Innate immune responses in ALV-J infected chicks and chickens with hemangioma in vivo

Avian leukosis virus subgroup J (ALV-J) infection can cause tumors and immunosuppression. Since the precise mechanism of the innate immune response induced by ALV-J is unknown, we investigated the antiviral innate immune responses induced by ALV-J in chicks and chickens that had developed tumors. Spleen levels of interleukin-6 (IL-6), IL-10, IL-1β and interferon-β (IFN-β) were not significantly different between the infected chick groups and the control groups from 1 day post hatch to 7 days post hatch. However, IL-6, IL-1β and IFN-β protein levels in the three clinical samples with hemangiomas were dramatically increased compared to the healthy samples. In addition, the anti-inflammatory cytokine IL-10 increased sharply in two of three clinical samples. We also found a more than 20-fold up-regulation of ISG12-1 mRNA at 1 day post infection (d.p.i.) and a 2-fold up-regulation of ZC3HAV1 mRNA at 4 d.p.i. However, there were no statistical differences in ISG12-1 and ZC3HAV1 mRNA expression levels in the tumorigenesis phase. ALV-J infection induced a significant increase of Toll-like receptor 7 (TLR-7) at 1 d.p.i. and dramatically increased the mRNA levels of melanoma differentiation-associated gene 5 (MDA5) in the tumorigenesis phase. Moreover, the protein levels of interferon regulatory factor 1 (IRF-1) and signal transducer and activator of transcription 1 (STAT1) were decreased in chickens with tumors. These results suggest that ALV-J was primarily recognized by chicken TLR7 and MDA5 at early and late in vivo infection stages, respectively. ALV-J strain SCAU-HN06 did not induce any significant antiviral innate immune response in one week old chicks. However, interferon-stimulated genes were not induced normally during the late phase of ALV-J infection due to a reduction of IRF1 and STAT1 expression

Altered methylation and expression of ER-associated degradation factors in long-term alcohol and constitutive ER stress-induced murine hepatic tumors

Mortality from liver cancer in humans is increasingly attributable to heavy or long-term alcohol consumption. The mechanisms by which alcohol exerts its carcinogenic effect are not well understood. In this study, the role of alcohol-induced endoplasmic reticulum (ER) stress response in liver cancer development was investigated using an animal model with a liver knockout of the chaperone BiP and under constitutive hepatic ER stress. Long-term alcohol and high fat diet (HFD) feeding resulted in higher levels of serum alanine aminotransferase (ALT), impaired ER stress response, and higher incidence of liver tumor in older (aged 16 months) knockout females than in either middle-aged (6 months) knockouts or older (aged 16 months) wild type females. In the older knockout females, stronger effects of the alcohol on methylation of CpG islands at promoter regions of genes involved in the ER associated degradation (ERAD) were also detected. Altered expression of ERAD factors including derlin 3, Creld2 (cysteine-rich with EGF-like domains 2), Herpud1 (ubiquitin-like domain member), Wfs1 (wolfram syndrome gene), and Yod1 (deubiquinating enzyme 1) was co-present with decreased proteasome activities, increased estrogen receptor alpha variant (ERa36), and enhanced phosphorylations of ERK1/2 (extracellular signal-regulated protein kinases 1 and 2) and STAT3 (the signal transducers and activators of transcription) in the older knockout female fed alcohol. Our results suggest that long-term alcohol consumption and ageing may promote liver tumorigenesis in females through interfering with DNA methylation and expression of genes involved in the ER associated degradation

Co-expression of xerophyte Zygophyllum xanthoxylum ZxNHX and ZxVP1-1 confers enhanced salinity tolerance in chimeric sugar beet (Beta vulgaris L.)

Salinity is one of the major abiotic stresses that limit the growth and productivity of sugar beet (Beta vulgaris L.). To improve sugar beet’s salinity tolerance, the ZxNHX and ZxVP1-1 genes encoding tonoplast Na+/H+ antiporter and H+-PPase from xerophyte Zygophyllum xanthoxylum were co-expressed by Agrobacterium tumefaciens-mediated transformation. It is showed here that co-expression of ZxNHX and ZxVP1-1 confers enhanced salinity tolerance to the transformed sugar beet plants compared with the wild-type (WT) plants. The chimeric plants grew well in the presence of high salinity (400 mM NaCl), whereas WT plants displayed chlorosis and died within 8 days. Compared to WT plants, the chimeric plants co-expressing ZxNHX and ZxVP1-1 accumulated more proline, Na+ and K+ in their leaves and petioles when exposed to high salinity, which caused lower solute potential, retained more water and thus subjected to lesser cell membrane damage. Interestingly, the chimeric plants accumulated higher sucrose, glucose and fructose contents in their storage roots than WT plants in the absence or presence of high salinity. Our results suggested that co-expression of ZxNHX and ZxVP1-1 improved the osmoregulatory capacity in chimeric sugar beet through increased compartmentalization of ions into the vacuoles by enhancing the activity of proton pumps and thus mitigated Na+-toxicity for plants

Suberoylanilide Hydroxamic Acid, A Histone Deacetylase Inhibitor, Attenuates Postoperative Cognitive Dysfunction in Aging Mice

Postoperative cognitive dysfunction (POCD) is a recognized clinical entity characterized with cognitive deficits after anesthesia and surgery, especially in aged patients. Previous studies have shown that histone acetylation plays a key role in hippocampal synaptic plasticity and memory formation. However, its role in POCD remains to be determined. Here, we show that suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, attenuates POCD in aging Mice. After exposed to the laparotomy, a surgical procedure involving an incision into abdominal walls to examine the abdominal organs, 16- but not 3-month old male C57BL/6 mice developed obvious cognitive impairments in the test of long-term contextual fear conditioning. Intracerebroventricular (i.c.v.) injection of SAHA at the dose of (20 μg/2 μl) 3 hours before and daily after the laparotomy restored the laparotomy-induced reduction of hippocampal acetyl-H3 and acetyl-H4 levels and significantly attenuated the hippocampus-dependent long-term memory impairments in 16-month old mice. SAHA also reduced the expression of cleaved caspase-3, inducible nitric oxide synthase and N-methyl-D-aspartate receptor-calcium/calmodulin dependent kinase II pathway, and increased the expression of brain-derived neurotrophic factor, synapsin 1, and postsynaptic density 95. Taken together, our data suggest that the decrease of histone acetylation contributes to POCD and may serve as a target to improve the neurological outcome of POCD