Ho-Yeon Chung

Inhibition of NF-κB prevents high glucose-induced proliferation and plasminogen activator inhibitor-1 expression in vascular smooth muscle cells

Recent epidemiologic studies clearly showed that early intensive glucose control has a legacy effect for preventing diabetic macrovascular complications. However, the cellular and molecular processes by which high glucose leads to macrovascular complications are poorly understood. Vascular smooth muscle cell (VSMC) dysfunction due to high glucose is a characteristic of diabetic vascular complications. Activation of nuclear factor-κB (NF-κB) may play a key role in the regulation of inflammation and proliferation of VSMCs. We examined whether VSMC proliferation and plasminogen activator inhibitor-1 (PAI-1) expression induced by high glucose were mediated by NF-κB activation. Also, we determined whether selective inhibition of NF-κB would inhibit proliferation and PAI-1 expression in VSMCs. VSMCs of the aorta of male SD rats were treated with various concentrations of glucose (5.6, 11.1, 16.7, and 22.2 mM) with or without an inhibitor of NF-κB or expression of a recombinant adenovirus vector encoding an IκB-α mutant (Ad-IκBαM). VSMC proliferation was examined using an MTT assay. PAI-1 expression was assayed by real-time PCR and PAI-1 protein in the media was measured by ELISA. NF-κB activation was determined by immunohistochemical staining, NF-κB reporter assay, and immunoblotting. We found that glucose stimulated VSMC proliferation and PAI-1 expression in a dose-dependent manner up to 22.2 mM. High glucose (22.2 mM) alone induced an increase in NF-κB activity. Treatment with inhibitors of NF-κB such as MG132, PDTC or expression of Ad-IκB-αM in VSMCs prevented VSMC proliferation and PAI-1 expression induced by high glucose. In conclusion, inhibition of NF-κB activity prevented high glucose-induced VSMC proliferation and PAI-1 expression.

The effects of A. senticosus supplementation on serum lipid profiles, biomarkers of oxidative stress, and lymphocyte DNA damage in postmenopausal women

This study examined the effects of Acanthopanax senticosus supplementation on serum lipid profiles, biomarkers of oxidative stress, and lymphocyte DNA damage in postmenopausal women. Forty postmenopausal women, ages 40-65, were randomly divided into two groups: (1) control group (calcium) and (2) treatment group (calcium plus A. senticosus). Both groups were treated for 6 months. Blood samples were obtained before and after supplementation at 6 months. The following blood parameters were measured: serum total cholesterol, triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), serum malondialdehyde (MDA), ccdd protein-carbonyl (PC) levels, the degree of lymphocyte DNA damage by comet assay, total ferric reducing antioxidant power (FRAP), uric acid, and total bilirubin in serum. The treatment group had significant decreases (p<0.001) in serum LDL (127.54+/-29.79mg/dL vs 110.33+/-22.26mg/dL) and the LDL/HDL ratio (2.40+/-0.65 vs 2.11+/-0.58) after A. senticosus supplementation. Serum MDA concentrations decreased by 2.2% in the control group and by 12.61% in the treatment group after 6 months of intervention; however, the reductions were not significant in either group. Protein-carbonyl levels and lymphocyte DNA damage decreased significantly (p<0.001 and p<0.05, respectively) after 6 months of A. senticosus supplementation. These results suggest that A. senticosus supplementation may have beneficial effects against oxidative stress and improve serum lipid profiles without subsequent side effects.

Bisphenol A reduces differentiation and stimulates apoptosis of osteoclasts and osteoblasts.

AIMS Bisphenol A (BPA), a major component of epoxy resins used in protective coatings, is a known endocrine-disrupting chemical. BPA has the ability of binding to estrogen receptors. In the current paper, we examine the direct effects of bisphenol A on in vitro osteoclast and osteoblast culture systems. MAIN METHODS We evaluated the effects of BPA on osteoclast formation using bone marrow-derived macrophages and RAW 264.7 cells and on osteoblast differentiation using MC3T3-E1 cells. KEY FINDINGS BPA significantly inhibited RANKL-induced, TRAP-positive multinucleated cell formation in bone marrow-derived macrophages and RAW 264.7 cell cultures in a dose-dependent manner (0.5 μM to 12.5 μM). We observed suppression of ERK, JNK, AKT, and p38 mitogen-activated protein kinases induced by RANKL in Western blotting after BPA treatment in RAW 264.7 cells. Furthermore, BPA suppressed Bcl-2 (anti-apoptotic) while stimulating Bax (pro-apoptotic) protein expression in RAW 264.7 cells. Bisphenol A also significantly suppressed ALP activities and bone nodule formation in MC3T3-E1 cell cultures. Specifically, the expression of Bcl-2 protein was decreased, and changes in expression of caspases 3, 8, and 9 were detected by BPA treatment in both cells. SIGNIFICANCE We found that bisphenol A directly suppressed both osteoclastic and osteoblastic activities in vitro. Our data suggest that bisphenol A suppresses cell differentiation and survival.

Validation of a New Food Frequency Questionnaire for Assessment of Calcium and Vitamin D Intake in Korean Women

Background Validated simple calcium questionnaires are available to assess the intake of calcium and vitamin D in western countries, but they are not appropriate for Koreans since dairy products are not the major source of calcium and vitamin D in Korea. Thus, the objective of the present study was to develop and validate a simple and easy food frequency questionnaire (FFQ) of calcium and vitamin D for Korean. Methods Two hundred and fifty-six women were asked to complete the validated FFQ used by the Korean National Health and Nutrition Examination Survey (KNHANES) and a newly developed FFQ, the Korean Calcium Assessment Tool (KCAT), which contain the 7 food groups with 24 categories of 45 food items that are consumed frequently by Koreans. Results Calcium intake was not significantly different between the two methods; Pearsons correlation coefficient of 0.98 indicated a positive correlation, and Cohens kappa coefficient of 0.78 indicated the subjects were correctly classified. Bland-Altman plot also showed that the mean differences of the calcium intake as assessed by the two methods were in high agreement. However, the vitamin D intake assessed by KCAT was significantly higher than that assessed by the FFQ used in KNHANES. The vitamin D intakes as assessed by the two methods were positively correlated but the two methods were in moderate agreement. Conclusions The results suggested that the newly developed KCAT was a valid tool for assessing the calcium intake in Korean women, but it might overestimate the vitamin D intake.

Efficacy of risedronate with cholecalciferol on 25‐hydroxyvitamin D level and bone turnover in Korean patients with osteoporosis

Background  We performed a randomized, double‐blind, prospective, 16‐week clinical trial to evaluate the efficacy and safety of risedronate with and without cholecalciferol on 25‐hydroxyvitamin D [25(OH)D] levels and bone markers in Korean patients with osteoporosis.

Serum Bisphenol A Concentration in Postmenopausal Women with Osteoporosis

Objectives Bishphenol A (BPA) is a representative endocrine disruptor and is also known as a xenoestrogen. The objective of the present study is to investigate how many patients are exposed to BPA and to analyze the relationships between serum BPA concentration, bone mineral density (BMD) and biochemical bone markers in postmenopausal women with osteoporosis. Methods Total 51 patients were enrolled for measuring BPA and clinical variables including BMD and bone markers. The relationship between BPA and clinical variables were analyzed by the Pearsons correlation test and the Kruskal-Wallis test. Serum BPA concentration was measured by enzyme linked immunosorbent assay (ELISA). Results BPA was detected in all samples. The mean BPA concentration was 1.44 ± 0.52 ng/mL. There was no statistically significant correlation between BPA and clinical variables. Conclusion There was no statistical significance between serum BPA concentration and clinical variables related to bone metabolism. To clarify the effect of BPA on bone metabolism, further large scaled and high risk group investigation may be needed.

Fulminant Type 1 diabetes mellitus associated with acute hepatitis A.

can improve glycaemia safely as well as quality of life in patients on TPN [12,16]. Formal guidelines in this area remain limited. Acknowledging the absence of clinical trials testing the effect of glycaemic control on outcomes in patients on TPN, CSII is an option for glycaemic control. We suggest that clinicians consider the possibility of primary adrenal insufficiency and other endocrine gland involvement in patients with Gardner’s syndrome. As there are no guidelines to guide therapy with CSII in this setting, clinical trials are needed that compare insulin regimes or glycaemic targets with respect to clinical outcomes. In the meantime, CSII provides an option for glycaemic control in complex TPN-dependent patients.

Effects of C-reactive protein on bone cells.

AIMS Inflammatory processes are involved in bone remodeling. C-reactive protein (CRP) is an acute phase reactant that reflects different degrees of inflammation. Accumulating evidence suggests that CRP is an inflammatory marker and a direct cause of disease. Therefore, we examined the direct effects of CRP on bone cells. MAIN METHODS We used RAW 264.7 cells to evaluate the direct effects of CRP on osteoclast differentiation. We carried out alkaline phosphatase (ALP) and bone nodule formation assays using MC3T3-E1 cells to evaluate osteoblast differentiation. Expression of osteoclast-specific and osteoblast-specific genes and effects on cell signaling pathways associated with cell differentiation were analyzed by reverse transcription polymerase chain reaction and Western blotting. KEY FINDINGS CRP significantly and dose-dependently inhibited TRAP-positive multinucleated cell formation in RANKL-induced RAW 264.7 cell cultures. We observed suppression of p38, ERK and AKT mitogen-activated protein kinases induced by RANKL in Western blots after CRP treatment of RAW 264.7 cells. CRP also suppressed ALP activity and mineralization by Alizarin red S staining of MC3T3-E1 cell cultures. CRP suppressed osteoclast-specific and osteoblast-specific genes. Furthermore, CRP increased interferon beta (IFN-β) mRNA expression and protein levels in RAW 264.7 and MC3T3-E1 cells, and these effects were suppressed by oxPAPC, an inhibitor of Toll-like receptor (TLR) signaling. SIGNIFICANCE These data indicated that CRP may have a direct role on osteoclast and osteoblast differentiation via TLR signaling pathways.

Fulminant Type 1 diabetes in a pregnant woman as an initial manifestation of the insulin autoimmune syndrome.

Diabet. Med. 29, 1335–1338 (2012)

Compound K attenuates glucose intolerance and hepatic steatosis through AMPK-dependent pathways in type 2 diabetic OLETF rats

Background/Aims Non-alcoholic fatty liver disease is associated with insulin resistance. Compound K (CK) is the final metabolite of panaxadiol ginsenosides that have been shown to exert antidiabetic effects. However, the molecular mechanism of the antidiabetic effects in the liver have not been elucidated; further, whether CK has beneficial effects in hepatosteatosis remains unclear. Therefore, we evaluated the effect of CK on hepatosteatosis as well as its mechanism in high-fat diet (HFD)-fed type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Methods Twenty-four-week-old male OLETF rats were assigned to four groups: control (saline), CK 10 mg/kg, CK 25 mg/kg, or metformin 300 mg/kg (positive control); all treatments were administered orally for 12 weeks. Results Fasting glucose levels of the CK25 group were significantly lower than those of the control group during the 12 weeks. The results of the oral glucose tolerance test showed that both the glucose concentration after glucose loading and the fasting insulin levels of the CK25 group were significantly lower than those of the control. Hepatosteatosis was significantly improved by CK25. CK25 and metformin significantly increased the phosphorylation of hepatic adenosine monophosphate-activated protein kinase (AMPK). CK25 significantly inhibited the expression of sterol regulatory element-binding protein-1c and fatty acid synthase, while upregulating that of peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase-1. Conclusions CK improved glucose intolerance and hepatosteatosis in HFD-fed OLETF rats through AMPK activation, which has dual mode of action that involves decreasing the synthesis of fatty acids and increasing fatty acid oxidation.