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  • 1
    Online Resource
    Online Resource
    Bentham Science Publishers Ltd. ; 2021
    In:  Current Medicinal Chemistry Vol. 28, No. 5 ( 2021-02), p. 1025-1041
    In: Current Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 28, No. 5 ( 2021-02), p. 1025-1041
    Abstract: Coronary heart disease (CHD) is closely related to hypercholesterolemia, and lowering serum cholesterol is currently the most important strategy in reducing CHD. In humans, the serum cholesterol level is determined mainly by three metabolic pathways, namely, dietary cholesterol intake, cholesterol synthesis, and cholesterol degradation in vivo. An intervention that targets the key molecules in the three pathways is an important strategy in lowering serum lipids. Statins inhibit 3-hydroxyl-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) to reduce low-density lipoprotein (LDL) by about 20% to 45%. However, up to 15% of patients cannot tolerate the potential side effects of high statin dosages, and several patients also still do not reach their optimal LDL goals after being treated with statins. Ezetimibe inhibits cholesterol absorption by targeting the Niemann–Pick C1-like 1 protein (NPC1L1), which is related to cholesterol absorption in the intestines. Ezetimibe lowers LDL by about 18% when used alone and by an additional 25% when combined with statin therapy. The proprotein convertase subtilisin/kexin type 9 (PCSK9) increases hepatic LDLR degradation, thereby reducing the liver’s ability to remove LDL, which can lead to hypercholesterolemia. Evolocumab, which is a PCSK9 monoclonal antibody, can reduce LDL from baseline by 53% to 56%. The three drugs exert lipid-lowering effects by regulating the three key pathways in lipid metabolism. Combining any with the two other drugs on the basis of statin treatment has improved the lipid-lowering effect. Whether the combination of the three musketeers will reduce the side effects of monotherapy and achieve the lipid-lowering effect should be studied further in the future.
    Type of Medium: Online Resource
    ISSN: 0929-8673
    Language: English
    Publisher: Bentham Science Publishers Ltd.
    Publication Date: 2021
    SSG: 15,3
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  • 2
    Online Resource
    Online Resource
    Bentham Science Publishers Ltd. ; 2023
    In:  Current Medicinal Chemistry Vol. 30, No. 38 ( 2023-11), p. 4340-4354
    In: Current Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 30, No. 38 ( 2023-11), p. 4340-4354
    Abstract: Long non-coding RNA (lncRNA) is a kind of biomolecule that can regulate important life activities such as cell proliferation, apoptosis, differentiation, aging, and body development. It has been found that lncRNAs are closely related to various diseases. In cardiovascular diseases, lncRNAs affect the expression level of related genes in atherosclerotic plaques, which are closely related to endothelial dysfunction, smooth muscle cell proliferation, macrophage dysfunction, abnormal lipid metabolism, and cellular autophagy, thus participating in regulating the occurrence and development of AS. In view of this, investigating the role of lncRNAs in regulating cardiac gene networks on cardiovascular system diseases has attracted much clinical attention and may be a novel target for AS therapy. This paper focuses on lncRNAs related to AS, explores the relationship between lncRNAs and AS, suggests the role of lncRNAs in the prevention and treatment of AS, and expects the application of more lncRNAs as the marker in the clinical diagnosis and treatment of AS.
    Type of Medium: Online Resource
    ISSN: 0929-8673
    Language: English
    Publisher: Bentham Science Publishers Ltd.
    Publication Date: 2023
    SSG: 15,3
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  • 3
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2022
    In:  Journal of Cardiovascular Translational Research Vol. 15, No. 3 ( 2022-06), p. 477-491
    In: Journal of Cardiovascular Translational Research, Springer Science and Business Media LLC, Vol. 15, No. 3 ( 2022-06), p. 477-491
    Type of Medium: Online Resource
    ISSN: 1937-5387 , 1937-5395
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2422411-X
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  • 4
    Online Resource
    Online Resource
    Wiley ; 2021
    In:  Journal of Cellular Physiology Vol. 236, No. 4 ( 2021-04), p. 2333-2351
    In: Journal of Cellular Physiology, Wiley, Vol. 236, No. 4 ( 2021-04), p. 2333-2351
    Abstract: Proprotein convertase subtilisin/kexin type‐9 (PCSK9), a member of the proprotein convertase family, is an important drug target because of its crucial role in lipid metabolism. Emerging evidence suggests a direct role of localized PCSK9 in the pathogenesis of vascular diseases. With this in our consideration, we reviewed PCSK9 physiology with respect to recent development and major studies (clinical and experimental) on PCSK9 functionality in vascular disease. PCSK9 upregulates low‐density lipoprotein (LDL)‐cholesterol levels by binding to the LDL‐receptor (LDLR) and facilitating its lysosomal degradation. PCSK9 gain‐of‐function mutations have been confirmed as a novel genetic mechanism for familial hypercholesterolemia. Elevated serum PCSK9 levels in patients with vascular diseases may contribute to coronary artery disease, atherosclerosis, cerebrovascular diseases, vasculitis, aortic diseases, and arterial aging pathogenesis. Experimental models of atherosclerosis, arterial aneurysm, and coronary or carotid artery ligation also support PCSK9 contribution to inflammatory response and disease progression, through LDLR‐dependent or ‐independent mechanisms. More recently, several clinical trials have confirmed that anti‐PCSK9 monoclonal antibodies can reduce systemic LDL levels, total nonfatal cardiovascular events, and all‐cause mortality. Interaction of PCSK9 with other receptor proteins (LDLR‐related proteins, cluster of differentiation family members, epithelial Na + channels, and sortilin) may underlie its roles in vascular disease. Improved understanding of PCSK9 roles and molecular mechanisms in various vascular diseases will facilitate advances in lipid‐lowering therapy and disease prevention.
    Type of Medium: Online Resource
    ISSN: 0021-9541 , 1097-4652
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1478143-8
    SSG: 12
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  • 5
    In: Lipids, Wiley, Vol. 50, No. 2 ( 2015-02), p. 177-183
    Abstract: Oxidized low‐density lipoprotein (ox‐LDL) is an independent risk factor of atherosclerosis. However, the mechanism underlying its pro‐atherosclerosis roles has not yet been well explored. DNA demethylation modification, via DNA methyltransferases or ten‐eleven‐translocation (TET) family, is a crisis epigenetic regulation for various biological and pathological processes. This study aimed to investigate the effects of ox‐LDL on macrophage autophagy and its potential epigenetic mechanism. Results showed that after treatment with 0, 10, 20, 40 or 80 mg/L ox‐LDL for 24 h, the autophagy markers Beclin 1 and LC3 expression were obviously decreased at protein levels ( P 〈 0.05). The mRNA and protein expression of TET2 was evidently decreased ( P 〈 0.05). After pre‐treatment with TET2 siRNA, the mRNA and protein levels of Beclin 1 and LC3 decreased compared with the 80 mg/L treatment group ( P 〈 0.01). The mRNA and protein levels of Beclin 1 and LC3‐II were up‐regulated ( P 〈 0.05) in the 5‐aza‐2′‐deoxycytidine (a DNA methyltransferase inhibitor) of pretreatment group. Consistent with the Western blot results, cell immunofluorescence showed that the protein concentration of LC3‐II decreased in the TET2 siRNA group and increased in the 5‐aza‐2′‐deoxycytidine group. Taken together, these results showed that DNA demethylation modifications regulate ox‐LDL‐treated THP‐1 macrophages autophagy and TET2 might be a novel regulator.
    Type of Medium: Online Resource
    ISSN: 0024-4201 , 1558-9307
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2030265-4
    SSG: 12
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  • 6
    In: Current Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 31 ( 2023-08-07)
    Abstract: Atherosclerosis, the pathological basis of most cardiovascular diseases, is a main risk factor causing about 20 million deaths each year worldwide. Oxidized low-density lipoprotein is recognized as the most important and independent risk factor in initiating and promoting atherosclerosis. Numerous antioxidants are extensively used in clinical practice, but they have no significant effect on reducing the morbidity and mortality of cardiovascular diseases. This finding suggests that researchers should pay more attention to the important role of non-oxidative modified low-density lipoprotein in atherosclerosis with a focus on oxidized low-density lipoprotein. This review briefly summarizes several important non-oxidative modified low-density lipoproteins associated with atherosclerosis, introduces the pathways through which these non-oxidative modified low-density lipoproteins induce the development of atherosclerosis in vivo, and discusses the mechanism of atherogenesis induced by these non-oxidative modified low-density lipoproteins. New therapeutic strategies and potential drug targets are provided for the prevention and treatment of atherosclerotic cardiovascular diseases.
    Type of Medium: Online Resource
    ISSN: 0929-8673
    Language: English
    Publisher: Bentham Science Publishers Ltd.
    Publication Date: 2023
    SSG: 15,3
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  • 7
    Online Resource
    Online Resource
    JMIR Publications Inc. ; 2020
    In:  Journal of Medical Internet Research Vol. 22, No. 8 ( 2020-8-21), p. e19995-
    In: Journal of Medical Internet Research, JMIR Publications Inc., Vol. 22, No. 8 ( 2020-8-21), p. e19995-
    Abstract: Since January 2020, the coronavirus disease (COVID-19) swept over China and then the world, causing a global public health crisis. People’s adoption of preventive and intervening behaviors is critical in curbing the spread of the virus. Objective The aim of this study is to evaluate Chinese people’s adoption of health behaviors in responding to COVID-19 and to identify key determinants for their engagement. Methods An anonymous online questionnaire was distributed in early February 2020 among Mainland Chinese (18 years or older) to examine their engagement in preventive behaviors (eg, frequent handwashing, wearing masks, staying at home) and intervening behaviors (eg, advising family to wash hands frequently), and to explore potential determinants for their adoption of these health behaviors. Results Out of 2949 participants, 55.3% (n=1629) reported frequent engagement in preventive health behaviors, and over 84% (n=2493) performed at least one intervening health behavior. Greater engagement in preventive behaviors was found among participants who received higher education, were married, reported fewer barriers and greater benefits of engagement, reported greater self-efficacy and emotional support, had greater patient-centered communication before, had a greater media literacy level, and had greater new media and traditional media use for COVID-19 news. Greater engagement in intervening behaviors was observed among participants who were married, had lower income, reported greater benefits of health behaviors, had greater patient-centered communication before, had a lower media literacy level, and had a greater new media and traditional media use for COVID-19 news. Conclusions Participants’ engagement in coronavirus-related preventive and intervening behaviors was overall high, and the associations varied across demographic and psychosocial variables. Hence, customized health interventions that address the determinants for health behaviors are needed to improve people’s adherence to coronavirus-related behavior guidelines.
    Type of Medium: Online Resource
    ISSN: 1438-8871
    Language: English
    Publisher: JMIR Publications Inc.
    Publication Date: 2020
    detail.hit.zdb_id: 2028830-X
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  • 8
    In: Molecular Biomedicine, Springer Science and Business Media LLC, Vol. 4, No. 1 ( 2023-07-14)
    Abstract: Atherosclerosis (AS) is a major contributor to morbidity and mortality worldwide. However, the molecular mechanisms and mediator molecules involved remain largely unknown. Copper, which plays an essential role in cardiovascular disease, has been suggested as a potential risk factor. Copper homeostasis is closely related to the occurrence and development of AS. Recently, a new cell death pathway called cuproptosis has been discovered, which is driven by intracellular copper excess. However, no previous studies have reported a relationship between cuproptosis and AS. In this study, we integrated bulk and single-cell sequencing data to screen and identify key cuproptosis-related genes in AS. We used correlation analysis, enrichment analysis, random forest, and other bioinformatics methods to reveal their relationships. Our findings report, for the first time, the involvement of cuproptosis-related genes FDX1, SLC31A1, and GLS in atherogenesis. FDX1 and SLC31A1 were upregulated, while GLS was downregulated in atherosclerotic plaque. Receiver operating characteristic curves demonstrate their potential diagnostic value for AS. Additionally, we confirm that GLS is mainly expressed in vascular smooth muscle cells, and SLC31A1 is mainly localized in macrophages of atherosclerotic lesions in experiments. These findings shed light on the cuproptosis landscape and potential diagnostic biomarkers for AS, providing further evidence about the vital role of cuproptosis in atherosclerosis progression.
    Type of Medium: Online Resource
    ISSN: 2662-8651
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 3033856-6
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  • 9
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 42, No. 1 ( 2022-01), p. 67-86
    Abstract: PCSK9 (proprotein convertase subtilisin/kexin type 9) plays a critical role in cholesterol metabolism via the PCSK9–LDLR (low-density lipoprotein receptor) axis in the liver; however, evidence indicates that PCSK9 directly contributes to the pathogenesis of various diseases through mechanisms independent of its LDL-cholesterol regulation. The objective of this study was to determine how PCSK9 directly acts on vascular smooth muscle cells (SMCs), contributing to degenerative vascular disease. Approach and Results: We first examined the effects of PCSK9 on cultured human aortic SMCs. Overexpression of PCSK9 downregulated the expression of ApoER2 (apolipoprotein E receptor 2), a known target of PCSK9. Treatment with soluble recombinant human ApoER2 or the DNA synthesis inhibitor, hydroxyurea, inhibited PCSK9-induced polyploidization and other cellular responses of human SMCs. Treatment with antibodies against ApoER2 resulted in similar effects to those observed with PCSK9 overexpression. Inducible, SMC-specific knockout of Pcsk9 accelerated neointima formation in mouse carotid arteries and reduced age-related arterial stiffness. PCSK9 was expressed in SMCs of human atherosclerotic lesions and abundant in the “shoulder” regions of vulnerable atherosclerotic plaques. PCSK9 was also expressed in SMCs of abdominal aortic aneurysm, which was inversely related to the expression of smooth muscle α-actin. Conclusions: Our findings demonstrate that PCSK9 inhibits proliferation and induces polyploidization, senescence, and apoptosis, which may be relevant to various degenerative vascular diseases.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1494427-3
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  • 10
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2022
    In:  Nutrition & Metabolism Vol. 19, No. 1 ( 2022-03-18)
    In: Nutrition & Metabolism, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2022-03-18)
    Abstract: This meta-analysis was performed to investigate the effects of nicotinamide adenine dinucleotide (NAD+) precursor supplementation on glucose and lipid metabolism in human body. Methods PubMed, Embase, CENTRAL, Web of Science, Scopus databases were searched to collect clinical studies related to the supplement of NAD+ precursor from inception to February 2021. Then the retrieved documents were screened, the content of the documents that met the requirements was extracted. Meta-analysis and quality evaluation was performed detection were performed using RevMan5.4 software. Stata16 software was used to detect publication bias, Egger and Begg methods were mainly used. The main research terms of NAD+ precursors were Nicotinamide Riboside (NR), Nicotinamide Mononucleotide (NMN), Nicotinic Acid (NA), Nicotinamide (NAM). The changes in the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and fasting blood glucose were mainly concerned. Results A total of 40 articles were included in the meta-analysis, with a sample of 14,750 cases, including 7406 cases in the drug group and 7344 cases in the control group. The results of meta-analysis showed that: NAD+ precursor can significantly reduce TG level (SMD = − 0.35, 95% CI (− 0.52, − 0.18), P   〈  0.0001), and TC (SMD = − 0.33, 95% CI (− 0.51, − 0.14), P  = 0.0005), and LDL (SMD = − 0.38, 95% CI (− 0.50, − 0.27), P   〈  0.00001), increase HDL level (SMD = 0.66, 95% CI (0.56, 0.76), P   〈  0.00001), and plasma glucose level in the patients (SMD = 0.27, 95% CI (0.12, 0.42), P  = 0.0004). Subgroup analysis showed that supplementation of NA had the most significant effect on the levels of TG, TC, LDL, HDL and plasma glucose. Conclusions In this study, a meta-analysis based on currently published clinical trials with NAD+ precursors showed that supplementation with NAD+ precursors improved TG, TC, LDL, and HDL levels in humans, but resulted in hyperglycemia, compared with placebo or no treatment. Among them, NA has the most significant effect on improving lipid metabolism. In addition, although NR and NAM supplementation had no significant effect on improving human lipid metabolism, the role of NR and NAM could not be directly denied due to the few relevant studies at present. Based on subgroup analysis, we found that the supplement of NAD+ precursors seems to have little effect on healthy people, but it has a significant beneficial effect on patients with cardiovascular disease and dyslipidemia. Due to the limitation of the number and quality of included studies, the above conclusions need to be verified by more high-quality studies.
    Type of Medium: Online Resource
    ISSN: 1743-7075
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2160376-5
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