Bile reflux is an independent risk factor for precancerous gastric lesions and gastric cancer: An observational cross-sectional study.

OBJECTIVE: To identify whether bile reflux on endoscopy and other related variables are risk factors for precancerous gastric lesions and gastric cancer (GC). METHODS: A multicenter, cross-sectional and observational study was conducted in five centers in China from June to October 2019, 1162 patients were recruited and divided into the chronic gastritis (CG), the precancerous lesion (low-grade intraepithelial neoplasia and intestinal metaplasia), and GC groups (including high-grade intraepithelial neoplasia). All participants underwent detailed interviews, endoscopy and biopsy, and completed questionnaires. Odds ratio and 95% confidence interval were calculated with multivariate logistic regression models with or without adjustment for Helicobacter pylori infection. RESULTS: We recruited 668 patients with CG, 411 with precancerous lesions and 83 with GC. By comparing the CG and precancerous lesion groups, independent risk factors for cancerous gastric lesions were the grade of bile reflux, patient's age, dietary habits and family history of GC. Similar results were obtained when comparing the CG and GC groups. In addition, bile reflux was confirmed as an independent risk factor for progression from precancerous lesions to cancer. CONCLUSIONS: Bile reflux on endoscopy as well as age, dietary habits and a family history of GC were independent risk factors for the development of precancerous gastric lesions and GC.

Angiotensin-(1-7) administration attenuates Alzheimer's disease-like neuropathology in rats with streptozotocin-induced diabetes via Mas receptor activation.

Diabetes mellitus (DM) is associated with cognitive deficits and an increased risk of Alzheimer's disease (AD). Recently, a newly identified heptapeptide of the renin-angiotensin system (RAS), angiotensin-(1-7) [Ang-(1-7)], was found to protect against brain damage. This study investigated the effects of Ang-(1-7) on diabetes-induced cognitive deficits. Sprague-Dawley rats were randomly divided into four groups. Diabetes was induced via single i.p. streptozotocin (STZ) injections. Ten weeks after diabetes induction, rats in each group received an intracerebral-ventricular (ICV) infusion of either vehicle, Ang-(1-7) alone, or Ang-(1-7)+A779 daily for two weeks. At the end of the study, Morris water maze (MWM) tests were performed to test cognitive functions before the rats were euthanized. Ang-(1-7) treatment significantly reduced escape latencies in diabetic rats in acquisition trials and markedly enhanced platform area crossing frequency and time spent in the target quadrant in probe trials (3.0±0.39 vs. 1.0±0.33, 39.39±1.11% vs. 25.62±3.07%, respectively, P<0.01). Ang-(1-7) treatment ameliorated damage to the ultrastructure of hippocampal synapses, reduced the expression of hippocampal phospho-tau at Ser396 (P<0.01), Ser404 (P<0.01) and Ser202/Thr205 (P<0.05), and decreased amyloid-ß oligomer and both soluble and insoluble ß-amyloid peptide 1-42 (Aß 1-42) and Aß 1-40 levels (P<0.01). These protective effects were significantly reversed by the co-administration of A779. These findings show that Ang-(1-7) is a promising therapeutic target for diabetes-induced cognitive impairment. The neuroprotective effects of Ang-(1-7) were mainly through Mas receptor (MasR) activation.

Characterization and expression analysis of BCA2 gene in large yellow croaker, Larimichthys crocea.

BCA2, as an E3 ubiquitin ligase, is an important anti-virus immune factor in mammals. Up to date, there are not any related reports on BCA2 protein in fishes yet. In the present investigation, BCA2 in large yellow croaker Larimichthys crocea (named as LcBCA2) was identified and characterized. The full-length cDNA of LcBCA2 was 1571 bp, including an ORF of 888 bp encoding a polypeptide of 295 amino acids. The putative LcBCA2 protein contained a RING-H2 motif at C terminal. The LcBCA2 transcripts were broadly distributed in all detected tissues, with high expression in muscle, moderate in blood, skin, heart, liver and spleen, weak in other tissue as indicated by qPCR analysis. Significant increases were observed in skin, gill and spleen after infection of Cryptocaryon irritans, and in spleen and head-kidney after inactivated Vibrio. parahaemolyticus, LPS and Poly I:C stimulations. Tissue localization by in-situ hybridization showed that LcBCA2 mainly expressed in the spleen of the fish in the test group. Our findings showed that LcBCA2 inclined to sharply increase in immune organs, especially in head-kidney after bacterial and viral stimulations, while in locations (skin and gill) of parasites infections, suggesting that BCA2 may play an important role in fish defense against bacteria, virus and parasites infections, but the immune mechanisms is are different.

Characterization of E3 ubiquitin ligase neuregulin receptor degradation protein-1 (Nrdp1) in the large yellow croaker (Larimichthys crocea) and its immune responses to Cryptocaryon irritans.

Neuregulin receptor degradation protein-1 (Nrdp1) was recently identified in humans as an important immune factor responding to the challenge of virus, LPS or cytokine. Its role in fish immune defense and whether it is involved in anti-parasite immunity have not been proven yet. In this report, the full-length cDNA sequence and genomic structure of Nrdp1 in the large yellow croaker Larimichthys crocea (LcNrdp1) were identified and characterized. The full-length cDNA of LcNrdp1 was 1248bp, including a 5' untranslated region (UTR) of 32bp, a 3' UTR of 259bp and an open reading frame (ORF) of 937bp, encoding a polypeptide of 318 amino acid residues. The full-length genomic DNA sequence of LcNrdp1 was composed of 2635 nucleotides, including four exons and three introns. The putative LcNrdp1 protein had no signal peptide sequence and contained a characteristic Nrdp1 consensus motif C3HC3D ring finger and a Coiled-coil domain. Phylogenetic analysis showed that Nrdp1 in fish was closer with that in other vertebrates (79%-90% amino acid identity) than in invertebrates and bacteria (27%-65%). In fishes, Nrdp1 in large yellow croaker was closer with that in Takifugu rubripes. The expression profile showed that LcNrdp1 was constitutively expressed in all tested tissues, especially highly expressed in brain, muscle and kidney. Post-infection (PI) with Cryptocaryon irritans, an increased expression of LcNrdp1 was induced in infection sites (skin and gill), whereas in immune organs, the expression of LcNrdp1 was up-regulated in spleen (except the 1st d and 10th d PI) but suppressed in head kidney. These results suggested that LcNrdp1 might play an important immune role in the finfish L. crocea in the defense against the parasite C. irritans.