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Heparin resistance in severe thermal injury:a prospective cohort study

Burns & Trauma 2021年第1期9卷 157-169页

作者： Liam D Cato Benjamin Bailiff Joshua Price Christos Ermogeneous Jon Hazeldine William Lester Gillian Lowe Christopher Wearn jonathan rb bishop Janet M Lord Naiem Moiemen Paul Harrison Scar Free Foundation Birmingham Centre for Burns Research University Hospitals Birmingham Foundation TrustQueen Elizabeth Hospital BirminghamMindelsohn WayBirminghamB152WBUK Department of Haematology University Hospitals Birmingham Foundation TrustMindelsohnWayBirminghamB152WBUK Institute of Inflammation and Ageing University of BirminghamBirminghamB152TTUK NIHR Surgical Reconstruction and Microbiology Research Centre University Hospitals Birmingham Foundation TrustMindelsohn WayBirminghamB152WBUK

Background:Low molecular-weight heparin(LMWH)is routinely administered to burn patients for *** studies have reported heparin resistance,yet the mechanism(s)and prevalence have not been systematically *** hypothesized that nucleosomes,composed of histone structures with associated DNA released from injured tissue and activated immune cells in the form of neutrophil extracellular traps(NETs or NETosis),neutralize LMWH resulting in suboptimal anticoagulation,assessed by reduction in anti-factor Xa ***:Blood was sampled from>15%total body surface area(TBSA)burn patients receiving LMWH on days 5,10 and *** anti-factor Xa(AFXa)activity,anti-thrombin(ATIII)activity,cellfree DNA(cfDNA)levels and nucleosome levels were *** effects regression was adjusted for multiple confounders,including injury severity and ATIII activity,and was used to test the association between nucleosomes and ***:A total of 30 patients with severe burns were *** TBSA 43%(SD 17).Twentythree(77%)patients were affected by heparin resistance(defined by AFXa activity<0.2 IU/mL).Mean peak AFXa activity across samples was 0.18 IU/mL(SD 0.11).Mean ATIII was 81.9%activity(SD 20.4).Samples taken at higher LWMH doses were found to have significantly increased AFXa activity,though the effect was not observed at all doses,at 8000 IU no samples were heparin *** levels were negatively correlated with AFXa(r=−0.29,p=0.050)consistent with the *** final model,with peak AFXa as the response variable,was adjusted for nucleosome levels(p=0.0453),ATIII activity(p=0.0053),LMWH dose pre-sample(p=0.0049),drug given(enoxaparin or tinzaparin)(p=0.03),and other confounders including severity of injury,age,gender,time point of ***:Heparin resistance is a prevalent issue in severe *** levels were increased post-burn,and showed an inverse association with AFXa consistent with the hypothesis that they ma

关键词： Burn Heparin resistance Low molecular-weight heparin Nucleosomes Neutrophil extracellular traps Factor-Xa Thrombosis Enoxaparin NETosis

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Impact of a single bout of high-intensity interval exercise and short-term interval training on interleukin-6, FNDC5, and METRNL mRNA expression in human skeletal muscle

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Journal of Sport and Health Science 2018年第2期7卷 191-196页

作者： Malcolm Eaton Cesare Granata Julianne Barry Adeel Safdar David bishop jonathan P.Little School of Health and Exercise Science University of British Columbia Okanagan Institute of Sport Exercise and Active Living (ISEAL)College of Sport and Exercise ScienceVictoria University Department of Pediatrics Mc Master University

Background: Exercise promotes numerous phenotypic adaptations in skeletal muscle that contribute to improved function and metabolic capacity. An emerging body of evidence suggests that skeletal muscle also releases a myriad of factors during exercise, termed "myokines". The purpose of this study was to examine the effects of high-intensity interval training(HIIT) on the acute regulation of the mRNA expression of several myokines, including the prototypical myokine interleukin-6(IL-6), and recently identified myokines fibronectin type III domain-containing protein 5(FNDC5)(irisin) and meteorin-like protein(METRNL).Methods: Both before and after a 20-day period of twice-daily high-volume HIIT, 9 healthy males(20.5 ± 1.5 years performed a standardized bout of high-intensity interval exercise(HIIE; 5 × 4 min at ~80% pretraining peak power output) with skeletal muscle biopsy samples(vastus lateralis) obtained at rest, immediately following exercise, and at 3 h ***: Before training, a single bout of HIIE increased IL-6(p < 0.05) and METRNL(p < 0.05) mRNA expression measured at 3 h recovery when compared to rest. Following 20 days of HIIT, IL-6 and FNDC5 mRNA were increased at 3 h recovery from the standardized HIIE bout when compared to rest(both p < 0.05). Resting METRNL and FNDC5 mRNA expression were higher following training(p < 0.05), and there was an overall increase in FNDC5 mRNA post-training(main effect of training, p < 0.05).Conclusion: In human skeletal muscle(1) an acute bout of HIIE can induce upregulation of skeletal muscle IL-6 mRNA both before and after a period of intensified HIIT;(2) Resting and overall FNDC5 mRNA expression is increased by 20 days of HIIT; and(3) METRNL mRNA expression is responsive to both acute HIIE and short-term intense HIIT. Future studies are needed to confirm these findings at the protein and secretion level in humans.

关键词： Brown adipose tissue Exerkines High-intensity interval training Intermittent exercise Myokine Obesity

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Traumatic injury is associated with reduced deoxyribonuclease activity and dysregulation of the actin scavenging system

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Burns & Trauma 2021年第1期9卷 558-572页

作者： Jon Hazeldine Robert J.Dinsdale David N.Naumann Animesh Acharjee jonathan R.B.bishop Janet M.Lord Paul Harrison Institute of Inflammation and Ageing University of BirminghamEdgbastonBirminghamWest MidlandsB152TTUnited Kingdom National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre Heritage BuildingQueen Elizabeth Hospital BirminghamMindelsohnWayEdgbastonBirminghamWest MidlandsB152THUnited Kingdom Scar Free Foundation Birmingham Centre for Burns Research University Hospital Birmingham Foundation TrustQueen Elizabeth Hospital BirminghamMindelsohnWayEdgbastonBirminghamWest MidlandsB152THUnited Kingdom Academic Department of Military Surgery and Trauma Royal Centre for Defence MedicineQueen Elizabeth Hospital BirminghamMindelsohnWayEdgbastonBirminghamWest MidlandsB152THUnited Kingdom Institute of Cancer and Genomic Sciences Centre for Computational BiologyUniversity of BirminghamEdgbastonBirminghamWest MidlandsB152TTUnited Kingdom

Background:Traumatic injury is associated with increased concentrations of cell-free DNA(cfDNA)in the circulation,which contribute to post-injury *** endonuclease deoxyribonuclease 1(DNase-1)is responsible for removing 90%of circulating ***,DNase activity was reported to be significantly reduced following major non-traumatic brain injury(TBI),but the processes responsible were not ***,it is not known how quickly following injury DNase activity is reduced and whether this also occurs after ***:At 3 post-injury time points(≤1,4–12 and 48–72 hours),blood samples were obtained from 155 adult trauma patients that had sustained an isolated TBI(n=21),TBI with accompanying extracranial injury(TBI^(+))(n=53)or an extracranial injury only(ECI)(n=81).In addition to measuring cfDNA levels and the activity and expression of DNase,circulating concentrations of monomeric globular action(G-actin),an inhibitor of DNase-1,and the actin scavenging proteins gelsolin(GSN)and vitamin D binding protein(VDBP)were determined and values compared to a cohort of healthy ***:Significantly elevated concentrations of plasma cfDNA were seen in TBI,TBI^(+)and ECI patients at all study time points when compared to healthy *** levels were significantly higher at≤1 hour post-injury in ECI patients who subsequently developed multiple organ dysfunction syndrome when compared to those who did *** DNase-1 protein was significantly elevated in all patient groups at all sampling time *** contrast,DNase enzyme activity was significantly reduced,with this impaired function evident in TBI^(+)patients within minutes of *** concentrations of G-actin were elevated in all patient cohorts in the immediate aftermath of injury and this was accompanied by a significant reduction in the levels of GSN and ***:The post-traumatic increase in circulating cfDNA that occurs following extracranial trauma and TBI

关键词： Cell-free DNA Deoxyribonuclease Extracellular actin scavenging system Pre-hospital Trauma

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Deciphering 3D periodontal fibroblast-macrophage crosstalk in bioactive nanoparticle-guided immunomodulation for treating traumatic dental avulsion

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Bioactive Materials 2024年第11期41卷 400-412页

作者： Hadagalu Revana Siddappa Rajeshwari Emily bishop Aiman Ali Anil Kishen The Kishen Lab Dental Research InstituteUniversity of TorontoTorontoONM5G 1G6Canada Faculty of Dentistry University of TorontoTorontoONM5G 1G6Canada Oral and Maxillofacial Pathology and Oral Medicine Faculty of DentistryUniversity of Toronto124 Edward StreetTorontoOntario M5G 1G6Canada Department of Dentistry Mount Sinai Health SystemMount Sinai HospitalTorontoONM5G 1X5Canada

Prolonged extra-oral period in dental avulsion is often associated with loss of viability of Periodontal fibroblasts (PDLF) and increased risk of ankylosis. Root surface treatment with bioactive agents to reduce the risk of ankylosis can be a potential strategy. The objective of the study was to investigate the impact of an engineered chitosan nanoparticles (CSNP), photosensitizer Rose Bengal (rb) functionalized CSNP (CSrb) and sustained dexamethasone (CSDEX) releasing CSNP for application in management of delayed replantation of avulsed teeth. The 3D PDLF-macrophage (Mϕ) collagen model was developed and exposed to LPS, MCSF, RANKL with and without CSDEX/CSNP. Immunofluorescence and cytokine analysis was done at 2 and 7 days to assess cellular interactions. Maxillary right incisors in male Wistar rats were extracted, exposed to extraoral dry or LPS for 1 h and treated with or without CSDEX/CSrb for 1 min before replantation. Rats were euthanized after 21 days for micro-CT, TRAP, and immunofluorescence analysis. CSDEX/CSNP treatment in 3D model significantly reduced CD80, NFATc1, STAT6 and increased CD206 and periostin expression (p rb in animal study significantly reduced resorption, ankylosis, TRAP activity and osteocalcin expression and increased periostin (prb with periostin upregulation and sustained releasing CSDEX showed potential for hampering root resorption and ankylosis in dental avulsion.

关键词： Root resorption Chitosan nanoparticles Immunomodulation Periodontal fibroblasts Macrophages

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Probing the subcellular nanostructure of engineered human cardiomyocytes in 3D tissue

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Microsystems & Nanoengineering 2021年第1期7卷 133-140页

作者： Josh Javor Jourdan K.Ewoldt Paige E.Cloonan Anant Chopra Rebeccah J.Luu Guillaume Freychet Mikhail Zhernenkov Karl Ludwig jonathan G.Seidman Christine E.Seidman Christopher S.Chen David J.bishop Department of Mechanical Engineering Boston UniversityBostonMA 02215USA Department of Biomedical Engineering Boston UniversityBostonMA 02215USA SMI Beamline 12-ID Brookhaven National LaboratoryUptonNY 11973USA Department of Physics Boston UniversityBostonMA 02215USA Division of Materials Science Boston UniversityBostonMassachusetts 02215USA Department of Genetics Harvard Medical SchoolBostonMA 02215USA Department of Electrical Engineering Boston UniversityBostonMA 02215USA

The structural and functional maturation of human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)is essential for pharmaceutical testing,disease modeling,and ultimately therapeutic *** 3D-tissue platforms have improved the functional maturation of hiPSC-CMs,but probing cardiac contractile properties in a 3D environment remains challenging,especially at depth and in live *** small-angle X-ray scattering(SAXS)imaging,we show that hiPSC-CMs matured and examined in a 3D environment exhibit a periodic spatial arrangement of the myofilament lattice,which has not been previously detected in *** contractile force is found to correlate with both the scattering intensity(R^(2)=0.44)and lattice spacing(R^(2)=0.46).The scattering intensity also correlates with lattice spacing(R^(2)=0.81),suggestive of lower noise in our structural measurement than in the functional ***,we observed decreased myofilament ordering in tissues with a myofilament mutation known to lead to hypertrophic cardiomyopathy(HCM).Our results highlight the progress of human cardiac tissue engineering and enable unprecedented study of structural maturation in hiPSC-CMs.

关键词： cardiac cardiomyocytes spacing

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Advanced biomedical hydrogels:molecular architecture and its impact on medical applications

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Regenerative Biomaterials 2021年第6期8卷 297-317页

作者： jonathan T.Peters Marissa E.Wechsler Nicholas A.Peppas McKetta Department of Chemical Engineering The University of Texas at AustinAustin200 E.Dean KeetonAustinTX 78712USA Institute for Biomaterials Drug Deliveryand Regenerative MedicineThe University of Texas at Austin107 W.Dean KeetonAustinTX 78712USA Department of Biomedical Engineering and Chemical Engineering The University of Texas at San AntonioOne UTSA CircleSan AntonioTX78249USA Department of Biomedical Engineering The University of Texas at Austin107 W.Dean KeetonAustinTX 78712USA Division of Molecular Pharmaceutics and Drug Delivery College of PharmacyThe University of Texas at Austin107 W.Dean KeetonAustinTX 78712USA Department of Surgery and Perioperative Care and Department of PediatricsDell Medical SchoolThe University of Texas at Austin1601 Trinity St.Bldg.BAustinTX 78712USA

Hydrogels are cross-linked polymeric networks swollen in water,physiological aqueous solutions or biological *** are synthesized by a wide range of polymerization methods that allow for the introduction of linear and branched units with specific molecular *** addition,they can be tuned to exhibit desirable chemical characteristics including hydrophilicity or *** synthesized hydrogels can be anionic,cationic,or amphiphilic and can contain multifunctional crosslinks,junctions or tie *** these characteristics,hydrogels exhibit compatibility with biological systems,and can be synthesized to render systems that swell or collapse in response to external *** versatility and compatibility have led to better understanding of how the hydrogel’s molecular architecture will affect their physicochemical,mechanical and biological *** present a critical summary of the main methods to synthesize hydrogels,which define their architecture,and advanced structural characteristics for macromolecular/biological applications.

关键词： hydrogels networks mesh size hydrogel reactions biological applications biomedical applications

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Surface hydrolysis-mediated PEGylation of poly(N-isopropyl acrylamide)based nanogels

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Regenerative Biomaterials 2017年第5期4卷 281-287页

作者： jonathan T.Peters Stanley Verghese Deepak Subramanian Nicholas A.Peppas McKetta Department of Chemical Engineering The University of Texas at AustinAustinTXUSA Institute for Biomaterials Drug Deliveryand Regenerative MedicineThe University of Texas at AustinAustinTXUSA Department of Biomedical Engineering The University of Texas at AustinAustinTXUSA Department of Pediatrics and Department of Surgery and Perioperative CareDell Medical SchoolThe University of Texas at AustinAustinTXUSA Division of Pharmaceutics College of PharmacyThe University of Texas at AustinAustinTXUSA

In this work,poly(N-isopropyl acrylamide-co-acrylamide)[P(NIPAAm-co-AAm)]nanogels were modified by hydrolysis above the lower critical solution temperature(LCST)to localize carboxylic acid functional groups at the surface(surface hydrolysis).PNIPAAm copolymerized with 15%and 20%nominal AAm in the feed were prepared and compared to equivalent hydrogels with acrylic *** effect and extent of surface hydrolysis was confirmed by potentiometric titration and zeta *** surface modified nanogels were then modified with primary amine functionalized PEG *** hydrolysis-mediated PEGylation had little effect on the swelling response of the nanogels,while also preventing adsorption of model proteins in physiological relevant *** both 15%and 20%AAm gels both decreased protein adsorption,only the 20%AAm gels resulted in fully preventing protein *** results presented here point to surface hydrolysis as a new route to passivate nanogels for use in vivo.

关键词： PNIPMAAm hydrogels PEG passivation

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Photoelectrochemical CO_(2) electrolyzers: From photoelectrode fabrication to reactor configuration

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Journal of Energy Chemistry 2023年第10期85卷 455-480,I0012页

作者： Jose Antonio Abarca Guillermo Díaz-Sainz Ivan Merino-Garcia Angel Irabien jonathan Albo Departamento de Ingenierías Química y Biomolecular Universidad de CantabriaETSIITAvenida de los Castros s/n39005 SantanderSpain

The photoelectrochemical conversion of CO_(2) into value-added products emerges as an attractive approach to alleviate climate change. One of the main challenges in deploying this technology is, however, the development and optimization of(photo)electrodes and photoelectrolyzers. This review focuses on the fabrication processes, structure, and characterization of(photo)electrodes, covering a wide range of fabrication techniques, from rudimentary to automated fabrication processes. The work also highlights the most relevant features of(photo)electrodes, with special emphasis on how to measure and optimize them. Finally, the review analyses the integration of(photo)electrodes in different photoelectrolyzer architectures, analyzing the most recent research work that comprises photocathode, photoanode,photocathode-photoanode, and tandem photoelectrolyzer configurations to ideally achieve self-sustained CO_(2) conversion systems. Overall, comprehensive guidelines are provided for future advancements in developing effective devices for CO_(2) conversion, bridging the gap towards the use of sunlight as the unique energy input and practical applications.

关键词： Decarbonization CO_(2)photoelectroreduction (Photo)Electrodes Fabrication techniques Photoelectrolyzer configuration

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Geochemistry, Geochronology and Lu-Hf Isotopes of Peraluminous Granitic Porphyry from the Walegen Au Deposit, West Qinling Terrane

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Acta Geologica Sinica(English Edition) 2017年第6期91卷 2024-2040页

作者： GUO Xianqing YAN Zhen jonathan C.AITCHISON FU Changlei WANG Zongqi MLR Key Laboratory of Metallogeny and Mineral Assessment Institute of Mineral ResourcesChinese Academy of Geological Sciences Institute of Geology Chinese Academy of Geological Sciences School of Earth and Environmental Sciences (SEES) Faculty of ScienceThe University of Queensland

Walegen Au deposit is closely correlated with granitic intrusions of Triassic age, which are composed of granite and quartz porphyries. Both granite porphyry and quartz porphyry consist of quartz, feldspar and muscovite as primary minerals. WeaMy peraluminous granite porphyry （A/ CNK=1.10-1.15） is enriched in LREE, depleted in HREE with Nb-Ta-Ti anomalies, and displays subduction-related geochemistry. Quartz porphyry is strongly peraluminous （A/CNK=1.64-2.81） with highly evolved components, characterized by lower TiO2, REE contents, Mg#, K/rb, Nb/Ta, Zr/Hf ratios and higher rb/Sr ratios than the granite porphyry. REE patterns of quartz porphyry exhibit lanthanide tetrad effect, resulting from mineral fractionation or participation of fluids with enriched F and CI. LA- ICP-MS zircon U-Pb dating indicates quartz porphyry formed at 233±3 Ma. The ages of relict zircons from Triassic magmatic rocks match well with the detrital zircons from regional area. In addition, εHf（t） values of Triassic magmatic zircons from the granite and quartz porphyries are -14.2 to -9.1 （with an exception of ＋4.1） and -10.8 to -8.6 respectively, indicating a crustal-dominant source. Regionally, numerous Middle Triassic granitoids were previously reported to be formed under the consumption of Paleotethyan Ocean. These facts indicate that the granitic porphyries from Walegen Au deposit may have been formed in the processes of the closing of Paleotethyan Ocean, which could correlate with the arc-related magmatism in the Kunlun orogen to the west and the Qinling orogen to the east.

关键词： Triassic granites lanthanide tetrad effect subduction-related magmatism Walegen Au deposit West Qinling terrane

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Role of β-microseminoprotein from prostate cancer initiationto recurrence: A mini-review

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World Journal of Clinical Urology 2014年第1期3卷 20-30页

作者： Nishi Karunasinghe Karen bishop Pamela Murray Yuanye Xu Megan Goudie Lance Ng Shuotun Zhu Dug Yeo Han Lynnette R Ferguson jonathan Masters Benji Benjamin Michael Holmes Auckland Cancer Society Research Centre Faculty of Medical and Health Sciences The University of Auckland Discipline of Nutrition Faculty of Medical and Health Sciences The University of Auckland Urology Department Auckland Hospital Radiology Department Auckland Hospital Urology Department Waikato Hospital

Medline/Pubmed articles relevant to this topic were considered using the search terms ?-microseminoprotein, MSMB, prostate secretory protein of 94 amino acids and PSP94. Full articles were retrieved when the abstract was considered relevant. In addition, other data related to this topic including our own are discussed. Summary of fi ndings-?-microseminoprotein(MSMB) is increasingly being considered as a marker for prostatecancer, as reduced levels have been associated with the disease. Here we review various aspects of this protein including its biological and physiological variants, binding proteins and immune modulation; its importance as a marker for biochemical recurrence of prostate cancer; prostate cancer related splice variants and its therapeutic utility. Two of the most important properties of MSMB are related to anticancer functions and immune modulation. Predominant expression of two(short and full-length) splice variants of MSMB has been observed from normal prostate and several other tissues. In benign prostate hyperplasia the short isoform is dominant, constituting 98% of this isoform, whereas in prostate cancer 96% constitute the fulllength isoform. The MSMB promoter single nucleotide polymorphism rs10993994 with the C allele functions as an activated cyclic adenosine monophosphate response element binding protein binding site. This C variant of rs10993994 could be responsible for the production of splice variants under variable conditions. MSMB has binding motifs to a few known proteins including immunoglobulin G and several Cysteine-rich secretory proteins family proteins. MSMB bound to these proteins is considered as immune modulating. Use of MSMB as a urinary marker for detecting aggressive prostate cancers that could resist radiation and surgical treatments, seems possible, but needs further investigation. The ratio of MSMB splice variants could also be a possible approach in understanding prostate cancers, with higher ratios indicating severe di

关键词： β-microseminoprotein Anticancer properties Immune modulation Splice variants Promoter single nucleotide polymorphism rs10993994 Biochemical recurrence

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