the four soluble fractions. A compound was isolated by reversed-phase high-performance liquid chromatography from the ethyl acetate soluble fraction and this was identified to be tricin. Tricin inhibited the LPS-induced NO production in a dose-dependent manner without any evidence of cytotoxity at a concentration range of 1-100 µg/ml. Tricin also inhibited the LPS-induced production of prostaglandin E2. Western blot analysis indicated that tricin decreased the LPS-induced increase in the protein levels of inducible NO synthase and cyclooxygenase. In addition, tricin suppressed the production of intracellular reactive oxygen species in the LPS-stimulated RAW 264.7 cells, as measured by flow cytometry. Taken together, our results clearly indicate that tricin is a major functional anti-inflammatory compound which can be isolated from A. aequalis extracts.

Acute toxicity and cytotoxicity evaluation of Dendrobium moniliforme aqueous extract in vivo and in vitro.

Dendrobium moniliforme (L.) Sw., an herb of the Orchidaceae family, has long been used in traditional medicine to strengthen bones, nourish the stomach, and promote the production of bodily fluid. Recently, polysaccharides isolated from Dendrobium have been used in functional foods and nutraceutical products. A traditional method to process Dendrobium is to soak fresh stems in an ethanol solution, which is the most important factor to ensure high yields of aqueous-extractable polysaccharides. The present study was carried out to investigate the potential acute toxicity of D. moniliforme aqueous extract (DMAE), by a single oral dose in Sprague-Dawley rats. The test article was orally administered once by gavage to male and female rats at doses of 0, 2,500, and 5,000 mg/kg body weight (n=5 male and female rats for each dose). Throughout the study period, no treatment-related deaths were observed and no adverse effects were noted in clinical signs, body weight, food consumption, serum biochemistry, organ weight, or gross findings at any dose tested. The results show that a single oral administration of DMAE did not induce any toxic effects at a dose below 5,000 mg/kg in rats, and the minimal lethal dose was considered to be over 5,000 mg/kg body weight for both sexes. With respect to cytotoxicity, the cell viability of human embryonic kidney (HEK293) cells was less than 50% when the cells were treated with 10 mg/mL aqueous extract for 24 h.

Anti-inflammatory Constituents from the Aerial Parts of Iris minutiaurea.

Phytochemical investigation of the methanol extract of the aerial parts of Iris minutiaurea (Iridaceae) using column chromatography led to the isolation of a new xanthone glycoside, 1-hydroxy-3,5-dimethoxy-xanthone-6-O-ß-D-glucoside (1), together with one known flavonoid glycoside (2). The structure of this new compound was elucidated by analysis of spectroscopic, including 1D (1H, 13C), 2D NMR (COSY, HMQC, HMBC), and high resolution fast atom bombardment mass spectrometric (HR-FAB-MS) data and enzyme hydrolysis. We found that compounds 1 and 2 significantly suppressed production of NO, and pro-inflammatory cytokine in LPS-induced RAW264.7 cells. These results suggest that compound 1 and 2 have anti-inflammatory activity related with production of TNF-α, IL-6, IL-1ß, and NO in macrophages, and then compound 1 were more efficient than compound 2 in lowering the level of proinflammatory cytokine.

Anti-inflammatory effects of 6'-O-acetyl mangiferin from Iris rossii Baker via NF-κb signal blocking in lipopolysaccharide-stimulated RAW 264.7 cells.

A series of acylated xanthone C-glucosides were identified from the methanolic extract of whole Iris rossii Baker. The major constituent was characterized as 6'-O-acetyl mangiferin (OAM), and complete structure elucidation was carried out using 2D NMR (COSY, HSQC, and HMBC) and LC-IT-TOF-MS analyses. The present study is the first to report the anti-inflammatory effects of 6'-O-acetyl mangiferin from Iris rossii Baker on the lipopolysaccharide (LPS)-induced inflammatory response in RAW264.7 macrophage cells. OAM strongly suppressed protein expression of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2), thereby inhibiting the production of nitric oxide (NO), prostaglandin E2 (PGE2), and cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). Furthermore, OAM inhibited the LPS-induced phosphorylation of ERK, JNK, and p38, which led to the blockade of nuclear factor-kappa B (NF-κB) and inhibitor kappa B (IκB)-α activation. These results suggest that the anti-inflammatory effects of OAM may be attributed to the downregulation of COX-2 and iNOS via the suppression of NF-κB and the MAPK signaling pathway in RAW264.7 macrophages.

AKT-induced PKM2 phosphorylation signals for IGF-1-stimulated cancer cell growth.

Pyruvate kinase muscle type 2 (PKM2) exhibits post-translational modifications in response to various signals from the tumor microenvironment. Insulin-like growth factor 1 (IGF-1) is a crucial signal in the tumor microenvironment that promotes cell growth and survival in many human cancers. Herein, we report that AKT directly interacts with PKM2 and phosphorylates it at Ser-202, which is essential for the nuclear translocation of PKM2 protein under stimulation of IGF-1. In the nucleus, PKM2 binds to STAT5A and induces IGF-1-stimulated cyclin D1 expression, suggesting that PKM2 acts as an important factor inducing STAT5A activation under IGF-1 signaling. Concordantly, overexpression of STAT5A in cells deficient in PKM2 expression failed to restore IGF-induced growth, whereas reconstitution of PKM2 in PKM2 knockdown cells restored the IGF-induced growth capacity. Our findings suggest a novel role of PKM2 in promoting the growth of cancers with dysregulated IGF/phosphoinositide 3-kinase/AKT signaling.

Development of a Tonometric Sensor with a Decoupled Circular Array for Precisely Measuring Radial Artery Pulse.

The radial artery pulse is one of the major diagnostic indices used clinically in both Eastern and Western medicine. One of the prominent methods for measuring the radial artery pulse is the piezoresistive sensor array. Independence among channels and an appropriate sensor arrangement are important for effectively assessing the spatial-temporal information of the pulse. This study developed a circular-type seven-channel piezoresistive sensor array using face-down bonding (FDB) as one of the sensor combination methods. The three-layered housing structure that included independent pressure sensor units using the FDB method not only enabled elimination of the crosstalk among channels, but also allowed various array patterns to be created for effective pulse measurement. The sensors were arranged in a circular-type arrangement such that they could estimate the direction of the radial artery and precisely measure the pulse wave. The performance of the fabricated sensor array was validated by evaluating the sensor sensitivity per channel, and the possibility of estimating the blood vessel direction was demonstrated through a radial artery pulse simulator. We expect the proposed sensor to allow accurate extraction of the pulse indices for pulse diagnosis.