Enchanced levels of apolipoprotein M during HBV infection feedback suppresses HBV replication

<p>Abstract</p> <p>Background</p> <p>Chronic liver diseases can interfere with hepatic metabolism of lipoproteins, apolipoproteins. Hepatitis B virus (HBV) is a major etiological agent causing acute and chronic liver diseases. Apolipoprotein M (ApoM) is a high-density lipoprotein (HDL) apolipoprotein and exclusively expressed in the liver parenchyma cells and in the tubular cells of the kidney. This study was to determine the correlation between HBV infection and ApoM expression.</p> <p>Materials and methods</p> <p>Serum ApoM levels in patients with HBV infection and in healthy individuals were measured by ELISA, ApoM mRNA expression were determined by RT-PCR, and the expression of S and E proteins of HBV, as well as the synthesis of viral DNA were measured by ELISA and real-time PCR.</p> <p>Results</p> <p>The levels of serum ApoM was significantly elevated in patients as compared to healthy individuals (<it>P </it>< 0.001), ApoM promoter activity, mRNA and protein expression were all stimulated in cells transfected with infectious HBV clone. In addition, ApoM decreases the expression of S and E proteins of HBV and the synthesis of viral DNA.</p> <p>Conclusion</p> <p>Raised ApoM levels in HBV infection may in turn suppress HBV replication, one of the protective mechanisms of nature.</p

Assessing the concentration and potential health risk of heavy metals in China's main deciduous fruits

AbstractTo assess levels of contamination and human health risk, we analyzed the concentrations of the heavy metals lead (Pb), cadmium (Cd), chromium (Cr), and nickel (Ni) in China's main deciduous fruits — apple, pear, peach, grape, and jujube. The concentration order of the heavy metals was Ni>Cr>Pb>Cd. In 97.5% of the samples, heavy metal concentrations were within the maximum permissible limits. Among the fruits studied, the heavy metal concentrations in jujube and peach proved to be the highest, and those in grape proved to be the lowest. Only 2.2% of the samples were polluted by Ni, only 0.4% of the samples were polluted by Pb, and no samples were polluted by Cd or Cr. Compared with the other fruits, the combined heavy metal pollution was significantly higher (P<0.05) in peach and significantly lower (P<0.05) in grape. For the combined heavy metal pollution, 96.9% of the samples were at safe level, 2.32% at warning level, 0.65% at light level, and 0.13% at moderate level. In the fruits studied, the contribution of heavy metals to the daily intake rates (DIR) followed the order of Ni>Cr>Pb>Cd. The highest DIR came from apple, while the lowest DIR came from grape. For each of the heavy metals, the total DIR from five studied fruits corresponded to no more than 1.1% of the tolerable daily intake, indicating that no significant adverse health effects are expected from the heavy metals and the fruits studied. The target hazard quotients and the total target hazard quotients demonstrated that none of the analyzed heavy metals may pose risk to consumers through the fruits studied. The highest risk was posed by apple, followed in decreasing order by peach and pear, jujube, and grape. We suggest that the main deciduous fruits (apple, pear, peach, grape, and jujube) of China's main producing areas are safe to eat

Molecular and biochemical characterization of key enzymes in the cysteine and serine metabolic pathways of Acanthamoeba castellanii

Abstract Background Acanthamoeba spp. can cause serious human infections, including Acanthamoeba keratitis, granulomatous amoebic encephalitis and cutaneous acanthamoebiasis. Cysteine biosynthesis and the L-serine metabolic pathway play important roles in the energy metabolism of Acanthamoeba spp. However, no study has confirmed the functions of cysteine synthase (AcCS) in the cysteine pathway and phosphoglycerate dehydrogenase (AcGDH) or phosphoserine aminotransferase (AcSPAT) in the non-phosphorylation serine metabolic pathway of Acanthamoeba. Methods The AcCS, AcGDH and AcSPAT genes were amplified by PCR, and their recombinant proteins were expressed in Escherichia coli. Polyclonal antibodies against the recombinant proteins were prepared in mice and used to determine the subcellular localisation of each native protein by confocal laser scanning microscopy. The enzymatic activity of each recombinant protein was also analysed. Furthermore, each gene expression level was analysed by quantitative PCR after treatment with different concentrations of cysteine or L-serine. Results The AcCS gene encodes a 382-amino acid protein with a predicted molecular mass of 43.1 kDa and an isoelectric point (pI) of 8.11. The AcGDH gene encodes a 350-amino acid protein with a predicted molecular mass of 39.1 kDa and a pI of 5.51. The AcSPAT gene encodes a 354-amino acid protein with a predicted molecular mass of 38.3 kDa and a pI of 6.26. Recombinant AcCS exhibited a high cysteine synthesis activity using O-acetylserine and Na2S as substrates. Both GDH and SPAT catalysed degradation, rather than synthesis, of serine. Exogenous L-serine or cysteine inhibited the expression of all three enzymes in a time- and dose-dependent manner. Conclusions This study demonstrated that AcCS participates in cysteine biosynthesis and serine degradation via the non-phosphorylation serine metabolic pathway, providing a molecular basis for the discovery of novel anti-Acanthamoeba drugs

G protein kinase 4gammaA142V overexpression induced hypertension by downregulating D1 receptors in transgenic mice

OBJECTIVE: Abnormalities in dopamine production and receptor function have been described in human essential hypertension and rodent models of genetic hypertension. We investigated the role of G protein kinase (GRK) 4gamma in essential hypertension in GRK4gamma mutant A142V transgenic mice. METHODS: Blood pressure, renal sodium excretion, D(1) receptor protein expression and phosphorylation were measured in GRK4gammaA142V transgenic mice and control mice. Moreover, the effects of GRK4 inhibition by antisense oligonucleotides on D(1) receptor expressions were determined in HK-2 cells. RESULTS: As compared with their control mice, GRK4gammaA142V transgenic mice had higher blood pressure, lower D(1) receptor expression (0.6 +/- 0.2 vs. 1.5 +/- 0.2, P \u3c 0.05), higher D(1) receptor phosphorylation [(65 +/- 7) DU vs. (35 +/- 7) DU, P \u3c 0.05] in renal cortical membranes and the diuretic and natriuretic effects after stimulation of renal D(1) receptor were impaired in GRK4gammaA142V transgenic mice. Inhibition of GRK4 expression (0.60 +/- 0.10 vs. 1.30 +/- 0.09, P \u3c 0.05) by GRK4 antisense oligonucleotides upregulated D(1) receptor expression (1.5 +/- 0.2 vs. 0.8 +/- 0.1, P \u3c 0.05) in HK-2 cells. CONCLUSIONS: Our results show that GRK4gammaA142V overexpression induced hypertension is mediated by dowregulated renal D(1) receptor expressions in GRK4gammaA142V transgenic mice

New Caffeoylquinic Acid Derivatives and Flavanone Glycoside from the Flowers of <i>Chrysanthemum morifolium</i> and Their Bioactivities

The Chrysanthemum morifolium flower is widely used in China and Japan as a food, beverage, and medicine for many diseases. In our work, two new caffeoylquinic acid derivatives (1, 2), a new flavanone glycoside (3), and six reported flavanones (4&#8315;9) were isolated and identified from the flowers of C. morifolium. The chemical structures of all isolates were elucidated by the analysis of comprehensive spectroscopic data as well as by comparison with previously reported data. The isolated constituents 1&#8315;8 were evaluated for their neuroprotective activity, and compounds 3 and 4 displayed neuroprotective effects against hydrogen peroxide-induced neurotoxicity in human neuroblastoma SH-SY5Y cells