Quercetin Antagonizes Esophagus Cancer by Modulating miR-1-3p/TAGLN2 Pathway-Dependent Growth and Metastasis.

The progression of esophagus cancer (EC) is associated with the alterative expressions of multiple microRNAs (miRs). MiR-1-3p is reported to inhibit the development of EC by targeting TAGLN2. Quercetin (Que) is a natural compound capable of antagonizing esophagus carcinoma (EC). In the current study, the role of miR-1-3p/TAGLN2 axis in the anti-EC function of Que was explored. Human EC cell lines KYSE-510 and TE-7 were treated with Que. Then the effects of Que on the growth and metastasis of EC cells, and on the activity of miR-1-3p/TAGLN2 axis were detected. The interaction between Que and miR-1-3p axis was further assessed by inhibiting miR-1-3p level in EC cells. The results showed that the treatment of Que impaired the growth and induced cell apoptosis in EC cells. The invasive ability of EC cells was also suppressed by Que. At molecular level, the expression of miR-1-3p was induced, while the expression of TAGLN2 was suppressed by Que. Moreover, the anti-EC effects of Que were blocked by miR-1-3p inhibition, which was represented by the restored growth and invasion of EC cells. Collectively, the current study demonstrated that Que exerted inhibitory effects on EC cells by inducing miR-1-3p.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1972125.

Suppression of long non-coding RNA MALAT1 inhibits survival and metastasis of esophagus cancer cells by sponging miR-1-3p/CORO1C/TPM3 axis.

Esophageal cancer (EC) is a malignancy causing lots of mortality worldwide. Long non-coding RNAs (lncRNAs) are involved in the progression of multiple cancer types. The present study aimed to explore the function and associated mechanisms of lncRNA metastasis-associated lung adenocarcinoma transcript1 (MALAT1) in EC development by focusing on its interaction with miR-1-3p. The levels of MALAT1 and miR-1-3p were investigated in clinical EC specimens. Then, the expression of MALAT1 was knocked down in EC cell lines, and the effects of MALAT1 inhibition on the viability, migration, and invasion, and miR-1-3p/Coronin-1C (CORO1C)/Tropomyosin3 (TPM3) axis in EC cells were detected. The interaction between MALAT1 and miR-1-3p in the progression of EC was further determined by suppressing the expression of miR-1-3p in MALAT1 inhibition cells. The results were further verified with EC xenograft mice model. MALAT1 level was downregulated, while miR-1-3p level was upregulated in EC specimens. The inhibition of MALAT1 suppressed the viability, migration, and invasion in EC cell lines. The changes in phenotypes of EC cells were associated with the upregulation of miR-1-3p level and inhibition of CORO1C/TPM3 activity. Furthermore, the results of dual-luciferase assay showed the direct binding of MALAT1 to the seed sequence of miR-1-3p. The suppressed level of miR-1-3p not only induced the activity of CORO1C/TPM3 signaling, but also upregulated MALAT1 expression, indicating the reciprocal regulation between the two factors. The inhibition of MALAT1 also inhibited tumor growth and epithelial-mesenchymal transition (EMT) in mice model, which was reversed by miR-1-3p inhibition. Collectively, MALAT1 was important to the survival and metastasis of EC cells by sponging miR-1-3p.

Helicobacter pylori infection alters gastric microbiota structure and biological functions in patients with gastric ulcer or duodenal ulcer.

BACKGROUND: Helicobacter pylori (H. pylori) infection is closely associated with gastrointestinal diseases. Our preliminary studies have indicated that H. pylori infection had a significant impact on the mucosal microbiome structure in patients with gastric ulcer (GU) or duodenal ulcer (DU). AIM: To investigate the contributions of H. pylori infection and the mucosal microbiome to the pathogenesis and progression of ulcerative diseases. METHODS: Patients with H. pylori infection and either GU or DU, and healthy individuals without H. pylori infection were included. Gastric or duodenal mucosal samples was obtained and subjected to metagenomic sequencing. The compositions of the microbial communities and their metabolic functions in the mucosal tissues were analyzed. RESULTS: Compared with that in the healthy individuals, the gastric mucosal microbiota in the H. pylori-positive patients with GU was dominated by H. pylori, with significantly reduced biodiversity. The intergroup differential functions, which were enriched in the H. pylori-positive GU patients, were all derived from H. pylori, particularly those concerning transfer RNA queuosine-modification and the synthesis of demethylmenaquinones or menaquinones. A significant enrichment of the uibE gene was detected in the synthesis pathway. There was no significant difference in microbial diversity between the H. pylori-positive DU patients and healthy controls. CONCLUSION: H. pylori infection significantly alters the gastric microbiota structure, diversity, and biological functions, which may be important contributing factors for GU.

Self-assembled amphiphilic copolymers-doxorubicin conjugated nanoparticles for gastric cancer therapy with low in vivo toxicity and high efficacy.

Amphiphilic copolymers have long been utilized to turn hydrophobic anticancer drugs into nanoparticles administered to patients with cancer. A lack of stability in these monotherapies may be blamed for their poor clinical results in patients with cancer. We propose novel nanotherapies based on polymeric small prodrugs that preserve pharmacologic effectiveness while significantly reducing the toxicity of the fabricated drugs in animals to overcome this problem. Doxorubicin is attached to the end of the PLA fragments through a hydrolyzable ester bond utilizing methoxypolyethylene glycol-block-poly(d, l-lactic acid) (mPEG-PCL(2K)) with conjugates to mimic the self-assembly of colloidal nanotherapies. In a gastric cancer xenograft model, this nanotherapy displays a long-lasting suppression of tumor growth once a reasonable dosage is administered. Our findings imply that a toxic chemical and hydrophobic can be converted into therapeutic effective self-delivery nanotreatment.

Fabrication of novel ruthenium loaded silk fibroin nanomaterials for fingolimod release improved antitumor efficacy in hepatocellular carcinoma.

Cancer targeted nanomaterials-based drug delivery systems have been described as promising. In this work, we employed silk fibroin (SF), ruthenium nanomaterials (RuNMs), heptapeptide (T7), and fingolimod (FTY720) to construct a pH-responsive smart nanomaterials drug delivery system. They were spherical with a mean size of around 120 nm, which may have contributed to the improved penetration and retention of the NMs in tumour areas. T7-FTY720@SF-RuNMs had an encapsulation efficiency (EE) of 72.51 ± 4.02%. When the pH of an environment is acidic, the release of FTY720 from nanocarriers is enhanced. T7-FTY720@SF-RuNMs demonstrated increased cellular uptake selective and anticancer efficacy for hepatocellular cancer in both in vitro and in vivo experiments. Additionally, the in vivo biodistribution investigation showed that T7-FTY720@SF-RuNMs could efficiently aggregate in the tumour location, improving their in vivo potential to kill cancer cells. T7-FTY720@SF-RuNMs demonstrated little toxicity to tumour-bearing animals in investigations of histology and immunohistochemistry, showing that the fabricated NMs are biocompatible in vivo. For the treatment of hepatocellular cancer, the T7-FTY720@SF-RuNMs delivery method offers significant promise.

Long non-coding RNA LINC00240 promotes gastric cancer progression via modulating miR-338-5p/METTL3 axis.

Gastric cancer (GC) is a common cancer with high incidence. Understanding the epidemiology and physiopathology of GC is crucial for formulating novel therapeutic strategies. Recent studies have implicated long non-coding RNA LINC00240, miR-338-5p and methyltransferase-like 3 (METTL3) in the progression of GC. In this study, we investigated the functional role of LINC00240/miR-338-5p/METTL3 axis in regulating the aggressiveness of GC cells. We first demonstrated that LINC00240 was upregulated in GC tissues and GC cell lines. High expression of LINC00240 was associated with advanced TNM stage, a higher extent of distant metastasis and lymph nodes metastasis, and the poor overall and disease-free survival of the patients. In GC cell lines, the knockdown of LINC00240 inhibited GC cell proliferation and migration, but induced cell apoptosis. We further identified and validated the functional interaction between LINC00240 and miR-338-5p. miR-338-5p seemed to function as a downstream target negatively regulated by LINC00240, and miR-338-5p could target METTL3 at 3' UTR to downregulate its expression. In GC tissues, the expression of miR-338-5p was negatively correlated with LINC00240, and the expression of miR-338-5p was negatively correlated with METTL3. Importantly, miR-338-5p inhibitor or METTL3 overexpression could rescue the inhibitory effect of LINC00240 knockdown on cell proliferation and migration, and inhibit the apoptosis induction in GC cells. Taken together, our data imply that the upregulation of LINC00240 in GC cells promotes the malignant phenotype by modulating miR-338-5p/METTL3 axis, which could serve as potential therapeutic targets for GC treatment.

SLC39A4 as a Novel Prognosis Marker Promotes Tumor Progression in Esophageal Squamous Cell Carcinoma.

BACKGROUND: Solute carrier family 39 member 4 (SLC39A4) has been reported to play an oncogenic role in several cancers. However, the role of SLC39A4 in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we aimed to explore the clinical significance and function of SLC39A4 in ESCC. METHODS: The Cancer Genome Atlas and Gene Expression Omnibus databases were analyzed to assess the level of SLC39A4 in ESCC. The expression level of SLC39A4 was measured by RT-qPCR and immunohistochemistry in a cohort of 73 patients aged 45-65 years with ESCC. Kaplan-Meier analysis was used to identify the correlation between SLC39A4 and the prognosis of ESCC patients. In vitro experiments were conducted to explore the biological function of SLC39A4 in ESCC cell line TE-1 and TE-10. RESULTS: The mRNA level of SLC39A4 was significantly enhanced in ESCC specimens, which was in line with the outcome of online databases analysis. Moreover, the aberrant expression of SLC39A4 was positively correlated with clinical stage, T categories and lymph node metastasis. Kaplan-Meier analysis indicated that elevated SLC39A4 expression predicted poor prognosis of patients with ESCC. Furthermore, the in vitro experiments showed that SLC39A4 knockdown not only impaired the proliferation and motility capacities of ESCC cells but also enhanced the sensitivity to cisplatin treatment. CONCLUSION: Our findings suggest that SLC39A4 could serve as a novel prognosis biomarker to promote ESCC progression; however, the mechanism of SLC39A4 in ESCC remains to be further explored.

Association between Helicobacter pylori infection and non-alcoholic fatty liver disease in North Chinese: a cross-sectional study.

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease. Previous studies on the association between Helicobacter pylori (HP) infection and NAFLD are inconsistent. Our study was aimed to find out the relationship between HP infection and NAFLD. We performed a large cross-sectional study in northern Chinese adults in 2015. 13C-urea breath tests were used to determine HP infection status. Abdominal ultrasonography was performed to diagnose NAFLD. Multivariable logistic regression was conducted to identify the association between HP infection and NAFLD. A total of 4081 individuals were included in this study; 2137 (52.36%) participants were HP-positive, and 1022 (47.82%) were diagnosed with NAFLD in HP-positive individuals. The odds ratios (OR) and 95% confidence intervals (CI) of participants with HP infection for NAFLD were 1.20 (1.06-1.36) in crude model and 1.27 (1.07-1.50) in fully adjusted model. When stratified by sex and dyslipidemia, the fully adjusted OR and 95% CI for NAFLD were 1.22 (1.10-1.80) in females and 1.44 (1.18-1.75) in subjects with dyslipidemia. There were not significant increased OR for NAFLD when stratified by age. The study indicate that HP infection is associated with NAFLD, particularly in females and patients with dyslipidemia, suggesting that HP eradication might be an alternative method for the prevention or treatment of NAFLD treatment.

Comparisons Between Bacterial Communities in Mucosa in Patients With Gastric Antrum Ulcer and a Duodenal Ulcer.

Objective: To identify and compare the bacterial community profile of mucosal tissues from a gastric antrum ulcer and a duodenal ulcer in Helicobacter pylori (Hp) positive dyspeptic patients. Methods: Genomic DNA was extracted from the mucosal tissues obtained from 18 patients diagnosed with gastric antrum or duodenal ulcers. A library was constructed using 16S rRNA gene amplification, and Miseq high-throughput sequencing was used to analyse the amplified products. Bioinformatics methods, including operational taxonomic units (OTUs), hierarchical clustering, and a diversity analysis, were performed to investigate and characterize the community composition. Results: The proportion of Helicobacter in the mucosa of patients with a gastric antrum ulcer was significantly higher than that of patients with a duodenal ulcer. However, the diversity of the bacterial community in the gastric antrum ulcer mucosa was significantly lower compared with the mucosa of the duodenal ulcer. There were significant differences in microbial community structure between the gastric antrum ulcer and the duodenal ulcer. Notably, Helicobacter, Prevotella, Neisseria, and Streptococcus were also predominant genera in the bacterial community of the duodenal ulcer mucosa, and they outnumbered those species in gastric antrum ulcer mucosa. Conclusion: The bacterial community composition and the corresponding abundance differ between the mucosal tissues of Hp positive gastric antrum ulcer and duodenal ulcer patients. Additionally, the bacterial community diversity in the mucosal tissues from gastric duodenal ulcer patients is higher than that from gastric antrum ulcer patients, and Helicobacter is not the absolutely predominant genus.

Schistosoma japonicum ova maintains epithelial barrier function during experimental colitis.

AIM: To evaluate the impacts of Schistosoma japonicum (S. japonicum) ova on the tight junction barriers in a trinitrobenzenesulfonic acid (TNBS)-induced colitis model. METHODS: Balb/c mice were randomly divided into three groups: control group; TNBS(+)ova(-) group and TNBS(+)ova(+) group. TNBS was used intracolonic to induce colitis and mice of the TNBS(+)ova(+) group were pre-exposed to S. japonicum ova as a prophylactic intervention. Colon inflammation was quantified using following variables: mouse mortality, weight loss, colon extent and microscopic inflammation score. Serum expression of tumor necrosis factor-α and interferon-γ were assessed to evaluate the systemic inflammatory response. NOD2 and its mRNA were also tested. Bacterial translocations were tested by culturing blood and several tissues. ZO-1 and occludin were chosen as the representations of tight junction proteins. Both the proteins and mRNA were assessed. RESULTS: Ova pre-treatment contributed to the relief of colitis and decreased the mortality of the models. NOD2 expression was significantly downregulated when pretreated with the ova. The TNBS injection caused a significant downregulation of ZO-1 and occludin mRNA together with their proteins in the colon; ova pre-exposure reversed these alterations. Treatment with S. japonicum ova in the colitis model caused lower intestinal bacterial translocation frequency. CONCLUSION: S. japonicum ova can maintain epithelial barrier function through increasing tight junction proteins, thus causing less exposure of NOD2 to the luminal antigens which may activate a series of inflammatory factors and induce colitis.