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Artikel ; Online: Acceleration of Protein Degradation by 20S Proteasome-Binding Peptides Generated by In Vitro Artificial Evolution.

Zhu, Yunhao / Shigeyoshi, Kaishin / Hayakawa, Yumiko / Fujiwara, Sae / Kishida, Masamichi / Ohki, Hitoshi / Horibe, Tomohisa / Shionyu, Masafumi / Mizukami, Tamio / Hasegawa, Makoto

International journal of molecular sciences

2023 Band 24, Heft 24

Abstract: Although the 20S core particle (CP) of the proteasome is an important component of the 26S holoenzyme, the stand-alone 20S CP acts directly on intrinsically disordered and oxidized/damaged proteins to degrade them in a ubiquitin-independent manner. It ... ...

Abstract	Although the 20S core particle (CP) of the proteasome is an important component of the 26S holoenzyme, the stand-alone 20S CP acts directly on intrinsically disordered and oxidized/damaged proteins to degrade them in a ubiquitin-independent manner. It has been postulated that some structural features of substrate proteins are recognized by the 20S CP to promote substrate uptake, but the mechanism of substrate recognition has not been fully elucidated. In this study, we screened peptides that bind to the 20S CP from a random eight-residue pool of amino acid sequences using complementary DNA display an in vitro molecular evolution technique. The identified 20S CP-binding amino acid sequence was chemically synthesized and its effects on the 20S CP were investigated. The 20S CP-binding peptide stimulated the proteolytic activity of the inactive form of 20S CP. The peptide bound directly to one of the α-subunits, opening a gate for substrate entry on the α-ring. Furthermore, the attachment of this peptide sequence to α-synuclein enhanced its degradation by the 20S CP in vitro. In addition to these results, docking simulations indicated that this peptide binds to the top surface of the α-ring. These peptides could function as a key to control the opening of the α-ring gate.
Mesh-Begriff(e)	Proteolysis ; Proteasome Endopeptidase Complex/metabolism ; Proteins/metabolism ; Peptides/metabolism ; Acceleration
Chemische Substanzen	Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Proteins ; Peptides
Sprache	Englisch
Erscheinungsdatum	2023-12-14
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms242417486
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: The combined efficacy of OTS964 and temozolomide for reducing the size of power-law coded heterogeneous glioma stem cell populations.

Sugimori, Michiya / Hayakawa, Yumiko / Tamura, Ryoi / Kuroda, Satoshi

Oncotarget

2019 Band 10, Heft 24, Seite(n) 2397–2415

Abstract: Glioblastoma resists chemotherapy then recurs as a fatal space-occupying lesion. To improve the prognosis, the issues of chemoresistance and tumor size should be addressed. Glioma stem cell (GSC) populations, a heterogeneous power-law coded population in ...

Abstract	Glioblastoma resists chemotherapy then recurs as a fatal space-occupying lesion. To improve the prognosis, the issues of chemoresistance and tumor size should be addressed. Glioma stem cell (GSC) populations, a heterogeneous power-law coded population in glioblastoma, are believed to be responsible for the recurrence and progressive expansion of tumors. Thus, we propose a therapeutic strategy of reducing the initial size and controlling the regrowth of GSC populations which directly facilitates initial and long-term control of glioblastoma recurrence. In this study, we administered an anti-glioma/GSC drug temozolomide (TMZ) and OTS964, an inhibitor for T-Lak cell originated protein kinase, in combination (T&O), investigating whether together they efficiently and substantially shrink the initial size of power-law coded GSC populations and slow the long-term re-growth of drug-resistant GSC populations. We employed a detailed quantitative approach using clonal glioma sphere (GS) cultures, measuring sphere survivability and changes to growth during the self-renewal. T&O eliminated self-renewing GS clones and suppressed their growth. We also addressed whether T&O reduced the size of self-renewed GS populations. T&O quickly reduced the size of GS populations via efficient elimination of GS clones. The growth of the surviving T&O-resistant GS populations was continuously disturbed, leading to substantial long-term shrinkage of the self-renewed GS populations. Thus, T&O reduced the initial size of GS populations and suppressed their later regrowth. A combination therapy of TMZ and OTS964 would represent a novel therapeutic paradigm with the potential for long-term control of glioblastoma recurrence via immediate and sustained shrinkage of power-law coded heterogeneous GSC populations.
Sprache	Englisch
Erscheinungsdatum	2019-03-22
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.26800
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Muse Cell: A New Paradigm for Cell Therapy and Regenerative Homeostasis in Ischemic Stroke.

Kuroda, Satoshi / Koh, Masaki / Hori, Emiko / Hayakawa, Yumiko / Akai, Takuya

Advances in experimental medicine and biology

2018 Band 1103, Seite(n) 187–198

Abstract: Multilineage-differentiating stress enduring (Muse) cells are one of the most promising donor cells for cell therapy against ischemic stroke, because they can differentiate into any type of cells constructing the central nervous system (CNS), including ... ...

Abstract	Multilineage-differentiating stress enduring (Muse) cells are one of the most promising donor cells for cell therapy against ischemic stroke, because they can differentiate into any type of cells constructing the central nervous system (CNS), including the neurons. They can easily be isolated from the bone marrow stromal cells (BMSCs), which may also contribute to functional recovery after ischemic stroke as donor cells. In this chapter, we concisely review their biological features and then future perspective of Muse cell transplantation for ischemic stroke. In addition, we briefly refer to the surprising role of Muse cells to maintain the homeostasis in the living body under both physiological and pathological conditions.
Mesh-Begriff(e)	Brain Ischemia/therapy ; Homeostasis ; Humans ; Pluripotent Stem Cells/cytology ; Regeneration ; Stem Cell Transplantation ; Stroke/therapy
Sprache	Englisch
Erscheinungsdatum	2018-11-27
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-4-431-56847-6_10
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Targeting the T-Lak cell originated protein kinase by OTS964 shrinks the size of power-law coded heterogeneous glioma stem cell populations.

Sugimori, Michiya / Hayakawa, Yumiko / Koh, Masaki / Hayashi, Tomohide / Tamura, Ryoi / Kuroda, Satoshi

Oncotarget

2018 Band 9, Heft 3, Seite(n) 3043–3059

Abstract: Glioblastoma resists chemoradiotherapy, then, recurs to be a fatal space-occupying lesion. The recurrence is caused by re-growing cell populations such as glioma stem cells (GSCs), suggesting that GSC populations should be targeted. This study addressed ... ...

Abstract	Glioblastoma resists chemoradiotherapy, then, recurs to be a fatal space-occupying lesion. The recurrence is caused by re-growing cell populations such as glioma stem cells (GSCs), suggesting that GSC populations should be targeted. This study addressed whether a novel anti-cancer drug, OTS964, an inhibitor for T-LAK cell originated protein kinase (TOPK), is effective in reducing the size of the heterogeneous GSC populations, a power-law coded heterogeneous GSC populations consisting of glioma sphere (GS) clones, by detailing quantitative growth properties. We found that OTS964 killed GS clones while suppressing the growth of surviving GS clones, thus identifying clone-eliminating and growth-disturbing efficacies of OTS964. The efficacies led to a significant size reduction in GS populations in a dose-dependent manner. The surviving GS clones reconstructed GS populations in the following generations; the recovery of GS populations fits a recurrence after the chemotherapy. The recovering GS clones resisted the clone-eliminating effect of OTS964 in sequential exposure during the growth recovery. However, surprisingly, the resistant properties of the recovered-GS clones had been plastically canceled during self-renewal, and then the GS clones had become re-sensitive to OTS964. Thus, OTS964 targets GSCs to eliminate them or suppress their growth, resulting in shrinkage of the power-law coded GSC populations. We propose a therapy focusing on long-term control in recurrence of glioblastoma via reducing the size of the GSC populations by OTS964.
Sprache	Englisch
Erscheinungsdatum	2018-01-09
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.23077
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Novel biomarker, phosphorylated T-LAK cell-originated protein kinase (p-TOPK) can predict outcome in primary central nervous system lymphoma.

Koh, Masaki / Hayakawa, Yumiko / Akai, Takuya / Hayashi, Tomohide / Tomita, Takahiro / Nagai, Shoichi / Kuroda, Satoshi

Neuropathology : official journal of the Japanese Society of Neuropathology

2018 Band 38, Heft 3, Seite(n) 228–236

Abstract: This study aimed to assess whether T-lymphokine-activated killer cell-originated protein kinase (TOPK) can be a potent novel biomarker to predict the outcome in patients with primary central nervous system lymphoma (PCNSL). This study enrolled 20 ... ...

Abstract	This study aimed to assess whether T-lymphokine-activated killer cell-originated protein kinase (TOPK) can be a potent novel biomarker to predict the outcome in patients with primary central nervous system lymphoma (PCNSL). This study enrolled 20 patients who were histologically diagnosed as having diffuse large B-cell type PCNSL between 2005 and 2015. Using surgical specimens, the expression of TOPK and phosphorylated TOPK (p-TOPK) was analyzed on immunohistochemistry. Clinical features such as age, sex, Karnofsky performance status (KPS), ocular involvement, deep brain structure involvement, the number of lesions, chemotherapy and radiation therapy were also collected. Impacts of TOPK/p-TOPK expression on their progression-free survival (PFS) and overall survival (OS) were examined with multivariate analysis. Median PFS/OS were 24.2 and 39.0 months, respectively. On immunostaining, the mean percentage of TOPK-positive cells was 35.5 ± 20.8%, and the mean number of p-TOPK-positive cells was 13.7 ± 15.7 cells/mm
Mesh-Begriff(e)	Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Central Nervous System Neoplasms/diagnosis ; Central Nervous System Neoplasms/metabolism ; Central Nervous System Neoplasms/therapy ; Disease-Free Survival ; Female ; Humans ; Lymphoma/diagnosis ; Lymphoma/metabolism ; Male ; Middle Aged ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Phosphorylation
Chemische Substanzen	Biomarkers, Tumor ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2) ; PDZ-binding kinase (EC 2.7.12.2)
Sprache	Englisch
Erscheinungsdatum	2018-03-25
Erscheinungsland	Australia
Dokumenttyp	Journal Article
ZDB-ID	1483794-8
ISSN	1440-1789 ; 0919-6544
ISSN (online)	1440-1789
ISSN	0919-6544
DOI	10.1111/neup.12463
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: The roles and issues of P2Y12 percent inhibition assessed by VerifyNow assay for patients undergoing Neurointervention: a prospective study.

Kashiwazaki, Daina / Kuwayama, Naoya / Akioka, Naoki / Hayakawa, Yumiko / Kuroda, Satoshi

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association

2014 Band 23, Heft 7, Seite(n) 1830–1836

Abstract: Background: Antiplatelet agents have an important role in the prevention of ischemic complications during endovascular treatment. The aim of this study was to identify correlations between the clinical outcomes of neurointervention. This study also ... ...

Abstract	Background: Antiplatelet agents have an important role in the prevention of ischemic complications during endovascular treatment. The aim of this study was to identify correlations between the clinical outcomes of neurointervention. This study also aimed to determine the optimal cutoff for P2Y12 percent inhibition to prevent ischemic and bleeding complications and to confirm the accuracy of the cutoff value. Methods: A prospective study was conducted for all patients (n = 66) who received antiplatelet therapy during neurointervention at Toyama University Hospital during a 25-month period. Platelet reactivity was measured before the procedure using the VerifyNow and filter pressure methods. The primary outcome was the 30-day incidence of adverse clinical events, defined as ischemic or bleeding events, in relation to P2Y12 percent inhibition distribution. Results: Multivariate analysis showed that P2Y12 percent inhibition was an independent predictor for bleeding (P = .021, odds ratio [OR] = 3.45; 95% confidence interval [CI], 2.31-4.88) and ischemic (P = .045, OR = 3.63; 95% CI, 2.11-7.12) events. In receiver operating characteristic curve analysis, P2Y12 percent inhibition could significantly discriminate between patients with and without bleeding and ischemic events. The optimal cutoffs for bleeding (74%) and ischemic events (26%) were used to define 3 groups: those with poor response, sufficient response, and hyper-response. Ischemic and bleeding complications were significantly different among the 3 groups. Conclusions: Optimal threshold, measured using the VerifyNow P2Y12 assay, can be identified using specific thresholds (26% < percent inhibition < 74%) to define patients at lower risk for ischemic and bleeding events. The threshold for hyper-response can highly predict bleeding events in perioperative period. On the other hands, cutoff value for poor response may be affected by various factors.
Mesh-Begriff(e)	Aged ; Brain Ischemia/etiology ; Female ; Humans ; Intracranial Hemorrhages/etiology ; Male ; Middle Aged ; Neurosurgical Procedures/methods ; Platelet Aggregation Inhibitors/adverse effects ; Platelet Aggregation Inhibitors/therapeutic use ; Platelet Function Tests ; Postoperative Complications/epidemiology ; Prospective Studies ; Purinergic P2Y Receptor Antagonists/adverse effects ; Purinergic P2Y Receptor Antagonists/therapeutic use ; Receptors, Purinergic P2Y12/drug effects ; Ticlopidine/adverse effects ; Ticlopidine/analogs & derivatives ; Ticlopidine/therapeutic use ; Treatment Outcome
Chemische Substanzen	Platelet Aggregation Inhibitors ; Purinergic P2Y Receptor Antagonists ; Receptors, Purinergic P2Y12 ; clopidogrel (A74586SNO7) ; Ticlopidine (OM90ZUW7M1)
Sprache	Englisch
Erscheinungsdatum	2014-08
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	1131675-5
ISSN	1532-8511 ; 1052-3057
ISSN (online)	1532-8511
ISSN	1052-3057
DOI	10.1016/j.jstrokecerebrovasdis.2014.04.014
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Impact of a novel biomarker, T-LAK cell-originating protein kinase (TOPK) expression on outcome in malignant glioma.

Hayashi, Tomohide / Hayakawa, Yumiko / Koh, Masaki / Tomita, Takahiro / Nagai, Shoichi / Kashiwazaki, Daina / Sugimori, Michiya / Origasa, Hideki / Kuroda, Satoshi

Neuropathology : official journal of the Japanese Society of Neuropathology

2017 Band 38, Heft 2, Seite(n) 144–153

Abstract: This study aimed to evaluate the biological features of T-lymphokine-activated killer cell-originating protein kinase (TOPK) in vitro and to assess clinical impact of TOPK on the outcome in patients with malignant glioma. TOPK protein level and TOPK mRNA ...

Abstract	This study aimed to evaluate the biological features of T-lymphokine-activated killer cell-originating protein kinase (TOPK) in vitro and to assess clinical impact of TOPK on the outcome in patients with malignant glioma. TOPK protein level and TOPK mRNA and protein levels in six glioma cell lines were examined using Western blot and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Immunohistochemistry was performed to examine their subcellular localization of TOPK. Using surgical specimens from 57 patients with gliomas, TOPK and Ki-67 expressions were examined by immunohistochemistry. Their co-localization was also examined with double immunofluorescence immunohistochemistry. Impacts of TOPK/Ki-67 expression on the overall survival (OS) and progression-free survival (PFS) in 32 patients with glioblastoma multiforme (GBM) were examined, using Kaplan-Meier and Cox proportion hazard models. Immunohistochemistry revealed that approximately 20-30% of glioma cells were positive for TOPK in vitro. TOPK mRNA was identified in all glioma cell lines on RT-PCR. The value of TOPK/GAPDH was 0.27 ± 0.11. TOPK and Ki-67 expressions were significantly higher in GBM patients than in non-GBM patients. A majority of TOPK-positive cells were also positive for Ki-67 and vice versa. Multivariate analysis revealed that a low TOPK expression (≤ 12.7%) was an independent predictor of longer OS (P = 0.0372), and that gross total removal and a low TOPK expression (≤ 12.7%) were independent predictors of longer PFS (P = 0.0470 and P = 0.0189, respectively). The findings strongly suggest biological and clinical importance of TOPK expression in gliomas, indicating a novel therapeutic potential of TOPK inhibitors to treat malignant gliomas.
Mesh-Begriff(e)	Adolescent ; Adult ; Aged ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Brain Neoplasms/diagnosis ; Brain Neoplasms/enzymology ; Brain Neoplasms/genetics ; Cell Line, Tumor ; Female ; Glioblastoma/diagnosis ; Glioblastoma/metabolism ; Glioma/diagnosis ; Glioma/enzymology ; Glioma/genetics ; Humans ; Ki-67 Antigen/metabolism ; Male ; Middle Aged ; Mitogen-Activated Protein Kinase Kinases/genetics ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Prognosis ; Proportional Hazards Models ; Young Adult
Chemische Substanzen	Biomarkers, Tumor ; Ki-67 Antigen ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2) ; PDZ-binding kinase (EC 2.7.12.2)
Sprache	Englisch
Erscheinungsdatum	2017-12-21
Erscheinungsland	Australia
Dokumenttyp	Journal Article
ZDB-ID	1483794-8
ISSN	1440-1789 ; 0919-6544
ISSN (online)	1440-1789
ISSN	0919-6544
DOI	10.1111/neup.12446
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Decreased thrombin activity by a Congolese herbal medicine used in sickle cell anemia

Nsimba, Marie Miezi / Lami, José Nzunzu / Hayakawa, Yumiko / Yamamoto, Chika / Kaji, Toshiyuki

Journal of ethnopharmacology. 2013 July 30, v. 148, no. 3

2013

Abstract: Ethnopharmacological relevance: Aqueous extracts from Ceiba pentandra (Malvaceae/Bombacoideae) and Quassia africana (Simaroubaceae) are used as crude medicines for the management of sickle cell anemia (SCA) in the Democratic Republic of Congo (DR Congo). ...

Abstract	Ethnopharmacological relevance: Aqueous extracts from Ceiba pentandra (Malvaceae/Bombacoideae) and Quassia africana (Simaroubaceae) are used as crude medicines for the management of sickle cell anemia (SCA) in the Democratic Republic of Congo (DR Congo). Since it is postulated that the pathogenesis of SCA is associated with an increased blood coagulation activity, the present study is conducted to determine the effect of the two extracts on the coagulation by assessing the thrombin activity and the plasma clotting time.Materials and Methods: Thrombin activity was measured by chromogenic assay in the presence of the aqueous extracts (10, 100 or 200µg/ml); and plasma clotting times were measured by activated partial thromboplastin time (APTT) and prothrombin time (PT) in the presence of C. pentandra (10, 100 or 200µg/ml) and Q. africana (5, 20 or 50µg/ml).Results: Reduced thrombin activity and prolonged plasma clotting time measured by APTT were observed in the presence of C. pentandra extract only. However, plasma clotting time measured by PT was not modified by the use of the two extracts.Conclusions: This study suggests that the aqueous extract of C. pentandra may contain active components that reduce the thrombin activity and prolong the plasma clotting time by affecting the coagulation intrinsic pathway.
Schlagwörter	Ceiba pentandra ; Quassia ; blood coagulation ; coagulation ; medicine ; pathogenesis ; prothrombin ; sickle cell anemia ; thrombin ; thromboplastin ; Democratic Republic of the Congo
Sprache	Englisch
Erscheinungsverlauf	2013-0730
Umfang	p. 895-900.
Erscheinungsort	Elsevier Ireland Ltd
Dokumenttyp	Artikel
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2013.05.038
Datenquelle	NAL Katalog (AGRICOLA)

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Artikel: Effect of a Congolese herbal medicine used in sickle cell anemia on the expression of plasminogen activators in human coronary aortic endothelial cells culture

Nsimba, Marie Miezi / Yamamoto, Chika / Lami, José Nzunzu / Hayakawa, Yumiko / Kaji, Toshiyuki

Journal of ethnopharmacology. 2013 Mar. 27, v. 146, no. 2

2013

Abstract: ETHNOPHARMACOLOGICAL RELEVANCE: Aqueous extract of Ceiba pentandra, which is used for the management of sickle cell anemia (SCA) in DR Congo, exhibits antithrombin response by activation of Heparin cofactor II in vitro. This study examines the effect of ... ...

Abstract	ETHNOPHARMACOLOGICAL RELEVANCE: Aqueous extract of Ceiba pentandra, which is used for the management of sickle cell anemia (SCA) in DR Congo, exhibits antithrombin response by activation of Heparin cofactor II in vitro. This study examines the effect of the plant on the fibrinolytic activity to understand whether it can influence the coagulation–fibrinolysis system, since fibrinolysis disorder is one of the contributing causes of thrombotic crises in SCA. MATERIALS AND METHODS: Fibrinolysis proteins were determined by enzyme-immunoassay in the conditioned medium of cultured endothelial cells after treatment with the extract. Electrophoresis-zymography and RT-PCR tests were conducted to examine the activity and the RNA synthesis of these proteins, respectively. RESULTS: It was found that the extract decreased the activity of both tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA) and plasminogen activator inhibitor type-1 (PAI-1). However, it was revealed that this effect was not the result of an inhibition of their biosynthesis by endothelial cells. CONCLUSION: From the foregoing, it was revealed that the extract inhibited the secretion of the fibrinolytic proteins without affecting their synthesis by endothelial cells. Thus, the extract may not accelerate the digestion of fibrin clot resulting from thrombotic disorders in SCA.
Schlagwörter	Ceiba pentandra ; RNA ; biosynthesis ; digestion ; endothelial cells ; fibrin ; fibrinolysis ; heparin ; humans ; medicine ; plasminogen ; plasminogen activator ; secretion ; sickle cell anemia ; Democratic Republic of the Congo
Sprache	Englisch
Erscheinungsverlauf	2013-0327
Umfang	p. 594-599.
Erscheinungsort	Elsevier Ireland Ltd
Dokumenttyp	Artikel
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2013.01.031
Datenquelle	NAL Katalog (AGRICOLA)

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Artikel ; Online: Mobilization of Pluripotent Multilineage-Differentiating Stress-Enduring Cells in Ischemic Stroke.

Hori, Emiko / Hayakawa, Yumiko / Hayashi, Tomohide / Hori, Satoshi / Okamoto, Soushi / Shibata, Takashi / Kubo, Michiya / Horie, Yukio / Sasahara, Masakiyo / Kuroda, Satoshi

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association

2016 Band 25, Heft 6, Seite(n) 1473–1481

Abstract: Goal: This prospective study was aimed to prove the hypothesis that multilineage-differentiating stress-enduring (Muse) cells are mobilized from bone marrow into peripheral blood in patients with ischemic stroke.: Materials and methods: This study ... ...

Abstract	Goal: This prospective study was aimed to prove the hypothesis that multilineage-differentiating stress-enduring (Muse) cells are mobilized from bone marrow into peripheral blood in patients with ischemic stroke. Materials and methods: This study included 29 patients with ischemic stroke. To quantify the circulating Muse cells, peripheral blood was obtained from all patients on admission and at days 7 and 30. Using fluorescence-activated cell sorting, Muse cells were identified as stage-specific embryonic antigen-3-positive cells. The control values were obtained from 5 healthy volunteers. Separately, immunohistochemistry was performed to evaluate the distribution of Muse cells in the bone marrow of 8 autopsy cases. Findings: The number of Muse cells robustly increased within 24 hours after the onset, compared with the controls, but their baseline number and temporal profile widely varied among patients. No clinical data predicted the baseline number of Muse cells at the onset. Multivariate analysis revealed that smoking and alcohol intake significantly affect the increase in circulating Muse cells. The odds ratio was .0027 (P = .0336) and 1688 (P = .0220) for smoking and alcohol intake, respectively. The percentage of Muse cells in the bone marrow was .20% ± .17%. Conclusion: This study shows that pluripotent Muse cells are mobilized from the bone marrow into peripheral blood in the acute stage of ischemic stroke. Smoking and alcohol intake significantly affect their temporal profile. Therapeutic interventions that increase endogenous Muse cells or exogenous administration of Muse cells may improve functional outcome after ischemic stroke.
Mesh-Begriff(e)	Adult ; Aged ; Aged, 80 and over ; Alcohol Drinking/adverse effects ; Alcohol Drinking/blood ; Antigens, Tumor-Associated, Carbohydrate/blood ; Biomarkers/blood ; Brain Ischemia/blood ; Brain Ischemia/diagnostic imaging ; Brain Ischemia/pathology ; Case-Control Studies ; Cell Differentiation ; Cell Lineage ; Cell Movement ; Cell Separation/methods ; Chi-Square Distribution ; Female ; Flow Cytometry ; Humans ; Linear Models ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Phenotype ; Pluripotent Stem Cells/metabolism ; Pluripotent Stem Cells/pathology ; Prospective Studies ; Risk Factors ; Smoking/adverse effects ; Smoking/blood ; Stage-Specific Embryonic Antigens/blood ; Stroke/diagnostic imaging ; Stroke/pathology ; Time Factors
Chemische Substanzen	Antigens, Tumor-Associated, Carbohydrate ; Biomarkers ; Stage-Specific Embryonic Antigens ; stage-specific embryonic antigen-3
Sprache	Englisch
Erscheinungsdatum	2016-06
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	1131675-5
ISSN	1532-8511 ; 1052-3057
ISSN (online)	1532-8511
ISSN	1052-3057
DOI	10.1016/j.jstrokecerebrovasdis.2015.12.033
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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