Agrobacterium sp. ZX09 ß-Glucan Attenuates Enterotoxigenic Escherichia coli-Induced Disruption of Intestinal Epithelium in Weaned Pigs.

To explore the protective effect of dietary ß-glucan (BGL) supplementation on intestinal epithelium exposure to enterotoxigenic Escherichia coli (ETEC), thirty-two weaned pigs were assigned to four groups. Pigs were fed with a basal diet or basal diet containing 500 mg/kg BGL, and were orally infused with ETEC or culture medium. Results showed BGL supplementation had no influence on growth performance in weaned pigs. However, BGL supplementation increased the absorption of D-xylose, and significantly decreased the serum concentrations of D-lactate and diamine oxidase (DAO) in the ETEC-challenged pigs (p < 0.05). Interestingly, BGL significantly increased the abundance of the zonula occludens-1-(ZO-1) in the jejunal epithelium upon ETEC challenge (p < 0.05). BGL supplementation also increased the number of S-phase cells and the number of sIgA-positive cells, but significantly decreased the number of total apoptotic cells in the jejunal epithelium upon ETEC challenge (p < 0.05). Moreover, BGL significantly increased the duodenal catalase (CAT) activity and the ileal total superoxide dismutase (T-SOD) activity in the ETEC-challenged pigs (p < 0.05). Importantly, BGL significantly decreased the expression levels of critical inflammation related proteins such as the tumor necrosis factor-α (TNF-α), interlukin-6 (IL-6), myeloid differentiation factor 88 (MyD88), and nuclear factor-κB (NF-κB) in the jejunal and ileal mucosa upon ETEC challenge (p < 0.05). BGL also elevated the propanoic acid content and the abundance of Lactobacillus and Bacillus in the colon upon ETEC challenge (p < 0.05). These results suggested BGL could alleviate the ETEC-induced intestinal epithelium injury, which may be associated with suppressed inflammation and improved intestinal immunity and antioxidant capacity, as well as the improved intestinal macrobiotic.

Genome-wide analysis identify novel germline genetic variations in ADCY1 influencing platinum-based chemotherapy response in non-small cell lung cancer.

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.

Effect of ß-Glucan Supplementation on Growth Performance and Intestinal Epithelium Functions in Weaned Pigs Challenged by Enterotoxigenic Escherichia coli.

Background: To examine the effect of ß-glucan (BGL) supplementation on growth performance and intestinal epithelium functions in weaned pigs upon Enterotoxigenic Escherichia coli (ETEC) challenge. Methods: Thirty-two weaned pigs (Duroc × Landrace × Yorkshire) were assigned into four groups. Pigs fed with a basal diet or basal diet containing 500 mg/kg BGL were orally infused with ETEC or culture medium. Results: Results showed BGL tended to increase the average daily gain (ADG) in ETEC-challenged pigs (0.05 < p < 0.1). Dietary BGL supplementation had no significant influence on nutrient digestibility (p > 0.05). However, BGL improved the serum concentrations of immunoglobulin (Ig) A and IgG, and was beneficial to relieve the increasement of the concentrations of inflammatory cytokines such as the TNF-α and IL-6 upon ETEC-challenge (p < 0.05). Interestingly, BGL significantly increased the duodenal, jejunal and ileal villus height, and increased the jejunal ratio of villus height to crypt depth (V/C) upon ETEC challenge (p < 0.05). BGL also increased the activities of mucosal, sucrase and maltase in the ETEC-challenged pigs (p < 0.05). Moreover, BGL elevated the abundance of Lactobacillus and the concentration of propanoic acid in colon in the ETEC-challenged pigs (p < 0.05). Importantly, BGL elevated the expression levels of zonula occludins-1 (ZO-1) and mucin-2 (MUC-2) in the small intestinal mucosa upon ETEC challenge (p < 0.05). BGL also upregulated the expressions of functional genes such as the claudin-1, cationic amino acid transporter-1 (CAT-1), LAT-1, L amino acid transporter-1 (LAT1), fatty acid transport proteins (FATP1), FATP4, and sodium/glucose cotransporter-1 (SGLT-1) in the duodenum, and the occludin-1 and CAT-1 in the jejunum upon ETEC challenge (p < 0.05). Conclusions: These results suggested that BGL can attenuate intestinal damage in weaned pigs upon ETEC challenge, which was connected with the suppressed secretion of inflammatory cytokines and enhanced serum immunoglobulins, as well as improved intestinal epithelium functions and microbiota.

Association of variations in platinum resistance-related genes and prognosis in lung cancer patients.

Purpose: We aimed to investigate the association of single-nucleotide polymorphisms (SNPs) in HMGB1, REV3L, and NFE2L2 with prognosis in lung cancer patients with platinum-based chemotherapy. Methods: We have recruited 348 lung cancer patients treated with platinum. Log-rank test and Cox regression analysis were used to assess overall survival (OS) and progression-free survival (PFS) among SNP genotypes. Results: The results revealed that patients carrying TC or CC genotype in REV3L rs462779 (HR=0.67, 95% CI=0.51-0.90, P=0.007) and AG or GG genotype in HMGB1 rs1045411 (HR=0.61, 95% CI=0.38-0.99, P=0.046) had a better overall survival. Additionally, carrying TC or TT genotype in rs462779 had a lower risk (OR=0.38, 95% CI=0.17-0.89, P=0.025) of lymph node metastasis, carrying AG or AA genotype in rs1045411 was significantly related to early T stage (OR=0.47, 95% CI=0.29-0.76, P=0.002). In stratified analysis, patients with TC or CC genotype in rs462779 were significantly associated with overall survival in male patients, never-smokers, patients with younger age (≤56), no family history of cancer, adenocarcinoma, advanced stage (stage III or IV), or ECOG PS 0-1. While patients with AG or GG genotype in rs1045411 were significantly associated with overall survival in patients with advanced stage (stage III or IV) or ECOG PS 0-1. Conclusion: Our results indicate that the TC or CC genotype in rs462779 and AG or GG genotype in rs1045411 are contributed to better overall survival. The REV3L rs462779 and HMGB1 rs1045411 may serve as prognosis markers in lung cancer patients with platinum-based chemotherapy.