Paeoniflorin regulates RhoA/ROCK1 and Nrf2 pathways in PDLIM1-dependent or independent manners in oxidative stressed melanocytes.

BACKGROUND: The adhesive properties of vitiligo melanocytes have decreased under oxidative stress., cytoskeleton proteins can control cell adhesion. Paeoniflorin (PF) was proved to resist hydrogen peroxide (H2O2)-induced oxidative stress in melanocytes via nuclear factorE2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. OBJECTIVES: This study was to investigate whether PF exerts anti-oxidative effect through influencing cytoskeleton markers or potential signaling pathway. METHODS: Human Oxidative Stress Plus array was used to identify the differentially expressed genes between H2O2 + PF group and H2O2 only group, in PIG1 and PIG3V melanocyte cell lines respectively. Western blotting was used to verify the PCR array results and to test the protein expression levels of cytoskeleton markers including Ras homolog family member A (RhoA), Rho-associated kinase 1 (ROCK1) and antioxidative marker Nrf2. Small interfering RNA was used to knock down PDZ and LIM domain 1 (PDLIM1). RESULTS: PF increased the expressions of PDLIM1, RhoA and ROCK1 in H2O2-induced PIG1, in contrast, decreased the expressions of PDLIM1 and ROCK1 in H2O2-induced PIG3V. Knockdown of PDLIM1 increased the expressions of RhoA and Nrf2 in PF-pretreated H2O2-induced PIG1, and ROCK1 and Nrf2 in PF-pretreated H2O2-induced PIG3V. CONCLUSIONS: PF regulates RhoA/ROCK1 and Nrf2 pathways in PDLIM1-dependent or independent manners in H2O2-induced melanocytes. In PIG1, PF promotes PDLIM1 to inhibit RhoA/ROCK1 pathway or activates Nrf2/HO-1 pathway, separately. In PIG3V, PF directly downregulates ROCK1 in PDLIM1-independent manner or upregulates Nrf2 dependent of PDLIM1.

The association of pre-cancer diagnosis cardiovascular risk factors with memory aging after a cancer diagnosis, overall and by race/ethnicity.

PURPOSE: Cardiovascular risk factors (CVRFs) are associated with increased risk for cognitive impairment and decline in the general population, but less is known about how CVRFs might influence cognitive aging among older cancer survivors. We aimed to determine how CVRFs prior to a cancer diagnosis affect post-cancer diagnosis memory aging, compared to cancer-free adults, and by race/ethnicity. METHODS: Incident cancer diagnoses and memory (immediate and delayed recall) were assessed biennially in the US Health and Retirement Study (N = 5,736, 1998-2018). CVRFs measured at the wave prior to a cancer diagnosis included self-reported cigarette smoking, obesity, diabetes, heart disease, hypertension, and stroke. Multivariable-adjusted linear mixed-effects models evaluated the rate of change in standardized memory score (SD/decade) post-cancer diagnosis for those with no, medium, and high CVRFs, compared to matched cancer-free adults, overall and stratified by sex and race/ethnicity. RESULTS: Higher number of CVRFs was associated with worse baseline memory for both men and women, regardless of cancer status. Cancer survivors with medium CVRFs had slightly slower rates of memory decline over time relative to cancer-free participants (0.04 SD units/decade [95% CI: 0.001, 0.08]). Non-Hispanic Black (NHB) and Hispanic cancer-free participants and cancer survivors had worse baseline memory than their Non-Hispanic White (NHW) counterparts. CONCLUSIONS: CVRFs were associated with worse baseline memory function, but not decline, for cancer-free adults and cancer survivors. Racial disparities were largely similar between cancer survivors and cancer-free adults. IMPLICATIONS FOR CANCER SURVIVORS: These findings may inform hypotheses about pre-diagnosis multimorbidity and cognitive aging of cancer survivors from diverse groups.

Screening and verification of hub genes in esophageal squamous cell carcinoma by integrated analysis.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors. However, the mechanisms underlying ESCC tumorigenesis have not been fully elucidated. Thus, we aimed to determine the key genes involved in ESCC tumorigenesis. The following bioinformatics analyses were performed: identification of differentially expressed genes (DEGs); gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis; integrated analysis of the protein-protein interaction network and Gene Expression Profiling Interactive Analysis database for validation of hub genes. Finally, western blotting and qPCR were used to explore the expression of cell division cycle 6 (CDC6) in ESCC cell lines. Immunohistochemistry analysis of ESCC samples from patients and matched clinical characteristics was used to determine the effects of CDC6. A total of 494 DEGs were identified, and functional enrichment was mainly focused on cell cycle and DNA replication. Biological pathway analysis of the hub genes was closely related to the cell cycle. We found that CDC6 was upregulated in ESCC cell lines and patient tissues and was related to the clinicopathological characteristics of ESCC. In conclusion, this study identified hub genes and crucial biological pathways related to ESCC tumorigenesis and integrated analyses indicated that CDC6 may be a novel diagnostic and therapeutic target for ESCC.

Demographic Differences in Compliance with COVID-19 Vaccination Timing and Completion Guidelines in the United States.

BACKGROUND: The development of vaccines has been a significant factor in eliminating the pandemic caused by the novel coronavirus (SARS-CoV-2). However, the primary series vaccination rate still falls short of our expectations, with an even lower rate of uptake for booster shots. This study examined demographic patterns of COVID-19 vaccination compliance by assessing patterns in the timing of the vaccine series start and vaccination completion and characterizing people by compliance with vaccination recommendations. METHODS: A cross-sectional survey was conducted online in August 2022. Participants answered questions about the COVID-19 vaccine and questions related to their personal backgrounds. We assessed the impact of demographic factors on COVID-19 vaccination using multivariable regression modeling. RESULTS: Among 700 eligible participants, 61% (389) were highly adherent (i.e., started by late 2020 and received a booster dose), 22% (184) were moderately adherent (i.e., started later than June 2021, and/or did not receive the booster dose), and 17% (127) were unvaccinated. Compliance was relatively low among non-Hispanic Black Americans, those with no religious affiliation, and among Independents and Republicans. CONCLUSION: Vaccination compliance varies across demographic groups. Race/ethnicity, religion, and political affiliation are highly associated with vaccination compliance. To promote vaccination compliance and decrease vaccine hesitancy, the government and healthcare institutions should establish a positive image to obtain public trust and adopt effective vaccine education and intervention.

Spillover of Vaccine Hesitancy into Adult COVID-19 and Influenza: The Role of Race, Religion, and Political Affiliation in the United States.

BACKGROUND: Due to its potential to lead to vaccine delays and refusals, vaccine hesitancy has attracted increased attention throughout the COVID-19 pandemic. It is crucial to investigate whether demographic patterns differ between adult general vaccine hesitancy and COVID-19 and flu vaccine non-receipt. METHODS: A cross-sectional survey was conducted online in August 2022. In response to questions about vaccine hesitancy, participants indicated whether they would receive the vaccine given various safety and efficacy profiles. Through logistic regression models, we examined variations between general vaccine hesitancy and COVID-19 non-vaccination. RESULTS: Among the 700 participants, 49% of the respondents were classified as having general vaccine hesitancy, 17% had not received the COVID-19 vaccine, and 36% had not had flu vaccinations. In the multivariable analysis, general vaccine hesitancy and the non-receipt of COVID-19 vaccines were significantly higher in Non-Hispanic Black participants, those with no religious affiliation, and Republicans and Independents. CONCLUSIONS: Patterns of vaccine hesitancy and the non-receipt of the COVID-19 vaccination did not vary, indicating a substantial overlap and potential spillover in vaccine hesitancy over the course of the pandemic. Because changing people's opinions regarding vaccinations is generally a challenge, different interventions specific to demographic subgroups may be necessary.

Antibiotic resistant bacteria: A bibliometric review of literature.

Antibiotic-resistant bacteria (ARB) are a serious threat to the health of people and the ecological environment. With this problem becoming more and more serious, more countries made research on the ARB, and the research number has been sharply increased particularly over the past decade. Therefore, it is quite necessary to globally retrace relevant researches on the ARB published from 2010 to 2020. This will help researchers to understand the current research situation, research trends and research hotspots in this field. This paper uses bibliometrics to examine publications in the field of ARB from 2010 to 2020 that were retrieved from the Web of Science (WOS). Our study performed a statistical analysis of the countries, institutions, journals, authors, research areas, author keywords, Essential Science Indicators (ESI) highly cited papers, and ESI hotspots papers to provide an overview of the ARB field as well as research trends, research hotspots, and future research directions in the field. The results showed that the number of related studies is increasing year by year; the USA is most published in the field of ARB; China is the most active in this field in the recent years; the Chinese Acad Sci published the most articles; Sci. Total Environ. published the greatest number of articles; CM Manaia has the most contributions; Environmental Sciences and Ecology is the most popular research area; and "antibiotic resistance," "antibiotics," and "antibiotic resistance genes" were the most frequently occurring author keywords. A citation analysis showed that aquatic environment-related antibiotic resistance is a key research area in this field, while antimicrobial nanomaterial-related research is a recent popular topic.

Clinical guideline for the diagnosis and treatment of cutaneous warts (2022).

AIM: Cutaneous warts caused by human papillomavirus are benign proliferative lesions that occur at any ages in human lives. Updated, comprehensive and systematic evidence-based guidelines to guide clinical practice are urgently needed. METHODS: We collaborated with multidisciplinary experts to formulate this guideline based on evidences of already published literature, focusing on 13 clinical questions elected by a panel of experts. We adopted Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to form classification of recommendations as well as the improved Delphi method to retain respective recommendations with a consensus degree of over 80%. RESULTS: Our guideline covered aspects of the diagnosis and treatment of cutaneous warts such as diagnostic gold standard, transmission routes, laboratory tests, treatment principle, clinical cure criterion, definitions, and treatments of common warts, flat warts, plantar warts, condyloma acuminatum, and epidermodysplasia verruciformis. Recommendations about special population such as children and pregnant women are also listed. In total, 49 recommendations have been obtained. CONCLUSIONS: It is a comprehensive and systematic evidence-based guideline and we hope this guideline could systematically and effectively guide the clinical practice of cutaneous warts and improve the overall levels of medical services.

Activation of aryl hydrocarbon receptor ameliorates rosacea-like eruptions in mice and suppresses the TLR signaling pathway in LL-37-induced HaCaT cells.

BACKGROUND: Toll-like receptor (TLR) 2, along with some chemokines, were found to be overexpressed in rosacea patients. Aryl hydrocarbon Receptor (AhR) activation inhibited the inflammatory responses triggered by TLR activation. The current study was conducted to evaluate the underlying mechanisms of AhR activation in rosacea models. MATERIALS AND METHODS: Seven-week-old female BALB/c mice received twice daily intradermal injections of LL-37 for 2 consecutive days. Thirty minutes after the second LL-37 injection, 1% or 0.5% AhR agonist benvitimod was administrated topically once per day for 3 consecutive days. HaCaT cells were treated with different concentrations of LL-37 and benvitimod, and were further infected with lentivirus to over-express TLR2. Expressions of TLR2, CCL5, CXCL9, CXCL10 and CXCL11 were evaluated using qRT-PCR, Western Blot or ELISA. RESULTS: AhR activation ameliorated LL-37-induced rosacea-like eruptions in mice by reductions in redness scores, redness areas and dermal inflammatory cell infiltrates. Elevated expressions of TLR2 and chemokines (CCL5, CXCL9, CXCL10 and CXCL11) following LL-37 treatment were decreased by AhR activation. In HaCaT cells receiving LL-37, TLR2 and the four chemokines were up-regulated, and levels of these chemokines were further enhanced after over-expressing TLR2. At 8 h after an administration of 10 µM benvitimod, gene expressions of TLR2 and the four chemokines in LL-37 treated HaCat cells were decreased, while their protein expressions were decreased for 24 h. CONCLUSION: AhR activation is beneficial in treating rosacea in a LL-37-induced rosacea mouse model and involves a suppression of the TLR signaling pathway in an HaCaT cell model of rosacea.

How Is Knowledge Perceived as Power? A Multilevel Model of Knowledge Power in Innovation Networks.

Inter-organizational power relations have long been considered to be balanced in innovation networks, which are viewed as loosely coupled systems. Some recent studies, however, show that innovation networks are asymmetric and hierarchical, and the power of network actors has become a significant but rarely addressed issue. As knowledge is the most important resource in the network, this paper introduces the concept of knowledge power by combining related research perspectives and conducting some fundamental research on it as follows: (1) knowledge power's origins are analyzed by proposing the term "activated knowledge" and studying the path through which it is formed over multiple levels of the network; (2) a multilevel framework of characteristics of activated knowledge, which is considered the major determinant of knowledge power, is established, and suggestions are offered for how they impact knowledge power; and (3) a multilevel measurement model for knowledge power is built, and the above propositions are tested by mathematical inference. The purpose of this paper is not only to study knowledge power's formation, determinants, and measurement but also to offer a comprehensive view, combining multiple network levels and multiple research perspectives, that should be useful to researchers conducting future studies in this field.

Layer-by-layer coated hybrid nanoparticles with pH-sensitivity for drug delivery to treat acute lung infection.

Bacteria-induced acute lung infection (ALI) is a severe burden to human health, which could cause acute respiratory distress syndrome (ARDS) and kill the patient rapidly. Therefore, it is of great significance to develop effective nanomedicine and therapeutic approach to eliminate the invading bacteria in the lung and manage ALI. In this study, we design a layer-by-layer (LbL) liposome-polymer hybrid nanoparticle (HNP) with a pH-triggered drug release profile to deliver antibiotics for the eradication of bacteria to treat ALI. The liposome is prepared by the lipid film hydration method with a homogenous hydrodynamic diameter and low polydispersity index (PDI). The antibiotic spectinomycin is efficiently loaded into the liposomal core through the pH-gradient method. The pH-sensitive polycationic polymer poly(ß-amino ester) (PBAE) and polyanionic sodium alginate (NaAIg) layers are decorated on the surface of liposome in sequence via electrostatic interaction, resulting in spectinomycin-loaded layer-by-layer hybrid nanoparticles (denoted as Spe@HNPs) which have reasonable particle size, high stability, prolonged circulation time, and pH-triggered drug release profile. The in vitro results demonstrate that Spe@HNPs can efficiently induce the death of bacteria with low minimum inhibitory concentration (MIC) against Staphylococcus aureus (S. aureus) and drug-resistant MRSA BAA40 strains. The in vivo results reveal that Spe@HNPs can eradicate the invading MRSA BAA40 with improved antimicrobial efficacy and low side-effect for ALI treatment. This study not only reports a promising nanomedicine but also provides an effective method to prepare nanoplatforms for drug delivery and controlled release.

Effect of the acid suppressor omeprazole on the proliferation, migration, invasion and cell cycle of esophageal squamous cell carcinoma cells via the aryl hydrocarbon receptor pathway.

Esophageal cancer is a malignant tumor type with one of the highest mortality rates worldwide. The aryl hydrocarbon receptor (AHR), which has been investigated in recent years, has been confirmed to be associated with the occurrence and development of esophageal cancer. AHR has a variety of different ligands, which regulate its activity following binding. The widely known acid inhibitor omeprazole (OME) also affects AHR and its downstream proteins (such as the cytochrome P450 family) by non-ligand binding; however, the mechanisms have remained to be fully elucidated. Therefore, the aim of the present study was to investigate the role of OME in esophageal squamous cell carcinoma (ESCC), whether the mechanism proceeds via the AHR pathway and how OME regulates AHR to affect the occurrence and development of esophageal carcinoma. The AHR-selective regulator OME was used to treat the ESCC cell lines TE1 and KYSE150. Western blot analysis was used to verify the effect of OME on AHR and proliferating cell nuclear antigen (PCNA) protein expression levels, while Cell Counting Kit (CCK)-8, wound-healing and Transwell assays were used to determine the proliferation, migration and invasion of the ESCCs, respectively, following treatment with OME. In addition, flow cytometry was used to investigate the cell cycle distribution of the ESCCs following incubation with OME. AHR was highly expressed in the ESCCs and following treatment with OME, the protein expression levels of AHR and PCNA were downregulated. The CCK-8 assay indicated that the proliferation of the ESCCs was also reduced following treatment with OME. Furthermore, flow cytometry revealed a notable block of the cells in G1/G0 phase, while the results of the wound-healing and Transwell assays respectively suggested that cell migration and invasion were reduced. In conclusion, OME inhibited the proliferation, migration and invasion of ESCC cells and blocked the cell cycle via the AHR pathway, which may provide a therapeutic effect on esophageal squamous cell cancer.

Dual CO2 Responsiveness of an Oil-In-Water Emulsion by Using Sodium Oleate and Water-Soluble Tertiary Amines.

Two kinds of water-soluble tertiary amines (TAs), triethylamine (TEA, monoamine), and tetramethyltrimethylenediamine (TMA, diamine) were introduced into a NaOA stable oil-water (O/W) emulsion, respectively, and their dual reactivity to carbon dioxide was studied. TA was converted into bicarbonate after bubbling of CO2, which induced the increase of ionic strength of the aqueous phase, and formed ion pair with NaOA through electrostatic interaction. NaOA itself can also be protonated into oleic acid, which can be reverently deprotonated by alternating bubbles of CO2 at 25 °C and N2 at 50 °C, thus affecting the stability and demulsification process of the emulsion. In order to demonstrate TA's and NaOA's synergistic effect on CO2 responsiveness, gas chromatography-mass spectrometry, ζ potential, electrical conductivity, pH value, 1H nuclear magnetic resonance, morphological evolution, and interfacial tension were used to study the contributions of the single component and two components of NaOA, TEA, and TMA to emulsion stability and CO2 responsiveness, respectively. Combined with the composition distribution under different pH conditions, it was further proved that TAs had an effect on the stability and CO2 responsiveness of the NaOA emulsion.

Fabrication of pH/Redox Dual-Responsive Mixed Polyprodrug Micelles for Improving Cancer Chemotherapy.

In this work, we prepared pH/redox dual-responsive mixed polyprodrug micelles (MPPMs), which were co-assembled from two polyprodrugs, namely, poly(ethylene glycol) methyl ether-b-poly (ß-amino esters) conjugated with doxorubicin (DOX) via redox-sensitive disulfide bonds (mPEG-b-PAE-ss-DOX) and poly(ethylene glycol) methyl ether-b-poly (ß-amino esters) conjugated with DOX via pH-sensitive cis-aconityl bonds (mPEG-b-PAE-cis-DOX) for effective anticancer drug delivery with enhanced therapeutic efficacy. The particle size of MPPMs was about 125 nm with low polydispersity index, indicating the reasonable size and uniform dispersion. The particle size, zeta-potential, and critical micelle concentration (CMC) of MPPMs at different mass ratios of the two kinds of polyprodrugs were dependent on pH value and glutathione (GSH) level, suggesting the pH and redox responsiveness. The drug release profiles in vitro of MPPMs at different conditions were further studied, showing the pH-and redox-triggered drug release mechanism. Confocal microscopy study demonstrated that MPPMs can effectively deliver doxorubicin molecules into MDA-MB-231 cells. Cytotoxicity assay in vitro proved that MPPMs possessed high toxic effect against tumor cells including A549 and MDA-MB-231. The results of in vivo experiments demonstrated that MPPMs were able to effectively inhibit the tumor growth with reduced side effect, leading to enhanced survival rate of tumor-bearing mice. Taken together, these findings revealed that this pH/redox dual-responsive MPPMs could be a potential nanomedicine for cancer chemotherapy. Furthermore, it could be a straightforward way to fabricate the multifunctional system basing on single stimuli-responsive polyprodrugs.

Redox and Doubly pH-Switchable Pickering Emulsion.

In this work, a novel Pickering emulsion is stabilized by silica nanoparticles functioned with a redox and pH-responsive surfactant FA-DMDA-Ox that is prepared simply by direct neutralization of ferrocenecarboxylic acid (FA) and N,N-dimethyldodecylamine (DMDA) and exhibits redox and doubly pH-switchable behavior. Here, the Pickering emulsion can be stabilized easily by combining hydrophilic silica nanoparticles with less than 0.1 wt % FA-DMDA-Ox. After adding Na2SO3 and H2O2 alternately, the demulsification and emulsification of this Pickering emulsion are controlled reversibly. Moreover, the emulsion is switched "off" upon the addition of HCl and switched "on" upon the addition of NaOH and is also switched off upon the addition of NaOH and switched on upon the addition of HCl, which demonstrate the doubly pH-switchable behavior. Based on the analysis of ζ-potential, contact angle, and adsorbed amount of silica nanoparticles, the pH and redox-switchable mechanism of the Pickering emulsion are analyzed. Here, the redox-switchable behavior is induced by the reversible adsorption and desorption of FA-DMDA-Ox on the surface of silica nanoparticles. The pH-switchable behavior is driven by the controllable dispersion systems of silica nanoparticles and FA-DMDA-Ox because of the doubly pH switchability of FA-DMDA-Ox. More importantly, upon adding fresh oil after removing the original oil, the Pickering emulsion is recycled three times. Hence, the multiswitchable Pickering emulsion can be expected to be treated as a multifunctional material in practical applications, such as oil or wax removal in the petroleum industry.

Expression of collagen type 1 alpha 1 indicates lymph node metastasis and poor outcomes in squamous cell carcinomas of the lung.

BACKGROUND: Squamous cell carcinomas of the lung are an extremely common and deadly form of non-small cell lung cancers. Clinical management of the disease is dependent on staging and metastatic status. Metastasis to the lymph node is especially crucial to diagnose as it occurs at an earlier stage. However, lymphadenectomies are invasive and tumor cells may be overlooked during evaluation.There are limited approved biomarkers for predicting lymph node metastasis with squamous cell carcinomas of the lung (LSCC). METHODS: Genome data of 60 tumor-adjacent samples were downloaded from Genome Expression Omnibus. We identified over-expressed HUB genes using Cytoscape as key prognostic markers. The selected markers were further evaluated based on gene ontology and overall expression levels compared to normal tissue using The Cancer Genome Atlas. We further validated these results using clinical biopsy tissue taken from squamous cell carcinoma patients. RESULTS: Analysis of the genome expression data resulted in 13 relevant hub genes that were differentially expressed in cancerous samples. All of these genes are associated with collagen biosynthesis within the tumor microenvironment. We chose Collagen Type 1 Alpha 1 (COL1A1) as the most relevant prognostic marker due to its high number of pathway connections and over expression in the tumor microenvironment compared to the other 12 genes. Additionally, based on analysis of The Cancer Genome Atlas, tumors with higher levels of COL1A1 expression are associated with poorer overall survival. Finally, evaluation of clinical biopsy samples suggests that overexpression of COL1A1 in the LSCC microenvironment highly correlates with lymph node metastasis. These results suggest COL1A1 is a clinically relevant marker that should be used to justify lymphadenectomies.

TME-Responsive Polyprodrug Micelles for Multistage Delivery of Doxorubicin with Improved Cancer Therapeutic Efficacy in Rodents.

It is of great significance to develop multifunctional biomaterials to effectively deliver anticancer drug to tumor cells for cancer therapy. Here, inspired by the specific tumor microenvironment (TME) cues, a unique multistage pH/redox-responsive polyprodrug composed of amphiphilic pH-sensitive diblock copolymer poly(ethylene glycol) methyl ether-b-poly(ß-amino esters) conjugated with doxorubicin (DOX) via redox-sensitive disulfide bonds (mPEG-b-PAE-ss-DOX) is designed and developed. This polyprodrug can self-assemble into micelles (DOX-ss@PMs) at low concentration with high serum stability, indicating that DOX-ss@PMs have prolonged circulation time. The dual pH/redox-responsiveness of the multistage platform is thoroughly evaluated. In vitro results demonstrate that DOX-ss@PMs can highly accumulate at tumor site, followed by responding to the acidity for disassembly and effectively penetrating into the tumor cells. DOX is released from the platform due to the cleavage of disulfide bonds induced by high glutathione (GSH) concentration, thereby inducing the apoptosis of tumor cells. In vivo studies further reveal that multistage DOX-ss@PMs can more efficiently inhibit the growth of tumors and improve the survival of tumor-bearing mice in comparison to the free drug and control. These results imply that multistage delivery system might be a potential and effective strategy for drug delivery and DOX-ss@PMs could be a promising nanomedicine for cancer chemotherapy.

3,3'-Diindolylmethane modulates aryl hydrocarbon receptor of esophageal squamous cell carcinoma to reverse epithelial-mesenchymal transition through repressing RhoA/ROCK1-mediated COX2/PGE2 pathway.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive tumors in the world. Aryl hydrocarbon receptor (AHR) has been reported to promote tumor metastasis and epithelial-mesenchymal transition (EMT) is a vital process of conferring cancer cells capabilities of migration and invasion. However, the mechanism by which modulation of AHR can inhibit tumor metastasis remains unknown. Thus, we aim to investigate the underlying mechanism regarding reversing EMT process of ESCC through modulation of AHR. METHODS: We used AHR selective modulator 3,3'-diindolylmethane (DIM) to treat ESCC cell lines TE1 and KYSE150 so as to examine alterations of migration and invasion by wound healing and Transwell assay. Western blotting (WB) and qPCR were performed to detect relative genes and proteins changes regarding EMT process. Cell transfection was utilized for confirming pathways involved in DIM-induced reversal of EMT and in vivo assay was conducted for verification of the underlying mechanism. Co-IP assay was conducted for detecting protein-protein interactions. RESULTS: AHR was overexpressed in ESCC and modulation of AHR by DIM could inhibit migration and invasion as well as downregulate mesenchymal cell markers ß-Catenin, Vimentin and Slug and upregulate epithelial cell marker Claudin-1. Meanwhile, synergically overexpression of AHR, RhoA and ROCK1 correlated with poor clinical outcomes. DIM could inhibit COX2/PGE2 pathway by targeting AHR, and COX2 selective inhibitor Celecoxib could suppress EMT and metastasis. Results of PGE2 treatment were opposite to that of Celecoxib. Meanwhile, blockade of RhoA/ROCK1 pathway also exerted prohibitive effects on EMT and metastasis. WB results showed COX2/PGE2 pathway could be regulated by RhoA/ROCK1 pathway and DIM could inhibit RhoA/ROCK1 pathway through modulation of AHR. In vivo assay verified the results in vitro. Co-IP results showed DIM could modulate AHR to reverse EMT directly through inhibition of interaction between AHR and EGFR (epidermal growth factor receptor) so as to block RhoA/ROCK1-mediated COX2/PGE2 pathway which was connected by NF-κB. CONCLUSIONS: In brief, modulation of AHR by DIM can reverse EMT process and inhibit metastasis of ESCC through repressing RhoA/ROCK1-mediated COX2/PGE2 pathway.