10,693 results match your criteria Factor X


Newly synthesized mRNA escapes translational repression during the acute phase of the mammalian unfolded protein response.

PLoS One 2022 10;17(8):e0271695. Epub 2022 Aug 10.

Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio, United States of America.

Endoplasmic Reticulum (ER) stress, caused by the accumulation of misfolded proteins in the ER, elicits a homeostatic mechanism known as the Unfolded Protein Response (UPR). The UPR reprograms gene expression to promote adaptation to chronic ER stress. The UPR comprises an acute phase involving inhibition of bulk protein synthesis and a chronic phase of transcriptional induction coupled with the partial recovery of protein synthesis. Read More

View Article and Full-Text PDF

Succinate dehydrogenase and MYC-associated factor X mutations in pituitary neuroendocrine tumours.

Endocr Relat Cancer 2022 Aug 1. Epub 2022 Aug 1.

M Korbonits, Endocrinology, Barts and The London School of Medicine and Dentistry William Harvey Research Institute, London, United Kingdom of Great Britain and Northern Ireland.

Pituitary neuroendocrine tumours (PitNETs) associated with paragangliomas or phaeochromocytomas are rare. SDHx variants are estimated to be associated with 0.3-1. Read More

View Article and Full-Text PDF

Toward protein NMR at physiological concentrations by hyperpolarized water-Finding and mapping uncharted conformational spaces.

Sci Adv 2022 Aug 5;8(31):eabq5179. Epub 2022 Aug 5.

University of Vienna, Faculty of Chemistry, Institute of Biological Chemistry, Währinger Str. 38, 1090 Vienna, Austria.

Nuclear magnetic resonance (NMR) spectroscopy is a key method for determining the structural dynamics of proteins in their native solution state. However, the low sensitivity of NMR typically necessitates nonphysiologically high sample concentrations, which often limit the relevance of the recorded data. We show how to use hyperpolarized water by dissolution dynamic nuclear polarization (DDNP) to acquire protein spectra at concentrations of 1 μM within seconds and with a high signal-to-noise ratio. Read More

View Article and Full-Text PDF

Anti-factor X Activity Levels with Continuous Intravenous Infusion and Subcutaneous Administration of Enoxaparin after Coronary Artery Bypass Grafting: a Randomized Clinical Trial.

Acta Anaesthesiol Scand 2022 Jul 30. Epub 2022 Jul 30.

Tampere University Heart Hospital Tampere, Finland.

Background: Low-molecular-weight heparin enoxaparin is widely used in pharmacological thromboprophylaxis after coronary artery bypass grafting (CABG). The aim of this study was to compare anti-factor X activity (anti-Xa) levels when the thromboprophylactic dose of enoxaparin was provided after CABG, with two different administration routes: continuous intravenous infusion (CIV) and subcutaneous bolus (SCB) injection. We hypothesized that the current standard method of SCB administration might lead to lower anti-Xa levels than recommended in other patient groups, due to reduced bioavailability. Read More

View Article and Full-Text PDF

Preparation and blood compatibility of polyethersulfone dialysis membrane modified by apixaban as coagulation factor Xa inhibitor.

Biomater Adv 2022 Aug 4;139:213012. Epub 2022 Jul 4.

College of Electrical and Information Engineering, Changsha University of Science and Technology, China.

Blood purification therapy is widely used in the treatment of critically ill patients. However, most dialysis membranes are prone to thrombosis. Activated coagulation factor X (FXa) functions at the intersection of intrinsic, extrinsic, and common coagulation pathways and plays a central role in thrombogenesis. Read More

View Article and Full-Text PDF

Protective effect of zinc supplementation on tricalcium phosphate particles-induced inflammatory osteolysis in mice.

Microsc Res Tech 2022 Jul 25. Epub 2022 Jul 25.

College of Medicine, Shaoxing University, Shaoxing, People's Republic of China.

Zinc (Zn), an essential trace element, can stimulate bone formation and inhibit osteoclastic bone resorption, which controls the growth and maintenance of bone. However, the effect of Zn supplementation on tricalcium phosphate (TCP) wear particles-induced osteolysis remains unknown. Here, we doped Zn into TCP particles (ZnTCP), and explore the protective effects of Zn on TCP particles-induced osteolysis in vivo. Read More

View Article and Full-Text PDF

[IgD multiple myeloma mimicking free light chain myeloma complicated by factor X deficiency: a case report].

Pan Afr Med J 2022 27;41:338. Epub 2022 Apr 27.

Service d´Hématologie Clinique, Centre Hospitalier de Versailles André Mignot, Faculté de Médecine Xavier Bichat, Université Paris Diderot, Paris, France.

IgD myeloma is an extremely rare haemopathy with severe clinical presentation. It can be confused with non-secretory or free light chain myeloma. We here report the case of a 72-year old female patient presenting with bone pain and diffuse ecchymosis and deterioration of her general condition. Read More

View Article and Full-Text PDF

Activation of the canonical ER Stress IRE1-XBP1 Pathway by Insulin Regulates Glucose and Lipid Metabolism.

J Biol Chem 2022 Jul 18:102283. Epub 2022 Jul 18.

Departments of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Departments of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address:

Knockout of the transcription factor X-box binding protein (XBP1) is known to decrease liver glucose production and lipogenesis. However, whether insulin can regulate gluconeogenesis and lipogenesis through XBP1 and how insulin activates the inositol-requiring enzyme (IRE1)-XBP1 ER stress pathway remain unexplored. Here we report that in the fed state, insulin-activated kinase AKT directly phosphorylates IRE1 at S724, which in turn mediates the splicing of XBP1u mRNA, thus favoring the generation of the spliced form, XBP1s, in the liver of mice. Read More

View Article and Full-Text PDF

Prevalence, clinical characteristics and treatment outcome of factor X deficiency in a consecutive cohort of primary light-chain amyloidosis.

Leuk Res 2022 Jul 5;120:106917. Epub 2022 Jul 5.

Department of Hematology, Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address:

Factor X (FX) deficiency is prevalent in light-chain (AL) amyloidosis but its clinical significance was not investigated deeply. We conducted a retrospective analysis of a consecutive cohort with 207 primary AL amyloidosis patients. FX deficiency was present in 129 patients (62. Read More

View Article and Full-Text PDF

Vitamin K antagonist reversal strategies: Systematic review and network meta-analysis from the AABB.

Transfusion 2022 Aug 14;62(8):1652-1661. Epub 2022 Jul 14.

Department of Laboratory Medicine and Pathology, University of Minnesota WI, Minneapolis, Minnesota, USA.

Background: Anticoagulation requires urgent reversal in cases of life-threatening bleeding or invasive procedures.

Study Design And Methods: Network meta-analysis for comparing the safety and efficacy of warfarin reversal strategies including plasma and prothrombin complex concentrates (PCCs).

Results: Seven studies including 594 subjects using reversal agents plasma, 3-factor-PCC (Uman Complex and Konyne), and 4-factor-PCC (Beriplex/KCentra, Octaplex, and Cofact) met inclusion criteria. Read More

View Article and Full-Text PDF

Hsa_circ_0030042 Ameliorates Oxidized Low-Density Lipoprotein-Induced Endothelial Cell Injury via the MiR-616-3p/RFX7 Axis.

Int Heart J 2022 Jul 14;63(4):763-772. Epub 2022 Jul 14.

Department of Internal Medicine-Cardiovascular, The First Hospital of Qiqihar, Affiliated Qiqihar Hospital, Southern Medical University.

Atherosclerosis (AS) is a common etiology of cardiovascular disease. As an emerging functional biomarker, circular RNAs (circRNAs) are involved in various diseases, including cardiovascular disease. However, the mechanism of action of circ_0030042 in AS has not been reported. Read More

View Article and Full-Text PDF

Mitchell-Riley Syndrome: Improving Clinical Outcomes and Searching for Functional Impact of RFX-6 Mutations.

Front Endocrinol (Lausanne) 2022 22;13:802351. Epub 2022 Jun 22.

Department of Endocrinology, Metabolism and Diabetes, Inserm U1016, Cochin Institute, Paris, France.

Aims/hypothesis: Caused by biallelic mutations of the gene encoding the transcription factor , the rare Mitchell-Riley syndrome (MRS) comprises neonatal diabetes, pancreatic hypoplasia, gallbladder agenesis or hypoplasia, duodenal atresia, and severe chronic diarrhea. So far, sixteen cases have been reported, all with a poor prognosis. This study discusses the multidisciplinary intensive clinical management of 4 new cases of MRS that survived over the first 2 years of life. Read More

View Article and Full-Text PDF

Assessing the Role of a Malonamide Linker in the Design of Potent Dual Inhibitors of Factor Xa and Cholinesterases.

Molecules 2022 Jul 2;27(13). Epub 2022 Jul 2.

Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Via Orabona 4, 70125 Bari, Italy.

The rational discovery of new peptidomimetic inhibitors of the coagulation factor Xa (fXa) could help set more effective therapeutic options (to prevent atrial fibrillation). In this respect, we explored the conformational impact on the enzyme inhibition potency of the malonamide bridge, compared to the glycinamide one, as a linker connecting the P1 benzamidine anchoring moiety to the P4 aryl group of novel selective fXa inhibitors. We carried out structure-activity relationship (SAR) studies aimed at investigating - or -benzamidine as the P1 basic group as well as diversely decorated aryl moieties as P4 fragments. Read More

View Article and Full-Text PDF

Costs and Healthcare Resource Utilization Associated with Idarucizumab or Andexanet Alfa Oral Anticoagulant Reversal in Patients Hospitalized with Life-Threatening Bleeds.

Clin Appl Thromb Hemost 2022 Jan-Dec;28:10760296221110568

6893Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA.

To assess costs and healthcare resource utilization (HCRU) associated with the use of idarucizumab for the reversal of dabigatran and andexanet alfa for the reversal of direct oral Factor Xa inhibitors. This retrospective study utilizing Premier Healthcare Database (PHD) included patients aged ≥18 years on direct oral anticoagulants (DOACs) who experienced life-threatening bleeds, discharged from the hospital during 5/1/2018-6/30/2019, and received idarucizumab or andexanet alfa. Inverse of treatment probability weighting (IPTW) method was used to balance patient and clinical characteristics between treatment cohorts. Read More

View Article and Full-Text PDF

Put out the fire: The pleiotropic anti-inflammatory action of non-vitamin K oral anticoagulants.

Pharmacol Res 2022 Aug 30;182:106335. Epub 2022 Jun 30.

Cardiology Unit, Department of Medical Translational Sciences, University of Campania "Luigi Vanvitelli" - Monaldi Hospital, Naples, Italy.

Non-vitamin K antagonist oral anticoagulants (NOACs) should be the preferred anticoagulant strategy for preventing ischemic stroke in patients with atrial fibrillation (AF) at increased thromboembolic risk and for treating deep venous thromboembolism (DVT) in the general population. Beyond their inhibiting action on the activated factor X (FXa) or thrombin (FIIa), NOACs showed some pleiotropic anti-inflammatory effects. The present review aimed to describe the role of FXa and FIIa in the inflammation pathway and the potential anti-inflammatory effects of NOACs. Read More

View Article and Full-Text PDF

Evaluation of the mechanisms of heme-induced tissue factor activation: Contribution of innate immune pathways.

Exp Biol Med (Maywood) 2022 Jul 1:15353702221106475. Epub 2022 Jul 1.

School of Medical Sciences, University of Campinas, CEP 13083-894 Campinas, Brazil.

Hemolytic diseases such as Sickle Cell Disease (SCD) are characterized by a natural propensity for both arterial and venous thrombosis. The ability of heme to induce tissue factor (TF) activation has been shown both in animal models of SCD, and in human endothelial cells and monocytes. Moreover, it was recently demonstrated that heme can induce coagulation activation in the whole blood of healthy volunteers in a TF-dependent fashion. Read More

View Article and Full-Text PDF

Biochemistry and toxicology of proteins and peptides purified from the venom of .

Toxicon X 2022 Sep 12;15:100131. Epub 2022 Jun 12.

Laboratory of Environmental Toxicology, National Institute of Chemical Physics and Biophysics, Akadeemia Tee 23, 12618, Tallinn, Estonia.

The isolation and characterization of individual snake venom components is important for a deeper understanding of the pathophysiology of envenomation and for improving the therapeutic procedures of patients. It also opens possibilities for the discovery of novel toxins that might be useful as tools for understanding cellular and molecular processes. The variable venom composition, toxicological and immunological properties of the common vipers () have been reviewed. Read More

View Article and Full-Text PDF
September 2022

Coagulation factors promote brown adipose tissue dysfunction and abnormal systemic metabolism in obesity.

iScience 2022 Jul 7;25(7):104547. Epub 2022 Jun 7.

Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8431, Japan.

Brown adipose tissue (BAT) has a role in maintaining systemic metabolic health in rodents and humans. Here, we show that metabolic stress induces BAT to produce coagulation factors, which then-together with molecules derived from the circulation-promote BAT dysfunction and systemic glucose intolerance. When mice were fed a high-fat diet (HFD), the levels of tissue factor, coagulation Factor VII (FVII), activated coagulation Factor X (FXa), and protease-activated receptor 1 (PAR1) expression increased significantly in BAT. Read More

View Article and Full-Text PDF

The transcription factor RFX5 coordinates antigen-presenting function and resistance to nutrient stress in synovial macrophages.

Nat Metab 2022 06 23;4(6):759-774. Epub 2022 Jun 23.

Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.

Tissue macrophages (Mϕ) are essential effector cells in rheumatoid arthritis (RA), contributing to autoimmune tissue inflammation through diverse effector functions. Their arthritogenic potential depends on their proficiency to survive in the glucose-depleted environment of the inflamed joint. Here, we identify a mechanism that links metabolic adaptation to nutrient stress with the efficacy of tissue Mϕ to activate adaptive immunity by presenting antigen to tissue-invading T cells. Read More

View Article and Full-Text PDF

Andexanet alfa versus four-factor prothrombin complex concentrate for the reversal of apixaban- or rivaroxaban-associated intracranial hemorrhage: a propensity score-overlap weighted analysis.

Crit Care 2022 06 16;26(1):180. Epub 2022 Jun 16.

Department of Pharmacy Practice, University of Connecticut School of Pharmacy, 69 North Eagleville Road, Unit 3092, Storrs, CT, 06269, USA.

Background: Andexanet alfa is approved (FDA "accelerated approval"; EMA "conditional approval") as the first specific reversal agent for factor Xa (FXa) inhibitor-associated uncontrolled or life-threatening bleeding. Four-factor prothrombin complex concentrates (4F-PCC) are commonly used as an off-label, non-specific, factor replacement approach to manage FXa inhibitor-associated life-threatening bleeding. We evaluated the effectiveness and safety of andexanet alfa versus 4F-PCC for management of apixaban- or rivaroxaban-associated intracranial hemorrhage (ICH). Read More

View Article and Full-Text PDF

Shining a light on thrombin activation.

Authors:
P Clint Spiegel

Blood 2022 06;139(24):3451-3453

Western Washington University.

View Article and Full-Text PDF

Effect of lower-leg trauma and knee arthroscopy on procoagulant phospholipid-dependent activity.

Res Pract Thromb Haemost 2022 May 8;6(4):e12729. Epub 2022 Jun 8.

Department of Clinical Epidemiology Leiden University Medical Center Leiden The Netherlands.

Background: Lower-leg injury and knee arthroscopy are both associated with venous thromboembolism (VTE). The mechanism of VTE in both situations is unknown, including the role of procoagulant microparticles. This may provide useful information for individualizing thromboprophylactic treatment in both patient groups. Read More

View Article and Full-Text PDF

ZPI prevents ox-LDL-mediated endothelial injury leading to inhibition of EndMT, inflammation, apoptosis, and oxidative stress through activating Pi3k/Akt signal pathway.

Drug Dev Res 2022 Jun 2. Epub 2022 Jun 2.

Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Oxidized low-density lipoprotein (ox-LDL)-mediated endothelial dysfunction exerts an essential role in the development of atherosclerosis. Protein Z-dependent protease inhibitor (ZPI), a member of the serine protease inhibitor superfamily, could inhibit the function of activated coagulation factor X (FXa) via interaction with protein Z (PZ). Studies have pointed out that ZPI was statistically related to atherosclerotic diseases, which may have a robust cardiovascular protective effect. Read More

View Article and Full-Text PDF

Isolated coagulopathy without classic CRAB symptoms as the initial manifestation of multiple myeloma: A case report.

World J Clin Cases 2022 Apr;10(12):3822-3827

Department of Hematology, Mianyang Central Hospital, Mianyang 621000, Sichuan Province, China.

Background: Multiple myeloma patients usually present with CRAB symptoms (hypercalcemia, renal disease, anemia and bone diseases) as initial manifestations. Bleeding symptoms are less common, most of which result from thrombocytopenia or infiltration of plasmacytoma. Relatively, coagulopathy is not so common, especially isolated coagulopathy without CRAB manifestations, which is very rare. Read More

View Article and Full-Text PDF

Bilateral Pheochromocytoma with Germline MAX Variant without Family History.

Clin Pract 2022 May 7;12(3):299-305. Epub 2022 May 7.

Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

Recently, the genetic background of pheochromocytomas/paragangliomas (PPGLs) has been rapidly revealed. These tumors have been referred to as the "ten percent tumor"; however, the frequency of genetic variants of PPGLs has turned out to be more common than expected. PPGLs are potentially hereditary tumors and appear clinically sporadic. Read More

View Article and Full-Text PDF

Improving the selectivity of 3-amidinophenylalanine-derived matriptase inhibitors.

Eur J Med Chem 2022 Aug 12;238:114437. Epub 2022 May 12.

Institute of Pharmaceutical Chemistry, Philipps University, Marbacher Weg 6, D-35032, Marburg, Germany. Electronic address:

A rational structure-based approach was employed to develop novel 3-amidinophenylalanine-derived matriptase inhibitors with improved selectivity against thrombin and factor Xa. Of all 23 new derivatives, several monobasic inhibitors exhibit high matriptase affinities and strong selectivity against thrombin. Some inhibitors also possess selectivity against factor Xa, although less pronounced as found for thrombin. Read More

View Article and Full-Text PDF

Unexpected Dynamic Binding May Rescue the Binding Affinity of Rivaroxaban in a Mutant of Coagulation Factor X.

Front Mol Biosci 2022 5;9:877170. Epub 2022 May 5.

State Key Laboratory of Microbial Metabolism & Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

A novel coagulation factor X (FX) Tyr319Cys mutation (Y99C as chymotrypsin numbering) was identified in a patient with severe bleeding. Unlike the earlier reported Y99A mutant, this mutant can bind and cleave its specific chromogenetic substrate at a normal level, suggesting an intact binding pocket. Here, using molecular dynamics simulations and MM-PBSA calculations on a FX-rivaroxaban (RIV) complex, we confirmed a much stronger binding of RIV in Y99C than in Y99A on a molecular level, which is actually the average result of multiple binding poses in dynamics. Read More

View Article and Full-Text PDF

Clotting factor genes are associated with preeclampsia in high-altitude pregnant women in the Peruvian Andes.

Am J Hum Genet 2022 06 18;109(6):1117-1139. Epub 2022 May 18.

Department of Genetics, Stanford School of Medicine, Stanford, CA 94305, USA; Department of Biomedical Data Science, Stanford School of Medicine, Stanford, CA 94305, USA.

Preeclampsia is a multi-organ complication of pregnancy characterized by sudden hypertension and proteinuria that is among the leading causes of preterm delivery and maternal morbidity and mortality worldwide. The heterogeneity of preeclampsia poses a challenge for understanding its etiology and molecular basis. Intriguingly, risk for the condition increases in high-altitude regions such as the Peruvian Andes. Read More

View Article and Full-Text PDF

Comparative hemostatic efficacy of 4F-PCC in patients with intracranial hemorrhage on factor Xa inhibitors versus warfarin.

Am J Emerg Med 2022 07 30;57:149-152. Epub 2022 Apr 30.

Department of Pharmacy, Lakeland Regional Health, 1324 Lakeland Hills Blvd, Lakeland, FL 33805, United States of America.

Objective: Patients experiencing an intracranial hemorrhage (ICH) on oral anticoagulants often require rapid reversal. This study evaluated patients taking factor Xa inhibitors or warfarin that received reversal with 4-factor prothrombin complex concentrate (4F-PCC) for an ICH. The objective of the study was to determine if the efficacy of 4F-PCC for the reversal of factor Xa inhibitors is noninferior to its use in warfarin reversal in patients with ICH. Read More

View Article and Full-Text PDF

Deficiency of the splicing factor RBM10 limits EGFR inhibitor response in EGFR-mutant lung cancer.

J Clin Invest 2022 07;132(13)

Department of Medicine and.

Molecularly targeted cancer therapy has improved outcomes for patients with cancer with targetable oncoproteins, such as mutant EGFR in lung cancer. Yet, the long-term survival of these patients remains limited, because treatment responses are typically incomplete. One potential explanation for the lack of complete and durable responses is that oncogene-driven cancers with activating mutations of EGFR often harbor additional co-occurring genetic alterations. Read More

View Article and Full-Text PDF