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PAR1 biased signaling is required for activated protein C in vivo benefits in sepsis and stroke
Activated protein C (APC) cleaves protease-activated receptor 1 (PAR1) in vitro at R46 to initiate beneficial cell signaling; however, thrombin and APC can cleave at R41. To elucidate PAR1-dependent aspects of the pharmacologic in vivo mechanisms of APC, we generated C57BL/6 mouse strains carrying QQ41 or QQ46 point mutations in PAR1 (F2r gene). Using these strains, we determined whether or not recombinant murine signaling-selective APC mutants would reduce septic death or provide neuroprotection against ischemic stroke when mice carried PAR1-homozygous mutations that prevent cleavage at either R41 or R46. Intercrossing PA...
Source: Blood - March 15, 2018 Category: Hematology Authors: Sinha, R. K., Wang, Y., Zhao, Z., Xu, X., Burnier, L., Gupta, N., Fernandez, J. A., Martin, G., Kupriyanov, S., Mosnier, L. O., Zlokovic, B. V., Griffin, J. H. Tags: Plenary Papers, Thrombosis and Hemostasis, Vascular Biology Source Type: research

Severe Symptoms, but a Truly Treatable Disease
​BY NOURA MAHDI; DARRON LEWIS; JEREMY OSBORNE; & AHMED RAZIUDDIN, MDA 73-year-old man was brought to the emergency department from his nursing home for rectal bleeding and anemia. The patient mentioned he had had episodes of bright red rectal bleeding and constipation for a few months. A colonoscopy had been done prior to the visit, which revealed a large intestine tumor and biopsy confirming adenocarcinoma. He was awaiting an appointment with his surgeon.The patient reported bloody rectal leakage, and a CBC done at the nursing home showed a hemoglobin level of 7.2. He also complained of dyspnea but denied any other ...
Source: The Case Files - March 20, 2018 Category: Emergency Medicine Tags: Blog Posts Source Type: research

cDNA cloning of a snake venom metalloproteinase from the eastern diamondback rattlesnake (Crotalus adamanteus), and the expression of its disintegrin domain with anti-platelet effects.
Abstract A 5' truncated snake venom metalloproteinase was identified from a cDNA library constructed from venom glands of an eastern diamondback rattlesnake (Crotalus adamanteus). The 5'-rapid amplification of cDNA ends (RACE) was used to obtain the 1865 bp full-length cDNA sequence of a snake venom metalloproteinase (CamVMPII). CamVMPII encodes an open reading frame of 488 amino acids, which includes a signal peptide, a pro-domain, a metalloproteinase domain, a spacer, and an RGD-disintegrin domain. The predicted amino acid sequence of CamVMPII showed a 91%, 90%, 83%, and 82% sequence homology to the P-II class e...
Source: Toxicon - January 10, 2013 Category: Toxicology Authors: Suntravat M, Jia Y, Lucena SE, Sánchez EE, Pérez JC Tags: Toxicon Source Type: research

Molecular cloning of Reteplase and its expression in E. coli using tac promoter.
CONCLUSION: In the present study, reteplase cDNA was successfully cloned and expressed using tac promoter. This vector will be used for the optimization of the expression of reteplase in E. coli. PMID: 25298959 [PubMed]
Source: Biomed Res - October 12, 2014 Category: Research Authors: Aghaabdollahian S, Rabbani M, Ghaedi K, Sadeghi HM Tags: Adv Biomed Res Source Type: research

Pentraxin 3 in Cardiovascular Disease
Giuseppe Ristagno1*, Francesca Fumagalli1, Barbara Bottazzi2, Alberto Mantovani2,3,4, Davide Olivari1, Deborah Novelli1 and Roberto Latini1 1Department of Cardiovascular Research, Mario Negri Institute for Pharmacological Research IRCCS, Milan, Italy 2Humanitas Clinical and Research Center-IRCCS, Milan, Italy 3Humanitas University, Milan, Italy 4The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom The long pentraxin PTX3 is a member of the pentraxin family produced locally by stromal and myeloid cells in response to proinflammatory signals and microbial moieties. The p...
Source: Frontiers in Immunology - April 16, 2019 Category: Allergy & Immunology Source Type: research

Challenge to the Intestinal Mucosa During Sepsis
Conclusion The impact of sepsis on the gut is manifold, e.g., sepsis mediated alteration of the gut-blood barrier and increase in the intestinal permeability, which may correlate with the phenomena of bacterial translocation and lymphatic activation (“toxic-lymph”). Systemic consequences of sepsis are widespread and concern to the coagulative system, the microbiome as well as enzymes, such as pancreatic proteases, MMPs and IAPs. Nevertheless, the therapeutic approaches for modulating the mucosal immune system are still rarely effective in daily routine. Recent published studies showing that treatment with ...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

Introduction to Purinergic Signaling.
Abstract Purinergic signaling was proposed in 1972, after it was demonstrated that adenosine 5'-triphosphate (ATP) was a transmitter in nonadrenergic, noncholinergic inhibitory nerves supplying the guinea-pig taenia coli. Later, ATP was identified as an excitatory cotransmitter in sympathetic and parasympathetic nerves, and it is now apparent that ATP acts as a cotransmitter in most, if not all, nerves in both the peripheral nervous system and central nervous system (CNS). ATP acts as a short-term signaling molecule in neurotransmission, neuromodulation, and neurosecretion. It also has potent, long-term (trophic) ...
Source: Mol Biol Cell - October 27, 2019 Category: Molecular Biology Authors: Burnstock G Tags: Methods Mol Biol Source Type: research

Lipopolysaccharide-induced sepsis-like state compromises post-ischemic neurological recovery, brain tissue survival and remodeling via mechanisms involving microvascular thrombosis and brain T cell infiltration.
Abstract Sepsis predisposes for poor stroke outcome. This association suggests that sepsis disturbs post-ischemic tissue survival and brain remodeling. To elucidate this link, we herein exposed mice to 30 min intraluminal middle cerebral artery occlusion (MCAO) and induced a sepsis-like state at 72 hours post-ischemia by intraperitoneal delivery of Escherichia coli lipopolysaccharide (LPS; three doses of 0.1 or 1 mg/kg, separated by 6 hours), a major component of the bacterium's outer membrane. Neurological recovery, ischemic injury, brain remodeling and immune responses were evaluated over up to 56 days post-seps...
Source: Brain, Behavior, and Immunity - October 22, 2020 Category: Neurology Authors: Sardari M, Skuljec J, Yin D, Zec K, de Carvalho TS, Albers D, Wang C, Pul R, Popa-Wagner A, Doeppner TR, Kleinschnitz C, Dzyubenko E, Hermann DM Tags: Brain Behav Immun Source Type: research

Therapeutic Use and Chronic Abuse of CNS Stimulants and Anabolic Drugs
Curr Issues Mol Biol. 2022 Oct 15;44(10):4902-4920. doi: 10.3390/cimb44100333.ABSTRACTThe available evidence suggests that affective disorders, such as depression and anxiety, increase risk for accelerated cognitive decline and late-life dementia in aging individuals. Behavioral neuropsychology studies also showed that cognitive decline is a central feature of aging impacting the quality of life. Motor deficits are common after traumatic brain injuries and stroke, affect subjective well-being, and are linked with reduced quality of life. Currently, restorative therapies that target the brain directly to restore cognitive a...
Source: Current Issues in Molecular Biology - October 26, 2022 Category: Molecular Biology Authors: Daniela Coli ță Cezar-Ivan Coli ță Dirk M Hermann Eugen Coli ță Thorsten R Doeppner Ion Udristoiu Aurel Popa-Wagner Source Type: research

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