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The differences between mouse mAβ1–42 and human hAβ1–42, explored using CD and fluorescence spectroscopy, transmission electron microscopy, ROS fluorescent assay, and neuronal cell viability, revealed that mAβ1–42 as a three-site mutant (R5G, Y10F and H13R) of hAβ1–42 altered the metal (copper and zinc) binding sites, reduced the proneness to form β-sheet structures and aggregated fibrils, alleviated the generation of ROS, and decreased the cytotoxicity, in contrast to hAβ1–42. [ABSTRACT FROM AUTHOR]

MIF/CD74 signaling pathway and autophagy may be closely related to liver fibrosis. Vanillic acid (VA) is likely to have an anti-liver fibrosis effect, although related studies have not been reported. The aim of this study was to verify the role of hepatic stellate cells (HSCs) autophagy and the MIF/CD74 signaling pathway in the pathogenesis of liver fibrosis, and to investigate the effect of VA on liver fibrosis through in vivo and in vitro experiments. Our results showed that VA significantly attenuated CCl 4 -induced liver fibrosis. The alleviation of liver fibrosis with VA treatment was associated with a reduction of MIF, CD74, α-SMA, LC3B and Collagen 1. In addition, VA, MIF inhibitor (ISO-1) and autophagy inhibitor (3-MA) markedly inhibited the proliferation and migration of HSCs. This study indicates that VA could protect against HSCs activation, proliferation and migration by inhibiting the autophagy in HSCs via the MIF/CD74 signaling pathway so that alleviates liver fibrosis. [Display omitted] • Vanillic acid may have significant anti-liver fibrosis effects. • In liver fibrosis, autophagy of HSCs can be regulated by MIF/CD74 pathway. • Activation, proliferation and migration of HSCs can be inhibited by autophagy. • Vanillic acid alleviate liver fibrosis through MIF/CD74/autophagy pathway. [ABSTRACT FROM AUTHOR]

Purpose: There is not enough information to position medications for the treatment of Crohn's disease (CD). Therefore, using a network meta-analysis and systematic review, we evaluated the efficacy and safety of combination therapy and infliximab (IFX) monotherapy in CD patients. Methods: We identified randomized controlled trials (RCTs) in CD patients who were given IFX-containing combination therapy versus IFX monotherapy. Induction and maintenance of clinical remission were the efficacy outcomes, while adverse events were the safety outcomes. The surface under cumulative ranking (SUCRA) probabilities was used to assess ranking in the network meta-analysis. Results: In total, 15 RCTs with 1586 CD patients were included in this study. There was no statistical difference between different combination therapies in induction and maintenance of remission. In terms of inducing clinical remission, IFX + EN (SUCRA: 0.91) ranked highest; in terms of maintaining clinical remission, IFX + AZA (SUCRA: 0.85) ranked highest. There was no treatment that was significantly safer than the others. In terms of any adverse events, serious adverse events, serious infections, and infusion/injection-site reactions, IFX + AZA (SUCRA: 0.36, 0.12, 0.19, and 0.24) was ranked lowest for all risks; while IFX + MTX (SUCRA: 0.34, 0.06, 0.13, 0.08, 0.34, and 0.08) was rated lowest for risk of abdominal pain, arthralgia, headache, nausea, pyrexia, and upper respiratory tract infection. Conclusion: Indirect comparisons suggested that efficacy and safety of different combination treatments are comparable in CD patients. For maintenance therapies, IFX + AZA was ranked highest for clinical remission and lowest for adverse events. Further head-to-head trials are required. [ABSTRACT FROM AUTHOR]

• Poly (I: C) treatment inhibits REV replication in HD11. • Poly (I: C) switches HD11 into M1-like popularization post REV infection. • Poly (I: C) promotes IFN-β secretion from HD11 post REV infection. • Poly (I: C) increases TLR-3 expression in HD11 post REV infection. Reticuloendothelial virus (REV) is widely found in many domestic poultry areas and results in severe immunosuppression of infected chickens. This increases the susceptibility to other pathogens, which causes economic losses to the poultry industry. The aim of our study was to determine whether polyinosinic-polycytidylic acid [Poly (I: C)] treatment could inhibit REV replication in chicken macrophage-like cell line, HD11. We found that Poly (I: C) treatment could markedly inhibit REV replication in HD11 from 24 to 48 h post infection (hpi). Additionally, Poly (I: C) treatment could switch HD11 from an inactive type into M1-like polarization from 24 to 48 hpi. Furthermore, Poly (I: C) treatment promoted interferon-β secretion from HD11 post REV infection. Moreover, Toll-like receptor-3 (TLR-3) mRNA and protein levels in HD11 treated with Poly (I: C) were markedly increased compared to those of HD11 not treated with Poly (I: C). The above results suggested that Poly (I: C) treatment switches HD11 into M1-like polarization to secret more interferon-β and activate TLR-3 signaling, which contributes to block REV replication. Our findings provide a theoretical reference for further studying the underlying pathogenic mechanism of REV and Poly (I: C) as a potential therapeutic intervention against REV infection. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. The etiology and pathogenesis of HCC remain unclear. Macrophage migration inhibitory factor (MIF) plays a critical role in the pathogenesis of hepatocellular carcinoma. The association between MIF polymorphisms and its expression level in HCC has rarely been demonstrated. In the present study, the peripheral blood of 202 patients with HCC (HCC group), 242 patients with chronic hepatitis B (CHB group), 215 patients with liver cirrhosis (LC group) and 227 healthy volunteers (normal group) were collected, DNA was extracted and the target fragment of MIF gene was amplified using PCR. The products were then sequenced, and the expression levels of MIF protein were tested using ELISA. The results showed that the MIF rs755622 polymorphism was associated with an increased susceptibility and metastasis of HCC, and that the genotypes GC and CC were associated with poor prognosis of HCC. Compared with the normal, CHB and LC groups, the expression of MIF in the peripheral blood of the HCC group was significantly increased, and the high expression was associated with to poor prognosis. In the HCC group, MIF protein levels for genotypes GC and CC were increased compared with those of genotype GG. The current study indicated that the MIF rs755622 polymorphism is associated with susceptibility and metastasis of HCC, and that the GC and CC genotypes may be indicators of poor prognosis, which may be ascribed to the MIF rs755622 polymorphism leading to elevated MIF protein expression in peripheral blood. [ABSTRACT FROM AUTHOR]

Background: Reticuloendotheliosis virus (REV) is a retrovirus that causes severe immunosuppression in poultry. Animals grow slowly under conditions of oxidative stress. In addition, long-term oxidative stress can impair immune function, as well as accelerate aging and death. This study aimed to elucidate the pathogenesis of REV from the perspective of changes in oxidative-antioxidative function following REV infection. Methods: A total of 80 one-day-old specific pathogen free (SPF) chickens were randomly divided into a control group (Group C) and an REV-infected group (Group I). The chickens in Group I received intraperitoneal injections of REV with 104.62/0.1 mL TCID50. Thymus was collected on day 1, 3, 7, 14, 21, 28, 35, and 49 for histopathology and assessed the status of oxidative stress. Results: In chickens infected with REV, the levels of H2O2 and MDA in the thymus increased, the levels of TAC, SOD, CAT, and GPx1 decreased, and there was a reduction in CAT and Gpx1 mRNA expression compared with the control group. The thymus index was also significantly reduced. Morphological analysis showed that REV infection caused an increase in the thymic reticular endothelial cells, inflammatory cell infiltration, mitochondrial swelling, and nuclear damage. Conclusions: These results indicate that an increase in oxidative stress enhanced lipid peroxidation, markedly decreased antioxidant function, caused thymus atrophy, and immunosuppression in REV-infected chickens. [ABSTRACT FROM AUTHOR]

• Successfully applied the mode for reticuloendotheliosis viral (REV) infection in SPF chickens and assessed the replication ability of the REV gene in thymic lymphocytes cells. • Apoptosis and the inhibition of lymphocyte proliferation lead to atrophy of the thymus and decrease in the number of lymphocytes. • REV infection causes decrease in the number of thymic lymphocytes, changes T cell subsets and enhances the immunosuppressive effect. Reticuloendotheliosis virus (REV), an avian retrovirus is able to infect a variety of birds and can cause immunosuppression. The aim of this study was to investigate the relationship of thymic lymphocytes apoptosis, proliferation and T cell subtype with immunosuppression. In this study, a hundred and twenty one-day old SPF chickens were randomly divided into control groups (group C) and a REV infection groups (group I). The chickens of group I received intraperitoneal injections of REV with 104.62/0.1 ml TCID 50. On day 14, 21, 28 and 35 post-inoculation, the chickens of C group and I group were sacrificed by cardiac puncture blood collection, and the thymic lymphocytes was sterile collected. The proliferation ability of lymphocytes was tested by Cell Counting Kit-8. Flow cytometry was performed to detect apoptosis, cell cycle stage and the change in T cell subtype. The RNA genome copy numbers of REV virus were detected using real-time PCR. Real-time PCR and western blotting were performed to analyze the expression of CyclinD1 and Bcl-2. Our results showed that REV genome copy number steadily declined, the proliferation potential of thymic lymphocytes was inhibited, lymphocytes apoptosed, the ratio of CD4+/CD8+ decreased and the expression of CyclinD1 and Bcl-2 were firstly inhibited, then rapidly recovered. Thus, immunosuppression lead by REV is closely related to the change of T cell subtype, apoptosis, and proliferation of thymic lymphocytes. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the effects and mechanism of Lactobacillus on ameliorating ulcerative colitis chicks induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). There are three groups in this study, control, Lactobacillus and ulcerative colitis groups. 1-day-old chicks were fed with microcapsules containing Lactobacillus LA-5 daily for Lactobacillus group and clustered with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to make the model of ulcerative colitis at ten-day-old. Chicks in control and ulcerative colitis groups were fed with empty microcapsules daily at 1-day-old and then chicks in ulcerative colitis group were induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) for preparation of ulcerative colitis model at 10-day-old. We detected the changes of mRNA and protein expression of TNF-α and IL-10 in the colon by Real-Time PCR and Western Blot. Histopathology evaluation on colon was conducted. Results showed that chicks pretreated with Lactobacillus had striking injury improvement compared with ulcerative colitis group in histopathology. Compared with ulcerative colitis group, down-regulation of TNF-α and up-regulation of IL-10 were observed in Lactobacillus group chicks. Therefore, Lactobacillus could improve the injury of intestinal mucosa and reduce inflammatory response by regulating mRNA and protein expression levels of TNF-α and IL-10, respectively. In conclusion, Lactobacillus could ameliorate the effects on chicks of TNBS-induced ulcerative colitis by reducing the inflammation and regulating the expression of TNF-α and IL-10, respectively. [ABSTRACT FROM AUTHOR]

Reticuloendotheliosis virus (REV) is an avian retrovirus that causes immunosuppression, growth retardation, and oncogenesis in a variety of birds. REV infection is epidemic in many countries. In this study, we used high-throughput sequencing to identify microRNAs (miRNAs) associated with REV infection. A total of 88 differentially expressed miRNAs were identified in samples collected on days 21 and 28 post-REV infection. Possible target genes of the differentially expressed miRNAs were analyzed. We observed that expression of proapoptotic, proto-oncogene, and carcinogenic cytokine mRNAs was highly upregulated, whereas expression of antiapoptotic cytokine mRNAs was significantly downregulated. Our findings provide a potential link between miRNA expression and the pathogenesis of REV infection. [ABSTRACT FROM AUTHOR]

Haemophilus parasuis is an important pathogen causing severe infections in pigs. However, the specific bacterial factors that participate in pathogenic process are poorly understood. VacJ protein is a recently discovered outer membrane lipoprotein that relates to virulence in several pathogens. To characterize the function of the vacJ gene in H. parasuis virulent strain HS49, a vacJ gene-deletion mutant Δ vacJ and its complemented strain were constructed. Our findings supported that VacJ is essential for maintenance of cellular integrity and stress tolerance of H. parasuis , by the demonstrations that the Δ vacJ mutant showed morphological change, increased NPN fluorescence and, and decreased resistance to SDS-EDTA, osmotic and oxidation pressure. The increased susceptibility to several antibiotics in the Δ vacJ mutant further suggested that the stability of the outer membrane was impaired as a result of the mutation in the vacJ gene. Compared to the wild-type strain, the Δ vacJ mutant strain caused a decreased survival ratio from the serum and complement killing, and exhibited a significant decrease ability to adhere to and invade PK-15 cell. In addition, the Δ vacJ mutant showed reduced biofilm formation compared to the wild-type strain. Furthermore, the Δ vacJ was attenuated in a murine (Balb/C) model of infection and its LD 50 value was approximately fifteen-fold higher than that of the wild-type or complementation strain. The data obtained in this study indicate that vacJ plays an essential role in maintaining outer membrane integrity, stress tolerance, biofilm formation, serum resistance, and adherence to and invasion of host cells related to H. parasuis and further suggest a putative role of VacJ lipoprotein in virulence regulation. [ABSTRACT FROM AUTHOR]