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1.
Breast Cancer Res ; 26(1): 65, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38609935

ABSTRACT

BACKGROUND: Sentinel lymph node biopsy (SLNB) is recommended for patients with ductal carcinoma in situ (DCIS) undergoing mastectomy, given the concerns regarding upstaging and technical difficulties of post-mastectomy SLNB. However, this may lead to potential overtreatment, considering favorable prognosis and de-escalation trends in DCIS. Data regarding upstaging and axillary lymph node metastasis among these patients remain limited. METHODS: We retrospectively reviewed patients with DCIS who underwent mastectomy with SLNB or axillary lymph node dissection at Gangnam Severance Hospital between January 2010 and December 2021. To explore the feasibility of omitting SLNB, we assessed the rates of DCIS upgraded to invasive carcinoma and axillary lymph node metastasis. Binary Cox regression analysis was performed to identify clinicopathologic factors associated with upstaging and axillary lymph node metastasis. RESULTS: Among 385 patients, 164 (42.6%) experienced an invasive carcinoma upgrade: microinvasion, pT1, and pT2 were confirmed in 53 (13.8%), 97 (25.2%), and 14 (3.6%) patients, respectively. Seventeen (4.4%) patients had axillary lymph node metastasis. Multivariable analysis identified age ≤ 50 years (adjusted odds ratio [OR], 12.73; 95% confidence interval [CI], 1.18-137.51; p = 0.036) and suspicious axillary lymph nodes on radiologic evaluation (adjusted OR, 9.31; 95% CI, 2.06-41.99; p = 0.004) as independent factors associated with axillary lymph node metastasis. Among patients aged > 50 years and/or no suspicious axillary lymph nodes, only 1.7-2.3%) experienced axillary lymph node metastasis. CONCLUSIONS: Although underestimation of the invasive component was relatively high among patients with DCIS undergoing mastectomy, axillary lymph node metastasis was rare. Our findings suggest that omitting SLNB may be feasible for patients over 50 and/or without suspicious axillary lymph nodes on radiologic evaluation.


Subject(s)
Breast Neoplasms , Carcinoma, Intraductal, Noninfiltrating , Humans , Female , Sentinel Lymph Node Biopsy , Carcinoma, Intraductal, Noninfiltrating/surgery , Lymphatic Metastasis , Breast Neoplasms/surgery , Retrospective Studies , Mastectomy
2.
Glycobiology ; 34(2)2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38015989

ABSTRACT

Heparan sulfate (HS) is a linear polysaccharide that plays a key role in cellular signaling networks. HS functions are regulated by its 6-O-sulfation, which is catalyzed by three HS 6-O-sulfotransferases (HS6STs). Notably, HS6ST2 is mainly expressed in the brain and HS6ST2 mutations are linked to brain disorders, but the underlying mechanisms remain poorly understood. To determine the role of Hs6st2 in the brain, we carried out a series of molecular and behavioral assessments on Hs6st2 knockout mice. We first carried out strong anion exchange-high performance liquid chromatography and found that knockout of Hs6st2 moderately decreases HS 6-O-sulfation levels in the brain. We then assessed body weights and found that Hs6st2 knockout mice exhibit increased body weight, which is associated with abnormal metabolic pathways. We also performed behavioral tests and found that Hs6st2 knockout mice showed memory deficits, which recapitulate patient clinical symptoms. To determine the molecular mechanisms underlying the memory deficits, we used RNA sequencing to examine transcriptomes in two memory-related brain regions, the hippocampus and cerebral cortex. We found that knockout of Hs6st2 impairs transcriptome in the hippocampus, but only mildly in the cerebral cortex. Furthermore, the transcriptome changes in the hippocampus are enriched in dendrite and synapse pathways. We also found that knockout of Hs6st2 decreases HS levels and impairs dendritic spines in hippocampal CA1 pyramidal neurons. Taken together, our study provides novel molecular and behavioral insights into the role of Hs6st2 in the brain, which facilitates a better understanding of HS6ST2 and HS-linked brain disorders.


Subject(s)
Brain Diseases , Intellectual Disability , Sulfotransferases , Animals , Humans , Mice , Dendritic Spines/metabolism , Heparitin Sulfate/metabolism , Hippocampus/metabolism , Memory Disorders , Mice, Knockout , Neurons/metabolism , Pralidoxime Compounds , Sulfotransferases/genetics , Sulfotransferases/metabolism
3.
PeerJ ; 11: e16295, 2023.
Article in English | MEDLINE | ID: mdl-37941934

ABSTRACT

Background: The purpose of this study was to identify the total, direct, and indirect influence of spousal support on pregnancy stress among married immigrant pregnant women. The study aimed to determine the relative magnitudes of specific mediating effects of coping styles and self-esteem. Method: A cross-sectional correlational survey was conducted in Jeonnam with 206 married immigrant pregnant women. Data were collected from September 7 to November 7 in 2019. A self-report questionnaire was used to measure spousal support, pregnancy stress, coping styles, and self-esteem. The study employed a linear multiple regression analysis to examine the potential multi-mediating effects. The effect size was set at 0.15, the significance level at 0.05, and the power at 0.95. Through the analysis, the researchers explored the mediating mechanisms among the variables and identified the presence of multi-mediating effects. Results: The effect sizes (b) and statistical significance (p) for the predictors were as follows: problem-focused coping (b = 0.13, p = 0.001), emotion-focused coping (b = 0.11, p = 0.004), and self-esteem (b = 0.10, p < 0.001). Emotion-focused coping (b = 0.26, p = 0.001) and self-esteem (b = -0.20, p = 0.035) had a significant impact on pregnancy stress. The total effect of spousal support on pregnancy stress was significant at -0.25 (p < 0.001), and the direct effect was also significant at -0.26 (p < 0.001). We observed significant mediating effects for emotion-focused coping and self-esteem. Conclusions: As a result of this study, the self-esteem of married immigrant pregnant women can have a protective effect by preventing the aggravation of pregnancy stress in the relationship between spousal support and pregnancy stress. Meanwhile, the emotion-focused coping style can balance out the effect of self-esteem. Therefore, in order to alleviate the stress of pregnancy for women, it is necessary to provide intervention to help improve self-esteem with spousal support. In addition, nursing professionals should help them use appropriate coping styles.


Subject(s)
Pregnant Women , Stress, Psychological , Humans , Female , Pregnancy , Stress, Psychological/prevention & control , Cross-Sectional Studies , Adaptation, Psychological , Self Concept
4.
Front Psychiatry ; 14: 1195378, 2023.
Article in English | MEDLINE | ID: mdl-37663596

ABSTRACT

Background: Runaway behavior is reported to impede the growth, mental health development, and social adjustment of adolescents. Exposure to harmful media causes problematic behaviors in adolescents, sometimes inducing them to run away from home. Methods: This study examined the factors influencing adolescents' runaway behavior. Utilizing the data of 11,354 adolescents from the Survey of Media Usage and Harmful Environment among Adolescents, a hierarchical logistic regression analysis was conducted using the SPSS 24.0 program. Results: The significant predictors of runaway behavior were the grade of the adolescent, deviant behaviors (drinking, smoking), autonomous control ability, relationship with family, and harmful media (p < 0.001). This regression model explained 13.1% of the variance in runaway behavior. A significant outcome of this study is that harmful media was identified as one of the factors affecting adolescents' runaway behavior. Adjusted OR and 95% CI of harmful media was 1.23 (1.10-1.38). Conclusion: This study showed that individual, family, social factors, and harmful media influence adolescents' runaway behavior. The results emphasize the importance of health teachers and the need for early intervention programs, for the identification and prevention of risk factors for adolescents' runaway behavior.

5.
FASEB J ; 37(10): e23185, 2023 10.
Article in English | MEDLINE | ID: mdl-37695721

ABSTRACT

Sensory neurons in the dorsal root ganglia (DRG) convey somatosensory and metabolic cues to the central nervous system and release substances from stimulated terminal endings in peripheral organs. Sex-biased variations driven by the sex chromosome complement (XX and XY) have been implicated in the sensory-islet crosstalk. However, the molecular underpinnings of these male-female differences are not known. Here, we aim to characterize the molecular repertoire and the secretome profile of the lower thoracic spinal sensory neurons and to identify molecules with sex-biased insulin sensing- and/or insulin secretion-modulating activity that are encoded independently of circulating gonadal sex hormones. We used transcriptomics and proteomics to uncover differentially expressed genes and secreted molecules in lower thoracic T5-12 DRG sensory neurons derived from sexually immature 3-week-old male and female C57BL/6J mice. Comparative transcriptome and proteome analyses revealed differential gene expression and protein secretion in DRG neurons in males and females. The transcriptome analysis identified, among others, higher insulin signaling/sensing capabilities in female DRG neurons; secretome screening uncovered several sex-specific candidate molecules with potential regulatory functions in pancreatic ß cells. Together, these data suggest a putative role of sensory interoception of insulin in the DRG-islet crosstalk with implications in sensory feedback loops in the regulation of ß-cell activity in a sex-biased manner. Finally, we provide a valuable resource of molecular and secretory targets that can be leveraged for understanding insulin interoception and insulin secretion and inform the development of novel studies/approaches to fathom the role of the sensory-islet axis in the regulation of energy balance in males and females.


Subject(s)
Insulin , Transcriptome , Female , Male , Mice , Animals , Mice, Inbred C57BL , Insulin Secretion , Sex Characteristics , Secretome , Sensory Receptor Cells
6.
Article in English | MEDLINE | ID: mdl-36768010

ABSTRACT

The purpose of this study was to identify the characteristics and predictors of types of stress coping in women undergoing infertility treatment. The cross-sectional study included 120 women who were receiving infertility treatment at infertility hospitals. Self-report questionnaires were used to measure. K-means cluster analysis and multinomial logistic regression were used to examine the characteristics and predictors of stress-coping types. Out of all the women undergoing infertility treatment who completed a self-report survey, 30.8% had a weak mixed coping type, 35.9% had a strong mixed coping type, and 33.3% had a passive coping type. The strong mixed treatment type was compared to weak mixed treatment type, with the following results: infertility adaptation (OR = 17.71, p < 0.000), spousal support (OR = 4.50, p = 0.021), infertility counseling experience (OR = 7.14, p = 0.010). Comparing the strong mixed coping type with the passive coping type, resilience (OR = 9.11, p < 0.000) was shown. It is necessary to strengthen resilience and provide a receptive attitude and spousal support to women undergoing infertility adaptation to help them relieve stress and develop functional coping.


Subject(s)
Infertility , Stress, Psychological , Humans , Female , Stress, Psychological/epidemiology , Stress, Psychological/psychology , Cross-Sectional Studies , Adaptation, Psychological , Infertility/therapy , Infertility/psychology , Surveys and Questionnaires , Republic of Korea/epidemiology
7.
Mol Metab ; 66: 101647, 2022 12.
Article in English | MEDLINE | ID: mdl-36503893

ABSTRACT

OBJECTIVE: Insulin is a principal metabolic hormone. It regulates a plethora of metabolic pathways in peripheral tissues. The highly homologous insulin-like growth factor 1 (IGF-1), on the other hand, is important for development and growth. Recent studies have shown that insulin and IGF-1 signaling plays fundamental roles in the brain. Loss of insulin or IGF-1 receptors in astrocytes leads to altered glucose handling, mitochondrial metabolism, neurovascular coupling, and behavioral abnormalities in mice. Here, we aim to investigate molecular mechanisms by which insulin and IGF-1 signaling regulates astrocyte functions. METHODS: IR-flox and IRKO primary astrocytes were treated with 100 nM insulin or IGF-1 for 6 h, and their transcriptomes were analyzed. Astrocytes with either IR deletion, IGF1R deletion or both were used to examine receptor-dependent transcriptional regulations using qPCR. Additional immunoblotting and confocal imaging studies were performed to functionally validate pathways involved in protein homeostasis. RESULTS: Using next-generation RNA sequencing, we show that insulin significantly regulates the expression of over 1,200 genes involved in multiple functional processes in primary astrocytes. Insulin-like growth factor 1 (IGF-1) triggers a similar robust transcriptional regulation in astrocytes. Thus, over 50% of the differentially expressed genes are regulated by both ligands. As expected, these commonly regulated genes are highly enriched in pathways involved in lipid and cholesterol biosynthesis. Additionally, insulin and IGF-1 induce the expression of genes involved in ribosomal biogenesis, while suppressing the expression of genes involved in autophagy, indicating a common role of insulin and IGF-1 on protein homeostasis in astrocytes. Insulin-dependent suppression of autophagy genes, including p62, Ulk1/2, and several Atg genes, is blunted only when both IR and IGF1R are deleted. CONCLUSIONS: In summary, insulin and IGF-1 potently suppress autophagy in astrocytes through transcriptional regulation. Both IR and IGF1R can elicit ligand-dependent transcriptional suppression of autophagy. These results demonstrate an important role of astrocytic insulin/IGF-1 signaling on proteostasis. Impairment of this regulation in insulin resistance and diabetes may contribute to neurological complications related to diabetes.


Subject(s)
Insulin-Like Growth Factor I , Insulin , Animals , Mice , Insulin-Like Growth Factor I/genetics , Insulin-Like Growth Factor I/metabolism , Insulin/metabolism , Astrocytes/metabolism , Gene Expression Regulation , Autophagy/genetics
8.
Hum Mol Genet ; 31(24): 4207-4216, 2022 12 16.
Article in English | MEDLINE | ID: mdl-35899427

ABSTRACT

Kallmann syndrome (KS) is a congenital disorder characterized by idiopathic hypogonadotropic hypogonadism and olfactory dysfunction. KS is linked to variants in >34 genes, which are scattered across the human genome and show disparate biological functions. Although the genetic basis of KS is well studied, the mechanisms by which disruptions of these diverse genes cause the same outcome of KS are not fully understood. Here we show that disruptions of KS-linked genes affect the same biological processes, indicating convergent molecular mechanisms underlying KS. We carried out machine learning-based predictions and found that KS-linked mutations in heparan sulfate 6-O-sulfotransferase 1 (HS6ST1) are likely loss-of-function mutations. We next disrupted Hs6st1 and another KS-linked gene, fibroblast growth factor receptor 1 (Fgfr1), in mouse neuronal cells and measured transcriptome changes using RNA sequencing. We found that disruptions of Hs6st1 and Fgfr1 altered genes in the same biological processes, including the upregulation of genes in extracellular pathways and the downregulation of genes in chromatin pathways. Moreover, we performed genomics and bioinformatics analyses and found that Hs6st1 and Fgfr1 regulate gene transcription likely via the transcription factor Sox9/Sox10 and the chromatin regulator Chd7, which are also associated with KS. Together, our results demonstrate how different KS-linked genes work coordinately in a convergent signaling pathway to regulate the same biological processes, thus providing new insights into KS.


Subject(s)
Hypogonadism , Kallmann Syndrome , Receptor, Fibroblast Growth Factor, Type 1 , Sulfotransferases , Animals , Mice , Chromatin , Hypogonadism/genetics , Kallmann Syndrome/genetics , Kallmann Syndrome/metabolism , Mutation , Receptor, Fibroblast Growth Factor, Type 1/genetics , Sulfotransferases/genetics
9.
PLoS One ; 17(1): e0263082, 2022.
Article in English | MEDLINE | ID: mdl-35089962

ABSTRACT

Recursive splicing (RS) is a splicing mechanism to remove long introns from messenger RNA precursors of long genes. Compared to the hundreds of RS events identified in humans and drosophila, only ten RS events have been reported in mice. To further investigate RS in mice, we analyzed RS in the mouse brain, a tissue that is enriched in the expression of long genes. We found that nuclear total RNA sequencing is an efficient approach to investigate RS events. We analyzed 1.15 billion uniquely mapped reads from the nuclear total RNA sequencing data in the mouse cerebral cortex. Unexpectedly, we only identified 20 RS sites, suggesting that RS is a rare event in the mouse brain. We also identified that RS is constitutive between excitatory and inhibitory neurons and between sexes in the mouse cerebral cortex. In addition, we found that the primary sequence context is associated with RS splicing intermediates and distinguishes RS AGGT site from non-RS AGGT sites, indicating the importance of the primary sequence context in RS sites. Moreover, we discovered that cryptic exons may use an RS-like mechanism for splicing. Overall, we provide novel findings about RS in long genes in the mouse brain.


Subject(s)
Brain/metabolism , Exons , RNA Precursors , RNA Splicing/physiology , Animals , Mice , RNA Precursors/genetics , RNA Precursors/metabolism
10.
Glycobiology ; 31(10): 1308-1318, 2021 11 18.
Article in English | MEDLINE | ID: mdl-34132783

ABSTRACT

Heparan sulfate (HS) is a linear polysaccharide found in almost all animal cells and plays an important role in various biological processes. HS functions mainly via covalently binding to core proteins to form HS proteoglycans (HSPGs), which are heterogeneous in the lengths of the HS chain, the modifications on HS and the core proteins. The molecular mechanisms underlying HSPG heterogeneity, although widely studied, are not yet fully defined. The expression profiles of HS biosynthesis enzymes and HSPG core proteins likely contribute to the HSPG heterogeneity, but these expression profiles remain poorly characterized. To investigate the expression profiles of genes encoding HS biosynthesis enzymes and HSPG core proteins, we systematically integrated the publicly available RNA sequencing data in mice. To reveal the spatial expression of these genes, we analyzed their expression in 21 mouse tissues. To reveal the temporal expression of these genes, we analyzed their expression at 17 time points during the mouse forebrain development. To determine the cell-type-specific expression of these genes, we obtained their expression profiles in 23 cell types in the mouse cerebral cortex by integrating single nucleus RNA sequencing data. Our findings demonstrate the spatial, temporal and cell-type-specific expression of genes encoding HS biosynthesis enzymes and HSPG core proteins and represent a valuable resource to the HS research community.


Subject(s)
Glypicans/genetics , Heparan Sulfate Proteoglycans/metabolism , Heparitin Sulfate/biosynthesis , Sulfotransferases/genetics , Animals , Gene Expression Profiling , Glypicans/metabolism , Heparitin Sulfate/chemistry , Male , Mice , Mice, Inbred C57BL , Sulfotransferases/metabolism
11.
Arch Psychiatr Nurs ; 34(4): 211-217, 2020 08.
Article in English | MEDLINE | ID: mdl-32828351

ABSTRACT

This quasi-experimental study with a nonequivalent control group pretest-posttest design was conducted to evaluate the effects of a psychological intervention program for 50 women with infertility (experimental group: 26, control group: 24) utilizing assisted reproductive technology. The experimental group received six four-hour sessions of intervention, with outcomes measured at baseline and four weeks post-intervention. The experimental group demonstrated significant improvements in marital intimacy (z = 6.528, p < .001) and sexual satisfaction (z = 3.148, p = .003) and significant reductions in depression (z = -4.850, p < .001) and fatigue (z = -4.597, p < .001). Thus, the program can alleviate depression and fatigue. Further, psychological intervention centered on the marital and personal dimensions may improve marital intimacy and sexual satisfaction.


Subject(s)
Depression/psychology , Fatigue/psychology , Fertilization in Vitro , Infertility, Female , Psychosocial Intervention , Sexuality/psychology , Adult , Female , Humans , Infertility, Female/psychology , Infertility, Female/therapy , Marriage , Personal Satisfaction , Republic of Korea , Stress, Psychological/psychology , Surveys and Questionnaires
12.
Article in English | MEDLINE | ID: mdl-32492833

ABSTRACT

This study attempted to provide basic data for creating a program to help promote safe sexual behavior among runaway female at-risk adolescents by identifying factors related to the sexual experiences. This study conducted a logistic regression analysis using data regarding 182 female at-risk adolescents, which were sourced from the 2016 survey of Korean adolescents' contact with media usage and harmful environment. This study showed that adolescents' age, smoking, and harmful environments are associated with the occurrence of sexual activity among at-risk female adolescents. One significant outcome of this study was the identification of harmful environmental factors and their impact on sexual behavior. Since smoking and sex-related problems among adolescents can act as risk factors for adult sexual health in the future, schools should institute direct and indirect channels for assessing sex-related problems among runaway female at-risk adolescents and establishing proactive and preventive measures for promoting their sexual health. In addition, a social cooperation system should be established in order to assess, and mediate within, the environments around schools in order to minimize adolescents' exposure to harmful environments.


Subject(s)
Adolescent Behavior , Homeless Youth , Sexual Behavior , Adolescent , Adult , Female , Humans , Risk Factors , Smoking , Surveys and Questionnaires
13.
iScience ; 23(6): 101184, 2020 Jun 26.
Article in English | MEDLINE | ID: mdl-32502964

ABSTRACT

Connective tissue growth factor (CTGF) or cellular communication network 2 (CCN2) is a matricellular protein essential for normal embryonic development and tissue repair. CTGF exhibits cell- and context-dependent activities, but CTGF function in vascular development and barrier function is unknown. We show that endothelial cells (ECs) are one of the major cellular sources of CTGF in the developing and adult retinal vasculature. Mice lacking CTGF expression either globally or specifically in ECs exhibit impaired vascular cell growth and morphogenesis and blood barrier breakdown. The global molecular signature of CTGF includes cytoskeletal and extracellular matrix protein, growth factor, and transcriptional co-regulator genes such as yes-associated protein (YAP). YAP, itself a transcriptional activator of CTGF, mediates several CTGF-controlled angiogenic and barriergenic transcriptional programs. Re-expression of YAP rescues, at least partially, angiogenesis and barriergenesis in CTGF mutant mouse retinas. Thus, the CTGF-YAP regulatory loop is integral to retinal vascular development and barrier function.

14.
J Sch Nurs ; 36(4): 283-292, 2020 Aug.
Article in English | MEDLINE | ID: mdl-31109235

ABSTRACT

This study examines the factors influencing runaway experiences among at-risk youth. Using the data of 1,743 at-risk youth from the 2016 survey of Korean adolescents' contact with media usage and harmful environment, a logistic regression analysis was conducted. This study shows that factors associated with the adolescents' experiences of family relationships, violence victimization, and harmful environment influence the occurrence of runaway behavior in at-risk adolescents. A significant outcome of this study is the identification of a harmful environment as a factor affecting runaway behavior. The factors identified need to be considered in the development of prevention programs targeting runway behavior among at-risk youth. School nurses are uniquely positioned to review and revise educational strategies to raise adolescents' awareness regarding the effects of harmful environments and to promote violence prevention. This framework provides school nurses with systematic methods for early identification and management of risk factors among at-risk youth runway behavior.


Subject(s)
Adolescent Behavior/psychology , Exposure to Violence , Family Relations , Interpersonal Relations , Runaway Behavior/prevention & control , Schools , Social Environment , Adolescent , Female , Humans , Logistic Models , Male , Nurse's Role , Republic of Korea , Risk Factors , School Nursing , Young Adult
15.
Article in English | MEDLINE | ID: mdl-31614513

ABSTRACT

To determine whether Seoul's dementia screening program increased the rate of diagnosis and the appropriate use of healthcare services for people with dementia, a retrospective data analysis was conducted based on administrative data from the Health Insurance Review and Assessment Service. Two cohorts were constructed to represent the year before Seoul's dementia screening program began (2007) (control group) and the year after the implementation of the program (2009) (treatment group). A difference-in-difference analysis was used to compare the diagnosis rates, number of clinic visits, and dementia-related drug prescription rates for 4 districts that implemented dementia screening programs between 2007 and 2009 and 14 areas that did not. After the introduction of the program, there was a 55.4% increase in physician-diagnosed dementia. The "average drug cost per patient" increased by 52.2% (Exp(ß) = 1.522, p = 0.0264), the "average outpatient visits per patient" tended to increase by 13.5% (Exp(ß) = 1.135, p = 0.1852), and the "average outpatient treatment fees per visit per patient" tended to increase by 24.4% (Exp(ß) = 1.244, p = 0.0821). The implementation of dementia screening programs led to an increase in healthcare service utilization. Therefore, this program was found to be an effective strategy for reducing undiagnosed dementia cases and encouraging patients to use adequate healthcare services.


Subject(s)
Dementia/diagnosis , Dementia/therapy , Mass Screening/psychology , Mass Screening/statistics & numerical data , Patient Acceptance of Health Care/psychology , Patient Acceptance of Health Care/statistics & numerical data , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , Republic of Korea , Retrospective Studies
16.
Article in English | MEDLINE | ID: mdl-31340465

ABSTRACT

Due to an aging population, dementia incidence has rapidly increased in South Korea, heaping psychological and economic burdens upon families and the society. This study was aimed at investigating the associations of health insurance type and cardiovascular risk factors with the risk of dementia. The study was performed using data from 15,043 participants aged 60 years and above, enrolled in the Seoul Dementia Management Project in 2008 and followed up until 2012. Factors such as demographic data, health insurance type, lifestyle factors, and cardiovascular risk factors were subjected to Cox proportional hazard regression analysis to identify their associations with dementia incidence. During the follow-up, 495 participants (3.3%) developed dementia. Medical Aid beneficiaries were associated with an increase in the risk of dementia (hazard ratio [HR] 1.77, 95% confidence interval [CI] 1.421-2.215). Upon analyzing a composite cardiovascular risk score derived from all five cardiovascular risk factors, the risk for dementia incidence in participants increased from 1.56 for the presence of three risk factors to 2.55 for that of four risk factors (HR 2.55, 95% CI 1.174-5.546), compared with those who had no risk factors. The Medical Aid beneficiaries of health insurance type and the presence of multiple cardiovascular risk factors were found to be associated with a higher risk of dementia incidence.


Subject(s)
Cardiovascular Diseases/epidemiology , Dementia/epidemiology , Insurance, Health , Aged , Aged, 80 and over , Female , Humans , Incidence , Life Style , Male , Proportional Hazards Models , Prospective Studies , Risk Factors , Seoul/epidemiology
17.
Mol Cell Biol ; 39(18)2019 09 15.
Article in English | MEDLINE | ID: mdl-31262999

ABSTRACT

Cellular communication network factor 1 (CCN1) is a dynamically expressed, matricellular protein required for vascular development and tissue repair. The CCN1 gene is a presumed target of Yes-associated protein (YAP), a transcriptional coactivator that regulates cell growth and organ size. Herein, we demonstrate that the CCN1 promoter is indeed a direct genomic target of YAP in endothelial cells (ECs) of new blood vessel sprouts and that YAP deficiency in mice downregulates CCN1 and alters cytoskeletal and mitogenic gene expression. Interestingly, CCN1 overexpression in cultured ECs inactivates YAP in a negative feedback and causes its nuclear exclusion. Accordingly, EC-specific deletion of the CCN1 gene in mice mimics a YAP gain-of-function phenotype, characterized by EC hyperproliferation and blood vessel enlargement. CCN1 brings about its effect by providing cells with a soft compliant matrix that creates YAP-repressive cytoskeletal states. Concordantly, pharmacological inhibition of cell stiffness recapitulates the CCN1 deletion vascular phenotype. Furthermore, adeno-associated virus-mediated expression of CCN1 reversed the pathology of YAP hyperactivation and the subsequent aberrant growth of blood vessels in mice with ischemic retinopathy. Our studies unravel a new paradigm of functional interaction between CCN1 and YAP and underscore the significance of their interplay in the pathogenesis of neovascular diseases.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Cysteine-Rich Protein 61/genetics , Retinal Diseases/metabolism , Retinal Vessels/pathology , Transcription Factors/metabolism , Adaptor Proteins, Signal Transducing/genetics , Animals , Cell Line , Cell Proliferation , Cysteine-Rich Protein 61/metabolism , Disease Models, Animal , Endothelial Cells/cytology , Endothelial Cells/metabolism , Feedback, Physiological , Female , Gene Expression Regulation , Humans , Male , Mice , Promoter Regions, Genetic , Retinal Diseases/genetics , Retinal Diseases/pathology , Retinal Vessels/cytology , Retinal Vessels/metabolism , Transcription Factors/genetics , YAP-Signaling Proteins
18.
Amino Acids ; 49(8): 1373-1380, 2017 08.
Article in English | MEDLINE | ID: mdl-28516269

ABSTRACT

ß-Alanine is a non-essential amino acid and presents as a major component of various sports supplements. It is a non-proteogenic amino acid, formed in vivo by degradation of carnosine, anserine, balenine, and dihydrouracil. The present study was aimed at investigating the anti-tumor effects of ß-alanine in renal and cervical tumor cells. Sulforhodamine-B assay and flow cytometric analysis were used to measure cell viability. Lactate dehydrogenase (LDH) expression was analyzed using FITC-conjugated fluorescent antibody. The cellular adenosine triphosphate (ATP) content was measured using bioluminescence method. Cell migration was determined by the simple standard-scratch method. ß-Alanine reduced renal and cervical cell growth significantly. Percentage of inhibition of renal and cervical tumor cells was increased at higher concentration of ß-alanine. LDH expression and ATP content were significantly reduced in renal and cervical tumor cells in a dose-dependent manner. Renal and cervical tumor cell migration were significantly reduced following 10 and 100 mM of ß-alanine treatment. In our study, ß-alanine exerts no significant effect on normal MDCK cells except a marginal effect at the highest concentration (100 mM). In summary, our experimental data suggest that ß-alanine may be a potential anti-tumor agent exhibiting several anti-cancer effects in renal and cervical tumor cells.


Subject(s)
Cell Movement/drug effects , Cell Proliferation/drug effects , Kidney Neoplasms/metabolism , Uterine Cervical Neoplasms/metabolism , beta-Alanine/pharmacology , Female , Humans , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , L-Lactate Dehydrogenase/metabolism , Tumor Cells, Cultured , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/pathology
19.
Ann Occup Environ Med ; 28: 53, 2016.
Article in English | MEDLINE | ID: mdl-27761265

ABSTRACT

BACKGROUND: Night shift work has well-known adverse effects on health. However, few studies have investigated the relationship between thyroid diseases and night shift work. This study aimed to examine night shift workers and their changes in thyroid stimulating hormones (TSH) levels over time. METHODS: Medical check-up data (2011-2015) were obtained from 967 female workers at a university hospital in Incheon, Korea. Data regarding TSH levels were extracted from the records, and 2015 was used as a reference point to determine night shift work status. The relationships between TSH levels and night shift work in each year were analyzed using the general linear model (GLM). The generalized estimating equation (GEE) was used to evaluate the repeated measurements over the 5-year period. RESULTS: The GEE analysis revealed that from 2011 to 2015, night shift workers had TSH levels that were 0.303 mIU/L higher than the levels of non-night shift workers (95 % CI: 0.087-0.519 mIU/L, p = 0.006) after adjusting for age and department. When we used TSH levels of 4.5 ≥ mIU/L to identify subclinical hypothyroidism, night shift workers exhibited a 1.399 fold higher risk of subclinical hypothyroidism (95 % CI: 1.050-1.863, p = 0.022), compared to their non-night shift counterparts. CONCLUSIONS: This result of this study suggests that night shift workers may have an increased risk of thyroid diseases, compared to non-night shift workers.

20.
Ann Occup Environ Med ; 28: 49, 2016.
Article in English | MEDLINE | ID: mdl-27660716

ABSTRACT

BACKGROUND: Worldwide, exposure to second-hand smoke (SHS) has been responsible for more than 0.6 million deaths and 10.9 million disability-adjusted life years (DALYS) lost in never smokers in 2004. The world health organization (WHO) reported smoking-related death of 58,000 per year in South Korea. There is recent emerging evidence of the associations of SHS exposure with anxiety or depression and poor mental health. Although exposure to second-hand smoke (SHS) has been associated with various physical health conditions and mental health, we are unaware of any studies examining its association with psychological well-being as mental factor. This study aimed to investigate the association between self-reported exposure to SHS and well-being among non-smoking wageworkers. METHODS: The Third Korean Working Conditions Survey (KWCS, 2011) was conducted on a representative sample of economically active population aged 15 years or over, who were either employees or self-employed at the time of interview. In this study, after removing inconsistent data, 19,879 non-smoking wageworkers among 60,054 workers were participated. Psychological well-being was measured through the WHO-Five Well-Being Index (1998 version). Univariate and multiple logistic regression models were used to examine the association of SHS exposure with psychological well-being. RESULTS: The unadjusted OR of poor psychological well-being (OR: 1.594, 95 % CI: 1.421-1.787) was significantly higher for SHS exposure group compared to non-exposure group. Multiple logistic regression analysis results indicated that these relationships were still significant after adjusting for potential confounders (adjusted OR: 1.330, 95 % CI: 1.178-1.502). CONCLUSIONS: Exposure to SHS was associated with poor well-being measured by the WHO-5 well-being index, indicating the importance of reducing SHS exposure at the workplace for psychological well-being amongst non-smoking wageworkers.

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