Anti-Obesity Effect and Signaling Mechanism of Potassium Poly-γ-Glutamate Produced by Bacillus subtilis Chungkookjang in High-Fat Diet-Induced Obese Mice.

The purpose of this work was to examine the effects of potassium poly-γ-glutamate (PGA-K) on mice fed a high-fat diet consisting of 60% of total calories for 12 weeks. PGA-K administration reduced the increase in body weight, epididymal fat, and liver weight caused by a high-fat diet compared to the obese group. The triglyceride, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels, which are blood lipid indicators, were significantly increased in the obese group but were significantly decreased in the PGA-K-treated group. The administration of PGA-K resulted in a significant inhibition of pro-inflammatory cytokines, including tumor necrosis factor α and interleukin 6. Moreover, the levels of leptin and insulin, which are insulin resistance indicators, significantly increased in the obese group but were significantly decreased in the PGA-K-treated group. These results suggest that PGA-K exhibits a protective effect against obesity induced by a high-fat diet, underscoring its potential as a candidate for obesity treatment.

Anti-Photoaging Effects of Upcycled Citrus junos Seed Anionic Peptides on Ultraviolet-Radiation-Induced Skin Aging in a Reconstructed Skin Model.

Side streams and byproducts of food are established sources of natural ingredients in cosmetics. In the present study, we obtained upcycled low-molecular-weight anionic peptides (LMAPs) using byproducts of the post-yuzu-juicing process by employing an enzyme derived from Bacillus sp. For the first time, we isolated anionic peptides less than 500 Da in molecular weight from Citrus junos TANAKA seeds via hydrolysis using this enzyme. The protective effect of LMAPs against UVR-induced photoaging was evaluated using a reconstructed skin tissue (RST) model and keratinocytes. The LMAPs protected the keratinocytes by scavenging intracellular reactive oxygen species and by reducing the levels of paracrine cytokines (IL-6 and TNF-α) in UVR (UVA 2 J/cm2 and UVB 15 mJ/cm2)-irradiated keratinocytes. Additionally, the increase in melanin synthesis and TRP-2 expression in RST caused by UVR was significantly inhibited by LMAP treatment. This treatment strongly induced the expression of filaggrin and laminin-5 in UVR-irradiated RST. It also increased type I collagen expression in the dermal region and in fibroblasts in vitro. These results suggest that a hydrolytic system using the enzyme derived from Bacillus sp. can be used for the commercial production of LMAPs from food byproducts and that these LMAPs can be effective ingredients for improving photoaging-induced skin diseases.

Therapeutic Effect of Enzymatically Hydrolyzed Cervi Cornu Collagen NP-2007 and Potential for Application in Osteoarthritis Treatment.

Cervi cornu extracts have been used in traditional medicine for the treatment of various disorders, including osteoporosis. However, since it is not easy to separate the active ingredients, limited research has been conducted on their functional properties. In this study, we extracted the low-molecular-weight (843 Da) collagen NP-2007 from cervi cornu by enzyme hydrolyzation to enhance absorption and evaluated the therapeutic effect in monosodium iodoacetate-induced rat osteoarthritis (OA) model. NP-2007 was orally administered at 50, 100, and 200 mg/kg for 21 days. We showed that the production of matrix metalloproteinase-2, -3, and -9, decreased after NP-2007 treatment. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and prostaglandin E2 were also reduced after treatment of NP-2007. Furthermore, the administration of NP-2007 resulted in effective preservation of both the synovial membrane and knee cartilage and significantly decreased the transformation of fibrous tissue. We verified that the treatment of NP-2007 significantly reduced the production of nitric oxide and pro-inflammatory cytokines including TNF-α, IL-1ß, and IL-6 in lipopolysaccharides-stimulated RAW 264.7 cells by regulation of the NF-kB and MAPK signaling pathways. This study indicates that NP-2007 can alleviate symptoms of osteoarthritis and can be applied as a novel treatment for OA treatment.

Anti-Inflammatory Effect and Signaling Mechanism of Glycine max Hydrolyzed with Enzymes from Bacillus velezensis KMU01 in a Dextran-Sulfate-Sodium-Induced Colitis Mouse Model.

The purpose of this study was to investigate the effect that Glycine max hydrolyzed with enzymes from Bacillus velezensis KMU01 has on dextran-sulfate-sodium (DSS)-induced colitis in mice. Hydrolysis improves functional health through the bioconversion of raw materials and increase in intestinal absorption rate and antioxidants. Therefore, G. max was hydrolyzed in this study using a food-derived microorganism, and its anti-inflammatory effect was observed. Enzymatically hydrolyzed G. max (EHG) was orally administered once daily for four weeks before DSS treatment. Colitis was induced in mice through the consumption of 5% (w/v) DSS in drinking water for eight days. The results showed that EHG treatment significantly alleviated DSS-induced body weight loss and decreased the disease activity index and colon length. In addition, EHG markedly reduced tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 production, and increased that of IL-10. EHG improved DSS-induced histological changes and intestinal epithelial barrier integrity in mice. Moreover, we found that the abundance of 15 microorganisms changed significantly; that of Proteobacteria and Escherichia coli, which are upregulated in patients with Crohn's disease and ulcerative colitis, decreased after EHG treatment. These results suggest that EHG has a protective effect against DSS-induced colitis and is a potential candidate for colitis treatment.

Effects of Perilla frutescens var. acuta in amyloid ß toxicity and Alzheimer's disease-like pathology in 5XFAD mice.

Although accumulation of amyloid ß (Aß) plaque is a major hallmark of Alzheimer's disease (AD), various pathologies have been suggested therapeutic targets. Therefore, therapies-targeting multiple pathologies would be required for effective managements of AD. Accordingly, natural products, which has multiple active ingredients, have been receiving a lot of attention. In this study, we tested whether standardized ethanol extract of leaves of Perilla frutescens var. acuta (L.) Britt. (Lamiaceae) (ELPF) could modulate various pathologies in AD using 5XFAD mice. ELPF blocked Aß aggregation and disassembled pre-formed Aß aggregates. ELPF blocked Aß aggregates-induced LTP impairment and ELPF-disassembled Aß aggregates failed to impair hippocampal LTP. Systemic administration of ELPF blocked Aß aggregates-induced memory impairment in a passive avoidance test. ELPF-disassembled Aß aggregates failed to impair passive avoidance memory. Prolonged administration of ELPF ameliorated memory impairments in 5XFAD mice. In the hippocampus of 5XFAD mice, ELPF administration significantly reduced Aß deposits and neuroinflammation. These results demonstrate that ELPF could be a promising therapeutic candidate for AD.

Perception, knowledge and attitudes on advance medical directives among hospital staff: Using mixed methodology.

BACKGROUND: It is necessary to examine the level of perception, knowledge and attitudes of the medical staff for advance medical directives, which are practical alternatives to good practice for end-of-life care in the actual medical field. PURPOSE: This study was conducted to determine the degree of perception, knowledge and attitude of cancer hospital medical staff about advance medical directives, and to confirm the relationship between them. It also explored their experiences with advance medical directives. METHODS: This study used a convergent design to collect quantitative and qualitative data separately in the mixed methodology. This design adheres to the STROBE guidelines. Participants were a total of 140 subjects (70 doctors and 70 nurses) with more than 3 years and considered to have sufficient experience related to the study purpose. Focus group participants were a total 19 persons (9 doctors and 10 nurses). RESULTS: Mean score for perception was 35.40, which indicates lower perception when compared to the median value (37.50 points). Perception of advance medical directives had significant, positive relations with attitude of advance medical directives (p = .032). The perception on attitude of advance medical directives factor was significantly influencing (p = .021). As a result of the analysis based on qualitative research questions, six subjects and 11 categories were created by deriving meaningful sentences from the statements. CONCLUSION: This study suggests that the perception of medical professionals about advance medical directives has a positive correlation with attitudes, as well as a causal relationship. RELEVANCE TO CLINICAL PRACTICE: Based on the finding from this study, concrete strategies and interventions to improve the perception of advance medical directives among cancer hospital medical staff are needed.

Development and validation of a gas chromatography method for the determination of ß-caryophyllene in clove extract and its application.

The purpose of this study is to check the effectiveness of the analysis method that separates and quantifies ß-caryophyllene among clove extracts and validate according to current ICH guidelines. The ß-caryophyllene was active constituent of clove buds. The developed method gave a good detection response. In the specificity test, the standard solution was detected at about 17.32 min, and the test solution was detected at 17.32 min. The linearity of ß-caryophyllen was confirmed, and at this time, the correlation coefficient (R2) of the calibration curve showed a high linearity of 0.999 or more in the concentration range. The levels of LOD and LOQ were 1.28 ug/mL and 3.89 ug/mL, respectively. The accuracy was confirmed to be 101.6-102.2% and RSD 0.95 ~ 1.31%. As a result of checking the repeatability and inter-tester reproducibility to confirm the precision, the RSD was found to be 1.34 ~ 2.69%. This validated GC method was successfully applied to a soft capsule containing clove extract and other materials for clinical trials. Therefore, this method can be used as an analytical tool for quality control of various samples, including clove extracts and their products of food and pharmaceutical uses.

SOD1 suppresses pro-inflammatory immune responses by protecting against oxidative stress in colitis.

Superoxide dismutase 1 (SOD1) binds copper and zinc ions and is one of three superoxide dismutases responsible for destroying free superoxide radicals in the body. Reactive oxygen species (ROS), including free superoxide radicals, play important roles in colitis. However, the role of SOD1 in oxidative stress under colitis remains unclear. Here, we examined the role of SOD1 in the DSS-induced mouse model of colitis. SOD1 deficiency resulted in severe oxidative stress with body weight loss, epithelial barrier disruption and decreased antioxidant enzyme activities. The levels of neutrophils, monocytes, pro-inflammatory CD11c+ macrophages and CD11b+CD103- dendritic cells (DCs) were increased, while anti-inflammatory CD206+ macrophages and CD11b-CD103+ DCs were decreased, in DSS-treated SOD1-knockout (KO) mice compared to DSS-treated wild-type mice. Furthermore, rescue of SOD activity in SOD1-KO mice by oral gavage of B. amyloliquefaciens SOD (BA SOD) significantly ameliorated enhanced DSS-induced colitis in these mice by suppressing p38-MAPK/NF-κB signaling, which can induce inflammation and apoptosis. Taken together, our results suggest that SOD1-mediated inhibitory responses play a crucial role in limiting the development of DSS-induced colitis, and that BA SOD is a promising candidate for treating colitis.

Safety and efficacy of basic fibroblast growth factors for deep second-degree burn patients.

INTRODUCTION: Burn injuries are common afflictions; however, conservative wound care frequently leads to poor treatment compliance and physical disability in deep burn patients. Therefore, regenerative biologic materials, which are more effective for tissue repair, are required, particularly for deep second-degree burns. A novel spray formulation of basic fibroblast growth factors (bFGF) was produced by synthesizing fibroblast growth factor proteins. In this post-marketing surveillance (PMS) study, we assessed the safety and efficacy of bFGF and indirectly compared this formulation with cultured epidermal autografts (CEAs) for treating deep second-degree burns. MATERIALS AND METHODS: A total of 3173 patients treated at 15 hospitals were used for PMS of bFGF in South Korea for six years. In total, 1630 patients with deep second-degree burns were selected for assessing adverse events (AEs) of bFGF treatments. Efficacy was evaluated according to time periods until re-epithelialization, and clinical usefulness of bFGF was indirectly compared with that of CEAs. RESULTS: AEs occurred in 37 patients (2.3%) and included application site pain (1.7%) and contact dermatitis (0.6%). All AEs were mild and were evaluated as probably unrelated with bFGF. The average time for re-epithelialization was 8 days; this time span was significantly longer after major burns (9.7 days) than after minor (7.8 days) or moderate burns (7.9 days). Most treated burn wounds (99.8%) were assessed as improved. The indirect comparison included 534 patients using the same inclusion criteria for CEA patients (n = 35). The bFGF treatment demonstrated superior efficacy compared to CEAs by significantly reducing the average day to application (5.4 vs. 8.8 days) and re-epithelialization time (7.1 vs. 13.7 days). CONCLUSION: Our study demonstrated that bFGF is a compelling regenerative therapy with competitive clinical efficacy and safety for deep second-degree burns and reduced treatment time, which is expected to reduce medical costs, particularly for deep second-degree burn patients.

Effect of ß-caryophyllene from Cloves Extract on Helicobacter pylori Eradication in Mouse Model.

New antibacterial treatments against Helicobacter pylori are needed as H. pylori is acquiring antibiotic resistance. ß-caryophyllene is a natural bicyclic sesquiterpene, with anti-inflammatory and antimicrobial effects. This study investigates the effects of H-002119-00-001 from ß-caryophyllene on the eradication of H. pylori in a mouse model, and its effects on the inflammation of the gastric mucosa. To evaluate the anti-H.pylori efficacy of ß-caryophyllene, a total of 160 mice were divided into eight groups (n = 10 each) and were administered different treatments for 2 and 4 weeks. H. pylori eradication was assessed using a Campylobacter-like organism (CLO) test and H. pylori qPCR of the gastric mucosa. The levels of inflammation of gastric mucosa were assessed using histology and immunostaining. H-002119-00-001 decreased bacterial burden in vitro. When H-002119-00-001 was administered to mice once daily for 2 weeks, cure rates shown by the CLO test were 40.0%, 60.0%, and 70.0% in groups 6, 7, and 8, respectively. H. pylori levels in gastric mucosa decreased dose-dependently after H-002119-00-001 treatment. H-002119-00-001 also reduced levels of inflammation in gastric mucosa. H-002119-00-001 improved inflammation and decreased bacterial burden in H. pylori-infected mouse models. H-002119-00-001 is a promising and effective therapeutic agent for the treatment of H. pylori infection.

Role of Aggregatibacter actinomycetemcomitans-induced autophagy in inflammatory response.

BACKGROUND: Aggressive periodontitis is characterized by the early-onset and rapid progression of periodontal destruction and is closely associated with Aggregatibacter actinomycetemcomitans. Autophagy is a conserved process that is critical for removing damaged proteins, organelles, and even intracellular pathogens. Therefore, this study examined whether A. actinomycetemcomitans induces autophagy. In addition, the relationship among autophagy, bacterial internalization, and inflammatory molecules in periodontal aggressive inflammation was analyzed. METHODS: The expression of autophagy-related proteins in human gingival tissue and THP-1 cells was assessed by Western blot analysis. The formation of light chain 3 (LC3) puncta was examined by confocal microscopy. The degree of bacterial internalization into the cells was determined by the viable cell count. Phagocytosis and reactive oxygen species (ROS) production were measured using confocal microscopy and flow cytometry. RESULTS: When macrophages were infected with live A. actinomycetemcomitans, the autophagy influx was activated by the increase in LC3-II, autophagy-related gene 5/12, and Beclin-1 expression through the Toll-like receptors and extracellular signal-regulated kinase signaling pathways. The inhibition of A. actinomycetemcomitans-induced autophagy suppressed bacterial internalization via phagocytosis into the macrophages and increased interleukin (IL)-1ß production. Moreover, treatment with an ROS inhibitor inhibited these enhanced inflammatory responses. CONCLUSIONS: A. actinomycetemcomitans-induced autophagy promotes bacterial internalization by phagocytosis, which restricts the excessive inflammatory response by downregulating IL-1ß and ROS production in macrophages. Thus, A. actinomycetemcomitans-induced autophagy and its role in regulating the inflammatory response may play an important role in the aggressive periodontal inflammatory process, and be a target for the development of new periodontal therapies.

Catechin ameliorates Porphyromonas gingivalis-induced inflammation via the regulation of TLR2/4 and inflammasome signaling.

BACKGROUND: Porphyromonas gingivalis is a major periodontopathogen found in patients with chronic periodontitis that can lead to alveolar bone or tooth loss. Interleukin-1ß (IL-1ß), a proinflammatory cytokine, is most relevant to the pathogenesis of periodontitis. Catechin is one of the main polyphenol compounds found in green tea and possesses a range of health benefits. This study examined the anti-inflammatory effects of catechin in THP-1-derived macrophages infected with P. gingivalis as well as its effects on P. gingivalis-induced periodontitis in a mouse model. METHODS: The cytokine levels and relevant protein expression in THP-1 cells were measured using an enzyme-linked immunosorbent assay and Western blot analysis, respectively. An apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) pyroptosome formation was measured by confocal laser scanning microscopy. Micro-computed tomography was used to determine the level of bone loss induced by a P. gingivalis oral infection. RESULTS: Catechin attenuated the production of IL-1ß by inhibiting pro-IL-1ß expression via the downregulation of nuclear factor-κB, p38 mitogen-activated protein kinase, and Toll-like receptor signaling. In addition, catechin inhibited the activation of inflammasomes induced by P. gingivalis, but did not affect the growth of P. gingivalis. Catechin reduced the level of alveolar bone loss in a P. gingivalis-induced periodontitis mouse model. CONCLUSION: Catechin possesses anti-inflammatory properties by reducing the level of IL-1ß production, suggesting that it can potentially be used for the prevention and treatment of periodontal inflammation caused by P. gingivalis.

Parkin deficiency prevents chronic ethanol-induced hepatic lipid accumulation through ß-catenin accumulation.

BACKGROUND: Alcohol abuse and alcoholism lead to alcohol liver disease such as alcoholic fatty liver. Parkin is a component of the multiprotein E3 ubiquitin ligase complex and is associated with hepatic lipid accumulation. However, the role of parkin in ethanol-induced liver disease has not been reported. Here, we tested the effect of parkin on ethanol-induced fatty liver in parkin knockout (KO) mice with chronic ethanol feeding. METHODS: Male wild type (WT) and parkin KO mice (10-12 weeks old, n = 10) were fed on a Lieber-DeCarli diet containing 6.6% ethanol for 10 days. Liver histological, biochemical, and gene-expression studies were performed. RESULTS: Parkin KO mice exhibited lower hepatosteatosis after ethanol consumption. Because several studies reported that ß-catenin is a critical factor in ethanol metabolism and protects against alcohol-induced hepatosteatosis, we investigated whether parkin changes ß-catenin accumulation in the liver of ethanol-fed mice. Our results show that ß-catenin was greatly accumulated in the livers of ethanol-fed parkin KO mice compared to ethanol-fed WT mice, and that parkin binds to ß-catenin and promotes its degradation it by ubiquitination. Moreover, the ß-catenin inhibitor IWR-1 abrogated the attenuation of ethanol-induced hepatic lipid accumulation by parkin deficiency in the livers of parkin KO mice and parkin siRNA-transfected human hepatic cell line. CONCLUSIONS: Parkin deficiency prevents ethanol-induced hepatic lipid accumulation through promotion of ß-catenin signaling by failure of ß-catenin degradation.

Combination Effect of Titrated Extract of Centella asiatica and Astaxanthin in a Mouse Model of Phthalic Anhydride-Induced Atopic Dermatitis.

PURPOSE: In our previous study, we demonstrated that both titrated extract of Centella asiatica (TECA) and astaxanthin (AST) have anti-inflammatory effects in a 5% phthalic anhydride (PA) mouse model of atopic dermatitis (AD). The increasing prevalence of AD demands new therapeutic approaches for treating the disease. We investigated the therapeutic efficacy of the ointment form of TECA, AST and a TECA + AST combination in a mouse model of AD to see whether a combination of the reduced doses of 2 compounds could have a synergistic effect. METHODS: An AD-like lesion was induced by the topical application of 5% PA to the dorsal ear and back skin of an Hos:HR-1 mouse. After AD induction, TECA (0.5%), AST (0.5%) and the TECA (0.25%) + AST (0.25%) combination ointment (20 µg/cm²) were spread on the dorsum of the ear or back skin 3 times a week for 4 weeks. We evaluated dermatitis severity, histopathological changes and changes in protein expression by Western blotting for inducible nitric oxide synthase (iNOS), cyclocxygenase (COX)-2, and nuclear factor (NF)-κB activity. We also measured the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and immunoglobulin E (IgE) in the blood of AD mice by enzyme-linked immunosorbent assay (ELISA). RESULTS: PA-induced skin morphological changes and ear thickness were significantly reduced by TECA, AST and TECA + AST treatments, but these inhibiting effects were more pronounced in the TECA + AST treatment. TECA, AST and the TECA+AST reatments inhibited the expression of iNOS and COX-2; NF-κB activity; and the release of TNF-α, IL-6 and IgE. However, the TECA+AST treatment showed additive or synergistic effects on AD. CONCLUSIONS: Our results demonstrate that the combination of TECA and AST could be a promising therapeutic agent for AD by inhibiting NF-κB signaling.

Loss of parkin reduces lung tumor development by blocking p21 degradation.

Several epidemiological studies have demonstrated the reciprocal relationship between the development of cancer and Parkinson's disease (PD). However, the possible mechanisms underlying this relationship remain unclear. To identify this relationship, we first compared lung tumor growth in parkin knockout (KO) mice and wild-type (WT) mice. Parkin KO mice showed decreased lung tumor growth and increased expression of p21, a cell cycle arrester, as compared with WT mice. We also found that parkin interacts with p21, resulting in its degradation; however, parkin KO, knockdown, as well as mutation (R275W or G430D) reduced the degradation of p21. We investigated whether parkin KO increases the association of p21 with proliferating cell nuclear antigen (PCNA) or CDK2 by reducing p21 degradation, and, thus, arresting the cell cycle. The interaction between p21 and PCNA or CDK2 was also enhanced by parkin knockdown, and this increased interaction induced sub G0/G1 arrest, leading to cell death. Therefore, our data indicate that parkin KO reduces the development of lung tumors via cell cycle arrest by blocking the degradation of p21. These findings suggest that PD could be associated with lower lung cancer incidence.

Peroxiredoxin 6 Confers Protection Against Nonalcoholic Fatty Liver Disease Through Maintaining Mitochondrial Function.

Aims: Nonalcoholic fatty liver disease (NAFLD) is accompanied by excessive reactive oxygen species (ROS) production, which has been suggested in several studies to link with mitochondrial function. However, the mechanistic role of ROS-mediated regulation of mitochondrial function in NAFLD has not been elucidated. Since peroxiredoxin 6 (PRDX6) is the only member of the antioxidant PRDX family that translocates to damaged mitochondria, we investigated the PRDX6-mediated antisteatotic mechanism using genetically modified mice and cells. Results: PRDX6 mice were more protective to lipid accumulation, liver injury, and insulin resistance after a high-fat diet. Mechanistically, PRDX6 is required for induction of mitochondrial antioxidant action and beta-oxidation through maintaining mitochondrial integrity and subsequently prevents ROS-induced lipogenesis. Interestingly, oxidative stress-induced Notch signaling was suppressed in PRDX6 mice compared with wild-type mice, and genetic and pharmacological inhibition of Notch signaling improved lipid accumulation. Finally, PRDX knockdown or Notch inhibition reduced induction of mitophagy. PRDX6 antagonizes positive feedback loop between lipid accumulation and ROS production through regulation of mitochondrial function. Innovation: For the first time, we demonstrate that PRDX6 maintains mitochondria integrity under oxidative stress and protects against NAFLD progression by inhibition of Notch signaling. Conclusion: This study describes a novel molecular mechanism underlying the antisteatotic activity of PRDX6, which may be a new therapeutic strategy for the treatment of NAFLD.

NF-κB as a Key Mediator of Brain Inflammation in Alzheimer's Disease.

Alzheimer's disease is the most common form of dementia. It is characterized by betaamyloid peptide fibrils which are extracellular deposition of a specific protein, accompanied by extensive neuroinflammation. Various studies show the presence of a number of inflammation markers in the AD brain: elevated inflammatory cytokines and chemokines, and an accumulation of activated microglia in the damaged regions. NF-κB is a family of redox sensitive transcriptional factors, and it is known that NF-κB has binding sites in the promoter region of the genes involved in amyloidogenesis and inflammation. Long-term use of non-steroidal anti-inflammatory drugs prevents progression of AD and delays its onset, suggesting that there is a close correlation between NF-κB and AD pathogenesis. This study aims to (1) assess the association between NF-κB activity and AD through discussion of a variety of experimental and clinical studies on AD and (2) review treatment strategies designed to treat or prevent AD with NF-κB inhibitors.

PRDX6 Inhibits Neurogenesis through Downregulation of WDFY1-Mediated TLR4 Signal.

Impaired neurogenesis has been associated with several brain disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The role of peroxiredoxin 6 (PRDX6) in neurodegenerative diseases is very controversial. To demonstrate the role of PRDX6 in neurogenesis, we compared the neurogenesis ability of PRDX6-overexpressing transgenic (Tg) mice and wild-type mice and studied the involved molecular mechanisms. We showed that the neurogenesis of neural stem cells (NSCs) and the expression of the marker protein were lower in PRDX6 Tg-mice than in wild-type mice. To determine the factors involved in PRDX6-related neural stem cell impairment, we performed a microarray experiment. We showed that the expression of WDFY1 was dramatically decreased in PRDX6-Tg mice. Moreover, WDFY1 siRNA decreases the differentiation ability of primary neural stem cells. Interestingly, WDFY1 reportedly recruits the signaling adaptor TIR-domain-containing adapter-inducing interferon-ß (TRIF) to toll-like receptors (TLRs); thus, we showed the relationship among TLRs, PRDX6, and WDFY1. We showed that TLR4 was dramatically reduced in PRDX6 Tg mice, and reduced TLR4 expression and neurogenesis was reversed by the introduction of WDFY1 plasmid in the neural stem cells from PRDX6 Tg mice. This study indicated that PRDX6 inhibits the neurogenesis of neural precursor cells through TLR4-dependent downregulation of WDFY1 and suggested that the inhibitory effect of PRDX6 on neurogenesis play a role in the development of neurodegenerative diseases in the PRDX6 overexpressing transgenic mice.

Effects of Obesity Management Program Provided by Occupational Health Nurse in Worksite.

This study was conducted on 60 male adult technicians in the worksite to examine the impact of the obesity management program on their eating habits, exercise self-efficacy, quality of life, and body components. This was a nonrandomized pretest and posttest intervention study. The obesity management program was applied for 16 weeks on diet education, exercise, and counseling provided by the occupational health nurse in the worksite. The questionnaire for measure included the general characteristics, eating habits, exercise self-efficacy, and quality of life. Body components were measured by using the InBody 720 device. The participants who received the obesity management program showed better eating habits, a higher level of exercise self-efficacy, a higher level of quality of life, lower levels of body weight and body mass index (BMI), a smaller waist and hip circumference, and a higher level of muscle mass as compared with the preapplication.

Astaxanthin alleviated ethanol-induced liver injury by inhibition of oxidative stress and inflammatory responses via blocking of STAT3 activity.

Astaxanthin (AXT) is classified as a xanthophyll carotenoid compound which have broader functions including potent antioxidant, anti-inflammatory and neuroprotective properties. Considerable researches have demonstrated that AXT shows preventive and therapeutic properties against for Diabetes, Osteoarthritis and Rheumatoid Arthritis. However, the protective effect of AXT on liver disease has not yet been reported. In this study, we investigated effects of AXT on ethanol-induced liver injury in chronic plus binge alcohol feeding model. The hepatic steatosis and inflammation induced by ethanol administration were alleviated by AXT. Serum levels of aspartate transaminase and alanine transaminase were decreased in the livers of AXT administrated group. The ethanol-induced expression of cytochrome P450 2E1 (CYP2E1), pro-inflammatory proteins, cytokines, chemokines and reactive oxygen species (ROS) levels were also reduced in the livers of AXT administrated group. Moreover, ethanol-induced infiltration of neutrophils was decreased in the livers of AXT administrated group. Docking model and pull-down assay showed that AXT directly binds to the DNA binding site of STAT3. Moreover, AXT decreased STAT3 phosphorylation in the liver of AXT administration group. Therefore, these results suggest that AXT could prevent ethanol-induced hepatic injury via inhibition of oxidant and inflammatory responses via blocking of STAT3 activity.