Dexmedetomidine (DEX) is known to provide neuroprotection against cerebral ischemia and reperfusion injury (CIRI), but the exact mechanisms remain unclear. This study was conducted to investigate whether DEX pretreatment conferred neuroprotection against CIRI by inhibiting neuroinflammation through the JAK2/STAT3 signaling pathway. Middle cerebral artery occlusion (MCAO) was performed to establish a cerebral ischemia/reperfusion (I/R) model. Specific-pathogen-free male Sprague-Dawley rats were randomly divided into Sham, I/R, DEX, DEX+IL-6, and AG490 (a selective inhibitor of JAK2) groups. The Longa score, TTC staining, and HE staining were used to evaluate brain damage. ELISA was used to exam levels of TNF-α. Western blotting was used to assess the levels of JAK2, phosphorylated-JAK2 (p-JAK2), STAT3, and phosphorylated-STAT3 (p-STAT3). Our results suggested that both pretreatment with DEX and AG490 decreased the Longa score and cerebral infarct areas following cerebral I/R. After treatment with IL-6, the effects of DEX on abrogating these pathological changes were reduced. HE staining revealed that I/R-induced neuronal pathological changes were attenuated by DEX application, consistent with the AG490 group. However, these effects of DEX were abolished by IL-6. Furthermore, TNF-α levels were significantly increased in the I/R group, accompanied by an increase in the levels of the p-JAK2 and p-STAT3. DEX and AG490 pretreatment down-regulated the expressions of TNF-α, p-JAK2, and p-STAT3. In contrast, the down-regulation of TNF-α, p-JAK2, and p-STAT3 induced by DEX was reversed by IL-6. Collectively, our results indicated that DEX pretreatment conferred neuroprotection against CIRI by inhibiting neuroinflammation via negatively regulating the JAK2/STAT3 signaling pathway.

ABSTRACT Antiviral drug resistance is the most important factor contributing to treatment failure using nucleos(t)ide analogs such as lamivudine for chronic infection with hepatitis B virus (HBV). Development of a system supporting efficient replication of clinically resistant HBV strains is imperative, and new antiviral drugs are needed urgently to prevent selection of drug-resistant HBV mutants. A novel fluorinated cytidine analog, NCC (N-cyclopropyl-4′-azido-2′-deoxy-2′-fluoro-β-d-cytidine), was recently shown to strongly inhibit human HBV in vitro and in vivo. This study was designed to evaluate the antiviral activity of NCC against lamivudine-resistant HBV. We generated a stable cell line encoding the major pattern of lamivudine-resistant mutations rtL180M/M204V and designated it "HepG2.RL1". Immuno-transmission electron microscopic examination and enzyme-linked immunosorbent assay were used to detect secretion of HBV-specific particles and antigens. Quantification of extracellular DNA and intracellular DNA of HepG2.RL1 cells by quantitative real-time polymerase chain reaction revealed >625-fold and >5556-fold increases in the 50% inhibitory concentration of lamivudine, respectively, compared with that for the wild-type virus. The results showed that NCC inhibited DNA replication and HBeAg production in wild-type or lamivudine-resistant HBV in a dose-dependent manner. In conclusion, screening for antiviral compounds active against lamivudine-resistant HBV can be carried out with relative ease using hepG2.RL1 cells. NCC is a potential antiviral agent against wild-type HBV and clinical lamivudine-resistant HBV and deserves evaluation for the treatment of HBV infection.

A series of HPW/Zn-Ti layered double hydroxides (LDHs) were prepared by immobilizing phosphotungstic acid (HPW) on the Zn-Ti LDHs. Systematically characterizations were performed to elucidate their structure. These HPW/Zn-Ti LDHs hybrids were used as heterogeneous catalysts in the epoxidation of fatty acid methyl ester (FAMEs) with H2O2. The HPW/Zn-Ti LDHs showed higher activity than bulk HPW and Zn-Ti LDHs. The conversion of FAMEs and the selectivity to epoxy fatty acid methyl ester (EFAME) were up to 90.6 and 86.0%, respectively. (PO4[WO2(O2)]4)3- was presumed to be the active site for the epoxidation in this work. The formed oxygen-donating intermediate Ti-OOH transferred oxygen free radicals to (PO4[WO2(O2)]4)3- in the catalytic process, accelerating the transfer of oxygen free radicals. Therefore, high catalytic activity of HPW/Zn-Ti LDHs is related to the potential synergistic interactions of Ti-OOH and PW anions.

Abstract: Background: Hordeum vulgare is an economically important crop that is consumed in large quantities in the world. In a previous investigation, we found that cadmium (Cd) could induce some nucleolar materials containing the argyrophilic proteins scattered in the nuclei and located in the cytoplasm in the root tip cells of H. vulgare. However, what kinds of nucleolar proteins are affected has not been reported. In order to further confirm the cytological effects of Cd on nucleolus and nucleolar proteins, alterations in the cellular localization and expression of two major nucleolar proteins: fibrillarin and nucleolin in the root tips of H. vulgare were studied in the present investigation. Methods: Cytological effects of Cd on nucleolus were observed by silver-staining method and two nucleolarproteins: nucleolin and fibrillarin were observed and analyzed by means of indirect immunofluorescent microscopy and western blotting. Results: Results from the present investigation demonstrated that under Cd stress (cadmium chloride at 50 and 100 µM), Cd could disturb the nucleolar cycle with the extrusion of silver-stained materials containing argyrophilic proteins from the nucleolus into the cytoplasm. Nucleolar material containing nucleolin and fibrillarin and their movement into the cytoplasm following Cd stress was detected with indirect immunofluorescence techniques. Western blotting revealed higher expression of these two major nucleoproteins in Cd-treated roots, which was consistent with the results obtained by indirect immunofluorescence. Conclusion: The findings of the present study confirm that Cd can have toxic effects on nucleolus and affect the expression of nucleolar proteins, nucleolin and fibrillarin. The data obtained here can provide valuable information for monitoring and forecast early effects of exposure to Cd in polluted environments.

Glycoprotein hormones in the pituitary gland affect a myriad of biological processes such as development, growth, metabolic control and gametogenesis. The quantitative trait loci (QTL) near their common glycoprotein alpha(A) subunit gene (CGA) have been reported inconsistently. The aim of this study was to dissect potential genetic factors for these unstable results and validate the association or linkage relationship of CGA gene with growth and carcass traits. By resequencing all the exons and part of the introns of the porcine CGA gene, 22 polymorphisms in total were identified in this study. Five single nucleotide polymorphism (SNP) markers were chosen and evaluated in six pure-bred pig breeds (n = 228). Breed-specific haplotypes were found and a map of the porcine CGA polymorphisms' evolution history was inferred. A resource family (n = 365) with different genetic backgrounds from those used in other papers was used to perform an association study. The resource family was created based on crosses of Pietrain and Jinhua pigs (Central China type pigs). Results indicated that a low correlation between haplotype blocks may abolish each other's effects. Moreover, a significant association of SNP C-925T with growth rate and back-fat thickness in this study confirmed the existence of previously reported QTL. SNP C-925T and SNP A+15599G could be useful linkage markers and SNP C-925T may also be a candidate causative SNP for the corresponding traits. Further investigation for variants within of the CGA promoter region and their association with growth rate and back-fat traits is suggested.

The PPARγ2 gene is a key regulator of both proliferation and preadipocyte differentiation in mammals. Herein its genotype and allele frequencies were analyzed using PCR-SSCP in eight pig breeds (N = 416). Two kinds of polymorphisms of the PPARγ2 gene were detected, including a previously reported shift SNP A177G (Met59Val) in exon 1 and a novel silent mutation G876A in exon 5. The results revealed that European pig breeds carry a higher allele A frequency at the A177G locus and a fixed GG genotype at the G876A locus. Allele A at the G876A locus was only found in Jinhua pigs. The association between haplotype (A177G/G876A) and carcass and meat quality traits was analyzed in a Pietrain x Jinhua F2 population (N = 248). The PPARγ2 gene was found to be significantly associated with backfat thickness at the shoulder (p < 0.05), 6-7th ribs (p < 0.01), last rib (p < 0.01), gluteus medius (p <0.05) and ham weight (p < 0.01). Significant effects of different haplotypes on ham weight and backfat thickness at the 6-7th ribs, last rib, and gluteus medius were also observed.