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  • 1
    In: European Journal of Pharmacology, Elsevier BV, Vol. 854 ( 2019-07), p. 365-371
    Type of Medium: Online Resource
    ISSN: 0014-2999
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
    detail.hit.zdb_id: 1483526-5
    SSG: 15,3
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  • 2
    In: Experimental Cell Research, Elsevier BV, Vol. 432, No. 2 ( 2023-11), p. 113803-
    Type of Medium: Online Resource
    ISSN: 0014-4827
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 1466780-0
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-9-8)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-9-8)
    Abstract: Sepsis-associated organ dysfunction plays a critical role in its high mortality, mainly in connection with mitochondrial dysfunction. Whether the inhibition of mitochondrial fission is beneficial to sepsis-related organ dysfunction and underlying mechanisms are unknown. Cecal ligation and puncture induced sepsis in rats and dynamic related protein 1 knockout mice, lipopolysaccharide-treated vascular smooth muscle cells and cardiomyocytes, were used to explore the effects of inhibition of mitochondrial fission and specific mechanisms. Our study showed that mitochondrial fission inhibitor Mdivi-1 could antagonize sepsis-induced organ dysfunction including heart, vascular smooth muscle, liver, kidney, and intestinal functions, and prolonged animal survival. The further study showed that mitochondrial functions such as mitochondrial membrane potential, adenosine-triphosphate contents, reactive oxygen species, superoxide dismutase and malonaldehyde were recovered after Mdivi-1 administration via improving mitochondrial morphology. And sepsis-induced inflammation and apoptosis in heart and vascular smooth muscle were alleviated through inhibition of mitochondrial fission and mitochondrial function improvement. The parameter trends in lipopolysaccharide-stimulated cardiomyocytes and vascular smooth muscle cells were similar in vivo . Dynamic related protein 1 knockout preserved sepsis-induced organ dysfunction, and the animal survival was prolonged. Taken together, this finding provides a novel effective candidate therapy for severe sepsis/septic shock and other critical clinical diseases.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 4
    Online Resource
    Online Resource
    Elsevier BV ; 2020
    In:  European Journal of Pharmacology Vol. 870 ( 2020-03), p. 172873-
    In: European Journal of Pharmacology, Elsevier BV, Vol. 870 ( 2020-03), p. 172873-
    Type of Medium: Online Resource
    ISSN: 0014-2999
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 1483526-5
    SSG: 15,3
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Genetics Vol. 13 ( 2022-2-21)
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 13 ( 2022-2-21)
    Abstract: Sepsis is a heterogeneous disease state triggered by an uncontrolled inflammatory host response with high mortality and morbidity in severely ill patients. Unfortunately, the treatment effectiveness varies among sepsis patients and the underlying mechanisms have yet to be elucidated. The present aim is to explore featured metabolism-related genes that may become the biomarkers in patients with sepsis. In this study, differentially expressed genes (DEGs) between sepsis and non-sepsis in whole blood samples were identified using two previously published datasets (GSE95233 and GSE54514). A total of 66 common DEGs were determined, namely, 52 upregulated and 14 downregulated DEGs. The Gene Set Enrichment Analysis (GSEA) results indicated that these DEGs participated in several metabolic processes including carbohydrate derivative, lipid, organic acid synthesis oxidation reduction, and small-molecule biosynthesis in patients with sepsis. Subsequently, a total of 8 hub genes were screened in the module with the highest score from the Cytoscape plugin cytoHubba. Further study showed that these hub DEGs may be robust markers for sepsis with high area under receiver operating characteristic curve (AUROC). The diagnostic values of these hub genes were further validated in myocardial tissues of septic rats and normal controls by untargeted metabolomics analysis using liquid chromatography-mass spectrometry (LC-MS). Immune cell infiltration analysis revealed that different infiltration patterns were mainly characterized by B cells, T cells, NK cells, monocytes, macrophages, dendritics, eosinophils, and neutrophils between sepsis patients and normal controls. This study indicates that metabolic hub genes may be hopeful biomarkers for prognosis prediction and precise treatment in sepsis patients.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606823-0
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  • 6
    In: Frontiers in Physiology, Frontiers Media SA, Vol. 13 ( 2022-2-4)
    Abstract: Previous studies found that seawater immersion combined with hemorrhagic shock (SIHS) induced serious organ function disorder, and lethal triad was a critical sign. There were no effective treatments of SIHS. Fluid resuscitation was the initial measurement for early aid following hemorrhagic shock, while the proper fluid for SIHS is not clear. Effects of different osmotic pressures [lactated Ringer’s (LR) solution, 0.3% saline, 0.6% saline, and 0.9% normal saline] on the lethal triad, mitochondrial function, vital organ functions, and survival were observed following SIHS in rats. The results showed that SIHS led to an obvious lethal triad, which presented the decrease of the body temperature, acidosis, and coagulation functions disorder in rats. Fluid resuscitation with different osmotic pressures recovered the body temperature and corrected acidosis with different levels; effects of 0.6% normal saline were the best; especially for the coagulation function, 0.6% normal saline alleviated the lethal triad significantly. Further studies showed that SIHS resulted in the damage of the mitochondrial function of vital organs, the increase of the vascular permeability, and, at the same time, the organ function including cardiac, liver, and kidney was disordered. Conventional fluid such as LR or 0.9% normal saline could not improve the mitochondrial function and vascular leakage and alleviate the damage of the organ function. While moderate hypotonic fluid, the 0.6% normal saline, could lighten organ function damage via protecting mitochondrial function. The 0.6% normal saline increased the left ventricular fractional shortening and the left ventricular ejection fraction, and decreased the levels of aspartate transaminase, alanine transferase, blood urea nitrogen, and creatinine in the blood. The effects of fluids with different osmotic pressures on the mean arterial pressure (MAP) had a similar trend as above parameters. The survival results showed that the 0.6% normal saline group improved the survival rate and prolonged the survival time, the 72 h survival rate was 7/16, as compared with the LR group (3/16). The results indicate that appropriate hypotonic fluid is suitable after SIHS, which alleviates the lethal triad, protects the mitochondrial function and organ functions, and prolongs the survival time.
    Type of Medium: Online Resource
    ISSN: 1664-042X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564217-0
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  • 7
    In: Journal of Translational Medicine, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2022-12-13)
    Abstract: Myocardial dysfunction played a vital role in organ damage after sepsis. Fluid resuscitation was the essential treatment in which Lactate Ringer's solution (LR) was commonly used. Since LR easily led to hyperlactatemia, its resuscitation effect was limited. Malate Ringer's solution (MR) was a new resuscitation crystal liquid. Whether MR had a protective effect on myocardial injury in sepsis and the relevant mechanism need to be studied. Methods The cecal ligation and puncture (CLP) inducing septic model and lipopolysaccharide (LPS) stimulating cardiomyocytes were used, and the cardiac function, the morphology and function of mitochondria were observed. The protective mechanism of MR on myocardial injury was explored by proteomics. Then the effects of TPP@PAMAM-MR, which consisted of the mitochondria- targeting polymer embodied malic acid, was further observed. Results Compared with LR, MR resuscitation significantly prolonged survival time, improved the cardiac function, alleviated the damages of liver, kidney and lung following sepsis in rats. The proteomics of myocardial tissue showed that differently expressed proteins between MR and LR infusion involved oxidative phosphorylation, apoptosis. Further study found that MR decreased ROS, improved the mitochondrial morphology and function, and ultimately enhanced mitochondrial respiration and promoted ATP production. Moreover, MR infusion decreased the expression of apoptosis-related proteins and increased the expression of anti-apoptotic proteins. TPP@PAMAM@MA was a polymer formed by wrapping l -malic acid with poly amido amine (PAMAM) modified triphenylphosphine material. TPP@PAMAM-MR (TPP-MR), which was synthesized by replacing the l -malic acid of MR with TPP@PAMAM@MA, was more efficient in targeting myocardial mitochondria and was superior to MR in protecting the sepsis-inducing myocardial injury. Conclusion MR was suitable for protecting myocardial injury after sepsis. The mechanism was related to MR improving the function and morphology of cardiomyocyte mitochondria and inhibiting cardiomyocyte apoptosis. The protective effect of TPP-MR was superior to MR.
    Type of Medium: Online Resource
    ISSN: 1479-5876
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2118570-0
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  • 8
    In: Gerontology, S. Karger AG, Vol. 67, No. 3 ( 2021), p. 323-337
    Abstract: 〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 Vasoconstriction is triggered by an increase in intracellular-free calcium concentration. Growing evidence indicates that contraction is also regulated by calcium-independent mechanisms involving RhoA-Rho kinase (ROCK), protein kinase C (PKC), and so on. In this study, we studied the changes of vascular reactivity as well as the underlying signaling pathways in aging spontaneously hypertensive rats (SHRs). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 The artery tension induced by α1-adrenergic receptor activator (α1-AR) phenylephrine (PE) was measured in the absence or presence of myosin light chain kinase (MLCK), PKC, and ROCK inhibitors. The α1-AR, PKC, ROCK, phosphorylation of myosin light chain (MLC), and PKC-potentiated phosphatase inhibitors of 17 kDa (CPI-17) of rat mesenteric arteries were analyzed at the mRNA level or protein level. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 The vascular tension measurements showed that there was a significant increase in the mesenteric artery contraction induced by PE in old SHR. MLCK inhibitor ML-7 can similarly inhibit PE-induced vasoconstriction. PKC inhibitor GF109203X has the weakest inhibitory effect on PE-induced contraction in old SHR. At the presence of ROCK inhibitor H1152, PE-induced contraction was significantly reduced in young Wistar-Kyoto (WKY) rats, but this phenomenon disappeared in other rats. Furthermore, in old SHR the protein expression of α1-AR decreased and phosphorylation of MLC and CPI-17 were upregulated and MLC phosphatase (MLCP) activity was significantly lower. The expressions of PKC were upregulated in SHR and old rats. In addition, the expression of ROCK-1 was decreased and ROCK-2 was significantly upregulated with age in SHR. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 In aging hypertension, the expression/activity of PKC or ROCK-2/CPI-17 excessively increased, MLCP activity decreased and MLC phosphorylation enhanced, leading to increased α1-AR-induced vasoconstriction.
    Type of Medium: Online Resource
    ISSN: 0304-324X , 1423-0003
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 1482689-6
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  • 9
    In: Journal of Inflammation Research, Informa UK Limited, Vol. Volume 14 ( 2021-12), p. 6765-6782
    Type of Medium: Online Resource
    ISSN: 1178-7031
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2494878-0
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  • 10
    Online Resource
    Online Resource
    Elsevier BV ; 2020
    In:  Journal of Molecular and Cellular Cardiology Vol. 140 ( 2020-03), p. 34-35
    In: Journal of Molecular and Cellular Cardiology, Elsevier BV, Vol. 140 ( 2020-03), p. 34-35
    Type of Medium: Online Resource
    ISSN: 0022-2828
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 1469767-1
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