Quinic acid derivatives from Pimpinella brachycarpa exert anti-neuroinflammatory activity in lipopolysaccharide-induced microglia

Five new quinic acid derivatives (1–5), together with 10 known quinic acid derivatives (6–15), were isolated from the MeOH extract of Pimpinella brachycarpa (Umbelliferae). Their structures were established on the basis of spectroscopic analyses including extensive 2D NMR studies (COSY, HMQC and HMBC). Isolated compounds 1–15 were evaluated for their inhibitory activities on nitric oxide (NO) production in an activated murine microglial cell line. Compounds 2, 3, 8 and 11 significantly inhibited NO production without high cell toxicity in lipopolysaccharide (LPS)-activated BV-2 cells, a microglia cell line (IC₅₀ = 4.66, 12.52, 9.04 and 12.11 μM, respectively).     

Synthesis and biological evaluation of novel 3,4-diaryl lactam derivatives as triple reuptake inhibitors

A series of 3,4-diarylpyrrolidin-2-one was designed, prepared and evaluated as triple reuptake inhibitors for antidepressant. Most compounds exhibited comparable in vitro efficacy as norepinephrine and dopamine transporter reuptake inhibitors. Especially, 2i showed better potency than GBR-12909 (IC₅₀ = 14 nM) which was used as reference compound for dopamine transporter. In addition, 2a and 2b showed inhibition (5.17 μM–85.6 nM) for three transporters.     

A novel metformin derivative,HL010183, inhibits proliferation and invasion of triple-negative breast cancer cells

Mounting evidence suggests that metformin (N,N-dimethylbiguanide), a widely prescribed drug for the treatment of type II diabetes, exerts an anti-tumor effect on several cancers including breast cancer. Breast cancer has been estimated as one of the most commonly diagnosed types of cancer among women. In particular, triple-negative breast cancers are associated with poor prognosis and metastatic growth. In the present study, we synthesized a novel metformin derivative 5 (HL010183) and metformin salts, 9a, 9b, and 9c (metformin gamma-aminobutyric acid (GABA) salt, metformin pregabalin salt and metformin gabapentin salt), which exerted more potent inhibitory effects on the proliferation and invasiveness of Hs578T triple-negative breast carcinoma cells than metformin. Importantly, 5 showed approximately 100-fold more potent effects compared to metformin. In a triple-negative breast cancer xenograft model, 5 showed a comparable degree of inhibitory effect on in vivo tumor growth at the 100 mg/kg dose to that of metformin at 500 mg/kg. Our results clearly demonstrate that 5 exerts a potent anti-tumor effect both in vitro and in vivo, paving the way for a strategy for treatment of triple-negative breast cancer.     

Unintended polar metabolite profiling of carotenoid-biofortified transgenic rice reveals substantial equivalence to its non-transgenic counterpart

Substantial equivalence is a critical concept for biosafety assessment of genetically modified (GM) crops. To investigate substantial equivalence among carotenoid-biofortified GM rice and five conventional rice cultivars having common white (three) and red (two) grain colors, profiles of 52 polar metabolites were analyzed using gas chromatography time-of-flight mass spectrometry. The results were compared to evaluate the differences among GM and non-GM rice cultivars using principal components analysis. The GM rice is more comparable to its non-transgenic counterpart rice variety according to the closer co-separation than for other cultivars tested. This suggests that profiling of unintended polar metabolites could be a useful tool to reveal substantial equivalence of GM rice.     

Sarcopenia Is Independently Associated with Cardiovascular Disease in Older Korean Adults: The Korea National Health and Nutrition Examination Survey (KNHANES) from 2009

Background

The association between sarcopenia and cardiovascular disease (CVD) in elderly people has not been adequately assessed. The aim of this study was to investigate whether CVD is more prevalent in subjects with sarcopenia independent of other well-established cardiovascular risk factors in older Korean adults.

Method

This study utilized the representative Korean population data from the Korea National Health and Nutrition Examination Survey (KNHANES) which was conducted in 2009. Subjects older than 65 years of age with appendicular skeletal muscle mass (ASM) determined by dual energy X-ray absorptiometry were selected. The prevalence of sarcopenia in the older Korean adults was investigated, and it was determined whether sarcopenia is associated with CVD independent of other well-known risk factors.

Results

1,578 subjects aged 65 years and older with the data for ASM were selected, and the overall prevalence of sarcopenia was 30.3% in men and 29.3% in women. Most of the risk factors for CVD such as age, waist circumference, body mass index, fasting plasma glucose and total cholesterol showed significant negative correlations with the ratio between appendicular skeletal muscle mass and body weight. Multiple logistic regression analysis demonstrated that sarcopenia was associated with CVD independent of other well-documented risk factors, renal function and medications (OR, 1.768; 95% CI, 1.075–2.909, P = 0.025).

Conclusions

Sarcopenia was associated with the presence of CVD independent of other cardiovascular risk factors after adjusting renal function and medications.     

Social Welfare Centers Protect Outpatients with Mood Disorders from Risk of Hospital Admission

Background

South Korea faces difficulties in the management of mental disorders, and those difficulties are expected to gradually worsen. Therefore, we analyzed the relationship between social welfare centers and hospital admission after outpatient treatment for mood disorders.

Methods

We used data from the National Health Insurance Service National Sample Cohort 2002–2013, which included all medical claims filed for the 50,160 patients who were newly diagnosed with a mood disorder among the 1,025,340 individuals in a nationally representative sample. We performed a logistic regression analysis using generalized estimating equation (GEE) models to examine the relationship between social welfare centers and hospital admission after outpatient treatment for mood disorders (ICD-10: F3).

Results

There was a 3.9% admission rate among a total of 99,533 person-years. Outpatients who lived in regions with more social welfare centers were less likely to be admitted to a hospital (per increase of five social welfare centers per 100,000 people; OR: 0.958; 95% CI: 0.919–0.999). Social welfare centers had an especially strong protective effect on patients with relatively mild mood disorders and those who were vulnerable to medical expenditures.

Conclusions

Considering the protective role of social welfare centers in managing patients with mood disorders, health-policy makers need to consider strategies for activating mental healthcare.     

Assessing Seasonal and Inter-Annual Variations of Lake Surface Areas in Mongolia during 2000-2011 Using Minimum Composite MODIS NDVI

A minimum composite method was applied to produce a 15-day interval normalized difference vegetation index (NDVI) dataset from Moderate Resolution Imaging Spectroradiometer (MODIS) daily 250 m reflectance in the red and near-infrared bands. This dataset was applied to determine lake surface areas in Mongolia. A total of 73 lakes greater than 6.25 km²in area were selected, and 28 of these lakes were used to evaluate detection errors. The minimum composite NDVI showed a better detection performance on lake water pixels than did the official MODIS 16-day 250 m NDVI based on a maximum composite method. The overall lake area detection performance based on the 15-day minimum composite NDVI showed -2.5% error relative to the Landsat-derived lake area for the 28 evaluated lakes. The errors increased with increases in the perimeter-to-area ratio but decreased with lake size over 10 km². The lake area decreased by -9.3% at an annual rate of -53.7 km² yr^-1 during 2000 to 2011 for the 73 lakes. However, considerable spatial variations, such as slight-to-moderate lake area reductions in semi-arid regions and rapid lake area reductions in arid regions, were also detected. This study demonstrated applicability of MODIS 250 m reflectance data for biweekly monitoring of lake area change and diagnosed considerable lake area reduction and its spatial variability in arid and semi-arid regions of Mongolia. Future studies are required for explaining reasons of lake area changes and their spatial variability.