Density Functional Theory Approach to Interpret Elastowetting of Hydrogels.

Sessile hydrogel drops on rigid surfaces exhibit a wetting/contact morphology intermediate between liquid drops and glass spheres. Using density functional theory, we reveal the contact forces acting between a hydrogel and a rigid glass surface. We show that while transitioning from liquid-like to solid-like hydrogels, there exists a critical hydrogel elasticity that enables a switch from attractive-to-repulsive interaction with the underlying rigid glass surface. Our theoretical model is validated by experimental observations of sessile polyacrylamide hydrogels of varying elasticity on glass surfaces. Further, the proposed model successfully approaches Young's law in the pure liquid limit and work of adhesion in the glassy limit. Lastly, we show a modified contact angle relation, taking into account the hydrogel elasticity to explain the features of a distinct hydrogel foot.

Flexible hydrogels connecting adhesion and wetting.

Raindrops falling on window-panes spread upon contact, whereas hail can cause dents or scratches on the same glass window upon contact. While the former phenomenon resembles classical wetting, the latter is dictated by contact and adhesion theories. The classical Young-Dupre law applies to the wetting of pure liquids on rigid solids, whereas conventional contact mechanics theories account for rigid-on-soft or soft-on-rigid contacts with small deformations in the elastic limit. However, the crossover between adhesion and wetting is yet to be fully resolved. The key lies in the study of soft-on-soft interactions with material properties intermediate between liquids and solids. In this work, we translate adhesion to wetting by experimentally probing the static signature of hydrogels in contact with soft PDMS of varying elasticity of both the components. Consequently, we probe this transition across six orders of magnitude in terms of the characteristic elasto-adhesive parameter of the system. In doing so, we reveal previously unknown phenomenology and a theoretical model which smoothly bridges adhesion of glass spheres with total wetting of pure liquids on any given substrate.

Reduced Pressure Drop in Viscoelastic Polydimethylsiloxane Wall Channels.

Polydimethylsiloxane (PDMS) is an important viscoelastic material that finds applications in a large number of engineering systems, particularly lab-on-chip microfluidic devices built with a flexible substrate. Channels made of PDMS, used for transporting analytes, are integral to these applications. The PDMS viscoelastic nature can induce additional hydrodynamic contributions at the soft wall/fluid interface compared to rigid walls. In this research, we investigated the pressure drop within PDMS channels bounded by rigid tubes (cellulose tubes). The bulging effect of the PDMS was limited by the rigid tubes under flowing fluids. The PDMS viscoelasticity was modulated by changing the ratio of the base to the cross-linker from 10:1 to 35:1. We observed that the pressure drop of the flowing fluids within the channel decreased with the increased loss tangent of the PDMS in the examined laminar regime [Reynolds number (Re) ∼ 23-58.6 for water and Re ∼ 0.69-8.69 for glycerol solution]. The elastic PDMS 10:1 wall channels followed the classical Hagen Poiseuille's equation, but the PDMS walls with lower cross-linker concentrations and thicker walls decreased pressure drops. The friction factor (f) for the PDMS channels with the two working fluids could be approximated as f = 47/Re. We provide a correlation between the pressure drop and PDMS viscoelasticity based on experimental findings. In the correlation, the loss tangent predominates; the larger the loss tangent, the smaller is the pressure drop. The research findings appear to be unexpected if only considering the energy dissipation of viscoelastic PDMS walls. We attributed the reduction in the pressure drop to a lubricating effect of the viscoelastic PDMS walls in the presence of the working fluids. Our results reveal the importance of the subtle diffusion of the residual oligomers and water from the bulk to the soft wall/fluid interface for the observed pressure drop in soft wall channels.

Viscoelastic tribopairs in dry and lubricated sliding friction.

Soft contacts present different tribological responses compared to stiff materials, especially when soft materials exhibit viscoelastic behaviour, as viscoelastic materials have intermediate mechanical properties between viscous liquids and elastic solids. In this work, we investigated the influence of viscoelasticity of soft materials on sliding friction in dry and lubricated conditions. To achieve this, soft tribopairs with varying viscoelasticity were obtained by tuning the weight ratios of polydimethylsiloxane (PDMS) base and curing agent. The real-time friction force and preload were observed over multiple conditions, with systematic control of lubricant viscosity, preload, and sliding velocity. Tribopairs with a higher proportion of viscous character had more oscilliations in the friction force. They also presented a higher friction coefficient due to the increased contribution of viscoelastic hysteresis losses on friction. Through regression analysis, the models of the friction coefficient were found, which are in good agreement with experimental results. From the models, we found that in both dry and lubricated conditions, viscoelasticity of tribopairs, indicated as the loss modulus or loss tangent, plays a key role in determining the friction coefficient. This influence is particularly significant for dry contacts due to the direct interactions between surfaces of tribopairs. This study provides empirical proof and a focused analysis on the role of viscoelasticity in tribological contacts.

Non-intrinsic ATP-binding cassette proteins ABCI19, ABCI20 and ABCI21 modulate cytokinin response at the endoplasmic reticulum in Arabidopsis thaliana.

KEY MESSAGE: The non-intrinsic ABC proteins ABCI20 and ABCI21 are induced by light under HY5 regulation, localize to the ER, and ameliorate cytokinin-driven growth inhibition in young Arabidopsis thaliana seedlings. The plant ATP-binding cassette (ABC) I subfamily (ABCIs) comprises heterogeneous proteins containing any of the domains found in other ABC proteins. Some ABCIs are known to function in basic metabolism and stress responses, but many remain functionally uncharacterized. ABCI19, ABCI20, and ABCI21 of Arabidopsis thaliana cluster together in a phylogenetic tree, and are suggested to be targets of the transcription factor ELONGATED HYPOCOTYL 5 (HY5). Here, we reveal that these three ABCIs are involved in modulating cytokinin responses during early seedling development. The ABCI19, ABCI20 and ABCI21 promoters harbor HY5-binding motifs, and ABCI20 and ABCI21 expression was induced by light in a HY5-dependent manner. abci19 abci20 abci21 triple and abci20 abci21 double knockout mutants were hypersensitive to cytokinin in seedling growth retardation assays, but did not show phenotypic differences from the wild type in either control medium or auxin-, ABA-, GA-, ACC- or BR-containing media. ABCI19, ABCI20, and ABCI21 were expressed in young seedlings and the three proteins interacted with each other, forming a large protein complex at the endoplasmic reticulum (ER) membrane. These results suggest that ABCI19, ABCI20, and ABCI21 fine-tune the cytokinin response at the ER under the control of HY5 at the young seedling stage.

The Role of Fucoidans Isolated from the Sporophylls of Undaria pinnatifida against Particulate-Matter-Induced Allergic Airway Inflammation: Evidence of the Attenuation of Oxidative Stress and Inflammatory Responses.

Ambient particulate matter (PM) is a critical environment pollutant that promotes the onset and aggravation of respiratory diseases such as asthma through airway inflammation and hypersecretion of mucus. In this study, we aimed to identify the effects of fucoidans isolated from sporophylls of Undaria pinnatifida on asthma symptoms such as the inflammatory response and mucus secretion using a mouse model. Balb/c mice, intraperitoneally sensitized with ovalbumin (OVA, 10 µg) dissolved in 200 µL saline and 2 mg Al(OH)3, were exposed to PM (5 mg/m3) for 7 consecutive days. In parallel, along with PM exposure, we orally administrated fucoidans (100, 400 mg/Kg) or prednisone (5 mg/Kg), an anti-inflammatory drug. We found that oral administration of fucoidans significantly attenuated PM-induced lipid peroxidation and infiltration of inflammatory cells like F4/80+ macrophages, Gr-1+ granulocytes, and CD4+ T lymphocytes. Fucoidans also attenuated the level of PM-exacerbated IL-4, a primitive cytokine released in Th2 mediated eosinophilic asthma. This further suppressed mast cell activation, degranulation and IgE synthesis of PM exposed mice. Interestingly, fucoidans attenuated PM-exacerbated mucus hypersecretion and goblet cell hyperplasia. Therefore, our results suggest that fucoidans are effective at alleviating PM-exacerbated allergic asthma symptoms by attenuating the airway inflammatory response and mucus hypersecretion.

Dietary fat intake and age modulate the composition of the gut microbiota and colonic inflammation in C57BL/6J mice.

BACKGROUND: More than half of the adult population worldwide is overweight or obese, while excess adiposity has been linked to chronic low-grade inflammation, contributing to the development of chronic diseases. Recent studies have showed that diet-induced alterations to the gut microbiota composition play a pivotal role in the development of obesity. However, the cause-effect relationship between obesity and gut microbiota composition is not yet fully understood. In this study, we investigated the short-term responses of gut microbiota composition to diets with different fat contents and their associations with inflammatory biomarkers. RESULTS: Sixty male C57BL/6 J mice were fed a normal diet (ND; 15% fat) or a high-fat diet (HFD; 45% fat) for 10 or 20 weeks. The relative proportion of the phylum Actinobacteria was elevated by the HFD and was positively associated with body weight and proinflammatory cytokines including TNF-α, IL-1ß, and IL-6. The proportion of the phylum Firmicutes increased with aging and was also positively correlated with proinflammatory cytokines. The proportions of Actinobacteria and Firmicutes were inversely associated with tight junction proteins claudin-1 and E-cadherin, respectively. The proportions of the class Clostridia and the family Ruminococcaceae within the phylum Firmicutes were affected by both diet and age. In addition, the proportions of the phylum Bacteroidetes, the family Bacteroidaceae, and the genus Bacteroides decreased with aging and were inversely correlated with colonic proinflammatory cytokines representing a positive association with tight junction proteins. CONCLUSIONS: Host age and dietary fat intake are important elements that induce proportional changes in gut microbiota, and these changes are also associated with systemic inflammation. This study provides evidence that diet affects the gut microbiota composition within a short period of time.

Jeju ground water containing vanadium induces normal T cell development and immune activation in chronically stressed mice.

Containing high concentration of vanadium served by the volcanic bedrock, Jeju ground water has long been known for various implicit health benefits including immune-promotion. Exposure to stress has been reported to be associated with immunosuppression such as reducing lymphocyte population or antibody production due to stress hormones. In this study, we aimed at evaluating the effects of Jeju ground water on chronically stressed mice. C57BL/6 mice were subjected to various stressors such as restraint stress, water swimming stress, heat stress, acoustic stress, and Jeju ground water was supplied for 28 days with two different concentrations, S1 (vanadium 15-20 µg/l, pH 8.3) and S2 (vanadium 20-25 µg/l, pH 8.5). Treatment with Jeju ground water increased CD4+CD8- or CD4-CD8+ single-positive thymocytes. It also increased the proliferation of splenocytes and the populations of CD4+ T cells, CD45R/B220+ B cells, CD11b+ macrophages or Gr-1+ granulocytes in spleen. In addition, the production of IgG was increased in chronically stressed mice by treatment with Jeju ground water. These results suggest vanadium-rich Jeju ground water may be helpful in T cell development in thymus and immune cell proliferation and its function in spleen against chronic stress.

Synthetic Human ß Defensin-3-C15 Peptide in Endodontics: Potential Therapeutic Agent in Streptococcus gordonii Lipoprotein-Stimulated Human Dental Pulp-Derived Cells.

Human ß defensin-3-C15, an epithelium-derived cationic peptide that has antibacterial/antifungal and immuno-regulatory properties, is getting attention as potential therapeutic agent in endodontics. This study aimed to investigate if synthetic human ß defensin-3-C15 (HBD3-C15) peptides could inhibit inflammatory responses in human dental pulp cells (hDPCs), which had been induced by gram-positive endodontic pathogen. hDPC explant cultures were stimulated with Streptococcus gordonii lipoprotein extracts for 24 h to induce expression of pro-inflammatory mediators. The cells were then treated with either HBD3-C15 (50 µg/mL) or calcium hydroxide (CH, 100 µg/mL) as control for seven days, to assess their anti-inflammatory effects. Quantitative RT-PCR analyses and multiplex assays showed that S. gordonii lipoprotein induced the inflammatory reaction in hDPCs. There was a significant reduction of IL-8 and MCP-1 within 24 h of treatment with either CH or HBD3-C15 (p < 0.05), which was sustained over 1 week of treatment. Alleviation of inflammation in both medications was related to COX-2 expression and PGE2 secretion (p < 0.05), rather than TLR2 changes (p > 0.05). These findings demonstrate comparable effects of CH and HDB3-C15 as therapeutic agents for inflamed hDPCs.

Health behaviors and illness according to marital status in middle-aged Koreans.

Background: Marital status influences health and this association might differ by time and/or country. Divorce rates have increased abruptly in Korea. We investigated relationships between marital status and health behaviors and illness among middle-aged Koreans. Methods: Data from the fifth Korean National Health and Nutrition Examination Survey 2010-12 was used. Participants were middle-aged (40-65 years) Koreans (3015 male and 4498 female) who had been married. Health behaviors and physical and mental health status were evaluated separately for each gender according to marital status (currently married versus separated, divorced or widowed) using logistic regression analyses adjusted for age, income level and region. Results: About 5.4% of men and 13.0% of women lived without their spouses. Odd ratios (ORs) for smoking, binge drinking, inadequate sleep, hypertriglyceridemia and depression were significantly higher in participants not living with their spouses. ORs for non-participation in regular health examinations and cancer screenings, anemia, elevated alanine aminotransferase and suicidal ideation were significantly higher in men not living with their spouses. Conclusions: Health behaviors and illness were significantly worse in middle-aged Koreans not living with their spouses. Men were more susceptible to poor health screening, nutritional deficiencies and mental illness. Preventive services are necessary to improve their health status.

Immunostimulatory effect of pepsin enzymatic extract from Porphyra yezoensis on murine splenocytes.

BACKGROUND: Porphyra yezoensis is a red alga consumed mainly in Korea, Japan, and China for food. This study researches the immunological effect of pepsin extract of P. yezoensis (PPEE) on murine splenocytes. RESULTS: PPEE was not toxic on murine splenocytes and dramatically increased the proliferation of splenocytes compared with untreated control. Flow cytometry assay performed to sum up the effect of PPEE (31.3 and 62.5 µg mL-1 ) on major immune cells revealed that PPEE had no effect on the function of CD3e+ CD4+ T-helper cells, CD3e+ CD8+ T-cytotoxic cells, or CD44+ CD62L- effector T cells in splenocytes compared with untreated control. More importantly, CD45+ CD11b+ macrophage and dendritic cell populations and Ly-6C+ Ly-6G+ macrophages/monocytes in splenocytes were activated by PPEE treatment compared with untreated control. Further experiments showed that PPEE treatment increased the secretion of macrophage-derived cytokines such as interleukin-1ß, tumor necrosis factor-α, and interleukin-12, and macrophage-activating cytokines interferon-γ and interleukin-10 compared with untreated control. CONCLUSION: Taken together, these results suggest that PPEE has an immune stimulatory effect on macrophages, dendritic cells, and memory T cells. This property signifies the potential medicinal value of PPEE in clinical implications for immune-compromised diseases. © 2017 Society of Chemical Industry.

Estimating the economic value of counselling services using the contingent valuation method.

This study aimed to justify the use of the contingent valuation method to elicit the willingness to pay (WTP) for counselling services and to analyse the socio-demographic and psychological factors that influence WTP (through an increase in insurance premiums) for counselling services in South Korea. Regarding WTP for counselling services, the researchers asked 561 participants double-bounded dichotomous choice questions, which is one of the major estimation methods. Two survival analysis models were set up with their corresponding variables to investigate the factors affecting the WTP for an increase in insurance premiums to cover counselling services. The results indicate that a person in South Korea who makes KRW 2,500,000 (USD 2223.21) per month and pays KRW 66,625 (USD 59.25) per month in insurance premiums is willing to pay a roughly 1% premium to receive additional counselling services. The first regression analysis model for WTP showed that pocket money and counselling experience had significant positive effects while gender had a significant negative effect. The second model included four additional psychological factors and the significant effects of gender and counselling experience that had been found in the first model disappeared while only pocket money showed a significant effect on WTP.

Expression and antigenicity of recombinant human respiratory syncytial virus glycoproteins having different affinity tags.

Human respiratory syncytial virus (HRSV) is a main cause of lower respiratory tract infections in infants and the elderly. Glycoprotein (G) is major antigen on the viral surface, and plays a key role for virus entry. Therefore, purification of the glycoprotein of HRSV is critical for the development of HRSV vaccine and serological diagnosis. In this study, we report the design and characterization of glycoprotein engineered rationally to enhance the protein solubility and to facilitate efficient purification. We permuted HRSV glycoproteins with two tags: (i) an immunoglobulin (Ig) M signal peptide and a protein A B domain tag to render HRSV glycoprotein secret into the culture media and (ii) a foldon and 6 × histidine tag with or without transmembrane domain. Three recombinant baculoviruses were constructed: (i) transmembrane-truncated HRSV glycoprotein (amino acid positions 66-298) inserted with the N-terminal IgM signal peptide and protein A B domain (MG-GΔTM), (ii) truncated HRSV glycoprotein (amino acid positions 66-298) fused with a C-terminal foldon and 6 × histidine tag (GΔTM-FH), and (iii) full-length HRSV glycoprotein (amino acid positions 1-298) fused with a C-terminal foldon and 6 × histidine tag (G-FH). Highly soluble recombinant MG-GΔTM protein was clearly purified using one-step affinity chromatography with IgG-sepharose resin, whereas the recombinant G-FH protein and truncated GΔTM-FH were purified partially using nickel-resin. Although, the antigenicity of GΔTM-FH was stronger than highly mannose-rich MG-GΔTM protein, MG-GΔTM induced neutralizing antibodies efficiently in the mice to protect from infectious HRSV.

Beetroot (Beta vulgaris) rescues mice from γ-ray irradiation by accelerating hematopoiesis and curtailing immunosuppression.

CONTEXT: Beetroot [Beta vulgaris Linné (Chenopodiaceae)], a vegetable usually consumed as a food or a medicinal plant in Europe, has been reported to have antioxidant and anti-inflammatory properties. Since the lymphohematopoietic system is the most sensitive tissue to ionizing radiation, protecting it from radiation damage is one of the best ways to decrease detrimental effects from radiation exposure. OBJECTIVE: In this study, we evaluated the radio-protective effects of beetroot in hematopoietic stem cells (HSCs) and progenitor cells. MATERIALS AND METHODS: Beetroot extract was administered at a dose of 400 mg/mouse per os (p.o.) three times into C57BL/6 mice and, at day 10 after γ-ray irradiation, diverse molecular presentations were measured and compared against non-irradiated and irradiated mice with PBS treatments. Survival of beetroot-fed and unfed irradiated animal was also compared. RESULTS: Beetroot not only stimulated cell proliferation, but also minimized DNA damage of splenocytes. Beetroot also repopulated S-phase cells and increased Ki-67 or c-Kit positive cells in bone marrow. Moreover, beetroot-treated mice showed notable boosting of differentiation of HSCs into burst-forming units-erythroid along with increased production of IL-3. Also, beetroot-treated mice displayed enhancement in the level of hematocrit and hemoglobin as well as the number of red blood cell in peripheral blood. Beetroot diet improved survival rate of lethally exposed mice with a dose reduction factor (DRF) of 1.1. DISCUSSION AND CONCLUSION: These results suggest that beetroot has the potency to preserve bone marrow integrity and stimulate the differentiation of HSCs against ionizing radiation.

Variations in Spike Glycoprotein Gene of MERS-CoV, South Korea, 2015.

An outbreak of nosocomial infections with Middle East respiratory syndrome coronavirus occurred in South Korea in May 2015. Spike glycoprotein genes of virus strains from South Korea were closely related to those of strains from Riyadh, Saudi Arabia. However, virus strains from South Korea showed strain-specific variations.

6,6'-Bieckol suppresses inflammatory responses by down-regulating nuclear factor-κB activation via Akt, JNK, and p38 MAPK in LPS-stimulated microglial cells.

OBJECTIVE: Microglial activation has been implicated in many neurological disorders for its inflammatory and neurotrophic effects. In this study, we investigated the pharmaceutical properties of 6,6'-bieckol on the regulation of nuclear factor-κB (NF-κB) activation responsible to the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 using lipopolysaccharide (LPS)-stimulated BV2 and murine primary microglial cells. Meterials and methods: The levels of nitric oxide (NO), prostaglandin E2 (PGE)2, and pro-inflammatory cytokines were measured by Griess assay and enzyme-linked immunosorbent assay. The levels of iNOS, COX-2, mitogen-activated protein kinases (MAPKs), and Akt were measured using Western blot. Nuclear translocation and transcriptional activation of NF-κB were determined by immunofluorescence and reporter gene assay, respectively. RESULTS: We found that 6,6'-bieckol decreased the expression of iNOS and COX-2 as well as pro-inflammatory cytokines in LPS-stimulated BV2 and primary microglial cells in a dose-dependent manner. 6,6'-Bieckol inhibited activation of NF-κB by preventing the degradation of inhibitor κB (IκB)-α and led to prevent the nuclear translocation of NF-κB/p65 subunit. Moreover, 6,6'-bieckol inhibited the phosphorylation of Akt, JNK, and p38 MAPK. DISCUSSION AND CONCLUSION: These results indicate that the anti-inflammatory effect of 6,6'-bieckol on LPS-stimulated microglial cells is mainly regulated by the inhibition of IκB-α/NF-κB and JNK/p38 MAPK/Akt pathways, supporting biochemical characteristics of the compound for therapeutic agent against neuroinflammatory diseases caused by microglial activation.

Citrus hallabong [(Citrus unshiu × C. sinensis) × C. reticulata)] exerts potent anti-inflammatory properties in murine splenocytes and TPA-induced murine ear oedema model.

CONTEXT: Hallabong [(Citrus unshiu × C. sinensis) X C. reticulata)] (Rutaceae) is a hybrid citrus cultivated in temperate regions of South Korea. Its fruit is well-known for pharmacological properties. OBJECTIVE: This study examined the anti-inflammatory effect of 80% ethanol extract of Hallabong (HE) on concanavalin A (Con A)-stimulated splenocytes and mouse oedema model induced by 12-O-tetradecanoylphorbal acetate (TPA). MATERIALS AND METHODS: Murine splenocytes treated with HE were stimulated with Con A (10 µg/mL, for 24 h) were evaluated for T-cell population and production of inflammatory cytokines IL-2, IL-4 and IFN-γ. Anti-inflammatory effect of topically applied HE (100 µg/20 µL) on TPA (4 µg/20 µL/ear)-induced ear oedema was investigated in mouse model. RESULTS: HE-treated Con A-stimulated murine splenocytes showed a marked decrease in CD44/CD62L+ memory T-cell population, an important marker for anti-inflammatory activity, and a significant inhibition in the production of IL-2 and IFN-γ. HE treatment had reduced the mouse skin oedema (47%) and myeloperoxidase (MPO) activity significantly (40%) in TPA-challenged tissues. More importantly, immunohistochemical localization revealed the suppressed (p < 0.05) expression of inducible nitric oxide (iNOS), cyclooxygenase-2 (COX2). HE decreased the infiltration of CD3+ T cells and F4/80+ macrophages to the site of inflammation and a topical application of HE significantly suppressed the expression of TNF-α (20.2%). DISCUSSION AND CONCLUSION: A topical application of HE can exert a potential anti-inflammatory effect and HE can be explored further as a putative alternative therapeutic agent for inflammatory oedema.

Middle East Respiratory Syndrome in 3 Persons, South Korea, 2015.

In May 2015, Middle East respiratory syndrome coronavirus infection was laboratory confirmed in South Korea. Patients were a man who had visited the Middle East, his wife, and a man who shared a hospital room with the index patient. Rapid laboratory confirmation will facilitate subsequent prevention and control for imported cases.

Esculetin induces apoptosis in human colon cancer cells by inducing endoplasmic reticulum stress.

Colorectal cancer has become more common in many regions of the world. Recently, we showed that esculetin, a natural coumarin, induces apoptosis in HT-29 colon cancer cells via the reactive oxygen species-mediated mitochondrial pathway. The present study examined whether esculetin induces apoptosis in HT-29 colon cancer cells by inducing endoplasmic reticulum (ER) stress. We found that esculetin induced characteristic signs of ER stress, confirmed by ER staining, mitochondrial calcium overload and expression of ER stress-related proteins (i.e. glucose regulated protein 78, phosphorylated ribonucleic acid-dependent protein kinase-like ER kinase, phosphorylated inositol requiring enzyme 1, phosphorylated eukaryotic initiation factor-2α, spliced X-box binding protein 1 and cleaved activating transcription factor 6). Esculetin also induced the expression of the CCAAT/enhancer-binding protein-homologous protein (CHOP) and pro-apoptotic factors caspase-12. Moreover, transfection of colon cancer cells with a small interfering ribonucleic acid targeting CHOP attenuated esculetin-induced apoptosis. Taken together, these results suggest that the ER stress response plays an important role in esculetin-induced apoptosis in human colon cancer cells.

Cytoprotective effect of eckol against oxidative stress-induced mitochondrial dysfunction: involvement of the FoxO3a/AMPK pathway.

This study investigated the cytoprotective effect of Ecklonia cava-derived eckol against H2O2-induced mitochondrial dysfunction in Chang liver cells. While H2O2 augmented levels of mitochondrial reactive oxygen species (ROS), eckol decreased it. Eckol also attenuated high intracellular Ca(2+) levels stimulated by H2O2 and recovered H2O2-diminished ATP levels and succinate dehydrogenase activity. Eckol time-dependently increased the expression of manganese superoxide dismutase (Mn SOD), a mitochondrial antioxidant enzyme with cytoprotective effect against oxidative stress. Eckol recovered Mn SOD expression and activity that were decreased by H2O2. Finally, eckol induced Mn SOD through phosphorylated AMP-activated protein kinase (AMPK) and forkhead box O3a (FoxO3a). Specific silencing RNAs (siRNAs) against FoxO3a and AMPK reduced eckol-stimulated Mn SOD expression, and diethyldithiocarbamate (Mn SOD inhibitor) and siRNA against Mn SOD reduced the cytoprotective effect of eckol against H2O2-provoked cell death. These results demonstrate that eckol protects cells from mitochondrial oxidative stress by activating AMPK/FoxO3a-mediated induction of Mn SOD.