Association between tea consumption and colorectal cancer: a systematic review and meta-analysis of a population-based study.

PURPOSE: A meta-analysis study was performed to systematically assess the association between tea consumption and CRC risk. METHODS: Cochrane Library, Embase, PubMed, and Web of Science were retrieved to collect articles in English since 24 July 2023. Databases were searched and evaluated by two reviewers independently.We screened the literature based on inclusion and exclusion criteria. After determining the random effect model or fixed utility model based on a heterogeneity test, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: We included fourteen articles in this meta-analysis. We analyzed the data using a random effect model to explore the association between tea consumption and CRC because of apparent heterogeneity (P < 0.001, I2 = 99.5%). The combined results of all tests showed that there is no statistically significant association between tea consumption and CRC risk (OR = 0.756, 95%CI = 0.470-1.215, P = 0.247). Subsequently, subgroup analysis and sensitivity analysis were performed. Excluding any single study, the overall results ranged from 0.73 (95%CI = 0.44-1.20) to 0.86 (95%CI = 0.53-1.40). It was determined that there was no significant publication bias between tea consumption and CRC risk (P = 0.064) by Egger's tests. CONCLUSIONS: The results indicated that tea consumption may not be significantly associated with the development of CRC. IMPLICATIONS OF KEY FINDINGS: Tea reduces colon cancer risk by 24%, but the estimate is uncertain. The actual effect on risk can range from a reduction of 51% to an increase of 18%, but regional and population differences may cause differences.

Do wildfires exacerbate COVID-19 infections and deaths in vulnerable communities? Evidence from California.

Understanding whether and how wildfires exacerbate COVID-19 outcomes is important for assessing the efficacy and design of public sector responses in an age of more frequent and simultaneous natural disasters and extreme events. Drawing on environmental and emergency management literatures, we investigate how wildfire smoke (PM2.5) impacted COVID-19 infections and deaths during California's 2020 wildfire season and how public housing resources and hospital capacity moderated wildfires' effects on COVID-19 outcomes. We also hypothesize and empirically assess the differential impact of wildfire smoke on COVID-19 infections and deaths in counties exhibiting high and low social vulnerability. To test our hypotheses concerning wildfire severity and its disproportionate impact on COVID-19 outcomes in socially vulnerable communities, we construct a county-by-day panel dataset for the period April 1 to November 30, 2020, in California, drawing on publicly available state and federal data sources. This study's empirical results, based on panel fixed effects models, show that wildfire smoke is significantly associated with increases in COVID-19 infections and deaths. Moreover, wildfires exacerbated COVID-19 outcomes by depleting the already scarce hospital and public housing resources in local communities. Conversely, when wildfire smoke doubled, a one percent increase in the availability of hospital and public housing resources was associated with a 2 to 7 percent decline in COVID-19 infections and deaths. For California communities exhibiting high social vulnerability, the occurrence of wildfires worsened COVID-19 outcomes. Sensitivity analyses based on an alternative sample size and different measures of social vulnerability validate this study's main findings. An implication of this study for policymakers is that communities exhibiting high social vulnerability will greatly benefit from local government policies that promote social equity in housing and healthcare before, during, and after disasters.

Hsa_circ_0005100 regulates tumorigenicity of colorectal carcinoma via miR-145-5p/MACC1 axis.

BACKGROUND: Circular RNAs (circRNAs) are a kind of RNA molecules involved in the regulation of cancer progression, including colorectal carcinoma (CRC); nevertheless, their regulation mode is blurry. In the present work, we attempted to reveal the characteristics of hsa_hsa_circ_0005100 in CRC. METHODS: Differential expressions of hsa_circ_0005100, FMN2 mRNA, microRNA-145-5p (miR-145-5p), and MACC1 were indicated by qRT-PCR and Western blot. The capacities of cell growth and motility were validated by the MTT assay, flow cytometry assay, EdU assay, colony formation assay, and transwell assay. Moreover, the targeted relationship of miR-145-5p and hsa_circ_0005100 or MACC1 was distinguished by dual-luciferase reporter assay. The animal experiment was implemented to confirm the influence of hsa_circ_0005100 on tumorigenesis in vivo. RESULTS: Hsa_circ_0005100 and MACC1 expression levels were increased, but miR-145-5p expression level was diminished in CRC. Hsa_circ_0005100 knockdown repressed cell proliferation, cell cycle, migration, and invasion, while expedited cell apoptosis in CRC cells. Furthermore, miR-145-5p was disclosed to block CRC via overturning MACC1. Hsa_circ_0005100 targeted miR-145-5p to modulate MACC1. Additionally, hsa_circ_0005100 knockdown also attenuated tumorigenesis in vivo. CONCLUSION: Hsa_circ_0005100 was a vital regulator in the development of CRC by miR-145-5p/MACC1 axis, which deepened the understanding of CRC pathogenesis from circRNA insights.

Integration of single-cell transcriptomics and epigenetic analysis reveals enhancer-controlled TIMP1 as a regulator of ferroptosis in colorectal cancer.

BACKGROUND: Ferroptosis is an iron-dependent non-apoptotic programmed cell death. However, the regulatory mechanism of ferroptosis in colorectal cancer (CRC) is still unclear. OBJECTIVE: The aim of this study was to investigate the role and mechanism of enhancer-controlled genes in ferroptosis in CRC. METHODS: Dimensionality reduction and differentially expressed genes (DEGs) identification were conducted using Seurat algorithm based on single-cell RNA sequencing (scRNA-seq) data from the GSE200997 dataset. Ferroptosis-related pathway enrichment analysis was performed using the FerrDb V2 database. Enhancers were identified using HOMER algorithm based on H3K27ac ChIP-seq data from the GSE166254 dataset. Kaplan-Meier Plotter online tool was used to analyze prognosis and gene expression correlation. Transcription factors were predicted using the transcription factor affinity prediction web tool. The binding of enhancer to transcription factor and H3K27ac enrichment were detected by ChIP-qPCR. RSL3 was used to induce ferroptosis in CRC cells. Gene transcription was detected by qRT-PCR. Cell proliferation was detected by CCK8 assay. RESULTS: Nine cell clusters including T cells, natural killer cells, macrophages, mast cells, epithelial cells, fibroblasts, goblet cells, B cells and dendritic cells were identified in CRC and normal colonic tissue samples. Compared to normal colonic tissue-derived epithelial cells, 1075 DEGs were screened in CRC tissue-derived epithelial cells. Ferroptosis-related pathway enrichment suggested that DEGs were associated with the regulation of ferroptosis. DPEP1, ETV4, CEBPG, TIMP1, DUOX2 and LCN2 were identified as the significantly upregulated genes enriched in the "ferroptosis regulator" term, and their H3K27ac signals were significantly higher in CRC tissues than in normal colonic tissues. Of these, only the expression of TIMP1 predicted a poor prognosis of CRC patients. Transcription factor SPI1 drove TIMP1 transcription by binding to its enhancer. Overexpression of TIMP1 significantly promoted the resistance to ferroptosis induced by RSL3 in CRC cells, which was partially restored by SPI1 knockdown. CONCLUSION: Transcription of TIMP1 was driven by transcription factor SPI1 in combination with its enhancer, consequently promoting CRC cells against ferroptosis. The SPI1/TIMP1 axis confers ferroptosis resistance in CRC, and thus has the potential to be the molecular targets for CRC treatment.

Progress in reeducating tumor-associated macrophages in tumor microenvironment.

Malignant tumor, one of the most threatening diseases to human health, has been comprehensively treated with surgery, radiotherapy, chemotherapy and targeted therapy, but the prognosis has not always been ideal. In the past decade, immunotherapy has shown increased efficacy in tumor treatment; however, for immunotherapy to achieve its fullest potential, obstacles are to be conquered, among which tumor microenvironment (TME) has been widely investigated. In remodeling the tumor immune microenvironment to inhibit tumor progression, macrophages, as the most abundant innate immune population, play an irreplaceable role in the immune response. Therefore, how to remodel TME and alter the recruitment and polarization status of tumor-associated macrophages (TAM) has been of wide interest. In this context, nanoparticles, photodynamic therapy and other therapeutic approaches capable of affecting macrophage polarization have emerged. In this paper, we categorize and organize the existing means and methods for reprogramming TAM to provide ideas for clinical application of novel tumor-related therapies.

Rapamycin inhibits the mTOR/p70S6K pathway and attenuates cardiac fibrosis in adriamycin-induced dilated cardiomyopathy.

BACKGROUND: The objective of the present study was to investigate whether mTOR is involved in cardiac fibrosis evident in dilated cardiomyopathy, and whether rapamycin provides therapeutic potential for cardiac fibrosis. METHODS: Forty-five rats were divided into three groups. Fifteen rats in the Adriamycin group underwent 8 weeks of Adriamycin treatment (2.5 mg/kg, twice per week; i.v.) to induce cardiac fibrosis and dilated cardiomyopathy. Fifteen rats in the rapamycin group received rapamycin (2 mg/kg, per day, orally) and i.v. Adriamycin simultaneously for 8 weeks. Fifteen untreated rats served as controls. Cardiac morphology and function were quantified using echocardiography. mTOR and p70S6K1 mRNA expression were assessed using reverse transcription-PCR. RESULTS: Collagen volume fraction (CVF) was significantly elevated in the adriamycin group (3.36 ± 0.75) compared with controls (1.51 ± 0.31), whereas mTOR and p70S6K mRNA expression were significantly increased in the adriamycin group (0.68 ± 0.03 and 0.69 ± 0.03) compared with controls (0.38 ± 0.03 and 0.34 ± 0.02). The Adriamycin group was associated with cardiac dilation and decreased contractile function. The rapamycin group showed significantly decreased CVF (1.87 ± 0.45), accompanied with a significant decrease in mTOR and p70S6K mRNA expression (0.42 ± 0.05 and 0.45 ± 0.04) relative to the Adriamycin group. In addition, treatment with rapamycin recovered impairments in cardiac morphology and function. CONCLUSION: The mTOR/p70S6K pathway plays an important role in adriamycin-induced cardiac fibrosis resulting from dilated cardiomyopathy. Rapamycin is a potential therapeutic treatment that can be used to attenuate cardiac fibrosis and improve cardiac function.

Design and Motion Analysis of a Soft-Limb Robot Inspired by Bacterial Flagella.

Soft robots demonstrate an impressive ability to adapt to objects and environments. However, current soft mobile robots often use a single mode of movement. This gives soft robots good locomotion performance in specific environments but poor performance in others. In this paper, we propose a leg-wheel mechanism inspired by bacterial flagella and use it to design a leg-wheel robot. This mechanism employs a tendon-driven continuum structure to replicate the bacterial flagellar filaments, while servo and gear components mimic the action of bacterial flagellar motors. By utilizing twisting and swinging motions of the continuum structure, the robot achieves both wheeled and legged locomotion. The paper provides comprehensive descriptions and detailed kinematic analysis of the mechanism and the robot. To verify the feasibility of the robot, a prototype was implemented, and experiments were performed on legged mode, wheeled mode, and post-overturning motion. The experimental results demonstrate that the robot can achieve legged and wheeled motions. Moreover, it is also demonstrated that the robot still has mobility after overturning. This expands the applicability scenarios of the current soft mobile robot.

Activation of kappa opioid receptor (KOR) inhibits estrogen receptor (ER)-positive breast cancer through the KOR-ER-XBP1 pathway.

Opioids are commonly used in patients with breast cancer (BC), both for perioperative analgesia and for the relief of chronic cancer pain. Studies have suggested a potential association of opioid receptors (ORs) with the prognosis of BC patients. However, the exact roles of different ORs remain poorly understood. In this study, we found that κ opioid receptor (KOR) was the only OR (among the four types of ORs) that was significantly decreased in BC tumor tissues compared with peritumoral normal tissues. In addition, decreased expression of KOR correlated with poor clinical outcomes in patients with estrogen receptor (ER)-positive BC. In vitro studies confirmed the anti-tumor effects of KOR agonists in ER-positive MCF-7 and T47D cells by showing that activation of KOR significantly inhibited cellular proliferation and promoted apoptosis. Using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction network (PPI) analysis, we found that KOR-ER-XBP1 was the potential downstream signaling pathway mediating the anti-tumor effects of KOR agonist. Finally, the role of XBP1 was confirmed as KOR activation-induced increase in the proliferative and monoclonal formation abilities of ER-positive BC cells were both significantly abolished after silencing of XBP1. These findings provide us a better understanding of the roles of different ORs in BC, identifying KOR agonists as better opioids than traditional µ opioid receptor (MOR) agonists for providing analgesia in ER-positive BC patients owing to their association with better prognosis.

Establishment of clinical predictive model based on the study of influence factors in patients with colorectal polyps.

Background: Colorectal cancer (CRC) is the most common gastrointestinal malignancy and is generally thought to be caused by the transformation of colorectal polyps. It has been shown that early detection and removal of colorectal polyps may reduce the mortality and morbidity of colorectal cancer. Objective: Based on the risk factors associated with colorectal polyps, an individualized clinical prediction model was built to predict and evaluate the possibility of developing colorectal polyp. Methods: A case-control study was conducted. Clinical data were collected from 475 patients who underwent colonoscopy at the Third Hospital of Hebei Medical University from 2020 to 2021. All clinical data were then divided into training sets and validation sets by using R software (7:3). A multivariate logistic analysis was performed to identify the factors associated with colorectal polyps according to the training set, and a predictive nomogram was created by R software based on the multivariate analysis. The results were internally validated by receiver operating characteristic (ROC) curves, calibration curves, and externally validated by validation sets. Results: Multivariate logistic regression analysis showed that age (OR = 1.047, 95% CI = 1.029-1.065), history of cystic polyp (OR = 7.596, 95% CI = 0.976-59.129), and history of colorectal diverticulums (OR = 2.548, 95% CI = 1.209-5.366) were independent risk factors for colorectal polyps. History of constipation (OR = 0.457, 95% CI = 0.268-0.799) and fruit consumption (OR = 0.613, 95% CI 0.350-1.037) were protective factors for colorectal polyps. The nomogram demonstrated good accuracy for predicting colorectal polyps, with both C index and AUC being 0.747 (95% CI = 0.692-0.801). The calibration curves showed good agreement between the predicted risk by the nomogram and real outcomes. Both internal and external validation of the model showed good results. Conclusion: In our study, the nomogram prediction model is reliable and accurate, which can help early clinical screening of patients with high-risk colorectal polyps, improve polyp detection rate, and reduce the incidence of colorectal cancer (CRC).

Research Progress of Epithelial-mesenchymal Transition Treatment and Drug Resistance in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common malignancies in the world that seriously affects human health. Activation of epithelial-mesenchymal transition (EMT) is a physiological phenomenon during embryonic development that is essential for cell metastasis. EMT participates in various biological processes associated with trauma repair, organ fibrosis, migration, metastasis, and infiltration of tumor cells. EMT is a new therapeutic target for CRC; however, some patients with CRC develop resistance to some drugs due to EMT. This review focuses specifically on the status of treatments that target the EMT process and its role in the therapeutic resistance observed in patients with CRC.

Development and verification of a microsatellite instability-related risk signature for predicting survival and therapy effectiveness in gastric cancer.

Background: Gastric cancer (GC) is one of is one of the most common malignancy among digestive system cancers worldwide. Increasing evidence has revealed that microsatellite instability (MSI) status can affect the survival in various cancers. However, the role of MSI status in GC remains uncertain. Methods: The RNA-seq and clinicopathological features and mutation data of GC was obtained from The Cancer Genome Atlas (TCGA). Different bioinformatic and statistical methods were combined to construct a robust MSI-related gene signature for prognosis. Gene set enrichment analysis was conducted to explore Kyoto Encyclopedia of Genes and Genomes pathways associated with the MSI-related risk signature. Moreover, Kaplan-Meier (K-M) survival and receiver operating characteristic (ROC) analyses evaluate that the MSI-related risk signature. Immune-associated miRNAs were identified using immune scores calculated by the ssGSEA. In addition, 'pRRophetic' R package was used to assess the chemotherapeutic response by the GDSC website. Results: We firstly analyzed the influence of MSI status to GC survival based on the data from the TCGA database. GC patients in the TCGA database were divided into MSI-H and MSI-L/MSS groups. We counted the survival conditions of GC patients in these two groups. In addition, we also calculated the difference of TMB between these two groups and found that MSI-H group had a relatively high survival rate. Next, we identified 99 highly mutated genes in MSI-H group and constructed a MSI-related risk signature based on 10 robust genes for predicting the overall survival (OS) of GC patients. Moreover, analyses indicated that the MSI-related risk signature can accurately predict 1-, 3- and 5-year OS of GC patients. Furthermore, enrichment analysis suggested that genes between the high- and low-risk groups mainly involved in mutation and DNA repair related pathways. Finally, we also found that the MSI-related risk signature can affect the TME immune cell infiltration in GC and can be used to predict the clinical response to immunotherapy. Conclusions: In the present study, we develop a MSI-related risk signature for predicting the survival and therapy of GC, which may contribute to the clinical treatment of GC.

LncRNA HOXC-AS3 overexpression inhibits TGF-ß2-induced colorectal cancer cell migration and invasion by sponging miR-1269.

OBJECTIVE: Long non-coding RNA (lncRNA) HOXC-AS3 has been characterized as a cancer-related lncRNA in many types of cancer, while its role in colorectal cancer (CRC) is unknown. METHODS: The expression of HOXC-AS3 and TGF-ß2 were detected by RT-qPCR. Overexpression assays were performed to explore the interaction between HOXC-AS3 and TGF-ß2. A follow-up study was performed to explore the prognostic value of HOXC-AS3 for CRC. The direct interaction between HOXC-AS3 and miR-1269 was assessed with RNA-RNA pulldown assay. Transwell assays were performed to determine the role of HOXC-AS3 and TGF-ß2 in regulating CRC cell invasion and migration. RESULTS: HOXC-AS3 was significantly downregulated in CRC tissues, while TGF-ß2 was significantly upregulated in CRC tissues compared to that in adjacent non-cancer tissues of CRC patients. The follow-up study showed that low expression levels of HOXC-AS3 in CRC tissues were closely correlated with poor survival. Correlation analysis showed that HOXC-AS3 and TGF-ß2 were inversely correlated across CRC tissues but not non-cancer tissues. Overexpression of HOXC-AS3 in the two cell lines resulted in downregulation of TGF-ß2, while the expression of HOXC-AS3 was not affected by TGF-ß2. Transwell migration and invasion assay showed that overexpression of TGF-ß2 increased cell invasion and migration, while overexpression of HOXC-AS3 decreased cell migration and invasion. In addition, overexpression of HOXC-AS3 attenuated the effects of overexpression of TGF-ß2. MiR-1269 increased the expression of TGF-ß2. HOXC-AS3 directly interacted with miR-1269 in CRC cells. CONCLUSIONS: Upregulation of HOXC-AS3 inhibited TGF-ß2-induced colorectal cancer (CRC) cell migration and invasion possibly by sponging miR-1269.

LncRNA FEZF1-AS1 promotes colorectal cancer progression through regulating the miR-363-3p/PRRX1 pathway.

BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in the development of many cancers, including colorectal cancer (CRC). FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) is a key lncRNA in the regulation of CRC progression, but its potential molecular mechanisms need to be further explored. OBJECTIVES: To investigate the mechanism of lncRNA FEZF1-AS1 in the progression of CRC. MATERIAL AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure FEZF1-AS1 and miR-363-3p expression. Cell proliferation, migration and invasion were analyzed using Cell Counting Kit-8 (CCK-8) and transwell assays. Protein expression of epithelial-mesenchymal transformation (EMT)-related markers and paired-related homeobox 1 (PRRX1) were determined using western blot analysis. The interactions among FEZF1-AS1, miR-363-3p and PRRX1 were verified with dual-luciferase reporter assay. A xenograft model was constructed in vivo to confirm the role of FEZF1-AS1 in CRC tumor growth. RESULTS: We demonstrated that FEZF1-AS1 expression was upregulated in CRC, and its silencing reduced CRC cell proliferation, migration, invasion, and EMT. MiR-363-3p could be inhibited by FEZF1-AS1, which inhibitor could reverse the suppressive effect of FEZF1-AS1 silencing on CRC progression. Paired-related homeobox 1 could be targeted by miR-363-3p, and the inhibitory effect of FEZF1-AS1 knockdown on CRC progression could also be eliminated by PRRX1 overexpression. Furthermore, interference of FEZF1-AS1 reduced the tumor growth of CRC in vivo. CONCLUSIONS: Our data demonstrate that FEZF1-AS1 regulated PRRX1 expression to promote CRC progression via inhibition of miR-363-3p.

ANXA9 as a novel prognostic biomarker associated with immune infiltrates in gastric cancer.

BACKGROUND: Gastric cancer (GC) is the most prevalent malignancy among the digestive system tumors. Increasing evidence has revealed that lower mRNA expression of ANXA9 is associated with a poor prognosis in colorectal cancer. However, the role of ANXA9 in GC remains largely unknown. MATERIAL AND METHODS: The Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas databases were used to investigate the expression of ANXA9 in GC, which was then validated in the four Gene Expression Omnibus (GEO) datasets. The diagnostic value of ANXA9 for GC patients was demonstrated using a receiver operating characteristic (ROC) curve. The correlation between ANXA9 expression and clinicopathological parameters was analyzed in The Cancer Genome Atlas (TCGA) and UALCAN databases. The Kaplan-Meier (K-M) survival curve was used to elucidate the relationship between ANXA9 expression and the survival time of GC patients. We then performed a gene set enrichment analysis (GSEA) to explore the biological functions of ANXA9. The relationship of ANXA9 expression and cancer immune infiltrates was analyzed using the Tumor Immune Estimation Resource (TIMER). In addition, the potential mechanism of ANXA9 in GC was investigated by analyzing its related genes. RESULTS: ANXA9 was significantly up-regulated in GC tissues and showed obvious diagnostic value. The expression of ANXA9 was related to the age, gender, grade, TP53 mutation, and histological subtype of GC patients. We also found that ANXA9 expression was associated with immune-related biological function. ANXA9 expression was also correlated with the infiltration level of CD8+ T cells, neutrophils, and dendritic cells in GC. Additionally, copy number variation (VNV) of ANXA9 occurred in GC patients. Function enrichment analyses revealed that ANXA9 plays a role in the GC progression by interacting with its related genes. CONCLUSIONS: Our results provide strong evidence of ANXA9 expression as a prognostic indicator related to immune responses in GC.

Daphnoretin: An invasion inhibitor and apoptosis accelerator for colon cancer cells by regulating the Akt signal pathway.

The regulation of Daphnoretin on specific tumours (e.g. cervical cancer, lung cancer, osteosarcoma) has been documented, which still remains unclear for colon cancer cells. Our study explored the suppression of Daphnoretin and its molecular mechanism on the proliferation, apoptosis, invasion and migration of human colon cancer cell line HCT116. Our report showed the activity of HCT116 declined with time- and dose- dependence after Daphnoretin intervention, and a rise in G0/G1 ratio and decrease in G2/M ratio was observed. Daphnoretin-treated HCT116 had declined invasion and migration, increased apoptosis rate, and variations in gene expressions related to the Akt signal pathway. Those results indicated that Daphnoretin can inhibit the proliferation, invasion, and migration of HCT116 and promote its apoptosis by regulating the activity of Akt signal pathway.

Annexin A9 promotes invasion and metastasis of colorectal cancer and predicts poor prognosis.

Annexin A9 (ANXA9), a member of annexin family, has been reported be associated with colorectal cancer (CRC) carcinogenesis. However, the clinical significance of ANXA9 in CRC, particularly its correlation to invasion and metastasis remains ambiguous. The aim of the present study was to investigate the significance of ANXA9 in CRC and understand the molecular mechanism of ANXA9 in CRC invasion and metastasis. Expression levels of the ANXA9 protein in CRC tissues were detected using immunohistochemistry (IHC), and the clinical and prognostic value of ANXA9 was investigated. ANXA9­siRNA was utilized to investigate the effect and molecular mechanism of ANXA9 in HCT116 cells. The IHC result demonstrated that the positivity rate of the ANXA9 protein in CRC tissue was significantly higher than that in adjacent mucosa (P<0.05), which was consistent with the western blot results. ANXA9 protein expression levels are associated with invasion depth and lymphatic metastasis. Furthermore, patients with ANXA9­positive expression demonstrated a poor prognosis and ANXA9 was an independent risk factor for survival (P<0.05). After inhibiting ANXA9 in HCT116 cells, the activity and metastatic and invasion capacity of cells decreased significantly, and expression levels of ADAM metallopeptidase domain 17 and matrix metallopeptidase 9 were significantly downregulated, while the expression levels of tissue inhibitors of metalloproteinases­1 and E­cadherin were upregulated (P<0.05). Thus, positive ANXA9 expression may present as a novel marker for predicting poor prognosis in CRC patients, and ANXA9 may promote the invasion and metastasis of CRC by regulating invasion and metastasis­associated genes.

Functional analysis of HBO1 in tumor development and inhibitor screening.

The aim of the present study was to explore the functions of histone acetyltransferase binding to origin recog-nition complex (ORC) 1 (HBO1) during tumor development and to screen for HBO1 inhibitors. The chromatin immuno-precipitation sequencing (ChIP-seq) data of HBO1 in the RKO human colon cancer cell line (GSE33007) were downloaded from the Gene Expression Omnibus (GEO) database. The reads were then mapped back to a reference genome hg19. The PCR duplicate reads were removed by using SAMtools software and the shift was calculated using SPP and MaSC software. The peak calling was carried out using MACS 1.4.0 software. Furthermore, the inhibitors of HBO1 were screened out from the Specs database using Dock 6.6 software. The binding sites of HBO1 were mainly distributed in the intergenic, intronic and 3'-end regions. Further analysis revealed that a total of 9,467 target genes was identified around HBO1 binding sites in the RKO cell lines and those genes mainly participated in the cell cycle, biosynthetic process, as well as other processes. Finally, 5 inhibitors with best binding affinity in the positively charged cavity of HBO1 were screened out: i) 5-[(2-hydroxybenzylidene)amino] -2-(2­{4­[(2­hydroxy-benzylidene)amino]-2-sulfonatophenyl}vinyl)benzenesulfonate, ii) 3-[4-(3-bromo-4-{2-[4-(ethoxycarbonyl)anilino]-2-oxo-ethoxy}-5-methoxybenzylidene)­3­methyl­5­oxo -4,5-dihydro-1H-pyrazol-1-yl]benzoic acid, iii) 4-(4-{3-iodo­5­ methoxy­4-[2-(2-methoxyanilino)-2-oxoethoxy]benzylidene}-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoic acid, iv) 5-chloro-1,3-bis{[3,5,6-trihydroxy-4-(octyloxy)tetrahydro-2H-pyran-2-yl]methyl}-1,3-dihydro-2H-benzimidazol-2-one and v) 4-{[4-(tetradecylamino)-1-naphthyl]diazenyl}benzoic acid. As a whole, in this study, we identified the possible binding sites and biological functions of HBO1. The potential inhibitors of HBO1 were also screened, which prove to be helpful for the inhibition of HBO1 during tumor development.

Effects of phytoestrogen genistein on electrophysiology of human atrial fibers.

AIM: To study the electrophysiological effects of phytoestrogen genistein (GST) on human atrial fibers. METHODS: Parameters of action potential (AP) in human atrial special fibers were recorded using standard intracellular microelectrode technique. RESULTS: GST (10-100 micromol/L) decreased the velocity of diastolic (phase 4) depolarization (VDD) and rate of pacemaker firing (RPF), besides, GST (100 micromol/L) shortened the duration of 90 % repolarization of action potential (APD90). L-type Ca2+ channel agonist Bay K8644 (0.5 micromol/L) antagonized the inhibitory effects of GST on human atrial fibers, while pretreatment of the fibers with N(G)-nitro-L-arginine methyl ester (L-NAME, 1 mmol/L), an NO synthase inhibitor, failed to affect the electrophysiological effects of GST. CONCLUSION: GST exerted a negative chronotropic action and induced an accelerated repolarization of human atrial fibers. These effects were likely due to reduction in calcium influx.