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Oxidative stress can adversely affect the health status of the body, more specifically by causing intestinal damage by disrupting the permeability of the intestinal barrier. This is closely related to intestinal epithelial cell apoptosis caused by the mass production of reactive oxygen species (ROS). Baicalin (Bai) is a major active ingredient in Chinese traditional herbal medicine that has antioxidant, anti-inflammatory, and anti-cancer properties. The purpose of this study was to explore the underlying mechanisms by which Bai protects against hydrogen peroxide (H2O2)-induced intestinal injury in vitro. Our results indicated that H2O2 treatment caused injury to IPEC-J2 cells, resulting in their apoptosis. However, Bai treatment attenuated H2O2-induced IPEC-J2 cell damage by up-regulating the mRNA and protein expression of ZO-1, Occludin, and Claudin1. Besides, Bai treatment prevented H2O2-induced ROS and MDA production and increased the activities of antioxidant enzymes (SOD, CAT, and GSH-PX). Moreover, Bai treatment also attenuated H2O2-induced apoptosis in IPEC-J2 cells by down-regulating the mRNA expression of Caspase-3 and Caspase-9 and up-regulating the mRNA expression of FAS and Bax, which are involved in the inhibition of mitochondrial pathways. The expression of Nrf2 increased after treatment with H2O2, and Bai can alleviate this phenomenon. Meanwhile, Bai down-regulated the ratio of phosphorylated AMPK to unphosphorylated AMPK, which is indicative of the mRNA abundance of antioxidant-related genes. In addition, knockdown of AMPK by short-hairpin RNA (shRNA) significantly reduced the protein levels of AMPK and Nrf2, increased the percentage of apoptotic cells, and abrogated Bai-mediated protection against oxidative stress. Collectively, our results indicated that Bai attenuated H2O2-induced cell injury and apoptosis in IPEC-J2 cells through improving the antioxidant capacity through the inhibition of the oxidative stress-mediated AMPK/Nrf2 signaling pathway. [ABSTRACT FROM AUTHOR]

Heavy metals interact with each other in a coexisting manner to produce complex combined toxicity to organisms. At present, the toxic effects of chronic co-exposure to heavy metals hexavalent chromium [Cr(VI)] and divalent nickel [Ni(II)] on organisms are seldom studied and the related mechanisms are poorly understood. In this study, we explored the mechanism of the colon injury in mice caused by chronic exposure to Cr or/and Ni. The results showed that, compared with the control group, Cr or/and Ni chronic exposure affected the body weight of mice, and led to infiltration of inflammatory cells in the colon, decreased the number of goblet cells, fusion of intracellular mucus particles and damaged cell structure of intestinal epithelial. In the Cr or/and Ni exposure group, the activity of nitric oxide synthase (iNOS) increased, the expression levels of MUC2 were significantly down-regulated, and those of ZO-1 and Occludin were significantly up-regulated. Interestingly, factorial analysis revealed an interaction between Cr and Ni, which was manifested as antagonistic effects on iNOS activity, ZO-1 and MUC2 mRNA expression levels. Transcriptome sequencing further revealed that the expression of genes-related to inflammation, intestinal mucus and tight junctions changed obviously. Moreover, the relative contents of Cr(VI) and Ni(II) in the Cr, Ni and Cr+Ni groups all changed with in-vitro gastrointestinal （IVG）digestion, especially in the Cr+Ni group. Our results indicated that the chronic exposure to Cr or/and Ni can lead to damage to the mice colon, and the relative content changes of Cr(VI) and Ni(II) might be the main reason for the antagonistic effect of Cr+Ni exposure on the colon damage. [Display omitted] • Cr or/and Ni can cause colon damage in mouse. • Cr or/and Ni interfere gene expression in colon of mouse. • Cr and Ni showed antagonistic effects on iNOS activity, ZO-1 and MUC2 mRNA expression levels. • Cr(IV) and Ni (II) underwent valence changes in vitro gastrointestinal digestion phase. [ABSTRACT FROM AUTHOR]

Background: Pulmonary arterial hypertension, also known as Ascites syndrome (AS), remains a clinically challenging disease with a large impact on both humans and broiler chickens. Pulmonary arterial remodeling presents a key step in the development of AS. The precise molecular mechanism of pulmonary artery remodeling regulating AS progression remains unclear. Methodology/Principal Findings: We obtained pulmonary arteries from two positive AS and two normal broilers for RNA sequencing (RNA-seq) analysis and pathological observation. RNA-seq analysis revealed a total of 895 significantly differentially expressed genes (DEGs) with 437 up-regulated and 458 down-regulated genes, which were significantly enriched to 12 GO (Gene Ontology) terms and 4 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways (Padj<0.05) regulating pulmonary artery remodeling and consequently occurrence of AS. These GO terms and pathways include ribosome, Jak-STAT and NOD-like receptor signaling pathways which regulate pulmonary artery remodeling through vascular smooth cell proliferation, inflammation and vascular smooth cell proliferation together. Some notable DEGs within these pathways included downregulation of genes like RPL 5, 7, 8, 9, 14; upregulation of genes such as IL-6, K60, STAT3, STAT5 Pim1 and SOCS3; IKKα, IkB, P38, five cytokines IL-6, IL8, IL-1β, IL-18, and MIP-1β. Six important regulators of pulmonary artery vascular remodeling and construction like CYP1B1, ALDH7A1, MYLK, CAMK4, BMP7 and INOS were upregulated in the pulmonary artery of AS broilers. The pathology results showed that the pulmonary artery had remodeled and become thicker in the disease group. Conclusions/Significance: Our present data suggested some specific components of the complex molecular circuitry regulating pulmonary arterial remodeling underlying AS progression in broilers. We revealed some valuable candidate genes and pathways that involved in pulmonary artery remodeling further contributing to the AS progression. [ABSTRACT FROM AUTHOR]

Beclin1, also known as ATG6, has been shown to be closely related to coronavirus, however, the link between Beclin1 and nephropathogenic infectious bronchitis virus (NIBV) has been poorly investigated and there are no available antibodies specifically targeting the chicken Beclin1 protein. The study aimed to prepare and assay a polyclonal antibody to Beclin1, enabling a deeper understanding of the mechanism of action of Beclin1 in NIBV. In this study, we amplified the chicken Beclin1 target gene and constructed a recombinant plasmid using prokaryotic expression techniques, then obtained the recombinant target protein by induced expression. Finally, the serum is obtained by immunizing rabbits with the purified and concentrated protein. The results show that the antiserum potency of the ELISA assay was >1:204800. By western blotting and immunofluorescence, the antibodies we prepared specifically recognized the chicken Beclin1 protein, which is mainly found in the nucleus of trachea, lung, kidney, spleen and fabricant cells. NIBV infection significantly decreased the expression of Beclin1 in the trachea, but increased in others. We have successfully prepared specific rabbit anti-chicken Beclin1 polyclonal antibodies, and detected changes in tissues of diseased chickens infected with NIBV, laying the foundation for further studies on the role of Beclin1 in avian diseases. [ABSTRACT FROM AUTHOR]

In order to clarify the effects of the combination of Mo and Cd on goat and relationship between the two elements, combined chronic toxicity of cadmium with different levels of molybdenum in vivo on apoptosis gene and ultrastructure of spleen was evaluated with the methods of RT-qPCR and transmission electron microscopy. A total of thirty-six goats were randomly distributed in equal number into four groups. These groups were randomly assigned with one of three oral treatments of CdCl 2 (0.5 mgCd kg −1 ) and [(NH 4 ) 6 Mo 7 O 24 ·4H 2 O] (15 mg Mo kg −1 , group I; 30 mg Mo kg −1 , group II; 45 mg Mo kg −1 , group III), while the control group received deionized water. Spleen tissues were taken from individual goat at different time intervals to measure the levels of apoptosis genes including Bcl-2 , Bax , Cyt c , Caspase-3 , Smac and ceruloplasmin ( Cp ). The results revealed that a significant suppression in Bcl-2 expression and increase in Cyt c , Caspase-3 and Cp expression in splenic cells. The Bax expression in group I and II was up-regulated, however, it displayed reduction in group III, whereas no statistical significance was observed on Smac expression. In addition, histopathologic injury revealed remarkable morphplogical changes on the splenocytes in the means of apoptosis including fragmentized nucleus, apoptotic body and vesiculation of cytoplasma and mitochondria. Taken together, combined chronic toxicity of cadmium with different levels of molybdenum induce goat spleen cell apoptosis associated with mitochondrial intrinsic pathway, and the two elements showed possible antergic relationship. [ABSTRACT FROM AUTHOR]

Broiler ascites syndrome (AS), also called pulmonary artery hypertension, is a metabolic disorder that has been observed worldwide in fast-growing broilers. Pulmonary arterial remodeling is a key step in the development of AS. The precise relationship between mRNA and SNP of the pulmonary artery in regulating AS progression remains unclear. In this study, we obtained pulmonary artery tissues from broilers with AS to perform pathologic section and pathologic anatomic observation. SNP, InDel, and mRNA data analysis were carried out using GATK and ANNOVAR software to study the SNP loci of 985 previously reported genes (437 upregulated and 458 downregulated). The pathology results showed that there was a lot of yellow fluid in the abdominal cavity and pericardium, that the ascites cardiac index and hematocrit changed significantly, and that the pulmonary artery had remodeled and become thicker in the disease group. Myocardial sections showed vacuolar degeneration of myocytes and rupture of muscle fibers. In addition, ALDH7A1, IRG1, GGT5, IGSF1, DHX58, USP36, TREML2, SPAG1, CD34, and PLEKHA7 were found to be closely associated with the pathogenesis of pulmonary artery remodeling in AS progression. Taken together, our present study further illuminates the molecular mechanism of pulmonary artery remodeling underlying AS progression. [ABSTRACT FROM AUTHOR]