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Racial hate crimes against Asian Americans in the USA have recently risen. While many examined the domestic consequences of hate crimes, little is known about their impact on foreign public perception of the country. This study fills this gap by investigating how hate crimes in the USA influence attitudes toward the USA. Conducting a survey experiment in nine Asian countries, we found that exposure to information about hate crime incidents in the USA resulted in a significant increase in unfavourable views of the USA (−10.1pp), decreased confidence in the USA (−6.3pp), and increasingly negative perceptions of American democracy (−6.5pp), American ideas and customs (−11.0pp), and American people (−11.8pp). We also find that legislative actions can mitigate the negative effects of hate crime information. These findings underscore the global significance of addressing hate crimes in the USA for the country’s reputation and soft power.
The COVID-19 pandemic poses a major threat to mental health and is associated with an increased risk of suicide. An understanding of suicidal behaviours during the pandemic is necessary for establishing policies to prevent suicides in such social conditions.
Aims
We aimed to investigate vulnerable individuals and the characteristics of changes in suicidal behaviour during the COVID-19 pandemic.
Method
We retrospectively reviewed the medical records of patients with suicide attempts who visited the emergency department from February 2019 to January 2021. We analysed the demographic and clinical characteristics, risk factors and rescue factors of patients, and compared the findings between the pre-pandemic and pandemic periods.
Results
In total, 519 patients were included. During the pre-pandemic and pandemic periods, 303 and 270 patients visited the emergency department after a suicide attempt, respectively. The proportion of suicide attempts by women (60.1% v. 69.3%, P = 0.035) and patients with a previous psychiatric illness (63.4% v. 72.9%, P = 0.006) increased during the COVID-19 pandemic. In addition, patients’ rescue scores during the pandemic were lower than those during the pre-pandemic period (12 (interquartile range: 11–13) v. 13 (interquartile range: 12–14), P < 0.001).
Conclusions
Women and people with previous psychiatric illnesses were more vulnerable to suicide attempts during the COVID-19 pandemic. Suicide prevention policies, such as continuous monitoring and staying in touch with vulnerable individuals, are necessary to cope with suicide risk.
Large herbivores can disperse seeds over long distances through endozoochory. The Korean water deer (Hydropotes inermis argyropus), an internationally vulnerable species but locally considered a vermin, is a potential endozoochorous seed dispersal vector. In this study, feeding experiments were conducted to test the efficiency of seed dispersal through gut ingestion by the Korean water deer, its temporal pattern and the effect of gut passage on seed recovery and germination rate. Eight plant species, including species that formerly germinated from its faeces, were used to feed three Korean water deer. Once the deer had consumed all the provided seeds, their faeces were collected after 24, 48, 72 and 96 h. The collected faeces were air-dried, and the number of seeds retrieved from the faeces was counted every 24 h (0–24, 24–48, 48–72 and 72–96 h). Among the eight plant species, six species were retrieved with intact seeds. Panicum bisulcatum had the highest recovery rate of 33.7%, followed by Amaranthus mangostanus (24.5%) and Chenopodium album (14.4%). Most of the seeds were recovered within the 24–48 h time interval. Germination tests were conducted on the ingested and uningested seeds for the four species which had a sufficient recovery rate. The effects of gut passage on seed germination differed according to plant species. The germination rate substantially decreased after gut passage. The results suggest that the Korean water deer can disperse seeds, potentially over long distances albeit at a high cost of low seed recovery and germination rate.
Accumulating evidence suggests that alterations in inflammatory biomarkers are important in depression. However, previous meta-analyses disagree on these associations, and errors in data extraction may account for these discrepancies.
Methods
PubMed/MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from database inception to 14 January 2020. Meta-analyses of observational studies examining the association between depression and levels of tumor necrosis factor-α (TNF-α), interleukin 1-β (IL-1β), interleukin-6 (IL-6), and C-reactive protein (CRP) were eligible. Errors were classified as follows: incorrect sample sizes, incorrectly used standard deviation, incorrect participant inclusion, calculation error, or analysis with insufficient data. We determined their impact on the results after correction thereof.
Results
Errors were noted in 14 of the 15 meta-analyses included. Across 521 primary studies, 118 (22.6%) showed the following errors: incorrect sample sizes (20 studies, 16.9%), incorrect use of standard deviation (35 studies, 29.7%), incorrect participant inclusion (7 studies, 5.9%), calculation errors (33 studies, 28.0%), and analysis with insufficient data (23 studies, 19.5%). After correcting these errors, 11 (29.7%) out of 37 pooled effect sizes changed by a magnitude of more than 0.1, ranging from 0.11 to 1.15. The updated meta-analyses showed that elevated levels of TNF- α, IL-6, CRP, but not IL-1β, are associated with depression.
Conclusions
These findings show that data extraction errors in meta-analyses can impact findings. Efforts to reduce such errors are important in studies of the association between depression and peripheral inflammatory biomarkers, for which high heterogeneity and conflicting results have been continuously reported.
Background: Recently, healthcare-associated infections (HAIs) in long-term care hospitals (LTCHs) have markedly increased, but no infection control policy has been established in South Korea. We investigated the current HAI surveillance system and executed a point-prevalence pilot study in LTCHs. Methods: HAIs were defined by newly established surveillance manual based on McGeer criteria revised in 2012. Three LTCHs in Seoul and Gyeonggi province were voluntarily recruited, and data were collected from up to 50 patients who were hospitalized on August 1. The medical records from September to November 2018 were retrospectively reviewed by a charge nurse for infection control per each hospitals after 1 day of training specific for LTCH surveillance. All data were reviewed by a senior researcher visiting onsite. Results: The participating hospitals had 272.33 ± 111.01 beds. Only 1 hospital had an onsite microbiological laboratory. In total, 156 patients were enrolled and 5 HAIs were detected, for a prevalence rate of 3.2%. The average patient age was 79.04 ± 9.92 years. The HAIs included 2 urinary tract infections, skin and soft-tissue infection, low respiratory infection, and conjunctivitis. Conclusions: This is the first survey of HAI in LTCHs in South Korea. The 3.2% prevalence rate is lower than those from previous reports from the European Union or the United States. This study supports the development of a national HAI surveillance and infection control system in LTCHs, although implementation may be limited due to the lack of laboratory support and infection control infrastructure in Korea.
We report our experience with an emergency room (ER) shutdown related to an accidental exposure to a patient with coronavirus disease 2019 (COVID-19) who had not been isolated.
Setting:
A 635-bed, tertiary-care hospital in Daegu, South Korea.
Methods:
To prevent nosocomial transmission of the disease, we subsequently isolated patients with suspected symptoms, relevant radiographic findings, or epidemiology. Severe acute respiratory coronavirus 2 (SARS-CoV-2) reverse-transcriptase polymerase chain reaction assays (RT-PCR) were performed for most patients requiring hospitalization. A universal mask policy and comprehensive use of personal protective equipment (PPE) were implemented. We analyzed effects of these interventions.
Results:
From the pre-shutdown period (February 10–25, 2020) to the post-shutdown period (February 28 to March 16, 2020), the mean hourly turnaround time decreased from 23:31 ±6:43 hours to 9:27 ±3:41 hours (P < .001). As a result, the proportion of the patients tested increased from 5.8% (N=1,037) to 64.6% (N=690) (P < .001) and the average number of tests per day increased from 3.8±4.3 to 24.7±5.0 (P < .001). All 23 patients with COVID-19 in the post-shutdown period were isolated in the ER without any problematic accidental exposure or nosocomial transmission. After the shutdown, several metrics increased. The median duration of stay in the ER among hospitalized patients increased from 4:30 hours (interquartile range [IQR], 2:17–9:48) to 14:33 hours (IQR, 6:55–24:50) (P < .001). Rates of intensive care unit admissions increased from 1.4% to 2.9% (P = .023), and mortality increased from 0.9% to 3.0% (P = .001).
Conclusions:
Problematic accidental exposure and nosocomial transmission of COVID-19 can be successfully prevented through active isolation and surveillance policies and comprehensive PPE use despite longer ER stays and the presence of more severely ill patients during a severe COVID-19 outbreak.
The present study aimed to estimate heritability of Hwabyung (HB) symptoms in adolescent and young adult twins in South Korea. The sample included 1,601 twins consisting of 143 pairs of monozygotic male (MZM), 67 pairs of dizygotic male (DZM), 295 pairs of monozygotic female (MZF), 114 pairs of dizygotic female (DZF), and 117 pairs of opposite-sex dizygotic (OSDZ) twins and 129 twins with non-participating co-twins (mean age = 19.1 ± 3.1 years; range: 12–29 years). An HB symptom questionnaire was given to twins via a telephone interview. Consistent with the literature of HB, the mean level of HB was significantly higher in females than in males. Maximum likelihood twin correlations for HB were 0.31 (95% CI [0.16, 0.45]) for MZM, 0.19 (95% CI [-0.05, 0.41]) for DZM, 0.50 (95% CI [0.41, 0.58]) for MZF, 0.28 (95% CI [0.11, 0.44]) for DZF, and 0.23 (95% CI [0.05, 0.40]) for OSDZ twins. These patterns of twin correlations suggested the presence of additive genetic influences on HB. Model-fitting analysis showed that additive genetic and individual-specific environmental influences on HB were 44% (95% CI [37, 51]) and 56% (95% CI [49, 63]), respectively. Shared environmental influences were not significant. These parameter estimates were not significantly different between two sexes, and did not change significantly with age in the present sample, suggesting that genetic and environmental influences on HB in both sexes are stable across adolescence and young adulthood.
Our aim was to examine the prevalence, correlates, and association of depressive and anxiety disorders with quality of life (QoL) and such other outcomes as the need for psychosocial services in cancer patients.
Method:
A total of 400 patients participated in a multicenter survey involving five cancer centers located throughout Korea. The Short-Form Health Survey, the MD Anderson Symptom Inventory, the Mini-Mental Adjustment to Cancer (MINI-MAC), and Mini-International Neuropsychiatric Interview were administered.
Results:
The prevalence rates for depressive and anxiety disorders were 16 and 17.1%, respectively. Younger age and poor Eastern Cooperative Oncology Group performance status, and all physical symptoms, as well as helplessness/hopelessness, anxious preoccupation (AP), and cognitive avoidance (CA) on the MINI-MAC were found to be significantly related to depressive disorder (DD) in a univariate logistic regression analysis. Metastases, the symptoms of disturbed sleep, dry mouth, and numbness or tingling, as well as AP and CA were significantly correlated with anxiety disorder (AD) in the univariate analysis. In the multivariate analyses, only AP was significant for AD (odds ratio = 2.94, p < 0.001), while none reached statistical significance for DD. Psychiatric comorbidity status had a detrimental effect on various dimensions of QoL. Patients with DD or AD reported a significantly higher need for professional psychosocial services.
Significance of results:
Given the substantial prevalence and pervasive impact of DD and AD on various aspects of QoL, its assessment and care should be integrated as a regular part of oncological care throughout the cancer continuum.
Personality may predispose family caregivers to experience caregiving differently in similar situations and influence the outcomes of caregiving. A limited body of research has examined the role of some personality traits for health-related quality of life (HRQoL) among family caregivers of persons with dementia (PWD) in relation to burden and depression.
Methods:
Data from a large clinic-based national study in South Korea, the Caregivers of Alzheimer's Disease Research (CARE), were analyzed (N = 476). Path analysis was performed to explore the association between family caregivers’ personality traits and HRQoL. With depression and burden as mediating factors, direct and indirect associations between five personality traits and HRQoL of family caregivers were examined.
Results:
Results demonstrated the mediating role of caregiver burden and depression in linking two personality traits (neuroticism and extraversion) and HRQoL. Neuroticism and extraversion directly and indirectly influenced the mental HRQoL of caregivers. Neuroticism and extraversion only indirectly influenced their physical HRQoL. Neuroticism increased the caregiver's depression, whereas extraversion decreased it. Neuroticism only was mediated by burden to influence depression and mental and physical HRQoL.
Conclusions:
Personality traits can influence caregiving outcomes and be viewed as an individual resource of the caregiver. A family caregiver's personality characteristics need to be assessed for tailoring support programs to get the optimal benefits from caregiver interventions.
Polycyclic aromatic hydrocarbons (PAH) are common dietary exposures that cross the human placenta and are classified as a probable human carcinogen. The aim of the present study was to investigate the potential impact of exposure to PAH-containing meat consumed during pregnancy on birth outcomes.
Design
Prospective birth cohort study. Only non-smoking women with singleton pregnancies, who were free from chronic disease such as diabetes and hypertension, were included in the study. Maternal consumption of PAH-rich meat was estimated through FFQ. Multiple linear regression was used to assess factors related to higher intake and the association between dietary PAH and birth outcomes.
Setting
Republic of Korea, 2006–2011.
Subjects
Pregnant women (n 778) at 12–28 weeks of gestation enrolled in the Mothers and Children’s Environmental Health (MOCEH) study.
Results
The multivariable regression model showed a significant reduction in birth weight associated with higher consumption level of foods rich in PAH, such as grilled or roasted meat, during pregnancy (β=−17·48 g, P<0·05 for every 1 point higher in meat score). Further adjusting for biomarkers of airborne PAH did not alter this association. There was no evidence that higher consumption level of PAH-rich meat shortens the duration of gestation (P=0·561). Regression models performed for birth length and head circumference produced negative effects that were not statistically significant.
Conclusions
Consumption of higher levels of barbecued, fried, roasted and smoked meats during pregnancy was associated with reduced birth weight. Dietary risk of PAH exposure in Korean women is of concern.
Many transgenic domestic animals have been developed to produce therapeutic proteins in the mammary gland, and this approach is one of the most important methods for agricultural and biomedical applications. However, expression and secretion of a protein varies because transgenes are integrated at random sites in the genome. In addition, distal enhancers are very important for transcriptional gene regulation and tissue-specific gene expression. Development of a vector system regulated accurately in the genome is needed to improve production of therapeutic proteins. The objective of this study was to develop a knock-in system for expression of human fibroblast growth factor 2 (FGF2) in the bovine β-casein gene locus. The F2A sequence was fused to the human FGF2 gene and inserted into exon 3 of the β-casein gene. We detected expression of human FGF2 mRNA in the HC11 mouse mammary epithelial cells by RT-PCR and human FGF2 protein in the culture media using western blot analysis when the knock-in vector was introduced. We transfected the knock-in vector into bovine ear fibroblasts and produced knock-in fibroblasts using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system. Moreover, the CRISPR/Cas9 system was more efficient than conventional methods. In addition, we produced knock-in blastocysts by somatic cell nuclear transfer using the knock-in fibroblasts. Our knock-in fibroblasts may help to create cloned embryos for development of transgenic dairy cattle expressing human FGF2 protein in the mammary gland via the expression system of the bovine β-casein gene.
Decreased hemoglobin levels increase the risk of developing dementia among the elderly. However, the underlying mechanisms that link decreased hemoglobin levels to incident dementia still remain unclear, possibly due to the fact that few studies have reported on the relationship between low hemoglobin levels and neuroimaging markers. We, therefore, investigated the relationships between decreased hemoglobin levels, cerebral small-vessel disease (CSVD), and cortical atrophy in cognitively healthy women and men.
Methods:
Cognitively normal women (n = 1,022) and men (n = 1,018) who underwent medical check-ups and magnetic resonance imaging (MRI) were enrolled at a health promotion center. We measured hemoglobin levels, white matter hyperintensities (WMH) scales, lacunes, and microbleeds. Cortical thickness was automatically measured using surface based methods. Multivariate regression analyses were performed after controlling for possible confounders.
Results:
Decreased hemoglobin levels were not associated with the presence of WMH, lacunes, or microbleeds in women and men. Among women, decreased hemoglobin levels were associated with decreased cortical thickness in the frontal (Estimates, 95% confidence interval, −0.007, (−0.013, −0.001)), temporal (−0.010, (−0.018, −0.002)), parietal (−0.009, (−0.015, −0.003)), and occipital regions (−0.011, (−0.019, −0.003)). Among men, however, no associations were observed between hemoglobin levels and cortical thickness.
Conclusion:
Our findings suggested that decreased hemoglobin levels affected cortical atrophy, but not increased CSVD, among women, although the association is modest. Given the paucity of modifiable risk factors for age-related cognitive decline, our results have important public health implications.
Symptomatic intracranial atherosclerosis (ICAS) is a dynamic disease that frequently progresses. Statins have been shown to have anti-atherosclerotic activity. We therefore investigated whether statins could prevent progression of ICAS.
Methods:
This retrospective cohort study assessed 55 patients with acute ischemic stroke and symptomatic ICAS in the middle cerebral or basilar arteries as shown on magnetic resonance angiography (MRA), with follow-up MRA performed more than 1 year after the index stroke. Change in ICAS was classified as progressive, regressive, or stable. Baseline clinical characteristics and risk factor control during follow-up were assessed, and laboratory tests were performed at the time of follow-up MRA. The statin group was defined as patients regularly treated with statins for more than 75% of the follow-up period; the remaining patients were defined as the non-statin group.
Results:
At a median follow-up time of 21.8 months (range, 11.8-66.1 months), the statin group consisted of 26 (47.3%) patients and the non-statin group of 29 (52.7%). During follow-up, 6 (10.9%) patients progressed, 14 (25.5%) regressed, and 35 (63.6%) remained stable. Statin treatment was significantly associated with non-progression of ICAS (p=0.024). Two patients in the non-statin group had recurrent strokes. Border-zone infarcts were associated with progression of ICAS (3/6, 50%; p=0.007), whereas risk factors and inflammatory biomarkers were not related to progression.
Conclusions:
Treatment with statins may prevent progression of symptomatic ICAS. Prospective randomized controlled trials are required to confirm that statins protect against such progression.
This study aimed to investigate the influences of age, education, and gender on the two total scores (TS-I and TS-II) of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological assessment battery (CERAD-NP) and to provide normative information based on an analysis for a large number of elderly persons with a wide range of educational levels.
Methods:
In the study, 1,987 community-dwelling healthy volunteers (620 males and 1,367 females; 50–90 years of age; and zero to 25 years of education) were included. People with serious neurological, medical, and psychiatric disorders (including dementia) were excluded. All participants underwent the CERAD-NP assessment. TS-I was generated by summing raw scores from the CERAD-NP subtests, excluding Mini-Mental State Examination and Constructional Praxis (CP) recall subtests. TS-II was calculated by adding CP recall score to TS-I.
Results:
Both TS-I and TS-II were significantly influenced by demographic variables. Education accounted for the greatest proportion of score variance. Interaction effect between age and gender was found. Based on the results obtained, normative data of the CERAD-NP total scores were stratified by age (six overlapping tables), education (four strata), and gender.
Conclusions:
The normative information will be very useful for better interpretation of the CERAD-NP total scores in various clinical and research settings and for comparing individuals’ performance of the battery across countries.
Next-generation sequencing technique has been known as a useful tool for de novo transcriptome assembly, functional annotation of genes and identification of molecular markers. This study was carried out to mine molecular markers from de novo assembled transcriptomes of four chilli pepper varieties, the highly pungent ‘Saengryeg 211’ and non-pungent ‘Saengryeg 213’ and variably pigmented ‘Mandarin’ and ‘Blackcluster’. Pyrosequencing of the complementary DNA library resulted in 361,671, 274,269, 279,221, and 316,357 raw reads, which were assembled in 23,607, 19,894, 18,340 and 20,357 contigs, for the four varieties, respectively. Detailed sequence variant analysis identified numerous potential single-nucleotide polymorphisms (SNPs) and simple sequence repeats (SSRs) for all the varieties for which the primers were designed. The transcriptome information and SNP/SSR markers generated in this study provide valuable resources for high-density molecular genetic mapping in chilli pepper and Quantitative trait loci analysis related to fruit qualities. These markers for pepper will be highly valuable for marker-assisted breeding and other genetic studies.
We previously demonstrated that the chronic consumption of a high-fat diet (HFD) promotes lung and liver metastases of 4T1 mammary carcinoma cells in obesity-resistant BALB/c mice. To examine early transcriptional responses to tumour progression in the liver and lungs of HFD-fed mice, 4-week-old female BALB/c mice were divided into four groups: sham-injected, control diet (CD)-fed; sham-injected, HFD-fed (SH); 4T1 cell-injected, CD-fed (TC); 4T1 cell-injected, HFD-fed (TH). Following 16 weeks of either a CD or HFD, 4T1 cells were injected into the mammary fat pads of mice in the TC and TH groups and all mice were continuously fed identical diets. At 14 d post-injection, RNA was isolated from hepatic and pulmonary tissues for microarray analysis of mRNA expression. Functional annotation and core network analyses were conducted for the TH/SH Unique gene set. Inflammation in hepatic tissues and cell mitosis in pulmonary tissues were the most significant biological functions in the TH/SH Unique gene set. The biological core networks of the hepatic TH/SH Unique gene set were characterised as those genes involved in the activation of acute inflammatory responses (Orm1, Lbp, Hp and Cfb), disordered lipid metabolism and deregulated cell cycle progression. Networks of the pulmonary Unique gene set displayed the deregulation of cell cycle progression (Cdc20, Cdk1 and Bub1b). These HFD-influenced alterations may have led to favourable conditions for the formation of both pro-inflammatory and pro-mitotic microenvironments in the target organs that promote immune cell infiltration and differentiation, as well as the infiltration and proliferation of metastatic tumour cells.
Oxidative stress may be affected by lead exposure as well as antioxidants, yet little is known about the interaction between dietary antioxidants and blood lead levels (BLL) on oxidative stress level. We investigated the interaction between dietary antioxidants and BLL on oxidative stress level. As part of the Biomarker Monitoring for Environmental Health conducted in Seoul and Incheon, Korea, between April and December 2005, we analysed data from 683 adults (female = 47·4 %, mean age 51·4 (sd 8·4) years) who had complete measures on BLL, dietary intakes and oxidative stress marker (urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG)). Dietary intakes were assessed by a validated semi-quantitative FFQ, BLL was measured using atomic absorption spectrophotometry, and 8-OHdG by ELISA. Multivariate linear regression analyses were used to evaluate the influence of BLL on the association between dietary antioxidants and 8-OHdG. Geometric means of BLL and 8-OHdG concentrations were 4·1 (sd 1·5) μg/dl and 5·4 (sd 1·9) μg/g creatinine, respectively. Increases of vitamins C and E were significantly associated with the decrease of log10 8-OHdG in the adults from the lowest quartile of the BLL group ( ≤ 3·18 μg/dl, geometric mean = 2·36 μg/dl) than those of the highest quartile BLL group (>5·36 μg/dl, geometric mean = 6·78 μg/dl). Regarding antioxidant-related foods, vegetables excluding kimchi showed a higher inverse relationship with 8-OHdG in the lowest quartile BLL group than the highest group. These findings suggest a rationale for lowering the BLL and increasing the intake of dietary antioxidants in the urban population in Korea.
Anthropogenic land use within watersheds has substantial effects on aquatic habitats and biological communities. From September 2006 to December 2008, we investigated the effects of land use on benthic macroinvertebrate communities by comparing Song Stream and Odae Stream, two adjacent mountain streams in Korea whose watersheds have different land use patterns. Song Stream is significantly disturbed by agricultural activities in the watershed, whereas Odae Stream is relatively undisturbed and is surrounded by a well-conserved forest area. Song Stream had significantly higher levels of all nutrients and sediment-related factors due to the adjacent agricultural area. As a result, Song Stream had markedly lower species community indices, such as taxa richness and abundance. In Song Stream, macroinvertebrate scrapers and predators were most adversely affected, whereas collector-gatherers became a dominant group. Based on correlation and multivariate analyses, total dissolved solids had the strongest negative relationship with macroinvertebrate assemblages, followed by electrical conductivity, total nitrogen, and pH. The proportion of cobble in stream substrate was positively related to the richness and abundance of macroinvertebrates. Our results indicate that disturbances caused by agricultural land use, particularly sand deposition, had significant adverse effects on macroinvertebrate habitats and on the biotic integrity of benthic macroinvertebrate communities.
We investigated the pressure dependence of the inductive coupled plasma (ICP) oxidation on the electrical characteristics of the thin oxide films. Activation energies and electron temperatures with different pressures were estimated. To demonstrate the pressure effect on the plasma oxide quality, simple N type metal-oxide-semiconductor (NMOS) transistors were fabricated and investigated in a few electrical properties. At higher pressure than 200mTorr, plasma oxide has a slightly higher on-current and a lower interfacial trap density. The on-current gain seems to be related to the field mobility increase and the lower defective interface to the electron temperature during oxidation.
Cocoa polyphenols have antioxidant and anti-inflammatory effects. TNF-α is a pro-inflammatory cytokine that has a vital role in the pathogenesis of inflammatory diseases such as cancer and psoriasis. Vascular endothelial growth factor (VEGF) expression is associated with tumorigenesis, CVD, rheumatoid arthritis and psoriasis. We tested whether cocoa polyphenol extract (CPE) inhibited TNF-α-induced VEGF expression in promotion-sensitive JB6 mouse epidermal cells. CPE significantly inhibited TNF-α-induced up-regulation of VEGF via reducing TNF-α-induced activation of the nuclear transcription factors activator protein-1 (AP-1) and NF-κB, which are key regulators of VEGF expression. CPE also inhibited TNF-α-induced phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase. CPE blocked activation of their downstream kinases, p70 kDa ribosomal protein S6 kinase and p90 kDa ribosomal protein S6 kinase. CPE suppressed phosphoinositide 3-kinase (PI3K) activity via binding PI3K directly. CPE did not affect TNF-α-induced phosphorylation of mitogen-activated protein kinase kinase-1 (MEK1) but suppressed TNF-α-induced MEK1 activity. Collectively, these results indicate that CPE reduced TNF-α-induced up-regulation of VEGF by directly inhibiting PI3K and MEK1 activities, which may contribute to its chemopreventive potential.