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Background/Aims The etiology of irritable bowel syndrome (IBS) is associated with intestinal mucosal barrier damage. However, changes in the tight junction (TJ) proteins in IBS have not been fully elucidated. This study aimed to evaluate TJ protein changes in IBS patients and the relationship between aging and disease severity. Methods Thirty-six patients with IBS fulfilling the Rome IV criteria and twenty-four controls were included. To evaluate the change of TJ in the colonic mucosa, quantitative reverse transcription polymerase chain reaction, western blot, and immunohistochemistry (IHC) were performed, respectively. Results The entire IBS group (n = 36) exhibited decreased levels of claudin-1 and -2 mRNA compared to the control group (n = 24), with statistical significance (p < 0.05). Additionally, in western blot analyses, both claudin-1 and ZO-1 levels were significantly reduced in the IBS group compared to the control group (n = 24) (p < 0.05). IHC analysis further revealed that ZO-1 expression was significantly lower in the IBS group than in the control group (p < 0.001). This trend of reduced ZO-1 expression was also observed in the moderate-to-severe IBS subgroup (p < 0.001). Significantly, ZO-1 expression was notably lower in both the young- (p = 0.036) and old-aged (p = 0.039) IBS groups compared to their respective age-matched control groups. Subtype analysis indicated a more pronounced decrease in ZO-1 expression with advancing age. Conclusions ZO-1 expression was especially decreased in the aged IBS group. These results suggest that ZO-1 might be the prominent TJ protein causing IBS in the aging population.

Abstract Background Korea has a two-tiered universal health security system: the wage-based National Health Insurance (NHI) program and government-subsidized Medical Aid (MA) program. Beneficiaries of the MA program belong to the lowest economic class. This study aims to investigate the association between economic status—defined as NHI or MA enrollment—and health disparity of older people aged ≥ 65 years in South Korea. Methods The claims records of 672,525 older age population from the 2017 Health Insurance Review and Assessment Service-Adult Patient Sample were used to estimate adjusted odds ratios (aORs) of MA vs. NHI beneficiaries for prevalence for common geriatric diseases. Logistic regression and negative binomial regression were used to investigate the association between economic status and prevalence or healthcare utilization for each disease. Results MA beneficiaries showed significantly higher prevalence than NHI beneficiaries for seven out of nine diseases (aORs ranging from 1.18 to 1.95). The discrepancy in the prevalence between the two groups was highest among those aged 65–69 years (aORs: 1.34–2.94), and diminished as they got older (aORs: 1.05–1.67). MA beneficiaries had significantly more outpatient visits to treat six diseases (aORs: 1.07–1.28), and more hospitalization to treat seven diseases (aORs:1.08–1.73) than NHI beneficiaries. Conclusion The higher prevalence of common geriatric diseases among MA than NHI beneficiaries confirms unfavorable health disparity in the elderly living in extreme poverty. Similar or higher healthcare utilization in treating the same conditions among MA beneficiaries suggests a low possibility of inequity for access to healthcare resources covered by the universal health security system due to poor economic status. Greater excess use of inpatient than outpatient care by MA beneficiaries implies that the condition of poor older adults might be more severe when diagnosed with the same disease.

BRASH (Bradycardia, Renal failure, Atrioventricular [AV]-node blocker medications, Shock, and Hyperkalemia), a novel syndrome, is a synergistic interaction between AV node blockers and hyperkalemia, resulting in bradycardia. We report a case of BRASH syndrome with marked bradycardia in a patient with End-Stage Renal Disease (ESRD) associated with synergistic interaction between mild hyperkalemia and AV node blockers. Anesthesiologists should be aware of these clinical features, in which ESRD patients with baseline mild hyperkalemia are particularly susceptible to bradycardia. This report will help in its early recognition as well as enable comprehensive and appropriate treatment strategies without further invasive therapy.

BackgroundTailored therapy has been widely used for patients with Helicobacter pylori (H. pylori) infection in South Korea. Herein, we evaluated the treatment outcomes of tailored clarithromycin-based triple therapy (TT) in patients infected with H. pylori.MethodsWe enrolled 460 patients without A2142G and A2143G point mutations by dual priming oligonucleotide-based polymerase chain reaction who had taken TT and undergone the urease breath test to evaluate eradication in clinical practice. Eradication rates according to the treatment duration and dose of clarithromycin were analyzed.ResultsAmong 460 patients (164 women, median age 63.0 years), 250 patients underwent TT with full-dose clarithromycin (TT-full CLA), and 216 patients underwent TT with half-dose clarithromycin (TT-half CLA). The eradication rates were 88.0% (220/250) in patients with TT-full CLA and 85.2% (179/210) in patients with TT-half CLA. In 250 patients with TT-full CLA, the eradication rates were 86.8% (33/38) in patients with 7-day TT-full CLA and 88.2% (187/212) in patients with 10-day or 14-day TT-full CLA (P = 0.788). In 210 patients with TT-half CLA, the eradication rates were 84.2% (139/165) in those with a 7-day TT-half CLA and 88.9% (40/45) in those with a 10-day or 14-day TT-half CLA (P = 0.436).ConclusionFor patients with H. pylori infection without A2142G and A2143G point mutations by DPO-PCR in clinical practice, treatment extension above 7-day TT with full CLA did not improve the eradication rates. Future studies on the treatment outcomes of TT-half CLA considering effectiveness and compliance are warranted.

Abstract Combined carbon capture and storage and CO2-enhanced oil recovery (CCS-EOR) can reconcile the demands of business with the need to mitigate the effects of climate change. To improve the performance of CCS-EOR, liquefied petroleum gas (LPG) can be co-injected with CO2, leading to a reduction in the minimum miscibility pressure. However, gas injection can cause asphaltene problems, which undermines EOR and CCS performances simultaneously. Here, we systematically examine the mechanisms of asphaltene deposition using compositional simulations during CO2-LPG–comprehensive water–alternating-gas (WAG) injection. The LPG accelerates asphaltene deposition, reducing gas mobility, and increases the performance of residual trapping by 9.2% compared with CO2 WAG. In contrast, solubility trapping performance declines by only 3.7% because of the greater reservoir pressure caused by the increased formation damage. Adding LPG enhances oil recovery by 11% and improves total CCS performance by 9.1% compared with CO2 WAG. Based on reservoir simulations performed with different LPG concentrations and WAG ratios, we confirmed that the performance improvement of CCS-EOR associated with increasing LPG and water injection reaches a plateau. An economic evaluation based on the price of LPG should be carried out to ensure practical success.

ABSTRACT Alveolar bone is both morphologically and functionally different from other bones of the axial or peripheral skeleton. Because of its sensitive nature to external stimuli including mechanical stress, bone loss stimuli, and medication‐related osteonecrosis of the jaw, alveolar bone rendering is seen as an important factor in various dental surgical processes. Although multiple studies have validated the response of long bone to various factors, how alveolar bone responds to functional stimuli still needs further clarification. To examine the characteristics of bone in vitro, we isolated cells from alveolar, femur, and tibia bone tissue. Although primary cultured mouse alveolar bone‐derived cells (mABDCs) and mouse long bone‐derived cells (mLBDCs) exhibited similar osteoblastic characteristics, morphology, and proliferation rates, both showed distinct expression of neural crest (NC) and epithelial–mesenchymal interaction (EMI)‐related genes. Furthermore, they showed significantly different mineralization rates. RNA sequencing data demonstrated distinct transcriptome profiles of alveolar bone and long bone. Osteogenic, NC‐, and EMI‐related genes showed distinct expression between mABDCs and mLBDCs. When the gene expression patterns during osteogenic differentiation were analyzed, excluding several osteogenic genes, NC‐ and EMI‐related genes showed different expression patterns. Among EMI‐related proteins, BMP4 elevated the expression levels of osteogenic genes, Msx2, Dlx5, and Bmp2 the most, more noticeably in mABDCs than in mLBDCs during osteogenic differentiation. In in vivo models, the BMP4‐treated mABDC group showed massive bone formation and maturation as opposed to its counterpart. Bone sialoprotein expression was also validated in calcified tissues. Overall, our data suggest that alveolar bone and long bone have different responsiveness to EMI by distinct gene regulation. In particular, BMP4 has critical bone formation effects on alveolar bone, but not on long bone. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Witch hazel extracts have been used for decades as cosmetic ingredients in skin care products. Our present study aims to evaluate its potential in anti-pollution products using a previously reported in vitro model. Calcium is a universal second messenger, and we used human respiratory and skin cells to detect changes in intracellular Ca2+ concentrations upon particulate matter contact. Both an increase in pro-inflammatory markers and a decrease in tight junction proteins were confirmed, as previously reported. Witch hazel stem and leaf extract showed significant attenuation of Ca2+ response upon the challenge; it displayed systematic regulations of the signal generator, PAR-2; a pro-inflammatory marker, NF-κB; and a tight junction protein, Occludin. We identified hexagalloylglucose from the extract and concluded that it is a major component regulating protection from particulate matter. Based on these results, witch hazel extract containing hexagalloylglucose is an active ingredient in anti-pollution skin care products.

The microbial enhanced oil recovery (MEOR) method is an eco-friendly and economical alternative technology. The technology involves a variety of uncertainties, and its success depends on controlling microbial growth and metabolism. Though a few numerical studies have been carried out to reduce the uncertainties, no attempt has been made to consider temperature, pressure, and salinity in an integrated manner. In this study, a new modeling method incorporating these environmental impacts was proposed, and MEOR analysis was performed. As a result, accurate modeling was possible to prevent overestimating the performance of MEOR. In addition, oil recovery was maximized through sensitivity analysis and optimization based on an integrative model. Finally, applying MEOR to an actual reservoir model showed a 7% increase in oil recovery compared to waterflooding. This result proved the practical applicability of the method.

Dimethyl ether (DME) is a compound first introduced by Shell as a chemical solvent for enhanced oil recovery (EOR). This study aims to investigate the efficiency of EOR using the minimum miscible pressure (MMP) and viscous gravity number when a mixed solvent of CO2 and DME is injected. Adding DME to the CO2 water-alternating-gas process reduces the MMP and viscous gravity number. Reduction in MMP results in miscible conditions at lower pressures, which has a favorable effect on oil swelling and viscosity reduction, leading to improved mobility of the oil. In addition, the viscous gravity number decreases, increasing the sweep efficiency by 26.6%. Numerical studies were conducted through a series of multi-phase, multi-component simulations. At a DME content of 25%, the MMP decreased by 30.1% and the viscous gravity number decreased by 66.4% compared with the injection of CO2 only. As a result, the maximum oil recovery rate increased by 31% with simultaneous injection of DME and CO2 compared with only using CO2.

Dietary supplement and personal care products aiming to provide protection from air pollution have been of great interest for decades. Epidemiology demonstrated that PM10 and PM2.5 particulate matter (PM) are an actual threat to public health worldwide, but the detailed processes of how these particles attack the cells are not fully understood. Here, we report that the measurement of intracellular calcium concentration ([Ca2+]i) using human respiratory or skin cells can illustrate pollutant challenges by triggering Ca2+ influx in these cells. This signal was generated by proteinase-activated receptor-2 (PAR-2), confirmed by competition analyses, and Phellodendron amurense bark extract (PAE), a traditional medicine, was able to control the response and expression of PAR-2. Increase in proinflammatory cytokines and decrease in cell adhesion components could suggest a severe damage status by air pollutants and protection by PAE. Finally, we identified 4-O-feruloylquinic acid (FQA), an active compound of PAE, showing the same effects on Ca2+ influx and PAR-2 regulation. The results presented here should help understand the underlying mechanism of PM insults and the beneficial effect of standardized PAE as dietary supplement or cosmetical ingredient.

Background/Aims: Although Vitisin A, derived from wine grapes, is known to have cytotoxic, anti-adipogenic, anti-inflammatory and antioxidant effects, the underlying antitumor mechanism has not been investigated in prostate cancer cells to date. In the present study, the apoptotic mechanism of Vitisin A plus TNF-related apoptosis-inducing ligand (TRAIL) in prostate cancer cells was elucidated. Methods: The cytotoxicity of Vitisin A and/or TRAIL against PC-3, DU145 and LNCaP prostate cancer cells was measured by MTT colorimetric assay. Annexin V-FITC Apoptosis Detection kit was used to detect apoptotic cells by flow cytometry. Intracellular levels of ROS were measured by flow cytometry using 2070-diacetyl dichlorofluorescein (DCFDA). Results: Combined treatment with Vitisin A and TRAIL enhanced cytotoxicity and also increased sub-G1 population in PC-3 cells better than DU145 or LNCap prostate cancer cells. Similarly, Annexin V and PI staining revealed that combination increased early and late apoptosis in PC-3 cells compared to untreated control. Consistently, combination attenuated the expression of pro-caspases 7/8, DcR1, Bcl-XL or Bcl-2 and activated caspase 3, FADD, DR5 and DR4 in PC-3 cells. Also, combination increased DR5 promoter activity compared to untreated control. Furthermore, combination increased the production of reactive oxygen species (ROS) and DR5 cell surface expression. The ROS inhibitor NAC and silencing of DR5 by siRNA transfection inhibited the ability of combination to induce PARP cleavage and generate ROS. Conclusion: These findings provide evidence that Vitisin A can be used in conjunction with TRAIL as a potent TRAIL sensitizer for synergistic apoptosis induction via upregulation of DR5 and production of ROS in prostate cancer cells.

The addition of LPG to the CO2 stream leads to minimum miscible pressure (MMP) reduction that causes more oil swelling and interfacial tension reduction compared to CO2 EOR, resulting in improved oil recovery. Numerical study based on compositional simulation has been performed to examine the injectivity efficiency and transport behavior of water-alternating CO2-LPG EOR. Based on oil, CO2, and LPG prices, optimum LPG concentration and composition were designed for different wettability conditions. Results from this study indicate how injected LPG mole fraction and butane content in LPG affect lowering of interfacial tension. Interfacial tension reduction by supplement of LPG components leads to miscible condition causing more enhanced oil recovery. The maximum enhancement of oil recovery for oil-wet reservoir is 50% which is greater than 22% for water-wet reservoir. According to the result of net present value (NPV) analysis at designated oil, CO2, propane, and butane prices, the optimal injected LPG mole fraction and composition exist for maximum NPV. At the case of maximum NPV for oil-wet reservoir, the LPG fraction is about 25% in which compositions of propane and butane are 37% and 63%, respectively. For water-wet reservoir, the LPG fraction is 20% and compositions of propane and butane are 0% and 100%.

Sphingomonas paucimobilis is an aerobic Gram-negative bacillus found in soil and water. Knowledge regarding the role of this infectious agent is limited because it is rarely isolated from human material. Furthermore, it is an unusual pathogen in cases of peritoneal dialysis (PD)-associated peritonitis. The clinical courses and outcomes of peritonitis caused by S. paucimobilis are variable. Whereas some patients were cured with appropriate antibiotic therapy, others required catheter removal. Cases of PD-associated peritonitis caused by S. paucimobilis have been reported worldwide, and there was a case report of coinfection with S. paucimobilis and Chryseobacterium indologenes in Korea. However, there has been no case caused by S. paucimobilis as a single pathogen. We report a case of PD-associated peritonitis due to S. paucimobilis in which the patient recovered after catheter removal.

This study is empirical and descriptive one for analysing the nurse's job. This study used the methods of making the job descriptions and survey research about the nurses' perception of importance in their job and the frequency of job performance. The results were in following: the research divided the job of new nurse into 11 duties. And duties include the 65 tasks and 446 task elements. According to the survey research on the nurses' perception of importance and the frequency of job performance, the elements graded higher than 2.5 point in importance perception, were 47 elements(10.5%). And the elements from 2.0 to 2.5 were 93 elements(18.8%). Regarding the frequency of job performance, the 56 elements were graded higher than 2.5 point on average(12.6%), and 84 elements were from 2.0 to 2.5(18.8%). Especially, the elements which grade higher than 2.5 point in both two items, were 31 elements(7.0%). Based on these results, the elements graded higher than 2.0 point were grouped to the core competencies for registered nurse, these could be core concepts to develop the questions for national examination for nurse's registration.

Water-alternating-gas (WAG) method provides superior mobility control of CO 2 and improves sweep efficiency. However, WAG process has some problems in highly viscous oil reservoir such as gravity overriding and poor mobility ratio. To examine the applicability of carbon dioxide to recover viscous oil from highly heterogeneous reservoirs, this study suggests polymer-alternating-gas (PAG) process. The process involves a combination of polymer flooding and CO 2 injection. In this numerical model, high viscosity of oil and high heterogeneity of reservoir are the main challenges. To confirm the effectiveness of PAG process in the model, four processes (waterflooding, continuous CO 2 injection, WAG process, and PAG process) are implemented and recovery factor, WOR, and GOR are compared. Simulation results show that PAG method would increase oil recovery over 45% compared with WAG process. The WAG ratio of 2 is found to be the optimum value for maximum oil recovery. The additional oil recovery of 3% through the 2 WAG ratio is achieved over the base case of 1: 1 PAG ratio and 180 days cycle period.

Abstract Background Quantifying cell division and death is central to many studies in the biological sciences. The fluorescent dye CFSE allows the tracking of cell division in vitro and in vivo and provides a rich source of information with which to test models of cell kinetics. Cell division and death have a stochastic component at the single-cell level, and the probabilities of these occurring in any given time interval may also undergo systematic variation at a population level. This gives rise to heterogeneity in proliferating cell populations. Branching processes provide a natural means of describing this behaviour. Results We present a likelihood-based method for estimating the parameters of branching process models of cell kinetics using CFSE-labeling experiments, and demonstrate its validity using synthetic and experimental datasets. Performing inference and model comparison with real CFSE data presents some statistical problems and we suggest methods of dealing with them. Conclusion The approach we describe here can be used to recover the (potentially variable) division and death rates of any cell population for which division tracking information is available.

Background: Considering the interactions between heavy metals, a comprehensive evaluation of the effects of exposure to various types of co-interacting heavy metals on health is required. This study assessed the association between dyslipidemia markers and blood mercury, lead, cadmium, iron, zinc, and nickel levels in residents of an abandoned refinery plant., Methods: A total of 972 individuals (exposed group: 567, control group: 405) living near the Janghang refinery plant in the Republic of Korea were included. Blood mercury, lead, cadmium, iron, zinc, nickel, cholesterol, and triglyceride levels were measured. The combined effect of the six heavy metals on dyslipidemia markers was evaluated using a Bayesian kernel machine regression (BKMR) model and compared with the results of a linear regression analysis. The BKMR model results were compared using a stratified analysis of the exposed and control groups., Results: In the BKMR model, the combined effect of the six heavy metals was significantly associated with total cholesterol (TC) levels both below the 45th percentile and above the 55th percentile in the total population. The combined effect range between the 25th and 75th percentiles of the six metals on TC levels was larger in the exposed group than that in the total population. In the control group, the combined effects of the changes in concentration of the six heavy metals on the TC concentration were not statistically significant., Conclusion: These results suggest that the cholesterol levels of residents around the Janghang refinery plant may be elevated owing to exposure to multiple heavy metals., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: The global use of pesticides steadily increased until the early 2010s. Pesticides play a significant role in agriculture in Korea. Metabolic syndrome is more prevalent in rural areas than in urban areas. This study explored the potential association between organophosphate and pyrethroid pesticide exposure and metabolic syndrome., Methods: This study enrolled 1,317 individuals who participated in the Pesticide Exposure and Intoxication Study conducted by the Dankook University Hospital Center for Farmers' Safety and Health from 2014 to 2019. Urinary levels of dimethylphosphate, dimethylthiophosphat, diethylphosphate, and diethylthiophosphate were measured to assess organophosphate pesticide exposure and urinary levels cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid, and 3-phenoxybenzoic acid were measured to assess pyrethroid pesticide exposure., Results: The odds ratio for the 4th quartile group of organophosphate metabolites concentration was 1.48 (95% confidence interval: 1.06-2.09) compared to the 1st quartile group after adjustment for general factors. In addition, a positive trend was observed across the quartile groups of organophosphate metabolites concentration. A positive trend was noted across the quartile groups of organophosphate metabolites in males, while no significant association was observed in females. Furthermore, no significant associations were observed between metabolic syndrome and pyrethroid metabolites concentration., Conclusions: A positive correlation was observed between the prevalence of metabolic syndrome and the concentrations of urinary organophosphate metabolites, consistent with previous research finding. This association may be attributed to the action of organophosphates as acetylcholinesterase inhibitors, stimulating beta cells in the islets of Langerhans. This can lead to alterations in lipid metabolism and insulin resistance, ultimately leading to metabolic syndrome development. Metabolic syndrome is a major contributor to cardiovascular disease; therefore, it is necessary to identify the risk factors unique to rural areas, such as pesticide exposure.

Objective: Optimism, social support, and spirituality can be important factors related to coronavirus disease-2019 (COVID-19) stress. However, studies investigating the influence and interplay of optimism, social support, and spirituality on COVID-19 simultaneously are still few. This study is aimed to explore the influence of optimism, social support, and spirituality on COVID-19 stress in the Christian church community., Methods: A total 350 participants were included in this study. This study was cross-sectionally conducted by using an online survey on optimism, social support, spirituality, and COVID-19 stress that were measured by the Life Orientation Test-Revised (LOT-R), Multidimensional Scale of Perceived Social Support Scale (MSPSS), Spiritual Well-Being Scale (SWBS), and COVID-19 Stress Scale for Korean People (CSSK). The prediction models for COVID-19 stress were analyzed by using univariate and multiple linear regression., Results: Based on the results of univariate linear regression, subjective feelings on income (p<0.001) and health status (p<0.001), LOTR (p<0.001), MSPSS (p=0.025), and SWBS (p<0.001) scores were significantly associated with COVID-19 stress. The multiple linear regression model with subjective feelings on income and health status and SWSB score was significant (p<0.001) and explained 17.7% of the variance (R2=0.177)., Conclusion: This study showed that subjective feeling on low income, those who had poor health status, lower optimism, lower perceived social support, and lower spirituality were significantly affected with COVID-19 stress. Especially, the model with subjective feelings on income and health status, and spirituality showed highly significant effects, despite the interaction with associated factors. To cope with unpredictable stressful situations like the COVID-19 pandemic, integrated interventions on psycho-socio-spiritual aspect are warranted.

Sasa borealis (Hack.) Makino & Shibata or broad-leaf bamboo is famous for its richness of bioactive natural products and its uses in traditional medicine for its anti-inflammatory, diuretic, and antipyretic properties and preventive effects against hypertension, arteriosclerosis, cardiovascular disease, and cancer. The present study investigated the antioxidant activity of S. borealis hot water extract (SBH) and its effects in ameliorating hydrogen peroxide-induced oxidative stress, using an African green monkey kidney epithelial cell line (Vero). Known polyphenols in SBH were quantified by HPLC analysis. SBH indicated a dose-dependent increase for reducing power, ABTS + (IC 50 = 96.44 ± 0.61 µg/mL) and DPPH (IC 50 = 125.78 ± 4.41 µg/mL) radical scavenging activities. SBH markedly reduced intracellular reactive oxygen species (ROS) generation in the Vero cells and increased the protective effects against H 2 O 2 -induced oxidative stress by reducing apoptosis. Other than the direct involvement in neutralizing ROS, metabolites in SBH were also found to induce NRF2-mediated production of antioxidant enzymes, HO-1, and NQO1. These findings imply that S. borealis hot water extract can be utilized to create nutraceutical and functional foods that can help to relieve the effects of oxidative stress in both acute and chronic kidney injury.

The present study discloses the identification of phenolic compounds in Moringa oleifera hot water extract (MOH) and the evaluation of its antioxidant activity on H 2 O 2 -induced oxidative stress in Vero cells. Upon analysis, MOH was found to contain phenolic compounds and indicated 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS + ) radical scavenging with IC 50 values of 102.52 and 122.55 µg/mL, respectively. The ferric reducing antioxidant power (FRAP) of MOH indicated a dose-dependent increase with a maximum absorbance at 125 μg/mL and the oxygen radical absorbance capacity (ORAC) of MOH was 1004.95 µmol TE/mg. Results showed that MOH dose-dependently reduced intracellular ROS generation in H 2 O 2 -stimulated Vero cells while increasing the cell viability. Fluorescence microscopy and flowcytometric analyses have supported the above findings. MOH markedly suppressed the H 2 O 2 -induced mitochondrial depolarization and apoptosis through suppression of the mitochondrial-mediated apoptosis pathway and activated the Nrf2/HO-1 signaling pathway by possibly involving H 2 O 2 generation in cell media. Findings of western blot were supported by immunocytochemistry of Nrf2 nuclear translocation. Thus, MOH bioactivity would potentiate its applications in manufacturing functional food.

The purpose of this study was to evaluate the relationship between farmer's syndrome and neurotoxic symptoms in farming couples. The study was conducted on 348 farmers (174 couples) in Chungnam Province of South Korea. We obtained information on general and agricultural characteristics, farmer's syndrome, and neurotoxic symptoms through face-to-face surveys from 2014 to 2019. The Korean version of the diagnostic standard scale was used for farmer's syndrome, and the Swedish Q16 questionnaire was used for neurotoxic symptoms. Logistic regression analysis was used to identify neurotoxic symptoms affected by farmer's syndrome. The prevalence of 'positive' neurotoxic symptoms was higher in wives (72.4%) than in husbands (56.9%). Compared with husbands with 'negative and probable' farmer's syndrome (reference), husbands with 'positive' farmer's syndrome were more likely to have 'positive' neurotoxic symptoms (odds ratio [OR] = 5.37, 95% confidence interval [CI] = 2.01-14.30). Compared with wives with 'negative and probable' farmer's syndrome (reference), wives with 'positive' farmer's syndrome were more likely to have 'positive' neurotoxic symptoms (OR = 7.07, 95% CI = 2.58-19.38). Therefore, neurotoxic symptoms in both husbands and wives were significantly associated with farmer's syndrome. However, wives had a higher risk of neurotoxic symptoms than husbands. The findings of this study might be useful as important data for establishing and training agricultural safety and health policy.

Rationale: Acute rupture of the flexor halluces longus (FHL) tendon due to trauma or laceration is a well-known phenomenon. Partial rupture of the FHL tendon caused by tendinitis or stenosing tenosynovitis is common in ballet dancers and athletes. However, atraumatic complete rupture of the FHL is rare: as of 2018, only 7 cases of closed atraumatic complete rupture of the FHL tendon have been reported in the literature. Here, we report on a patient who presented with a closed atraumatic complete rupture of the FHL tendon during a forward lunge exercise., Patient Concerns: A 35-year-old female visited the clinic with pain in the plantar medial aspect of the left foot, along with weakness and loss of great toe flexion. The patient had a normal foot structure and no history of trauma or systemic disease. She performed a forward lunge exercise more than 50 times on 1 leg per day, more than once a week to strengthen her leg muscles. She reported that she felt a slight pain in her left, great toe while exercising for 3 weeks prior to her visit. One week prior to presentation, severe pain occurred suddenly when her left hallux dorsiflexed strongly during an anterior lunge exercise motion., Diagnosis: Magnetic resonance imaging revealed complete rupture of the FHL tendon near the level of the metatarsal head and neck junction. The lesion was prolonged, with the proximal end displaced to the metatarsal shaft region., Interventions: Complete rupture of the FHL tendon was treated with a primary suture., Outcomes: At the 1-year follow-up, active plantar flexion of the interphalangeal joint was possible but joint function had a range of 0° to 25°. Flexion strength was reduced slightly, measuring about 70% when compared to the contralateral side, but flexion strength of the metatarsophalangeal joint was normal., Lessons: We describe an extremely rare case of complete rupture of the FHL tendon at the level of metatarsal head and neck junction. It should be understood that this injury can occur not only in professional athletes but also in the general public, and we recommend educating personal trainers on how to prevent it.

Rationale: In competitive athletes, the upper extremity is subject to tremendous torsional forces with axial loading due to repetitive weight bearing. Approximately 25% of injuries in sports are related to the hand or wrist. Skeletal deformity on the wrist physis is common in athletes due to repetitive loading and presents at early ages between 6 and 13 years. Additionally, it is more common in female than in male athletes., Patient Concerns: An 11-year-old girl who was a climber complained of pain on her left wrist without direct trauma. She had participated in climbing exercise for several years and had no medical history. Thorough radiological evaluation, we diagnosed physeal injury of the left radius. After healing of the physeal injury of the radius, she complained of pain on fourth finger of right hand and radiographs revealed physeal injury of the right fourth finger., Diagnosis: Radiographs revealed physeal injury of the left radius. Magnetic resonance imaging revealed epiphyseal widening of the radial aspect of the wrist and bone marrow signal increase on T2-weighted imaging. Likewise, radiographs showed physeal injury of the right fourth finger INTERVENTIONS:: No surgery was performed and we applied wrist brace and finger splint for conservative treatment., Outcomes: The patient's pain was immediately relieved. The patient had no complications or recurrence of symptoms and was undergoing regular check-ups every 6 months., Lessons: During climbing exercise, repeated high pressure causes damage of the hand and wrist joints in young patients. Chronic pain in this group must be carefully evaluated, and radiographs should be obtained for diagnosis and early treatment. Conservative treatment of these injuries has good results, and avoiding intensive power training avoids the risk of this injury.

Rationale: Tarsal tunnel syndrome (TTS) is a compressive neuropathy of the posterior tibial nerve or one of its branches within the tarsal tunnel that is often caused by a variety of space-occupying lesions, such as ganglia, lipomas, varicosities, neural tumors, trauma, or systemic disease. The os sustentaculi is a small accessory bone, bridged to the posterior aspect of the sustentaculum tali by fibrocartilage. To the best of our knowledge, this is a rare case of successful treatment of TTS caused by the os sustantaculi., Patient Concerns: A 37-year-old male presented with insidious onset of right ankle and foot pain for 1 year. He also complained of a tingling sensation and paresthesia from the plantar and medial aspect of the forefoot to the middle foot area along the main distribution of the medial plantar nerve. The symptoms were mild at rest, but increased upon prolonged walking. He had an ankle sprain history during a football game 2 years previously and recurrent ankle sprains had occurred more frequently in this ankle since that trauma., Diagnoses: Plain standing anteroposterior and lateral view radiographic findings of the right ankle reveled an accessory ossicle located posterosuperomedial to the sustentaculum tali. A computed tomography scan showed that the ossicle articulated between the talus and calcaneus. A magnetic resonance image revealed mild bone marrow edema in the ossicle and medial displacement of the tarsal structures., Interventions: Surgery was performed under general anesthesia. The ossicle was delineated from its surrounding structures and was removed. Tension on the nerve was released., Outcomes: The patient's pain and hypoesthesia were immediately relieved, and the tingling sensation disappeared 6 months after surgery. The patient had no complications or recurrence of symptoms at the 1-year follow-up.

Insufficient sleep, insomnia, and sleep-related problems are important health issues, as their overall prevalence accounts for about 30% of the general population. The aim of this study was to systematically review previous studies investigating the effects of orally administered single plant-derived extracts on sleep-related outcomes in humans. Data sources were PubMed, Google Scholar, and Cochrane Library. The data search was conducted in two steps: step 1, names of plants which have been studied as sleep aids in humans were searched and retrieved; and step 2, each ingredient listed in step 1 was then added into the search term. Only original articles or reviews were applicable to the scope of this review. Studies on human subjects, with or without sleep-related disorders, were included. Sleep-related disorders refer to not only insomnia or sleep behavior disorders but also diseases with sleep-related symptoms. Studies were considered eligible for this review when the plant extracts were administered orally. Outcome measures relevant to sleep quality, duration, or other sleep-related problems were included. Twenty-one plants were listed in the first step of the search as potential candidates for natural sleep aids. Seventy-nine articles using these single plant-derived natural products were included in the final review. Although valerian was most frequently studied, conflicting results were reported, possibly due to the various outcome measures of each study. Other plants were not as rigorously tested in human studies. There was limited evidence with inconclusive results regarding the effects of single plant-derived natural products on sleep, warranting further studies.

Purpose: The purpose of this study is to present the effective design of N-plasty of the iliotibial band and surgical results of its use as a treatment for refractory external snapping hip., Materials and Methods: We evaluated 17 patients (24 cases) with external snapping hip who underwent N-plasty between October 2013 and May 2016 and who were followed up for at least 12 months. All patients were male and the mean age was 20.8 years. The mean duration of symptoms prior to surgical intervention was 28.5 months with an average follow up of 24.5 months. Surgery was defined as being successful when patients could carry out their daily activities and exercise without a clicking sensation or pain 6 months after surgery until their last follow-up. Failure was defined when either a clicking sensation or pain was present. The visual analog scale (VAS) and modified Harris hip score (mHHS) were measured and compared preoperatively and at last follow-up., Results: All patients had complete resolution of pain and snapping. The VAS decreased from 6.77 preoperatively to 0.09 postoperatively and mHHS improved from 69.5 to 97.8 after surgery., Conclusion: Modified designed N-plasty is considered to be an excellent treatment method facilitating operation reproducibility with maximum elongation effect of the iliotibial band., Competing Interests: CONFLICT OF INTEREST: The authors declare that there is no potential conflict of interest relevant to this article.

Mutations in isocitrate dehydrogenase ( IDH ) are the most prevalent genetic abnormalities in lower grade gliomas. The presence of these mutations in glioma is prognostic for better clinical outcomes with longer patient survival. In the present study, we found that defects in oxidative metabolism and 2-HG production confer chemosensitization in IDH1-mutated glioma cells. In addition, temozolomide (TMZ) treatment induced greater DNA damage and apoptotic changes in mutant glioma cells. The PARP1-associated DNA repair pathway was extensively compromised in mutant cells due to decreased NAD + availability. Targeting the PARP DNA repair pathway extensively sensitized IDH1-mutated glioma cells to TMZ. Our findings demonstrate a novel molecular mechanism that defines chemosensitivity in IDH-mutated gliomas. Targeting PARP-associated DNA repair may represent a novel therapeutic strategy for gliomas. Cancer Res; 77(7); 1709-18. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Cadmium (Cd) is a metal that is toxic to renal tubules. If renal tubules are damaged by Cd, urinary excretion of N-acetyl-β-D-glucosaminidase (NAG) and beta 2-microglobulin (β2-MG) increases. The aim of this study was to describe the changing patterns of urinary Cd, NAG, and β2-MG levels over a 3-year period in individuals living in a Cd-contaminated area. This follow-up study included 191 residents (65.6±9.3 years) who were living in the vicinity of a copper refinery. Urinary levels of Cd, NAG activity, and β2-MG levels were measured, and their determinants and changing patterns were analyzed statistically. The natural logarithm of urinary Cd levels decreased significantly over time. Sex and intake of locally cultivated rice were significant determinants of urinary Cd concentration. Urinary NAG activity decreased over time. Age and urinary Cd concentration were significant determinants of urinary NAG activity in subjects with urinary Cd concentrations >5μg/g creatinine. In subjects whose urinary Cd concentrations were >2μg/g creatinine, diabetes was found to be a significant risk factor for high urinary NAG activity. The slope for temporal changes in urinary β2-MG levels was negative in subjects whose urinary Cd levels were <2μg/g creatinine but was positive in those whose urinary Cd levels were 2-5μg/g creatinine or >5μg/g creatinine. The urinary β2-MG levels found in individuals whose urinary Cd levels were >2μg/g creatinine suggest that previous Cd-induced renal tubular damage had occurred., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We describe a new tensiometry method that allows for determination of wetting inside small diameter tubes or hollow fibers, where the maximum force from the ultimate rise height of liquid is used to estimate advancing contact angles. The technique was first validated with transparent tubes of glass, poly(carbonate) (PC) and poly(tetrafluoroethylene) (PTFE) using four liquids: isopropanol, silicone oil, ethylene glycol and water. Advancing contact angles measured with the tensiometer agreed well with those estimated from final rise height. As this tensiometry technique does not require a view of the liquid, it can be used to measure the wettability inside opaque tubes. We demonstrated this with poly(ether ether ketone) (PEEK) tubes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aim: To evaluate the association between genetic polymorphisms of the gene encoding AMP-activated protein kinase (PRKAA1) and the risk of gastric cancer., Methods: The study subjects consisted of 477 age- and sex-matched case-control pairs. Genotyping was performed for 5 tag single nucleotide polymorphisms (SNPs): rs13361707, rs154268, rs3805486, rs6882903, and rs10074991. Associations between gastric cancer and putative risk factors (including the SNPs) were analyzed with multivariate conditional logistic regression models, after adjusting for potential confounding factors. Multiple testing corrections were implemented following methodology for controlling the false discovery rate. Gene-based association tests were performed by using the versatile gene-based association study (VEGAS) method., Results: In the dominant model, SNPs rs13361707 [odds ratio (OR) = 1.51, 95%CI: 1.07-2.11)], rs154268 (OR = 1.65, 95%CI: 1.22-2.22), rs6882903 (OR = 1.48, 95%CI: 1.09-2.00), and rs10074991 (OR = 1.53, 95%CI: 1.09-2.16) were significantly associated with an increased risk of gastric cancer. In the recessive model, SNPs rs154268 (OR = 1.66, 95%CI: 1.22-2.26), rs3805486 (OR = 0.63, 95%CI: 0.46-0.85), and rs10074991 (OR = 1.47, 95%CI: 1.15-1.88) were significant risk or protective factors for gastric cancer. In the codominant model, the ORs of each of the 5 SNPs were statistically significant. All SNPs in the model showed a dose-response relationship between the minor allele frequency and the risk of gastric cancer. Most notably, subjects with a homozygous minor allele in SNP rs10074991 showed 2.15 times the risk of gastric cancer as subjects without a minor allele. The PRKAA1 gene showed a significant gene-based association with gastric cancer in the VEGAS test., Conclusion: All 5 tested tag SNPs of the PRKAA1 gene (rs13361707, rs154268, rs3805486, rs6882903, and rs10074991) were significantly associated with gastric cancer.

This study aimed to estimate the risks for renal tubular damage and osteoporosis in individuals with long-term environmental Cd exposure. This cross-sectional study comprised 1086 residents living in the vicinity of a copper refinery plant. As the urinary Cd levels increased, the proportion of female subjects with β₂-MG ≥300 μg/g creatinine also increased significantly, but this was not observed in the male subjects. The prevalence of osteoporosis was significantly higher in men with urinary Cd >5 μg/g creatinine than in those with urinary Cd ≤5 μg/g creatinine. This difference was not observed in the corresponding female groups. The association between increased urinary excretion of β₂-MG and decreased BMD was statistically significant only in the female subjects. We suggest that an increased Cd body burden directly decreases the BMD in male subjects; however, in female subjects, it first induces renal microtubular damage, which can lead to osteoporosis., (Copyright © 2014. Published by Elsevier B.V.)

Purpose: We investigated the effects of aflatoxin B1 (AFB1) intake, genetic polymorphisms of AFB1 metabolic enzymes, and interactions between the polymorphisms and intake of AFB1 with regard to the risk of gastric cancer in Korean., Methods: The participants in the study included 477 gastric cancer patients and 477 age- and sex-matched control subjects. Direct interviews and a structured questionnaire were used to determine the level of exposure to AFB1, and the GoldenGate assay and multiplex polymerase chain reaction were used for genotypic analyses of the cytochrome P450 1A2 (CYP1A2), cytochrome P450 1E1, epoxide hydrolase 1, and glutathione S-transferase genes., Results: The probable daily intake of AFB1 was significantly higher among gastric cancer patients than among control subjects (cases vs. controls: 1.91 ± 0.87 vs. 1.65 ± 0.72 ng/kg bw/day, p < 0.0001), and increased AFB1 intake was significantly associated with an elevated risk of gastric cancer (odds ratio 1.94; 95 % confidence interval 1.43-2.63). However, genetic polymorphisms of AFB1 metabolic enzymes were not associated with gastric cancer, with the exception of CYP1A2. Moreover, there was no interaction between AFB1 intake and the genotypes of metabolic enzymes that affect gastric cancer risk., Conclusions: Our results suggest that dietary AFB1 exposure might be associated with a risk of gastric cancer. However, the effect of AFB1 on gastric carcinogenesis may not be modulated by genetic polymorphisms of AFB1 metabolic enzymes.

As a way to modify both the physical and biological properties of a highly elastic and degradable polyurethane (PU), silk fibroin (SF) was blended with the PU at differing ratios. With increasing SF content, the tensile strength decreased as did the strain at break; the stiffness increased to around 35 MPa for the highest silk content. C2C12 (a mouse myoblast cell line) cells were used for in vitro experiments and showed significantly improved cell responses with increasing SF content. With increasing SF content the number of non-adherent cells was reduced at both 4 and 8h compared to the sample with the lowest SF content. In addition, muscle marker genes were upregulated compared to the sample containing no SF, and in particular sarcomeric actin and α-actin., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

We examined the forces and energies associated with liquid rising in a capillary tube. Glass and polytetrafluorethylene (PTFE) tubes with diameter ranging from 0.5 to 1.4mm were brought into contact with ethylene glycol, glycerol or silicone oil to initiate rise. We measured the force generated by the rising liquids with a tensiometer and plotted them against rise height. From these plots, we estimated the change in potential energy. For a given liquid-solid combination, the change in potential energy was equal to the difference between the work of wetting and viscous dissipation in the bulk of the liquid; potential energy values were independent of tube diameter and ranged from 7 mJ/m(2) for silicone oil rising through PTFE to 33 mJ/m(2) for glycerol and glass., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aim: To evaluate the association between the genetic polymorphisms and haplotypes of the ITGA1 gene and the risk of gastric cancer., Methods: The study subjects were 477 age- and sex-matched case-control pairs. Genotyping was performed for 15 single nucleotide polymorphisms (SNPs) in ITGA1. The associations between gastric cancer and these SNPs and haplotypes were analyzed with multivariate conditional logistic regression models. Multiple testing corrections were carried out following methodology for controlling the false discovery rate. Gene-based association tests were performed using the versatile gene-based association study (VEGAS) method., Results: In the codominant model, the ORs for SNPs rs2432143 (1.517; 95%CI: 1.144-2.011) and rs2447867 (1.258; 95%CI: 1.051-1.505) were statistically significant. In the dominant model, polymorphisms of rs1862610 and rs2447867 were found to be significant risk factors, with ORs of 1.337 (95%CI: 1.029-1.737) and 1.412 (95%CI: 1.061-1.881), respectively. In the recessive model, only the rs2432143 polymorphism was significant (OR = 1.559, 95%CI: 1.150-2.114). The C-C type of ITGA1 haplotype block 2 was a significant protective factor against gastric cancer in the both codominant model (OR = 0.602, 95%CI: 0.212-0.709, P = 0.021) and the dominant model (OR = 0.653, 95%CI: 0.483-0.884). The ITGA1 gene showed a significant gene-based association with gastric cancer in the VEGAS test. In the dominant model, the A-T type of ITGA1 haplotype block 2 was a significant risk factor (OR = 1.341, 95%CI: 1.034-1.741). SNP rs2447867 might be related to the severity of gastric epithelial injury due to inflammation and, thus, to the risk of developing gastric cancer., Conclusion: ITGA1 gene SNPs rs1862610, rs24321 43, and rs2447867 and the ITGA1 haplotype block that includes SNPs rs1862610 and rs2432143 were significantly associated with gastric cancer.

Aim: We conducted a pilot nested case-control study to prospectively evaluate the effects of polycyclic aromatic hydrocarbons (PAH) exposure, antioxidant capacity, and oxidative stress on lung carcinogenesis., Materials and Methods: Thirty-five patients with lung cancer and 140 age- and sex-matched controls were selected from a sub-cohort of the Korean Multi-center Cancer Cohort. PAH metabolites (1-hydroxypyrene and 2-naphthol), oxidative stress markers, and total antioxidant capacity (TAC) were assessed using urine samples collected at baseline., Results: The levels of urinary PAH metabolites and oxidative stress were not different between cases and controls. Urinary 1-hydroxypyrene and 2-naphthol levels were significantly associated with urinary oxidative stress markers only in lung cancer cases. Individuals with low urinary TAC and high urinary oxidative stress levels had significantly higher risk of lung cancer compared to those with high urinary TAC and low urinary oxidative stress levels., Conclusion: Oxidative stress induced by PAH exposure and TAC may be important determinants for the susceptibility to lung cancer.

Purpose: To assess the treatment outcome for disc infection in 35 patients., Methods: Records of 23 men and 12 women aged 36 to 62 (mean, 43) years who underwent treatment for pyogenic discitis after open discectomy were reviewed. All patients had single-level disc herniation of L4-5 (n=28) or L5-S1 (n=6), except for one who had 2-level disc herniation of L4-S1. Single antibiotic was given one day prior to discectomy and continued for 2 days. All excised discs were found to be sterile. Discitis was classified into acute (n=26), subacute (n=7), and chronic (n=2). Antibiotic therapy was started immediately when the clinical diagnosis was made. 31 patients were treated with antibiotics alone; the remaining 4 underwent surgery entailing simple posterior superficial wound drainage (n=1), anterior radical surgery (n=2), or posterior instrumentation and posterolateral fusion for post-discectomy syndrome (n=1). Six of the 12 patients who had percutaneous disc space aspiration underwent disc space irrigation., Results: The initial symptoms included mild-to-moderate fever (n=4), severe back pain (n=27), back muscle spasms (n=26), back pain radiating to the limb (n=2), Gower sign (n=11), and a draining wound (n=1). The wound aspirates of the 12 patients grew organisms, although blood cultures were negative in all. After antibiotic therapy, symptoms gradually subsided in parallel with normalisation of white blood cell count and inflammatory markers. Surgery was indicated only when symptoms worsened and the disease progressed. Spontaneous intercorporal fusion did not occur., Conclusion: Early diagnosis and treatment with appropriate antibiotics is important for post-discectomy discitis.

Background: Tuberculosis (TB) of hip constitutes nearly 15% of all cases of osteoarticular tuberculosis. We report a retrospective study carried out on 43 children with hip TB., Materials and Methods: Forty-three children of TB hip treated between 1971 and 2000 were analysed. Twenty-four children of the early series were treated with streptomycin (S), isoniazid (H) and PAS (Pa) for 18 months (3HPaS, 15 HPa), while 19 children in the later series were treated with isoniazid (H), rifampicin (R) and ethambutol (E) or pyrazinamide (Z) for 12 months [(12 RHE(Z)]. Five out of 18 children with radiologically normal appearing type hip TB were treated with chemotherapy alone and 38 children were subjected to surgery; simple synovectomy alone in 31 hips, joint debridement in six hips, and proximal femoral varisation osteotomy in one. After surgery hips were immobilized in cast for one to three months according to the severity of the disease and patients pain tolerance, and then were mobilized under leg traction in bed gradually till pain subsided completely., Results: TB of hip healed with minimum sequelae in all children. In 18 Type one hip TB, normal hip (synovial form) anatomy was maintained, and in 25 patients with advanced lesions some defect in the femoral head and acetabulum was noticed, though painless good hip motion was maintained. Excellent to good results were obtained in 31 children (73.1%), fair in eight (18.6%), and poor in four (9.3%). In four patients with poor results, there was some residual morphological defect in the hip. None developed ankylosis of hip., Conclusion: We achieved good outcome with minimum sequelae in this series. The management goal should be aimed not only to heal the disease but also to maintain a painless mobile hip and anatomical cephalocotyloid relationship until maturity, and retard the development of secondary osteoarthritis.

Background: Korean regression models for spirometric reference values are different from those of Americans. Using spirometry results of Korean adults, goodness-of-fits of the Korean and the USA Caucasian regression models for forced vital capacity (FVC) and forced expiratory volume in one second (FEV(1)) were compared., Methods: The number of study participants was 2,360 (1,124 males and 1,236 females). Spirometry was performed under the guidelines of the American Thoracic Society and the European Respiratory Society. After excluding unsuitable participants, spirometric data for 729 individuals (105 males and 624 females) was included in the statistical analysis. The estimated FVC and FEV(1) values were compared with those measured. Goodness-of-fits for Korean and USA Caucasian models were compared using an F-test., Results: In males, the expected values of FVC and FEV(1) using the Korean model were 12.5% and 5.7% greater than those measured, respectively. The corresponding values for the USA Caucasian model were 3.5% and 0.6%. In females, the difference in FVC and FEV(1) were 13.5% and 7.7% for the Korean model, and 6.3% and 0.4% for the USA model, respectively. Goodness-of-fit for the Korean model regarding FVC was not good to the study population, but the Korean regression model for FEV(1), and the USA Caucasian models for FVC and FEV(1) showed good fits to the measured data., Conclusion: These results suggest that the USA Caucasian model correlates better to the measured data than the Korean model. Using reference values derived from the Korean model can lead to an overestimation regarding the prevalence of abnormal lung function.

Indole-3-carbinol (I3C) has been found to act against several types of cancer, while ultraviolet B (UVB) is known to induce the apoptosis of human melanoma cells. Here, we investigated whether I3C can sensitize G361 human melanoma cells to UVB-induced apoptosis. We examined the effects of combined I3C and UVB (I3C/UVB) at various dosages. I3C (200 microM)/UVB (50 mJ/cm(2)) synergistically reduced melanoma cell viability, whereas I3C (200 microM) or UVB (50 mJ/cm(2)), separately, had little effect on cell viability. DNA fragmentation assays indicated that I3C/UVB induced apoptosis. Further results show that I3C/UVB activates caspase-8, -3, and Bid and causes the cleavage of poly(ADP-ribose) polymerase. Moreover, I3C decreased the expression of the anti-apoptotic protein, Bcl-2, whereas UVB increased the translocation of Bax to mitochondria. Thus, an increased Bax/Bcl-2 ratio by I3C/UVB may result in melanoma apoptosis. In conclusion, our study demonstrated that I3C sensitizes human melanoma cells by down-regulating Bcl-2.

The purpose of the present study was to investigate the mechanisms involved in the antiproliferative and apoptotic effects of MCS-C2, a novel analog of the pyrrolo[2,3-d]pyrimidine nucleoside toyocamycin and sangivamycin, in human prostate cancer LNCaP cells. MCS-C2, a selective inhibitor of cyclin-dependent kinase, was found to inhibit cell growth in a time- and dose-dependent manner, and inhibit cell cycle progression by inducing the arrest of the G1 phase and apoptosis in LNCaP cells. When treated with 3 microM MCS-C2, inhibited proliferation associated with apoptotic induction was found in the LNCaP cells in a concentration and time-dependent manner, and nuclear DAPI staining revealed the typical nuclear features of apoptosis. Furthermore, MCS-C2 induced cell cycle arrest in the G1 phase through the upregulated phosphorylation of the p53 protein at Ser-15 and activation of its downstream target gene p21WAF1/CIP1. Accordingly, these results suggest that MCS-C2 inhibits the proliferation of LNCaP cells by way of G1-phase arrest and apoptosis in association with the regulation of multiple molecules in the cell cycle progression.

The net balance of matrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinases (TIMP) system has been known to be a key factor in tumor cell invasion. In the present study, we investigated the molecular mechanisms of anti-invasive and antimigrative activity of transforming growth factor (TGF)-beta1 on HT1080 human fibrosarcoma cells. In in vitro Matrigel invasion and Transwell migration assays, TGF-beta1 dose-dependently inhibited the invasion and migration of HT1080 cells, respectively. Gelatin zymography, Western blot, and real-time PCR analysis showed that TGF-beta1 enhanced the expression and secretion of MMP-2, TIMP-1, and, to a lesser degree, MMP-9 but not membrane type 1-MMP and TIMP-2. The addition of recombinant TIMP-1 protein reduced the Matrigel invasion and Transwell migration of HT1080 cells, similar to TGF-beta1. Because augmentation of TIMP-1 might be the major factor for the anti-invasive and antimigrative activity of TGF-beta1, we investigated possible molecular mechanisms responsible for the expression of TIMP-1 induced by TGF-beta1. Treatment of HT1080 cells with TGF-beta1 rapidly phosphorylated three mitogen-activated protein kinases [MAPK; extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and c-Jun NH2-terminal kinase] and Akt. Among these kinases, the inhibition of only ERK1/2 pathway by PD98059, a specific inhibitor of MAPK/ERK kinase(MEK)-1, and transfection of dominant-negative MEK 1 effectively blocked the TIMP-1 induction by TGF-beta1. Mithramycin, a specific inhibitor of Sp1 transcription factor, but not curcumin, an inhibitor of activator protein-1, and transfection of Sp1 small interfering RNA significantly inhibited the TGF-beta1-induced expression of TIMP-1. In addition, electrophoretic mobility shift assay showed that TGF-beta1 up-regulated Sp1 DNA-binding activity, and PD98059 and mithramycin effectively inhibited these events. Finally, pretreatment of HT1080 cells with PD98059 and mithramycin, but not curcumin, restored the invasive activity of these cells. Taken together, these data suggest that TGF-beta1 modulates the net balance of the MMPs/TIMPs the systems in HT1080 cells for anti-invasion and antimigration by augmenting TIMP-1 through ERK1/2 pathway and Sp1 transcription factor.