Effects of uric acid on ischemic diseases, stratified by lipid levels: a drug-target, nonlinear Mendelian randomization study.

Although uric acid-lowering agents such as xanthine oxidase inhibitors have potential cardioprotective effects, studies on their use in preventing cardiovascular diseases are lacking. We investigated the genetically proxied effects of reducing uric acid on ischemic cardiovascular diseases in a lipid-level-stratified population. We performed drug-target Mendelian randomization (MR) analyses using UK Biobank data to select genetic instruments within a uric acid-lowering gene, xanthine dehydrogenase (XDH), and construct genetic scores. For nonlinear MR analyses, individuals were stratified by lipid level. Outcomes included acute myocardial infarction (AMI), ischemic heart disease, cerebral infarction, transient cerebral ischemic attack, overall ischemic disease, and gout. We included 474,983 non-gout individuals with XDH-associated single-nucleotide polymorphisms. The XDH-variant-induced uric acid reduction was associated with reduced risk of gout (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.78-0.93; P < 0.001), cerebral infarction (OR, 0.86; 95% CI, 0.75-0.98; P = 0.023), AMI (OR, 0.79; 95% CI, 0.66-0.94; P = 0.010) in individuals with triglycerides ≥ 188.00 mg/dL, and cerebral infarction in individuals with low-density lipoprotein cholesterol (LDL-C) ≤ 112.30 mg/dL (OR, 0.76; 95% CI, 0.61-0.96; P = 0.020) or LDL-C of 136.90-157.40 mg/dL (OR, 0.67; 95% CI, 0.49-0.92; P = 0.012). XDH-variant-induced uric acid reduction lowers the risk of gout, AMI for individuals with high triglycerides, and cerebral infarction except for individuals with high LDL-C, highlighting the potential heterogeneity in the protective effects of xanthine oxidase inhibitors for treating AMI and cerebral infarction depending on the lipid profiles.

Supplementary Effects of Allium hookeri Extract on Glucose Tolerance in Prediabetic Subjects and C57BL/KsJ-db/db Mice.

Allium hookeri (AH) has been used as a nutritional and medicinal food in Asia for many years. Our previous studies have described its anti-diabetic, anti-obesity, and anti-inflammatory activities in animal models and prediabetes. This study investigated whether AH could improve glycemia by modulating insulin secretion in prediabetic subjects through an in-depth study. Eighty prediabetic subjects (100 ≤ fasting plasma glucose < 140 mg/dL) were randomly assigned to a placebo (n = 40) group or an ethanol AH extract (500 mg/day, n = 40) group for 12 weeks. Dietary intake and physical activity, blood glucose (an oral glucose tolerance test for 120 min), insulin (insulin response to oral glucose for 120 min), area under the curve (AUC) of glucose or insulin after oral glucose intake, insulin sensitivity markers, C-peptide, adiponectin, glycated hemoglobin A1c (HbA1c) levels, hematological tests (WBC, RBC, hemoglobin, hematocrit, and platelet count), blood biochemical parameters (ALP, AST, total bilirubin, total protein, albumin, gamma-GT, BUN, creatinine, LD, CK, and hs-CRP), and urine parameters (specific gravity and pH) were examined at both baseline and 12 weeks after supplementation with placebo or AH capsules. Fifty-eight participants (placebo group: 20 men and 10 women; AH group: 13 men and 15 women) completed the study. AH supplementation moderately reduced postprandial blood glucose at 60 min (-6.14 mg/dL, p = 0.061), postprandial insulin levels at 90 min (-16.69 µU/mL, p = 0.017), the glucose AUC at 90 min (-412.52 mg*min/dL, p = 0.021), as well as the insulin AUC at 90 min (-978.77 µU*min/mL, p = 0.021) and 120 min (-1426.41 µU*min/mL, p = 0.015) when compared with the placebo group. However, there were no effects of AH on dietary intake and physical activity; HOMA index; HbAlc; C-peptide; or adiponectin, hematological-, blood biochemical-, and urinary markers. To confirm the effects of AH extract on blood glucose insulin sensitivity, C57BL/6J or C57BL/KsJ-db/db mice were used (n = 8/group). Body weight, fasting plasma glucose level, lipid profiles, liver and renal function, pancreatic histology, and insulin immunoreactivity were assessed. In the diabetic db/db mice, hyperglycemia, which was accompanied by an increase in insulin secretion in diabetic mice, was significantly reduced by AH treatment, resulting in the alleviation of ß-cell overcompensation and insulin resistance. We confirmed that AH supplementation can effectively control blood glucose and insulin levels by improving insulin sensitivity and may be a potential agent for glycemic control in subjects with prediabetes and type 2 diabetes mellitus.

Antioxidant and Immune Stimulating Effects of Allium cepa Skin in the RAW 264.7 Cells and in the C57BL/6 Mouse Immunosuppressed by Cyclophosphamide.

Allium cepa L. (onion) has been reported to have various pharmacological effects, such as preventing heart disease, and improving antimicrobial activity and immunological effects. The Republic of Korea produced 1,195,563 tons of onions (2022). The flesh of onion is used as food while the onion skin (OS) is thrown away as an agro-food by-product and is considered to induce environmental pollution. Thus, we hypothesize that increasing usage of OS as functional food material could help protect from the environment pollution. The antioxidant effects and immune-enhancing effects of OS were evaluated as functional activities of OS. In this study, OS showed high 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities and xanthine oxidase (XO) inhibitory activity. The antioxidant activities increased in a dose-dependent manner. The IC50 values of DPPH, ABTS radical scavenging activity, and XO inhibitory activity were 954.9 µg/mL, 28.0 µg/mL, and 10.7 µg/mL, respectively. Superoxide dismutase and catalase activities of OS in RAW 264.7 cells were higher than those of the media control. There was no cytotoxicity of OS found in RAW 264.7 cells. Nitric oxide and cytokines (IL-1ß, IL-6, IFN-γ, and TNF-α) concentrations in RAW 264.7 cells significantly increased in a dose dependent manner. Immune-stimulating effects of OS were evaluated in immunosuppressed mice induced by cyclophosphamide. White blood cell count and the B cell proliferation of splenocytes were higher in OS100 (OS extract 100 mg/kg body weight) and OS200 (OS extract 200 mg/kg body weight) groups than in the negative control (NC) group. Serum IgG and cytokine (IL-1ß and IFN-γ) levels were also higher in OS100 and OS200 groups than in the NC group. OS treatment increased NK cell activity compared with the NC group. The results suggested that OS can improve antioxidant and immune stimulating effects. The use of OS as functional supplement can reduce the agro-food by-product and it may contribute to carbon neutrality.

Community-based multi-site randomized controlled trial of behavioral activation for patients with negative symptoms of schizophrenia.

BACKGROUND: Negative symptoms are closely related to the poor prognosis of schizophrenia, for which there is no effective treatment to date. Behavioral activation (BA), which is an effective treatment for depression, is a behavioral approach that targets low levels of response-contingent positive reinforcement. This study aimed to explore BA as an effective intervention for relieving the negative symptoms of schizophrenia. METHODS: This was a randomized single-blind controlled trial. Eighty-four patients with schizophrenia were enrolled in community mental health settings. Excluding 14 patients who opted out of the study, 70 were randomly assigned to receive BA in addition to treatment-as-usual (BA + TAU) or treatment-as-usual (TAU) only. Negative symptoms were assessed using the Clinical Assessment Interview for Negative Symptoms (CAINS) and Brief Negative Symptom Scale (BNSS) at baseline, post-treatment, and 6-months follow-up. RESULTS: Significant differences between the BA + TAU and TAU only groups were observed in the measures of negative symptoms post-treatment. The total score of CAINS was significantly decreased after BA treatment (η2 = 0.13). The tendency of the BA + TAU treatment effect was also observed for the BNSS total score and PANSS negative symptom subscale (η2 = 0.10 and η2 = 0.11, respectively). However, the difference between the two groups was not sustained at the six-month follow-up. CONCLUSIONS: Our findings suggest that BA could be a promising time-limited and structured psychosocial intervention for schizophrenia-associated negative symptoms with the merit of easy dissemination. Further studies are needed to examine the factors involved in sustaining improvement.

Antioxidant and Immune Stimulating Effects of Allium hookeri Extracts in the RAW 264.7 Cells and Immune-Depressed C57BL/6 Mice.

We investigated the antioxidant and immune-enhancing effects of the extracts from Allium hookeri leaves and roots (AHL and AHR) in in vitro and in vivo models. Their antioxidant effects were determined by total phenolic content (TPC), DPPH and ABTS radical scavenging activities, and superoxide dismutase and catalase activities. The immunomodulatory effects were evaluated by nitric oxide (NO) production and cytokine concentrations produced from RAW 264.7, and by serum IgA and IgG levels, cytokine levels, and NK cell activities in the immunosuppressed C57BL/6 mice. AHL and AHR extracts improved antioxidant activities and productions of NO and cytokines without cytotoxicity in the RAW 264.7 cells. AHL and AHR groups showed significantly higher serum IgA and IgG levels, Th1 cytokine concentrations, splenocyte proliferations, and NK cell activities than the NC group which was not treated with AHL or AHR extract. AHR extract showed higher values than AHL extract in the factors evaluated in this study. The results show that they have high antioxidant and immunomodulatory effects and can be used as novel potential therapeutic candidates to treat related diseases and to improve public health.

Anti-Diabetic Effects of Allium hookeri Extracts Prepared by Different Methods in Type 2 C57BL/J-db/db Mice.

This study was conducted to evaluate whether Allium hookeri can control diabetic symptoms. Aqueous extract (AE1: 100 mg/kg BW, AE2: 200 mg/kg BW) and ethanol extract (EE1: 100 mg/kg BW, EE2: 200 mg/kg BW) of A. hookeri were orally administrated to diabetic mice (C57BL/J-db/db) for 8 weeks. The negative (NC) and the positive (PC) control groups were treated with 0.9% saline and metformin (150 mg/kg BW), respectively. Glucose and lipid profile (triglyceride, total cholesterol (TC), LDL-C, and HDL-C) as biochemical parameters, toxicological factors such as liver/kidney functional parameters (ALT, AST, BUN, and Cr), and NK cell activity in blood were measured. Oral glucose tolerance test (OGTT) and histopathological examination were also conducted. Compared with the NC group, AE and EE decreased blood glucose, HbA1c, area under the curve (AUC) during OGTT, and leptin levels while increasing adiponectin levels. Serum lipid profiles and toxicological factors levels were reduced by the A. hookeri extract. Interestingly, HDL-C, glomerular mesangial expansion score in the kidney, and NK cell activity were effectively controlled in EE groups. Based on the results, EE is considered to be more effective in reducing high blood glucose, lipid profile, and related factor levels than AE, and is comparable to metformin in some biomarkers. It can be presumed that EE can more effectively control the major anomalies in the diabetic model than AE, and it may be used to prevent diabetic symptoms without toxicity in the Type 2 diabetic model.

Community-Based Multi-Site Randomized Controlled Trial of Behavioral Activation for Patients with Depressive Disorders.

Behavioral activation (BA) is a beneficial and relatively cost-effective treatment option for depression. This study utilized a pragmatic randomized controlled research design to investigate whether BA, as compared with treatment as usual (TAU), led to superior treatment effects, when delivered in community mental health settings by retrained community mental health professionals. Patients with depressive disorders (n = 64) were randomly assigned to a 10-session BA (n = 31) or TAU (n = 33) group. The depressive symptoms and behavioral engagement were assessed at the baseline, post-treatment, and a six-month follow-up. Results showed that, as compared to the TAU group, the BA group had: (1) a reduction in depression severity, as evidenced by large effect sizes and greater response rates, and (2) an increase in behavioral engagement. However, the post-treatment gains were not maintained at the six-month follow-up. The implications and limitations of the study are also discussed (KCT0004098, June 27, 2019, retrospectively registered).

Effects of Platycodon grandiflorum on Gut Microbiome and Immune System of Immunosuppressed Mouse.

Platycodon grandiflorum (PG) is a perennial plant that has been used as a traditional remedy to control immune-related diseases. PG was steamed and dried to improve its taste (PGS). The aim of the study was to investigate the effects of PG and PGS (PG-diets) on the gut microbiome and immune system. We treated PG-diets to immunosuppressed mice via cyclophosphamide (CPA) injection. After two weeks of the supplement, we evaluated specific genera related to body weight and serum immunoglobulin levels and analyzed 16S rRNA sequencing and metagenomics statistical analysis. PG-diets groups showed an increased abundance of microorganisms in immunodeficient mice compared to the control group (NC). Moreover, Akkermansia significantly decreased in response to the CPA in the NC group at the genus level, whereas its abundance increased in the PG-diets groups. We also found that the modulation of the gut microbiome by PG-diets was correlated with body weight, IgA, and IgM levels. The results demonstrate that PG-diets may improve the health benefits of immunosuppressed mice by altering the gut microbiome, though not much difference was found between PG and PGS treatments. Finally, this is the first study showing the effects of PGS-diets on the gut microbiome and immune system as a potential nourishing immunity supplement.

Allium hookeri Extracts Improve Scopolamine-Induced Cognitive Impairment via Activation of the Cholinergic System and Anti-Neuroinflammation in Mice.

Allium hookeri (AH) is a medicinal food that has been used in Southeast Asia for various physiological activities. The objective of this study was to investigate the activation of the cholinergic system and the anti-neuroinflammation effects of AH on scopolamine-induced memory impairment in mice. Scopolamine (1 mg/kg body weight, i.p.) impaired the performance of the mice on the Y-maze test, passive avoidance test, and water maze test. However, the number of error actions was reduced in the AH groups supplemented with leaf and root extracts from AH. AH treatment improved working memory and avoidance times against electronic shock, increased step-through latency, and reduced the time to reach the escape zone in the water maze test. AH significantly improved the cholinergic system by decreasing acetylcholinesterase activity, and increasing acetylcholine concentration. The serum inflammatory cytokines (IL-1ß, IL-6, and IFN-γ) increased by scopolamine treatment were regulated by the administration of AH extracts. Overexpression of NF-κB signaling and cytokines in liver tissue due to scopolamine were controlled by administration of AH extracts. AH also significantly decreased Aß and caspase-3 expression but increased NeuN and ChAT. The results suggest that AH extracts improve cognitive effects, and the root extracts are more effective in relieving the scopolamine-induced memory impairment. They have neuroprotective effects and reduce the development of neuroinflammation.

Association between domain-specific physical activity and diabetes in Korean adults.

This study aimed to investigate the association between domain-specific physical activity (PA) and diabetes in Korean adults. We analyzed 26,653 men and women (aged > 18 years) from the Korea National Health and Nutrition Examination Survey (2014-2018). PA was measured using a validated Global PA Questionnaire. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) after adjustment for various confounders. Transport PA accounted for the majority of total PA (46%, men; 58%, women), followed by leisure-time PA (30%; 22%) and work PA (24%; 20%). In men, ORs (95% CI) of diabetes comparing ≥ 600 metabolic task of equivalent (MET)-min/week vs. no activity were 0.82 (0.71-0.95) for leisure-time PA, 0.85 (0.75-0.96) for transport PA, and 0.88 (0.78-0.99) for leisure-time + transport PA. In women, ORs (95% CI) of diabetes comparing the same groups were 0.73 (0.60-0.89) for leisure-time PA, 0.97 (0.85-1.10) for transport PA, and 0.88 (0.78-1.00) for leisure-time + transport PA. However, work PA showed no association with diabetes. In conclusion, leisure-time PA was inversely associated with diabetes in both men and women, while transport PA was inversely associated only in men. But work PA was not associated with diabetes in Korean adults.

Personality Traits in Individuals with the Dual Diagnosis of Psychosis and Substance Use Disorders: A Comprehensive Review and Meta-Analysis.

OBJECTIVE: Substance abuse comorbidity is highly prevalent and is linked to detrimental outcomes in individuals with psychotic disorder, but the role of personality traits as the underlying mechanism is being increasingly underscored. This study aimed to profile temperamental risks of comorbid substance use disorder in psychotic disorders by performing meta-analyses on personality trait differences between psychotic disorders with comorbidity (dual diagnosis; DD) and without it (psychotic disorders; PSD). Methods: A systematic review of English articles using PubMed, MEDLINE, Scopus, Google Scholar, and ProQuest Dissertation and Theses. Only original empirical studies including participants with diagnosis of psychotic disorders based on structured diagnostic interviews, with and without substance use disorder evaluated with reliable and valid tests were included. Articles were independently extracted by two authors using predefined data fields, including study quality indicators. All pooled analyses were based on random-effect models. Thirteen studies (N = 885) met our inclusion criteria. All effect-size estimates were calculated based on means and standard deviations of included measures. Separate effect size estimates were obtained for four traits in the UPPS model (negative urgency, low premeditation, low perseverance, sensation seeking), four traits in the HS model (unconscientious disinhibition, negative affect, disagreeable disinhibition, positive affect) and trait anhedonia. Results: Negative urgency (four studies with 262 participants; ES = 0.59; 95% confidence interval [CI] [0.34, 0.84]), low premeditation (five studies with 349 participants; ES = 0.60; 95% CI [0.39, 0.80]), sensation seeking (seven studies with 550 participants; ES = 0.63; 95% CI [0.17, 1.09]) and unconscientious disinhibition (five studies with 291 participants; ES = 0.36; 95% CI [0.13, 0.59]) were elevated in DD than PSD. Heterogeneity of sensation seeking was significant (I2 = 86.2%). Conclusions: The findings of the current meta-analysis highlight a unique profile of impulsive and externalizing trait personality domains pertaining to DD. The study emphasizes the importance of emotion regulation interventions targeting impulsivity or negative affect (i.e. negative urgency, low premeditation) in substance abuse comorbidity patients.

Deregulated Immune Pathway Associated with Palbociclib Resistance in Preclinical Breast Cancer Models: Integrative Genomics and Transcriptomics.

Recently, cyclin-dependent kinase (CDK) 4/6 inhibitors have been widely used to treat advanced hormone receptor-positive breast cancer. Despite promising clinical outcomes, almost all patients eventually acquire resistance to CDK4/6 inhibitors. Here, we screened genes associated with palbociclib resistance through genomics and transcriptomics in preclinical breast cancer models. Palbociclib-resistant cells were generated by exposing hormone receptor-positive breast cancer cell lines to palbociclib. Whole-exome sequencing (WES) and a mRNA microarray were performed to compare the genomic and transcriptomic landscape between both palbociclib-sensitive and resistant cells. Microarray analysis revealed 651 differentially expressed genes (DEGs), while WES revealed 107 clinically significant mutated genes. Furthermore, pathway analysis of both DEGs and mutated genes revealed immune pathway deregulation in palbociclib-resistant cells. Notably, DEG annotation revealed activation of type I interferon pathway, activation of immune checkpoint inhibitory pathway, and suppression of immune checkpoint stimulatory pathway in palbociclib-resistant cells. Moreover, mutations in NCOR1, MUC4, and MUC16 genes found in palbociclib-resistant cells were annotated to be related to the immune pathway. In conclusion, our genomics and transcriptomics analysis using preclinical model, revealed that deregulated immune pathway is an additional mechanism of CDK4/6 inhibitor resistance besides the activation of cyclin E-CDK2 pathway and loss of RB, etc. Further studies are warranted to evaluate whether immune pathways may be a therapeutic target to overcome CDK4/6 inhibitor resistance.

The effects of brief behavioral activation (BA) on children with physical disabilities: A randomized controlled trial.

The majority of children with physical disabilities experience significant restrictions in their daily lives. Notably, they are at a risk for lower levels of activity and involvement in critical life domains. To address this issue, this study investigated whether behavioral activation (BA), in tandem with the installment of power-assisted devices (PAD), would have beneficial effects on activity levels, overall involvement in life domains, mobility, and depressive symptoms among children with physical disabilities. From among 123 children with physical disabilities aged 6-13 who used a nonpowered wheelchair device, 40 who met the inclusion and exclusion criteria were randomized into either the PAD-only group or the BA + PAD group. The participants were assessed at 3 time periods (pretreatment, 4 weeks, and 8 weeks), using standardized self-report measures and digital odometers. Both groups showed an increase in the distance traveled. Although BA + PAD had no additional benefits over PAD-only in improving the distance traveled and depressive symptoms, the BA + PAD group showed significantly higher levels of activity and overall involvement in life domains than the PAD-only group did. The findings provide preliminary support for the provision of BA for children with physical disabilities. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Breath Acetone Measurement-Based Prediction of Exercise-Induced Energy and Substrate Expenditure.

The purpose of our study was to validate a newly developed breath acetone (BrAce) analyzer, and to explore if BrAce could predict aerobic exercise-related substrate use. Six healthy men ran on a treadmill at 70% of maximal oxygen consumption (VO2max) for 1 h after two days of a low-carbohydrate diet. BrAce and blood ketone (acetoacetate (ACAC), beta-hydroxybutyrate (BOHB)) levels were measured at baseline and at different time points of post-exercise. BrAce values were validated against blood ketones and respiratory exchange ratio (RER). Our results showed that BrAce was moderately correlated with BOHB (r = 0.68, p < 0.01), ACAC (r = 0.37, p < 0.01) and blood ketone (r = 0.60, p < 0.01), suggesting that BrAce reflect blood ketone levels, which increase when fat is oxidized. Furthermore, BrAce also negatively correlated with RER (r = 0.67, p < 0.01). In our multiple regression analyses, we found that when BMI and VO2max were added to the prediction model in addition to BrAce, R2 values increased up to 0.972 at rest and 0.917 at 1 h after exercise. In conclusion, BrAce level measurements of our BrAce analyzer reflect blood ketone levels and the device could potentially predict fat oxidation.

Effects of Allium hookeri on gut microbiome related to growth performance in young broiler chickens.

Healthy food promotes beneficial bacteria in the gut microbiome. A few prebiotics act as food supplements to increase fermentation by beneficial bacteria, which enhance the host immune system and health. Allium hookeri is a healthy food with antioxidant and anti-inflammatory activities. A. hookeri is used as a feed supplement for broiler chickens to improve growth performance. Although the underlying mechanism is unknown, A. hookeri may alter the gut microbiome. In the current study, 16S rRNA sequencing has been carried out using samples obtained from the cecum of broiler chickens exposed to diets comprising different tissue types (leaf and root) and varying amounts (0.3% and 0.5%) of A. hookeri to investigate their impact on gut microbiome. The microbiome composition in the groups supplemented with A. hookeri leaf varied from that of the control group. Especially, exposure to 0.5% amounts of leaf resulted in differences in the abundance of genera compared with diets comprising 0.3% leaf. Exposure to a diet containing 0.5% A. hookeri leaf decreased the abundance of the following bacteria: Eubacterium nodatum, Marvinbryantia, Oscillospira, and Gelria. The modulation of gut microbiome by leaf supplement correlated with growth traits including body weight, bone strength, and infectious bursal disease antibody. The results demonstrate that A. hookeri may improve the health benefits of broiler chickens by altering the gut microbiome.

Validation of the Brief Negative Symptom Scale in Korean patients with schizophrenia.

INTRODUCTION: The Brief Negative Symptom Scale (BNSS) was developed based on the current consensus on negative symptoms. We validated the Korean version of the BNSS (K-BNSS) and explored the factor structure of negative symptoms among 173 Koreans with schizophrenia. METHODS: Clinical interviews and neurocognitive assessments were administered to evaluate the factor structure, validity, and reliability of the K-BNSS. RESULTS: The five-factor model of the K-BNSS showed excellent reliability and validity. DISCUSSION: Our findings confirm that the K-BNSS is a promising instrument for assessing negative symptoms of schizophrenia, and that negative symptoms are best conceptualized in the form of five domains.

ZEB1 Collaborates with ELK3 to Repress E-Cadherin Expression in Triple-Negative Breast Cancer Cells.

ZEB1 has intrinsic oncogenic functions that control the epithelial-to-mesenchymal transition (EMT) of cancer cells, impacting tumorigenesis from its earliest stages. By integrating microenvironment signals and being implicated in feedback regulatory loops, ZEB1 appears to be a central switch that determines EMT and metastasis of cancer cells. Here, we found that ZEB1 collaborates with ELK3, a ternary complex factor belonging to the ETS family, to repress E-cadherin expression. ZEB1 functions as a transcriptional activator of ELK3. We first identified that ELK3 and ZEB1 have a positively correlated expression in breast cancer cells by using multiple databases for correlation analysis. Molecular analysis revealed that ZEB1 functions as a transcriptional activator of ELK3 expression. GST pull-down assay and coimmunoprecipitation analysis of wild-type or domain deletion mutants of ZEB1 and ELK3 showed that these 2 proteins directly bound each other. Furthermore, we demonstrated that ZEB1 and ELK3 collaborate to repress the expression of E-cadherin, a representative protein that initiates EMT. Our finding suggested that ELK3 is a novel factor of the ZEB1/E-cadherin axis in triple-negative breast cancer cells. IMPLICATIONS: ELK3 is a novel factor in the ZEB1/E-cadherin axis and ZEB1 has a dual role in ELK3 as a transcriptional activator and as a collaborator to repress E-cadherin expression in triple-negative breast cancer cells.