The Role of the Pleckstrin Homology Domain-containing Protein CKIP-1 in Activation of p21-activated Kinase 1 (PAK1).

Upon growth factor stimulation, PAK1 is recruited to the plasma membrane and activated by a mechanism that requires its phosphorylation at Ser-223 by the protein kinase CK2. However, the upstream signaling molecules that regulate this phosphorylation event are not clearly defined. Here, we demonstrate a major role of the CK2α-interacting protein CKIP-1 in activation of PAK1. CK2α, CKIP-1, and PAK1 are translocated to membrane ruffles in response to the epidermal growth factor (EGF), where CKIP-1 mediates the interaction between CK2α and PAK1 in a PI3K-dependent manner. Consistently, PAK1 mediates phosphorylation and modulation of the activity of p41-Arc, one of its plasma membrane substrate, in a fashion that requires PI3K and CKIP-1. Moreover, CKIP-1 knockdown or PI3K inhibition suppresses PAK1-mediated cell migration and invasion, demonstrating the physiological significance of the PI3K-CKIP-1-CK2-PAK1 signaling pathway. Taken together, these findings identify a novel mechanism for the activation of PAK1 at the plasma membrane, which is critical for cell migration and invasion.

The interactive association of smoking and drinking levels with presence of periodontitis in South Korean adults.

BACKGROUND: Periodontitis is a chronic and long-lasting low-grade inflammatory disease. Numerous studies have shown that the severity of periodontitis rose when there was an increase in the amount of smoking or alcohol consumption. However, as periodontitis known as a chronic disease, it is important to consider not only the amount but "duration" with frequency i.e., rates, of smoking or drinking. This study assessed impacts of the amount and duration of smoking and drinking on periodontal health in Korean adults. We also investigated whether or not there is an interactive effect of smoking and drinking on periodontal health. METHODS: Under a cross-sectional study design, we used data from the fourth and fifth the Korean National Health and Nutrition Examination Survey (KNHANES) sessions (2008-2010). A total of 18,488 subjects (over 19 years) answered both smoking and drinking status and were given the periodontal examination. Periodontal health status was determined by the community periodontal index (CPI) developed by the World Health Organization (WHO). According to the WHO guidelines, if a participant's CPI was 3 or larger, we classified the person as a case of periodontitis. Participants with a CPI < 3 were assigned to the control group. RESULTS: Prevalence of periodontitis for self-reported smokers or drinkers in South Korea was 35.0 or 28.0 %, respectively. We observed 1.20 (0.93~1.56) of odds ratio (95 % CI) for prevalence (POR) of periodontitis for those smoked <13 pack-year (PY) and drank ≥6.8 glass-year (GY). And we had POR of 1.91 (1.34~2.73) for those smoked ≥13 PY and drank <6.8 GY, compared to those nonsmoking nondrinkers. The observed POR of 2.41 (95 % CI: 1.94-3.00), for those smoked ≥13 PY and drank ≥6.8 GY, was higher than a multiplicative effect estimated, i.e., 1.20 (0.93~1.56) [those smoked <13 PY and drank ≥6.8 GY] × 1.91 (1.34~2.73) [those smoked ≥13 PY and drank <6.8 GY], or 2.29. CONCLUSIONS: We observed a multiplicative interactive effect of smoking and drinking on periodontal status among Korean adults.

Glucose starvation-induced turnover of the yeast glucose transporter Hxt1.

BACKGROUND: The budding yeast Saccharomyces cerevisiae possesses multiple glucose transporters with different affinities for glucose that enable it to respond to a wide range of glucose concentrations. The steady-state levels of glucose transporters are regulated in response to changes in the availability of glucose. This study investigates the glucose regulation of the low affinity, high capacity glucose transporter Hxt1. METHODS AND RESULTS: Western blotting and confocal microscopy were performed to evaluate glucose regulation of the stability of Hxt1. Our results show that glucose starvation induces endocytosis and degradation of Hxt1 and that this event requires End3, a protein required for endocytosis, and the Doa4 deubiquitination enzyme. Mutational analysis of the lysine residues in the Hxt1 N-terminal domain demonstrates that the two lysine residues, K12 and K39, serve as the putative ubiquitin-acceptor sites by the Rsp5 ubiquitin ligase. We also demonstrate that inactivation of PKA (cAMP-dependent protein kinase A) is needed for Hxt1 turnover, implicating the role of the Ras/cAMP-PKA glucose signaling pathway in the stability of Hxt1. CONCLUSION AND GENERAL SIGNIFICANCE: Hxt1, most useful when glucose is abundant, is internalized and degraded when glucose becomes depleted. Of note, the stability of Hxt1 is regulated by PKA, known as a positive regulator for glucose induction of HXT1 gene expression, demonstrating a dual role of PKA in regulation of Hxt1.

Retinoic acid receptor alpha: One of plasma biomarkers associated with exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Exacerbation of COPD is a major risk factor for bad prognosis of COPD. A few plasma proteins have been discovered to associate with hospital admission due to exacerbation up to date. We tried to find new plasma biomarkers to predict the exacerbation of COPD. METHODS: We examined the plasma of normal control (n = 8) and COPD stable (n = 8) and exacerbation (n = 8) using 2-Dimentional Electrophoresis. The differentially expressed protein spots were identified by MALDI-TOF. ELISA were performed for quantitative measurement of RARα in plasma from normal control (n = 37) and COPD (n = 35). RESULTS: 17 proteins were differentially expressed in plasma between stable and exacerbation state in the subjects with COPD. Identification using MALDI-TOF showed that retinoic acid receptor alpha, ninein, isoform CRA_a, alpha-1 antitrypsin, fibrinogen gamma, tyrosyl-DNA phosphodiesterase 2, and T cell receptor delta chain were increased in exacerbation of COPD, while fibrin beta, Crystal Structure Of An Autoimmune Complex Between A Human Igm RF* And Igg1 Fc, transferrin, serpin peptidase inhibitor member 6, complement factor B preproprotein, Chain B, Crig Bound To C3c, and WD repeat-containing protein 1 isoform 1 were decreased. Quantitative measurement showed that RARα plasma levels significantly increased in exacerbation state compared to stable state of COPD (n = 14). In the plasma of stable state, the COPD subjects (n = 14) having more than 0.4 time/yr of admission had very high levels of RAR alpha protein and those (n = 11) having less than 0.4 times/yr of admission had the intermediate levels compared to those having no exacerbation (n = 10). ROC analysis of RAR alpha levels to frequency of admission showed an area under the curve of 0.844. A cut-off of 0.154 ng/ml of RAR alpha predicted hospital admission with a sensitivity of 71.4% and a specificity of 92.8%. CONCLUSION: The proteomic analysis of plasma indicates that alteration of several proteins may be associated with admission of COPD. Among them, plasma RAR alpha level may predict hospital admission with a sensitivity of 71.4% and a specificity of 92.8%.

Elevation of S100 calcium binding protein A9 in sputum of neutrophilic inflammation in severe uncontrolled asthma.

BACKGROUND: Neutrophilic airway inflammation is frequently observed in severe uncontrolled asthma (UA) and controlled asthma (CA). However, there is no sputum biomarker to differentiate the 2 conditions. OBJECTIVE: To identify biomarkers of severe uncontrolled asthma with neutrophilic airway inflammation. METHODS: Sputum with a neutrophil content larger than 70% was pooled from 5 patients with severe UA and from 10 patients with CA. Two-dimensional electrophoresis was adopted for differential display proteomics, and candidate proteins were identified using matrix-assisted laser adsorption/ionization-time of flight mass spectrometric analysis. S100 calcium binding protein A9 (S100A9) was identified by western blot and its level was measured in sputum from asthmatics with varying disease severity, patients with chronic obstructive lung disease, and normal controls using enzyme-linked immunosorbent assay. RESULTS: Fourteen protein spots exhibited differences in relative intensity between patients with severe UA and those with CA. Matrix-assisted laser adsorption/ionization-time of flight/time of flight of these spots showed an increase in human neutrophil peptide-2, S100A9, ß-amylase, neutrophil gelatinase-associated lipocalin, 4-aminobutyrate transaminase, and cystatin SA in patients with UA compared with patients with CA. There was a decrease in the plunc precursor, complement C3 component, immunoglobulin heavy-chain variable region, glial fibrillary acidic protein isoform-1, IgM κIIIb SON, MLL-AF4 der(11) fusion protein, cytokeratin-8, and recombinant IgG4 heavy chain. S100A9 was detected at a higher level in western blots of neutrophilic sputum from patients with severe UA vs CA. S100A9 levels were significantly increased, as measured by enzyme-linked immunosorbent assay, in neutrophilic UA compared with CA, eosinophilic UA and CA, and chronic obstructive lung disease. CONCLUSION: S100A9 in sputum may be a biomarker of neutrophilic inflammation in severe UA.

Winter season temperature drops and sulfur dioxide levels affect on exacerbation of refractory asthma in South Korea: a time-trend controlled case-crossover study using soonchunhyang asthma cohort data.

OBJECTIVE: According to the American Thoracic Society, approximately 5% of all asthmatics have refractory asthma (RA); these patients fail to recover lost lung function even after long-term treatment with high doses of medications. METHODS: Using a time-trend controlled case-crossover study design, we calculated odds ratios to evaluate whether exposure to ambient air pollutants and certain meteorological conditions on the day of admission (Lag 0) and up to 3 days before admission (Lag1 through Lag 3) were associated with acute RA exacerbation. Results were obtained after controlling for the effects of seasonality, smoking, and allergen sensitivity; we stratified our data into four seasons with respect to the median temperature of each month and further stratified them according to self-reported smoking status and skin-prick test results. RESULTS: In our study, RA patients (n = 82), living in metropolitan city of Seoul and Kyunggi Province, accounted for 3.7% of all asthmatics (n = 2298) registered in our asthma cohort between 2005 and 2009. In winter, a 1°C decrease in ambient temperature and a 1 ppb increase in sulfur dioxide concentration on the day of Lag 1 were associated with 14.8% (95% confidence interval [CI]: 0.9-26.7) and 19.7% (95% CI: 3.3-38.7) increases in the risk of RA exacerbation among nonsmokers, respectively. Similar associations were obtained on the day of Lag 2. The association remained unchanged after excluding patients sensitive to Dermatophagoides farinae and Dermatophagoides pteronyssinus. CONCLUSIONS: Exposure to temperature drops and increased sulfur dioxide concentrations are positively associated with the occurrence of acute RA exacerbation during winter with 1 or 2 day lags.

Investigations for Design Estimation of an Anisotropic Polymer Matrix Composite Plate with a Central Circular Hole under Uniaxial Tension.

Composite plates with holes are common in engineering applications, such as the automotive and aerospace industries. Three-dimensional braided carbon/epoxy polymers are an advanced textile composite and are used in various structures due to their high damage resistance and relatively low manufacturing cost. When a braided polymer plate with a hole is used in engineering applications, it is necessary to know its mechanical behavior under loading conditions using analysis theory to design it better. However, the effects of stress distribution with shear deformation theories on the variable thickness of the braided polymer plate (carbon/epoxy) with a hole under tensile loading have not been reported yet. In this paper, a study is conducted to evaluate shear deformation theories for a braided polymer plate with variable thickness and a hole in the center, analyzing the stresses and their concentration variations. First, multiscale modeling and analysis are performed to determine the mechanical properties of the plate. Then, finite element analyses are performed on a homogenized macro plate with a hole. The analysis process is verified by comparison with the available literature. Results show that the first-order shear deformation theory calculates 37, 56, and 70 percent less maximum transverse shear stress than the high-order shear deformation theory (Reissner-Mindlin) and the elasticity theory for thin, moderately thick, and thick braided polymer plates, respectively. Additionally, changing the theory has no significant effect on circumferential stress, radial stress, Von Mises stress, and stress concentration factor. As a result, this research can provide researchers and designers with structural intuition for a braided polymer plate with a center hole.

Tetraspanin TM4SF5 mediates loss of contact inhibition through epithelial-mesenchymal transition in human hepatocarcinoma.

The growth of normal cells is arrested when they come in contact with each other, a process known as contact inhibition. Contact inhibition is lost during tumorigenesis, resulting in uncontrolled cell growth. Here, we investigated the role of the tetraspanin transmembrane 4 superfamily member 5 (TM4SF5) in contact inhibition and tumorigenesis. We found that TM4SF5 was overexpressed in human hepatocarcinoma tissue. TM4SF5 expression in clinical samples and in human hepatocellular carcinoma cell lines correlated with enhanced p27Kip1 expression and cytosolic stabilization as well as morphological elongation mediated by RhoA inactivation. These TM4SF5-mediated effects resulted in epithelial-mesenchymal transition (EMT) via loss of E-cadherin expression. The consequence of this was aberrant cell growth, as assessed by S-phase transition in confluent conditions, anchorage-independent growth, and tumor formation in nude mice. The TM4SF5-mediated effects were abolished by suppressing the expression of either TM4SF5 or cytosolic p27Kip1, as well as by reconstituting the expression of E-cadherin. Our observations have revealed a role for TM4SF5 in causing uncontrolled growth of human hepatocarcinoma cells through EMT.

Evaluation of an incentive-based obesity management program in a workplace.

This study is to analyze the effectiveness of an incentive-based obesity management program (the Midas Project aimed to improve good health habits) at an electronics company in 2005. A total of 95 company participants with a high body mass index (BMI) were recruited for a health promotion program for 3 months that awarded gold medals as an incentive for body fat loss. BMI decreased from 28.8 to 27.8 kg/m² (p = .000), body weight decreased from 87.2 to 83.5 kg (p = .000), and body fat weight decreased from 25.4 to 23.3 kg (p = .000). Systolic and diastolic blood pressure decreased from 130.5 to 125.1 mmHg (p = .002), from 86.4 to 81.7 mmHg (p = .009). The percentage of participants exercising more than 3 times per week increased from 27.3 to 52.3% (p = .000). The percentage who avoided overeating at parties and midnight eating increased from 65.9 to 72.7% (p = .767) and 70.5 to 84.1% (p = .172), respectively. This incentive-based obesity management program was effective in improving not only BMI but also health status.

Roles for Ndel1 in keratin organization and desmosome function.

Keratin intermediate filaments form dynamic polymer networks that organize in specific ways dependent on the cell type, the stage of the cell cycle, and the state of the cell. In differentiated cells of the epidermis, they are organized by desmosomes, cell-cell adhesion complexes that provide essential mechanical integrity to this tissue. Despite this, we know little about how keratin organization is controlled and whether desmosomes locally regulate keratin dynamics in addition to binding preassembled filaments. Ndel1 is a desmosome-associated protein in the differentiated epidermis, though its function at these structures has not been examined. Here, we show that Ndel1 binds directly to keratin subunits through a motif conserved in all intermediate filament proteins. Further, Ndel1 was necessary for robust desmosome-keratin association and sufficient to reorganize keratins at distinct cellular sites. Lis1, a Ndel1 binding protein, was required for desmosomal localization of Ndel1, but not for its effects on keratin filaments. Finally, we use mouse genetics to demonstrate that loss of Ndel1 results in desmosome defects in the epidermis. Our data thus identify Ndel1 as a desmosome-associated protein that promotes local assembly/reorganization of keratin filaments and is essential for robust desmosome formation.

An assessment of AKIN criteria for hospital-acquired acute kidney injury: a prospective observational cohort study.

BACKGROUND AND AIMS: The Acute Kidney Injury Network (AKIN) criteria assert a new definition for acute kidney injury (AKI). We investigated the incidence of hospital-acquired AKI, along with the clinical characteristics and outcomes in hospitalized patients according to AKIN stage. METHODS: We performed a prospective, observational, single-center study. We monitored serum creatinine everyday for all patients using a hospital data survey system during the study period from September 2007 to February 2008. RESULTS: Hospital-acquired AKI occurred in 1.2% of all hospitalized patients during the study period. Among patients with AKI, 29.2% were in stage 1, 36.5% were in stage 2 and 34.4% were in stage 3. A significantly higher rate of renal recovery was observed in patients with lower-stage injuries (71.4, 60.0, and 21.2% for stages 1, 2, and 3, respectively). Mortality for patients with stage 3 AKI (51.5%) was significantly higher than that for patients with stages 1 or 2 (p < 0.013). Independent risk factors for mortality in patients with AKI included malignancy, stage 3 AKI, diuretic use, and intensive care unit admission prior to AKI. CONCLUSIONS: Our findings support the utility of the AKIN criteria for hospital-acquired AKI, and demonstrate that stage 3 AKI poses a significant risk for poor patient and renal outcomes.

Serum prostate-specific antigen is better correlated to body surface area than body mass index in a population of healthy Korean men.

It has been suggested that the larger vascular volume among obese men causes a dilution effect, decreasing the concentration of serum prostate-specific antigen (PSA). However, plasma volume is proportional to body surface area (BSA) rather than to body mass index (BMI). We determined whether serum PSA level is better correlated to BSA than BMI in a population of ostensibly healthy Korean men. Data from 2604 men who visited our health promotion center were evaluated. All men underwent anthropometric measurements, digital rectal examination, serum PSA determination, and transrectal ultrasound examination. The correlation between serum PSA and other parameters was statistically analyzed. The mean age was 49.9 years and the mean serum PSA level was 1.14 ng/mL. The multivariate analysis revealed that the serum PSA was positively correlated with age, prostate volume, and negatively correlated with BSA only and not with BMI. In addition, BSA, rather than BMI, was the significant factor in predicting the prostate volume. Our results suggest that men with larger BSA (rather than BMI), have larger prostate volumes, and lower serum PSA.

Syndecan-2 overexpression regulates adhesion and migration through cooperation with integrin alpha2.

Syndecan-2, a transmembrane heparan sulfate proteoglycan, is known to serve as an adhesion receptor, but details of the regulatory mechanism governing syndecan-2 cell adhesion and migration remain unclear. Here, we examined this regulatory mechanism, showing that overexpression of syndecan-2 enhanced collagen adhesion, cell migration and invasion of normal rat intestinal epithelial cells (RIE1), and increased integrin alpha2 expression levels. Interestingly, RIE1 cells transfected with either syndecan-2 or integrin alpha2 showed similar adhesion and migration patterns, and a function-blocking anti-integrin alpha2 antibody abolished syndecan-2-mediated adhesion and migration. Consistent with these findings, transfection of integrin alpha2 siRNA diminished syndecan-2-induced cell migration in HCT116 human colon cancer cells. Taken together, these results demonstrate a novel cooperation between syndecan-2 and integrin alpha2beta1 in adhesion-mediated cell migration and invasion. This interactive dynamic might be a possible mechanism underlying the tumorigenic activities of colon cancer cells.

Magnetic resonance imaging of breast cancer and correlation with prognostic factors.

BACKGROUND: Prognostic factors of breast cancer have been used for the prediction of clinical outcome or selection of patients for complementary treatment. Some of the imaging features of breast cancer, e.g. magnetic resonance imaging (MRI), are associated with these prognostic factors. PURPOSE: To evaluate the relationship between dynamic enhanced MR features and prognostic factors of clinical outcome of breast cancer. MATERIAL AND METHODS: A total of 136 patients with 151 breast cancers underwent 1.5T dynamic MR imaging with the use of a dynamic T1-weighted three-dimensional fast low-angle shot (FLASH) subtraction imaging technique. Morphological and kinetic analyses of MR features were evaluated using the American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) MRI lexicon. Pathological prognostic factors were correlated with MR imaging characteristics, including tumor size, histological grade, lymph node status, expression of estrogen receptor (ER), expression of progesterone receptor (PR), expression of c-erbB2, determination of Ki-67 index, and microvascular density (MVD), using univariate and multivariate statistical analyses. RESULTS: Based on univariate and multivariate analyses, spiculated tumor margins correlated significantly with lower histological grade (I-II) and positive PR expression. Rim enhancement was significantly correlated with high histological grade, presence of axillary lymph node metastasis, large tumor size, increased Ki-67 index, and increased MVD. Early peak enhancement, as seen on the first scan after contrast medium injection, was correlated with negative ER expression. CONCLUSION: The presence of a lesion with a spiculated margin may predict a relatively good prognosis, and the presence of a lesion with rim enhancement may predict a relatively poor prognosis.

Programming of macrophages by UV-irradiated apoptotic cancer cells inhibits cancer progression and lung metastasis.

Apoptotic cell clearance by phagocytes is essential in tissue homeostasis. We demonstrated that conditioned medium (CM) from macrophages exposed to apoptotic cancer cells inhibits the TGFß1-induced epithelial-mesenchymal transition (EMT), migration, and invasion of cancer cells. Apoptotic 344SQ (ApoSQ) cell-induced PPARγ activity in macrophages increased the levels of PTEN, which was secreted in exosomes. Exosomal PTEN was taken up by recipient lung cancer cells. ApoSQ-exposed CM from PTEN knockdown cells failed to enhance PTEN in 344SQ cells, restore cellular polarity, or exert anti-EMT and anti-invasive effects. The CM that was deficient in PPARγ ligands, including 15-HETE, lipoxin A4, and 15d-PGJ2, could not reverse the suppression of PPARγ activity or the PTEN increase in 344SQ cells and consequently failed to prevent the EMT process. Moreover, a single injection of ApoSQ cells inhibited lung metastasis in syngeneic immunocompetent mice with enhanced PPARγ/PTEN signaling both in tumor-associated macrophages and in tumor cells. PPARγ antagonist GW9662 reversed the signaling by PPARγ/PTEN; the reduction in EMT-activating transcription factors, such as Snai1 and Zeb1; and the antimetastatic effect of the ApoSQ injection. Thus, the injection of apoptotic lung cancer cells may offer a new strategy for the prevention of lung metastasis.

The signaling network of transforming growth factor beta1, protein kinase Cdelta, and integrin underlies the spreading and invasiveness of gastric carcinoma cells.

Integrin-mediated cell adhesion and spreading enables cells to respond to extracellular stimuli for cellular functions. Using a gastric carcinoma cell line that is usually round in adhesion, we explored the mechanisms underlying the cell spreading process, separate from adhesion, and the biological consequences of the process. The cells exhibited spreading behavior through the collaboration of integrin-extracellular matrix interaction with a Smad-mediated transforming growth factor beta1 (TGFbeta1) pathway that is mediated by protein kinase Cdelta (PKCdelta). TGFbeta1 treatment of the cells replated on extracellular matrix caused the expression and phosphorylation of PKCdelta, which is required for expression and activation of integrins. Increased expression of integrins alpha2 and alpha3 correlated with the spreading, functioning in activation of focal adhesion molecules. Smad3, but not Smad2, overexpression enhanced the TGFbeta1 effects. Furthermore, TGFbeta1 treatment and PKCdelta activity were required for increased motility on fibronectin and invasion through matrigel, indicating their correlation with the spreading behavior. Altogether, this study clearly evidenced that the signaling network, involving the Smad-dependent TGFbeta pathway, PKCdelta expression and phosphorylation, and integrin expression and activation, regulates cell spreading, motility, and invasion of the SNU16mAd gastric carcinoma cell variant.

Metal transporters in intestine and brain: their involvement in metal-associated neurotoxicities.

The transport of essential metals and other nutrients across tight membrane barriers such as the gastrointestinal tract and blood-brain barrier is mediated by specific transport mechanisms. Specific transporters take up metals at the apical surface and export them at the basolateral surface, and are involved in their intracellular distribution. Transporters for each of the major essential metals, calcium, iron and zinc, have been identified. These transporters also mediate the transport of non-essential metals across tight membrane barriers. For example, the intestinal iron transporter divalent metal transporter 1 mediates the uptake of lead and cadmium. The levels of essential metals are strictly regulated by transporters. When dietary levels of essential metals are low, levels of the corresponding transporters increase in the intestine, after which there is a greater potential for increased transport of toxic metals. In the brain, the strict regulation of metals prevents injury that potentially would result from oxidative damage induced by the essential metals iron, copper and zinc. Indeed, the oxidative damage found in neurodegenerative diseases is likely to be due to higher levels of these metals. Involvement of intracellular transporters for copper and zinc has been shown in animal models of Alzheimer's disease, raising the possibility that higher levels of iron, zinc and copper might be due to a disruption in the activity of transporters. Accordingly, exposure to toxicants that affect the activity of transporters potentially could contribute to the aetiology/progression of neurodegenerative diseases.

Is the Location of the Tumor Another Prognostic Factor for Patients With Colon Cancer?

PURPOSE: In this study, we investigated both the characteristics of right colon cancer (RTCC) in comparison with those of left colon cancer (LTCC) and the impact of the location of the colon cancer on the prognosis. METHODS: We retrospectively analyzed the cases of 974 patients with nonmetastatic colon cancer who had undergone surgery with a curative intent from January 2001 to December 2011. RTCC was defined as a tumor located proximal to the splenic flexure. The characteristics of RTCC cancer were investigated by using descriptive analyses, and their impacts on the prognosis were assessed by using a Cox multivariate regression. RESULTS: Compared to LTCC, RTCC showed a female-dominant feature, and an undifferentiated pathology was more frequently observed. The number of lymph nodes retrieved from patients with RTCC was significantly higher than that retrieved from patients with LTCC. During 75 months of follow-up, peritoneal recurrence was more common in patients with RTCC than it was in patients with LTCC, and among the patients with stage III colon cancer, the disease-free and the overall survival rates were significantly worse in patients with RTCC. After adjustments with the other prognostic factors associated with colon cancer had been made, a tumor located at the right colon was found to be independently associated with poor prognosis. CONCLUSION: RTCC showed unique clinicopathologic features and was associated with a poorer prognosis.

Interaction of macrophages with apoptotic cells inhibits transdifferentiation and invasion of lung fibroblasts.

The invasion of activated fibroblasts is a key mechanism of tissue fibrosis pathology. The recognition and uptake of apoptotic cells can induce the anti-fibrogenic programming of macrophages. We demonstrate that after interacting with apoptotic cells, macrophages secrete bioactive molecules that antagonize TGF-ß1-induced increases in myofibroblast (fibroproliferative) phenotypic markers and reduce the enhanced invasive capacity of TGF-ß1- or EGF-treated mouse lung fibroblasts (MLg). Furthermore, numerous treatment strategies prevented the anti-fibrotic effects of conditioned media, including transfection of macrophages with COX-2 or RhoA siRNAs or treatment of MLg cells with receptor antagonists for prostaglandin E2 (PGE2), PGD2, or hepatocyte growth factor (HGF). Additionally, administration of apoptotic cells in vivo inhibited the bleomycin-mediated invasive capacity of primary fibroblasts, as well as adhesion and extracellular matrix protein mRNA expression. These data suggest that the anti-fibrogenic programming of macrophages by apoptotic cells can be used as a novel tool to control the progressive fibrotic reaction.

Association of urinary 3-phenoxybenzoic acid levels with self-reported depression symptoms in a rural elderly population in Asan, South Korea.

OBJECTIVES: This study aimed to evaluate the association between presence of depression symptoms and the exposure level to insecticides among aged population in rural area, determined via measured levels of urinary 3-phenoxybenzoic acid (3-PBA), after controlling for socioeconomic confounding factors. METHODS: Using a cross-sectional study design, we randomly recruited participants for our study (161 male and 239 female) from rural areas of Asan, Chungnam, Korea. Environmental risk factor exposure was assessed using a questionnaire, and gas chromatography- mass spectrometry was used to analyze urinary 3-PBA levels. We used a logistic regression analysis to assess the association of urinary 3-PBA levels with the presence of self-reported depression symptoms. RESULTS: After controlling for creatinine levels, the median (interquartile range) concentration of 3-PBA was approximately 1.5 times (p<0.05) higher among female (1.54 [0.90 to 2.35]) µg/g) than among male (1.06 [0.64 to 1.81] µg/g). Our study found that among female participants, the unit increase in 3-PBA levels exhibited a likely positive association (odds ratio, 1.12; 95% confidence interval, 1.00 to 1.25) with an increased risk of presence of self-reported depression symptoms, after adjusting for socioeconomic insurance type, daily physical condition, marital status, smoking status, and age. CONCLUSIONS: Given our finding of a potential association between the presence of selfreported depression symptoms and 3-PBA levels, precautions should be considered to minimize exposure to insecticides and thus protect the health of aged residents in rural areas.