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wen, b.

Publications and source records attributed to wen, b..

3 recordsLinked to original sources

IDOL deficiency inhibits cholesterol-rich diet-induced atherosclerosis in rabbits

BACKGROUNDThe E3 ubiquitin ligase IDOL (Inducible Degrader of the LDL-Receptor) contributes to regulation of cholesterol metabolism through degradation of LDLR, VLDLR and ApoER2. Human genetic studies support the hypothesis that IDOL could serve as a target for the treatment of dyslipidemia. However, species-specific differences in overall lipid metabolism and IDOL regulation require new preclinical models to realize its therapeutic potential. We leveraged the advantages afforded by the rabbit model to address those limitations and generated a novel rabbit IDOL knockout, which we characterized in the context of atherosclerosis. METHODSIDOL-/- rabbits were generated by CRISPR/Cas9 technology. IDOL-/- and wildtype littermates, on standard (SD) and atherogenic high-cholesterol diets (HCDs) were compared through assessment of lipid and lipoprotein profiles, triglyceride clearance, lipoprotein lipase (LPL) activity, liver pathology, atherosclerosis development, and fecal cholesterol, with bile acid contents assessed by mass spectrometry. ResultsHepatic IDOL expression was increased in response to hypercholesterolemia and hypertriglyceridemia induced by HCD. On SD, loss of IDOL increased LDLR stability with reduced total cholesterol in plasma. On HCD, IDOL-/- rabbits showed simultaneous and remarkable reduction in hypercholesterolemia and hypertriglyceridemia associated with enhanced lipid clearance and LPL activity as well as increased bile acid excretion in feces. IDOL-/- rabbits presented markedly reduced HCD-induced atherosclerosis in the aorta and left coronary artery, without enhanced liver steatosis. CONCLUSIONSLoss of IDOL in rabbits recapitulates human genetic findings, thus setting the stage to accelerate preclinical studies towards development of strategies targeting IDOL for the treatment of atherosclerotic cardiovascular disease.

physiology↗

Sensitivity in the antioxidant system of discus fish (Symphysodon spp.) to cold temperature: evidence for species-specific cold resistance

The discus fish (Symphysodon spp.) is an endemic species of the Amazon that is among the most popular ornamental fish around the world, and is usually used as the model animal for studying the diversification of Amazon fish. Here, a comparative analysis of two species of discus fish, i.e., S. haraldi and S. aequifasciatus, based on several antioxidant indexes was conducted, to test the hypothesis that cold resistance might correlate with the diversification of discus fish. We set up a continuous sequence of three temperature programs, namely cooling (28 {degrees}C to 14 {degrees}C; -1 {degrees}C/h), cold maintenance (14 {degrees}C for 12 h) and recovery (14 {degrees}C to 28 {degrees}C; +1 {degrees}C/h). Subordinate function (SF) combined with principal component analysis (PCA) showed that the cold hardiness of S. haraldi during cold treatment was in the order of cooling > cold maintenance {approx} recovery, but the cold hardiness of S. aequifasciatus during cold treatment was in the order of cold maintenance > cooling > recovery. Specifically, the lowest cold hardiness was observed in S. aequifasciatus during recovery, indicating that cold stress resulted in more seriously oxidative stress in S. aequifasciatus than in S. haraldi. Overall, these results show a significant interspecific variation, indicating the correlation between environmental adaptation and the diversification of discus fish.

ecology↗

Identification and characterization of cherry (Cerasus pseudocerasus G. Don) genes in response to parthenocarpy induced by GA3 through transcriptome analysis

Fruit set after successful pollination is a key process in the production of sweet cherries, but low fruit rate is the main problem for crop production in sweet cherries. Gibberellin treatment can directly induce parthenogenesis without pollination; therefore, gibberellin treatment is a very important method to improve the fruit setting rate of sweet cherries. Exogenous gibberellin can satisfy the hormone requirement during fruit growth and development. Some related studies have mainly focused on physiological aspects, such as breeding, branching, fertilization, etc., and the molecular mechanism is not clear. In this study, we analyzed the transcriptome of Meizao sweet cherry fruit treated with gibberellin during the anthesis and hard-core period to determine the genes associated with parthenocarpic fruit set. A total of 765 and 186 differentially expressed genes (DEGs) were found at anthesis and the hard-core stage after gibberellin 3 (GA3) treatment, respectively. The differentially expressed genes between the control and GA3 treatment showed that the GA3 response mainly included parthenocarpic fruit set and cell division. Exogenous gibberellin stimulated sweet cherry parthenocarpy and enlargement, which were verified by qRT-PCR results of related genes and the parthenocarpic fruit set and fruit size. Based on our research and previous studies on Arabidopsis thaliana, we identified the key genes associated with parthenocarpic fruit set and cell division. Briefly, we found patterns in the sweet cherry fruit setting-related DEGs, especially those associated with hormone balance, cytoskeleton formation and cell wall modification. Overall, the result provides a possible molecular mechanism regulating parthenocarpic fruit set, which is important for basic research and industrial development of sweet cherries.\n\nHighlightcherry genes in response to parthenocarpy and promote to fruit setting induced by GA3.

molecular biology↗