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1.
BMC Plant Biol ; 21(1): 602, 2021 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-34922457

RESUMEN

BACKGROUND: The plant hormone auxin is a major coordinator of plant growth and development in response to diverse environmental signals, including nutritional conditions. Sole ammonium (NH4+) nutrition is one of the unique growth-suppressing conditions for plants. Therefore, the quest to understand NH4+-mediated developmental defects led us to analyze auxin metabolism. RESULTS: Indole-3-acetic acid (IAA), the most predominant natural auxin, accumulates in the leaves and roots of mature Arabidopsis thaliana plants grown on NH4+, but not in the root tips. We found changes at the expressional level in reactions leading to IAA biosynthesis and deactivation in different tissues. Finally, NH4+ nutrition would facilitate the formation of inactive oxidized IAA as the final product. CONCLUSIONS: NH4+-mediated accelerated auxin turnover rates implicate transient and local IAA peaks. A noticeable auxin pattern in tissues correlates with the developmental adaptations of the short and highly branched root system of NH4+-grown plants. Therefore, the spatiotemporal distribution of auxin might be a root-shaping signal specific to adjust to NH4+-stress conditions.


Asunto(s)
Compuestos de Amonio/metabolismo , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Metabolismo , Oxidación-Reducción , Raíces de Plantas/metabolismo , Brotes de la Planta/metabolismo , Análisis Espacio-Temporal , Estrés Fisiológico , Distribución Tisular
2.
PLoS One ; 16(12): e0261210, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34965259

RESUMEN

Salinity normalization of total alkalinity (TA) and dissolved inorganic carbon (DIC) data is commonly used to account for conservative mixing processes when inferring net metabolic modification of seawater by coral reefs. Salinity (S), TA, and DIC can be accurately and precisely measured, but salinity normalization of TA (nTA) and DIC (nDIC) can generate considerable and unrecognized uncertainties in coral reef metabolic rate estimates. While salinity normalization errors apply to nTA, nDIC, and other ions of interest in coral reefs, here, we focus on nTA due to its application as a proxy for net coral reef calcification and the importance for reefs to maintain calcium carbonate production under environmental change. We used global datasets of coral reef TA, S, and modeled groundwater discharge to assess the effect of different volumetric ratios of multiple freshwater TA inputs (i.e., groundwater, river, surface runoff, and precipitation) on nTA. Coral reef freshwater endmember TA ranged from -2 up to 3032 µmol/kg in hypothetical reef locations with freshwater inputs dominated by riverine, surface runoff, or precipitation mixing with groundwater. The upper bound of freshwater TA in these scenarios can result in an uncertainty in reef TA of up to 90 µmol/kg per unit S normalization if the freshwater endmember is erroneously assumed to have 0 µmol/kg alkalinity. The uncertainty associated with S normalization can, under some circumstances, even shift the interpretation of whether reefs are net calcifying to net dissolving, or vice versa. Moreover, the choice of reference salinity for normalization implicitly makes assumptions about whether biogeochemical processes occur before or after mixing between different water masses, which can add uncertainties of ±1.4% nTA per unit S normalization. Additional considerations in identifying potential freshwater sources of TA and their relative volumetric impact on seawater are required to reduce uncertainties associated with S normalization of coral reef carbonate chemistry data in some environments. However, at a minimum, researchers should minimize the range of salinities over which the normalization is applied, precisely measure salinity, and normalize TA values to a carefully selected reference salinity that takes local factors into account.


Asunto(s)
Álcalis/química , Arrecifes de Coral , Metabolismo , Salinidad , Agua de Mar/química , Simulación por Computador , Incertidumbre
3.
Mol Cell ; 81(18): 3659-3664, 2021 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-34547228

RESUMEN

To celebrate our Focus Issue, we asked a selection of researchers working on different aspects of metabolism what they are excited about and what is still to come. They discuss emerging concepts, unanswered questions, things to consider, and technologies that are enabling new discoveries, as well as developing and integrating approaches to drive the field forward.


Asunto(s)
Metabolismo/fisiología , Investigación/tendencias , Humanos , Investigadores
4.
Mol Cell ; 81(18): 3775-3785, 2021 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-34547238

RESUMEN

With the elucidation of myriad anabolic and catabolic enzyme-catalyzed cellular pathways crisscrossing each other, an obvious question arose: how could these networks operate with maximal catalytic efficiency and minimal interference? A logical answer was the postulate of metabolic channeling, which in its simplest embodiment assumes that the product generated by one enzyme passes directly to a second without diffusion into the surrounding medium. This tight coupling of activities might increase a pathway's metabolic flux and/or serve to sequester unstable/toxic/reactive intermediates as well as prevent their access to other networks. Here, we present evidence for this concept, commencing with enzymes that feature a physical molecular tunnel, to multi-enzyme complexes that retain pathway substrates through electrostatics or enclosures, and finally to metabolons that feature collections of enzymes assembled into clusters with variable stoichiometric composition. Lastly, we discuss the advantages of reversibly assembled metabolons in the context of the purinosome, the purine biosynthesis metabolon.


Asunto(s)
Redes y Vías Metabólicas/fisiología , Metabolismo/fisiología , Metaboloma/fisiología , Animales , Humanos , Complejos Multienzimáticos/metabolismo , Mapas de Interacción de Proteínas/fisiología , Purinas/metabolismo
5.
Eur J Endocrinol ; 185(5): R113-R129, 2021 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-34478405

RESUMEN

Glucocorticoids regulate a remarkable variety of essential functions, including development, immunomodulation, maintenance of circadian rhythm and the response to stress. Glucocorticoids acutely increase energy availability; this is accomplished not only by mobilizing energy stores but also by diverting energy away from anabolic processes in tissues such as skeletal muscle and bone. While this metabolic shift is advantageous in the short term, prolonged glucocorticoid exposure frequently results in central obesity, insulin resistance, hyperglycaemia, dyslipidaemia, muscle wasting and osteoporosis. Understanding how glucocorticoids affect nutrient partitioning is, therefore, critical for preventing the side effects of glucocorticoid treatment. Independently of circulating glucocorticoids, intracellular glucocorticoid activity is regulated by the 11ß-hydroxysteroid dehydrogenases 1 and 2 (HSD11B1 and 2), which activate and inactivate glucocorticoids, respectively. Excessive HSD11B1 activity and amplification of local glucocorticoid activity in tissues such as adipose tissue and bone may contribute to visceral obesity, insulin resistance and ageing-related bone loss in humans. Several recent findings in animals have considerably expanded our understanding of how glucocorticoids exert their dysmetabolic effects. In mice, disrupting glucocorticoid signalling in either adipose tissue or bone produces marked effects on energy homeostasis. Glucocorticoids have also been shown to influence brown adipose tissue thermogenesis (acute activation, chronic suppression), in both rodents and humans. Lastly, recent studies in mice have demonstrated that many dysmetabolic effects of glucocorticoids are sexually dimorphic, although corresponding results in humans are lacking. Together, these studies have illuminated mechanisms by which glucocorticoids exert their metabolic effects and have guided us towards more targeted future treatments for metabolic diseases.


Asunto(s)
Glucocorticoides/farmacología , Metabolismo/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Glucocorticoides/fisiología , Humanos , Enfermedades Metabólicas/metabolismo
6.
Cells ; 10(9)2021 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-34572149

RESUMEN

The inflammatory cytokine interleukin-26 (IL-26) is highly expressed in the serum and synovial fluid of patients with inflammatory arthritis. The effect of IL-26 on human articular chondrocytes (HACs) remains unclear. Obesity is associated with disability of patients with rheumatoid arthritis and disease activity in those with ankylosing spondylitis. The saturated free fatty acid palmitate with IL-1ß can synergistically induce catabolic effects in HACs. The aim of this study was to evaluate the effects of IL-26 and palmitate in HACs. In this study, palmitate markedly synergizes the IL-26-induced proinflammatory effects and matrix protease, including COX-2, IL-6, and MMP-1, in HACs via the toll-like receptor 4 (TLR4)-ERK1/2-c-Jun signal transduction pathway. The synergistic catabolic effects of palmitate and IL-26 were attenuated by inhibitors of TLR4 (TAK242), ERK1/2 (U0126), or c-Jun (SP600125) in HACs and cartilage matrix. In addition, metformin, a potential inhibitor of TLR4, also decreased expression of COX-2 and IL-6 induced by co-incubation with IL-26 and palmitate. IL-26 and palmitate synergistically induced expression of inflammatory and catabolic mediators, resulting in articular cartilage matrix breakdown. The present study also revealed a possible mechanism and therapeutic targets against articular cartilage degradation by increased saturated fatty acids in patients with inflammatory arthritis.


Asunto(s)
Condrocitos/metabolismo , Interleucinas/metabolismo , Palmitatos/metabolismo , Artritis/inmunología , Artritis/metabolismo , Artritis/fisiopatología , Artritis Reumatoide/metabolismo , Cartílago Articular/metabolismo , Condrocitos/fisiología , Genes jun/fisiología , Humanos , Interleucinas/inmunología , Sistema de Señalización de MAP Quinasas/fisiología , Metabolismo/fisiología , Osteoartritis/metabolismo , Transducción de Señal/genética , Membrana Sinovial/metabolismo , Taiwán , Receptor Toll-Like 4/metabolismo
7.
Int J Mol Sci ; 22(18)2021 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-34575972

RESUMEN

Glutamine and lipids are two important components of proliferating cancer cells. Studies have demonstrated that glutamine synthetase (GS) boosts glutamine-dependent anabolic processes for nucleotide and protein synthesis, but the role of GS in regulating lipogenesis remains unclear. This study identified that insulin and glutamine deprivation activated the lipogenic transcription factor sterol regulatory element-binding protein 1 (SREBP1) that bound to the GS promoter and increased its transcription. Notably, GS enhanced the O-linked N-acetylglucosaminylation (O-GlcNAcylation) of the specificity protein 1 (Sp1) that induced SREBP1/acetyl-CoA carboxylase 1 (ACC1) expression resulting in lipid droplet (LD) accumulation upon insulin treatment. Moreover, glutamine deprivation induced LD formation through GS-mediated O-GlcNAc-Sp1/SREBP1/ACC1 signaling and supported cell survival. These findings demonstrate that insulin and glutamine deprivation induces SREBP1 that transcriptionally activates GS, resulting in Sp1 O-GlcNAcylation. Subsequently, O-GlcNAc-Sp1 transcriptionally upregulates the expression of SREBP1, resulting in a feedforward loop that increases lipogenesis and LD formation in liver and breast cancer cells.


Asunto(s)
Acetil-CoA Carboxilasa/genética , Glutamato-Amoníaco Ligasa/genética , Neoplasias Hepáticas/genética , Factor de Transcripción Sp1/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Glutamina/metabolismo , Humanos , Insulina/metabolismo , Lípidos/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Metabolismo/genética , Regiones Promotoras Genéticas/genética , Biosíntesis de Proteínas/genética , Transducción de Señal , beta-N-Acetilhexosaminidasas/genética
8.
Crit Care Med ; 49(12): 2112-2120, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34582409

RESUMEN

OBJECTIVES: Sepsis is a common condition in the ICU. Despite much research, its prognosis remains poor. In 2017, a retrospective before/after study reported promising results using a combination of thiamine, ascorbic acid, and hydrocortisone called "metabolic resuscitation cocktail" and several randomized controlled trials assessing its effectiveness were performed. DESIGN: We conducted a systematic review and meta-analysis of randomized controlled trials in septic ICU patients to assess the effects of this combination therapy. SETTING: PubMed, Embase, and the Cochrane library databases were searched from inception to March of 2021. Data were extracted independently by two authors. The main outcome was the change in Sequential Organ Failure Assessment score within 72 hours. Secondary outcomes included renal composite endpoints (acute kidney injury) Kidney Disease - Improving Global Outcome organization stage 3 or need for renal replacement therapy, vasopressor duration, and 28-day mortality. SUBJECTS: We included randomized controlled trials with patients admitted to the ICU with sepsis or septic shock. INTERVENTION: The trials compared a combination of thiamine, ascorbic acid, and hydrocortisone to standard care or placebo in patients admitted to ICU with sepsis or septic shock. MEASUREMENTS AND MAIN RESULTS: We included eight randomized controlled trials (n = 1,335 patients). Within 72 hours, the median of mean improvement was -1.8 and -3.2 in the control and intervention groups, respectively (eight randomized controlled trials, n = 1,253 patients); weighted mean difference -0.82 (95% CI, -1.15 to -0.48). Data were homogeneous and the funnel plot did not suggest any publication bias. Duration of vasopressor requirement was significantly reduced in the intervention group (six randomized controlled trials). There was no evidence of a difference regarding the ICU mortality and the renal composite outcome (acute kidney injury KDIGO 3 or need for renal replacement therapy, seven randomized controlled trials). CONCLUSIONS: Metabolic resuscitation cocktail administrated in ICU septic patients improves change in Sequential Organ Failure Assessment score within 72 hours. However, this improvement is modest and its clinical relevance is questionable. The impact on renal failure and mortality remains unclear.


Asunto(s)
Ácido Ascórbico/metabolismo , Hidrocortisona/metabolismo , Metabolismo/efectos de los fármacos , Sepsis/tratamiento farmacológico , Tiamina/metabolismo , Ácido Ascórbico/farmacología , Ácido Ascórbico/uso terapéutico , Combinación de Medicamentos , Humanos , Hidrocortisona/farmacología , Hidrocortisona/uso terapéutico , Ontario , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Sepsis/fisiopatología , Tiamina/farmacología , Tiamina/uso terapéutico
9.
Acta amaz ; 51(3): 207-213, set 2021.
Artículo en Inglés | LILACS | ID: biblio-1353494

RESUMEN

O pirarucu, Arapaima gigas é um peixe carnívoro nativo da bacia amazônica. Como peixes carnívoros possuem baixa atividade de amilase, enzimas exógenas melhoram a digestibilidade de carboidratos em rações para aquacultura. O objetivo deste estudo foi avaliar a digestibilidade de níveis crescentes de complexo enzimático em dietas para juvenis de pirarucu (65,2 ± 0,4 g). O desenho experimental foi randomizado com quatro tratamentos [dietas contendo 0,25, 0,50, 0,75 e 1 g kg-1 de complexo enzimático adicionado (Allzyme® SSF®, EUA)] e um controle, com três réplicas com densidade de cinco peixes por unidade e 30 dias de duração. A digestibilidade aparente da matéria seca, proteína bruta e energia bruta foi calculada por quantificação de nutrientes e óxido de cromo nas dietas e fezes. A atividade enzimática, o glicogênio hepático e a proteína total foram determinados a partir de amostras do fígado e intestino anterior. A dieta com 1 g kg-1 de complexo enzimático resultou em um aumento da digestibilidade aparente de proteina bruta, energia bruta, matéria seca, glicogênio hepático e proteínas totais no fígado e intestino, mostrando a eficácia do complexo enzimático na dieta dos pirarucus. A acumulação mais alta de matéria seca, energia bruta e extrato etéreo na carcaça indicou o aumento de peso dos peixes tratados com complexo enzimático. A redução da atividade enzimática endógena (protease, lipase e amilase) sugeriu um aumento da eficácia do processo digestivo. Nossos resultados indicam que a inclusão de 1 g kg-1 do complexo enzimático na dietas de juvenis de pirarucu pode ser recomendada para obter maior digestibilidade de nutientes e performance produtiva. (AU)


Asunto(s)
Enzimas , Peces/metabolismo , Aditivos Alimentarios , Metabolismo
10.
Elife ; 102021 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-34350825

RESUMEN

Understanding the origin and maintenance of biodiversity is a fundamental problem. Many theoretical approaches have been investigating ecological interactions, such as competition, as potential drivers of diversification. Classical consumer-resource models predict that the number of coexisting species should not exceed the number of distinct resources, a phenomenon known as the competitive exclusion principle. It has recently been argued that including physiological tradeoffs in consumer-resource models can lead to violations of this principle and to ecological coexistence of very high numbers of species. Here, we show that these results crucially depend on the functional form of the tradeoff. We investigate the evolutionary dynamics of resource use constrained by tradeoffs and show that if the tradeoffs are non-linear, the system either does not diversify or diversifies into a number of coexisting species that do not exceed the number of resources. In particular, very high diversity can only be observed for linear tradeoffs.


Asunto(s)
Biodiversidad , Evolución Biológica , Metabolismo , Fenómenos Bioquímicos , Ecosistema , Modelos Biológicos , Dinámica Poblacional , Especificidad de la Especie
11.
Bioessays ; 43(10): e2100103, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34426986

RESUMEN

The systems view on life and its emergence from complex chemistry has remarkably increased the scientific attention on metabolism in the last two decades. However, during this time there has not been much theoretical discussion on what constitutes a metabolism and what role it actually played in biogenesis. A critical and updated review on the topic is here offered, including some references to classical models from last century, but focusing more on current and future research. Metabolism is considered as intrinsically related to the living but not necessarily equivalent to it. More precisely, the idea of "minimal metabolism", in contrast to previous, top-down conceptions, is formulated as a heuristic construct, halfway between chemistry and biology. Thus, rather than providing a complete or final characterization of metabolism, our aim is to encourage further investigations on it, particularly in the context of life's origin, for which some concrete methodological suggestions are provided. Also see the video abstract here: https://youtu.be/DP7VMKk2qpA.


Asunto(s)
Metabolismo/fisiología
12.
Nat Protoc ; 16(9): 4299-4326, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34321638

RESUMEN

Metabolic phenotyping is an important tool in translational biomedical research. The advanced analytical technologies commonly used for phenotyping, including mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy, generate complex data requiring tailored statistical analysis methods. Detailed protocols have been published for data acquisition by liquid NMR, solid-state NMR, ultra-performance liquid chromatography (LC-)MS and gas chromatography (GC-)MS on biofluids or tissues and their preprocessing. Here we propose an efficient protocol (guidelines and software) for statistical analysis of metabolic data generated by these methods. Code for all steps is provided, and no prior coding skill is necessary. We offer efficient solutions for the different steps required within the complete phenotyping data analytics workflow: scaling, normalization, outlier detection, multivariate analysis to explore and model study-related effects, selection of candidate biomarkers, validation, multiple testing correction and performance evaluation of statistical models. We also provide a statistical power calculation algorithm and safeguards to ensure robust and meaningful experimental designs that deliver reliable results. We exemplify the protocol with a two-group classification study and data from an epidemiological cohort; however, the protocol can be easily modified to cover a wider range of experimental designs or incorporate different modeling approaches. This protocol describes a minimal set of analyses needed to rigorously investigate typical datasets encountered in metabolic phenotyping.


Asunto(s)
Técnicas Genéticas , Metabolómica/métodos , Fenotipo , Programas Informáticos , Estadística como Asunto , Humanos , Metabolismo
13.
J Trauma Acute Care Surg ; 91(2S Suppl 2): S176-S181, 2021 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-34117171

RESUMEN

BACKGROUND: Severe burn injury results in profound catabolic deterioration. Although burn-related catabolism has been well stated, it is unclear when the catabolic response begins. This study characterized acute changes of muscle protein breakdown at the admission and the day after in severely burned adults. METHODS: Twelve patients (43 ± 19 years old) with 40% ± 21% total body surface area burns were prospectively enrolled into an observational study approved by institutional review board. Urinary samples were collected on admission day and the day after (day 1). Patient demographic and clinical data of vital signs, blood gas and chemistry, and coagulation status were collected. Catabolic changes of muscle breakdown were quantified by urinary excretion of 3-methylhisitidine, determined by gas chromatography and mass spectrometry analysis. RESULTS: Compared with admission day, burned patients had elevated mean ± SD arterial pressure (from 90 ± 5 mm Hg to 108 ± 7 mm Hg) and heart rate (from 102 ± 7 beats per minute to 119 ± 4 beats per minute both p < 0.05) after 24 hours. Their 24-hour urinary output was 1,586 ± 813 mL at admission day to 1,911 ± 1,048 mL on day 1. The 24-hour urea excretion was elevated from 172 ± 101 mg/kg per day at admission day to 302 ± 183 mg/kg per day on day 1 (both p < 0.05), with no change in creatinine excretion. Urinary 3-methylhisitidine excretion increased from 0.75 ± 0.74 mg/kg per day at admission to 1.14 ± 0.86 mg/kg per day on day 1 (p < 0.05). The estimated skeletal muscle protein breakdown was increased from 1.1 ± 1.0 g/kg per day at admission day to 1.6 ± 1.2 g/kg per day on day 1 (p < 0.05). There were no changes in prothrombin time, activated partial thromboplastin time, or platelets. CONCLUSION: In severely burned patients, catabolic muscle protein breakdown is elevated within 24 hours after admission and before changes in coagulation. These findings suggest that early interventions may be needed to effectively attenuate the catabolic responses in burn patients. LEVEL OF EVIDENCE: Prospective and observational study, level II.


Asunto(s)
Quemaduras/complicaciones , Músculo Esquelético/patología , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/análisis , Proteínas Sanguíneas/análisis , Quemaduras/patología , Femenino , Cromatografía de Gases y Espectrometría de Masas , Hemodinámica , Humanos , Masculino , Metabolismo , Metilhistidinas/orina , Persona de Mediana Edad , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Estudios Prospectivos , Factores de Tiempo , Equilibrio Hidroelectrolítico , Adulto Joven
14.
Curr Opin Pediatr ; 33(4): 423, 2021 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-34138779
15.
Dev Cell ; 56(13): 1961-1975.e5, 2021 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-34107300

RESUMEN

Autophagy is an essential catabolic process induced to provide cellular energy sources in response to nutrient limitation through the activation of kinases, like AMP-activated protein kinase (AMPK) and ULK1. Although glucose starvation induces autophagy, the exact mechanism underlying this signaling has yet to be elucidated. Here, we reveal a role for ULK1 in non-canonical autophagy signaling using diverse cell lines. ULK1 activated by AMPK during glucose starvation phosphorylates the lipid kinase PIKfyve on S1548, thereby increasing its activity and the synthesis of the phospholipid PI(5)P without changing the levels of PI(3,5)P2. ULK1-mediated activation of PIKfyve enhances the formation of PI(5)P-containing autophagosomes upon glucose starvation, resulting in an increase in autophagy flux. Phospho-mimic PIKfyve S1548D drives autophagy upregulation and lowers autophagy substrate levels. Our study has identified how ULK1 upregulates autophagy upon glucose starvation and induces the formation of PI(5)P-containing autophagosomes by activating PIKfyve.


Asunto(s)
Homólogo de la Proteína 1 Relacionada con la Autofagia/genética , Autofagia/genética , Fosfatidilinositol 3-Quinasas/genética , Proteínas Quinasas/genética , Autofagosomas/genética , Autofagosomas/metabolismo , Línea Celular , Regulación de la Expresión Génica/genética , Glucosa/metabolismo , Humanos , Metabolismo/genética , Fosfatos de Fosfatidilinositol/genética , Fosfolípidos/genética , Transducción de Señal/genética
16.
Acta Orthop Traumatol Turc ; 55(3): 246-252, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34100366

RESUMEN

OBJECTIVE: The aim of this study was to explore the alterations in levels of pro-inflammatory and catabolic mediators following vertebral fusion in a rabbit model of intervertebral disc degeneration. METHODS: In this study, 24 female New Zealand albino rabbits (aged 4 to 5 months and weighing 3 to 3.5 kg) were used. All the animals were randomly categorized into four groups, and dorsal spinal exposure of all lumbar vertebrae was routinely performed in each group. While disc degeneration was created in groups B, C, and D, spinal fusion was added to disc degeneration in groups C and D. Disc degeneration was typically created by puncturing the discs with an 18-gauge needle under the guidance of C-arm imaging. Fusion was achieved with posterior/posterolateral decortication and iliac bone grafts. The rabbits in groups A, B, and C were euthanized, and the discs were removed in the first week after the surgery. The rabbits in Group D were sacrificed, and the discs were harvested at 5 weeks after the surgery. The levels of Interleukin (IL)-1ß, IL-6, Nitric Oxide (NO), Matrix Metalloproteinase (MMP)-3, MMP-13, and Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) in the discs were analyzed using enzyme-linked immunosorbent assay kits. RESULTS: Significant increase was observed in the protein levels of both pro-inflammatory and catabolic mediators in disc degeneration groups (Group B, C, and D) compared to Group A. In the fusion groups (Group C and D), these increased mediators decreased, compared to non-fusion group (Group B), (IL1-ß P = 0.017, TIMP-1 P = 0.03, NO P = 0.03). However, there was no statistically significant difference in mediator levels between the short- and long-term fusion (Group C versus D). CONCLUSION: The results of this study have shown that a significant decrease in pro-inflammatory and catabolic mediators may be expected after vertebral fusion whereas there may be no significant difference between the first and fourth week of fusion surgery. These findings may contribute to clarifying the mechanism of action of vertebral fusion in the treatment of low back pain.


Asunto(s)
Degeneración del Disco Intervertebral , Disco Intervertebral , Vértebras Lumbares/cirugía , Fusión Vertebral/métodos , Animales , Mediadores de Inflamación/análisis , Interleucina-1beta/análisis , Interleucina-6/análisis , Disco Intervertebral/metabolismo , Disco Intervertebral/cirugía , Degeneración del Disco Intervertebral/inmunología , Degeneración del Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/cirugía , Dolor de la Región Lumbar/etiología , Dolor de la Región Lumbar/inmunología , Dolor de la Región Lumbar/prevención & control , Metaloproteinasa 3 de la Matriz/análisis , Metabolismo , Óxido Nítrico/análisis , Conejos
17.
Dev Cell ; 56(13): 1989-2006.e6, 2021 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-34118203

RESUMEN

Oncogenes can alter metabolism by changing the balance between anabolic and catabolic processes. However, how oncogenes regulate tumor cell biomass remains poorly understood. Using isogenic MCF10A cells transformed with nine different oncogenes, we show that specific oncogenes reduce the biomass of cancer cells by promoting extracellular vesicle (EV) release. While MYC and AURKB elicited the highest number of EVs, each oncogene selectively altered the protein composition of released EVs. Likewise, oncogenes alter secreted miRNAs. MYC-overexpressing cells require ceramide, whereas AURKB requires ESCRT to release high levels of EVs. We identify an inverse relationship between MYC upregulation and activation of the RAS/MEK/ERK signaling pathway for regulating EV release in some tumor cells. Finally, lysosome genes and activity are downregulated in the context of MYC and AURKB, suggesting that cellular contents, instead of being degraded, were released via EVs. Thus, oncogene-mediated biomass regulation via differential EV release is a new metabolic phenotype.


Asunto(s)
Aurora Quinasa B/genética , Vesículas Extracelulares/metabolismo , Oncogenes/genética , Proteínas Proto-Oncogénicas c-myc/genética , Metabolismo Energético/genética , Vesículas Extracelulares/genética , Regulación Neoplásica de la Expresión Génica , Genes ras/genética , Humanos , Lisosomas/genética , Quinasas Quinasa Quinasa PAM/genética , Sistema de Señalización de MAP Quinasas/genética , Metabolismo/genética , Transducción de Señal/genética
18.
Artículo en Inglés | MEDLINE | ID: mdl-34118407

RESUMEN

Fish skeletal muscles are composed of two distinct types, slow and fast muscles, and they play important roles in maintaining the body's movement and energy metabolism. The two types of muscle are easy to separate, so they are often used as the model system for studies on their physiological and functional characteristics. In this study, we revealed that the carbohydrate and lipid metabolic KEGG pathways are different between slow and fast muscles of Chinese perch with transcriptome analysis. In fast muscle, glucose metabolism was catabolic with higher glycolysis capacity, while in slow muscle, glucose metabolism was anabolic with more glycogen synthesis. In addition, oxidative metabolism in slow muscle was stronger than that in fast muscle. By analyzing the expression levels of 40 miRNAs involved in metabolism in the muscles of Chinese perch, 18 miRNAs were significantly upregulated and 7 were significantly downregulated in slow muscle compared with fast muscle. Based on functional enrichment analysis of their target genes, the differential expression levels of 17 miRNAs in slow and fast muscles were reflected in their carbohydrate and lipid metabolism. Among these, 15 miRNAs were associated with carbohydrate metabolism, and 6 miRNAs were associated with lipid metabolism. After 3 days of starvation, the expression levels of 15 miRNAs involved in glucose metabolism in fast and slow muscles increased. However, after 7 days of starvation, the mRNA levels of miR-22a, miR-23a, miR-133a-3p, miR-139, miR-143, miR-144, miR-181a and miR-206 decreased to basal levels. Our data suggest that the possible reason for the difference in glucose and lipid metabolism is that more miRNAs inhibit the expression of target genes in slow muscle.


Asunto(s)
Metabolismo Energético , Perfilación de la Expresión Génica , MicroARNs/metabolismo , Músculo Esquelético/metabolismo , Percas/fisiología , Ciencias de la Nutrición Animal , Animales , Conducta Alimentaria , Biblioteca de Genes , Glucosa/metabolismo , Glucógeno/metabolismo , Glucólisis , Metabolismo de los Lípidos , Metabolismo , Miosinas/química , Oxígeno/metabolismo , Isoformas de Proteínas
19.
Cambios rev. méd ; 20(1): 99-106, 30 junio 2021. tabs.
Artículo en Español | LILACS | ID: biblio-1292979

RESUMEN

En la actualidad, la obesidad es conside-rada una pandemia, cuya incidencia se ha triplicado en los últimos 30 años, y ha ge-nerado problemas de salud pública cada vez mayores. Tomando como base las guías de la Asociación Americana de Endocrinólogos (AACE), la Sociedad para la Obesidad, la Sociedad Americana de Cirugía Bariátrica y Metabólica (ASMBS), la Asociación para Medicina de la Obe-sidad y la Asociación Americana de Anes-tesiólogos, se realiza el presente docu-mento, con el fin de que se constituya en la hoja de ruta que guíe el procedimiento a seguir en los pacientes que padecen de esta enfermedad crónica y que acuden al Hospital General San Francisco (HGSF)1. La obesidad se caracteriza por el uso de varios medicamentos debido a las co-morbilidades relacionadas: enfermedad cardiovascular, diabetes mellitus tipo 2, enfermedad renal crónica, hígado graso no alcohólico, síndrome metabólico y varios tipos de cánceres2. Este protocolo contiene el más alto nivel de evidencia disponible hasta la fecha, en relación al manejo quirúrgico y no quirúrgico del paciente con diagnóstico de obesidad, incluyendo temas como la identificación de los pacientes candidatos para los pro-cedimientos bariátricos, tipo de proce-dimientos que deberían ser ofertados, el manejo preoperatorio, transoperatorio y el cuidado post operatorio de seguimiento2-4.Desde la publicación por parte de la Ame-rican Society for Metabolic and Bariatric Surgery (ASMBS) en el año 2013 de las guías de manejo del paciente con obe-sidad, se ha evidenciado un incremento significativo en las publicaciones que avalan excelentes resultados para el tra-tamiento de los pacientes con obesidad y con diabetes mellitus tipo 2 mediante la cirugía bariátrica y metabólica 2,5,6. En el año 2016 la publicación del Diabetes Sur-gery Summit (DSS2)7 marca diferencia en el manejo de los pacientes con diabetes mellitus tipo 2, es así que las mismas han crecido sustancialmente y la evidencia demuestra que el manejo metabólico ba-riátrico de estos pacientes es superior al manejo médico y cambios de estilo de vida cuando se evalúa el control glucémico y remisión de las comorbilidades. Con la evaluación previa del equipo mul-tidisciplinario, tendremos información científica del más alto nivel que nos per-mita tener un paciente con recuperación óptima aplicando los criterios de En-hanced Recovery after Bariatric Surgery (ERASB)8. En el Ecuador, la obesidad se ha conver-tido en un problema de salud pública, es así que en la población pediátrica ha au-mentado desde el año 1986 pasando del 8,0% al 26,0% para el año 2012 en el grupo de 11 a 19 años. La prevalencia de sobrepeso y obesidad en población adulta en el Ecuador es del 62,8%, según el sexo es 5,5% mayor en las mujeres (65,5%) que en los hombres (60,0%), y el mayor índice de obesidad y sobrepeso se pre-senta entre la cuarta y quinta décadas de vida, con prevalencias superiores a 73,0%9,10.


Currently, obesity is considered a pan-demic, the incidence of which has tripled in the last 30 years, and has generated in-creasing public health problems. Based on the guidelines of the American As-sociation of Endocrinologists (AACE), the Obesity Society, the American So-ciety for Metabolic and Bariatric Surgery (ASMBS), the Association for Obesity Medicine and the American Association of Anesthesiologists, this document is intended to serve as a roadmap to guide the procedure to be followed in patients suffering from this chronic disease who come to San Francisco General Hospital (HGSF)1.Obesity is characterized by the use of se-veral medications due to related comor-bidities: cardiovascular disease, type 2 diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease, meta-bolic syndrome and several types of can-cers2. This protocol contains the highest level of evidence available to date, in relation to the surgical and non-surgical management of the patient with a diag-nosis of obesity, including issues such as the identification of candidate patients for bariatric procedures, type of proce-dures that should be offered, preopera-tive, trans-operative management and fo-llow-up post-operative care2-4.Since the publication by the American So-ciety for Metabolic and Bariatric Surgery (ASMBS) in 2013 of the guidelines for the management of patients with obesity, there has been a significant increase in publications that support excellent results for the treatment of patients with obesity and type 2 diabetes mellitus through bariatric and metabolic surgery2,5,6. In 2016 the pu-blication of the Diabetes Surgery Summit (DSS2)7 makes a difference in the mana-gement of patients with type 2 diabetes mellitus, it is so that the same have grown substantially and the evidence shows that bariatric metabolic management of these patients is superior to medical manage-ment and lifestyle changes when glycemic control and remission of comor-bidities are evaluated. With the previous evaluation of the multidisciplinary team, we will have scientific information of the highest level that will allow us to have a patient with optimal recovery applying the criteria of Enhanced Recovery after Bariatric Surgery (ERASB)8.In Ecuador, obesity has become a public health problem; thus, in the pediatric population it has increased since 1986 from 8,0% to 26,0% in 2012 in the 11 to 19 years age group. The prevalence of overweight and obesity in the adult po-pulation in Ecuador is 62,8%, according to sex is 5,5% higher in women (65,5%) than in men (60,0%), and the highest rate of obesity and overweight occurs between the fourth and fifth decades of life, with prevalences higher than 73,0%9,10.


Asunto(s)
Humanos , Masculino , Femenino , Cirugía Bariátrica , Programas de Reducción de Peso , Manejo de la Obesidad , Enfermedades Nutricionales y Metabólicas , Obesidad , Peso Corporal , Pérdida de Peso , Trastornos de Alimentación y de la Ingestión de Alimentos , Índice de Masa Corporal , Nutrición, Alimentación y Dieta , Metabolismo
20.
Arch. latinoam. nutr ; 71(2): 114-126, jun. 2021. tab
Artículo en Español | LILACS, LIVECS | ID: biblio-1290833

RESUMEN

La mayoría de los estudios apoyan la tesis de que el desayuno es la comida más importante del día. Un desayuno adecuado contribuye a lograr un patrón dietético global saludable y a mejorar la calidad de la dieta. El objetivo de este estudio fue determinar los principales patrones de desayuno en tres poblaciones universitarias de España, Túnez y Estados Unidos, analizar sus semejanzas y diferencias y estudiar la influencia de factores antropométricos, sociodemográficos y de estilo de vida en la adherencia a cada patrón. Se realizó un estudio transversal con datos de 730 estudiantes matriculados en las Universidades de Castilla-La Mancha, Cartago e Internacional de Florida en 2013. El consumo de alimentos se obtuvo mediante dos recordatorios de 24 horas, no consecutivos, uno de ellos en fin de semana. Los patrones se identificaron mediante análisis factorial exploratorio. La adherencia de los estudiantes a cada patrón se evaluó usando las puntuaciones factoriales. Se obtuvieron cuatro patrones para cada país. El principal patrón de los universitarios españoles incluyó pan, tomate, sal y aceite de oliva (varianza explicada: 20,85%); el principal de los tunecinos contenía pan, mermelada, nata y mantequilla (varianza explicada: 12,73%) y el principal de los americanos incluyó huevos, leche entera y azúcares (varianza explicada: 10,77%). Género, peso, IMC o comer fuera de casa fueron factores que influyeron en la adherencia a diferentes patrones. El estudio mostró la coexistencia de patrones tradicionales con otros occidentalizados y modelos transicionales intermedios. No se determinó un patrón generalizable asociado a mejores resultados del IMC(AU)


Most studies support the conclusion that breakfast is the most important meal of the day. An adequate breakfast contributes to achieving a healthy global dietary pattern and improving quality of diet. The objective of this study was to determine the main breakfast patterns of three university populations from Spain, Tunisia, and The United States of America, analyze their similarities and differences, and study the impact of anthropometric, sociodemographic and lifestyle factors on the adherence to each pattern. A cross-sectional study was developed with data from 730 students enrolled at the University of Castilla-La Mancha, University of Carthage, and Florida International University, during 2013. Food consumption data were obtained by means of two non-consecutive 24-hour recalls including one weekend day. Exploratory factor analysis was conducted to identify breakfast patterns. Factor scores were used to assess students' adherence to each pattern. Four breakfast patterns were obtained for each country. The main pattern of the Spanish students included bread, tomato, salt, and olive oil (explained variance: 20.85%); the main model of the Tunisians included bread, jam, cream and butter (explained variance: 12.73%); and the first pattern of the Americans was characterized by eggs, whole milk and sugars (explained variance: 10.77%). Gender, weight, BMI or eating out of home were factors that influenced the adherence to different patterns. Breakfast patterns obtained in this work showed the coexistence of traditional models with westernized and transitional ones. It was not determined a generalizable pattern associated with better BMI results(AU)


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Ingestión de Alimentos , Conducta Alimentaria , Desayuno , Estilo de Vida , Índice de Masa Corporal , Nutrientes , Antropometría , Metabolismo
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