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  • Ovid Technologies (Wolters Kluwer Health)  (4)
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  • Ovid Technologies (Wolters Kluwer Health)  (4)
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  • 1
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. 6 ( 2020-08-11), p. 556-574
    Abstract: Stroke is a leading cause of adult disability that can severely compromise the quality of life of patients, yet no effective medication currently exists to accelerate rehabilitation. A variety of circular RNA (circRNA) molecules are known to function in ischemic brain injury. Lentivirus-based expression systems have been widely used in basic studies of circRNAs, but safety issues with such delivery systems have limited exploration of the potential therapeutic roles for circRNAs. Methods: Circular RNA SCMH1 (circSCMH1) was screened from the plasma of patients with acute ischemic stroke by using circRNA microarrays. Engineered rabies virus glycoprotein-circSCMH1-extracellular vesicles were generated to selectively deliver circSCMH1 to the brain. Nissl staining was used to examine infarct size. Behavioral tasks were performed to evaluate motor functions in both rodent and nonhuman primate ischemic stroke models. Golgi staining and immunostaining were used to examine neuroplasticity and glial activation. Proteomic assays and RNA-sequencing data combined with transcriptional profiling were used to identify downstream targets of circSCMH1. Results: CircSCMH1 levels were significantly decreased in the plasma of patients with acute ischemic stroke, offering significant power in predicting stroke outcomes. The decreased levels of circSCMH1 were further confirmed in the plasma and peri-infarct cortex of photothrombotic stroke mice. Beyond demonstrating proof-of-concept for an RNA drug delivery technology, we observed that circSCMH1 treatment improved functional recovery after stroke in both mice and monkeys, and we discovered that circSCMH1 enhanced the neuronal plasticity and inhibited glial activation and peripheral immune cell infiltration. CircSCMH1 binds mechanistically to the transcription factor MeCP2 (methyl-CpG binding protein 2), thereby releasing repression of MeCP2 target gene transcription. Conclusions: Rabies virus glycoprotein-circSCMH1-extracellular vesicles afford protection by promoting functional recovery in the rodent and the nonhuman primate ischemic stroke models. Our study presents a potentially widely applicable nucleotide drug delivery technology and demonstrates the basic mechanism of how circRNAs can be therapeutically exploited to improve poststroke outcomes.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1466401-X
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  • 2
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 100, No. 12 ( 2021-03-26), p. e24884-
    Abstract: Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease characterized by excess accumulation of fat in hepatocytes. Because no drug has been approved for NAFLD treatment, this work analyzed the effects of agents resulting from 2 research hotspots, metabolic target agents, and natural plant drugs, on NAFLD with network meta-analysis. Methods: Public databases were searched through August 14, 2020. Randomized controlled trials that compared obeticholic acid, elafibranor, cenicriviroc, selonsertib, curcumin, silymarin, and resveratrol to placebo were included. Liver pathology improvement, hepatic biochemical indicators, and lipid metabolism indicators were analyzed. Results: Thirty-five studies were included in the meta-analysis. Obeticholic acid was found to significantly increase the frequency of liver biopsy improvement compared to placebo (OR: 2.10; 95% CI: 1.60, 2.77). The ranking results among the hepatic biochemical indicators showed that obeticholic acid (94.9%) and elafibranor (86.3%) have a relative advantage in reducing alanine aminotransferase (ALT) levels, and obeticholic acid also had an advantage (95.4%) in reducing aspartate aminotransferase (AST) levels. Considering lipid metabolic indicators, elafibranor (expSMD: 0.01; 95% CI: 0.00, 0.05; SUCRA: 100%), and obeticholic acid (expSMD: 0.48; 95% CI: 0.28,0.84; SUCRA: 75.6%) significantly reduced triglyceride (TG) levels compared with placebo; moreover, obeticholic acid, but not elafibranor, caused a serious increase in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and a decrease in high-density lipoprotein cholesterol (HDL-C) levels. Conclusions: Novel metabolic targeted agents generally have better effects than natural plant drugs, especially obeticholic acid, and elafibranor. However, obeticholic acid showed serious adverse effects such as increasing LDL-C levels and decreasing HDL-C levels. Curcumin showed potential advantages for NAFLD but lacked statistical significance.
    Type of Medium: Online Resource
    ISSN: 0025-7974 , 1536-5964
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2049818-4
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  • 3
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Medicine Vol. 98, No. 17 ( 2019-04), p. e15073-
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 98, No. 17 ( 2019-04), p. e15073-
    Abstract: A mismatch between the femoral bow and intramedullary nails causes a series of complications. Previous investigations have sought to determine the curvature of the femur using the radius of the femoral bow. However, the radius of the curvature is affected by femur length. To eliminate the influence of femur length, we instead used an angle to indicate femoral curvatures. Forty patients with intertrochanteric fractures who underwent a surgical procedure at our institution were enrolled in this study. We conducted a lateral X-ray of the contralateral femur before operation. We drew a triangle in the X-ray images using Digimizer software. The tangent values of the acute angle were used to indicate femoral curvature. The tangent values were then compared with the dimensions of currently used nails. The average tangent value of the femurs was 0.0835 ± 0.0147, as measured from the inner cortex and 0.0798 ± 0.0150, as measured from the outer cortex. The tangent values were related to sex, with males having straighter femurs than females, and there was no obvious correlation between tangent values and age or femur length. Tangent value is a reliable method with a high intersurveyor consistency; femur curvatures were significantly greater than the curvatures of currently used nails.
    Type of Medium: Online Resource
    ISSN: 0025-7974 , 1536-5964
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2049818-4
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  • 4
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 100, No. 17 ( 2021-04-30), p. e25636-
    Type of Medium: Online Resource
    ISSN: 0025-7974 , 1536-5964
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2049818-4
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