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1.
Tree Physiol ; 44(7)2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38857382

RESUMEN

Nonstructural carbohydrate reserves of stems and roots underpin overall tree fitness and productivity under short-rotation management practices such as coppicing for bioenergy. While sucrose and starch comprise the predominant stem carbohydrate reserves of Populus, utilization for fitness and agricultural productivity is understood primarily in terms of starch turnover. The tonoplast sucrose transport protein SUT4 modulates sucrose export from source leaves to distant sinks during photoautotrophic growth, but the possibility of its involvement in remobilizing carbohydrates from storage organs during heterotrophic growth has not been explored. Here, we used PtaSUT4-knockout mutants of Populus tremula × P. alba (INRA 717-1B4) in winter (cool) and summer (warm) glasshouse coppicing experiments to assess SUT4 involvement in reserve utilization. Conditions preceding and supporting summer sprouting were considered favorable for growth, while those preceding and supporting cool temperature sprouting were suboptimal akin to conditions associated with coppicing as generally practiced. Epicormic bud emergence was delayed in sut4 mutants following lower temperature 'winter' but not summer coppicing. Winter xylem hexose increases were observed in control but not in sut4 stumps after coppicing. The magnitude of starch and sucrose reserve depletion was similar in control and sut4 stumps during the winter and did not explain the sprouting and xylem hexose differences. However, winter maintenance costs appeared higher in sut4 based partly on Krebs cycle intermediate levels. In control plants, bark accrual of abundant defense metabolites, including salicinoids and condensed tannins, was higher in summer than in winter, but this increase of summer defense allocations was attenuated in sut4 mutants. Temperature-sensitive trade-offs between growth and other priorities may therefore depend on SUT4 in Populus.


Asunto(s)
Metabolismo de los Hidratos de Carbono , Proteínas de Plantas , Populus , Estaciones del Año , Sacarosa , Populus/metabolismo , Populus/crecimiento & desarrollo , Populus/genética , Sacarosa/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Almidón/metabolismo , Transporte Biológico , Tallos de la Planta/metabolismo , Tallos de la Planta/crecimiento & desarrollo
2.
JACC Asia ; 3(5): 689-706, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38095005

RESUMEN

Coronary physiologic assessment is performed to measure coronary pressure, flow, and resistance or their surrogates to enable the selection of appropriate management strategy and its optimization for patients with coronary artery disease. The value of physiologic assessment is supported by a large body of evidence that has led to major recommendations in clinical practice guidelines. This expert consensus document aims to convey practical and balanced recommendations and future perspectives for coronary physiologic assessment for physicians and patients in the Asia-Pacific region based on updated information in the field that including both wire- and image-based physiologic assessment. This is Part 1 of the whole consensus document, which describes the general concept of coronary physiology, as well as practical information on the clinical application of physiologic indices and novel image-based physiologic assessment.

3.
JACC Asia ; 3(6): 825-842, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38155788

RESUMEN

Coronary physiologic assessment is performed to measure coronary pressure, flow, and resistance or their surrogates to enable the selection of appropriate management strategy and its optimization for patients with coronary artery disease. The value of physiologic assessment is supported by a large body of clinical data that has led to major recommendations in all practice guidelines. This expert consensus document aims to convey practical and balanced recommendations and future perspectives for coronary physiologic assessment for physicians and patients in the Asia-Pacific region, based on updated information in the field that includes both wire- and image-based physiologic assessment. This is Part 2 of the whole consensus document, which provides theoretical and practical information on physiologic indexes for specific clinical conditions and patient statuses.

4.
Plant J ; 116(4): 1003-1017, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37675609

RESUMEN

Populus species play a foundational role in diverse ecosystems and are important renewable feedstocks for bioenergy and bioproducts. Hybrid aspen Populus tremula × P. alba INRA 717-1B4 is a widely used transformation model in tree functional genomics and biotechnology research. As an outcrossing interspecific hybrid, its genome is riddled with sequence polymorphisms which present a challenge for sequence-sensitive analyses. Here we report a telomere-to-telomere genome for this hybrid aspen with two chromosome-scale, haplotype-resolved assemblies. We performed a comprehensive analysis of the repetitive landscape and identified both tandem repeat array-based and array-less centromeres. Unexpectedly, the most abundant satellite repeats in both haplotypes lie outside of the centromeres, consist of a 147 bp monomer PtaM147, frequently span >1 megabases, and form heterochromatic knobs. PtaM147 repeats are detected exclusively in aspens (section Populus) but PtaM147-like sequences occur in LTR-retrotransposons of closely related species, suggesting their origin from the retrotransposons. The genomic resource generated for this transformation model genotype has greatly improved the design and analysis of genome editing experiments that are highly sensitive to sequence polymorphisms. The work should motivate future hypothesis-driven research to probe into the function of the abundant and aspen-specific PtaM147 satellite DNA.


Asunto(s)
ADN Satélite , Populus , ADN Satélite/genética , Haplotipos/genética , Populus/genética , Ecosistema , Retroelementos , Centrómero/genética
5.
New Phytol ; 239(6): 2248-2264, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37488708

RESUMEN

Plant establishment requires the formation and development of an extensive root system with architecture modulated by complex genetic networks. Here, we report the identification of the PtrXB38 gene as an expression quantitative trait loci (eQTL) hotspot, mapped using 390 leaf and 444 xylem Populus trichocarpa transcriptomes. Among predicted targets of this trans-eQTL were genes involved in plant hormone responses and root development. Overexpression of PtrXB38 in Populus led to significant increases in callusing and formation of both stem-born roots and base-born adventitious roots. Omics studies revealed that genes and proteins controlling auxin transport and signaling were involved in PtrXB38-mediated adventitious root formation. Protein-protein interaction assays indicated that PtrXB38 interacts with components of endosomal sorting complexes required for transport machinery, implying that PtrXB38-regulated root development may be mediated by regulating endocytosis pathway. Taken together, this work identified a crucial root development regulator and sheds light on the discovery of other plant developmental regulators through combining eQTL mapping and omics approaches.


Asunto(s)
Populus , Sitios de Carácter Cuantitativo , Sitios de Carácter Cuantitativo/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raíces de Plantas/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Ácidos Indolacéticos/metabolismo
6.
J Interv Cardiol ; 2023: 2434516, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36873570

RESUMEN

Objectives: We aimed to assess the effectiveness of the sheathless Eaucath guiding catheter (SEGC) in overcoming severe spasm. Background: Radial spasm is a frequent challenge in transradial access (TRA) and can be difficult to manage. Methods: We performed a prospective observational study of 1000 consecutive patients undergoing coronary angiography with or without percutaneous coronary intervention. Patients with primary transfemoral access (TFA) or primary use of a sheathless guide catheter were excluded. Patients who developed angiographically confirmed severe spasm were treated with further sedation and vasodilators. If the conventional catheter would still not advance, it was exchanged for a SEGC. The primary endpoint was the successful passage of the SEGC through the radial with successful engagement of the coronary artery in patients with resistant severe spasm. Results: Primary TFA access was used in 58 (5.8%) and primary radial access with a SEGC in 44 (4.4%) patients. Of the remaining 898 patients, 888 (98.9%) had a radial sheath successfully inserted. Of these, 49 (5.5%) developed severe radial spasm with inability to advance the catheter. Following treatment with additional sedation and vasodilators, the severe spasm resolved in 5 (10.2%) patients. Passage of a SEGC was attempted in the remaining 44 patients with resistant severe spasm. Passage of the SEGC and engagement of coronary arteries were successful in all cases. There were no complications related to use of the SEGC. Conclusions: Our findings suggest that use of the SEGC for resistant severe spasm is highly effective, safe, and may reduce the need for conversion to TFA.


Asunto(s)
Catéteres , Intervención Coronaria Percutánea , Humanos , Angiografía Coronaria , Vasos Coronarios , Vasodilatadores
7.
J Invasive Cardiol ; 34(11): E763-E775, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36227013

RESUMEN

OBJECTIVES: Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) can improve patient symptoms, but it remains controversial whether it impacts subsequent clinical outcomes. METHODS: In this systematic review and meta-analysis, we queried PubMed, ScienceDirect, Cochrane Library, Web of Science, and Embase databases (last search: September 15, 2021). We investigated the impact of CTO-PCI on clinical events including all-cause mortality, cardiovascular death, myocardial infarction (MI), major adverse cardiovascular event (MACE), stroke, subsequent coronary artery bypass surgery, target-vessel revascularization, and heart failure hospitalizations. Pooled analysis was performed using a random-effects model. RESULTS: A total of 58 publications with 54,540 patients were included in this analysis, of which 33 were observational studies of successful vs failed CTO-PCI, 19 were observational studies of CTO-PCI vs no CTO-PCI, and 6 were randomized controlled trials (RCTs). In observational studies, but not RCTs, CTO-PCI was associated with better clinical outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) for all-cause mortality, MACE, and MI were 0.52 (95% CI, 0.42-0.64), 0.46 (95% CI, 0.37-0.58), 0.66 (95% CI, 0.50-0.86), respectively for successful vs failed CTO-PCI studies; 0.38 (95% CI, 0.31-0.45), 0.57 (95% CI, 0.42-0.78), 0.65 (95% CI, 0.42-0.99), respectively, for observational studies of CTO-PCI vs no CTO-PCI; 0.72 (95% CI, 0.39-1.32), 0.69 (95% CI, 0.38-1.25), and 1.04 (95% CI, 0.46-2.37), respectively for RCTs. CONCLUSIONS: CTO-PCI is associated with better subsequent clinical outcomes in observational studies but not in RCTs. Appropriately powered RCTs are needed to conclusively determine the impact of CTO-PCI on clinical outcomes.


Asunto(s)
Oclusión Coronaria , Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Oclusión Coronaria/cirugía , Resultado del Tratamiento , Intervención Coronaria Percutánea/efectos adversos , Infarto del Miocardio/etiología , Oportunidad Relativa , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Observacionales como Asunto
8.
Heart Vessels ; 37(12): 2029-2038, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35896723

RESUMEN

The clinical utility of combining extracellular matrix (ECM) biomarkers to predict the development of impaired systolic function following acute myocardial infarction (AMI) remains largely undetermined. A combination of ELISA and multiplexing assays were performed to measure matrix metalloproteinase (MMP)-2, MMP-3, MMP-8, MMP-9, periostin, N-terminal type I procollagen (PINP) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in plasma samples from 120 AMI patients. All patients had an echocardiogram within 1 year of AMI, and were divided into impaired (n = 37, LVEF < 50%) and preserved (n = 83, LVEF ≥ 50%) systolic function groups. Exploratory factor analysis was performed on log-transformed biomarkers using principle axis analysis with Oblimin rotation. Cluster analysis was performed on log-transformed and normalised biomarkers using Ward's method of minimum variance and the squared Euclidean distance metric. Upon univariate analysis, current smoking, prescription of ACE inhibitors at discharge, peak hsTnT > 610 ng/L (median), MMP-8 levels, Factor 1 scores and Cluster One assignment were predictive of impaired systolic function. Upon multivariate analysis, Cluster One assignment (odds ratio [95% CI], 2.74 [1.04-7.23], p = 0.04) remained an independent predictor of systolic dysfunction in combination with clinical variables. These observations support the usefulness of combining ECM biomarkers using cluster analysis for predicting the development of impaired systolic function in AMI patients.


Asunto(s)
Metaloproteinasa 9 de la Matriz , Infarto del Miocardio , Humanos , Inhibidor Tisular de Metaloproteinasa-1 , Metaloproteinasa 8 de la Matriz , Metaloproteinasa 3 de la Matriz , Metaloproteinasa 1 de la Matriz , Biomarcadores , Matriz Extracelular , Análisis por Conglomerados , Inhibidores de la Enzima Convertidora de Angiotensina
9.
Plant Cell Physiol ; 63(8): 1117-1129, 2022 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-35727111

RESUMEN

Leaf osmotic adjustment by the active accrual of compatible organic solutes (e.g. sucrose) contributes to drought tolerance throughout the plant kingdom. In Populus tremula x alba, PtaSUT4 encodes a tonoplast sucrose-proton symporter, whose downregulation by chronic mild drought or transgenic manipulation is known to increase leaf sucrose and turgor. While this may constitute a single drought tolerance mechanism, we now report that other adjustments which can occur during a worsening water deficit are damped when PtaSUT4 is constitutively downregulated. Specifically, we report that starch use and leaf relative water content (RWC) dynamics were compromised when plants with constitutively downregulated PtaSUT4 were subjected to a water deficit. Leaf RWC decreased more in wild-type and vector control lines than in transgenic PtaSUT4-RNAi (RNA-interference) or CRISPR (clustered regularly interspersed short palindromic repeats) knockout (KO) lines. The control line RWC decrease was accompanied by increased PtaSUT4 transcript levels and a mobilization of sucrose from the mesophyll-enriched leaf lamina into the midvein. The findings suggest that changes in SUT4 expression can increase turgor or decrease RWC as different tolerance mechanisms to reduced water availability. Evidence is presented that PtaSUT4-mediated sucrose partitioning between the vacuole and the cytosol is important not only for overall sucrose abundance and turgor, but also for reactive oxygen species (ROS) and antioxidant dynamics. Interestingly, the reduced capacity for accelerated starch breakdown under worsening water-deficit conditions was correlated with reduced ROS in the RNAi and KO lines. A role for PtaSUT4 in the orchestration of ROS, antioxidant, starch utilization and RWC dynamics during water stress and its importance in trees especially, with their high hydraulic resistances, is considered.


Asunto(s)
Populus , Antioxidantes/metabolismo , Sequías , Hojas de la Planta/metabolismo , Populus/genética , Populus/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Almidón/metabolismo , Sacarosa/metabolismo , Vacuolas/metabolismo
10.
N Z Med J ; 135(1555): 24-31, 2022 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-35728232

RESUMEN

AIM: Previous research in New Zealand has demonstrated high rates of statin prescription in patients with acute coronary syndromes (ACS), but how widely a treat to target approach is adopted is unclear. METHODS: We retrospectively examined cholesterol management in 100 consecutive patients admitted with confirmed ACS. The primary end point was reaching low-density lipoprotein-cholesterol (LDL-C) target of <1.8 mmol/L within six months. Following this a change in practice was implemented, documenting patients' current LDL-C and the LDL-C target of <1.8mmol/L in the discharge summary. A prompt to arrange a follow-up lipid test was also added to the discharge process. A second cohort of 100 patients with confirmed ACS was prospectively examined and the same endpoints reassessed. RESULTS: Lipid testing increased post intervention, both in-hospital (70% vs 98%, P<0.001) and during outpatient follow-up (60% vs 82%, P=0.01). In the intervention group, the primary outcome was achieved in more frequently (47% vs. 64% P=0.02) and follow-up LDL-C was lower (2.01.1 mmol/L vs 1.730.77 mmol/L, P=0.002). Non-statin cholesterol medication was rarely used. CONCLUSION: At baseline a treat to target approach was infrequent. Stating a target in discharge documentation was associated with significant improvements in lipid testing and patients achieving LDL-C targets.


Asunto(s)
Síndrome Coronario Agudo , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Síndrome Coronario Agudo/terapia , Colesterol/uso terapéutico , LDL-Colesterol , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Nueva Zelanda , Estudios Retrospectivos , Resultado del Tratamiento
11.
Plant Physiol ; 189(2): 516-526, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-35298644

RESUMEN

As the focus for CRISPR/Cas-edited plants moves from proof-of-concept to real-world applications, precise gene manipulation will increasingly require concurrent multiplex editing for polygenic traits. A common approach for editing across multiple sites is to design one guide RNA (gRNA) per target; however, this complicates construct assembly and increases the possibility of off-target mutations. In this study, we utilized one gRNA to target MYB186, a known positive trichome regulator, as well as its paralogs MYB138 and MYB38 at a consensus site for mutagenesis in hybrid poplar (Populus tremula × P. alba INRA 717-1B4). Unexpected duplications of MYB186 and MYB138 resulted in eight alleles for the three targeted genes in the hybrid poplar. Deep sequencing and polymerase chain reaction analyses confirmed editing across all eight targets in nearly all of the resultant glabrous mutants, ranging from small indels to large genomic dropouts, with no off-target activity detected at four potential sites. This highlights the effectiveness of a single gRNA targeting conserved exonic regions for multiplex editing. Additionally, cuticular wax and whole-leaf analyses showed a complete absence of triterpenes in the trichomeless mutants, hinting at a previously undescribed role for the nonglandular trichomes of poplar.


Asunto(s)
Populus , ARN Guía de Kinetoplastida , Sistemas CRISPR-Cas/genética , Edición Génica/métodos , Populus/genética , ARN Guía de Kinetoplastida/genética , Tricomas
12.
J Interv Cardiol ; 2022: 5668728, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35281588

RESUMEN

Background: Use of sheathless guiding catheters for transradial PCI has the potential to reduce radial trauma and allow use of larger catheters to facilitate complex PCI. The new sheathless Hyperion guide catheter (SHGC) system allows direct insertion of the SHGC using a 20G needle or IV cannula, a 0.025″ Silverway wire, and a dilator. We report the first clinical experience. Methods: We prospectively evaluated outcomes in consecutive patients undergoing PCI using radial access and the SHGC catheter at our institution between June 2020 and June 2021. There were no exclusion criteria. Results: The study included 120 patients, mean age 67 ± 12.6 years, 79.2% male. Insertion of a SHGC was attempted in 128 radial arteries and was successful in all cases. The SHGC was inserted directly in 74 (57.8%), following initial sheath removal in 24 (20.5%) and through the initial sheath in 30 (26.2%). Coronary artery engagement with a SHGC was successful in 126 (98.4%). A total of 150 lesions were treated, the majority being complex: 16.1% chronic total occlusions, 37.1% calcified, 30.6% bifurcation, and 43.5% long lesions. Angiographic success was achieved in 149 (99.2%) lesions. Periprocedural myocardial infarction occurred in 5 (4.2%) patients. There was no in-hospital urgent revascularisation or death and no major bleeding or vascular complications. Occlusion occurred in 2 (1.6%) radial arteries. Conclusion: This first clinical experience with the SHGC demonstrates that direct insertion is safe and effective and that the use of the SHGC allows complex interventions to be undertaken transradially with a high success rate.


Asunto(s)
Infarto del Miocardio , Intervención Coronaria Percutánea , Anciano , Catéteres , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arteria Radial , Resultado del Tratamiento
13.
Biomark Med ; 16(3): 147-161, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35107387

RESUMEN

Aim: This study investigated an optimal extracellular matrix (ECM) biomarker panel for measurement in acute myocardial infarction (AMI). Materials & methods: Blood samples were collected from 12 healthy volunteers, and from 23 patients during hospital admission (day 1-3) and 6 months following AMI. Protein assays measured: FGFb, MMP-2, -3, -8, -9, osteopontin, periostin, PINP, TGF-ß1, TIMP-1, -4 and VEGF. Results: When compared with healthy levels, seven ECM biomarkers were significantly altered in AMI patients, and six of these biomarkers displayed stable expression during hospital admission. Clinical characteristics and baseline cardiac function were not well correlated with ECM biomarkers. Conclusion: We suggest, MMP-2, MMP-3, MMP-8, MMP-9, periostin, PINP and TIMP-1 may be useful ECM biomarkers for future studies in AMI patients.


Plain language summary The cardiac extracellular matrix (ECM) maintains the structural integrity of the heart, and can be measured in human circulation using ECM biomarkers. Understanding the levels of variation and temporal dynamics that exist in ECM biomarkers following a heart attack is important for establishing an optimal biomarker panel that may be useful in heart research. A single blood sample was collected from 12 healthy volunteers. Multiple bloods samples were collected from 23 heart attack patients during hospital admission (day 1­3) and 6 months post heart attack. About 12 ECM biomarkers were measured from these blood samples. When compared with healthy levels, seven ECM biomarkers were significantly altered in heart attack patients, and six of these biomarkers displayed stable expression during hospital admission. Variability existed within biomarker levels and this was not well described by traditional heart attack risk factors, such as age or heart attack size. Thus, the source of biomarker variability remains unknown in this study. Overall, we suggest these seven ECM biomarkers may be of interest for future studies in the setting of heart attack research.


Asunto(s)
Matriz Extracelular , Infarto del Miocardio , Biomarcadores , Matriz Extracelular/metabolismo , Humanos , Infarto del Miocardio/metabolismo
14.
Catheter Cardiovasc Interv ; 99(3): 699-705, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34132465

RESUMEN

OBJECTIVES: To describe a novel technique for ostial stent placement using real-time IVUS guidance. BACKGROUND: Accurate placement of coronary stents at ostial locations is challenging with the true ostium frequently being missed increasing the risk of adverse events. We have developed a novel technique for ostial stent placement and report our benchtop testing and initial clinical experience. METHODS: Benchtop testing was performed to validate the appearance of the stent and delivery system on IVUS. Benchtop testing of real-time IVUS guided ostial stent positioning was carried out in a left main bifurcation phantom. Real-time IVUS guidance of stent placement in aorto-ostial, ostial left anterior descending (LAD), or ostial circumflex lesions was assessed in a prospective registry. RESULTS: Bench model IVUS demonstrated clear differences between the appearances of the stent and other components of the delivery system. Positioning of 10 consecutive stents into the ostial LAD using real-time IVUS guidance was assessed in a left main bifurcation model. Median distance from proximal stent edge to LAD ostium was 0.39 mm (interquartile range 0.31 to 0.73). Real-time IVUS guidance of ostial stent placement was performed in 50 patients (51 lesions). Angiographic success was 100%. IVUS post-stenting demonstrated median distance from the proximal stent edge to the ostium was 0.2 mm (interquartile range 0.1 to 0.5 mm). There was one periprocedural myocardial infarction but no other major adverse cardiac events at 30-days. CONCLUSIONS: We have developed a novel technique using real-time IVUS guidance allowing accurate ostial stent placement.


Asunto(s)
Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Humanos , Stents , Resultado del Tratamiento , Ultrasonografía Intervencional/métodos
15.
JACC Case Rep ; 3(16): 1753-1755, 2021 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-34825203
16.
Sci Rep ; 11(1): 12705, 2021 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-34135421

RESUMEN

Extracellular matrix (ECM) biomarkers are useful for measuring underlying molecular activity associated with cardiac repair following acute myocardial infarction (AMI). The aim of this study was to conduct exploratory factor analysis (EFA) to examine the interrelationships between ECM biomarkers, and cluster analysis to identify if distinct ECM profiles could distinguish patient risk in AMI. Ten ECM biomarkers were measured from plasma in 140 AMI patients: MMP-2, -3, -8, -9, periostin, procollagen I N-Terminal propeptide, osteopontin, TGF-ß1, TIMP-1 and -4. EFA grouped eight ECM biomarkers into a two-factor solution, which comprised three biomarkers in Factor 1 and five biomarkers in Factor 2. Notably, ECM biomarkers were not separated based on biological function. Cluster analysis grouped AMI patients into three distinct clusters. Cluster One (n = 54) had increased levels of MMP-8, MMP-9, and TGF-B1. Cluster Two (n = 43) had elevated levels of MMP-2, MMP-3, osteopontin, periostin and TIMP-1, and increased high-sensitivity troponin T and GRACE scores. Cluster Three (n = 43) had decreased levels of ECM biomarkers. Circulating ECM biomarkers demonstrated collinearity and entwined biological functions based on EFA analysis. Using cluster analysis, patients with similar clinical presentations could be separated into distinct ECM profiles that were associated with differential patient risk. Clinical significance remains to be determined.


Asunto(s)
Matriz Extracelular/metabolismo , Infarto del Miocardio/sangre , Biomarcadores/sangre , Moléculas de Adhesión Celular/sangre , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Masculino , Metaloproteinasas de la Matriz/sangre , Persona de Mediana Edad , Infarto del Miocardio/metabolismo , Osteopontina/sangre , Fragmentos de Péptidos/sangre , Procolágeno/sangre , Inhibidores Tisulares de Metaloproteinasas/sangre , Factor de Crecimiento Transformador beta1/sangre
17.
Thromb Haemost ; 121(12): 1637-1649, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33984869

RESUMEN

BACKGROUND: Activation of both platelets and neutrophils can contribute to the risk of major adverse cardiovascular events (MACE) following acute myocardial infarction (AMI). Neutrophil extracellular traps (NETs) are an important product of the platelet-neutrophil axis and exaggerate vascular damage in cardiovascular disease. Additionally, activated platelets can drive NETosis and are directly linked to thromboembolic risk. Investigating the combined effect of biomarkers for NETosis and platelet activation represents a novel approach to risk prediction post-AMI. Here, we examined the utility of a composite biomarker score, inclusive of both pathways, for predicting MACE post-AMI. METHODS AND RESULTS: In a case-control design, 100 case patients who experienced MACE within 1 year of index admission were matched in a 1:2 ratio with control patients. Serum levels of myeloperoxidase-DNA, neutrophil elastase-DNA, and citrullinated histone H3 were assayed by enzyme-linked immunosorbent assay (ELISA) as markers of NET burden. To measure platelet activation, soluble P-selectin was assayed by ELISA in parallel. Platelet and neutrophil counts were also recorded. Composite biomarker scores, inclusive of biomarkers for NETosis and platelet activation, were assessed using multivariate regression modeling. These composite biomarker scores were independent predictors of 1-year MACE. The strongest association with MACE was observed using a composite of platelet count, soluble P-selectin, and all NET markers (odds ratio: 1.94; 1.16-3.25). CONCLUSION: Here, we demonstrate the importance of combining biomarkers of NETosis and platelet activation for risk prediction in patients with AMI. Combining biomarkers from closely linked, but distinct, biological pathways was more effective than utilizing either type of biomarker alone.


Asunto(s)
Plaquetas/metabolismo , Trampas Extracelulares/metabolismo , Infarto del Miocardio/sangre , Neutrófilos/metabolismo , Selectina-P/sangre , Activación Plaquetaria , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Recuento de Plaquetas , Valor Predictivo de las Pruebas , Pronóstico , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo
18.
Plant Physiol ; 185(4): 1443-1456, 2021 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-33793953

RESUMEN

Nonphotosynthetic holoparasites exploit flexible targeting of phylloquinone biosynthesis to facilitate plasma membrane redox signaling. Phylloquinone is a lipophilic naphthoquinone found predominantly in chloroplasts and best known for its function in photosystem I electron transport and disulfide bridge formation of photosystem II subunits. Phylloquinone has also been detected in plasma membrane (PM) preparations of heterotrophic tissues with potential transmembrane redox function, but the molecular basis for this noncanonical pathway is unknown. Here, we provide evidence of PM phylloquinone biosynthesis in a nonphotosynthetic holoparasite Phelipanche aegyptiaca. A nonphotosynthetic and nonplastidial role for phylloquinone is supported by transcription of phylloquinone biosynthetic genes during seed germination and haustorium development, by PM-localization of alternative terminal enzymes, and by detection of phylloquinone in germinated seeds. Comparative gene network analysis with photosynthetically competent parasites revealed a bias of P. aegyptiaca phylloquinone genes toward coexpression with oxidoreductases involved in PM electron transport. Genes encoding the PM phylloquinone pathway are also present in several photoautotrophic taxa of Asterids, suggesting an ancient origin of multifunctionality. Our findings suggest that nonphotosynthetic holoparasites exploit alternative targeting of phylloquinone for transmembrane redox signaling associated with parasitism.


Asunto(s)
Vías Biosintéticas , Membrana Celular/metabolismo , Orobanchaceae/metabolismo , Orobanchaceae/parasitología , Plantas/parasitología , Striga/metabolismo , Striga/parasitología , Vitamina K 1/metabolismo
19.
Plant Direct ; 4(9): e00268, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33015535

RESUMEN

The tonoplast sucrose transporter PtaSUT4 is well expressed in leaves of Populus tremula × Populus alba (INRA 717-IB4), and its inhibition by RNA-interference (RNAi) alters leaf sucrose homeostasis. Whether sucrose partitioning between the vacuole and the cytosol is modulated by PtaSUT4 for specific physiological outcomes in Populus remains unexplored. In this study, partial defoliation was used to elicit compensatory increases in photosynthesis and transpiration by the remaining leaves in greenhouse-grown poplar. Water uptake, leaf gas exchange properties, growth and nonstructural carbohydrate abundance in source and sink organs were then compared between wild-type and SUT4-RNAi lines. Partial defoliation increased maximum photosynthesis rates similarly in all lines. There was no indication that source leaf sugar levels changed differently between wild-type and RNAi plants following partial defoliation. Sink levels of hexose (glucose and fructose) and starch decreased similarly in all lines. Interestingly, plant water uptake after partial defoliation was not as well sustained in RNAi as in wild-type plants. While the compensatory increase in photosynthesis was similar between genotypes, leaf transpiration increased less robustly in RNAi than wild-type plants. SUT4-RNAi and wild-type source leaves differed constitutively in their bulk modulus of elasticity, a measure of leaf turgor, and storage water capacitance. The data demonstrate that reduced sucrose partitioning due to PtaSUT4-RNAi altered turgor control and compensatory transpiration capacity more strikingly than photosynthesis and sugar export. The results are consistent with the interpretation that SUT4 may control vacuolar turgor independently of sink carbon provisioning.

20.
Heliyon ; 6(4): e03704, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32280800

RESUMEN

BACKGROUND: Inflammatory cytokines are involved in the pathophysiology of acute coronary syndromes (ACS) and have been associated with major adverse cardiovascular events (MACE). We systematically reviewed studies investigating the ability of multiple cytokines to predict MACE in ACS patients with follow-up of at least one year. METHODS: A Medical Subject Heading search criteria was applied on Ovid Medline(R), EMBASE, EMBASE Classic and Cochrane Library to systematically identify relevant studies published between 1945 and 2017 that had an observational study design or were randomised controlled trials. Studies were excluded if only one cytokine was analysed, follow-up period was less than one year, subjects were non-human, or blood samples were taken more than 10 days from symptom onset. RESULTS: Ten observational studies met the inclusion criteria. Six had acceptable internal validity when evaluated for quality. The studies were varied in terms of study methods (time of blood collection, study population, cytokines assessed, MACE definition, follow-up length) and result reporting, so a meta-analysis could not be conducted. Six of the studies found significant associations between individual cytokines and MACE. Four studies measured the combined effects of multiple cytokines to predict MACE, and all had statistically significant results. CONCLUSION: A combination of multiple cytokines had a better association with MACE than individual cytokines. It appears promising for future studies to determine the optimal multi-marker methodology and confirm its predictive value.

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