St. John’s Wort Regulates Proliferation and Apoptosis in MCF-7 Human Breast Cancer Cells by Inhibiting AMPK/mTOR and Activating the Mitochondrial Pathway

St. John’s Wort (SJW) has been used as an estrogen agonist in the systems affected by menopause. Also, hypericin, a bioactive compound of SJW, has been used as a photosensitizer in photodynamic therapy. In the present study, we investigate the anti-proliferative and pro-apoptotic effects of SJWto demonstrate the chemo-preventive effect in human breast cancer cells. MCF-7 cellswere culturedwith DMSO or various concentrations of SJWethanol extract (SJWE). Cell viability, proliferation, apoptosis, the expression of proteins involved in cell growth and apoptosis, and caspase-3/7 activity were examined. SJWE dose-dependently suppressed cell growth and induced apoptosis ofMCF-7 cells. Mechanistically, SJWE enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and decreased the expression of p-mammalian target of rapamycin (p-mTOR) and p-eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1). Also, SJWE inhibited the phosphorylation of protein kinase B (Akt) and showed increases in the expression of pro-apoptotic proteins Bax and Bad with decreases in the expression of anti-apoptotic proteins including B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), and p-Bcl-2-associated death promoter (p-Bad). SJWE at 50 µg/mL showed markedly enhanced caspase-7 activation. Taken together, our results provide evidence that SJWE shows anti-proliferative and pro-apoptotic effects via inhibition of AMPK/mTOR and activation of a mitochondrial pathway. Therefore, SJWE can be used as a chemo-preventive agent without photo-activation

Effect of Seyoeum on Obesity, Insulin Resistance, and Nonalcoholic Fatty Liver Disease of High-Fat Diet-Fed C57BL/6 Mice

Background. This study was performed to evaluate the effect of Seyoeum (SYE), a novel herbal meal replacement, on insulin resistance and nonalcoholic fatty liver disease (NAFLD) in obese mice fed with a high-fat diet (HFD). Methods. SYE contained six kinds of herbal powder such as Coix lacryma-jobi, Oryza sativa, Sesamum indicum, Glycine max, Liriope platyphylla, and Dioscorea batatas. Male C57BL/6 mice were divided into four groups: normal chow (NC), HFD, SYE, and HFD plus SYE (HFD + SYE). The mice in groups other than NC were fed HFD for 9 weeks to induce obesity and then were fed each diet for 6 weeks. Clinical markers related to obesity, diabetes, and NAFLD were examined and gene expressions related to inflammation and insulin receptor were determined. Results. Compared with HFD group, body weight, serum glucose, serum insulin, HOMA-IR, total cholesterol, triglyceride, epididymal fat pad weight, liver weight, and inflammatory gene expression were significantly reduced in SYE group. Insulin receptor gene expression increased in SYE group. Conclusions. Based on these results, we conclude that SYE improved obesity and insulin resistance in high-fat fed obese mice. Our findings suggest that SYE could be a beneficial meal replacement through these antiobesity and anti-insulin resistance effects

Increased interleukin-17 production via a phosphoinositide 3-kinase/Akt and nuclear factor κB-dependent pathway in patients with rheumatoid arthritis

Inflammatory mediators have been recognized as being important in the pathogenesis of rheumatoid arthritis (RA). Interleukin (IL)-17 is an important regulator of immune and inflammatory responses, including the induction of proinflammatory cytokines and osteoclastic bone resorption. Evidence for the expression and proinflammatory activity of IL-17 has been demonstrated in RA synovium and in animal models of RA. Although some cytokines (IL-15 and IL-23) have been reported to regulate IL-17 production, the intracellular signaling pathways that regulate IL-17 production remain unknown. In the present study, we investigated the role of the phosphoinositide 3-kinase (PI3K)/Akt pathway in the regulation of IL-17 production in RA. Peripheral blood mononuclear cells (PBMC) from patients with RA (n = 24) were separated, then stimulated with various agents including anti-CD3, anti-CD28, phytohemagglutinin (PHA) and several inflammatory cytokines and chemokines. IL-17 levels were determined by sandwich enzyme-linked immunosorbent assay and reverse transcription–polymerase chain reaction. The production of IL-17 was significantly increased in cells treated with anti-CD3 antibody with or without anti-CD28 and PHA (P < 0.05). Among tested cytokines and chemokines, IL-15, monocyte chemoattractant protein-1 and IL-6 upregulated IL-17 production (P < 0.05), whereas tumor necrosis factor-α, IL-1β, IL-18 or transforming growth factor-β did not. IL-17 was also detected in the PBMC of patients with osteoarthritis, but their expression levels were much lower than those of RA PBMC. Anti-CD3 antibody activated the PI3K/Akt pathway; activation of this pathway resulted in a pronounced augmentation of nuclear factor κB (NF-κB) DNA-binding activity. IL-17 production by activated RA PBMC is completely or partly blocked in the presence of the NF-κB inhibitor pyrrolidine dithiocarbamate and the PI3K/Akt inhibitor wortmannin and LY294002, respectively. However, inhibition of activator protein-1 and extracellular signal-regulated kinase 1/2 did not affect IL-17 production. These results suggest that signal transduction pathways dependent on PI3K/Akt and NF-κB are involved in the overproduction of the key inflammatory cytokine IL-17 in RA

Red pepper seed water extract inhibits preadipocyte differentiation and induces mature adipocyte apoptosis in 3T3-L1 cells

BACKGROUND/OBJECTIVES: Reducing the number of adipocytes by inducing apoptosis of mature adipocytes as well as suppressing differentiation of preadipocytes plays an important role in preventing obesity. This study examines the anti-adipogenic and pro-apoptotic effect of red pepper seed water extract (RPS) prepared at 4°C (RPS4) in 3T3-L1 cells. MATERIALS/METHODS: Effect of RPS4 or its fractions on lipid accumulation was determined in 3T3-L1 cells using oil red O (ORO) staining. The expressions of AMP-activated protein kinase (AMPK) and adipogenic associated proteins [peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding proteins α (C/EBP α), sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC)] were measured in 3T3-L1 cells treated with RPS4. Apoptosis and the expression of Akt and Bcl-2 family proteins [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad), Bcl-2 like protein 4 (Bax), Bal-2 homologous antagonist/killer (Bak)] were measured in mature 3T3-L1 cells treated with RPS4. RESULTS: Treatment of RPS4 (0-75 ug/mL) or its fractions (0-50 ug/mL) for 24 h did not have an apparent cytotoxicity on pre and mature 3T3-L1 cells. RPS4 significantly suppressed differentiation and cellular lipid accumulation by increasing the phosphorylation of AMPK and reducing the expression of PPAR-γ, C/EBP α, SREBP-1c, FAS, and ACC. In addition, all fractions except ethyl acetate fraction significantly suppressed cellular lipid accumulation. RPS4 induced the apoptosis of mature adipocytes by hypophosphorylating Akt, increasing the expression of the pro-apoptotic proteins, Bak, Bax, and Bad, and reducing the expression of the anti-apoptotic proteins, Bcl-2 and p-Bad. CONCLUSIONS: These finding suggest that RPS4 can reduce the numbers as well as the size of adipocytes and might useful for preventing and treating obesity

The Korean urban rural elderly cohort study: study design and protocol

BACKGROUND: Korea is one of the fastest aging countries and is expected to become a super-aged society within 12 years. The Korean Urban Rural Elderly (KURE) study was developed to evaluate the epidemiological characteristics and establish the prevention and management of major disorders of the elderly in Korea. METHODS/DESIGN: The KURE study is a community-based prospective cohort study on health, aging, and common geriatric disorders of Korean elderly persons aged at least 65 years. To construct a cohort reflecting both urban and rural areas, we selected 2 representative communities in the country. To establish multidisciplinary approaches to geriatric health, this study was performed by researchers in the divisions of geriatrics, preventive medicine, endocrinology, and sociology. The baseline examinations began in 2012; the study will follow more than 4,000 elderly Koreans over 10 years. The first and second follow-up health examinations will be performed every 4 years. Every 2 years after each health examination, inter-assessment interview will be conducted to improve participant retention. DISCUSSION: The KURE study will provide longitudinal epidemiologic data on health, aging, and common geriatric disorders of the elderly in Korea. This is a comprehensive, multidisciplinary study of the elderly with respect to biological, physical, socio-economic, and environmental factors. The results of this study will contribute to improve public health and welfare policies for the aging society in Korea

Relationship between theory of planned behavior factors and optimistic bias and vegetable and fruit intake in college students.

The purpose of this study is to verify the validity of the theory of planned behavior on the vegetable and fruit consumption behavior of college students and to explore the influence of the theory of planned behavior variables on the vegetable and fruit consumption behavior and the role of optimism bias in the relationship. The participants in this study were 249 college students (male: 107, female: 142), and their average age was 20.57 (SD = 2.14) years. In this study, we used a vegetable and fruit consumption frequency list based on Korean nutritional intake standards, the Fruit and Vegetable Module questionnaire, and a questionnaire measuring attitudes toward vegetable and fruit consumption, subjective norms, perceived behavioral control and intention, and optimistic bias. As a result of the analysis, it was verified that it was appropriate to adopt the theory of planned behavior model, which includes a direct path from perceived behavioral control to vegetable and fruit consumption behavior. In hierarchical regression analysis, the Theory of Planned Behavior variables explained about 28.8% of vegetable and fruit consumption behavior, and perceived behavioral control was the strongest predictor, and optimism bias accounted for an additional 1.9% of vegetable and fruit consumption behavior. appeared to explain it. In addition, optimistic bias moderated the relationship between attitude toward vegetable and fruit consumption and vegetable and fruit consumption behavior. Considering the results, it is reasonable to explain vegetable and fruit consumption behavior with the theory of planned behavior, and it was found that optimistic bias plays an important role in the relationship between attitudes toward vegetable and fruit consumption and vegetable and fruit consumption behavior.

Lung cancer with superior vena cava syndrome diagnosed by intravascular biopsy using EBUS-TBNA

AbstractSince superior vena cava syndrome (SVCS) is a critical condition, immediate diagnostic approach and therapy are imperative to avoid potentially life-threatening complications. Here, we report a case of lung cancer with SVCS, which was diagnosed through intravascular tumor biopsy using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). EBUS-TBNA enabled us to obtain tissue sufficient for diagnosis, without significant complications. Prompt diagnosis was followed by appropriate anticancer treatment and improvement in the symptoms. For patients suspected of SVCS and requiring prompt pathologic diagnosis, we can consider EBUS-TBNA to diagnose intravascular or mediastinal tumors and provide an accurate diagnosis

A case of dermatomyositis in a patient with central core disease: unusual association with autoimmunity and genetic muscle disease

Background Dermatomyositis is an inflammatory muscle disease caused by immune-mediated muscle injury, and central core disease (CCD) is a congenital myopathy associated with disturbed intracellular calcium homeostasis and excitation-contraction coupling. To date, CCD has not been reported to have autoantibodies or coexist with inflammatory myopathy. Case presentation Here, we described the case of a 25-year-old woman who had progressive proximal muscle weakness, myalgia, pruritic macular rash, skin ulcers, and calcinosis. Dermatomyositis was initially suspected based on the clinical symptoms accompanied by elevated muscle enzyme levels, electromyography abnormalities, and a positive antinuclear antibody test. However, the patients muscle biopsy revealed the characteristic findings of both dermatomyositis and CCD, suggesting that dermatomyositis occurred in this patient with previously asymptomatic CCD. The patient did not have any pathogenic gene mutations associated with congenital myopathy, including RYR1 and SEPN1 in targeted next-generation sequencing. She received high-dose glucocorticoid therapy and azathioprine with a significant improvement in muscle strength. Conclusions We present a case of rare coexistence of dermatomyositis and CCD. Clinicians should be aware that patients with CCD may have inflammatory myopathy that responds well to immunosuppressive therapy.This study was funded by a grant from the Ministry of Science, ICT, and Future Planning (NRF-2020M3E5E2037430 to Y-W.S.)