Exercise affects high-fat diet-stimulated breast cancer metastasis through irisin secretion by altering cancer stem cell properties.

Background: Regular physical activities reduce the growth of breast cancer, but research on the effects of steady exercise on metastasis and its mechanisms is limited. In this study, the effects of steady exercise on breast cancer metastasis and its possible mechanism were demonstrated. Methods: Experimental metastasis was induced after 8 weeks of steady exercise using a mouse model. Furthermore, one of the myokines, irisin, was studied to elucidate the effects of metastasis-regulating protein expression, and colony and sphere formation, which are cancer stem cell properties. Results: Low- and moderate-intensity exercise significantly reduced the number and volume of metastasized tumors. Among myokines, only irisin was significantly increased by steady exercise but decreased by a high-fat diet. In vitro studies, irisin significantly decreased the number of colonies and sphere formation. Irisin also inhibited cell migration and invasion and suppressed the malignancy of breast cancer cells by reducing the expression of vimentin, MMP-2, MMP-9, and HIF-1 and by increasing the expression of TIMP-1 and TIMP-2. Conclusion: Steady exercise modulates myokine secretions and among them, irisin suppresses breast cancer metastasis by decreasing self-renewal properties and invasion regulating protein expressions. Thus, regular exercise may be beneficial in the prevention of breast tumor metastasis.

A single-ion conducting covalent organic framework for aqueous rechargeable Zn-ion batteries.

Despite their potential as promising alternatives to current state-of-the-art lithium-ion batteries, aqueous rechargeable Zn-ion batteries are still far away from practical applications. Here, we present a new class of single-ion conducting electrolytes based on a zinc sulfonated covalent organic framework (TpPa-SO3Zn0.5) to address this challenging issue. TpPa-SO3Zn0.5 is synthesised to exhibit single Zn2+ conduction behaviour via its delocalised sulfonates that are covalently tethered to directional pores and achieve structural robustness by its ß-ketoenamine linkages. Driven by these structural and physicochemical features, TpPa-SO3Zn0.5 improves the redox reliability of the Zn metal anode and acts as an ionomeric buffer layer for stabilising the MnO2 cathode. Such improvements in the TpPa-SO3Zn0.5-electrode interfaces, along with the ion transport phenomena, enable aqueous Zn-MnO2 batteries to exhibit long-term cyclability, demonstrating the viability of COF-mediated electrolytes for Zn-ion batteries.

Study on Consumer Exposure to Sun Spray and Sun Cream in South Korea.

When conducting risk assessments of cosmetic ingredients, it is important that reliable exposure information is obtained for cosmetic products. As cosmetics are becoming more diverse, continuous effort must be made to obtain exposure data that reflect their growth and usage trends. The usage pattern of cosmetics, such as the application area and amount used, may differ by product type and also by country. We conducted a survey to compare the amount of sun spray and sun cream used in a usage environment in South Korea. The study was conducted on Haeundae Beach, one of the most popular beaches in South Korea. A total of 1,255 beachgoers participated in this study; 604 and 651 participants used the sun spray and sun cream, respectively, while sunbathing and enjoying water activities on the beach for one day. Exposure was analyzed following a probabilistic method. On comparing all subjects, it was found that the group that used sun spray (mean: 44.52 g/day) used significantly more product (p = 0.000) than those who used sun cream (mean: 20.51 g/day). By analyzing the daily exposure of sun spray and sun cream per unit body weight according to age and gender, the exposure amount of sun spray and sun cream was found to be highest among 2~9 year-old girls (mean for sun spray: 2.51 g/kg/day, p95: 5.50 g/kg/day, mean for sun cream: 0.79 g/kg/day, p95: 1.79 g/kg/day). The amount of sun spray used is approximately twice that of sun cream. Among both the sun spray and sun cream groups, the exposure amount per unit body weight was highest in girls younger than 10. These factors should be considered when conducting risk assessments of sun spray and sun cream.

Solvent-Free, Single Lithium-Ion Conducting Covalent Organic Frameworks.

Porous crystalline materials such as covalent organic frameworks and metal-organic frameworks have garnered considerable attention as promising ion conducting media. However, most of them additionally incorporate lithium salts and/or solvents inside the pores of frameworks, thus failing to realize solid-state single lithium-ion conduction behavior. Herein, we demonstrate a lithium sulfonated covalent organic framework (denoted as TpPa-SO3Li) as a new class of solvent-free, single lithium-ion conductors. Benefiting from well-designed directional ion channels, a high number density of lithium-ions, and covalently tethered anion groups, TpPa-SO3Li exhibits an ionic conductivity of 2.7 × 10-5 S cm-1 with a lithium-ion transference number of 0.9 at room temperature and an activation energy of 0.18 eV without additionally incorporating lithium salts and organic solvents. Such unusual ion transport phenomena of TpPa-SO3Li allow reversible and stable lithium plating/stripping on lithium metal electrodes, demonstrating its potential use for lithium metal electrodes.

Small leucine zipper protein functions as a negative regulator of estrogen receptor α in breast cancer.

The nuclear transcription factor estrogen receptor α (ERα) plays a critical role in breast cancer progression. ERα acts as an important growth stimulatory protein in breast cancer and the expression level of ERα is tightly related to the prognosis and treatment of patients. Small leucine zipper protein (sLZIP) functions as a transcriptional cofactor by binding to various nuclear receptors, including glucocorticoid receptor, androgen receptor, and peroxisome proliferator-activated receptor γ. However, the role of sLZIP in the regulation of ERα and its involvement in breast cancer progression is unknown. We found that sLZIP binds to ERα and represses the transcriptional activity of ERα in ERα-positive breast cancer cells. sLZIP also suppressed the expression of ERα target genes. sLZIP disrupted the binding of ERα to the estrogen response element of the target gene promoter, resulting in suppression of cell proliferation. sLZIP is a novel co-repressor of ERα, and plays a negative role in ERα-mediated cell proliferation in breast cancer.

Effect of a Traditional Herbal Prescription, Kyung-Ok-Ko, on Male Mouse Spermatogenic Ability after Heat-Induced Damage.

Kyung-Ok-Ko (KOK), a well-known traditional Korean medicinal formula, has long been used to invigorate the essential qi. This use of KOK may be associated with reproductive ability as a more modern concept. The protective effect of KOK was evaluated against deterioration of testicular function induced by heat exposure in male mice. Male fertility was disrupted by scrotal heat stress at 43°C for 5 weeks. KOK (0.25, 0.50, and 2.00 g/kg/day) was administered orally at 3 h after the stress. To evaluate the protective effect of KOK, body weight, testicular weight, sperm count, sperm motility, and histopathological changes in the testes were evaluated. KOK-treated mice significantly recovered their general health, as evidenced by body weight. KOK-treated mice also showed significantly higher testes weights, sperm counts, and sperm motility than did the heat stress group. KOK-treated mice significantly recovered the morphological appearance of the seminiferous tubules and seminiferous epithelium. Furthermore, KOK-treated mice significantly increased antioxidant enzyme activities and reduced the protein expressions of apoptosis in the testes. KOK significantly protects against heat-induced damage to testicular function in male mice by inhibiting oxidative stress and apoptosis, indicating that KOK may be an effective agent for treatment of heat-induced male infertility.

14-3-3ß and γ differentially regulate peroxisome proliferator activated receptor γ2 transactivation and hepatic lipid metabolism.

Peroxisome proliferator activated receptor (PPAR) γ2 plays important roles in glucose and lipid metabolism in hepatocytes. PPARγ2 is involved in metabolic disorders, including obesity, diabetes, and fatty liver disease. Although the 14-3-3 proteins participate in a variety of cell signal pathways, the roles of the 14-3-3 proteins in regulating PPARγ2 transactivation and hepatic lipid metabolism are unknown. We identified 14-3-3ß and γ as PPARγ2 transcriptional regulators. We found that 14-3-3ß and γ competitively interacted with the phosphorylated Ser273 of PPARγ2, which is important for regulating glucose and lipid metabolism. 14-3-3ß increased the transcriptional activity of PPARγ2 and enhanced the expression levels of PPARγ2 target genes involved in lipogenesis and lipid transport. In contrast, 14-3-3γ decreased PPARγ2 transactivation and reduced the expression levels of PPARγ2 target genes. A high concentration of free fatty acids increased PPARγ2 expression and lipid accumulation. 14-3-3ß enhanced hepatic lipogenesis, which is a major symptom of non-alcoholic fatty liver disease. However, 14-3-3γ suppressed hepatic lipid accumulation in the presence of high free fatty acids. These findings indicate that 14-3-3ß and γ are novel PPARγ2 regulators and are involved in hepatic lipid metabolism. 14-3-3ß and γ can be therapeutic target molecules to treat non-alcoholic fatty liver disease.

The role of heat shock protein 90 in migration and proliferation of vascular smooth muscle cells in the development of atherosclerosis.

The molecular chaperone heat shock protein 90 (HSP90) is overexpressed in plaques of atherosclerosis patients, and is associated with plaque instability. However, the role of HSP90 in atherosclerosis remains unclear. The present study investigated the effects of HSP90 inhibition on migration and proliferation of vascular smooth muscle cells (VSMCs) and involvement in atherosclerosis. To examine the role of HSP90 in VSMC migration, VSMCs were treated with the specific HSP90 inhibitors, 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) and STA-9090. Results of a chemotaxis assay showed that the HSP90 inhibitors suppress migration of VSMCs. HSP90 inhibition also prevented invasion and sprout formation of VSMCs via inhibition of matrix metalloproteinase-2 proteolytic activity. Results of a flow cytometric analysis showed that HSP90 inhibition induces cell cycle arrest via regulation of cyclin D3, PCNA and pRb. To investigate the role of HSP90 in the development of atherosclerosis, low-density lipoprotein receptor (LDLR) deficient mice were fed with a high cholesterol diet for 4weeks and treated with 17-AAG for 8weeks. HSP90 inhibition suppressed migration of VSMCs into atherosclerotic plaque lesions in high cholesterol diet-stimulated LDLR(-/-) mice. Inhibition of HSP90 attenuates formation of atherosclerotic plaques via suppression of VSMC migration and proliferation, indicating that HSP90 inhibitors can be used as therapeutic agents for atherosclerosis and in stent restenosis.