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Condition: Bleeding

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Total 36 results found since Jan 2013.

Titrating haemophilia B phenotypes using siRNA strategy: evidence that antithrombotic activity is separated from bleeding liability.
Abstract Haemophilia A and B are characterised by a life-long bleeding predisposition, and several lines of evidence suggest that risks of atherothrombotic events may also be reduced. Establishing a direct correlation between coagulation factor levels, thrombotic risks and bleeding propensity has long been hampered by an inability to selectively and specifically inhibit coagulation factor levels. Here, the exquisite selectivity of gene silencing combined with a gene knockout (KO) approach was used to define the relative contribution of factor IX (fIX) to thrombosis and primary haemostasis in the rat. Using a lipid...
Source: Thrombosis and Haemostasis - March 19, 2015 Category: Hematology Authors: Metzger JM, Tadin-Strapps M, Thankappan A, Strapps WR, Di Poetro M, Leander K, Zhang Z, Shin MK, Levorse J, Desai K, Xu Y, Lai K, Wu W, Chen Z, Cai TQ, Jochnowitz N, Bentley R, Hoos L, Zhou Y, Sepp-Lorenzino L, Seiffert D, Andre P Tags: Thromb Haemost Source Type: research

Targeting of antithrombin in hemophilia A or B with investigational siRNA therapeutic fitusiran - results of the phase 1 inhibitor cohort.
CONCLUSIONS: Monthly fitusiran was generally well tolerated, lowered antithrombin levels from baseline, and resulted in improved thrombin generation. These preliminary results suggest that monthly fitusiran treatment may reduce bleeding episodes and improve QoL in participants with hemophilia A or B with inhibitors. PMID: 33587824 [PubMed - as supplied by publisher]
Source: Thrombosis and Haemostasis - February 15, 2021 Category: Hematology Authors: Pasi KJ, Lissitchkov T, Mamonov V, Mant T, Timofeeva M, Bagot C, Chowdary P, Georgiev P, Gercheva-Kyuchukova L, Madigan K, Nguyen H, Yu Q, Mei B, Benson CC, Ragni MV Tags: J Thromb Haemost Source Type: research

Title: Genistein Disrupts Glucocorticoid Receptor Signaling in Human Uterine Endometrial Ishikawa Cells
Conclusions: Using Ishikawa cells, we observed that exposure to genistein resulted in distinct changes in gene expression and unique differences in the GR transcriptome. Citation: Whirledge S, Senbanjo LT, Cidlowski JA. 2015. Genistein disrupts glucocorticoid receptor signaling in human uterine endometrial Ishikawa cells. Environ Health Perspect 123:80–87; http://dx.doi.org/10.1289/ehp.1408437 Address correspondence to J.A. Cidlowski, NIH/NIEHS, MD F3-07, P.O. Box 12233, Research Triangle Park, NC 27709 USA. Telephone: (919) 541-1564. E-mail: cidlows1@niehs.nih.gov We thank X. Xu (Integrative Bioinformatic...
Source: EHP Research - December 31, 2014 Category: Environmental Health Authors: Web Admin Tags: Research Article January 2015 Source Type: research

Silencing of protease‐activated receptors attenuates synovitis and cartilage damage following a joint bleed in haemophilic mice
ConclusionThis study demonstrates that synovial and chondrocyte PAR expression is altered upon a joint bleed, and that treatment with PAR1–4 siRNA attenuates synovitis and plasmin‐induced cartilage damage.
Source: Haemophilia - July 1, 2015 Category: Hematology Authors: L. Nieuwenhuizen, R. E. G. Schutgens, K. Coeleveld, S. C. Mastbergen, R. M. Schiffelers, G. Roosendaal, D. H. Biesma, F. P. J. G. Lafeber Tags: Original Article Source Type: research

Correction of a dominant-negative von Willebrand factor multimerization defect by small interfering RNAs-mediated allele-specific inhibition of mutant von Willebrand factor.
CONCLUSIONS: Allele-specific siRNAs are able to distinguish VWF alleles based on one nucleotide variation and are able to improve a severe multimerization defect caused by VWF p.Cys2773Ser. This holds promise for the therapeutic application of allele-specific siRNAs in dominant-negative VWD. This article is protected by copyright. All rights reserved. PMID: 29734512 [PubMed - as supplied by publisher]
Source: Thrombosis and Haemostasis - May 7, 2018 Category: Hematology Authors: de Jong A, Dirven RJ, Oud JA, Tio D, van Vlijmen BJM, Eikenboom J Tags: J Thromb Haemost Source Type: research

Tristetraprolin attenuates brain edema in a rat model of cerebral hemorrhage
ConclusionTaken together, these data indicate that TTP has a protective role against brain edema by reducing inflammation, apoptosis, and water content in the brain at 48  hr after cerebral hemorrhage. Our findings may be useful for developing important approaches to treating brain injury.
Source: Brain and Behavior - February 6, 2019 Category: Neurology Authors: Peiyu Li, Junwu Zhang, Xin Li, Hongwei Gao Tags: ORIGINAL RESEARCH Source Type: research

17{beta}-Estradiol Attenuates Hematoma Expansion Through Estrogen Receptor {alpha}/Silent Information Regulator 1/Nuclear Factor-kappa B Pathway in Hyperglycemic Intracerebral Hemorrhage Mice Basic Sciences
Conclusions— E2 treatment prevented hyperglycemia-enhanced HE and improved neurological deficits in ICH mice mediated by ERα/Sirt1/nuclear factor-kappa B pathway. E2 may serve as an alternative treatment to decrease early HE after ICH.
Source: Stroke - January 26, 2015 Category: Neurology Authors: Zheng, Y., Hu, Q., Manaenko, A., Zhang, Y., Peng, Y., Xu, L., Tang, J., Tang, J., Zhang, J. H. Tags: Animal models of human disease, Neuroprotectors Basic Sciences Source Type: research

Factor XII full and partial null in rat confers robust antithrombotic efficacy with no bleeding
This report aims at exploring quantitatively the relationship between FXII inhibition and thromboprotection. FXII full and partial null in rats were established via zinc finger nuclease-mediated knockout and siRNA-mediated knockdown, respectively. The rats were subsequently characterized in thrombosis and hemostasis models. Knockout rats exhibited complete thromboprotection in both the arteriovenous shunt model (∼100% clot weight reduction) and the FeCl3-induced arterial thrombosis model (no reduction in blood flow), without any increase in cuticle bleeding time compared with wild-type control rats. Ex-vivo aPTT and the ...
Source: Blood Coagulation and Fibrinolysis - October 31, 2015 Category: Hematology Tags: Original Articles Source Type: research

UII/GPR14 is involved in NF- κB-mediated colonic inflammation in vivo and in vitro.
In conclusion, UII/GPR14 signaling was involved in the DSS-induced colonic inflammation and its inhibition may serve as a potential therapeutic target, which may be associated with the NF-κB signaling pathway. PMID: 27600191 [PubMed - as supplied by publisher]
Source: Oncology Reports - September 8, 2016 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

G protein-dependent basal and evoked endothelial cell vWF secretion
von Willebrand factor (vWF) secretion by endothelial cells (ECs) is essential for hemostasis and thrombosis; however, the molecular mechanisms are poorly understood. Interestingly, we observed increased bleeding in EC-Gα13–/–;Gα12–/– mice that could be normalized by infusion of human vWF. Blood from Gα12–/– mice exhibited significantly reduced vWF levels but normal vWF multimers and impaired laser-induced thrombus formation, indicating that Gα12 plays a prominent role in EC vWF secretion required for hemostasis and thrombosis. In isolated buffer-perfused mouse lun...
Source: Blood - January 16, 2014 Category: Hematology Authors: Rusu, L., Andreeva, A., Visintine, D. J., Kim, K., Vogel, S. M., Stojanovic-Terpo, A., Chernaya, O., Liu, G., Bakhshi, F. R., Haberichter, S. L., Iwanari, H., Kusano-Arai, O., Suzuki, N., Hamakubo, T., Kozasa, T., Cho, J., Du, X., Minshall, R. D. Tags: Thrombosis and Hemostasis, Vascular Biology Source Type: research

Role of Transient Receptor Potential Vanilloid 4 activation in indomethacin-induced intestinal damage.
Abstract Gastrointestinal ulcers and bleeding are serious complications of non-steroidal anti-inflammatory drug (NSAID) use. While administration of antibiotics and Toll-like receptor 4 knockdown mitigate NSAID-induced enteropathy, the molecular mechanism of these effects is poorly understood. Intestinal hyperpermeability is speculated to trigger the initial damage due to NSAID use. Transient receptor potential vanilloid 4 (TRPV4) is a non-selective cation channel expressed throughout the gastrointestinal (GI) tract epithelium, which is activated by temperature, extension, and chemicals such as 5,6-epoxyeicosatrie...
Source: Am J Physiol Gastroi... - May 1, 2014 Category: Gastroenterology Authors: Yamawaki H, Mihara H, Suzuki N, Nishizono H, Uchida K, Watanabe S, Tominaga M, Sugiyama T Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

The protective effect of piperine on dextran sulfate sodium induced inflammatory bowel disease and its relation with pregnane X receptor activation
Conclusion Piperine is a potential agonist of PXR and an inducer of PXR, which may induce CYP3A4 gene expression at the mRNA and protein levels. These results establish that piperine may contribute to prevention or reduction of colonic inflammation. Graphical abstract
Source: Journal of Ethnopharmacology - May 18, 2015 Category: Drugs & Pharmacology Source Type: research

New and Emerging Agents for the Treatment of Hemophilia: Focus on Extended Half-Life Recombinant Clotting Proteins
Abstract Hemophilia A and B are X-linked disorders caused by deficient or defective clotting factor VIII (FVIII) or IX factor (FIX) proteins, and characterized by spontaneous or traumatic bleeding into joints and muscles. Previous use of plasma and plasma-derived clotting factors that lacked appropriate viral inactivation steps in manufacturing led to significant morbidity associated with transfusion-transmitted HIV and hepatitis C virus (HCV). The development of recombinant proteins revolutionized their treatment, and, with no new HIV or HCV infection via clotting proteins for nearly 30 years, greatly improved t...
Source: Drugs - August 27, 2015 Category: Drugs & Pharmacology Source Type: research

Alternative therapies for the management of inhibitors
The development of inhibitors to factor VIII (FVIII) or factor IX (FIX) remains a major treatment complication encountered in the treatment of haemophilia. Not all patients with even the same severity and genotype develop inhibitors suggesting an underlying mechanism of tolerance against FVIII‐ or FIX‐related immunity. One mechanism may be central tolerance observed in patients in whom the FVIII mutation enables some production of the protein. The other is a peripheral tolerance mechanism which may be evident in patients with null mutation. Recently, recombinant porcine FVIII (rpFVIII, Obixur, OBI‐1, BAX801) has been...
Source: Haemophilia - July 12, 2016 Category: Hematology Authors: M. Shima, D. Lillicrap, R. Kruse‐Jarres Tags: Original Article Source Type: research

miRNA-133a-UCP2 pathway regulates inflammatory bowel disease progress by influencing inflammation, oxidative stress and energy metabolism.
CONCLUSION: The miR-133a-UCP2 pathway participates in IBD by altering downstream inflammation, oxidative stress and markers of energy metabolism, which provides novel clues and potential therapeutic targets for IBD. PMID: 28104982 [PubMed - in process]
Source: World Journal of Gastroenterology : WJG - January 6, 2017 Category: Gastroenterology Authors: Jin X, Chen D, Zheng RH, Zhang H, Chen YP, Xiang Z Tags: World J Gastroenterol Source Type: research