Serum amyloid A expression in liver promotes synovial macrophage activation and chronic arthritis via NFAT5.

Nuclear factor of activated T-cells 5 (NFAT5), an osmo-sensitive transcription factor, can be activated by isotonic stimuli, such as infection. It remains unclear, however, whether NFAT5 is required for damage-associated molecular pattern-triggered (DAMP-triggered) inflammation and immunity. Here, we found that several DAMPs increased NFAT5 expression in macrophages. In particular, serum amyloid A (SAA), primarily generated by the liver, substantially upregulated NFAT5 expression and activity through TLR2/4-JNK signalling pathway. Moreover, the SAA-TLR2/4-NFAT5 axis promoted migration and chemotaxis of macrophages in an IL-6- and chemokine ligand 2-dependent (CCL2-dependent) manner in vitro. Intraarticular injection of SAA markedly accelerated macrophage infiltration and arthritis progression in mice. By contrast, genetic ablation of NFAT5 or TLR2/4 rescued the pathology induced by SAA, confirming the SAA-TLR2/4-NFAT5 axis in vivo. Myeloid-specific depletion of NFAT5 also attenuated SAA-accelerated arthritis. Of note, inflammatory arthritis in mice strikingly induced SAA overexpression in the liver. Conversely, forced overexpression of the SAA gene in the liver accelerated joint damage, indicating that the liver contributes to bolstering chronic inflammation at remote sites by secreting SAA. Collectively, this study underscores the importance of the SAA-TLR2/4-NFAT5 axis in innate immunity, suggesting that acute phase reactant SAA mediates mutual interactions between liver and joints and ultimately aggravates chronic arthritis by enhancing macrophage activation.

GABA and Fermented Curcuma longa L. Extract Enriched with GABA Ameliorate Obesity through Nox4-IRE1α Sulfonation-RIDD-SIRT1 Decay Axis in High-Fat Diet-Induced Obese Mice.

Gamma-aminobutyric acid (GABA) is a natural amino acid with antioxidant activity and is often considered to have therapeutic potential against obesity. Obesity has long been linked to ROS and ER stress, but the effect of GABA on the ROS-associated ER stress axis has not been thoroughly explored. Thus, in this study, the effect of GABA and fermented Curcuma longa L. extract enriched with GABA (FCLL-GABA) on the ROS-related ER stress axis and inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) sulfonation were examined with the HFD model to determine the underlying anti-obesity mechanism. Here, GABA and FCLL-GABA supplementations significantly inhibited the weight gain in HFD fed mice. The GABA and FCLL-GABA supplementation lowered the expressions of adipogenic transcription factors such as PPAR-γ, C/EBPα, FAS, and SREBP-1c in white adipose tissue (WAT) and liver from HFD-fed mice. The enhanced hyper-nutrient dysmetabolism-based NADPH oxidase (Nox) 4 and the resultant IRE1α sulfonation-RIDD-SIRT1 decay under HFD conditions were controlled with GABA and FCLL-GABA. Notably, GABA and FCLL-GABA administration significantly increased AMPK and sirtuin 1 (SIRT1) levels in WAT of HFD-fed mice. These significant observations indicate that ER-localized Nox4-induced IRE1α sulfonation results in the decay of SIRT1 as a novel mechanism behind the positive implications of GABA on obesity. Moreover, the investigation lays a firm foundation for the development of FCLL-GABA as a functional ingredient.

Pregnancy loss and Income in the Republic of Korea using National Health Insurance Service Data, 2008-2014.

BACKGROUND: Although unintentional pregnancy loss is common, national representative statistics are lacking in high-income East Asian countries undergoing rapid demographic changes. It is necessary to confirm the income inequality of pregnancy loss even in universal national health insurance. METHOD: Using National Health Insurance Service data between 2008 and 2014, the annual prevalence of pregnancy loss was enumerated, and differences in pregnancy loss according to age and income levels were assessed by multivariable Poisson regression. Joint-point regression was used to examine the trend of pregnancy loss. RESULT: On average, there was a 15.0% annual pregnancy loss among 3,941,020 pregnancy cases from 2008 to 2014. Pregnancy loss inequality increased stepwise with income levels except for the highest income group. After adjusting for income levels, the annual percent change of age-standardized prevalence significantly increased by 2.6% every year since 2011. CONCLUSION: Even in high-income countries with universal national health insurance, income inequality in pregnancy loss is observed. Further appraisal is needed to explain the increasing trend of pregnancy loss between 2011 and 2014 even after adjusting income.

A Long-Term Incidence of Heart Failure and Predictors Following Newly Developed Acute Myocardial Infarction: A 10 Years Retrospective Cohort Study with Korean National Health Insurance Data.

Heart failure (HF) is the major mechanism of mortality in acute myocardial infarction (AMI) during early or intermediate post-AMI period. But heart failure is one of the most common long-term complications of AMI. Applied the retrospective cohort study design with nation representative population data, this study traced the incidence of late-onset heart failure since 1 year after newly developed acute myocardial infarction and assessed its risk factors. Methods and Results: Using the Korea National Health Insurance database, 18,328 newly developed AMI patients aged 40 years or older and first hospitalized in 2010 for 3 days or more, were set up as baseline cohort (12,403). The incidence rate of AMI per 100,000 persons was 79.8 overall, and 49.6 for women and 112.3 for men. A total of 2010 (1073 men, 937 women) were newly developed with HF during 6 years following post AMI. Cumulative incidences of HF per 1000 AMI patients for a year at each time period were 37.4 in initial hospitalization, 32.3 in 1 year after discharge, and 8.9 in 1-6 years. The overall and age-specific incidence rates of HF were higher in women than men. For late-onset HF, female, medical aid, pre-existing hypertension, severity of AMI, duration of hospital stay during index admission, reperfusion treatment, and drug prescription pattern including diuretics, affected the occurrence of late-onset HF. Conclusion: With respect to late-onset HF following AMI, appropriate management including hypertension and medical aid program in addition to quality improvement of AMI treatment are required to reduce the risk of late-onset heart failure.

Effect of Rosa laevigata on PM10-Induced Inflammatory Response of Human Lung Epithelial Cells.

Particulate matter 10 (PM10) with a diameter of less than 10 mm causes inflammation and allergic reactions in the airways and lungs, which adversely affects asthmatic patients. In this study, we examined the anti-inflammatory effects of Rosa laevigata (RL), which has been previously investigated medicinally in Korea and China for the discovery of plant-derived anti-inflammatory agents with low side effects, using a PM10-induced lung inflammatory disease model. Using MTT assay, we confirmed that in A549 cells pretreated with RL, cytotoxicity induced by PM10 (100 µg/mL) exposure was attenuated. In addition, western blotting revealed that RL suppressed the expression level of MAPK/NF-κB pathways and its downstream signal, COX-2 in PM10-induced A549 cells. Moreover, real-time PCR demonstrated that RL downregulated the mRNA expression level of inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-13, and IL-17) in PM10-induced A549 cells. Based on the results of this study, RL has been shown to relieve inflammation in the lungs due to PM10 exposure. Therefore, RL may be developed as a natural remedy for respiratory diseases caused by PM10 exposure.

A Computational Approach with Biological Evaluation: Combinatorial Treatment of Curcumin and Exemestane Synergistically Regulates DDX3 Expression in Cancer Cell Lines.

DDX3 belongs to RNA helicase family that demonstrates oncogenic properties and has gained wider attention due to its role in cancer progression, proliferation and transformation. Mounting reports have evidenced the role of DDX3 in cancers making it a promising target to abrogate DDX3 triggered cancers. Dual pharmacophore models were generated and were subsequently validated. They were used as 3D queries to screen the InterBioScreen database, resulting in the selection of curcumin that was escalated to molecular dynamics simulation studies. In vitro anti-cancer analysis was conducted on three cell lines such as MCF-7, MDA-MB-231 and HeLa, which were evaluated along with exemestane. Curcumin was docked into the active site of the protein target (PDB code 2I4I) to estimate the binding affinity. The compound has interacted with two key residues and has displayed stable molecular dynamics simulation results. In vitro analysis has demonstrated that both the candidate compounds have reduced the expression of DDX3 in three cell lines. However, upon combinatorial treatment of curcumin (10 and 20 µM) and exemestane (50 µM) a synergism was exhibited, strikingly downregulating the DDX3 expression and has enhanced apoptosis in three cell lines. The obtained results illuminate the use of curcumin as an alternative DDX3 inhibitor and can serve as a chemical scaffold to design new small molecules.

Anti-Cancer Potential of Oxialis obtriangulata in Pancreatic Cancer Cell through Regulation of the ERK/Src/STAT3-Mediated Pathway.

As a plant medicine, Oxalidaceae has been used to treat various diseases in Korea. However, there is little data on the anti-cancer efficacy of Oxalidaceae, particularly O. obtriangulata. This study aimed to investigate the anti-cancer effect of O. obtriangulata methanol extract (OOE) and its regulatory actions on pancreatic carcinoma. OOE showed anti-proliferative effects and induced cell death in the colony formation and cell viability assays, respectively. The Fluorescence-activated cell sorting (FACS) data confirmed that OOE significantly induced cell cycle accumulation at the G2/M phase and apoptotic effects. Additionally, OOE inhibited the activated ERK (extracellular-signal-regulated kinase)/Src (Proto-oncogene tyrosine-protein kinase Src)/STAT3 (signal transducers and activators of transcription 3) pathways including nuclear translocation of STAT3. Furthermore, suppression of Ki67, PARP(Poly ADP-ribose polymerase), caspase-3, P27(Cyclin-dependent kinase inhibitor 1B), and c-Myc as well as the STAT3 target genes CDK(cyclin-dependent kinase)1, CDK2, Cyclin B1, VEGF-1(vascular endothelial growth factor-1), MMP-9(Matrix metallopeptidase 9), and Survivin by OOE was observed in BxPC3. We speculate that these molecular actions might support an anti-cancer effect of OOE. In this study, we demonstrated that OOE may be a promising anti-cancer material and may serve as a natural therapy and alternative remedy for pancreatic cancer treatment.

Pigmentation Effect of Rice Bran Extract in Hair Follicle-Like Tissue and Organ Culture Models.

BACKGROUND: Melanogenesis is a biological process resulting in the production of melanin pigment, which plays an important role in the prevention of sun-induced skin injury and determines the hair and skin color. Melanin has the ability to block ultraviolet radiation and scavenge free oxygen radicals, thus protecting the skin from their harmful effects. Agents that increase melanin synthesis in melanocytes may reduce the risk of photodamage and skin cancer. Hence, various approaches have been proposed to increase the synthesis of melanin. METHODS: The current study aimed to develop a three-dimensional hair follicle-like tissue (HFLT) model with human dermal papilla, melanocytes, and outer root sheaths cells. This model showed enhanced melanogenesis-related protein expression after rice bran ash extract (RBE) treatment. Next, we investigated the melanogenic effect of RBE in the HFLT and compared the results to those of hair follicle (HF) organ culture model. RESULTS: RBE was found to significantly increase the expression of microphthalmia-associated transcription factor, a key transcription factor involved in melanin production, in both HFLT and organ culture models. Results showed that melanogenesis-related protein expression levels were higher in the RBE group compared to those in the control group. Similar results were obtained by immunohistochemistry. CONCLUSION: Our data suggested that RBE promotes melanin biosynthesis. Taken together, this simple in vitro HFLT model system has the potential to provide significant insights into the underlying molecular mechanisms of HF melanogenesis, and hence can be used for controlled evaluation of the efficacy of new materials for melanogenesis.

Ophiopogonin D ameliorates DNCB-induced atopic dermatitis-like lesions in BALB/c mice and TNF-α- inflamed HaCaT cell.

Atopic dermatitis (AD) can occur in both children and adults, and the symptoms include itching and eczema, which in turn cause patients to suffer. Ophiopogonin D (OP-D) is a steroidal glycoside from Radix Ophiopogon japonicus, which is well known as an effective anti-inflammatory herbal medicine in many Asian countries. In this study, we aimed to investigate the anti-inflammatory effects of OP-D, using an AD mouse model and inflamed HaCaT cells. Through a histopathological analysis, we were able to confirm the suppressive effects of OP-D on skin thickening and the mast cell activation in AD-like mouse back skin tissues stimulated by DNCB. In addition, we detected significant decreases in cytokine expression levels through multiplex assessment assays of the OP-D-treated mice blood. We observed the anti-inflammatory effect of OP-D in the spleen, causing weight loss in the spleen and in the mRNA expression levels related to diverse cytokines. In human keratinocytes inflamed by TNF-α, OP-D inhibited p38 and ERK protein activation and showed a reduction of NF-κB nuclear translocation. Furthermore, OP-D attenuated pro-inflammatory cytokine mRNA expressions in TNF-α-inflamed HaCaT cells. Accordingly, we came to the conclusion that OP-D is a potential natural drug which can be used in order to treat inflammatory skin diseases, such as AD.

Rice Bran Ash Mineral Extract Increases Pigmentation through the p-ERK Pathway in Zebrafish (Danio rerio).

The purpose of the present study is to evaluate the effect of rice bran ash mineral extract (RBM) on pigmentation in zebrafish (Danio rerio). Melanin has the ability to block ultraviolet (UV) radiation and scavenge free oxygen radicals, thus protecting the skin from their harmful effects. Agents that increase melanin synthesis in melanocytes may reduce the risk of photodamage and skin cancer. The present study investigates the effect of RBM on pigmentation in zebrafish and the underlying mechanism. RBM was found to significantly increase the expression of microphthalmia-associated transcription factor (MITF), a key transcription factor involved in melanin production. RBM also suppressed the phosphorylation of extracellular signal-regulated kinase (ERK), which negatively regulates zebrafish pigmentation. Together, these results suggest that RBM promotes melanin biosynthesis in zebrafish.

Apoptosis and G2/M cell cycle arrest induced by a timosaponin A3 from Anemarrhena asphodeloides Bunge on AsPC-1 pancreatic cancer cells.

BACKGROUND: Timosaponin A3 (TA3), one of the active components of spirostanol saponin isolated from A. asphodeloides, is widely used as an anticancer agent in a variety of cancer cell lines. However, the research on the anticancer efficacy is very limited in human pancreatic cancer models. PURPOSE: In this study, we investigated the molecular targets in the active components of A. asphodeloides, which showed anti-cancer effects in human pancreatic cancer cells, and confirmed the pathways involved. STUDY DESIGN: The apoptotic effects of five solvent extracts of A. asphodeloides in human pancreatic cancer cells (AsPC-1) was studied, and the phytochemical leading to their effects identified. Next, we determined whether the phytochemical inhibit STAT3 and ERK1/2, and investigated the pathways involved. METHODS: Five solvent extracts of A. asphodeloides (100  µg/ml, 24  h) was investigated for their cytotoxicity against AsPC-1 cells. The active ingredient of the extract exhibiting the highest toxicity were analyzed by liquid chromatography-mass spectrometry. Next, we studied the mechanism of action of the phytochemical in pancreatic cancer. Cell cycle and annexin V/FITC assays were performed to assess cell growth and apoptosis capacity. The effects on apoptosis and proliferation-related pathways, STAT3, and MAPKs were confirmed at the protein level using immunoblotting. The factors regulated in the pathways were investigated using reverse transcription polymerase chain reaction. RESULTS: The results showed that the ethyl acetate extract of A. asphodeloides (EAA) induced apoptotic and anti-proliferative activities through the STAT3 and MAPKs pathways. We found that TA3, an active component of EAA, inhibits constitutive STAT3 and ERK1/2 proteins. EAA and TA3 decreased the viability of AsPC-1 cells, leading to cell cycle arrest at the sub-G1 and G2/M phases. Moreover, TA3 inhibited the expression of various genes encoding anti-apoptotic (Bcl-2, Bcl-xl), proliferative (Cyclin D1), metastatic (MMP-9), and angiogenic (VEGF-1) proteins. CONCLUSION: The results indicated that TA3, an active phytochemical from A. asphodeloides, could induce apoptosis and suppress cell proliferation by inhibiting the STAT3 and ERK1/2 pathways. Thus, TA3 is a candidate cancer chemotherapeutic agent instead to treat human pancreatic cancer.

Synergistic effect of rice bran extract and extremely low-frequency electromagnetic fields on dermal papilla/melanocytes in melanogenesis.

Melanocytes in hair are located around dermal papilla cells at the tip of the hair follicle. In this study, we examined the melanogenesis of a three-dimensional (3D) hair dermal papilla model treated with natural extracts and electromagnetic fields (EMFs). The 3D model involved dermal papilla-like tissue (DPLT), an aggregation of a mixture of dermal papilla cells, and melanocytes in microwells. Rice bran extract (RBE), an EMF, and RBE/EMF were applied to different DPLT groups. The LDH assay indicated no cell stress in all experimental groups, and detection of tyrosinase activity demonstrated high activity in the RBE/EMF group. Western blot analysis of the RBE, EMF, and RBE/EMF groups revealed increased MITF, TRP-1, and tyrosinase expression. In addition, the mRNA expression of ET-1, laminin, bFGF, ß-catenin, MITF, and tyrosinase was increased in the RBE/EMF group, as demonstrated by RT-qPCR analysis. HMB45 and Fontana-Masson immunostaining showed that the RBE/EMF group had the highest melanin content. Therefore, RBE and EMF may be used as a material and therapy, respectively, for the treatment of vitiligo and white hair, through activation of melanogenesis in melanocytes. Bioelectromagnetics. 39:595-603, 2018. © 2018 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc..

The therapeutic effects of Yongdamsagan-tang on autoimmune hepatitis models.

Autoimmune hepatitis (AIH) is an immunity disorder that is the result of antibodies in the liver tissue of the patient that are attacked by activated immune cells due to an unknown cause. In this study, we aimed to investigate the anti-inflammatory effect of Yongdamsagan-tang (YST) extracts and confirm effects on autoimmune hepatitis models as the therapeutic agent using the YST extracted by various solvents. YST, a mixture of 11 herbal extracts, is known in traditional Korean medicine as a widely used treatment for inflammatory diseases. We proposed the AIH-condition in vitro model by the addition of recombinant IL-17A and then observed several markers linked to AIH symptoms, including an increase of IL-6 expression, lipid accumulation, and fibrosis. In AIH-condition hepatic cell model, YST reduced IL-6 expression and lipid accumulation caused by treatment of IL-17 combination in hepatocyte cells. Also, YST blocked several activated fibrosis factors including transforming growth factor-ß (TGF- ß1), collagen type 1 (Col-α1(I)), and α-smooth muscle actin (α-SMA) in liver stellate cells. Furthermore, pretreatment with YST protected hepatic damage and reduces histological injury by suppressing apoptosis mediator and inflammatory cytokines expression in concanavalin A (Con A)-induced autoimmune hepatitis mice model. The findings here improve our understanding of YST extracted by 80% ethanol, suggesting that YST can be used as a therapeutic treatment for AIH.

Ginkgolide A ameliorates non-alcoholic fatty liver diseases on high fat diet mice.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases worldwide and has continuously increased. NAFLD refers to a spectrum of diseases ranging from fatty liver to steatohepatitis, cirrhosis, and even to hepatocyte carcinoma. Excessive fatty acid enters the cell and the mitochondria undergo stress and unremoved ROS can trigger a form of cell apoptosis known as 'lipoapoptosis'. NASH arises from damaged liver hepatocytes due to lipotoxicity. NASH not only involves lipid accumulation and apoptosis but also inflammation. Ginkgo biloba has been tested clinical trials as a traditional medicine for asthma, bronchitis and cardiovascular disease. The effects of Ginkgolide A (GA), derived from the ginkgo biloba leaf, are still unknown in NAFLD. To determine the protective effects of GA in NAFLD, we examined the fatty liver disease condition in the non-esterified fatty acid (NEFA)-induced HepG2 cell line and in a high fat diet mouse model. The findings of this study suggest that GA is non-toxic at high concentrations in hepatocytes. Moreover, GA was found to inhibit cellular lipogenesis and lipid accumulation by causing mitochondrial oxidative stress. GA showed hepatoprotective efficacy by inducing cellular lipoapoptosis and by inhibiting cellular inflammation. The results demonstrated that GA may be feasible as a therapeutic agent for NAFLD patients.

Metabolic Profiling of Liver Tissue in Diabetic Mice Treated with Artemisia Capillaris and Alisma Rhizome Using LC-MS and CE-MS.

Artemisia Capillaris (AC) and Alisma Rhizome (AR) are natural products for the treatment of liver disorders in oriental medicine clinics. Here, we report metabolomic changes in the evaluation of the treatment effects of AC and AR on fatty livers in diabetic mice, along with a proposition of the underlying metabolic pathway. Hydrophobic and hydrophilic metabolites extracted from mouse livers were analyzed using HPLC-QTOF and CE-QTOF, respectively, to generate metabolic profiles. Statistical analysis of the metabolites by PLS-DA and OPLA-DA fairly discriminated between the diabetic, and the AC- and AR-treated mice groups. Various PEs mostly contributed to the discrimination of the diabetic mice from the normal mice, and besides, DG (18:1/16:0), TG (16:1/16:1/20:1), PE (21:0/20:5), and PA (18:0/21:0) were also associated with discrimination by s-plot. Nevertheless, the effects of AC and AR treatment were indistinct with respect to lipid metabolites. Of the 97 polar metabolites extracted from the CE-MS data, 40 compounds related to amino acid, central carbon, lipid, purine, and pyrimidine metabolism, with [Formula: see text] values less than 0.05, were shown to contribute to liver dysregulation. Following treatment with AC and AR, the metabolites belonging to purine metabolism preferentially recovered to the metabolic state of the normal mice. The AMP/ATP ratio of cellular energy homeostasis in AR-treated mice was more apparently increased ([Formula: see text]) than that of AC-treated mice. On the other hand, amino acids, which showed the main alterations in diabetic mice, did not return to the normal levels upon treatment with AR or AC. In terms of metabolomics, AR was a more effective natural product in the treatment of liver dysfunction than AC. These results may provide putative biomarkers for the prognosis of fatty liver disorder following treatment with AC and AR extracts.

Anti-lipoapoptotic effects of Alisma orientalis extract on non-esterified fatty acid-induced HepG2 cells.

BACKGROUND: Liver steatosis was caused by lipid accumulation in the liver. Alisma orientale (AO) is recognized as a promising candidate with therapeutic efficacy for the treatment of nonalcoholic fatty liver disease (NAFLD). HepG2 hepatocyte cell line is commonly used for liver disease cell model. METHOD: The HepG2 cells were cultured with the NEFAs mixture (oleic and palmitic acids, 2:1 ratio) for 24 h to induce hepatic steatosis. Then different doses of Alisma orientale extract (AOE) was treated to HepG2 for 24 h. Incubated cells were used for further experiments. RESULTS: The AOE showed inhibitory effects on lipid accumulation in the Oil Red O staining and Nile red staining tests with no cytotoxicity at a concentration of 300 µg/mL. Fatty acid synthase (FASN) and acetyl-CoA carboxylase 1 (ACC1) mRNA and protein expression level were down-regulated after AOE treatment. Bcl-2 associated X protein (Bax) and c-Jun N-terminal kinase (JNK) mRNA expression level were decreased as well as p-JNK (activated form of JNK), Bax, cleaved caspase-9, caspase-3 protein expression level. Anti-apopototic B-cell lymphoma 2 (Bcl-2) protein level increased after AOE treatment. In addition, inflammatory protein expression including p-p65, p65, COX-2 and iNOS were inhibited by AOE treatment. CONCLUSION: The results suggest that AOE has anti-steatosis effects that involve lipogenesis, anti-lipoapoptosis, and anti-inflammation in the NEFA-induced NAFLD pathological cell model.

Anti-diabetic and anti-obesitic effects of aqueous extracts of Yangkyuksanhwa-tang and its two major compositions on db/db mice.

Type 2 diabetes mellitus (T2DM) is a metabolic syndrome that results from target-tissue resistance to insulin. Obesity is the condition of excess body fat accumulation. T2DM and obesity are both associated with hypertension, hyperlipidemia, and abdominal obesity. In Korean medicine, Yangkyuksanhwa-tang (YKSHT) has been prescribed for patients with T2DM. Oral glucose tolerance tests (OGTT), multiplex assays and hemoglobin A1C (HbA1C) assessments were performed to determine the anti-diabetic effects of YKSHT and two major compositions of YKSHT, Lonicera japonica Thunb. (LJT) and Rehmannia glutinosa (RG) on db/db mice, a rodent model for T2DM. To study the anti-obesitic effects of LJT, RG or YKSHT, blood profiling including the triglycerides (TGs) and the total, LDL and HDL cholesterol levels were measured. In addition, body index measures such as the liver, retroperitoneal and epididymal fat tissues were collected and weighed. Mice treated with RG or YKSHT showed reduced blood glucose levels after stimulating the plasma GLP-1 levels. The multiplex assay results support the weight-controlling effects of the LJT, RG and YKSHT treatments, showing reducing levels of ghrelin and the induction of peptide YY (PYY) secretion. The YKSHT treatment reduced plasma TG levels and increased HDL cholesterol levels. The weights of the liver, retroperitoneal and epididymal fat tissues were reduced after the YKSHT treatment. Hence, we suggest that YKSHT can be utilized for the prevention and treatment of T2DM and obesity simultaneously.

Antihyperglycemic and Antiobesity Effects of JAL2 on db/db Mice.

Lonicera japonica Thunb. (LJT) and Rehmannia glutinosa Libosch. (RGL) have been used traditionally as a herbal medicine in Korean medicine. Using LC/Q-TOF was performed to profile the two herbal medicines and the mixture of LJR and RGL (JAL2, ratio 1 : 1). We performed oral glucose tolerance test (OGTT) and plasma GLP-1 and insulin secretion by multiplex assays to investigate antidiabetic effects of LJT, RGL, and JAL2 in db/db mice, the mice model of type 2 diabetes mellitus (T2DM). Also, the antiobesity-related factors such as plasma peptide YY (PYY), triglyceride, total cholesterol, HDL, LDL, and weight of liver, epididymal, and retroperitoneal fat tissue were investigated. Through the multiplex assay, it was found that JAL2 treatment more efficiently attenuated high levels of blood glucose by stimulating GLP-1 secretion and reduced LDL concentration and weight of liver and retroperitoneal fat tissue compared to LJT or RGL treated separately. These results suggest that the JAL2 has antidiabetes and antiobesity effects in T2DM mice model.

Association between Low-level Mercury Exposure and Neurobehavioral Functions in Korean Adults Living in a Coastal City.

OBJECTIVES: The aim of this study was to determine the association between low-level mercury exposure and neurobehavioral functions in adults living in coastal regions of Korea. METHODS: We selected 172 adults aged 20-65 years living in a city in the coastal region of Korea. A sociodemographic survey was conducted, mercury levels in the blood, urine, and hair were measured, and the associations according to computerized neurobehavioral tests were determined using univariate analysis. After adjustment for associated variables, a multivariate linear regression analysis was performed. RESULTS: The geometric mean mercury levels in the blood, urine, and hair were 5.41 µg/L (range, 0.00-15.84 µg/L), 1.17 µg/g-creatinine (range, 0.00-32.86 µg/g-creatinine), and 1.37 mg/kg (range, 0.42-6.56 mg/kg), respectively. Variables that were associated with simple reaction time according to the neurobehavioral test results were age and urine mercury level. Variables associated with choice reaction time were the recent use of Korean traditional medicine and urine mercury level. Variables associated with the right-hand finger tapping speed test were age, gender, smoking behavior, education level, monthly household income, and urine mercury level. Variables associated with the left-hand finger tapping speed test were age, gender, education level, and urine mercury level. After adjustment for associated variables, there was no significant association between urine mercury level and simple reaction time (ß=25.96; p=0.47), choice reaction time (ß=50.37; p=0.32), or the number of left-hand finger taps (ß=-1.54; p=0.21). However, urine mercury level was significantly associated with the number of right-hand finger taps (ß=-3.86; p=0.01). CONCLUSIONS: We found no evidence that low-level mercury exposure in adults is associated with deficits in neurobehavioral functions. A longer follow-up study is required to confirm this conclusion.

Impact of hydrotherapy on skin blood flow: How much is due to moisture and how much is due to heat?

Hydrotherapy and whirlpool are used to increase skin blood flow and warm tissue. However, recent evidence seems to show that part of the increase in skin blood flow is not due to the warmth itself but due to the moisture content of the heat. Therefore, two series of experiments were accomplished on 10 subjects with an average age of 24.2 +/- 9.7 years and free of diabetes and cardiovascular disease. Subjects sat in a 37 degrees C hydrotherapy pool under two conditions: one in which a thin membrane protecting their skin from moisture while their arm was submerged in water and the second where their arm was allowed to be exposed to the water for 15 minutes. During this period of time, skin and body temperature were measured as well as skin blood flow by a Laser Doppler Imager. The results of the experiments showed that the vapor barrier blocked any change in skin moisture content during submersion in water, and while skin temperature was the same as during exposure to the water, the blood flow with the arm exposed to water increased from 101.1 +/- 10.4 flux to 224.9 +/- 18.2 flux, whereas blood flow increased to only 118.7 +/- 11.4 flux if the moisture of the water was blocked. Thus, a substantial portion of the increase in skin blood flow associated with warm water therapy is probably associated with moisturizing of the skin rather than the heat itself.