Heat-killed Akkermansia muciniphila ameliorates allergic airway inflammation in mice.

Allergic asthma (AA) is a common inflammatory airway disease characterized by increased airway hyper-responsiveness (AHR), inflammation, and remodeling. Akkermansia muciniphila is a strictly anaerobic bacterium residing in the gut and is a promising next-generation probiotic to improve metabolic inflammatory syndrome. A recent study suggested the beneficial effect of live A. muciniphila on allergic airway inflammation (AAI) in mice. However, whether the heat-killed form can improve AAI requires further investigation. Mice sensitized and challenged with house dust mites (HDM) develop AA hallmarks including inflammatory cell infiltration, goblet cell hyperplasia, and subepithelial collagen deposition in the lungs. These phenomena were reversed by oral administration of the heat-killed A. muciniphila strain EB-AMDK19 (AMDK19-HK) isolated from the feces of healthy Koreans. Furthermore, AMDK19-HK diminished the HDM-induced AHR to inhaled methacholine, lung mast cell accumulation, and serum HDM-specific IgE levels. It also led to the overall suppression of IL-4, IL-13, and eotaxin production in bronchoalveolar lavage fluids, and Il4, Il5, Il13, and Ccl17 gene expression in lung tissues. Moreover, AMDK19-HK suppressed Th2-associated cytokine production in the splenocytes of HDM-sensitized mice in vitro. Additionally, a combination of 16S rRNA gene sequencing and short-chain fatty acid (SCFA) analysis in cecal samples revealed that AMDK19-HK modulated the relative abundance of circulating SCFA-associated gut genera, including a positive correlation with Lachnospiraceae_ NK4A136_group and a negative correlation with Lachnoclostridium and significantly increased cecal SCFA concentrations. Finally, AMDK19-HK improved intestinal mucosal barrier function. These results suggest that the oral administration of AMDK19-HK ameliorates HDM-induced AAI in mice by suppressing Th2-mediated immune responses and could have a protective effect against AA development.

Balanced Free Essential Amino Acids and Resistance Exercise Training Synergistically Improve Dexamethasone-Induced Impairments in Muscle Strength, Endurance, and Insulin Sensitivity in Mice.

Our previous study shows that an essential amino acid (EAA)-enriched diet attenuates dexamethasone (DEX)-induced declines in muscle mass and strength, as well as insulin sensitivity, but does not affect endurance. In the present study, we hypothesized that the beneficial effects will be synergized by adding resistance exercise training (RET) to EAA, and diet-free EAA would improve endurance. To test hypotheses, mice were randomized into the following four groups: control, EAA, RET, and EAA+RET. All mice except the control were subjected to DEX treatment. We evaluated the cumulative rate of myofibrillar protein synthesis (MPS) using 2H2O labeling and mass spectrometry. Neuromuscular junction (NMJ) stability, mitochondrial contents, and molecular signaling were demonstrated in skeletal muscle. Insulin sensitivity and glucose metabolism using 13C6-glucose tracing during oral glucose tolerance tests were analyzed. We found that EAA and RET synergistically improve muscle mass and/or strength, and endurance capacity, as well as insulin sensitivity, and glucose metabolism in DEX-treated muscle. These improvements are accomplished, in part, through improvements in myofibrillar protein synthesis, NMJ, fiber type preservation, and/or mitochondrial biogenesis. In conclusion, free EAA supplementation, particularly when combined with RET, can serve as an effective means that counteracts the adverse effects on muscle of DEX that are found frequently in clinical settings.

Epigallocatechin Gallate Protects against Hypoxia-Induced Inflammation in Microglia via NF-κB Suppression and Nrf-2/HO-1 Activation.

Hypoxia-induced neuroinflammation in stroke, neonatal hypoxic encephalopathy, and other diseases subsequently contributes to neurological damage and neuronal diseases. Microglia are the primary neuroimmune cells that play a crucial role in cerebral inflammation. Epigallocatechin gallate (EGCG) has a protective antioxidant and anti-inflammatory effects against neuroinflammation. However, the effects of EGCG on hypoxia-induced inflammation in microglia and the underlying mechanism remain unclear. In this study, we investigated whether EGCG might have a protective effect against hypoxia injury in microglia by treatment with CoCl2 to establish a hypoxic model of BV2 microglia cells following EGCG pre-treatment. An exposure of cells to CoCl2 caused an increase in inflammatory mediator interleukin (IL)-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2 expression, which were significantly ameliorated by EGCG via inhibition of NF-κB pathway. In addition, EGCG attenuated the expression of hypoxia-inducible factor (HIF)-1α and the generation of ROS in hypoxic BV2 cells. Furthermore, the suppression of hypoxia-induced IL-6 production by EGCG was mediated via the inhibition of HIF-1α expression and the suppression of ROS generation in BV2 cells. Notably, EGCG increased the Nrf-2 levels and HO-1 levels in the presence of CoCl2. Additionally, EGCG suppressed hypoxia-induced apoptosis of BV2 microglia with cleavage of poly (ADP-ribose) polymerase (PARP) and caspase-3. In summary, EGCG protects microglia from hypoxia-induced inflammation and oxidative stress via abrogating the NF-κB pathway as well as activating the Nrf-2/HO-1 pathway.

Toll-Like Receptor 5 Promotes the Neurogenesis From Embryonic Stem Cells and Adult Hippocampal Neural Stem Cells in Mice.

Toll-like receptors (TLRs) make a crucial contribution to the innate immune response. TLR5 was expressed in embryoid body derived from mouse embryonic stem cells (mESCs) and ßIII-tubulin-positive cells under all-trans retinoic acid-treated condition. TLR5 was upregulated during neural differentiation from mESCs and augmented the neural differentiation of mESCs via nuclear factor-κB and interleukin 6/CREB pathways. Besides, TLR5 was expressed in SOX2- or doublecortin-positive cells in the subgranular zone of the hippocampal dentate gyrus where adult neurogenesis occurs. TLR5 inhibited the proliferation of adult hippocampal neural stem cells (NSCs) by regulating the cell cycle and facilitated the neural differentiation from the adult hippocampal NSCs via JNK pathway. Also, TLR5 deficiency impaired fear memory performance in mice. Our data suggest that TLR5 is a crucial modulator of neurogenesis from mESCs and adult hippocampal NSCs in mice and represents a new therapeutic target in neurological disorders related to cognitive function.

Essential Amino Acid-Enriched Diet Alleviates Dexamethasone-Induced Loss of Muscle Mass and Function through Stimulation of Myofibrillar Protein Synthesis and Improves Glucose Metabolism in Mice.

Dexamethasone (DEX) induces dysregulation of protein turnover, leading to muscle atrophy and impairment of glucose metabolism. Positive protein balance, i.e., rate of protein synthesis exceeding rate of protein degradation, can be induced by dietary essential amino acids (EAAs). In this study, we investigated the roles of an EAA-enriched diet in the regulation of muscle proteostasis and its impact on glucose metabolism in the DEX-induced muscle atrophy model. Mice were fed normal chow or EAA-enriched chow and were given daily injections of DEX over 10 days. We determined muscle mass and functions using treadmill running and ladder climbing exercises, protein kinetics using the D2O labeling method, molecular signaling using immunoblot analysis, and glucose metabolism using a U-13C6 glucose tracer during oral glucose tolerance test (OGTT). The EAA-enriched diet increased muscle mass, strength, and myofibrillar protein synthesis rate, concurrent with improved glucose metabolism (i.e., reduced plasma insulin concentrations and increased insulin sensitivity) during the OGTT. The U-13C6 glucose tracing revealed that the EAA-enriched diet increased glucose uptake and subsequent glycolytic flux. In sum, our results demonstrate a vital role for the EAA-enriched diet in alleviating the DEX-induced muscle atrophy through stimulation of myofibrillar proteins synthesis, which was associated with improved glucose metabolism.

Promoting Physical Activity and Weight Loss With mHealth Interventions Among Workers: Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Physical activity (PA) is a vital factor in promoting health in the workforce. Mobile health (mHealth) interventions have recently emerged in workplace health promotion as an effective strategy for inducing changes in health behaviors among workers; however, the effectiveness of mHealth interventions in promoting PA and weight loss for workers is unclear. OBJECTIVE: This study aims to provide a comprehensive analysis of current evidence on the effectiveness of mHealth interventions in promoting PA and weight loss among workers. METHODS: We searched relevant databases, including PubMed, Embase, CINAHL Complete, and the Cochrane Library, for publications on mHealth interventions in the English or Korean language from inception to December 2020. Randomized controlled trials that evaluated the effectiveness of mHealth in improving PA and weight loss were retrieved. A meta-analysis with a random effects model and subgroup analyses was performed on PA types and mHealth intervention characteristics. RESULTS: A total of 8 studies were included in this analysis. More than half of the studies (5/8, 63%) were identified as having a high risk of bias. The mHealth intervention group showed a significant improvement in PA (standardized mean difference [SMD] 0.22, 95% CI 0.03-0.41; P<.001; I2=78%). No significant difference in weight loss was observed when comparing the intervention group with the control groups (SMD 0.02, 95% CI -0.07 to 0.10; P=.48; I2=0%). A subgroup analysis was also performed; walking activity (SMD 0.70, 95% CI 0.21-1.19; P<.001; I2=83.3%), a multicomponent program (SMD 0.19, 95% CI 0.05-0.33; P=.03; I2=57.4%), objective measurement (SMD 0.58, 95% CI 0.05-1.10; P<.001; I2=87.3%), and 2 or more delivery modes (SMD 0.44, 95% CI 0.01-0.87; P<.001; I2=85.1%) were significantly associated with an enhancement in PA. CONCLUSIONS: This study suggests that mHealth interventions are effective for improving PA among workers. Future studies that assess long-term efficacy with a larger population are recommended.

Age-related digestibility of nutrients depending on the moisture content in aged dogs.

Digestibility of pet food can affect the health of dog, especially of aged animals. To maintain the health of dogs in an overall good status it is necessary to provide nutritionally balanced food. For example, the digestibility of dogs was known to be decreased along aging. In addition, losing teethes is an often event in aged dogs that could induce a problem to eat a large size dry pet food. Nonetheless, few detailed information is available on the most suited feeding for aged dogs. As part of the nutritional study of food for aged dogs, in this study, we tested whether food type impacts on digestibility on adult versus senior dogs. The methodology to measure the digestibility of nutrients was chosen the index method using chromium oxide. Dogs were fed the same commercial dry or wet diets, which were supplemented with 0.5% chromium oxide. The wet food was prepared by adding twice volume of water in the dry food prior to incubated overnight (14-16 hours) at room temperature. After five days, their feces were collected up to a total weight of > 200 g which was the amount to analyze undigested nutrients in feces as 3 repeats. In the apparent total tract digestibility analysis of the experimental breed, no difference in the digestibility of crude protein, crude fat, crude fiber, ash, and energy was observed regarding the moisture content of the food. Noteworthy, the digestibility of nitrogen free extract was significantly increased in senior dogs fed dry dog food compared with adult dogs fed the same diet, whereas no difference was observed between senior and adult dogs fed wet food. The small breed dogs showed similar results to the experimental breed dogs. However, the digestibility of crude fat was additionally affected by age and food type unlike the experimental breed dogs. This finding suggests that the food moisture content affects the digestibility of nutrients in dogs with aging. Hence, it may be helpful to determine the nutrient contents in foods for senior dogs depending on the food type.

Effects of the Resilience of Nurses in Long-Term Care Hospitals during on Job Stress COVID-19 Pandemic: Mediating Effects of Nursing Professionalism.

PURPOSE: To investigate nursing professionalism as a mediating factor in the relationship between resilience and job stress levels for nurses working in long-term care hospitals during the COVID-19 pandemic. METHODS: A cross-sectional survey was conducted from January to March 2021 in seven long-term care hospitals in the Seoul metropolitan area to measure resilience, nursing professionalism, and job stress among nurses. Simple and multiple regression analyses along with the Sobel test were performed to verify the mediating effect of nursing professionalism. RESULTS: Data from 200 nurses were included in the final analysis. Results showed that individual and occupational characteristics could lead to differences in nurses' resilience, job stress levels, and nursing professionalism. Nursing professionalism had a significant mediating effect on the relationship between resilience and job stress levels. The effect of resilience on job stress levels was significant (ß = -0.16, p = 0.024). After controlling for nursing professionalism, the effect declined and was not statistically significant (ß = -0.09, p = 0.251). CONCLUSION: There is a need to increase individual resilience and nursing professionalism through intervention programs and policy proposals to manage job stress among long-term care hospital nurses during the COVID-19 pandemic.

Effect of rhBMP-2 applied with a 3D-printed titanium implant on new bone formation in rabbit calvarium.

OBJECTIVE: This study sought to compare the biocompatibility of a three-dimensional (3D)-printed titanium implant with a conventional machined titanium product, as well as the effect of such implant applied with recombinant human Bone Morphogenetic Protein Type 2 (rhBMP-2) for guided bone regeneration. METHODOLOGY: Disk-shaped titanium specimens fabricated either by the conventional machining technique or by the 3D-printing technique were compared by MC3T3-E1 cells cytotoxicity assay. New bone formation was evaluated using a rapid prototype titanium cap applied to the calvaria of 10 rabbits, which were divided into two groups: one including an atelopeptide collagen plug on one side of the cap (group I) and the other including a plug with rhBMP-2 on the other side (group II). At six and 12 weeks after euthanasia, rabbits calvaria underwent morphometric analysis through radiological and histological examination. RESULTS: Through the cytotoxicity assay, we identified a significantly higher number of MC3T3-E1 cells in the 3D-printed specimen when compared to the machined specimen after 48 hours of culture. Moreover, morphometric analysis indicated significantly greater bone formation at week 12 on the side where rhBMP-2 was applied when evaluating the upper portion immediately below the cap. CONCLUSION: The results suggest that 3D-printed titanium implant applied with rhBMP-2 enables new bone formation.

Myostatin Inhibition-Induced Increase in Muscle Mass and Strength Was Amplified by Resistance Exercise Training, and Dietary Essential Amino Acids Improved Muscle Quality in Mice.

It has been frequently reported that myostatin inhibition increases muscle mass, but decreases muscle quality (i.e., strength/muscle mass). Resistance exercise training (RT) and essential amino acids (EAAs) are potent anabolic stimuli that synergistically increase muscle mass through changes in muscle protein turnover. In addition, EAAs are known to stimulate mitochondrial biogenesis. We have investigated if RT amplifies the anabolic potential of myostatin inhibition while EAAs enhance muscle quality through stimulations of mitochondrial biogenesis and/or muscle protein turnover. Mice were assigned into ACV (myostatin inhibitor), ACV+EAA, ACV+RT, ACV+EAA +RT, or control (CON) over 4 weeks. RT, but not EAA, increased muscle mass above ACV. Despite differences in muscle mass gain, myofibrillar protein synthesis was stimulated similarly in all vs. CON, suggesting a role for changes in protein breakdown in muscle mass gains. There were increases in MyoD expression but decreases in Atrogin-1/MAFbx expression in ACV+EAA, ACV+RT, and ACV+EAA+RT vs. CON. EAA increased muscle quality (e.g., grip strength and maximal carrying load) without corresponding changes in markers of mitochondrial biogenesis and neuromuscular junction stability. In conclusion, RT amplifies muscle mass and strength through changes in muscle protein turnover in conjunction with changes in implicated signaling, while EAAs enhance muscle quality through unknown mechanisms.

Job Stress and Cardiometabolic Lifestyle Modification Behaviors Among Workers in High-risk and Low-risk Workplaces.

OBJECTIVE: There is scarce evidence revealing an association between job stress and cardiometabolic lifestyle modification behaviors among workers. METHODS: A cross-sectional, correlation study was conducted among workers in high-risk and low-risk workplaces by work characteristics. RESULTS: Workers in high-risk workplaces had significantly higher job stress levels than low-risk workplaces. Higher job stress was significantly associated with lower cardiometabolic lifestyle modification behaviors (ß = -0.14, P = .001). This significant association was evident only for high-risk workplaces in total job stress (ß = -0.16, P = .001), including job demand (ß = -0.16, P = .005) and job insecurity (ß = -0.11, P = .026). CONCLUSIONS: Strategies for alleviating job stress should be prioritized to high-risk workplaces, and these efforts may concomitantly contribute to cardiometabolic risk reduction.

Effectiveness of a Mobile Health Management Program With a Challenge Strategy for Improving the Cardiovascular Health of Workers.

BACKGROUND: Workers' cardiovascular health can be influenced by individual willingness to practice healthy behaviors. A mobile health management program with a challenge strategy was administered to promote workers' healthy behaviors among small to medium-sized enterprises. METHODS: A 12-week program consisted of health communication with a challenge strategy was administered to the workers. RESULTS: The intervention group showed significantly improved scores for cardiovascular disease-related health behavior (Z = -2.44, P = 0.013), the job stress contributing factor of inadequate social support (F = 4.10, P = 0.049), and the cardiovascular disease-related health status of waist circumference (t = 3.22, P = 0.004), body fat (Z = -2.23, P = 0.024), and triglycerides (Z = -3.04, P = 0.001). CONCLUSION: This study's significance is its potential for increasing the convenience and joy of participating in intervention programs and acquiring health information through mobile platforms, which are easily accessible to the workers.

SLPI in periodontal Ligament is not sleepy during biophysical force-induced tooth movement.

AIM: We aimed to identify a key molecule that maintains periodontal tissue homeostasis during biophysical force-induced tooth movement (BTM) by orchestrating alveolar bone (AB) remodelling. MATERIALS AND METHODS: Differential display-PCR was performed to identify key molecules for BTM in rats. To investigate the localization and expression of the identified molecules, immunofluorescence, real-time RT-PCR and Western blotting were performed in rats and human periodontal ligament (PDL) cells. Functional test and micro-CT analysis were performed to examine the in vivo effects of the identified molecules on BTM. RESULTS: Secretory leucocyte peptidase inhibitor (SLPI) in the PDL was revealed as a key molecule for BTM-induced AB remodelling. SLPI was enhanced in the PDL under both compression and tension, and downregulated by an adenyl cyclases inhibitor. SLPI induced osteoblastogenic genes including runt-related transcription factor 2 (Runx2) and synergistically augmented tension-induced Runx2 expression. SLPI augmented mineralization in PDL cells. SLPI induced osteoclastogenic genes including receptor activator of nuclear factor kappa-Β ligand (RANKL) and synergistically augmented the compression-induced RANKL and macrophage colony-stimulating factor (MCSF) expression. Finally, the in vivo SLPI application into the AB significantly augmented BTM. CONCLUSIONS: SLPI or its inhibitors might serve as a biological target molecule for therapeutic interventions to modulate BTM.

Mineral trioxide aggregate-induced AMPK activation stimulates odontoblastic differentiation of human dental pulp cells.

AIM: To investigate the role of autophagy in MTA-induced odontoblastic differentiation of human dental pulp cells (HDPCs). METHODOLOGY: In MTA-treated HDPCs, odontoblastic differentiation was assessed based on expression levels of dentine sialophosphoprotein (DSPP) and dentine matrix protein 1 (DMP1), alkaline phosphatase activity (ALP) activity by ALP staining and the formation of mineralized nodule by Alizarin red S staining. Expression of microtubule-associated protein 1A/1B-light chain3 (LC3), adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signalling molecules and autophagy-related genes was analysed by Western blot analysis and Acridine orange staining was used to detect autophagic lysosome. For in vivo experiments, tooth cavity preparation models on rat molars were established and the expression of proteins-related odontogenesis and autophagy markers was observed by Immunohistochemistry and Western blot analysis. Kruskal-Wallis with Dunn's multiple comparison was used for statistical analysis. RESULTS: Mineral trioxide aggregate (MTA) promoted odontoblastic differentiation of HDPCs, accompanied by autophagy induction, including formation of autophagic lysosome and cleavage of LC3 to LC3II (P < 0.05). Conversely, inhibition of autophagy through 3MA significantly attenuated the expression level of DSPP (P < 0.05) and DMP1 (P < 0.05) as well as formation of mineralized nodules (P < 0.05), indicating the functional significance of autophagy in MTA-induced odontoblastic differentiation. Also, MTA increased the activity of AMPK (P < 0.01), whereas inhibition of AMPK by compound C downregulated DSPP (P < 0.01) and DMP1 (P < 0.05), but increased the phosphorylation of mTOR (P < 0.05), p70S6 (P < 0.01) and Unc-51-like kinases 1 (ULK1) (ser757) (P < 0.01), explaining the involvement of AMPK pathway in MTA-induced odontoblast differentiation. In vivo study, MTA treatment after tooth cavity preparation on rat molars upregulated DMP-1 and DSPP as well as autophagy-related proteins LC3II and p62, and enhanced the phosphorylation of AMPK. CONCLUSION: MTA induced odontoblastic differentiation and mineralization by modulating autophagy with AMPK activation in HDPCs. Autophagy regulation is a new insight on regenerative endodontic therapy using MTA treatment.

Effect of rhBMP-2 applied with a 3D-printed titanium implant on new bone formation in rabbit calvarium

Abstract Objective This study sought to compare the biocompatibility of a three-dimensional (3D)-printed titanium implant with a conventional machined titanium product, as well as the effect of such implant applied with recombinant human Bone Morphogenetic Protein Type 2 (rhBMP-2) for guided bone regeneration. Methodology Disk-shaped titanium specimens fabricated either by the conventional machining technique or by the 3D-printing technique were compared by MC3T3-E1 cells cytotoxicity assay. New bone formation was evaluated using a rapid prototype titanium cap applied to the calvaria of 10 rabbits, which were divided into two groups: one including an atelopeptide collagen plug on one side of the cap (group I) and the other including a plug with rhBMP-2 on the other side (group II). At six and 12 weeks after euthanasia, rabbits calvaria underwent morphometric analysis through radiological and histological examination. Results Through the cytotoxicity assay, we identified a significantly higher number of MC3T3-E1 cells in the 3D-printed specimen when compared to the machined specimen after 48 hours of culture. Moreover, morphometric analysis indicated significantly greater bone formation at week 12 on the side where rhBMP-2 was applied when evaluating the upper portion immediately below the cap. Conclusion The results suggest that 3D-printed titanium implant applied with rhBMP-2 enables new bone formation.

Patterns of change in cardiovascular risks of Korean male workers: a 10-year cohort analysis using the National Health Insurance Service-National Sample Cohort (NHIS-NSC) 2.0 database.

OBJECTIVE: Health behaviour is one of the major determinants of cardiovascular diseases in working population. This study was tried to investigate the trend of cardiovascular health level, the relationship between continuous health behaviours, and changes in the risk of cardiovascular diseases of male workers by using a nationwide database. DESIGN: This study is a retrospective cohort study. SETTING AND PARTICIPANTS: The study analysed data of 57 837 male workers whose personal health examination data were continuously traced using Korea's National Health Insurance Service-National Sample Cohort 2.0 database. PRIMARY OUTCOME MEASURES: A 10-year trend for all cardiovascular risks and change for the risks according to the consistent performance of healthy behaviours. RESULTS: The results showed that the risk of being overweight (adjusted OR (aOR) 1.63, 95% CI 1.59 to 1.68) and obese (aOR 1.51, 95% CI 1.47 to 1.56) increased. The index of cardiovascular risk also increased for high fasting glucose (aOR 1.77, 95% CI 1.62 to 1.95) and high total cholesterol (aOR 1.68, 95% CI 1.60 to 1.76), respectively. The risks of high fasting glucose (aOR 2.09, 95% CI 1.40 to 3.13), high triglycerides (aOR 1.27, 95% CI 1.14 to 1.42) and high low-density lipoprotein cholesterol (aOR 1.38, 95% CI 1.14 to 1.66) were increased among high-risk smokers. Similarly, the risk of high total cholesterol (aOR 2.20, 95% CI 1.35 to 3.58) and high triglycerides (aOR 1.42, 95% CI 1.09 to 1.85) were increased among high-risk drinkers. In addition, the increase in the risk of being overweight (aOR 2.20, 95% CI 1.83 to 2.65) and obese (aOR 1.90, 95% CI 1.59 to 2.27) were analysed among who had not consistently exercised. CONCLUSIONS: Since the pattern of change in the level of cardiovascular risk related to the continuous health behaviours of male workers was identified, the findings of the present study can be used as basic data to develop health promotion policies for the population.

APE1 Promotes Pancreatic Cancer Proliferation through GFRα1/Src/ERK Axis-Cascade Signaling in Response to GDNF.

Pancreatic cancer is the worst exocrine gastrointestinal cancer leading to the highest mortality. Recent studies reported that aberrant expression of apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is involved in uncontrolled cell growth. However, the molecular mechanism of APE1 biological role remains unrevealed in pancreatic cancer progression. Here, we demonstrate that APE1 accelerates pancreatic cancer cell proliferation through glial cell line-derived neurotrophic factor (GDNF)/glial factor receptor α1 (GFRα1)/Src/ERK axis-cascade signaling. The proliferation of endogenous APE1 expressed-MIA PaCa-2, a human pancreatic carcinoma cell line, was increased by treatment with GDNF, a ligand of GFRα1. Either of downregulated APE1 or GFRα1 expression using small interference RNA (siRNA) inhibited GDNF-induced cancer cell proliferation. The MEK-1 inhibitor PD98059 decreased GDNF-induced MIA PaCa-2 cell proliferation. Src inactivation by either its siRNA or Src inhibitor decreased ERK-phosphorylation in response to GDNF in MIA PaCa-2 cells. Overexpression of GFRα1 in APE1-deficient MIA PaCa-2 cells activated the phosphorylation of Src and ERK. The expression of both APE1 and GFRα1 was gradually increased as progressing pancreatic cancer grades. Our results highlight a critical role for APE1 in GDNF-induced pancreatic cancer cell proliferation through APE1/GFRα1/Src/ERK axis-cascade signaling and provide evidence for future potential therapeutic drug targets for the treatment of pancreatic cancer.

Sex Differences in Cardiovascular Disease Risk by Socioeconomic Status (SES) of Workers Using National Health Information Database.

The socioeconomic status (SES) and health behaviors of workers are associated with the risks of developing obesity, diabetes, hypertension, hyperlipidemia, and other cardiovascular diseases. Herein, we investigated the factors influencing cardiovascular disease (CVD) risk based on the SES of male and female workers. This cross-sectional analysis used the National Health Information Database to assess the associations between gender, SES (income level, residential area), health behaviors, and CVD-related health status of workers, through multinomial logistic regression. Upon analysis of a large volume of data on workers during 2016, the smoking and drinking trends of male and female workers were found to differ, causing different odds ratio (OR) tendencies of the CVD risk. Also, while for male workers, higher ORs of obesity or abdominal obesity were associated with higher incomes or residence in metropolitan cities, for female workers, they were associated with lower incomes or residence in rural areas. Additionally, among the factors influencing CVD risk, lower income and residence in rural areas were associated with higher CVD risk for male and female workers. The study findings imply the importance of developing gender-customized intervention programs to prevent CVD, due to gender-specific associations between CVD-related health status and health behaviors according to SES.

Health promotion program for office workers with SEM based on the WHO's healthy workplace framework.

This study attempts to develop and verify the effectiveness of a health promotion program for office workers based on the social ecological model and the World Health Organization's Healthy Workplace Framework. This study involved 272 office workers of a small and medium-sized enterprise in Korea. Data were analyzed through descriptive statistics, repeated measures analysis of variance (ANOVA) and Bonferroni correction using SPSS/WIN 23.0. Workplace environmental support was provided to all workers, while a 6-month intensive core program based on social support was implemented for the intensive management group. Based on the participation rate, individuals were divided into the core and dropout groups. In all office workers, there were negative changes in high-density lipoprotein cholesterol and job stress during the period. Meanwhile, the intensive group showed significant changes in body mass index and diastolic blood pressure. The study suggests that the organization's support for a healthy environment and an individual's continued participation based on social support are essential for the effectiveness of a health promotion program for office workers.

Combination of mineral trioxide aggregate and propolis promotes odontoblastic differentiation of human dental pulp stem cells through ERK signaling pathway.

The aim of this study is to investigate combined effects of mineral trioxide aggregate (MTA) and propolis on odontoblastic differentiation of human dental pulp stem cells (DPSCs) and to find a signaling pathway involved. Combination of MTA and propolis significantly up-regulated the expression of DSPP and DMP1, and facilitated a mineral nodule formation (p < 0.05). Treatments with MTA, propolis or combined increased the phosphorylation of extracellular signal-regulated kinases (ERK), one of mitogen-activated protein kinases signaling cascades during odontogenic differentiation of DPSCs (p < 0.05), and U0126, an inhibitor of ERK, decreased calcium deposits (p < 0.05). Combination of MTA and propolis promotes odontogenic differentiation and mineralization of DPSCs through ERK pathway.