RESUMEN
Acremonium strictum Elicitor Subtilisin (AsES) is a fungal elicitor that activates innate immunity, conferring disease resistance in strawberry (Fragaria × ananassa Duch.), Arabidopsis and other plant species. The aim of the present work was to evaluate the involvement of the ethylene (ET) signalling pathway in AsES-mediated immune response in strawberry. Ethylene production and expression of the genes responsible for ET synthesis, perception and response were measured after AsES treatment. ROS (H2 O2 ) accumulation and immunity induced by AsES were studied after ET perception was blocked by 1-methylcyclopropene (1-MCP). Biochemical and molecular results showed that AsES induced a marked increase in local and systemic biosynthesis of ET, both in a biphasic manner. Blocking of ET perception by 1-MCP prior to AsES induction reduced production of ROS (H2 O2 ) and prevented AsES from eliciting defence against fungal pathogens having different lifestyles, such as Botrytis cinerea (necrotrophic) and Colletotrichum acutatum (hemibiotrophic). These findings contribute to elucidate the mode of action of the novel elicitor subtilase, AsES, specifically regarding the role of ET signalling in the activation of plant innate immunity, in addition to the multitude of processes regulated by ET in plants.
Asunto(s)
Etilenos , Fragaria , Transducción de Señal , Subtilisina , Etilenos/metabolismo , Fragaria/efectos de los fármacos , Fragaria/inmunología , Fragaria/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Hypocreales/química , Transducción de Señal/efectos de los fármacos , Subtilisina/farmacologíaRESUMEN
The therapeutic management of aortic stenosis has been drastically changed by the advent of percutaneous valve replacement (TAVI). Since the first implantation, the indications have progressively been extended from the inoperable patient to the patient at low surgical risk. The main objective of this review is to describe the currently recommended main indications of TAVI depending on an individualized assessment of each patient's risk, technical characteristics and anatomical valvular criteria.
Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Selección de Paciente , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Válvula Aórtica/patología , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/patología , Contraindicaciones de los Procedimientos , Prótesis Valvulares Cardíacas , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Guías de Práctica Clínica como Asunto , Falla de Prótesis , Reoperación , Medición de Riesgo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversosRESUMEN
[This corrects the article on p. 32 in vol. 25, PMID: 29507481.].
RESUMEN
BACKGROUND: In 2016, everolimus was approved by Health Canada for the treatment of unresectable, locally advanced or metastatic, well-differentiated, non-functional, neuroendocrine tumours (NET) of gastrointestinal (GI) or lung origin in adult patients with progressive disease. This analysis evaluated the cost-effectiveness of everolimus in this setting from a Canadian societal perspective. METHODS: A partitioned survival model was developed to compare the cost per life-year (LY) gained and cost per quality-adjusted life-year (QALY) gained of everolimus plus best supportive care (BSC) versus BSC alone in patients with advanced or metastatic NET of GI or lung origin. Model health states included stable disease, disease progression, and death. Efficacy inputs were based on the RADIANT-4 trial and utilities were mapped from quality-of-life data retrieved from RADIANT-4. Resource utilization inputs were derived from a Canadian physician survey, while cost inputs were obtained from official reimbursement lists from Ontario and other published sources. Costs and efficacy outcomes were discounted 5% annually over a 10-year time horizon, and sensitivity analyses were conducted to test the robustness of the base case results. RESULTS: Everolimus had an incremental gain of 0.616 QALYs (0.823 LYs) and CA$89,795 resulting in an incremental cost-effectiveness ratio of CA$145,670 per QALY gained (CA$109,166 per LY gained). The probability of cost-effectiveness was 52.1% at a willingness to pay (WTP) threshold of CA$150,000 per QALY. CONCLUSIONS: Results of the probabilistic sensitivity analysis indicate that everolimus has a 52.1% probability of being cost-effective at a WTP threshold of CA$150,000 per QALY gained in Canada.
RESUMEN
Induced systemic resistance (ISR) is one of the indirect mechanisms of growth promotion exerted by plant growth-promoting bacteria, and can be mediated by ethylene (ET). We assessed ET production and the expression of related genes in the Azospirillum-strawberry plant interaction. Ethylene production was evaluated by gas chromatography in plants inoculated or not with A. brasilense REC3. Also, plants were treated with AgNO3 , an inhibitor of ET biosynthesis; with 1-aminocyclopropane-1-carboxylic acid (ACC), a precursor of ET biosynthesis; and with indole acetic acid (IAA). Plant dry biomass and the growth index were determined to assess the growth-promoting effect of A. brasilense REC3 in strawberry plants. Quantitative real time PCR (qRT-PCR) was performed to analyse relative expression of the genes Faetr1, Faers1 and Faein4, which encode ET receptors; Factr1 and Faein2, involved in the ET signalling pathway; Faacs1 encoding ACC synthase; Faaco1 encoding ACC oxidase; and Faaux1 and Faami1 for IAA synthesis enzymes. Results showed that ET acts as a rapid and transient signal in the first 12 h post-treatment. A. brasilense REC3-inoculated plants had a significantly higher growth index compared to control plants. Modulation of the genes Faetr1, Faers1, Faein4, Factr1, Faein2 and Faaco1 indicated activation of ET synthesis and signalling pathways. The up-regulation of Faaux1 and Faami1 involved in IAA synthesis suggested that inoculation with A. brasilense REC3 induces production of this auxin, modulating ET signalling. Ethylene production and up-regulation of genes associated with ET signalling in strawberry plants inoculated with A. brasilense REC3 support the priming activation characteristic of ISR. This type of resistance and the activation of systemic acquired resistance previously observed in this interaction indicate that both are present in strawberry plants, could act synergistically and increase protection against pathogens.
Asunto(s)
Azospirillum brasilense/metabolismo , Etilenos/metabolismo , Fragaria/microbiología , Aminoácidos Cíclicos/farmacología , Biomasa , Etilenos/antagonistas & inhibidores , Fragaria/crecimiento & desarrollo , Fragaria/metabolismo , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Ácidos Indolacéticos/farmacología , Proteínas de Plantas/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores de Superficie Celular/metabolismo , Nitrato de Plata/farmacologíaRESUMEN
Hopanes are abundant in ancient sedimentary rocks at discrete intervals in Earth history, yet interpreting their significance in the geologic record is complicated by our incomplete knowledge of what their progenitors, hopanoids, do in modern cells. To date, few studies have addressed the breadth of diversity of physiological functions of these lipids and whether those functions are conserved across the hopanoid-producing bacterial phyla. Here, we generated mutants in the filamentous cyanobacterium, Nostoc punctiforme, that are unable to make all hopanoids (shc) or 2-methylhopanoids (hpnP). While the absence of hopanoids impedes growth of vegetative cells at high temperature, the shc mutant grows faster at low temperature. This finding is consistent with hopanoids acting as membrane rigidifiers, a function shared by other hopanoid-producing phyla. Apart from impacting fitness under temperature stress, hopanoids are dispensable for vegetative cells under other stress conditions. However, hopanoids are required for stress tolerance in akinetes, a resting survival cell type. While 2-methylated hopanoids do not appear to contribute to any stress phenotype, total hopanoids and to a lesser extent 2-methylhopanoids were found to promote the formation of cyanophycin granules in akinetes. Finally, although hopanoids support symbiotic interactions between Alphaproteobacteria and plants, they do not appear to facilitate symbiosis between N. punctiforme and the hornwort Anthoceros punctatus. Collectively, these findings support interpreting hopanes as general environmental stress biomarkers. If hopanoid-mediated enhancement of nitrogen-rich storage products turns out to be a conserved phenomenon in other organisms, a better understanding of this relationship may help us parse the enrichment of 2-methylhopanes in the rock record during episodes of disrupted nutrient cycling.
Asunto(s)
Nostoc/fisiología , Estrés Fisiológico , Triterpenos/metabolismo , Mutación , Nostoc/genética , Nostoc/metabolismo , Nostoc/efectos de la radiación , TemperaturaRESUMEN
Over the 65-100°C range and at a water content of 1.6kgkg(-1)db, a comparison was conducted between plantain paste (dispersion made of flour and water) and pulp pieces after cooking to evaluate their respective degree of starch gelatinization (α) and in vitro digestibility. Below 76°C and at 100°C, the gelatinization behaviour of starch into pulp pieces and paste was similar, whereas at 85°C a significant mean relative difference was observed in between. For α in the 0-1 range, pieces of plantain pulp exhibited a lower rapidly digestible starch fraction (30%) and a higher resistant starch fraction (33%) than the flour paste, suggesting some structural effects. Both Weibull and exponential models showed a good fit for α over temperature range and starch digestibility fractions over α. Although no explicit relationship was established between the intact pulp structure and grinded flour state of plantain, the evaluation of the degree of starch gelatinization and digestibility of a plantain flour paste, could be used to predict the gelatinization and digestibility behaviour of plantain starch in entire pieces of pulp.
Asunto(s)
Calor , Plantago/metabolismo , Almidón/metabolismo , Culinaria , DigestiónRESUMEN
Since inflammatory bowel diseases (IBD) represent significant morbidity and mortality in the US, the need for defining novel drug targets and inflammatory mechanisms would be of considerable benefit. Although protein tyrosine kinase 6 (PTK6, also known as breast tumor kinase BRK) has been primarily studied in an oncogenic context, it was noted that PTK6 null mice exhibited significantly enhanced colonic epithelial barrier function. Considering that the inflammatory functions of PTK6 have not yet been explored, we hypothesized that cytokines responsible for mediating IBD, such as TNFα/IFNγ, may solicit the action of PTK6 to alter barrier function. After first assessing critical mediators of TNFα/IFNγ driven epithelial barrier dysfunction, we further explored the possibility of PTK6 in this inflammatory context. In this report, we showed that PTK6 siRNA and PTK6 null young adult mouse colonic epithelial cells (YAMC) exhibited significant attenuation of TNFα/IFNγ induced barrier dysfunction as measured by electric cell-substrate impedance sensing (ECIS) assay and permeability assays. In addition, PTK6 null cells transfected with PTK6 cDNA displayed restored barrier dysfunction in response to TNFα/IFNγ, while the cells transfected with vector alone showed similar attenuation of barrier dysfunction. Furthermore, using subcellular fractionation and immunocytochemistry experiments, we found that PTK6 plays a role in FoxO1 nuclear accumulation leading to down-regulation of claudin-3, a tight junction protein. Moreover, we searched for relevant miRNA candidates putative for targeting PTK6 in order to identify and assess the impact of microRNA that target PTK6 with respect to TNFα/IFNγ induced barrier dysfunction. Subsequently, we assayed likely targets and determined their effectiveness in attenuating PTK6 expression as well as cytokine induced barrier dysfunction. Results showed that miR-93 reduced PTK6 expression and attenuated TNFα/IFNγ imposed decrease in transepithelial electrical resistance (TER), as well as excluded FoxO1 from the nucleus. Our results indicate that PTK6 may act as a novel mediator of intestinal epithelial permeability during inflammatory injury, and miR-93 may protect intestinal epithelial barrier function, at least in part, by targeting PTK6.
Asunto(s)
Células Epiteliales/metabolismo , Regulación de la Expresión Génica , Interferón gamma/metabolismo , MicroARNs/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Claudina-3/metabolismo , Colon/citología , ADN Complementario/metabolismo , Impedancia Eléctrica , Proteína Forkhead Box O1/metabolismo , Humanos , Inmunohistoquímica , Inflamación , Mucosa Intestinal/metabolismo , MAP Quinasa Quinasa 4/metabolismo , Ratones , Ratones Transgénicos , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Permeabilidad , Proteínas Tirosina Quinasas/genética , Uniones Estrechas/metabolismoRESUMEN
The occurrence of peritoneal carcinomatosis is a major cause of treatment failure in colorectal cancer and is considered incurable. However, new therapeutic approaches have been proposed, including cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Although HIPEC has been effective in selected patients, it is not known how HIPEC prolongs a patient's lifespan. Here, we have demonstrated that HIPEC-treated tumor cells induce the activation of tumor-specific T cells and lead to vaccination against tumor cells in mice. We have established that this effect results from the HIPEC-mediated exposure of heat shock protein (HSP) 90 at the plasma membrane. Inhibition or blocking of HSP90, but not HSP70, prevented the HIPEC-mediated antitumoral vaccination. Our work raises the possibility that the HIPEC procedure not only kills tumor cells but also induces an efficient anticancer immune response, therefore opening new opportunities for cancer treatment.
Asunto(s)
Vacunas contra el Cáncer/farmacología , Proteínas HSP90 de Choque Térmico/metabolismo , Hipertermia Inducida/métodos , Neoplasias Peritoneales/inmunología , Neoplasias Peritoneales/terapia , Animales , Vacunas contra el Cáncer/inmunología , Línea Celular Tumoral , Membrana Celular/metabolismo , Técnicas de Cocultivo , Terapia Combinada , Células Dendríticas/inmunología , Proteínas HSP90 de Choque Térmico/genética , Humanos , Ratones Endogámicos BALB C , Neoplasias Peritoneales/tratamiento farmacológico , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
AsES (Acremonium strictum Elicitor and Subtilisin) is a novel extracellular elicitor protein produced by the avirulent isolate SS71 of the opportunist strawberry fungal pathogen A. strictum. Here we describe the activity of AsES in the plant-pathogen system Arabidopsis thaliana-Botrytis cinerea. We show that AsES renders A. thaliana plants resistant to the necrotrophic pathogen B. cinerea, both locally and systemically and the defense response observed is dose-dependent. Systemic, but not local resistance is dependent on the length of exposure to AsES. The germination of the spores in vitro was not inhibited by AsES, implying that protection to B. cinerea is due to the induction of the plant defenses. These results were further supported by the findings that AsES differentially affects mutants impaired in the response to salicylic acid, jasmonic acid and ethylene, suggesting that AsES triggers the defense response through these three signaling pathways.
Asunto(s)
Acremonium/química , Arabidopsis/inmunología , Arabidopsis/microbiología , Botrytis/efectos de los fármacos , Proteínas Fúngicas/farmacología , Enfermedades de las Plantas/prevención & control , Inmunidad de la Planta , Ciclopentanos/metabolismo , Resistencia a la Enfermedad , Etilenos/metabolismo , Oxilipinas/metabolismo , Enfermedades de las Plantas/microbiología , Reguladores del Crecimiento de las Plantas/metabolismo , Ácido Salicílico/metabolismo , Transducción de SeñalRESUMEN
NF-κB-inducing kinase (NIK) is well-known for its role in promoting p100/NF-κB2 processing into p52, a process defined as the alternative, or non-canonical, NF-κB pathway. Here we reveal an unexpected new role of NIK in TNFR1-mediated RIP1-dependent apoptosis, a consequence of TNFR1 activation observed in c-IAP1/2-depleted conditions. We show that NIK stabilization, obtained by activation of the non-death TNFRs Fn14 or LTßR, is required for TNFα-mediated apoptosis. These apoptotic stimuli trigger the depletion of c-IAP1/2, the phosphorylation of RIP1 and the RIP1 kinase-dependent assembly of the RIP1/FADD/caspase-8 complex. In the absence of NIK, the phosphorylation of RIP1 and the formation of RIP1/FADD/caspase-8 complex are compromised while c-IAP1/2 depletion is unaffected. In vitro kinase assays revealed that recombinant RIP1 is a bona fide substrate of NIK. In vivo, we demonstrated the requirement of NIK pro-death function, but not the processing of its substrate p100 into p52, in a mouse model of TNFR1/LTßR-induced thymus involution. In addition, we also highlight a role for NIK in hepatocyte apoptosis in a mouse model of virus-induced TNFR1/RIP1-dependent liver damage. We conclude that NIK not only contributes to lymphoid organogenesis, inflammation and cell survival but also to TNFR1/RIP1-dependent cell death independently of the alternative NF-κB pathway.
Asunto(s)
Proteínas Activadoras de GTPasa/metabolismo , FN-kappa B/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Animales , Apoptosis/efectos de los fármacos , Caspasa 8/química , Caspasa 8/metabolismo , Línea Celular , Proteína de Dominio de Muerte Asociada a Fas/química , Proteína de Dominio de Muerte Asociada a Fas/metabolismo , Proteínas Activadoras de GTPasa/química , Células HEK293 , Humanos , Proteínas Inhibidoras de la Apoptosis/genética , Proteínas Inhibidoras de la Apoptosis/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Receptor beta de Linfotoxina/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fosforilación , Proteínas Serina-Treonina Quinasas/deficiencia , Proteínas Serina-Treonina Quinasas/genética , Transducción de Señal/efectos de los fármacos , Timo/metabolismo , Timo/patología , Factor de Necrosis Tumoral alfa/farmacología , Quinasa de Factor Nuclear kappa BRESUMEN
Hopanoids are bacterial steroid-like lipids that can be preserved in the rock record on billion-year timescales. 2-Methylhopanoids are of particular interest to geobiologists because methylation is one of the few chemical modifications that remain after diagenesis and catagenesis. 2-Methylhopanes, the molecular fossils of 2-methylhopanoids, are episodically enriched in the rock record, but we do not have a robust interpretation for their abundance patterns. Here, we exploit the evolutionary record found in molecular sequences from extant organisms to reconstruct the biosynthetic history of 2-methylhopanoids using the C-2 hopanoid methylase, HpnP. Based on HpnP phylogenetic analysis, we find that 2-methylhopanoids originated in a subset of the Alphaproteobacteria. This conclusion is statistically robust and reproducible in multiple trials varying the outgroup, trimming stringency, and ingroup dataset used to infer the evolution of this protein family. The capacity for 2-methylhopanoid production was likely horizontally transferred from the Alphaproteobacteria into the Cyanobacteria after the Cyanobacteria's major divergences. Together, these results suggest that the ancestral function of 2-methylhopanoids was not related to oxygenic photosynthesis but instead to a trait already present in the Alphaproteobacteria. Moreover, given that early 2-methylhopane deposits could have been made solely by Alphaproteobacteria before the acquisition of hpnP by Cyanobacteria, and that the Alphaproteobacteria are thought to be ancestrally aerobic, we infer that 2-methylhopanoids likely arose after the oxygenation of the atmosphere. This finding is consistent with the geologic record-the oldest syngenetic 2-methylhopanes occur after the rise of oxygen, in middle Proterozoic strata of the Barney Creek Formation.
Asunto(s)
Alphaproteobacteria/metabolismo , Fotosíntesis , Filogenia , Triterpenos/metabolismo , Alphaproteobacteria/genética , Evolución Biológica , Cianobacterias/metabolismoRESUMEN
Neurological disorders are rare complications of foam sclerotherapy. Visual disturbances and headache are the most commonly reported events and are thought to be equivalent to migraine with aura. Exceptionally, strokes have been reported. Papillary fibroelastoma is a rare cardiac tumor, which may embolize in cerebral arteries. We report the case of a patient in whom neurological disorders occurred during a session of foam sclerotherapy, and led to the discovery of a cardiac fibroelastoma.
Asunto(s)
Fibroma/diagnóstico , Neoplasias Cardíacas/diagnóstico , Enfermedades del Sistema Nervioso/etiología , Escleroterapia/efectos adversos , Escleroterapia/métodos , Femenino , Fibroma/cirugía , Neoplasias Cardíacas/cirugía , Humanos , Imagen por Resonancia Magnética , Persona de Mediana EdadRESUMEN
Deregulated expression of glycolytic enzymes contributes not only to the increased energy demands of transformed cells but also has non-glycolytic roles in tumors. However, the contribution of these non-glycolytic functions in tumor progression remains poorly defined. Here, we show that elevated expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), but not of other glycolytic enzymes tested, increased aggressiveness and vascularization of non-Hodgkin's lymphoma. Elevated GAPDH expression was found to promote nuclear factor-κB (NF-κB) activation via binding to tumor necrosis factor receptor-associated factor-2 (TRAF2), enhancing the transcription and the activity of hypoxia-inducing factor-1α (HIF-1α). Consistent with this, inactive mutants of GAPDH failed to bind TRAF2, enhance HIF-1 activity or promote lymphomagenesis. Furthermore, elevated expression of gapdh mRNA in biopsies from diffuse large B-cell non-Hodgkin's lymphoma patients correlated with high levels of hif-1α, vegf-a, nfkbia mRNA and CD31 staining. Collectively, these data indicate that deregulated GAPDH expression promotes NF-κB-dependent induction of HIF-1α and has a key role in lymphoma vascularization and aggressiveness.
Asunto(s)
Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Gliceraldehído 3-Fosfato Deshidrogenasa (NADP+)/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Linfoma no Hodgkin/metabolismo , Subunidad p50 de NF-kappa B/metabolismo , Animales , Biopsia , Línea Celular Tumoral , Inhibidores Enzimáticos/química , Células HeLa , Humanos , Linfoma/metabolismo , Ratones , Ratones Transgénicos , Fenotipo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Factor 2 Asociado a Receptor de TNF/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The effect of temperature (T=55-120°C) and water content (X1=1.4-2.0 kg kg(-1) dry basis) on the gelatinization and digestibility of plantain flour (Dominico Harton genotype) were investigated. The degree of plantain starch gelatinization (α) was measured by DSC and modelled as a function of T and X1, using the Weibull model. Rapidly digestible starch (RDS) and resistant starch (RS) fractions were evaluated for different α values. An appropriate dimensionless variable was introduced to the analyzed and modelled RDS and RS as a function of α. Starch gelatinization begins at a temperature above 59.6 ± 0.5°C and α is strongly dependent on T in non-limiting water conditions. The combined effects of T and X1 on the RDS and RS can be explained by α. We demonstrate that various heat treatments and water contents lead to the same α, with the same RDS and RS values.
Asunto(s)
Plantago/química , Almidón/química , Agua/química , Valor Nutritivo , TemperaturaRESUMEN
The plant growth-promoting strain REC3 of Azospirillum brasilense, isolated from strawberry roots, prompts growth promotion and systemic protection against anthracnose disease in this crop. Hence, we hypothesised that A. brasilense REC3 can induce different physiological, structural and molecular responses in strawberry plants. Therefore, the aim of this work was to study these traits activated in Azospirillum-colonised strawberry plants, which have not been assessed until now. Healthy, in vitro micropropagated plants were root-inoculated with REC3 under hydroponic conditions; root and leaf tissues were sampled at different times, and oxidative burst, phenolic compound content, malondialdehyde (MDA) concentration, callose deposition, cell wall fortification and gene expression were evaluated. Azospirillum inoculation enhanced levels of soluble phenolic compounds after 12 h post-inoculation (hpi), while amounts of cell wall bound phenolics were similar in inoculated and control plants. Other early responses activated by REC3 (at 24 hpi) were a decline of lipid peroxidation and up-regulation of strawberry genes involved in defence (FaPR1), bacterial recognition (FaFLS2) and H2O2 depuration (FaCAT and FaAPXc). The last may explain the apparent absence of oxidative burst in leaves after bacterial inoculation. Also, REC3 inoculation induced delayed structural responses such as callose deposition and cell wall fortification (at 72 hpi). Results showed that A. brasilense REC3 is capable of exerting beneficial effects on strawberry plants, reinforcing their physiological and cellular characteristics, which in turns contribute to improve plant performance.
Asunto(s)
Azospirillum brasilense , Biomasa , Resistencia a la Enfermedad , Fragaria/microbiología , Expresión Génica , Peroxidación de Lípido , Fenoles/metabolismo , Pared Celular/metabolismo , Resistencia a la Enfermedad/genética , Fragaria/crecimiento & desarrollo , Fragaria/fisiología , Genes de Plantas , Glucanos/metabolismo , Peróxido de Hidrógeno/metabolismo , Malondialdehído/metabolismo , Datos de Secuencia Molecular , Oxidación-Reducción , Hojas de la Planta/metabolismo , Raíces de Plantas/metabolismo , Simbiosis , Regulación hacia ArribaRESUMEN
Rapidly proliferating cells, such as cancer cells, have adopted aerobic glycolysis rather than oxidative phosphorylation to supply their energy demand; this phenomenon is known as 'the Warburg effect'. It is now widely accepted that during apoptosis the loss of energy production, orchestrated by caspases, contributes to the dismantling of the dying cell. However, how this loss of energy production occurs is still only partially known. In the present work, we established that during apoptosis the level of cellular ATP decreased in a caspase-dependent manner. We demonstrated that this decrease in ATP content was independent of any caspase modification of glucose uptake, ATP consumption or reactive oxygen species production but was dependent on a caspase-dependent inhibition of glycolysis. We found that the activity of the two glycolysis-limiting enzymes, phosphofructokinase and pyruvate kinase, were affected by caspases, whereas the activity of phosphoglycerate kinase was not, suggesting specificity of the effect. Finally, using a metabolomic analysis, we observed that caspases led to a decrease in several key metabolites, including phosphoserine, which is a major regulator of pyruvate kinase muscle isozyme activity. Thus, we have established that during apoptosis, caspases can shut down the main energy production pathway in cancer cells, leading to the impairment in the activity of the two enzymes controlling limiting steps of glycolysis.
Asunto(s)
Caspasas/metabolismo , Glucosa/metabolismo , Adenosina Trifosfato/metabolismo , Clorometilcetonas de Aminoácidos/farmacología , Apoptosis/efectos de los fármacos , Inhibidores de Caspasas/farmacología , Caspasas/química , Desoxiglucosa/farmacología , Glucólisis/efectos de los fármacos , Células HeLa , Humanos , Fosfofructoquinasa-1/metabolismo , Piruvato Quinasa/metabolismo , Quinolinas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Rutamicina/farmacología , Estaurosporina/farmacologíaRESUMEN
We present an unusual case of air-containing liver abscess demonstrated on plain film and ultrasonography with successful treatment utilizing ultrasound-guided drainage in a patient in septic shock. Although surgical drainage is often indicated, ultrasound-guided catheter drainage along with supportive antibiotic therapy can be a safe treatment alternative in critical patients.
Asunto(s)
Infecciones por Escherichia coli/diagnóstico , Infecciones por Klebsiella/diagnóstico , Klebsiella pneumoniae , Absceso Hepático/diagnóstico , Absceso Hepático/terapia , Insuficiencia Multiorgánica/complicaciones , Aire , Infecciones por Escherichia coli/complicaciones , Infecciones por Escherichia coli/terapia , Femenino , Humanos , Infecciones por Klebsiella/complicaciones , Infecciones por Klebsiella/terapia , Absceso Hepático/complicaciones , Persona de Mediana Edad , Insuficiencia Multiorgánica/diagnóstico , Insuficiencia Multiorgánica/terapiaRESUMEN
Aberrant elevation in the levels of the pro-inflammatory cytokine interleukin-1ß (IL-1ß) contributes to neuroinflammatory diseases. Blood-brain barrier (BBB) dysfunction is a hallmark phenotype of neuroinflammation. It is known that IL-1ß directly induces BBB hyperpermeability but the mechanisms remain unclear. Claudin-5 (Cldn5) is a tight junction protein found at endothelial cell-cell contacts that are crucial for maintaining brain microvascular endothelial cell (BMVEC) integrity. Transcriptional regulation of Cldn5 has been attributed to the transcription factors ß-catenin and forkhead box protein O1 (FoxO1), and the signaling molecules regulating their nuclear translocation. Non-muscle myosin light chain kinase (nmMlck, encoded by the Mylk gene) is a key regulator involved in endothelial hyperpermeability, and IL-1ß has been shown to mediate nmMlck-dependent barrier dysfunction in epithelia. Considering these factors, we tested the hypothesis that nmMlck modulates IL-1ß-mediated downregulation of Cldn5 in BMVECs in a manner that depends on transcriptional repression mediated by ß-catenin and FoxO1. We found that treating BMVECs with IL-1ß induced barrier dysfunction concomitantly with the nuclear translocation of ß-catenin and FoxO1 and the repression of Cldn5. Most importantly, using primary BMVECs isolated from mice null for nmMlck, we identified that Cldn5 repression caused by ß-catenin and FoxO1 in IL-1ß-mediated barrier dysfunction was dependent on nmMlck.
Asunto(s)
Barrera Hematoencefálica/fisiopatología , Claudina-5/genética , Células Endoteliales/fisiología , Factores de Transcripción Forkhead/fisiología , Interleucina-1beta/fisiología , Quinasa de Cadena Ligera de Miosina/fisiología , beta Catenina/fisiología , Animales , Antígenos CD/metabolismo , Encéfalo/irrigación sanguínea , Cadherinas/metabolismo , Células Cultivadas , Claudina-5/metabolismo , Regulación hacia Abajo , Endotelio Vascular/fisiopatología , Proteína Forkhead Box O1 , Ratones , Microvasos/patología , Secuencias Reguladoras de Ácidos Nucleicos , Transducción de Señal , Activación TranscripcionalRESUMEN
Turkey breast cubes underwent acidic marination in the presence of salt. The transfer of water, salt and acid was measured, and texture was assessed on the cooked meat. While significant mass gains were observed during marination, from 20 minutes of immersion onwards, only long durations produced an overall matter balance greater than that of non-marinated meat. From the first minutes of immersion, these transfers caused hardening, regardless of the presence of salt in the marinade. For longer durations, only in the absence of salt was significant tenderizing seen in comparison to the non-marinated control. This effect appears to be due on the one hand to passing the isoelectric pH of the meat during acidification, and on the other hand to setting up antagonistic mechanisms breaking down or reinforcing connective tissues by acid and salt respectively. The high degree of tenderization observed in a water-acid solution can be explained partly by dilution of the fiber load per section unit due to protein solubilization.