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Lactobacillus-containing and Bifidobacterium-containing probiotic compound preparation during initial H. pylori eradication therapy in the adult may have beneficial effects on eradication rate and incidence of total side effects.

Reversible post-translational modifications represent a mechanism to control tumor metabolism. Here we show that mitochondrial Sirtuin5 (SIRT5), which mediates lysine desuccinylation, deglutarylation, and demalonylation, plays a role in colorectal cancer (CRC) glutamine metabolic rewiring. Metabolic profiling identifies that deletion of SIRT5 causes a marked decrease in 13C-glutamine incorporation into tricarboxylic-acid (TCA) cycle intermediates and glutamine-derived non-essential amino acids. This reduces the building blocks required for rapid growth. Mechanistically, the direct interaction between SIRT5 and glutamate dehydrogenase 1 (GLUD1) causes deglutarylation and functional activation of GLUD1, a critical regulator of cellular glutaminolysis. Consistently, GLUD1 knockdown diminishes SIRT5-induced proliferation, both in vivo and in vitro. Clinically, overexpression of SIRT5 is significantly correlated with poor prognosis in CRC. Thus, SIRT5 supports the anaplerotic entry of glutamine into the TCA cycle in malignant phenotypes of CRC via activating GLUD1.

Background Currently, tRNA-derived small RNAs (tsRNAs) are recognized as a novel and potential type of non-coding RNAs (ncRNAs), which participate in various cellular processes and play an essential role in cancer progression. However, tsRNAs involvement in colorectal cancer (CRC) progression remains unclear. Methods Sequencing analyses were performed to explore the tsRNAs with differential expression in CRC. Gain- and loss-of functions of 5’tiRNA-His-GTG were performed in CRC cells and xenograft tumor to discover its role in the progression of CRC. Hypoxia culture and hypoxia inducible factor 1 subunit alpha (HIF1α) inhibitors were performed to uncover the biogenesis of 5’tiRNA-His-GTG. The regulation of 5’tiRNA-His-GTG for large tumor suppressor kinase 2 (LATS2) were identified by luciferase reporter assay, western blot, and rescue experiments. Results Here, our study uncovered the profile of tsRNAs in human CRC tissues and confirmed a specific tRNA half, 5’tiRNA-His-GTG, is upregulated in CRC tissues. Then, in vitro and in vivo experiments revealed the oncogenic role of 5’tiRNA-His-GTG in CRC and found that targeting 5’tiRNA-His-GTG can induce cell apoptosis. Mechanistically, the generation of 5’tiRNA-His-GTG seems to be a responsive process of tumor hypoxic microenvironment, and it is regulated via the HIF1α/angiogenin (ANG) axis. Remarkably, LATS2 was found to be an important and major target of 5’tiRNA-His-GTG, which renders 5’tiRNA-His-GTG to “turn off” hippo signaling pathway and finally promotes the expression of pro-proliferation and anti-apoptosis related genes. Conclusions In summary, the findings revealed a specific 5’tiRNA-His-GTG-engaged pathway in CRC progression and provided clues to design a novel therapeutic target in CRC.

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ObjectiveInterferon γ release assay (IGRA) is commonly used to diagnose latent TB infection (LTBI). Immunosuppressive therapy may affect its performance but data are conflicting. We aimed to determine the effect of immunosuppressive therapy on the performance of IGRA in patients with autoimmune diseases.MethodsWe searched PubMed, MEDLINE, EMBASE and the Cochrane Library up to December 2014. We included studies that reported the IGRA results in patients with autoimmune disease with or without immunosuppressive therapy. The pooled effect of immunosuppressive therapy on IGRA was estimated using a Peto fixed-effects model.ResultsWe included 17 studies with 3197 participants in the meta-analysis. Among the subjects, 71.5% were taking immunosuppressive therapy and 56.7% had received Bacillus Calmette–Guérin vaccination. Compared with patients not on immunosuppressants, patients receiving immunosuppressive therapy were less likely to have a positive IGRA result (OR 0.66, 95% CI 0.53 to 0.83, I2=23%), especially patients receiving anti-tumour necrosis factor (anti-TNF) treatment (OR 0.50, 95% CI 0.29 to 0.88). The use of immunosuppressive therapy was also associated with a lower rate of positive tuberculin skin test result (OR 0.51, 95% CI 0.42 to 0.61).ConclusionsOur meta-analysis showed that IGRA results are negatively affected by immunosuppressive therapy. IGRA alone may not be sufficiently sensitive to diagnose LTBI in patients on immunosuppressive therapy. Patients should preferably be screened for LTBI before initiation of immunosuppressive therapy, especially before anti-TNF therapy.

Our meta-analysis showed that serrated polyps are associated with a more than twofold increased risk of detection of synchronous advanced neoplasia. Individuals with proximal and large serrated polyps have the highest risk. These individuals deserve surveillance colonoscopy.

Natural antisense transcripts (NATs) exist ubiquitously in mammalian genomes and play roles in the regulation of gene expression. However, both the existence of bidirectional antisense RNA regulation and the possibility of proteincoding genes that function as antisense RNAs remain speculative. Here, we found that the protein-coding gene, deoxyhypusine synthase (DHPS), as the NAT of WDR83, concordantly regulated the expression of WDR83 mRNA and protein. Conversely, WDR83 also regulated DHPS by antisense pairing in a concordant manner. WDR83 and DHPS were capable of forming an RNA duplex at overlapping 3′ untranslated regions and this duplex increased their mutual stability, which was required for the bidirectional regulation. As a pair of protein-coding cis-sense/antisense transcripts, WDR83 and DHPS were upregulated simultaneously and correlated positively in gastric cancer (GC), driving GC pathophysiology by promoting cell proliferation. Furthermore, the positive relationship between WDR83 and DHPS was also observed in other cancers. The bidirectional regulatory relationship between WDR83 and DHPS not only enriches our understanding of antisense regulation, but also provides a more complete understanding of their functions in tumor development.