Paclitaxel-resistant related lncRNA DBH-AS1 promotes the proliferation and invasion of esophageal cancer.

OBJECTIVE: Chemoresistance is one of the main obstacles in the clinical treatment of cancer. However, secondary resistance to paclitaxel poses new challenges for cancer treatment. Long noncoding RNAs regulate cellular functions at different levels and mechanisms and play an important role in the biological behavior of tumors. MATERIALS AND METHODS: LncRNA microarrays were used to detect lncRNAs in Paclitaxel-resistant cells and corresponding parental cells. Cell counting kit 8 and Transwell analysis were used to test the effect of lncRNA on function. RESULTS: The expression of lncRNA DBH-AS1 in TE-4 TAX-R cells was significantly higher than that in TE-4 cells. Transwell analysis showed that the overexpression of lncRNA DBH-AS1 increased the invasion of Eca cells. Cell scratches and Transwell analysis showed that the overexpression of lncRNA DBH-AS1 in Eca cell culture supernatants promoted the migration and invasion of HUVEC. In addition, lncRNA DBH-AS1 relies on miR-21 to regulate the expression of YOD1. CONCLUSIONS: Paclitaxel-resistant lncRNA DBH-AS1 appears to promote ECa cell proliferation and invasion by acting as a ceRNA and regulating miR-21-5p /YOD1 signaling pathway.

Exploration and validation of the prognostic value of RNA-binding proteins in hepatocellular carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Increasing evidence suggests that the dysregulation of RNA-binding proteins (RBPs) is involved in the development of various cancers. However, there is a paucity of studies investigating the roles of RBPs in HCC. MATERIALS AND METHODS: Data on HCC samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases (available at: www.ncbi.nlm.nih.gov/geo), and data regarding human RBPs were integrated from SONAR, XRNAX, and CARIC results. We identified modules associated with prognosis using weighted gene co-expression network analysis (WGCNA) and performed functional enrichment analysis. Univariate and least absolute shrinkage and selection operator (LASSO) regression analyses were used to identify prognostic RBPs and establish a prediction model. According to the median risk score, we separated patients into high- and low-risk groups and investigated the differences in immune cell infiltration, somatic mutations, and gene set enrichment. Univariate and multivariate regression analyses were used to identify prognostic factors for HCC. A nomogram was constructed, and its performance was evaluated with calibration curves. RESULTS: Sixteen RBPs (MEX3A, TTK, MRPL53, IQGAP3, PFN2, IMPDH1, TCOF1, DYNC1LI1, EIF2B4, NOL10, GNL2, EIF1B, PSMD1, AHSA1, SEC61A1, and YBX1) were identified as prognostic genes, and a prognostic model was established. Survival analysis indicated that the model had good predictive performance and that a high-risk score was significantly related to a poor prognosis. Additionally, there were significant differences in immune cell infiltration, somatic mutations, and gene set enrichment between the high- and low-risk groups. Univariate and multivariate regression analyses indicated that the RBP-based signature was an independent prognostic factor for HCC. The nomogram based on 16 RBPs performed well in predicting the overall survival of HCC patients. CONCLUSIONS: The RBP-based signature is an independent prognostic factor for HCC, and this study could provide an innovative method for analyzing prognostic biomarkers and therapeutic targets for HCC.

Intervention effects of four exercise modalities on nonalcoholic fatty liver disease: a systematic review and Bayesian network meta-analysis.

OBJECTIVE: This study aimed to evaluate the effect of four exercise modalities on patients with nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: Databases of CNKI, Wanfang, VIP, Web of Science, PubMed, Cochrane Library, Medline, and Embase were searched for relevant studies. The literature search was restricted to those published between January 2010 and June 2021. Randomized controlled trials of exercise interventions on NAFLD were collected. Data were presented as statistical graphics using ADDIS 1.16.5 and R-Studio 4.1. RESULTS: Seventeen controlled studies analyzing 1627 patients with NAFLD were included. Patients were divided into the control group (n=688), aerobic training group (AT, n=554), resistance training group (RT, n=232), high-intensity interval training group (HIIT, n=53), and aerobic training with resistance training group (AT+RT, n=100). Results of the statistical analysis showed that the combined exercise intervention had the most significant effect on the total serum cholesterol of patients' mean difference [MD=0.47(0.23, 0.73), p<0.05]. Levels of alanine aminotransferase and aspartate aminotransferase were improved, but no significant difference was found in their levels in the four groups of exercise intervention. The intervention effect of the four exercises on blood lipid and liver enzymes in patients with NAFLD was in the order of AT+RT > HIIT > RT > AT > control. CONCLUSIONS: Exercise interventions are recommended as stand-alone or adjunctive therapy. For patients with NAFLD who can tolerate various exercises, priority should be given to AT+RT exercise 4-5 times per week. The exercise intensity should be 50%-70% of the maximum heart rate and performed for >3 months to improve the effectiveness of the exercise supervision intervention.

MiRNA-338-3p regulates cervical cancer cells proliferation by targeting MACC1 through MAPK signaling pathway.

OBJECTIVE: Aberrant expression of miR-338-3p has recently involved in the progression and development of various types of malignant tumors, but its role in the progression of cervical cancer remains unknown. This study aims to investigate the role of miR-338-3p/MACC1 axis in the progression of cervical cancer. PATIENTS AND METHODS: MiR-338-3p and metastasis-associated in colon cancer 1 (MACC1) expression was determined in cervical cancer by quantitative real-time PCR (qRT-PCR). We explored the association of miR-338-3p expression with pathology and prognosis in cervical cancer patients. We explored the function of miR-338-3p and MACC1 on cell proliferation. A luciferase reporter assay was conducted to confirm the target gene of miR-338-3p in cervical cancer cells. RESULTS: In the present work, our data showed that the expression of miR-338-3p was substantially decreased in cervical cancer tissues and associated with advanced FIGO stage, lymph node metastasis, depth of cervical invasion and poor overall survival. However, the MACC1 had an opposite expression. Mechanistically, we identified that MACC1 which acted as a functional downstream target for miR-338-3p. Furthermore, overexpression of miR-338-3p decreased expression of MACC1 in cervical cancer cells could significantly inhibit cervical cancer cell proliferation and induce cells apoptosis. Interestingly, miR-338-3p and MACC1 had proven to be involved in the progression of cervical cancer cells by regulating mitogen-activated protein kinase (MAPK) signaling pathway. CONCLUSIONS: Our results suggested miR-338-3p/MACC1/MAPK regulatory pathway play an important role in the progression of cervical cancer.

Submucosal tunneling endoscopic resection using methylene-blue guidance for cardial subepithelial tumors originating from the muscularis propria layer.

Submucosal tunneling endoscopic resection (STER) of subepithelial tumors (SETs) originating from the muscularis propria (MP) layer in the cardia is rarely performed due to the difficulty of creating a submucosal tunnel for resection. The aim of this study is to evaluate the feasibility of STER using methylene-blue guidance for SETs originating from the MP layer in the cardia. From January 2012 to December 2014, 56 patients with SETs originating from the MP layer in the cardia were treated with STER using methylene-blue guidance. The complete resection rate and adverse event rate were the main outcome measurements. Successful complete resection by STER was achieved in all 56 cases (100%). The median size of the tumor was 1.8 cm. Nine patients (15.3%) had adverse events including subcutaneous emphysema, pneumoperitoneum, pneumothorax, and pleural effusion. These nine patients recovered successfully after conservative treatment without endoscopic or surgical intervention. No residual or recurrent tumors were detected in any patient during the follow-up period (median, 25 months). The adverse event rate was significantly higher for tumors originating in the deeper MP layers (46.7%) than in the superficial MP layers (4.9%) (P < 0.05), differed significantly according to tumor size (5.4% for tumors < 2.0 cm vs. 36.8% for tumors ≥ 2.0 cm; P < 0.05), and also differed significantly in relation to the tumor growth pattern (4.1% for the intraluminal growth vs. 100% for the extraluminal growth; P < 0.001). STER using methylene-blue guidance appears to be a feasible method for removing SETs originating from the MP layer in the cardia.

TRAF1 is a key mediator for hepatic ischemia/reperfusion injury.

Tumor necrosis factor receptor-associated factor 1 (TRAF1), an adapter in signal transduction, is involved in immunity and in apoptotic processes in various cell types. However, little is known about its function and the molecular mechanism of its activation during liver injury. This study tested the hypothesis that TRAF1 is a mediator of cell injury after hepatic ischemia/reperfusion injury (I/R). In a mouse hepatic I/R injury model, we found that TRAF1 expression was highly induced. TRAF1 deficiency was liver protective, whereas sustained TRAF1 overexpression aggravated liver injury in response to hepatic I/R injury. Mechanistic studies demonstrated that a deficiency of TRAF1 in cultured hepatocytes led to the inhibition of NF-κB-mediated inflammatory responses, suppression of the ASK/JNK pro-death pathway and promotion of cellular regeneration capacity. In contrast, the converse occurred in hepatocyte-specific TRAF1 transgenic mice. TRAF1 activated the ASK1/JNK pathway and promoted hepatic injury. Our study demonstrates that TRAF1 is a crucial early mediator of hepatic I/R injury and suggests that TRAF1 may be a potential gene therapy target for the treatment of liver injury.

IRF4 is a novel mediator for neuronal survival in ischaemic stroke.

Neuroprotection following ischaemic stroke is driven by the interplay between regulatory transcription factors and endogenous protective factors. IRF4, a member of the interferon regulatory factor (IRF) family, is implicated in the survival of tumour cells. However, its role in the survival of normal cells including neurons remains elusive. Using genetic approaches, we established a central role for IRF4 in protection against ischaemia/reperfusion (I/R)-induced neuronal death. IRF4 was expressed in neurons, and induced by ischaemic stroke. Neuron-specific IRF4 transgenic (IRF4-TG) mice exhibited reduced infarct lesions, and this effect was reversed in IRF4-knockout mice. Notably, we revealed that IRF4 rescues neurons from I/R-induced death both in vivo and in vitro. Integrative transcriptional and cell survival analyses showed that IRF4 functions mechanistically as a transcription activator of serum response factor (SRF) crucial to salvage neurons during stroke. Indeed, the expression of SRF and SRF-dependent molecules was significantly upregulated upon IRF4 overexpression and conversely inhibited upon IRF4 ablation. Similar results were observed in oxygen glucose deprivation (OGD)-treated primary cortical neurons. Furthermore, we identified the IRF4-binding site in the promoter region of the SRF gene essential for its transcription. To verify the IRF4-SRF axis in vivo, we generated neuron-specific SRF knockout mice, in which SRF exerted profound cerebroprotective effects similar to those of IRF4. More importantly, the phenotype observed in IRF4-TG mice was completely reversed by SRF ablation. Thus, we have shown that the IRF4-SRF axis is a novel signalling pathway critical for neuronal survival in the setting of ischaemic stroke.

A genome-specific repetitive DNA sequence from Oryza eichingeri: characterization, localization, and introgression to O. sativa.

In the course of transferring the brown planthopper resistance from a diploid, CC-genome wild rice species, Oryza eichingeri (IRGC acc. 105159 and 105163), to the cultivated rice variety 02428, we have isolated many alien addition and introgression lines. The O. eichingeri chromatin in some of these lines has previously been identified using genomic in situ hybridization and molecular-marker analysis. Here we cloned a tandemly repetitive DNA sequence from O. eichingeri IRGC acc105163, and detected it in 25 introgression lines. This repetitive DNA sequence showed high specificity to the rice CC genome, but was absent from all the four tetraploid species with BBCC or CCDD genomes. The monomer in this repetitive DNA sequence is 325-366-bp long, with a copy number of about 5,000 per 1 C of the O. eichingerigenome, showing 88% homology to a repetitive DNA sequence isolated from Oryza officinalis(2n=2 x=24, CC). Fluorescent in situ hybridization revealed 11 signals distributed over eight O. eichingeri chromosomes, mostly in terminal or subterminal regions.

The Arabidopsis phytochrome B gene influences growth of the apple rootstock M26.

The apple rootstock M26 (Malus domestica) was infected with a binary vector system of Agrobacterium tumefaciens carrying the neomycin phosphotransferase II and Arabidopsis phyB genes. Thirteen transformed clones were obtained from 329 infected leaves. Five of the clones had a single copy integration, six clones had two copies, one clone had five copies and one of the clones had eight copies of the phyB gene integrated. No differences in rooting were found between transformed and untransformed plants. The stem length was reduced in nine of the 13 transgenic clones, and shoot, root and plant dry weights were reduced in all transformed clones compared with untransformed control plants. Northern analysis showed that the Arabidopsis phyB gene was expressed in the transformed clones.