Qinggan Huoxue Recipe Alleviates Alcoholic Liver Injury by Suppressing Endoplasmic Reticulum Stress Through LXR-LPCAT3.

Endoplasmic reticulum stress (ERS) plays a key role in alcohol liver injury (ALI). Lysophosphatidylcholine acyltransferase 3 (LPCAT3) is a potential modifier of ERS. It was examined whether the protective effect of Qinggan Huoxue Recipe (QGHXR) against ALI was associated with LPCAT3 by suppressing ERS from in vivo and in vitro experiment. Male C57BL/6 mice were randomly divided into five groups (n = 10, each) and treated for 8 weeks as follows: the control diet-fed group (pair-fed), ethanol diet-fed group (EtOH-fed), QGHXR group (EtOH-fed + QGHXR), Qinggan recipe group (EtOH-fed + QGR), and Huoxue recipe group (EtOH-fed + HXR). QGHXR, QGR, and HXR groups attenuated liver injury mainly manifested in reducing serum ALT, AST, and liver TG and reducing the severity of liver cell necrosis and steatosis in ALI mouse models. QGHXR mainly inhibited the mRNA levels of Lxrα, Perk, Eif2α, and Atf4 and activated the mRNA levels of Lpcat3 and Ire1α, while inhibiting the protein levels of LPCAT3, eIF2α, IRE1α, and XBP1u and activating the protein levels of GRP78 to improve ALI. QGR was more inclined to improve ALI by inhibiting the mRNA levels of Lxrα, Perk, Eif2α, Atif4, and Chop and activating the mRNA levels of Lpcat3 and Ire1α while inhibiting the protein levels of LPCAT3, PERK, eIF2α, IRE1α, and XBP1u. HXR was more inclined to improve ALI by inhibiting the mRNA levels of Perk, Eif2α, Atf4, and Chop mRNA while inhibiting the protein levels of LPCAT3, PERK, eIF2α, IRE1α, and XBP1u and activating the protein levels of GRP78. Ethanol (100 mM) was used to intervene HepG2 and AML12 to establish an ALI cell model and treated by QGHXR-, QGR-, and HXR-medicated serum (100 mg/L). QGHXR, QGR, and HXR groups mainly reduced the serum TG level and the expression of inflammatory factors such as IL-6 and TNF-α in the liver induced by ethanol. In AML12 cells, QGHXR and its disassembly mainly activated Grp78 mRNA expression together with inhibiting Lxrα, Lpcat3, Eif2α, Atf4, and Xbp1 mRNA expression. The protein expression of eIF2α and XBP1u was inhibited, and the expression of PERK and GRP78 was activated to alleviate ALI. In HepG2 cells, QGHXR mainly alleviated ALI by inhibiting the mRNA expression of LPCAT3, CHOP, IRE1α, XBP1, eIF2α, CHOP, and IRE1α protein. QGR was more inclined to inhibit the protein expression of PERK, and HXR was more likely to inhibit the protein expression of ATF4.

Assessment of persistent organic pollutants accumulation and lipid peroxidation in two reproductive stages of wild silverside (Odontesthes bonariensis).

Persistent organic pollutants (POPs) in streamwater can sometimes exceed the guidelines values reported for biota and human protection in watersheds with intensive agriculture. Oxidative stress and cytotoxicity are some of the markers of exposure to POPs in fish. Accumulation of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) as well as lipid peroxidation (LPO) was assessed in wild silverside (Odontesthes bonariensis) from maturation and pre-spawning stages sampled in a typical soybean growing area. Pollutants were quantified by gas chromatography with electron capture detection and LPO by the method of thiobarbituric acid reactive substances. Concentrations of POPs were in the following order: OCPs>PCBs>PBDEs in all organs and stages. Liver, gills and gonads had the highest OCP concentrations in both sexes and stages with a predominance of endosulfan in all samples. Matured individuals, sampled after endosulfan application period, showed higher endosulfan concentrations than pre-spawning individuals. The predominance of endosulfan sulfate could be due to direct uptake from diet and water column, as well as to the metabolism of the parent compounds in fish. The prevalence of p,p'-DDE in liver would also reflect both the direct uptake and the metabolic transformation of p,p'-DDT to p,p'-DDE by fish. The highest levels of PBDEs and PCBs were found in gills and brain of both stages of growth. The pattern BDE-47>BDE-100 in all samples corresponds to pentaBDE exposure. In the case of PCBs, penta (#101 and 110) and hexa-CB congeners (#153 and 138) dominated in the maturation stages and tri (#18) and tetra-CB (#44 and 52) in pre-spawning stages, suggesting biotransformation or preferential accumulation of heavier congeners during gonadal development. Differences in LPO levels in ovaries were associated with growth dilution and reproductive stage. Differences in LPO levels in gills were related with pesticide application periods. As a whole, endosulfan, a current-use pesticide, constituted the main pollutant found in wild silverside reflecting the intense agriculture activity in the study area. Moreover endosulfan was positively correlated with LPO.

Quercetin-3-O-(2"-galloyl)-α-l-rhamnopyranoside prevents TRAIL-induced apoptosis in human keratinocytes by suppressing the caspase-8- and Bid-pathways and the mitochondrial pathway.

Quercetin and its derivatives have antioxidant and anti-inflammatory effects. Nevertheless, in human keratinocytes, compared to the reports on other toxic insults, researches on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis that may be involved in skin diseases are rare. Furthermore, the effect of quercetin-3-O-(2"-galloyl)-α-l-rhamnopyranoside (QGR), a new quercetin derivative, on TRAIL-induced apoptosis in keratinocytes has not been studied. In this respect, we investigated the effect of QGR on TRAIL-induced apoptosis in human keratinocytes. TRAIL triggers apoptosis by inducing a decrease in Bid, Bcl-2, Bcl-xL and survivin protein levels, increase in Bax and VDAC1 levels, loss of the mitochondrial transmembrane potential, release of cytochrome c, activation of caspases (-8, -9 and -3), cleavage of PARP-1, and an increase in the tumor suppressor p53 levels. Treatment with QGR prevented TRAIL-induced apoptosis-related protein activation, formation of reactive oxygen species, nuclear damage, and cell death. In contrast, quercetin induces cytotoxicity and had an additive effect on TRAIL-induced apoptosis-related protein activation and cell death. These results suggest that the QGR, unlike quercetin, may reduce TRAIL-induced apoptosis in human keratinocytes by suppressing the activation of the caspase-8- and Bid-pathways and the mitochondria-mediated cell death pathway, which is associated with the formation of reactive oxygen species. These data suggest that QGR could be effective in the prevention of TRAIL-induced apoptosis-mediated skin diseases.

MODELS OF CHARACTER DISPLACEMENT AND THE THEORETICAL ROBUSTNESS OF TAXON CYCLES.

The appropriateness of the techniques used in modeling character displacement has been the focus of vigorous debate. In this paper, the three competing methods (the coevolutionarily stable community (CSC), the evolutionarily stable strategy (ESS), and quantitative genetic recursion (QGR)) are compared in models using a common ecological setting. Specific predictions of the CSC model have been used to understand features of character displacement among Cnemidophorous lizards on islands off Mexico, Anolis lizards in the Lesser Antilles and Galápagos finches. Nonetheless, the validity of the approach has been repeatedly questioned. Conceptually the three formalisms vary in the degree to which within species variability is allowed in the models. The predictions of the CSC are found not to be robust to even small violation of its fundamental assumption of absolute species monomorphy. We show by simulation and analytical observations that the CSC is not valid under frequency dependent selection, and that the ESS is the limiting case of QGR as intraspecific phenotypic variation goes to zero. Thus the ESS and the QGR models agree closely when the between-phenotype component (BPC) of the niche width is small. However, as the BPC increases, quantitative discrepancies between ESS and QGR predictions increase, although model behavior remains qualitatively similar. A fourth approach, termed "Quantitative Genetic Optimization" (QGO) analysis, is suggested, combining advantages of both the ESS and QGR. Although all approaches support the possibility of taxon cycles, the cycle patterns predicted are qualitatively different and strongly model dependent.