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  • Ovid Technologies (Wolters Kluwer Health)  (44)
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  • Ovid Technologies (Wolters Kluwer Health)  (44)
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  • 1
    Online Resource
    Online Resource
    Abstract 635: β 2 -adrenergic Stimulation Compartmentalizes β 1 Signaling Into Nanoscale Local Domains by Targeting the C-terminus of β 1 -adrenoceptors
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Circulation Research Vol. 125, No. Suppl_1 ( 2019-08-02)
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 125, No. Suppl_1 ( 2019-08-02)
    Abstract: β-adrenergic receptors (βARs) are prototypical G-protein coupled receptors that play a pivotal role in sympathetic regulation. In heart cells, β 1 R signaling mediates a global cAMP response, regulating both L-type Ca 2+ channels in the sarcolemma/T-tubules (SL/TTs) and ryanodine receptors in the sarcoplasmic reticulum (SR). In contrast, β 2 AR mediates local cAMP signaling with little effect on the function of SR proteins. Accumulating evidence in pathological and transgenic models has suggested a functional complexity of β 2 AR beyond its regulation of L-type Ca 2+ influx. So we investigated the signaling relationship between β 1 ARs and β 2 ARs. Using whole-cell patch clamp combined with confocal calcium imaging, we simultaneously measured L-type Ca 2+ currents and Ca 2+ transients in adult cardiomyocytes. β 1 AR stimulation with norepinephrine or isoproterenol increased both Ca 2+ currents and Ca 2+ transients. β 2 AR stimulation with Zinterol or Salbutamol only increased Ca 2+ currents (onside compartmentalization) and surprisingly inhibited the ability of β 1 AR in upregulating Ca 2+ transients (offside compartmentalization). Further evidence showed that β 2 AR activation recruited G-protein coupled receptor kinase 2 (GRK2) to cell membrane, which phosphorylated the ‘SSES’ serine cluster on β 1 AR carboxyl terminal. Phosphorylated β 1 AR coupled to β-arrestin1 and further recruited phosphodiesterase-4, leading to localized cAMP degradation. Immunocytochemical and biochemical analysis showed the β 2 AR-mediated offside compartmentalization was confined to the nanoscale domain. A knock-in rat model harboring mutations of the three serine residues in ‘SSES’ cluster of the β 1 AR C-terminus, a component of the putative β-arrestin1 binding site and GRK2 phosphorylation site, eliminated the offside compartmentalization conferred by β 2 AR activation. This finding reveals a fundamental “negative feed-forward” mechanism that serves to avoid the cytotoxicity of circulating catecholamine and to sharpen the transient β 1 AR response of sympathetic excitation, providing many potential novel targets for drug discovery against cardiovascular diseases.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/res.125.suppl_1.635
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 1467838-X
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  • 2
    Online Resource
    Online Resource
    Deletion of BACH1 Attenuates Atherosclerosis by Reducing Endothelial Inflammation
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Circulation Research Vol. 130, No. 7 ( 2022-04), p. 1038-1055
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 130, No. 7 ( 2022-04), p. 1038-1055
    Abstract: The transcription factor BACH1 (BTB and CNC homology 1) suppressed endothelial cells (ECs) proliferation and migration and impaired angiogenesis in the ischemic hindlimbs of adult mice. However, the role and underlying mechanisms of BACH1 in atherosclerosis remain unclear. Methods: Mouse models of atherosclerosis in endothelial cell (EC)-specific-Bach1 knockout mice were used to study the role of BACH1 in the regulation of atherogenesis and the underlying mechanisms. Results: Genetic analyses revealed that coronary artery disease-associated risk variant rs2832227 was associated with BACH1 gene expression in carotid plaques from patients. BACH1 was upregulated in ECs of human and mouse atherosclerotic plaques. Endothelial Bach1 deficiency decreased turbulent blood flow- or western diet-induced atherosclerotic lesions, macrophage content in plaques, expression of endothelial adhesion molecules (ICAM1 [intercellular cell adhesion molecule-1] and VCAM1 [vascular cell adhesion molecule-1] ), and reduced plasma TNF-α (tumor necrosis factor-α) and IL-1β levels in atherosclerotic mice. BACH1 deletion or knockdown inhibited monocyte–endothelial adhesion and reduced oscillatory shear stress or TNF-α-mediated induction of endothelial adhesion molecules and/or proinflammatory cytokines in mouse ECs, human umbilical vein ECs, and human aortic ECs. Mechanistic studies showed that upon oscillatory shear stress or TNF-α stimulation, BACH1 and YAP (yes-associated protein) were induced and translocated into the nucleus in ECs. BACH1 upregulated YAP expression by binding to the YAP promoter. BACH1 formed a complex with YAP inducing the transcription of adhesion molecules. YAP overexpression in ECs counteracted the antiatherosclerotic effect mediated by Bach1-deletion in mice. Rosuvastatin inhibited BACH1 expression by upregulating microRNA let-7a in ECs, and decreased Bach1 expression in the vascular endothelium of hyperlipidemic mice. BACH1 was colocalized with YAP, and the expression of BACH1 was positively correlated with YAP and proinflammatory genes, as well as adhesion molecules in human atherosclerotic plaques. Conclusions: These data identify BACH1 as a mechanosensor of hemodynamic stress and reveal that the BACH1-YAP transcriptional network is essential to vascular inflammation and atherogenesis. BACH1 shows potential as a novel therapeutic target in atherosclerosis.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/CIRCRESAHA.121.319540
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467838-X
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  • 3
    Online Resource
    Online Resource
    Systolic Blood Pressure Control Targets to Prevent Major Cardiovascular Events and Death in Patients With Type 2 Diabetes: A Systematic Review and Network Meta-Analysis
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Hypertension Vol. 80, No. 8 ( 2023-08), p. 1640-1653
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 80, No. 8 ( 2023-08), p. 1640-1653
    Abstract: Previous meta-analyses using traditional pairwise comparisons did not support intensive systolic blood pressure (SBP) control in patients with diabetes and included trials published before 2015. We aimed to identify the optimal SBP control targets in patients with type 2 diabetes using a systematic review and network meta-analysis of accumulating evidence. METHODS: We systematically searched PubMed, Embase, and Cochrane Library from inception to August 29, 2022 for randomized controlled trials comparing different blood pressure targets, antihypertensive agents against placebo, or dual antihypertensive agents against single agent in patients with type 2 diabetes. Network meta-analysis was used to obtain pooled results of direct and indirect comparisons of each 5 mm Hg SBP category in association with clinical outcomes adjusted for baseline risk and intervention duration (PROSPERO [International Prospective Register of Systematic Reviews], CRD42022316697). RESULTS: We identified 30 trials including 59 934 patients with type 2 diabetes. The mean achieved SBP levels ranged from 117 mm Hg to 144 mm Hg among treatment groups. A total of 7799 major cardiovascular diseases events and 4130 deaths were reported. The lowest risk of major cardiovascular diseases was found in patients with achieved SBP level of 120 to 124 mm Hg. The hazard ratio and 95% CI were 0.73 (0.52–1.02) compared with 130 to 134 mm Hg, 0.60 (0.41–0.85) compared with 140 to 144 mm Hg, and 0.41 (0.26–0.63) compared with ≥150 mm Hg. Similar results were found for cardiovascular diseases components including stroke, myocardial infarction, heart failure, and cardiovascular death. All-cause death was reduced at an achieved SBP 〈 140 mm Hg but further reduction did not show additional benefits. CONCLUSIONS: Our findings support an intensive blood pressure-lowering strategy to prevent major cardiovascular diseases in patients with type 2 diabetes.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.123.20954
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2094210-2
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  • 4
    Online Resource
    Online Resource
    Safety and immunological responses to human mesenchymal stem cell therapy in difficult-to-treat HIV-1-infected patients
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  AIDS Vol. 27, No. 8 ( 2013-05-15), p. 1283-1293
    Details
    In: AIDS, Ovid Technologies (Wolters Kluwer Health), Vol. 27, No. 8 ( 2013-05-15), p. 1283-1293
    Type of Medium: Online Resource
    ISSN: 0269-9370
    URL: Article
    DOI: 10.1097/QAD.0b013e32835fab77
    RVK:
    XA 16838
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 2012212-3
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  • 5
    Online Resource
    Online Resource
    Clinical study on Yanghe decoction in improving neo-adjuvant chemotherapy efficacy and immune function of breast cancer patients
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Medicine Vol. 101, No. 10 ( 2022-03-11), p. e29031-
    Details
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 101, No. 10 ( 2022-03-11), p. e29031-
    Abstract: Neoadjuvant chemotherapy (NAC) plays an important role in downgrading preoperative tumor size, providing information on regimen activity, and increases treatment efficacy in breast cancer patients. An increasing number of patients have sought Traditional Chinese Medicine (TCM) during NAC to relieve discomfort, regulate immune function, and improve survival. However, limited evidence is available on how concurrent TCM treatment combined with NAC affects tumor response. This study aims to assess the efficacy of Yanghe decoction, a classical warming Yang formula, on pathological complete response (pCR) and explore its mechanism via the phosphatidylinositol-3-kinase/ protein kinase B/nuclear factor kappa-B (PI3K/Akt/NF-κB) pathway-mediated immune-inflammation microenvironment. Methods: A single-center, randomized, placebo-controlled, double-blinded randomized control trial (RCT) was designed. This trial aims to recruit 128 participants with breast cancer scheduled to receive NAC in China. All participants will be randomly assigned (1:1) to the Neo-Yanghe group (Yanghe decoction plus NAC) or the control group (placebo plus NAC). The primary outcome will be evaluated by the proportion of participants achieving pCR. The secondary outcomes include the expression level of PI3K/Akt/NF-κB pathway-related proteins, the objective response rate, the time to response, serum level of immune-inflammatory indicators, quality of life, disease-free survival, and overall survival. Discussion: This study will be the first RCT to evaluate the efficacy of Yanghe decoction combined with NAC in treating breast cancer patients, and elucidate the antitumor mechanism via the PI3K/Akt/NF-κB pathway-mediated immune-inflammation microenvironment. If possible, Neo-Yanghe treatment pattern will be a better pharmacological intervention to manage breast cancer than chemotherapy alone. The results of the trial will provide research-based evidence for the development of integrated Chinese and Western medicine guidelines and expert consensus. Trial registration: Chinese Clinical Trial Registry ChiCTR-INR-2000036943. Registered on September 28, 2020 (https://www.chictr.org.cn/hvshowproject.aspx?id=57141).
    Type of Medium: Online Resource
    ISSN: 0025-7974 , 1536-5964
    URL: Article
    DOI: 10.1097/MD.0000000000029031
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2049818-4
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  • 6
    Online Resource
    Online Resource
    Study on the mechanism of Shujin Tongluo granules in treating cervical spondylosis based on network pharmacology and molecular docking
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Medicine Vol. 102, No. 29 ( 2023-07-21), p. e34030-
    Details
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 102, No. 29 ( 2023-07-21), p. e34030-
    Abstract: To investigate the potential active ingredients and possible mechanisms of Shujin Tongluo granules (SJTLG) in the treatment of cervical spondylosis (CS) by network pharmacology and molecular docking. Methods: The active ingredients and potential targets of SJTLG were obtained through databases such as traditional Chinese medicine system (TCMSP) and BATMAN-traditional Chinese medicine (TCM), and the relevant human targets of CS were identified through databases such as OMIM, GeneCards, and DisGeNET. The intersection targets were imported into STRING for protein-protein interaction (PPI) analysis. The obtained data were imported into Cytoscape 3.9.0 software for visualization, and module analysis was performed using the MCODE plug-in. The representative targets were screened through the Metascape website for pathway enrichment analysis in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Cytoscape software was used to build networks such as “drug-compound-target” and “drug-compound-target-pathway.” Finally, the key targets were selected for molecular docking with the corresponding compounds by Autodock Tools 1.5.7 and visualized by PyMol. Results: A total of 132 active compounds and 996 targets from SJTLG and 678 targets from CS were screened with 116 intersection targets. The key targets were AKT1, GAPDH, ALB, IL-6, TP53, TNF, VEGFA, IL-1β, EGFR, HSP90AA1, ESR1, and JUN. The results of GO and KEGG enrichment analysis showed that the treatment of CS was mainly related to biological processes such as cellular response to nitrogen compound, cellular response to organonitrogen compound, and positive regulation of locomotion, and the targets were mainly focused on pathways in cancer, Kaposi sarcoma-associated herpesvirus infection, PI3K-Akt signaling pathway, lipid, and atherosclerosis. Molecular docking results showed that the minimum binding energy between the core targets and the corresponding compound was 〈 −5.0 kcal·mol −1 . Conclusion: This study preliminarily elucidates the potential active ingredients and mechanism of anti-inflammatory, analgesic, microcirculation improvement, vasodilation, osteoporosis inhibition and nerve nutrition effects of SJTLG in the treatment of CS and provides a reference for its clinical application.
    Type of Medium: Online Resource
    ISSN: 0025-7974
    URL: Article
    DOI: 10.1097/MD.0000000000034030
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2049818-4
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  • 7
    Online Resource
    Online Resource
    NAD+ salvage governs mitochondrial metabolism, invigorating natural killer cell antitumor immunity
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Hepatology Vol. 78, No. 2 ( 2023-08), p. 468-485
    Details
    In: Hepatology, Ovid Technologies (Wolters Kluwer Health), Vol. 78, No. 2 ( 2023-08), p. 468-485
    Abstract: Natural killer (NK) cells are key players in tumor immunosurveillance, and metabolic adaptation manipulates their fate and functional state. The nicotinamide adenine dinucleotide (NAD + ) has emerged as a vital factor to link cellular metabolism and signaling transduction. Here, we identified NAD + metabolism as a central hub to determine the homeostasis and function of NK cells. Approach and Results: NAD + level was elevated in activated NK cells. NAD + supplementation not only enhanced cytokine production and cytotoxicity but also improved the proliferation and viability of NK cells. Intriguingly, the salvage pathway was involved in maintaining NAD + homeostasis in activated NK cells. Genetic ablation or pharmacological blockade of nicotinamide phosphoribosyltransferase (NAMPT), the rate‐limiting enzyme in the NAD + salvage pathway, markedly destroyed the viability and function of NK cells. Mechanistically, NAD + salvage dictated the mitochondrial homeostasis and oxidative phosphorylation activity to support the optimal function of NK cells. However, in human HCC tissues, NAMPT expression and NAD + level were significantly down‐regulated in tumor‐infiltrating NK cells, which negatively correlated with patient survival. And lactate accumulation in the tumor microenvironment was at least partially responsible for the transcriptional repression of NAMPT in NK cells. Further, deficiency of Nampt in NK cells accelerated the growth of HCC and melanoma. Supplementation of the NAD + precursor nicotinamide mononucleotide (NMN) significantly improved NK antitumor response in both mouse and human cell‐derived xenografts. Conclusions: These findings reveal NAD + salvage as an essential factor for NK‐cell homeostasis and function, suggesting a potential strategy for invigorating NK cell–based immunotherapy.
    Type of Medium: Online Resource
    ISSN: 0270-9139
    URL: Article
    DOI: 10.1002/hep.32658
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1472120-X
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  • 8
    Online Resource
    Online Resource
    Mechanism and early intervention research on ALI during emergence surgery of Stanford type-A AAD : Study protocol for a prospective, double-blind, clinical trial
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Medicine Vol. 95, No. 42 ( 2016-10), p. e5164-
    Details
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 95, No. 42 ( 2016-10), p. e5164-
    Type of Medium: Online Resource
    ISSN: 0025-7974
    URL: Article
    DOI: 10.1097/MD.0000000000005164
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2049818-4
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  • 9
    Online Resource
    Online Resource
    A modified percutaneous atrial balloon septoplasty for difficult transseptal puncture
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Medicine Vol. 100, No. 28 ( 2021-07-16), p. e26525-
    Details
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 100, No. 28 ( 2021-07-16), p. e26525-
    Abstract: Catheter ablation of atrial fibrillation sometimes encounters difficulty in passing the interatrial septum. This study reports a modified percutaneous atrial balloon septoplasty with short balloon to gain access to left atrium (LA) during challenging transseptal puncture (TSP). We retrospectively analyzed 20 patients (61.75 ± 7.31 years, 45% male) who received modified percutaneous atrial balloon septoplasty from August 2015 to October 2018. Soft-headed balance middle weight (BMW) guidewire was inserted into left superior pulmonary vein (LSPV) and short non-compliant balloon (15 mm in length and 4.0 or 5.0 mm in diameter) was used for atrial balloon septoplasty (ABS). Interatrial septum was located with inflated balloon and contrast “Hitting Wall” sign. All patients were followed-up for iatrogenic atrial septal defect (iASD) and other related complications. ABS and LA access were performed successfully without complications in all 20 patients. Time needed for ABS was correlated to the number of prior TSP ( P  = .007). During the 6-month follow-up, no remaining iASD was found by echocardiography. For atrial fibrillation patients with difficulty in passing the interatrial septum, this modified percutaneous ABS might be an alternative strategy which is safe to obtain transseptal access without short or long term complications.
    Type of Medium: Online Resource
    ISSN: 0025-7974 , 1536-5964
    URL: Article
    DOI: 10.1097/MD.0000000000026525
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2049818-4
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  • 10
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    Online Resource
    Epidemiological study on severe acute respiratory syndrome coronavirus 2 virus transmission network in northeast China
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Medicine Vol. 100, No. 26 ( 2021-07-02), p. e26298-
    Details
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 100, No. 26 ( 2021-07-02), p. e26298-
    Abstract: In this study, corona virus disease 2019 (COVID-19) transmission networks were built to analyze the epidemic situation of COVID-19 in Liaoning and Jilin provinces in early 2020. We explore the characteristics of the spread of COVID-19, and put forward effective recommendations for epidemic prevention and control. We collected demographic characteristics, exposure history, and course of action of COVID-19 cases. We described the demographic and case characteristics of these cases to show the basic characteristics of COVID-19 cases in both provinces. Combined with the spatial analysis of confirmed cases, the distribution law of the number of confirmed cases in different regions was analyzed. We exhibit the relationship among COVID-19 cases with a transmission network. The transmission characteristics of COVID-19 were analyzed through the transmission network. Mainly cases in Liaoning and Jilin provinces were imported cases from other provinces and the vast majority of these cases were related to Hubei province. The number of confirmed cases in different regions was positively correlated with their GDP and population. The main clinical symptoms of the cases were fever. Judge from the transmission network relationship between the 2 provinces, the transmission chain in Liaoning province contains fewer cases than that in Jilin province. The main transmission routes of the local cases in the 2 provinces were the family members, and the infection of the imported cases were mainly occurred in public places. It was estimated that the unidentified asymptomatic infected cases in the 2 provinces account for approximately 7.3% of the total number of infected cases. The length of the transmission chain suggests that the spread of COVID-19 can be effectively controlled with effective prevention measures.
    Type of Medium: Online Resource
    ISSN: 0025-7974 , 1536-5964
    URL: Article
    DOI: 10.1097/MD.0000000000026298
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2049818-4
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