A potential role of protein extractions from Metagonimus yokogawai in amelionating inflammation in patients with ankylosing spondylitis.

Helminth infections and their components has been recognized to have a positive impact on the immune system. This study aimed to investigate the potential of Metagonimus yokogawai-derived proteins (MYp) to provide protection against ankylosing spondylitis (AS) through modulation of immune responses. The cytotoxicity of MYp at various doses was first assessed using MTS and flow cytometry. Peripheral blood mononuclear cells (PBMCs) were collected from AS patients, and the production of inflammatory cytokines was analyzed through flow cytometry. In the experiments with SKG mice, MYp or vehicle was administered and inflammation was evaluated through immunohistochemistry and enzyme-linked immunosorbent assay. The results showed that MYp did not decrease cell viability of PBMCs even after 48 h. Additionally, the frequencies of IFN-γ and IL-17A producing cells were significantly reduced after MYp treatment in the PBMC cultures. Furthermore, MYp treatment significantly suppressed arthritis and enthesitis in the SKG mouse model. The results suggest the first evidence that MYp can effectively alleviate clinical symptoms and restore cytokine balance in patients with AS.

Core contents for a menopausal health literacy intervention for South Korean middle-aged women: an e-Delphi study.

BACKGROUND: The attention on improving health literacy (HL) for self-management at the population level in many countries has been increasing. Although self-management among middle-aged women in the menopausal transition are important public health issues, few studies have developed the menopausal HL intervention reflecting the multidimensional aspects of HL. We aimed to generate consensus from an expert panel on the core contents of the menopausal HL intervention for middle-aged women based on the HL conceptual framework of the European Health Literacy Survey. METHODS: The panel comprised 20 experts from multiple disciplines (nursing, medicine, public health, and food and nutrition). We conducted the e-Delphi process in three rounds, asking the panel to evaluate and prioritize the appropriateness of the core contents and provide open-ended responses to additional comments about the menopausal HL intervention. The e-Delphi questionnaire was developed based on the HL framework, integrating health and HL domains. RESULTS: The experts reached a consensus on 38 components of the intervention. Among the 19 components of the four health domains, health topics in healthcare and disease prevention were more appropriate than those in health promotion. For the 19 HL competency components, strengthening the ability to access, appraise, and apply health information was more important than strengthening the ability to understand information. Finally, a consensus was achieved on the 12 priorities for intervention content by HL domains integrated with health domains. For example, contents included proper access to reliable information resources, understanding the definition and process of menopause, judging abnormal health symptoms, and performing the health checkups necessary for menopausal women. CONCLUSIONS: Our findings provide evidence for HL skills that nurses and other health professionals can consider when developing interventions to improve self-management among middle-aged women. Future research should focus on incorporating the core contents of multidimensional HL skills into menopausal HL interventions to improve self-management among middle-aged women.

Natural peloids originating from subsea depths of 200 m in the hupo basin, South Korea: physicochemical properties for potential pelotherapy applications.

The present study firstly reports surface sediment from the subsea depth of 200 m as a potential natural peloid. The fine-silt sediment exhibited a consistent clay mineral composition dominated by illite, chlorite, kaolinite, and diatomite. The most abundant clay mineral was illite/mica, with other minerals loosely packed in a face-to-face orientation. The thermal conductivity, specific heat capacity, and cation-exchange capacity of the sediment were in the range 0.855-0.885 W/m K, 2.718-2.821 J/g °C, and 23.06-32.96 cmol/kg, respectively. The concentrations of most toxic elements in the sediment were considerably lower than the limits set by domestic cosmetic regulations and other international standards. The analyzed samples exhibited similar properties to those of previously reported peloids, thus making them suitable for use in the field of pelotherapy; furthermore, the consistency in data across a wide peloid-distribution area is expected to enable economically viable mining. Future investigations should aim to to evaluate the long-term effects on the skin, the bioavailability of potentially hazardous substances, and the therapeutic efficacy for various skin conditions.

CCL20 inhibition for treating inflammation in ankylosing spondylitis.

OBJECTIVES: Th17 cells are known to play a significant role in AS. C-C motif chemokine ligand 20 (CCL20) binds to C-C chemokine receptor 6 (CCR6) on Th17 cells, promoting their migration to inflammation sites. The aim of this research is to examine the effectiveness of CCL20 inhibition in treating inflammation in AS. METHODS: Mononuclear cells from peripheral blood (PBMC) and SF (SFMC) were collected from healthy individuals and AS. Flow cytometry was used to analyse cells producing inflammatory cytokines. CCL20 levels were determined using ELISA. The impact of CCL20 on Th17 cell migration was verified using a Trans-well migration assay. The in vivo efficacy of CCL20 inhibition was evaluated using an SKG mouse model. RESULTS: The presence of Th17 cells and CCL20 expressing cells was higher in SFMCs from AS patients compared with their PBMCs. The CCL20 level in AS SF was significantly higher than in OA patients. The percentage of Th17 cells in PBMCs from AS patients increased when exposed to CCL20, whereas the percentage of Th17 cells in SFMCs from AS patients decreased when treated with CCL20 inhibitor. The migration of Th17 cells was found to be influenced by CCL20, and this effect was counteracted by the CCL20 inhibitor. In the SKG mouse model, the use of CCL20 inhibitor significantly reduced joint inflammation. CONCLUSION: This research validates the critical role of CCL20 in AS and suggests that targeting CCL20 inhibition could serve as a novel therapeutic approach for AS treatment.

Clinical effects of bacteremia in sepsis patients with community-acquired pneumonia.

BACKGROUND: Data regarding the clinical effects of bacteremia on severe community-acquired pneumonia (CAP) are limited. Thus, we investigated clinical characteristics and outcomes of severe CAP patients with bacteremia compared with those of subjects without bacteremia. In addition, we evaluated clinical factors associated with bacteremia at the time of sepsis awareness. METHODS: We enrolled sepsis patients diagnosed with CAP at emergency departments (EDs) from an ongoing nationwide multicenter observational registry, the Korean Sepsis Alliance, between September 2019 and December 2020. For evaluation of clinical factors associated with bacteremia, we divided eligible patients into bacteremia and non-bacteremia groups, and logistic regression analysis was performed using the clinical characteristics at the time of sepsis awareness. RESULT: During the study period, 1,510 (47.9%) sepsis patients were caused by CAP, and bacteremia was identified in 212 (14.0%) patients. Septic shock occurred more frequently in the bacteremia group than in the non-bacteremia group (27.4% vs. 14.8%; p < 0.001). In multivariable analysis, hematologic malignancies and septic shock were associated with an increased risk of bacteremia. However, chronic lung disease was associated with a decreased risk of bacteremia. Hospital mortality was significantly higher in the bacteremia group than in the non-bacteremia group (27.3% vs. 40.6%, p < 0.001). The most prevalent pathogen in blood culture was Klebsiella pneumoniae followed by Escherichia coli in gram-negative pathogens. CONCLUSION: The incidence of bacteremia in severe CAP was low at 14.0%, but the occurrence of bacteremia was associated with increased hospital mortality. In severe CAP, hematologic malignancies and septic shock were associated with an increased risk of bacteremia.

Influence of gender on age-associated in-hospital mortality in patients with sepsis and septic shock: a prospective nationwide multicenter cohort study.

BACKGROUND: Numerous epidemiological studies investigating gender-dependent clinical outcomes in sepsis have shown conflicting evidence. This study aimed to investigate the effect of gender on in-hospital mortality due to sepsis according to age group. METHODS: This study used data from the Korean Sepsis Alliance, an ongoing nationwide prospective multicenter cohort from 19 participating hospitals in South Korea. All adult patients diagnosed with sepsis in the emergency departments of the participating hospitals between September 2019 and December 2021 were included in the analysis. Clinical characteristics and outcomes were compared between male and female. Eligible patients were stratified by age into 19-50 years, 50-80 years, and ≥ 80 years old individuals. RESULTS: During the study period, 6442 patients were included in the analysis, and 3650 (56.7%) were male. The adjusted odds ratio (OR) [95% confidence interval (CI)] for in-hospital mortality for male compared with female was 1.15 (95% CI = 1.02-1.29). Interestingly, in the age 19-50 group, the risk of in-hospital mortality for males was significantly lower than that of females [0.57 (95% CI = 0.35-0.93)]. For female, the risk of death remained relatively stable until around age 80 (P for linearity = 0.77), while in males, there was a linear increase in the risk of in-hospital death until around age 80 (P for linearity < 0.01). Respiratory infection (53.8% vs. 37.4%, p < 0.01) was more common in male, whereas urinary tract infection (14.7% vs. 29.8%, p < 0.01) was more common in female. For respiratory infection, male had significantly lower in-hospital mortality than female in the age 19-50 groups (adjusted OR = 0.29, 95% CI = 0.12-0.69). CONCLUSIONS: Gender may influence age-associated sepsis outcomes. Further studies are needed to replicate our findings and fully understand the interaction of gender and age on the outcomes of patients with sepsis.

Differential patterns of lifestyle behaviors among low- and high-income postmenopausal women in Korea: a latent class analysis.

BACKGROUND: Healthy lifestyle behaviors among postmenopausal women are important to prevent chronic diseases and improve health later in life. Heterogeneous lifestyle patterns may exist among postmenopausal women, and socioeconomic status (SES) is a critical determinant of lifestyle behaviors. However, little is known about distinct SES-specific patterns of lifestyle behaviors among postmenopausal women. Thus, this study used latent class analysis to identify subgroups of postmenopausal women with different health behaviors according to income and to examine the predictors of income-specific subgroups. METHODS: We analyzed nationally representative data from the Eighth Korea National Health and Nutrition Examination Survey, collected in 2019 and 2020. We used nine lifestyles (i.e., current smoking and drinking, high-risk drinking, walking, muscle-strengthening exercise, sleep, vegetable and fruit intakes, and weight control efforts). We conducted a multiple-group latent class analysis using monthly household income as a proxy for SES. The monthly household income variable was calculated by standardizing monthly household income by the number of family members and then divided into quintiles. We classified the participants into low- (i.e., Q1 and Q2) and high-income (i.e., Q3, Q4, and Q5) groups. RESULTS: Although the three-class models best fit the data of low- and high-income groups, we found differential patterns by income: (a) for low-income group, "relatively healthy (RH)," "lowest physical activity, insufficient fruit intake, and no intention to control weight," and "high-risk drinking and insufficient fruit intake" classes and (b) for high-income group, "RH," "lowest physical activity," "high-risk drinking and insufficient fruit intake and sleep" classes. The proportion of the RH class was largest in both groups. However, lifestyle patterns in low-income group showed multiple and unhealthy characteristics than those in high-income group. CONCLUSIONS: This study suggests that different underlying lifestyle patterns exist in postmenopausal women with low- and high-income. To promote healthy behaviors among postmenopausal women, health professionals should develop and apply lifestyle interventions tailored to lifestyle pattern characteristics according to income.

Health-related quality of life associated with coexisting chronic conditions in postmenopausal women.

We aimed to examine the association between metabolic syndrome (MetS), depressive symptoms, and health-related quality of life in postmenopausal women. We conducted a descriptive cross-sectional study in naturally postmenopausal women aged 45-65 years using data from the 8th Korea National Health and Nutrition Examination Survey. We classified the participants into four groups: normal (neither MetS nor depressive symptoms), MetS, depressive symptoms, and MetS + depressive symptoms. Compared to the other three groups, the MetS + depressive symptoms group had the worst self-rated health. High fasting glucose, high triglyceride and low high-density lipoprotein-cholesterol levels were the most common in the MetS + depressive symptoms group. After adjusting for covariates, the MetS + depressive symptoms group was more likely to have problems with usual activities and pain/discomfort than the normal group.

IL-6 activates pathologic Th17 cell via STAT 3 phosphorylation in inflammatory joint of Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease, which is characterized by inflammation of the axial skeleton and the peripheral arthritis. An increase in the number of Th17 cells in patients with AS has been reported. Although Th17 cells have been involved in the induction of inflammation, recent data suggest that not all Th17 cells are pathogenic, showing regulatory function of Th17 cell. Cells producing both interferon-gamma (IFN-γ) and interleukin (IL)-17 have been reported to be the main pathologic Th17 (pTh17) cells that induce inflammation at sites of joint. Emerging evidence demonstrated that IL-6 has a main role in regulating the balance between inflammatory and regulatory T cells. However, there is no direct study to assess pTh17 cell with IL-6 in AS. Therefore, we evaluated the effect of IL-6 on pTh17 cell activation, and it's mechanism, using ex vivo and mouse model of AS. As a result, we found that pTh17 cell is dependent on the cytokine milieu with IL-6. We confirmed pTh17 cells play a pathogenic role at sites of inflammation. As a mechanism, it was revealed that IL-6 induced STAT 3 phosphorylation contributes to the increased pTh17 responses in AS patients with peripheral arthritis. Though validation of our results is required, IL-6 inhibitor can be a promising treatment for inflammation in AS patients with peripheral arthritis.

Enhancement of anti-tumor activity in melanoma using arginine deiminase fused with 30Kc19α protein.

Arginine deiminase (ADI) is a microbial-derived enzyme which catalyzes the conversion of L-arginine into L-citrulline. ADI originating from Mycoplasma has been reported to present anti-tumor activity against arginine-auxotrophic tumors, including melanoma. Melanoma cells are sensitive to arginine depletion due to reduced expression of argininosuccinate synthase 1 (ASS1), a key enzyme for arginine biosynthesis. However, clinical applications of recombinant ADI for melanoma treatment present some limitations. Since recombinant ADI is not human-derived, it shows instability, proteolytic degradation, and antigenicity in human serum. In addition, there is a problem of drug resistance issue due to the intracellular expression of once-silenced ASS1. Moreover, recombinant ADI proteins are mainly expressed as inclusion body forms in Escherichia coli and require a time-consuming refolding process to turn them back into active form. Herein, we propose fusion of recombinant ADI from Mycoplasma hominis and 30Kc19α, a cell-penetrating protein which also increases stability and soluble expression of cargo proteins, to overcome these problems. We inserted matrix metalloproteinase-2 cleavable linker between ADI and 30Kc19α to increase enzyme activity in melanoma cells. Compared to ADI, ADI-LK-30Kc19α showed enhanced solubility, stability, and cell penetration. The fusion protein demonstrated selective cytotoxicity and reduced drug resistance in melanoma cells, thus would be a promising strategy for the improved efficacy in melanoma treatment. KEY POINTS: • Fusion of ADI with 30Kc19α enhances soluble expression and productivity of recombinant ADI in E. coli • 30Kc19α protects ADI from the proteolytic degradation by shielding effect, helping ADI to remain active • Intracellular delivery of ADI by 30Kc19α overcomes ADI resistance in melanoma cells by degrading intracellularly expressed arginine.

Role of alcohol media literacy in alcohol use among children and adolescents: a systematic review.

Enhancing alcohol media literacy (AML) is a critical strategy to attenuate negative effects of alcohol-related media messages. We aimed to systematically review previous studies on AML in children and adolescents. Through database and hand searches, we identified four non-experimental and 13 experimental studies. From the 17 studies, we extracted data on theoretical framework, AML measures, intervention contents and main findings. Our review revealed the following. First, nine and four studies used a single theory and at least two theories, respectively. The most frequently used theory was the Message Interpretation Process model. Second, 13 studies assessed AML using participant self-reporting or evaluators' ratings of participant performance, but no study reported validities of AML measures. Eight studies assessed tobacco or general media literacy as well as AML. Third, all experimental studies used three to five media literacy core concepts proposed by the Center for Media Literacy in AML interventions. Finally, all non-experimental studies found strong cross-sectional associations between higher AML and improved drinking outcomes; all experimental studies found strong intervention effects, such as an increase in AML or improvement in drinking outcomes. In addition, intervention effects differed across participants' gender and drinking experiences. Given our review, health professionals should implement strategies to enhance children and adolescents' AML. Future research should investigate (i) causal inferences in non-experimental studies, (ii) long-term intervention effects in experimental studies and (iii) differences in intervention effects across participants' characteristics, while using solid theoretical frameworks and multidimensional AML concepts.

Currently, alcohol consumption and great exposure to alcohol-related media messages in youth are significant public health concerns. After systematically reviewing non-experimental studies on alcohol media literacy (AML) in children and adolescents, we found that high AML levels were associated with improved drinking-related characteristics: a decrease in positive alcohol expectancies, intention to drink and risk of alcohol consumption. Additionally, we found that AML education targeting children and adolescents was effective in enhancing AML and improving the aforementioned drinking-related characteristics. Given our findings, we strongly recommend providing AML education to children and adolescents in order to attenuate negative effects of alcohol-related media messages on drinking-related characteristics.

A Probabilistic-Geometric Approach for UAV Detection and Avoidance Systems.

This paper proposes a collision avoidance algorithm for the detection and avoidance capabilities of Unmanned Aerial Vehicles (UAVs). The proposed algorithm aims to ensure minimum separation between UAVs and geofencing with multiple no-fly zones, considering the sensor uncertainties. The main idea is to compute the collision probability and to initiate collision avoidance manoeuvres determined by the differential geometry concept. The proposed algorithm is validated by both theoretical and numerical analysis. The results indicate that the proposed algorithm ensures minimum separation, efficiency, and scalability compared with other benchmark algorithms.

My video game console is so cool! A coolness theory-based model for intention to use video game consoles.

With the outbreak of COVID-19, the video game console market is thriving again. In this study, we attempted to explore users' intention to use video game consoles by developing a causal model mainly based on coolness theory and the technology acceptance model. To better illustrate user experience for video game consoles, we added several concepts to the causal model, including hedonic motivation, system and service quality, perceived cost, and game variety. Through examining survey-based data from 360 Koreans, we discovered that the model had a high explanatory power for users' intention to use video game consoles. The key findings were as follows: First, among the components of coolness theory, individuals' attitude toward consoles was significantly related to subcultural appeal and originality, but not to attractiveness. Second, originality positively influenced subcultural appeal significantly. Overall, this study implied that the novel coolness theory is effective for exploring user experience regarding of specific devices and services.

Protective Effects of Methoxsalen Supplementation on Chronic Alcohol-Induced Osteopenia and Steatosis in Rats.

Osteopenia or osteoporosis occurs frequently in alcoholics and patients with alcoholic fatty liver disease. Methoxsalen (MTS), 8-methoxypsoralen, improved osteoporosis in ovariectomized and diabetic mouse models; however, its effects on alcohol-induced osteopenia and steatosis have not been reported. This study examined the effects of MTS on alcohol-induced bone loss and steatosis. Rats in the alcohol groups were fed a Liber-DeCarli liquid diet containing 36% of its calories as alcohol. MTS was at 0.005% in their diet, while alendronate (positive control; 500 µg/kg BW/day) was administered orally for eight weeks. The pair-fed group received the same volume of isocaloric liquid diet containing dextrin-maltose instead of alcohol as the alcohol control group consumed the previous day. In the alcohol-fed rats, the MTS and alendronate increased the bone volume density, bone surface density and trabecular number, while the bone specific surface, trabecular separation and structure model index were decreased in the tibia. MTS down-regulated tibial tartrate-resistant acid phosphatase 5 (TRAP) expression compared to the alcohol control group. MTS or alendronate prevented chronic alcohol-induced hepatic lipid accumulation and the triglyceride level in the alcohol-fed rats by decreasing the lipogenic enzyme activities and increasing the fatty acid oxidation enzyme activities. MTS reduced significantly the serum levels of alcohol, TRAP and tumor necrosis factor-α compared to the alcohol control group. Overall, these results suggest that MTS is likely to be an alternative agent for alcoholic osteopenia and hepatosteatosis.

Gentiopicroside isolated from Gentiana scabra Bge. inhibits adipogenesis in 3T3-L1 cells and reduces body weight in diet-induced obese mice.

Gentiopicroside is a major active component of the Gentiana scabra Bge., which is commonly used as herbal medicine for the treatment of inflammation in Asia. Gentiopicroside significantly down-regulated expression of key adipogenic transcription factors (PPARγ, C/EBPα, SREBP-1c) and dose-dependently inhibited the lipid uptake-related gene (LPL), fatty acid transport-related gene (FABP4) and triglyceride (TG) synthesis-related gene (DGAT2), as well as fatty acid synthesis-related genes (FAS, SCD1), which resulted in reduced intracellular lipid droplet accumulation and TG content in 3T3-L1 cells. Gentiopicroside also down-regulated expression of inflammatory cytokine genes (NFκB1, TNFα, IL6) compared with vehicle. Oral administration of gentiopicroside (50 mg/kg) in mice fed with high-fat diet for 12 weeks resulted in reduced body weight and visceral fat mass compared with the control group. Overall, the results of this study showed that gentiopicroside had positive anti-obesity effects by regulating the expression of adipogenesis/lipogenesis-related genes and inflammatory genes in 3T3-L1, and that it effectively reduced body weight and visceral fat mass in vivo.

Methoxsalen and Bergapten Prevent Diabetes-Induced Osteoporosis by the Suppression of Osteoclastogenic Gene Expression in Mice.

This study evaluated whether bergapten and methoxsalen could prevent diabetes-induced osteoporosis and its underlying mechanism. For 10 weeks, bergapten or methoxsalen (0.02%, w/w) was applied to diabetic mice that were provided with a high-fat diet and streptozotocin. Bone mineral density (BMD) and microarchitecture quality were significantly reduced in the diabetic control group; however, both bergapten and methoxsalen reversed serum osteocalcin, bone-alkaline phosphatase and femur BMD. These coumarin derivatives significantly increased bone volume density and trabecular number, whereas they decreased the structure model index of femur tissue in diabetic mice. Conversely, tartrate-resistant acid phosphatase 5 (TRAP) staining revealed that these derivatives reduced osteoclast numbers and formation in diabetic bone tissue. Additionally, both bergapten and methoxsalen tended to downregulate the expression of osteoclast-related genes such as receptor activator of nuclear factor kappa-B ligand (RANKL), nuclear of activated T-cells, cytoplasmic 1 (NFATc1) and TRAP in diabetic femurs, with NFATc1 and TRAP expression showing significant reductions. Our data suggest that both bergapten and methoxsalen prevent diabetic osteoporosis by suppressing bone resorption.

High-Speed Lateral Flow Strategy for a Fast Biosensing with an Improved Selectivity and Binding Affinity.

We report a high-speed lateral flow strategy for a fast biosensing with an improved selectivity and binding affinity even under harsh conditions. In this strategy, biosensors were fixed at a location away from the center of a round shape disk, and the disk was rotated to create the lateral flow of a target solution on the biosensors during the sensing measurements. Experimental results using the strategy showed high reaction speeds, high binding affinity, and low nonspecific adsorptions of target molecules to biosensors. Furthermore, binding affinity between target molecules and sensing molecules was enhanced even in harsh conditions such as low pH and low ionic strength conditions. These results show that the strategy can improve the performance of conventional biosensors by generating high-speed lateral flows on a biosensor surface. Therefore, our strategy can be utilized as a simple but powerful tool for versatile bio and medical applications.

Scopoletin Supplementation Ameliorates Steatosis and Inflammation in Diabetic Mice.

Scopoletin is a bioactive component in many edible plants and fruits. This study investigated the effects of scopoletin on hepatic steatosis and inflammation in a high-fat diet fed type 1 diabetic mice by comparison with metformin. Scopoletin (0.01%, w/w) or metformin (0.5%, w/w) was provided with a high-fat diet to streptozotocin-induced diabetic mice for 11 weeks. Both scopoletin and metformin lowered blood glucose and HbA1c , serum ALT, TNF-α and IL-6 levels, glucose intolerance, and hepatic lipid accumulation compared with the diabetic control group. Scopoletin or metformin down-regulated hepatic gene expression of triglyceride (Pparg, Plpp2, and Dgat2) and cholesterol (Hmgcr) synthesis as well as inflammation (Tlr4, Myd88, Nfkb1, Tnfa, and Il6), while it up-regulated Cyp7a1 gene. Hepatic PPARγ and DGAT2 protein levels were also down-regulated in scopoletin or metformin group compared with the control group. Scopoletin or metformin also inhibited hepatic fatty acid synthase and phosphatidate phosphohydrolase activities. These results suggest that scopoletin protects against diabetes-induced steatosis and inflammation by inhibiting lipid biosynthesis and TLR4-MyD88 pathways. Copyright © 2017 John Wiley & Sons, Ltd.

Anti-adipogenic and anti-diabetic effects of cis-3',4'-diisovalerylkhellactone isolated from Peucedanum japonicum Thunb leaves in vitro.

Peucedanum japonicum Thunb is a medicinal plant belonging to the family Umbelliferae. This study evaluated the anti-diabetic and anti-obesity effects of cis-3',4'-diisovalerylkhellactone (cDIVK) isolated from Peucedanum japonicum Thunb leaves. cDIVK (30 and 50µM) effectively inhibited adipocyte differentiation and fat accumulation, whereas it stimulated glucose uptake compared with the control in 3T3-L1 cells. cDIVK significantly increased AMPK activation and suppressed protein and mRNA expression of major adipogenic transcriptional factors such as C/EBPα, PPARγ and SREBP-1c in 3T3-L1 cells. In addition, cDIVK had potential α-glucosidase inhibitory activity. These results indicated that cDIVK may act as a natural dual therapeutic agent for diabetes and obesity.

DNA Microarray-Based Identification of Genes Regulated by NtrC in Bradyrhizobium japonicum.

The Bradyrhizobium japonicum NtrBC two-component system is a critical regulator of cellular nitrogen metabolism, including the acquisition and catabolism of nitrogenous compounds. To better define the roles of this system, genome-wide transcriptional profiling was performed to identify the NtrC regulon during the response to nitrogen limitation. Upon cells perceiving low intracellular nitrogen, they stimulate the phosphorylation of NtrC, which induces genes responsible for alteration of the core glutamine synthetase/glutamate synthase nitrogen assimilation pathway, including the genes for the glutamine synthetases and PII proteins. In addition, genes responsible for the import and utilization of multiple nitrogen sources, specifically nitrate and nitrite, were upregulated by NtrC activation. Mutational analysis of a candidate nitrite reductase revealed a role for NtrC in regulating the assimilation of nitrite, since mutations in both ntrC and the gene encoding the candidate nitrite reductase abolished the ability to grow on nitrite as a sole nitrogen source.