Adjuvant effects of bacterium-like particles in the intranasal vaccination of chickens against Newcastle disease.

Given that the respiratory mucosa is an important site for the initial replication of Newcastle disease virus (NDV), developing intranasal vaccines for chickens is an effective strategy to protect against this disease. The low immunogenicity of inactivated NDV administered by the mucosal route motivated us to identify a safe and potent adjuvant. Previous studies have shown that bacterium-like particles (BLPs), which serve as mucosal adjuvants, induce effective local and systemic immune responses through TLR2 signaling in both mammals and humans. Here, we report that BLPs could activate the innate immune system of chickens in a manner that was dependent on the combination of chicken TLR2 type 1 (chTLR2t1) and chicken TLR1 type 1 (chTLR1t1). The chicken macrophage-like HD11 cell line was stimulated with BLPs, resulting in the production of nitric oxide and the expression of the proinflammatory cytokines IFN-γ, IL-1ß and IL-6. Chickens intranasally immunized with inactivated NDV vaccines mixed with BLP adjuvants exhibited significantly increased levels of local SIgA in their tracheal lavage fluid and as well as hemagglutination-inhibiting antibodies in serum samples. The strong systemic and local immune responses induced by BLP-adjuvanted vaccines provided 100 % protection against intranasal challenge with a lethal dose of virulent NDV without showing any signs of disease. These results indicate that BLPs should be considered for use as a potential mucosal adjuvant for inactivated NDV vaccines and other vaccines for poultry.

The role of fluoroaluminate complexes on the adsorption of fluoride onto hydrous alumina in aqueous solutions.

Activated alumina (AA) has been extensively applied in the defluorination of industrial wastewaters and groundwater. Although the dissolution of AA due to formation of fluoroaluminate complexes (AlFx3-x), especially in acidic condition, has been observed, its role on fluoride uptake by alumina has not been discussed in any previous literature, most of which consider F- as the sole adsorbed species. The present study described the effect of fluoroaluminate complexes on fluoride adsorption onto alumina. Results indicated that fluoroaluminate complexes, major fluoride species at pH < 6, were responsible for total fluoride adsorbed. Free fluoride ions were adsorbed mainly in the alkaline pH region, e.g., pH > 6. The dissolution of AA during defluorination was measured and analyzed by the thermodynamic solubility model. The surface concentration of F- and AlFx3-x were calculated considering electrostatic interactions. Characterization of fluoride-laden AA by XPS revealed that the fraction of surface Al-F species decreased with pH, which suggested the transition of the surface fluorinated species to that of free fluoride ions. The stability constants of four surface complexes, namely, AlOH-FAl2+, AlOH-F2Al+, AlOH2+-F- and AlOH-F-, were 106.88, 105.36, 102.72 and 102.36, respectively. Obviously fluoroaluminate complexes exhibited stronger chemical bonds with the surface hydroxy species than free fluoride.

Microarray­based analysis of COL11A1 and TWIST1 as important differentially­expressed pathogenic genes between left and right­sided colon cancer.

Colonic cancer has become a main reason of mortality associated with cancer; however, left and right­sided colonic cancer have diverse outcomes in terms of epidemiological, histological, clinical parameters and prognosis. We aimed to examine the discrepancies between these two types of colon cancers to identify potential therapeutic targets. In the present study, three gene expression profiles (GSE44076, GSE31595, GSE26906) from Gene Expression Omnibus (GEO) database were downloaded and further analyzed. A PPI (protein­protein interaction) network of the differentially­expressed genes (DEGs) of GSE44076 between tumor and normal was established with the Search Tool for the Retrieval of Interacting Genes database. Then, the DEGs of these two colon cancers (left, right) samples were identified. Subsequently, the intersection of DEGs of left and right­sided colon cancer samples obtained from three databases, and DEGs of tumor and normal samples were analyzed. Collagen type XI α1 chain (COL11A1), Twist family bHLH transcription factor 1 (TWIST1), insulin­like 5 and chromogranin A were upregulated proteins, while 3ß­hydroxysteroid dehydrogenase was downregulated protein in right colon cancer than in left­sided tumor samples. Through further experimental verification, we revealed that COL11A1 and TWIST1 were significantly upregulated at the mRNA and protein levels within right­sided colon cancer compared with in left­sided colon cancer samples (P<0.05), consistent with bioinformatical analysis. Furthermore, a positive correlation between COL11A1 and TWIST1 protein expression was observed (P<0.0276). Collectively, our data showed that COL11A1 and TWIST1 may be potential prognostic indicators and molecular targets for the treatment of right­sided colon cancer.

Targeting posttranslational modifications of RIOK1 inhibits the progression of colorectal and gastric cancers.

RIOK1 has recently been shown to play important roles in cancers, but its posttranslational regulation is largely unknown. Here we report that RIOK1 is methylated at K411 by SETD7 methyltransferase and that lysine-specific demethylase 1 (LSD1) reverses its methylation. The mutated RIOK1 (K411R) that cannot be methylated exhibits a longer half-life than does the methylated RIOK1. FBXO6 specifically interacts with K411-methylated RIOK1 through its FBA domain to induce RIOK1 ubiquitination. Casein kinase 2 (CK2) phosphorylates RIOK1 at T410, which stabilizes RIOK1 by antagonizing K411 methylation and impeding the recruitment of FBXO6 to RIOK1. Functional experiments demonstrate the RIOK1 methylation reduces the tumor growth and metastasis in mice model. Importantly, the protein levels of CK2 and LSD1 show an inverse correlation with FBXO6 and SETD7 expression in human colorectal cancer tissues. Together, this study highlights the importance of a RIOK1 methylation-phosphorylation switch in determining colorectal and gastric cancer development.

miR-181d and c-myc-mediated inhibition of CRY2 and FBXL3 reprograms metabolism in colorectal cancer.

Colorectal cancer (CRC) is the second major cause of tumor-related deaths. MicroRNAs (miRNAs) have pivotal roles in CRC progression. Here, we describe the effect of miR-181d on CRC cell metabolism and underlying molecular mechanism. Our data firmly demonstrated that knockdown of miR-181d suppressed CRC cell proliferation, migration, and invasion by impairing glycolysis. Mechanistically, miR-181d stabilized c-myc through directly targeting the 3'-UTRs of CRY2 and FBXL3, which subsequently increased the glucose consumption and the lactate production. Inhibition of c-myc via siRNA or small molecular inhibitor abolished the oncogenic effects of miR-181d on the growth and metastasis of CRC cells. Furthermore, c-myc/HDAC3 transcriptional suppressor complex was found to co-localize on the CRY2 and FBXL3 promoters, epigenetically inhibit their transcription, and finally induce their downregulation in CRC cells. In addition, miR-181d expression could be directly induced by an activation of c-myc signaling. Together, our data indicate an oncogenic role of miR-181d in CRC by promoting glycolysis, and miR-181d/CRY2/FBXL3/c-myc feedback loop might be a therapeutic target for patients with CRC.

Clinical significance of TIPE expression in gastric carcinoma.

BACKGROUND: TNFAIP8, also known as TIPE, is a suppressor of apoptosis. High expression of both TIPE mRNA and protein has been detected in various cancer cell lines and clinical specimens compared to healthy tissues. Many reports have shown that there is a strong correlation between TIPE overexpression and cancer progression and poor prognosis in human solid cancers. METHODS: To illustrate the functional and clinical significance of TIPE in gastric cancer, we used reverse transcription polymerase chain reaction, quantitative real-time polymerase chain reaction, and immunohistochemistry to measure TIPE expression in clinical gastric specimens. Then, TIPE expression was knocked down by using shRNA and anti-DR5ScFv, to examine different expressions of TIPE in BGC823 cell lines, while cell proliferation and apoptosis were induced. RESULTS: We found that there was a strong correlation between TIPE expression and TNM stage (P=0.044), tumor depth (P=0.016), lymph node metastasis (P=0.026), and distant metastasis (P=0.045). No significant correlation was found between TIPE expression with the patients' age (P=0.062) or sex (P=0.459). Anti-DR5ScFv induced TIPE depletion both in vitro and in vivo and resulted in apoptosis and suppression of proliferation. CONCLUSION: Our results suggested that TIPE expression was associated with gastric cancer progression, and most importantly, suppressing TIPE expression might be an effective therapeutic strategy.

Laparoscopic-Assisted Natural Orifice Specimen Extraction Radical Descending Colectomy Using a Cai Tube.

AIM: To overcome the technical difficulty of exteriorizing a specimen through the descending colon stump, we applied laparoscopic-assisted natural orifice specimen extraction (LA-NOSE) using a Cai tube. METHODS: From April 2014 to February 2015, we successfully performed total laparoscopic radical surgery with LA-NOSE in six patients with descending colon lesions. The time of operation, blood loss amount, lymph nodes harvested, postoperative recovery, postoperative complications and follow-up were observed. RESULTS: Total laparoscopic dissection and anastomosis with natural orifice removal using a Cai tube was successful in all 6 patients; no deaths, anastomotic bleeding, fistulas, infections, or any other complications were recorded. The median operating time was 327.7 ± 73.4 min, and the estimated blood loss was 66.7 ± 69.2 mL. The mean number of lymph nodes harvested was 15.7 ± 4.4. Recovery of gastrointestinal function ranged from 2 to 4 days after the operation. The mean length of postoperative hospital stay was 12.3 ± 3.2 days. The six cases were followed up for 6-16 (12.5 ± 3.6) months, and all patients avoided auxiliary incision which demonstrated potential cosmetic advantages and uneventful recovery with no additional complications or cancer recurrence. CONCLUSION: In this pilot study of six patients, LA-NOSE radical descending colectomy using a Cai tube was feasible and safe.

MiR-448 promotes glycolytic metabolism of gastric cancer by downregulating KDM2B.

MicroRNAs are critical in various human cancers, including gastric cancer (GC). However, the mechanism underlying the GC development remains elusive. In this study, we demonstrate that miR-448 is increased in GC samples and cell lines. Overexpression of miR-448 facilitated the proliferation of GC cells by stimulating glycolysis. Mechanistically, we identified KDM2B, a reader for methylated CpGs, as the target of miR-448 that represses glycolysis and promotes oxidative phosphorylation. Overexpression of miR-448 reduced both the mRNA and protein levels of KDM2B, whereas KDM2B re-expression abrogated the miR-448-mediated glycolytic activities. Furthermore, we discovered Myc as a key target of KDM2B that controls metabolic switch in GC. Importantly, a cohort of 81 GC tissues revealed that miR-448 level closely associated with a battery of glycolytic genes, in which KDM2B showed the strongest anti-correlation coefficient. In addition, enhanced miR-448 level was significantly associated with poor clinical outcomes of GC patients. Hence, we identified a previously unappreciated mechanism by which miR-448 orchestrate epigenetic, transcriptional and metabolic networks to promote GC progression, suggesting the possibility of therapeutic intervention against cancer metabolic pathways.

[Laparoscopic-assisted natural orifice specimen extraction radical left colectomy].

OBJECTIVE: To explore the feasibility of laparoscopic-assisted natural orifice specimen extraction radical left colectomy. METHODS: Retrospective analysis was performed on clinicopathological dada of 15 colorectal patients who were treated by laparoscopic-assisted anal specimen extraction radical left colectomy with self-developed surgical instrument Cai tube between January and September in 2014. Tumor location included descending colon (n=3), the junction of descending colon and sigmoid colon (n=2), the sigmoid colon (n=6) and upper rectum (n=4). Clinical efficacy of patients was observed. RESULTS: There were no perioperative deaths or postoperative complications, such as anastomotic bleeding or leakage. The median operation time was 257 (range 103-337) min, median blood loss was 50(range 20-200) ml, median time to first flatus was 3 (range 1-5) d and median hospital stay was 14 (range 11-21) d. All the patients had good quality of life and normal defecation function without tumor recurrence or metastasis after 1-8 months of follow-up. CONCLUSION: Laparoscopic-assisted anal specimen extraction radical left colectomy is safe and feasible.