The role of non-coding RNA in the diagnosis and treatment of Helicobacter pylori-related gastric cancer, with a focus on inflammation and immune response.

Helicobacter pylori (H. pylori) is one of the globally recognized causative factors of gastric cancer (GC). Currently, no definite therapy and drugs for H. pylori-related GC have been widely acknowledged although H. pylori infection could be eradicated in early stage. Inflammation and immune response are spontaneous essential stages during H. pylori infection. H pylori may mediate immune escape by affecting inflammation and immune response, leading to gastric carcinogenesis. As an important component of transcriptome, non-coding RNAs (ncRNAs) have been proven to play crucial roles in the genesis and development of H. pylori-induced GC. This review briefly described the effects of ncRNAs on H. pylori-related GC from the perspective of inflammation and immune response, as well as their association with inflammatory reaction and immune microenvironment. We aim to explore the potential of ncRNAs as markers for the early diagnosis, prognosis, and treatment of H. pylori-related GC. The ncRNAs involved in H. pylori-related GC may all hold promise as novel therapeutic targets for immunotherapy.

RNA-sequencing reveals the expression profiles of tsRNAs and their potential carcinogenic role in cholangiocarcinoma.

BACKGROUND: Recently, the incidence of cholangiocarcinoma (CCA) has gradually increased. As CCA has a poor prognosis, the ideal survival rate is scarce for patients. The abnormal expressed tsRNAs may regulate the progression of a variety of tumors, and tsRNAs is expected to become a new diagnostic biomarker of cancer. However, the expression of tsRNAs is obscure and should be elucidated in CCA. METHODS: High-throughput RNA sequencing technology (RNA-seq) was utilized to determine the overall expression profiles of tsRNAs in three pairs CCA and adjacent normal tissues and to screen the tsRNAs that were differentially expressed. The target genes of dysregulated tsRNAs were predicted and the biological effects and potential signaling pathways of these target genes were explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate 11 differentially expressed tRFs with 12 pairs CCA and adjacent normal tissues. RESULTS: High-throughput RNA-seq totally demonstrated 535 dysregulated tsRNAs, of which 241 tsRNAs were upregulated, such as tRF-21-YLKZKWE5D，tRF-16-9NF5W8B，tRF-27-78YLKZKWE52，tRF-19-RLXN48KP，tRF-33-IK9NJ4S2I7L7DV，tRF-19-F8DHXYIV, and 294 tsRNAs were downregulated (tRF-20-739P8WQ0, tRF-34-JJ6RRNLIK898HR, tRF-17-VL8RPY5, tRF-23-YP9LON4VDP, tRF-39-EH623K76IR3DR2I2, tRF-17-18YKISM, tRF-19-Q1Q89PJZ, etc.) in CCA compared with adjacent normal tissues (|log2 [fold change] | ≥ 1 and p value <0.05). GO and KEGG enrichment analyses indicated that the target genes of dysregulated tRFs (tRF-34-JJ6RRNLIK898HR, tRF-38-0668K87SERM492V, and tRF-39-0668K87SERM492E2) were mainly enriched in the Notch signaling pathway, Hippo signaling pathway, cAMP signaling pathway and in growth hormone synthesis, secretion and action, etc. qRT-PCR result showed that tRF-34-JJ6RRNLIK898HR/tRF-38-0668K87SERM492V/tRF-39-0668K87SERM492E2 was downregulated (p = 0.021), and tRF-20-LE2WMK81 was upregulated in CCA (p = 0.033). CONCLUSION: Differentially expressed tRFs in CCA are enriched in many pathways associated with neoplasms, which may impact the tumor progression and have potential to be diagnostic biomarkers and therapeutic targets of CCA.

Predicting Prognosis of Hepatocellular Carcinoma Patients Based on the Expression Signatures of Mitophagy Genes.

Background: The unbalance of mitophagy was closely related to hepatocellular carcinoma (HCC) progression. At present, it has not been uncovered about the influence of mitophagy genes on HCC prognosis and their potential pathogenesis. Materials and Methods: The expression and clinical information of HCC in TCGA cohort were used to identify mitophagy differentially expressed genes (MDEGs) with prognostic value. The prognostic model of mitophagy genes was built and externally validated by LASSO regression in TCGA cohort and ICGC cohort, respectively. The function of the prognostic signature and its association with immune cell infiltration were explored. The profile of MDEGs was validated with 39 pairs HCC and paracarcinoma tissues by quantitative reverse transcription-PCR (qRT-PCR). Results: A total of 18 mitophagy genes that were upregulated and contributed to poor prognosis in HCC were identified. These genes could interact with each other. The correlation analysis showed that there was positively correlation among mitophagy genes. According to optimal λ value, 8 mitophagy gene signatures were involved in prognostic model. Based on median risk scores, HCC patients were divided into high-risk group and low-risk group. Compared with the low-risk group, the high-risk group has worse overall survival in TCGA cohort and ICGC cohort. The univariate and multivariate Cox regression analysis suggested that risk score was an independent prognostic factor of HCC patients. Time-dependent ROC curve was used to identify and validate good predicting performance of the prognostic model. Enrichment analysis showed that risk differentially expressed genes were enriched in various metabolism and cell division processes. The immune cell infiltration score and immune function were significantly different in two groups. qRT-PCR validation result showed that QSTM1, CSNK2B, PGAM5, and ATG5 were upregulated. Conclusion: Mitophagy genes could influence HCC progression through regulating the metabolism and immune functions and could be used to predict prognosis and considered as potential prognostic biomarker and precise therapeutic target of HCC.

Nucleotide excision repair pathway gene polymorphisms are associated with risk and prognosis of colorectal cancer.

BACKGROUND: Single nucleotide polymorphisms (SNPs) are universally present in nucleotide excision repair (NER) pathway genes, which could make impacts on colorectal carcinogenesis and prognosis. AIM: To explore the association of all tagSNPs in NER pathway genes with colorectal cancer (CRC) risk and prognosis in a northern Chinese population by a two-stage case-control design composed of a discovery and validation stage. METHODS: Genotyping for NER SNPs was performed using kompetitive allele specific PCR. In the discovery stage, 39 tagSNPs in eight genes were genotyped in 368 subjects, including 184 CRC cases and 184 individual-matched controls. In the validation stage, 13 SNPs in six genes were analyzed in a total of 1712 subjects, including 854 CRC cases and 858 CRC-free controls. RESULTS: Two SNPs (XPA rs10817938 and XPC rs2607775) were associated with an increased CRC risk in overall and stratification analyses. Significant cumulative and interaction effects were also demonstrated in the studied SNPs on CRC risk. Another two SNPs (ERCC2 rs1052555 and ERCC5 rs2228959) were newly found to be associated with a poor overall survival of CRC patients. CONCLUSION: Our findings suggest novel SNPs in NER pathway genes that can be predictive for CRC risk and prognosis in a large-scale Chinese population. The present study has referential values for the identification of all-round NER-based genetic biomarkers in predicting the susceptibility and clinical outcome of CRC.

Synthesis, crystal structure and biological evaluation of a main group seven-coordinated bismuth(III) complex with 2-acetylpyridine N4-phenylthiosemicarbazone.

Up to now, bismuth(III) complexes with thiosemicarbazones have been comparatively rare. Here, a main group seven-coordinated bismuth(III) complex [Bi(L)(NO3)2(CH3CH2OH)] (1) (HL = 2-acetylpyridine N(4)-phenylthiosemicarbazone) has been synthesized and characterized by elemental analysis, IR, (1)H NMR and single-crystal X-ray diffraction studies. The cytotoxicity data suggest that 1 exhibits higher in vitro antiproliferative activity in four human cancer cells tested. Its possible apoptotic mechanism has been evaluated in HepG2 cells. Compound 1 promotes a dose-dependent apoptosis in HepG2 cells and the apoptosis is associated with an increase in intracellular reactive oxygen species (ROS) production and reduction of mitochondrial membrane potential (MMP).

[Analysis of sucrose esters by thin-layer chromatography].

The thin-layer chromatographic method of sucrose esters was developed by the use of toluene-ethyl acetate-methanol-water (10:5:4.5:0.2 in volume ratio) as a mobile phase. Sucrose esters were developed by ascending technique on the silica gel G plate, visualized by urea-phosphoric acid-n-butanol with blue spots. The Rf value of monoester was 0.16 and those of higher esters were 0.38 - 0.93. The calibration curve was linear in the range of 25 microg - 250 microg with the detection limit of 0.1 microg. Accuracies were certified by normalization method and external standard method with t-test. The results were /t/ = 0.627(< 2.571) and /t/ = 1.123(<2.571) and RSDs were 3.03% and 3.08% (n = 6) respectively for S-1570. Contents of monoester of different sucrose esters were determined, which could provide reference for synthetic conditions and application range of sucrose esters.