HOTAIR as a diagnostic and prognostic biomarker of gastrointestinal cancers: an updated meta-analysis and bioinformatics analysis based on TCGA data.

Gastrointestinal cancers are the most common type of cancer affecting humans. High expression of HOX transcript antisense intergenic RNA (HOTAIR), a long noncoding RNA (lncRNA), in various types of different tumors may be associated with poor prognosis. In the present study, we performed a meta-analysis of the relationship between HOTAIR expression and gastrointestinal cancers. Five databases were comprehensively searched for all literature until January 2023. Moreover, the target genes of HOTAIR were predicted by coexpression analysis based on The Cancer Genome Atlas (TCGA) gene expression matrix for six gastrointestinal cancer types. Finally, the mechanism through which HOTAIR affects tumors of the digestive system was systematically reviewed. Our results showed that the high HOTAIR expression group had worse outcomes with a pooled hazard ratio (HR) of 1.56 (95% confidence interval [CI] = 1.38-1.75, P<0.001). Furthermore, HOTAIR was identified as an unfavorable prognostic factor for overall survival (OS) in the esophageal carcinoma (ESCA) and gastric cancer (GC), as the HR were 1.94 and 1.58, respectively. The high correlation between the expression of homeobox C (HOXC) family genes and HOTAIR, with correlation coefficients of 0.863 (HOXC11), 0.664 (HOXC10), 0.645 (HOXC8), and 0.581 (HOXC12). The 'cell cycle' pathway and pathways relating to infections, namely 'herpes simplex virus 1 infection' and 'complement and coagulation cascades' were significantly enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Also, we perform a systematic review to summarize the related oncogenic mechanism of HOTAIR. In conclusion, the HOTAIR has been identified as a potential prognostic factor in patients with gastrointestinal cancers.

Sublethal toxicity of graphene oxide in Caenorhabditis elegans under multi-generational exposure.

Nanomaterials have received increasing attentions owing to their potential hazards to the environment and human health; however, the multi-generational toxicity of graphene oxide under consecutive multi-generational exposure scenario still remains unclear. In the present study, Caenorhabditis elegans as an in vivo model organism was employed to explore the multi-generational toxicity effects of graphene oxide and the underlying mechanisms. Endpoints including development and lifespan, locomotion behaviors, defecation cycle, brood sizes, and oxidative response were evaluated in the parental generation and subsequent five filial generations. After continuous exposure for several generations, worms grew smaller and lived shorter. The locomotion behaviors were reduced across the filial generations and these reduced trends were following the impairments of locomotion-related neurons. In addition, the extended defecation cycles from the third filial generation were in consistency with the relative size reduction of the defecation related neuron. Simultaneously, the fertility function of the nematode was impaired under consecutive exposure as reduced brood sizes and oocytes numbers, increased apoptosis of germline, and aberrant expression of reproductive related genes ced-3, ced-4, ced-9, egl-1 and ced-13 were detected in exposed worms. Furthermore, the antioxidant enzyme, SOD-3 was significantly increased in the parent and filial generations. Thus, continuous multi-generational exposure to graphene oxide caused damage to the neuron development and the reproductive system in nematodes. These toxic effects could be reflected by indicators such as growth inhibition, shortened lifespan, and locomotion behavior impairment and induced oxidative response.

Sulforaphane induces S-phase arrest and apoptosis via p53-dependent manner in gastric cancer cells.

Sulforaphane (SFN) extracted from broccoli sprout has previously been investigated for its potential properties in cancers, however, the underlying mechanisms of the anticancer activity of SFN remain not fully understood. In the present study, we investigate the effects of SFN on cell proliferation, cell cycle, cell apoptosis, and also the expression of several cell cycle and apoptosis-related genes by MTT assay, flow cytometry and western blot analysis in gastric cancer (GC) cells. The results showed that SFN could impair the colony-forming ability in BGC-823 and MGC-803 cell lines compared with the control. In addition, SFN significantly suppressed cell proliferation by arresting the cell cycle at the S phase and enhancing cell apoptosis in GC cells in a dose-dependent manner. Western blot results showed that SFN treatment significantly increased the expression levels of p53, p21 and decreased CDK2 expression, which directly regulated the S phase transition. The Bax and cleaved-caspase-3 genes involved in apoptosis executive functions were significantly increased in a dose-dependent manner in BGC-823 and MGC-803 cells. These results suggested that SFN-induced S phase cell cycle arrest and apoptosis through p53-dependent manner in GC cells, which suggested that SFN has a potential therapeutic application in the treatment and prevention of GC.

Effects of Vitamin D3 on Intestinal Flora in a Mouse Model of Inflammatory Bowel Disease Treated with Rifaximin.

BACKGROUND Rifaximin is an antimicrobial agent used to treat inflammatory bowel disease (IBD). Vitamin D3 can control IBD due to its effects on inflammatory cytokines. The purpose of this study was to assess the effect of vitamin D3 on the intestinal flora of a dextran sulfate sodium (DSS)-induced mouse model treated with rifaximin. MATERIAL AND METHODS The mouse model of IBD was developed using DSS (4%) administered via the drinking water. Twenty-four male C57BL6 mice were divided into the control group with a normal diet (N=6), the DSS group with a normal diet (N=6), the DSS group with a normal diet treated with rifaximin (N=6), and the DSS group with a normal diet treated with rifaximin and vitamin D3 (N=6). After 14 days, the colonic tissue was studied histologically. Serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1ß (IL-1ß) and enzyme-linked immunosorbent assay (ELISA) were used to measure the level of IL-6 and P65, and phospho-p65 was measured by western blot. 16S rRNA gene sequencing was used to analyze fecal samples. RESULTS In the DSS mouse model of IBD, rifaximin reduced the inflammation severity of the colon and reduced the expression of phospho-p65, p65, TNF-alpha, and IL-6. In the DSS+rifaximin+vitamin D3 group, the therapeutic influences of rifaximin, in terms of weight loss and colonic disease activity, were significantly reduced, and the gut microbiota of the mice were completely changed in composition and diversity. CONCLUSIONS In a mouse model of IBD, treatment with vitamin D3 significantly increased the metabolism of rifaximin and reduced its therapeutic effects.