Increased T-helper 17 cell differentiation mediated by exosome-mediated microRNA-451 redistribution in gastric cancer infiltrated T cells.

MicroRNA (miR)-451 is a cell metabolism-related miRNA that can mediate cell energy-consuming models by several targets. As miR-451 can promote mechanistic target of rapamycin (mTOR) activity, and increased mTOR activity is related to increased differentiation of T-helper 17 (Th17) cells, we sought to investigate whether miR-451 can redistribute from cancer cells to infiltrated T cells and enhance the distribution of Th17 cells through mTOR. Real-time PCR was used for detecting expression of miR-451 in gastric cancer, tumor infiltrated T cells and exosomes, and distribution of Th17 was evaluated by both flow cytometry and immunohistochemistry (IHC). Immunofluorescence staining was used in monitoring the exosome-enveloped miR-451 from cancer cells to T cells with different treatments, and signaling pathway change was analyzed by western blot. miR-451 decreased significantly in gastric cancer (GC) tissues but increased in infiltrated T cells and exosomes; tumor miR-451 was negatively related to infiltrated T cells and exosome miR-451. Exosome miR-451 can not only serve as an indicator for poor prognosis of post-operation GC patients but is also related to increased Th17 distribution in gastric cancer. miR-451 can redistribute from cancer cells to T cells with low glucose treatment. Decreased 5' AMP-activated protein kinase (AMPK) and increased mTOR activity was investigated in miR-451 redistributed T cells and the Th17 polarized differentiation of these T cells were also increased. Exosome miR-451 derived from tumor tissues can serve as an indicator for poor prognosis and redistribution of miR-451 from cancer cells to infiltrated T cells in low glucose treatment can enhance Th17 differentiation by enhancing mTOR activity.

Continuous venovenous hemofiltration decreases mortality and ameliorates acute lung injury in canine model of severe salt water drowning.

BACKGROUND: Pulmonary edema is an important cause of complications and death in severe drowning. Continuous veno-venous hemofiltration (CVVH) may reduce pulmonary edema and thus may be a treatment modality for severe sea water drowning resuscitation. METHOS: 20 dogs were anesthetized and tracheally intubated. 10 ml/kg of sea water was infused into trachea in a minute. All animals developed signs of respiratory distress and severe hypoxia (PaO2 < 40 mmHg) within 15 minutes after infusion. They were then mechanical ventilated and randomized to receive either CVVH (n = 10) or no additional treatment (control, n = 10) and followed over 4 hours. Arterial gas, hemodynamic parameters, and the levels of circulating inflammatory cytokines including interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor α (TNFα) were determined. Additionally, blood endothelin and the levels of oxidative stress in lung were measured at sacrifice. RESULTS: 5 animals in the control group (50%) died within 4 hours after sea water aspiration, while 10 animals received CVVH all survived (p < 0.05). Importantly, CVVH significantly improved blood gas exchange as evidenced by higher PaO2, normal oxygen saturation, and no carbon dioxide retention after 3 hour of CVVH, while also correcting against acidosis. Levels of circulating IL-6, IL-8, and TNFα were elevated in control but not in CVVH group (p < 0.01). CVVH also reduced plasma endothelin and alleviated oxidative stress. Histology examination further revealed reductions in pulmonary alveolar injury, blood congestion, and inflammation by CVVH. DISCUSSION AND CONCLUSIONS: CVVH decreased mortality and pulmonary injury and largely maintained hemodynamic and acid-base balance in animals with severe sea water drowning and thus, may be added as a new measure to aid in resuscitation from severe sea water drowning. TRIAL REGISTRATION: Animal protocol number: FZG0001859 http://www.fzzyy.com.

Function analysis of rs9589207 polymorphism in miR-92a in gastric cancer.

MiR-92a was identified as an essential oncogene by promoting the cell proliferation through FBXW7 in gastric cancer (GC). The function of the single nucleotide polymorphism (SNP) located in the mature region of miR-92a (rs9589207) has not been investigated. We found that rs9589207 in miR-92a was involved in the occurrence of GC by acting as a tumor protective factor and was highly associated with tumor size in GC patients instead of tumor number or metastasis in 554 GC patients and 531 cancer-free controls. Besides, the AA genotype in miR-92a could attenuate the promoting function of miR-92a in cell proliferation with an incapacitation in downregulating the expression of FBXW7. In conclusion, rs9589207 in miR-92a was highly associated with a decreased risk of GC in Chinese Han population and might serve as a novel biomarker for the disease.

The Functional Variant in the 3'UTR of PTPRT with the Risk of Esophageal Squamous Cell Carcinoma in a Chinese Population.

BACKGROUND/AIMS: PTPRT is an essential tumor suppressor that plays crucial roles in regulating the mechanisms of tumorigenesis. Polymorphisms in PTPRT have been reported associated with human longevity, but their association with the risk of esophageal squamous cell carcinoma (ESCC) has not been found so far. In this study, we focused on the miRNAs associated SNPs in the 3'-UTR of PTPRT to investigate the further relationship of the SNPs with miRNAs among Chinese ESCC patients. METHODS: We performed case-control study including 790 ESCC patients and 749 cancer-free controls. Genotyping, real time PCR assay, cell transfection and the dual luciferase reporter assay were used in our study. RESULTS: We found that patients suffering from smoking exposure, drinking exposure and the history of cancer indicated to be the susceptible population by comparing with controls. Besides, SNP rs2866943 in PTPRT 3'-UTR was involved in the occurrence of ESCC by acting as a protective factor while rs6029959 acting a risk factor. SNP rs2866943 was also could be regulated by miR-218 which caused a down-regulation of PTPRT in patients with CT and TT genotype. Furthermore, the carriers of CT and TT genotype presented a small tumor size as well as the low probability of metastasis. CONCLUSION: Our findings have shown that the SNP rs2866943 in PTPRT 3'-UTR, through disrupting the regulatory role of miR-218 in PTPRT expression, rs2866943 in PTPRT might act as a protective factor in the pathogenesis of ESCC.

Vaccination of attenuated EIS-producing Salmonella induces protective immunity against enterohemorrhagic Escherichia coli in mice.

There is an urgent need for vaccine against enterohemorrhagic Escherichia coli (EHEC), which causes a wide range of life-threatening diseases in human and animals. E. coli secreted protein A (EspA), intimin and shiga toxin (Stx) are important pathogenic factors and protective antigens of EHEC. In our previous study, we found that recombinant trivalent protein EIS, which is composed of EspA (E), the 300 amino acids of the carboxyl terminus of intimin (I) and the B subunit of Stx2 (S), was able to efficiently elicit protective immunity against EHEC. The application of live attenuated Salmonella as a carrier for vaccine against mucosal pathogens provided unparalleled merits. Therefore, in this study we constructed live attenuated EIS-producing Salmonella vaccine and tested it as vaccine in mice model. We found that the vaccination of EIS-producing recombinant Salmonella was able to induce significant increases of EspA, intimin and Stx2 specific IgG in serum and secretory IgA in feces. Antigen specific T cell proliferation was also observed in the mice immunized with recombinant EIS-producing Salmonella. In addition, this immunity was able to protect mice from a challenge of a lethal dose of EHEC, even after a period of 70 days. Moreover, the EIS-producing Salmonella induced immunity can be boosted by a single subcutaneous injection of purified EIS protein, even after an interval of 70 days. This EIS-producing Salmonella vaccine provides an alternative approach for the prevention of EHEC infection.