Residue Behavior of Methoxyfenozide and Pymetrozine in Chinese Cabbage and Their Health Risk Assessment.

Methoxyfenozide and pymetrozine are used for pest control in the cultivation of Chinese cabbage. This has raised concerns in recent years due to health risks. Therefore, this study aimed to determine the residual concentrations of pesticides in the target crop and associated health risks. The dynamics and influence of environmental factors on the dissipation of methoxyfenozide and pymetrozine residues in Chinese cabbage were investigated. Analyses were performed using a modified QuEchERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) and an optimized high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The observed half-lives of methoxyfenozide and pymetrozine in cabbage samples ranged between two sampling seasons: in May−June, half-lives of methoxyfenozide and pymetrozine were 1.20 days and 1.89 days, respectively; during October−November, half-lives of methoxyfenozide and pymetrozine were 11.8 and 2.80 days, respectively. Meanwhile, a negative Spearman correlation was found between the residual concentrations and temperature (p < 0.01). This indicates that higher temperatures resulted in higher dissipation rates for methoxyfenozide and pymetrozine, suggesting that these pesticides degraded faster at higher temperatures. Additionally, higher pesticide residues in Chinese cabbage during low-temperature seasons resulted in higher risk quotients (RQ) (RQ > 1) for both analyzed compounds, which suggests that the effect of temperature on pesticide degradation needs to be considered as an essential factor while setting up the maximum residue limits (MRL).

A Mixed-Methods Study of Early Childhood Education and Care in South Korea: Policies and Practices During COVID-19.

This study of South Korea's response to COVID-19 has three purposes. First, it uses document analysis to examine policies, strategies, and resources offered by the South Korean government and public organizations to support young children and families during the first 6 months of the pandemic. Next, it uses open-ended surveys with 30 directors of early childhood institutions to explore institutional-level supports and needs during the pandemic. Finally, it looks at the discrepancies between stated policies outlining the South Korea's response to COVID-19 and the lived experiences of early childhood educators as a route to arriving at recommendations for education policymakers and other stakeholders. To that end, we reviewed government documents (n = 84) containing early childhood education-related responses to Covid-19 established by the Ministry of Education, the Ministry of Health and Welfare, and other relevant government sectors. An online survey with 17 kindergarten and 13 child care center directors was also analyzed. Using content analysis, the findings revealed that the government's policies and guidance for Early Childhood Education and Care (ECEC) as well as the institutional supports for children and families were overall comprehensive in its scope. The analysis, based on the five tenets of the Whole Child approach, also indicated that the government's policy responses and services for ECEC focused mainly on the 'Safe' and 'Supported' tenets, while 'Challenged' was given the least amount of consideration. The survey responses demonstrated different measures taken by kindergartens and child care centers highlighting the separate nature of 'education' and 'care' in South Korea, while also indicating limited resources for supporting children's psychological well-being and for children and families in need. This overview provides a foundation for further discussion and research on the impact of Covid-19 on ECEC in South Korea and beyond.

Short- and Long-Term Exposure to Particulate Matter and Pulse Wave Velocity.

BACKGROUND: In hemodialysis patients, brachial-ankle pulse wave velocity (baPWV) levels are affected by particulate matter with an aerodynamic diameter of 10 µm or less (PM10). We conducted this study to determine whether there is an association between short- and long-term PM10 exposure and baPWV in apparently healthy adults aged 40 years and older. METHODS: A total of 1,628 subjects who underwent health examinations between 2006 and 2009 were included in the study. On the basis of the day of medical screening, the 1-3-day and 365-day moving averages of PM10 concentrations were used to evaluate the association between short- and long-term exposure to PM10 and high baPWV (≥the third quartile of baPWV, 1,534 cm/s) using logistic regression models. Additional subgroup analyses were conducted according to age, sex, obesity (body mass index ≥25.0 kg/m2), and comorbidities such as metabolic syndrome. RESULTS: No statistically significant associations were identified between short-term and long-term exposure to PM10 and baPWV in any of the subjects and subgroups. A 10-µg/m3 increase in the 2-day moving average of PM10 exposure was marginally associated with high baPWV in non-obese subjects (odds ratio, 1.059; P=0.058). This association in non-obese subjects was significantly different from that in obese subjects (P=0.038). CONCLUSION: This study did not show statistically significant associations between short-term and long-term exposure to PM10 and baPWV in apparently healthy subjects. With short-term exposure to PM10, non-obese subjects showed a marginally unfavorable association with baPWV. Further studies are necessary to validate and elucidate the mechanism underlying the effect of PM10 on baPWV.

Body weight variability and cancer incidence in men aged 40 years and older-Korean National Insurance Service Cohort.

Repeated weight fluctuation has been proposed as a potential risk factor for increasing morbidity and mortality including cancer. We aimed to investigate the association between body weight variability (BWV) and all cancer and site-specific cancer incidence and the impact of smoking on these associations. A total of 1,759,848 cancer-free male subjects who had their weight measured at least 5 times from the National Health Insurance Service-Health Screening Cohort from 2002 to 2011 were included and followed up until 2015. BWV was defined as the average absolute difference between successive values (ASV). The risk of cancer and site-specific cancer from BWV was identified using Cox proportional hazards regression analysis using hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for potential confounders including weight, and stratified analysis was also conducted according to smoking status. During the 7,015,413 person-years of follow-up, 11,494 patients (0.65%) developed new-onset cancers. BWV was associated with a higher risk of all cancers after adjustment for confounders. The highest BWV quintile group compared to the lowest had greater risks of all cancers and site-specific cancers including lung, liver, and prostate cancer (HR 1.22, 95% CI 1.15-1.30; HR 1.22, 95% CI 1.07-1.39; HR 1.46, 95% CI 1.19-1.81; HR 1.36, 95% CI 1.15-1.62, in all cancers, lung, liver and prostate cancer, respectively). Due to small number of cancer occurrence, the risk of kidney cancer was increased, but statistically insignificant (HR 1.38, 95% CI 0.91-2.10). Similar results were observed in noncurrent smokers. However, in current smokers, the risks of all cancers and only prostate cancer were significantly increased in the highest BWV quintile group (HR 1.19, 95% CI 1.09-1.31; HR 1.51, 95% CI 1.08-2.11). The risk of kidney cancer also increased in this group, although the finding was not statistically significant (HR 1.77, 95% CI 0.87-3.63) This study suggested BWV is an independent risk factor for cancer in men, especially in lung, liver, and prostate cancer, but evidence was weaker in kidney cancer. This association remained significant only in prostate cancer in current smokers.

Risk of coronary heart disease among cancer survivors with different prediagnosis body mass index.

Association between body mass index (BMI) and coronary heart disease (CHD) in cancer survivors is not clearly established. This study analyzed the prediagnosis BMI-CHD association by examining 13,500 cancer survivors identified from the National Health Insurance Service-Health Screening Cohort from January 1, 2004 to December 31, 2009 including the patients who were free of cardiovascular disease at enrollment. The Cox proportional hazards model (adjusted for socioeconomic, health behavior, health status, and medical characteristics) was used for calculating hazard ratios (HR) and 95% confidence intervals (95% CI) for CHD in each prediagnosis BMI category among cancer survivors. Compared to cancer survivors with a prediagnosis BMI between 18.5 and 22.9 kg/m2, those with a prediagnosis BMI of 23.0-24.9 kg/m2 and ≥ 25.0 kg/m2 had significantly higher CHD risk (HR = 1.51; 95% CI: 1.13-2.01 and HR = 1.38; 95% CI: 1.04-1.84, respectively). Cancer survivors with a low prediagnosis BMI (< 18.5 kg/m2) also had significantly higher CHD risk (HR = 1.97; 95% CI: 1.20-3.24) compared to those with a BMI of 18.5-22.9 kg/m2. Similar associations were found after stratifying analyses based on first cancer site and sociodemographic and medical characteristic subgroups. Our study suggests that prediagnosis underweight among patients with cancer is a predictor of CHD risk.

Sex- and age-specific effects of energy intake and physical activity on sarcopenia.

Sarcopenia is a common health issue that is not limited to only elderly patients. However, many studies have reported factors to prevent sarcopenia only in susceptible groups. This study evaluates the relationship of the total energy intake to basal metabolic rate ratio (EI/BMR) and physical activity (PA) with sarcopenia. A second aim was to analyze the interaction between EI/BMR and PA by sex and age. We analyzed 16,313 subjects aged ≥ 19 years who had dual‒energy X-ray absorptiometry data. Sarcopenia was defined as appendicular lean mass/weight (%) that was 1 standard deviation below the sex-specific mean value for a young reference group. Multivariate logistic regression analysis was used to examine the interaction between EI/BMR and PA. In this study, as EI/BMR increased, the risk of sarcopenia decreased, particularly in the older groups. Both high PA and high EI/BMR were independently related to the reduced risk of sarcopenia and showed additive effects on reducing the risk in young male and older groups. However, high PA was associated with an increased risk of sarcopenia in the young female group with low energy intake. Our findings suggest that an adequate balance between energy intake and PA is related to a low risk of sarcopenia, especially in young females.

The Association between the Ratio of Energy Intake to Basal Metabolic Rate and Physical Activity to Sarcopenia: Using the Korea National Health and Nutrition Examination Surveys (2008-2011).

BACKGROUND: Sarcopenia is an important health problem, the risk factors of which a few studies have reported on. The purpose of this study was to evaluate the correlation between sarcopenia and the ratio of total energy intake to basal metabolic rate (BMR) as well as physical activity, and determine whether the relationship was different between younger and older age groups using data from the 2008-2011 Korea National Health and Nutrition Examination Survey. METHODS: We analyzed 16,313 subjects older than 19 years who had dual energy X-ray absorptiometry data. Sarcopenia was defined as an appendicular lean mass/weight (%) ratio of 1 standard deviation below the sex-specific mean value for a younger reference group, and BMR was calculated using the Harris-Benedict equation. A chi-squared test and logistic regression analyses were performed to evaluate the factors associated with sarcopenia. RESULTS: In this study, 15.2% of males and 15.4% of females had sarcopenia. Energy intake/BMR as well as physical activity was negatively related to sarcopenia risk. In stratified analysis by age and sex, strength exercises showed an inverse association with sarcopenia only in males under the age of 50 years (odds ratio, 0.577; P<0.0001), whereas higher energy intake/BMR was negatively associated with sarcopenia in each age and sex group. CONCLUSION: Our findings suggest that adequate energy intake is important to prevent sarcopenia regardless of whether one exercises.

An Oligoimide Particle as a Pickering Emulsion Stabilizer.

A pyromellitic dianhydride (PMDA) and 4,4'-oxydianiline (ODA)-based oligoimide (PMDA-ODA) was synthesized by a one-step procedure using water as a solvent. The PMDA-ODA particles showed excellent partial wetting properties and were stably dispersed in both water and oil phases. A stable dispersion was not obtained with comparison PMDA-ODA particles that were synthesized by a conventional two-step method using an organic solvent. Both oil-in-water and water-in-oil Pickering emulsions were prepared using the oligoimide particles synthesized in water, and the size of the emulsion droplet was controlled based on the oligoimide particle concentration. The oligoimide particles were tested to prepare Pickering emulsions using various kinds of oils. The oil-in-water Pickering emulsions were successfully applied to prepare microcapsules of the emulsion droplets. Our new Pickering emulsion stabilizer has the advantages of easy synthesis, no need for surface modification, and the capability of stabilizing both oil-in-water and water-in-oil emulsions.

Low-Temperature Self-Healing of a Microcapsule-Type Protective Coating.

Low-temperature self-healing capabilities are essential for self-healing materials exposed to cold environments. Although low-temperature self-healing concepts have been proposed, there has been no report of a microcapsule-type low-temperature self-healing system wherein the healing ability was demonstrated at low temperature. In this work, low-temperature self-healing of a microcapsule-type protective coating was demonstrated. This system employed silanol-terminated polydimethylsiloxane (STP) as a healing agent and dibutyltin dilaurate (DD) as a catalyst. STP underwent a condensation reaction at -20 °C in the presence of DD to give a viscoelastic product. The reaction behavior of STP and the viscoelasticity of the reaction product were investigated. STP and DD were separately microencapsulated by in situ polymerization and interfacial polymerization methods, respectively. The STP- and DD-loaded microcapsules were mixed into a commercial enamel paint, and the resulting formulation was applied to glass slides, steel panels, and mortars to prepare self-healing coatings. When the self-healing coatings were damaged at a low temperature (-20 °C), STP and DD were released from broken microcapsules and filled the damaged area. This process was effectively visualized using a fluorescent dye. The self-healing coatings were scratched and subjected to corrosion tests, electrochemical tests, and saline solution permeability tests. The temperature of the self-healing coatings was maintained at -20 °C before and after scratching and during the tests. We successfully demonstrated that the STP/DD-based coating system has good low-temperature self-healing capability.

Microcapsule-Type Self-Healing Protective Coating for Cementitious Composites with Secondary Crack Preventing Ability.

A microcapsule-type self-healing protective coating with secondary crack preventing capability has been developed using a silanol-terminated polydimethylsiloxane (STP)/dibutyltin dilaurate (DD) healing agent. STP undergoes condensation reaction in the presence of DD to give a viscoelastic substance. STP- and DD-containing microcapsules were prepared by in-situ polymerization and interfacial polymerization methods, respectively. The microcapsules were characterized by Fourier-transform infrared (FT-IR) spectroscopy, optical microscopy, and scanning electron microscopy (SEM). The microcapsules were integrated into commercial enamel paint or epoxy coating formulations, which were applied on silicon wafers, steel panels, and mortar specimens to make dual-capsule self-healing protective coatings. When the STP/DD-based coating was scratched, self-healing of the damaged region occurred, which was demonstrated by SEM, electrochemical test, and water permeability test. It was also confirmed that secondary crack did not occur in the healed region upon application of vigorous vibration to the self-healing coating.

Involvement of DDX6 gene in radio- and chemoresistance in glioblastoma.

CCRT (concomitant chemotherapy and radiation therapy) is often used for glioblastoma multiforme (GBM) treatment after surgical therapy, however, patients treated with CCRT undergo poor prognosis due to development of treatment resistant recurrence. Many studies have been performed to overcome these problems and to discover genes influencing treatment resistance. To discover potential genes inducing CCRT resistance in GBM, we used whole genome screening by infecting shRNA pool in patient-derived cell. The cells infected ~8,000 shRNAs were implanted in mouse brain and treated RT/TMZ as in CCRT treated patients. We found DDX6 as the candidate gene for treatment resistance after screening and establishing DDX6 knock down cells for functional validation. Using these cells, we confirmed tumor associated ability of DDX6 in vitro and in vivo. Although proliferation improvement was not found, decreased DDX6 influenced upregulated clonogenic ability and resistant response against radiation treatment in vivo and in vitro. Taken together, we suggest that DDX6 discovered by using whole genome screening was responsible for radio- and chemoresistance in GBM.

Tunable and Diastereoselective Brønsted Acid Catalyzed Synthesis of ß-Enaminones.

The Brønsted acid catalyzed Meyer-Schuster reaction of hemiaminals was studied for the stereoselective synthesis of ß-enaminones. Hemiaminals were formed from propargyl aldehydes (or the oxidation of propargyl alcohols) and amines in the presence of Brønsted acids. A critical step to control the stereochemistry of the products is the protonation of the corresponding allenol intermediate, which is dictated by the Brønsted acid used, the steric effect of the amine, and the electronic effect of the propargyl aldehyde.

Experimental and clinical factors influencing long-term stable in vitro expansion of multipotent neural cells from human adult temporal lobes.

Autologous adult human neural stem cells may be used for regenerative cell therapies bypass potential ethical problems. However, stable in vitro expansion protocols and experimental/clinical factors influencing primary cultures need to be further elucidated for clinically applicable techniques. To address these issues, we obtained biopsy specimens from 23 temporal lobe epilepsy patients and adult human multipotent neural cells (ahMNCs) were primarily cultured in a defined attachment culture condition. When the success of primary cultures was defined as stable expansion of cells (>ten in vitro passages) and expression of NSC markers, success rate of the primary culture was 39% (nine of 23 temporal lobes). During the long-term expansion, expressions of NSC markers and differentiation potentials into astrocytes and neurons were maintained. After the 18th sub-culture, spontaneous senescence and differentiation were observed, and the cultivated ahMNCs ceased their proliferation. The culture results were not affected by seizure characteristics; however, an older age (>40 years) and a smaller sample volume (<2 ml) were found to exert negative influences on the primary culture results. Furthermore therapeutic effects of ahMNCs against stroke were analyzed in an animal model. Transplantation of ahMNCs cells reduced infarction volumes and enhanced motor activity, significantly. The results here would provide promising experimental and clinical strategy of using patient-specific autologous ahMNCs in regenerative medicine in the future.

Therapeutic effects of human adipose stem cell-conditioned medium on stroke.

Stem cell therapy is a promising approach for stroke. However, low survival rates and potential tumorigenicity of implanted cells could undermine the efficacy of the cell-based treatment. The use of stem cell-conditioned medium (CM) may be a feasible approach to overcome these limitations. Especially, specific stem cell culture condition and continuous infusion of CM into ischemic brains would have better therapeutic results. The CM was prepared by culturing human adipose-derived stem cells in a three-dimensional spheroid form to increase the secretion of angiogenic/neuroprotective factors. Ischemic stroke was induced by standard middle cerebral artery occlusion methods in the brain of 8-week-old Sprague-Dawley rats. Continuous infusion of CM or αMEM media (0.5 µl/hr) into the lateral ventricle was initiated 8 days after the surgery and maintained for 7 days. Alteration in the motor function was monitored by the rotarod test. Infarction volume and the number of microvessels or TUNEL-positive neural cells were analyzed 15 days after the surgery. Compared with αMEM, continuous CM infusion reduced the infarction volume and maintained motor function. The number of CD31-positive microvessels and TUNEL-positive neural cells significantly increased and decreased, respectively, in the penumbra regions. Although the apoptosis of all neural cell types decreased, reduction in the microglial apoptosis and astrogliosis was prominent and significant. In this study, the therapeutic effects of the CM against stroke were confirmed in an animal model. Increased endothelial cell proliferation, reduced neural cell apoptosis, and milder astrogliosis may play important roles in the treatment effects of CM.

Trans-differentiation of neural stem cells: a therapeutic mechanism against the radiation induced brain damage.

Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs) would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases.

Replacement of microglial cells using Clodronate liposome and bone marrow transplantation in the central nervous system of SOD1(G93A) transgenic mice as an in vivo model of amyotrophic lateral sclerosis.

Disease progression of amyotrophic lateral sclerosis (ALS) is partially mediated by the toxic microenvironment established by microglia. In the present study, we used SOD1G93A transgenic mice as an in vivo ALS model and replaced microglia expressing mutant SOD1 (mSOD1) with microglia expressing wild-type SOD1 (w/tSOD1) to modulate the toxic microenvironment. Stereotactic injection of Clodronate liposome, a selective toxin against the monocyte/macrophage system, into the fourth ventricle of the brains of 12-week-old asymptomatic ALS mice reduced the number of microglia effectively in the central nervous system. Subsequent bone marrow transplantation (BMT) with bone marrow cells (BMCs) expressing w/tSOD1 and GFP leads to replacement of the endogenous microglia of the ALS mice with microglia expressing w/tSOD1 and GFP. The expression of mSOD1 in the other neural cells was not influenced by the replacement procedures, and immunological side effects were not observed. The replacement of microglia significantly slowed disease progression and prolonged survival of the ALS mice compared with the ALS mice treated by stereotactic injection of PBS-liposome and BMT with BMCs expressing mSOD1 or w/tSOD1. These results suggest that replacement of microglia would improve the neural cell microenvironment, thereby slowing disease progression. The mechanisms and functional implications of this replacement require further elucidation.

Immunohistochemical study on the expression of calcium binding proteins (calbindin-D28k, calretinin, and parvalbumin) in the cerebral cortex and in the hippocampal region of nNOS knock-out(-/-) mice.

Nitric oxide (NO) modulates the activities of various channels and receptors to participate in the regulation of neuronal intracellular Ca(2+) levels. Ca(2+) binding protein (CaBP) expression may also be altered by NO. Accordingly, we examined expression changes in calbindin-D28k, calretinin, and parvalbumin in the cerebral cortex and hippocampal region of neuronal NO synthase knockout(-/-) (nNOS(-/-)) mice using immunohistochemistry. For the first time, we demonstrate that the expression of CaBPs is specifically altered in the cerebral cortex and hippocampal region of nNOS(-/-) mice and that their expression changed according to neuronal type. As changes in CaBP expression can influence temporal and spatial intracellular Ca(2+) levels, it appears that NO may be involved in various functions, such as modulating neuronal Ca(2+) homeostasis, regulating synaptic transmission, and neuroprotection, by influencing the expression of CaBPs. Therefore, these results suggest another mechanism by which NO participates in the regulation of neuronal Ca(2+) homeostasis. However, the exact mechanisms of this regulation and its functional significance require further investigation.

Immunohistochemical study on the expression of calcium binding proteins (calbindin-D28k, calretinin, and parvalbumin) in the cerebellum of the nNOS knock-out(-/-) mice.

Nitric Oxide (NO) actively participates in the regulation of neuronal intracellular Ca(2+) levels by modulating the activity of various channels and receptors. To test the possibility that modulation of Ca(2+) buffer protein expression level by NO participates in this regulatory effect, we examined expression of calbindin-D28k, calretinin, and parvalbumin in the cerebellum of neuronal NO synthase knock-out (nNOS((-/-))) mice using immunohistochemistry. We observed that in the cerebellar cortex of the nNOS((-/-)) mice, expression of calbindin-D28k and parvalbumin were significantly increased while expression of calretinin was significantly decreased. These results suggest another mechanism by which NO can participate in the regulation of Ca(2+) homeostasis.

Glycogen synthase kinase-3ß does not correlate with the expression and activity of ß-catenin in gastric cancer.

The regulation of ß-catenin activation by glycogen synthase kinase-3ß (GSK-3ß) in cancer has been shown to be cell type-specific. This study was performed to investigate the relationship between activated GSK-3ß (phosphorylated at Tyr216) and ß-catenin in gastric cancer. Immunohistochemical tissue array analysis of 278 human gastric carcinoma specimens showed positive immunoreactivity for activated GSK-3ß in 44% of the samples, whereas membranous ß-catenin and nuclear ß-catenin were observed in 19% and 20% of the samples, respectively. However, GSK-3ß activation was not correlated with the expression of either membranous ß-catenin or nuclear ß-catenin. Moreover, SNU gastric cancer cell lines over-expressing kinase dead GSK-3ß and the same cells treated with a GSK-3ß inhibitor showed that GSK-3ß inhibition did not alter either the protein expression or transcriptional activity of ß-catenin. In addition, GSK-3ß activation was positively correlated with the expressions of anti-adenomatous polyposis coli (p = 0.002), p16 (p < 0.001), p21 (p < 0.001), p27 (p = 0.001), and p53 (p = 0.013). On the other hand, the nuclear expression of ß-catenin was positively correlated with those of Bcl-2 (p = 0.025) and cyclin D1 (p = 0.043), but these expressions were not correlated with GSK-3ß activation. Thus, the GSK-3ß pathway seems to function in gastric cancer cells without involving the ß-catenin pathway.

Constitutive activation of glycogen synthase kinase-3beta correlates with better prognosis and cyclin-dependent kinase inhibitors in human gastric cancer.

BACKGROUND: Aberrant regulation of glycogen synthase kinase-3beta (GSK-3beta) has been implicated in several human cancers; however, it has not been reported in the gastric cancer tissues to date. The present study was performed to determine the expression status of active form of GSK-3beta phosphorylated at Tyr216 (pGSK-3beta) and its relationship with other tumor-associated proteins in human gastric cancers. METHODS: Immunohistochemistry was performed on tissue array slides containing 281 human gastric carcinoma specimens. In addition, gastric cancer cells were cultured and treated with a GSK-3beta inhibitor lithium chloride (LiCl) for immunoblot analysis. RESULTS: We found that pGSK-3beta was expressed in 129 (46%) of 281 cases examined, and was higher in the early-stages of pathologic tumor-node-metastasis (P < 0.001). The expression of pGSK-3beta inversely correlated with lymphatic invasion (P < 0.001) and lymph node metastasis (P < 0.001) and correlated with a longer patient survival (P < 0.001). In addition, pGSK-3beta expression positively correlated with that of p16, p21, p27, p53, APC, PTEN, MGMT, SMAD4, or KAI1 (P < 0.05), but not with that of cyclin D1. This was confirmed by immunoblot analysis using SNU-668 gastric cancer cells treated with LiCl. CONCLUSIONS: GSK-3beta activation was frequently observed in early-stage gastric carcinoma and was significantly correlated with better prognosis. Thus, these findings suggest that GSK-3beta activation is a useful prognostic marker for the early-stage gastric cancer.