272 research outputs found

    Identification of the main flavonoids of Abelmoschus manihot (L.) medik and their metabolites in the treatment of diabetic nephropathy

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    Introduction: Huangkui capsule (HKC) is made from the ethanol extract of Abelmoschus manihot (L.) Medik [Malvaceae; abelmoschi corolla] and received approval from the China Food and Drug Administration (Z19990040) in 1999. Currently, HKC is used for treatment of the patients with diabetic nephropathy (DN) in China. The bioactive chemical constituents in HKC are total flavonoids of A. manihot (L.) Medik (TFA). The present study aims to identify the primary flavonoid metabolites in HKC and TFA and their metabolism fates in db/db mice, the animal model for the study of type 2 diabetes and DN.Methods: HKC (0.84聽g/kg/d) and TFA (0.076聽g/kg/d) or vehicle were respectively administered daily via oral gavage in db/db mice for 4 weeks. The metabolism fate of the main metabolites of HKC in serum, liver, kidney, heart, jejunum, colon, jejunal contents, colonic contents, and urine of db/db mice were analyzed with a comprehensive metabolite identification strategy.Results and Discussion: In db/db mice administered with HKC and TFA, 7 flavonoid prototypes and 38 metabolites were identified. The related metabolic pathways at Phases I and II reactions included dehydroxylation, deglycosylation, hydrogenation, methylation, glucuronidation, sulphation, and corresponding recombined reactions. Quercetin, isorhamnetin, quercetin sulphate, quercetin monoglucuronide, and isorhamnetin monoglucuronide presented a high exposure in the serum and kidney of db/db mice. Thereby, the present study provides a pharmacodynamic substance basis for better understanding the mechanism of A. manihot (L.) Medik for medication of DN

    Physiological and pathological characteristics of vascular endothelial injury in diabetes and the regulatory mechanism of autophagy

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    Vascular endothelial injury in diabetes mellitus (DM) is the major cause of vascular disease, which is closely related to the occurrence and development of a series of vascular complications and has a serious negative impact on a patient鈥檚 health and quality of life. The primary function of normal vascular endothelium is to function as a barrier function. However, in the presence of DM, glucose and lipid metabolism disorders, insulin resistance, inflammatory reactions, oxidative stress, and other factors cause vascular endothelial injury, leading to vascular endothelial lesions from morphology to function. Recently, numerous studies have found that autophagy plays a vital role in regulating the progression of vascular endothelial injury. Therefore, this article compares the morphology and function of normal and diabetic vascular endothelium and focuses on the current regulatory mechanisms and the important role of autophagy in diabetic vascular endothelial injury caused by different signal pathways. We aim to provide some references for future research on the mechanism of vascular endothelial injury in DM, investigate autophagy鈥檚 protective or injurious effect, and study potential drugs using autophagy as a target

    Targeting matrix metalloproteases in diabetic wound healing

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    Chronic inflammation participates in the progression of multiple chronic diseases, including obesity, diabetes mellitus (DM), and DM related complications. Diabetic ulcer, characterized by chronic wounds that are recalcitrant to healing, is a serious complication of DM tremendously affecting the quality of life of patients and imposing a costly medical burden on society. Matrix metalloproteases (MMPs) are a family of zinc endopeptidases with the capacity of degrading all the components of the extracellular matrix, which play a pivotal part in healing process under various conditions including DM. During diabetic wound healing, the dynamic changes of MMPs in the serum, skin tissues, and wound fluid of patients are in connection with the degree of wound recovery, suggesting that MMPs can function as essential biomarkers for the diagnosis of diabetic ulcer. MMPs participate in various biological processes relevant to diabetic ulcer, such as ECM secretion, granulation tissue configuration, angiogenesis, collagen growth, re-epithelization, inflammatory response, as well as oxidative stress, thus, seeking and developing agents targeting MMPs has emerged as a potential way to treat diabetic ulcer. Natural products especially flavonoids, polysaccharides, alkaloids, polypeptides, and estrogens extracted from herbs, vegetables, as well as animals that have been extensively illustrated to treat diabetic ulcer through targeting MMPs-mediated signaling pathways, are discussed in this review and may contribute to the development of functional foods or drug candidates for diabetic ulcer therapy. This review highlights the regulation of MMPs in diabetic wound healing, and the potential therapeutic ability of natural products for diabetic wound healing by targeting MMPs

    Rola miRNA w toksyczno艣ci nanocz膮stek srebra

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    Toksyczne dzia艂anie nanocz膮stek srebra zosta艂o potwierdzone na wielu liniach kom贸rkowych w tym na linii kom贸rek Hep G2. Na r贸偶nice w odpowiedzi kom贸rki na dzia艂anie nanocz膮stek srebra w r贸偶nych mediach hodowlanych mo偶e sk艂ada膰 si臋 wiele czynnik贸w, takich jak interferencja mikroRNA (miRNA) oraz stan metaboliczny. Interferencja miRNA jest jednym z proces贸w epigenetycznych, kt贸re s艂u偶膮 kom贸rkom prawid艂owym do przeprowadzania proces贸w fizjologicznych niezb臋dnych do utrzymania zdrowej kondycji tkanki i ca艂ego organizmu. Zar贸wno wzrost jak i spadek odpowiednich miRNA mo偶e nie艣膰 za sob膮 konsekwencje w postaci spadku poziom贸w produkt贸w gen贸w supresorowych lub zwi臋kszenie poziomu bia艂ek b臋d膮cych produktem onkogen贸w. W niniejszej pracy zbadano wp艂yw nanocz膮stek srebra na kom贸rki o r贸偶nym fenotypie metabolicznym, wp艂yw nanocz膮stek srebra na profil miRNA istotnych w powstawaniu i progresji nowotworu oraz wp艂yw modulacji miRNA na fenotyp kom贸rek poddanych toksycznemu dzia艂aniu nanocz膮stek srebra. Na model badawczy wybrano kom贸rki raka w膮trobowokom贸rkowego linii Hep G2, hodowane w po偶ywce zawieraj膮cej glukoz臋 w st臋偶eniu odzwierciedlaj膮cym st臋偶enie prawid艂owe u cz艂owieka oraz w po偶ywce o podwy偶szonym st臋偶eniu glukozy wyst臋puj膮cym przy ostrym stanie cukrzycowym. Przeprowadzone w toku rozprawy eksperymenty wykaza艂y, 偶e w zale偶no艣ci od warunk贸w hodowli kom贸rek Hep G2 ich odpowied藕 na toksyczne dzia艂anie wywo艂ane nanocz膮stkami srebra jest r贸偶na. Stwierdzono, 偶e nanocz膮stki srebra wywo艂uj膮 zmiany w profilach miRNA w kom贸rkach Hep G2. Transfekcja kom贸rek wykazuj膮cych zmieniony profil pod wp艂ywem czynnika badanego, syntetycznymi analogami miRNA nawet w niewielkich st臋偶eniach, mo偶e cofa膰 zmiany wywo艂ane tym czynnikiem.Diamentowy Grant Ministerstwa Nauki i Szkolnictwa Wy偶szego o numerze DI2016009546; Dofinansowanie na dzia艂alno艣膰 polegaj膮c膮 na prowadzeniu bada艅 naukowych lub prac rozwojowych oraz zada艅 z nimi zwi膮zanych, s艂u偶膮cych rozwojowi m艂odych naukowc贸w oraz uczestnik贸w studi贸w doktoranckich finansowanych w wewn臋trznym trybie konkursowym Uniwersytetu 艁贸dzkiego na rok 201

    Ferroptosis: new insight into the mechanisms of diabetic nephropathy and retinopathy

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    Diabetic nephropathy (DN) and diabetic retinopathy (DR) are the most serious and common diabetes-associated complications. DN and DR are all highly prevalent and dangerous global diseases, but the underlying mechanism remains to be elucidated. Ferroptosis, a relatively recently described type of cell death, has been confirmed to be involved in the occurrence and development of various diabetic complications. The disturbance of cellular iron metabolism directly triggers ferroptosis, and abnormal iron metabolism is closely related to diabetes. However, the molecular mechanism underlying the role of ferroptosis in DN and DR is still unclear, and needs further study. In this review article, we summarize and evaluate the mechanism of ferroptosis and its role and progress in DN and DR, it provides new ideas for the diagnosis and treatment of DN and DR

    Potential therapeutic effects of Chinese meteria medica in mitigating drug-induced acute kidney injury

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    Drug-induced acute kidney injury (DI-AKI) is one of the leading causes of kidney injury, is associated with high mortality and morbidity, and limits the clinical use of certain therapeutic or diagnostic agents, such as antineoplastic drugs, antibiotics, immunosuppressants, non-steroidal anti-inflammatory drugs, and contrast media. In recent years, numerous studies have shown that many Chinese meteria medica, metabolites derived from botanical drugs, and Chinese medicinal formulas confer protective effects against DI-AKI by targeting a variety of cellular or molecular mechanisms, such as oxidative stress, inflammatory, cell necrosis, apoptosis, and autophagy. This review summarizes the research status of common DI-AKI with Chinese meteria medica interventions, including cisplatin, gentamicin, contrast agents, methotrexate, and acetaminophen. At the same time, this review introduces the metabolites with application prospects represented by ginseng saponins, tetramethylpyrazine, panax notoginseng saponins, and curcumin. Overall, this review provides a reference for the development of promising nephroprotectants

    Protective effect of ginsenoside Rg1 on 661W cells exposed to oxygen-glucose deprivation/reperfusion via keap1/nrf2 pathway

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    AIM: To construct an in vitro model of oxygen-glucose deprivation/reperfusion (OGD/R) induced injury to the optic nerve and to study the oxidative damage mechanism of ischemia-reperfusion (I/R) injury in 661W cells and the protective effect of ginsenoside Rg1. METHODS: The 661W cells were treated with different concentrations of Na2S2O4 to establish OGD/R model in vitro. Apoptosis, intracellular reactive oxygen species (ROS) levels and superoxide dismutase (SOD) levels were measured at different time points during the reperfusion injury process. The injury model was pretreated with graded concentrations of ginsenoside Rg1. Real-time polymerase chain reaction (PCR) was used to measure the expression levels of cytochrome C (cyt C)/B-cell lymphoma-2 (Bcl2)/Bcl2 associated protein X (Bax), heme oxygenase-1 (HO-1), caspase9, nuclear factor erythroid 2-related factor 2 (nrf2), kelch-like ECH-associated protein 1 (keap1) and other genes. Western blot was used to detect the expression of nrf2, phosphorylated nrf2 (pnrf2) and keap1 protein levels. RESULTS: Compared to the untreated group, the cell activity of 661W cells treated with Na2S2O4 for 6 and 8h decreased (P<0.01). Additionally, the ROS content increased and SOD levels decreased significantly (P<0.01). In contrast, treatment with ginsenoside Rg1 reversed the cell viability and SOD levels in comparison to the Na2S2O4 treated group (P<0.01). Moreover, Rg1 reduced the levels of caspase3, caspase9, and cytC, while increasing the Bcl2/Bax level. These differences were all statistically significant (P<0.05). Western blot analysis showed no significant difference in the protein expression levels of keap1 and nrf2 with Rg1 treatment, however, Rg1 significantly increased the ratio of pnrf2/nrf2 protein expression compared to the Na2S2O4 treated group (P<0.001). CONCLUSION: The OGD/R process is induced in 661W cells using Na2S2O4. Rg1 inhibits OGD/R-induced oxidative damage and alleviates the extent of apoptosis in 661W cells through the keap1/nrf2 pathway. These results suggest a potential protective effect of Rg1 against retinal I/R injury

    A comprehensive and systemic review of ginseng-based nanomaterials: Synthesis, targeted delivery, and biomedical applications

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    Among 17 Panax species identified across the world, Panax ginseng (Korean ginseng), Panax quinquefolius (American ginseng), and Panax notoginseng (Chinese ginseng) are highly recognized for the presence of bioactive compound, ginsenosides and their pharmacological effects. P. ginseng is widely used for synthesis of different types of nanoparticles compared to P. quinquefolius and P. notoginseng. The use of nano-ginseng could increase the oral bioavailability, membrane permeability, and thus provide effective delivery of ginsenosides to the target sites through transport system. In this review, we explore the synthesis of ginseng nanoparticles using plant extracts from various organs, microbes, and polymers, as well as their biomedical applications. Furthermore, we highlight transporters involved in transport of ginsenoside nanoparticles to the target sites. Size, zeta potential, temperature, and pH are also discussed as the critical parameters affecting the quality of ginseng nanoparticles synthesis

    Investigating the Soil Mycobiome of American Ginseng

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    American ginseng (Panax quinquefolius L.) is a perennial herbaceous plant cultivated for its medicinal properties. Growers report that when ginseng is replanted in a field previously used to cultivate ginseng, it soon succumbs to disease, known as ginseng replant disease. I examined changes in composition in the ginseng mycobiome throughout cultivation in a newly planted garden and beyond (i.e., 3鈥14 years post-harvest) with a third-generation metabarcoding approach (Pacific Biosciences, single-molecule real-time sequencing). Amplicons of about 600 nucleotides from the nuclear ribosomal internal transcribed spacer (ITS) region and translation elongation factor 1-伪 gene were chosen to help discriminate between closely related fungal species. The ITS data showed community variations in fungal plant pathogens Fusarium oxysporum and F. solani over cultivation, and traces of Ilyonectria mors-panacis in ginseng garden soil. The mycobiome data generated provides insight into the dynamics of ginseng garden soil during ginseng cultivation and beyond

    螣 蟻蠈位慰蟼 蟿蠅谓 渭畏 魏蠅未喂魏慰蟺慰喂萎蟽喂渭蠅谓 蟻喂尾慰谓慰蠀魏位蔚蠆魏蠋谓 慰尉苇蠅谓 蟽蟿畏谓 伪胃畏蟻蠅渭维蟿蠅蟽畏 蟽蔚 维蟿慰渭伪 蠂蠅蟻委蟼 魏伪蟻未喂伪纬纬蔚喂伪魏萎 谓蠈蟽慰

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    违蟺维蟻蠂慰蠀蟽伪 纬谓蠋蟽畏- 蟽魏慰蟺蠈蟼: 韦慰 渭畏 魏蠅未喂魏慰蟺慰喂蠈 伪谓蟿喂蟺位畏蟻慰蠁慰蟻喂伪魏蠈 渭蔚蟿维纬蟻伪蠁慰 (non-coding antisense transcript) 蟿畏蟼 尾-蟽蔚魏蟻蔚蟿维蟽畏蟼-1 (BACE1-AS) 蔚委谓伪喂 苇谓伪 渭伪魏蟻维蟼 伪位蠀蟽委未伪蟼 蟻喂尾慰谓慰蠀魏位蔚蠆魏蠈 慰尉蠉 渭蔚 蟺蟻蠅蟿蔚蠉慰谓蟿伪 蟻蠈位慰 蟽蟿畏 蟻蠉胃渭喂蟽畏 蟿畏蟼 慰未慰蠉 蟺伪蟻伪纬蠅纬萎蟼 蟿慰蠀 尾-伪渭蠀位慰蔚喂未慰蠉蟼 (螒尾). 螘蟺喂未喂蠋尉伪渭蔚 谓伪 伪尉喂慰位慰纬萎蟽慰蠀渭蔚 蟿畏谓 魏位喂谓喂魏萎 伪尉委伪 蟿蠅谓 蔚蟺喂蟺苇未蠅谓 苇魏蠁蟻伪蟽畏蟼 蟿慰蠀 BACE1-AS 蟽蟿畏谓 伪胃畏蟻慰蟽魏位畏蟻蠀谓蟿喂魏萎 魏伪蟻未喂伪纬纬蔚喂伪魏萎 谓蠈蟽慰 (螒螝螡). 螠蔚胃慰未慰位慰纬委伪: 韦伪 蔚蟺委蟺蔚未伪 苇魏蠁蟻伪蟽畏蟼 蟿慰蠀 BACE1-AS 魏伪喂 蟿慰蠀 蟽蟿蠈蠂慰蠀 蟿慰蠀, 尾-蟽蔚魏蟻蔚蟿维蟽畏 1 (BACE1) 渭蔚蟿蟻萎胃畏魏伪谓 蟽蔚 渭慰谓慰蟺蠉蟻畏谓伪 魏蠉蟿蟿伪蟻伪 蟺蔚蟻喂蠁蔚蟻喂魏慰蠉 伪委渭伪蟿慰蟼, 蟺慰蠀 蟺蟻慰苇蟻蠂慰谓蟿伪谓 伪蟺蠈 434 蟽蠀渭渭蔚蟿苇蠂慰谓蟿蔚蟼, 蔚魏 蟿蠅谓 慰蟺慰委蠅谓 259 维蟿慰渭伪 蠂蠅蟻委蟼 蔚纬魏伪蟿蔚蟽蟿畏渭苇谓畏 魏伪蟻未喂伪纬纬蔚喂伪魏萎 谓蠈蟽慰, 90 伪蟽胃蔚谓蔚委蟼 渭蔚 喂蟽蟿慰蟻喂魏蠈 蟽蟿伪胃蔚蟻萎蟼 蟽蟿蔚蠁伪谓喂伪委伪蟼 谓蠈蟽慰蠀 魏伪喂 85 伪蟽胃蔚谓蔚委蟼 渭蔚 慰尉蠉 蟽蟿蔚蠁伪谓喂伪委慰 蟽蠉谓未蟻慰渭慰. 螤蟻伪纬渭伪蟿慰蟺慰喂萎胃畏魏伪谓 未慰渭喂魏苇蟼 魏伪喂 位蔚喂蟿慰蠀蟻纬喂魏苇蟼 伪纬纬蔚喂慰位慰纬喂魏苇蟼 蔚尉蔚蟿维蟽蔚喂蟼, 蠈蟺蠅蟼 畏 渭苇蟿蟻畏蟽畏 蟿慰蠀 蟺维蠂慰蠀蟼 蟿慰蠀 苇蟽蠅-渭苇蟽慰蠀 蠂喂蟿蠋谓伪, 畏 伪谓蔚蠉蟻蔚蟽畏 伪胃畏蟻蠅渭伪蟿喂魏蠋谓 蟺位伪魏蠋谓 蟽蟿慰 蔚谓未慰胃萎位喂慰 蟿蠅谓 魏伪蟻蠅蟿委未蠅谓 魏伪喂 蟿蠅谓 渭畏蟻喂伪委蠅谓 伪蟻蟿畏蟻喂蠋谓, 畏 伪谓维位蠀蟽畏 蟿蠅谓 伪蟻蟿畏蟻喂伪魏蠋谓 魏蠀渭伪蟿慰渭慰蟻蠁蠋谓 魏伪喂 畏 渭苇蟿蟻畏蟽畏 蟿畏蟼 蟿伪蠂蠉蟿畏蟿伪蟼 蟿慰蠀 蟽蠁蠀纬渭喂魏慰蠉 魏蠉渭伪蟿慰蟼, 渭苇蟽蠅 蠀蟺蔚蟻畏蠂慰纬蟻伪蠁委伪蟼, 魏伪胃蠋蟼 伪蟺慰蟿蔚位慰蠉谓 伪谓蟿喂蟺蟻慰蟽蠅蟺蔚蠀蟿喂魏慰蠉蟼 未蔚委魏蟿蔚蟼 蠀蟺慰魏位喂谓喂魏萎蟼 魏伪蟻未喂伪纬纬蔚喂伪魏萎蟼 谓蠈蟽慰蠀. 韦蠀蠂伪委慰 未蔚委纬渭伪 蟿慰蠀 蟽蠀谓慰位喂魏慰蠉 蟺位畏胃蠀蟽渭慰蠉 蟺伪蟻伪魏慰位慰蠀胃萎胃畏魏蔚 纬喂伪 未喂维渭蔚蟽慰 蠂蟻慰谓喂魏蠈 未喂维蟽蟿畏渭伪 52 渭畏谓蠋谓 渭蔚蟿维 蟿畏谓 伪蟻蠂喂魏萎 蔚蟺委蟽魏蔚蠄畏 渭蔚 蟽魏慰蟺蠈 蟿畏谓 魏伪蟿伪纬蟻伪蠁萎 谓苇蠅谓 渭蔚喂味蠈谓蠅谓 伪谓蔚蟺喂胃蠉渭畏蟿蠅谓 魏伪蟻未喂伪纬纬蔚喂伪魏蠋谓 蟽蠀渭尾伪渭维蟿蠅谓. 螒蟺慰蟿蔚位苇蟽渭伪蟿伪: 危蟿慰 蟽蠀纬蠂蟻慰谓喂魏蠈 蟽魏苇位慰蟼 蟿畏蟼 渭蔚位苇蟿畏蟼, 蟿伪 蔚蟺委蟺蔚未伪 苇魏蠁蟻伪蟽畏蟼 蟿慰蠀 BACE1-AS 蟺伪蟻慰蠀蟽委伪味伪谓 蟽蠀蟽蠂苇蟿喂蟽畏 渭蔚 蟿伪 蔚蟺委蟺蔚未伪 苇魏蠁蟻伪蟽畏蟼 蟿慰蠀 BACE1 (r=0.396, p&lt;0.001) 魏伪喂 慰蟻喂伪魏萎 蟽蠀蟽蠂苇蟿喂蟽畏 渭蔚 蟿伪 蔚蟺委蟺蔚未伪 蟺位维蟽渭伪蟿慰蟼 蟿慰蠀 螒尾1-40 (r=0.141, p=0.008). 螤伪蟻伪蟿畏蟻萎胃畏魏蔚 蠈蟿喂 蟿伪 蔚蟺委蟺蔚未伪 苇魏蠁蟻伪蟽畏蟼 蟿慰蠀 BACE1-AS 萎蟿伪谓 蠀蠄畏位蠈蟿蔚蟻伪 蟽蟿慰蠀蟼 蟽蠀渭渭蔚蟿苇蠂慰谓蟿蔚蟼 蠂蠅蟻委蟼 魏伪蟻未喂伪纬纬蔚喂伪魏萎 谓蠈蟽慰 蟺慰蠀 蟺伪蟻慰蠀蟽委伪味伪谓 渭蔚纬伪位蠉蟿蔚蟻慰 魏伪蟻未喂伪纬纬蔚喂伪魏蠈 魏委谓未蠀谓慰, 蠈蟺蠅蟼 蠀蟺慰位慰纬委味蔚蟿伪喂 伪蟺蠈 蟿慰 Heartscore (鈮5%) 魏伪胃蠋蟼 魏伪喂 蟽蟿慰蠀蟼 蟽蠀渭渭蔚蟿苇蠂慰谓蟿蔚蟼 蟿慰蠀 蟽蠀谓慰位喂魏慰蠉 蟺位畏胃蠀蟽渭慰蠉 蟿畏蟼 渭蔚位苇蟿畏蟼 渭蔚 蠀蠄畏位蠈 萎 蟺慰位蠉 蠀蠄畏位蠈 魏伪蟻未喂伪纬纬蔚喂伪魏蠈 魏委谓未蠀谓慰, 渭蔚 尾维蟽畏 蟿喂蟼 慰未畏纬委蔚蟼 蟿畏蟼 螘蠀蟻蠅蟺伪蠆魏萎蟼 螝伪蟻未喂慰位慰纬喂魏萎蟼 螘蟿伪喂蟻蔚委伪蟼 (p&lt;0.05 魏伪喂 纬喂伪 蟿喂蟼 未蠉慰 魏伪蟿畏纬慰蟻委蔚蟼). 韦伪 伪蠀尉畏渭苇谓伪 蔚蟺委蟺蔚未伪 苇魏蠁蟻伪蟽畏蟼 蟿慰蠀 BACE1-AS 蟽蠀蟽蠂蔚蟿委蟽蟿畏魏伪谓 渭蔚 伪蠀尉畏渭苇谓畏 蔚蟺委蟺蟿蠅蟽畏 蟽蟿蔚蠁伪谓喂伪委伪蟼 谓蠈蟽慰蠀 [OR=1.85 (95% CI: 1.37-2.5)], 蟺慰位蠀伪纬纬蔚喂伪魏萎蟼 蟽蟿蔚蠁伪谓喂伪委伪蟼 谓蠈蟽慰蠀 [OR=1.36 (95% CI:1.06-1.75)], 魏伪胃蠋蟼 魏伪喂 渭蔚 伪蠀尉畏渭苇谓慰 魏委谓未蠀谓慰 蠉蟺伪蟻尉畏蟼 蟺慰位位伪蟺位蠋谓 谓慰蟽慰蠉谓蟿蠅谓 伪纬纬蔚喂伪魏蠋谓 未喂魏蟿蠉蠅谓 [OR=1.31, (95% CI: 1.07-1.61) 纬喂伪 蟺慰位位伪蟺位维 谓慰蟽慰蠉谓蟿伪 伪纬纬蔚喂伪魏维 未委魏蟿蠀伪], 渭蔚蟿维 伪蟺蠈 蟺慰位蠀蟺伪蟻伪纬慰谓蟿喂魏萎 伪谓维位蠀蟽畏 位慰纬喂蟽蟿喂魏萎蟼 蟺伪位喂谓未蟻蠈渭畏蟽畏蟼, 蟽蟿伪胃渭喂蟽渭苇谓畏蟼 纬喂伪 蟿慰蠀蟼 魏位伪蟽喂魏慰蠉蟼 蟺伪蟻维纬慰谓蟿蔚蟼 魏伪蟻未喂伪纬纬蔚喂伪魏慰蠉 魏喂谓未蠉谓慰蠀. 危蟿慰 蟺蟻慰慰蟺蟿喂魏蠈 蟽魏苇位慰蟼 蟿畏蟼 渭蔚位苇蟿畏蟼, 蟿伪 伪蠀尉畏渭苇谓伪 蔚蟺委蟺蔚未伪 苇魏蠁蟻伪蟽畏蟼 蟿慰蠀 BACE1-AS 蟺伪蟻苇渭蔚喂谓伪谓 伪谓蔚尉维蟻蟿畏蟿慰蟼 蟺蟻慰纬谓蠅蟽蟿喂魏蠈蟼 蟺伪蟻维纬慰谓蟿伪蟼 纬喂伪 蟿畏谓 蔚渭蠁维谓喂蟽畏 渭蔚喂味蠈谓蠅谓 伪谓蔚蟺喂胃蠉渭畏蟿蠅谓 魏伪蟻未喂伪纬纬蔚喂伪魏蠋谓 蟽蠀渭尾伪渭维蟿蠅谓 蟽蔚 伪蟽胃蔚谓蔚委蟼 蠀蠄畏位慰蠉 魏伪蟻未喂伪纬纬蔚喂伪魏慰蠉 魏喂谓未蠉谓慰蠀 [蟽蟿伪胃渭喂蟽渭苇谓慰 HR= 1.86 伪谓维 伪蠉尉慰谓 蟿蟻喂蟿畏渭蠈蟻喂慰 BACE1-AS, (95% CI: 1.011-3.43), p=0.046]. 危蠀渭蟺蔚蟻维蟽渭伪蟿伪: 韦伪 蔚蟺委蟺蔚未伪 苇魏蠁蟻伪蟽畏蟼 蟿慰蠀 BACE1-AS 蟽蠀蟽蠂蔚蟿委味慰谓蟿伪喂 渭蔚 蟿畏谓 蔚蟺委蟺蟿蠅蟽畏 魏伪喂 蟿畏 尾伪蟻蠉蟿畏蟿伪 蟿畏蟼 伪胃畏蟻慰蟽魏位畏蟻蠀谓蟿喂魏萎蟼 魏伪蟻未喂伪纬纬蔚喂伪魏萎蟼 谓蠈蟽慰蠀.Background and aims: The non-coding antisense transcript for beta-secretase-1 (BACE1-AS) is a long non-coding RNA with a pivotal role in the regulation of amyloid-beta (A尾). We aimed to explore the clinical value of BACE1-AS expression in atherosclerotic cardiovascular disease (ASCVD). Methods: Expression of BACE1-AS and its target, beta-secretase 1 (BACE1) mRNA, was measured in peripheral blood mononuclear cells (PBMCs) derived from 434 individuals [259 without established cardiovascular disease (non-CVD), 90 with stable coronary artery disease (CAD) and 85 with acute coronary syndrome]. Intima-media thickness and atheromatous plaques evaluated by ultrasonography, as well as arterial wave reflections and pulse wave velocity were measured as markers of subclinical CVD. Patients were followed for a median of 52 months for major adverse cardiac events (MACE). Results: In the cross-sectional arm, BACE1-AS expression correlated with BACE1 expression (r=0.396, p&lt;0.001) and marginally with A尾1-40 levels in plasma (r=0.141, p=0.008). Higher BACE1-AS was associated with higher estimated CVD risk assessed by HeartScore for non-CVD subjects and by ESC clinical criteria for the total population (p&lt;0.05 for both). BACE1-AS was associated with higher prevalence of CAD [OR=1.85 (95% CI: 1.37-2.5)], multivessel CAD [OR=1.36 (95% CI:1.06-1.75)] and with higher number of diseased vascular beds [OR=1.31, (95% CI: 1.07-1.61) for multiple diseased vascular beds] after multivariable adjustment for traditional cardiovascular risk factors. In the prospective arm, BACE1-AS was an independent predictor of MACE in high cardiovascular risk patients [adjusted HR= 1.86 per ascending tertile, (95% CI: 1.011-3.43), p=0.046]. Conclusions: BACE1-AS is associated with the incidence and severity of atherosclerotic cardiovascular disease
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