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1.
Int J Mol Sci ; 25(3)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38338718

RESUMO

Sarcopenia, a complex and debilitating condition characterized by progressive deterioration of skeletal muscle, is the primary cause of age-associated disability and significantly impacts healthspan in elderly patients. Despite its prevalence among the aging population, the underlying molecular mechanisms are still under investigation. The NLRP3 inflammasome is crucial in the innate immune response and has a significant impact on diseases related to inflammation and aging. Here, we investigated the expression of the NLRP3 inflammasome pathway and pro-inflammatory cytokines in skeletal muscle and peripheral blood of dependent and independent patients who underwent hip surgery. Patients were categorized into independent and dependent individuals based on their Barthel Index. The expression of NLRP3 inflammasome components was significantly upregulated in sarcopenic muscle from dependent patients, accompanied by higher levels of Caspase-1, IL-1ß and IL-6. Among older dependent individuals with sarcopenia, there was a significant increase in the MYH3/MYH2 ratio, indicating a transcriptional shift in expression from mature to developmental myosin isoforms. Creatine kinase levels and senescence markers were also higher in dependent patients, altogether resembling dystrophic diseases and indicating muscle degeneration. In summary, we present evidence for the involvement of the NLRP3/ASC/NEK7/Caspase-1 inflammasome pathway with activation of pro-inflammatory SASP in the outcome of sarcopenia in the elderly.


Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR , Sarcopenia , Humanos , Idoso , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Sarcopenia/etiologia , Caspase 1/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Músculo Esquelético/metabolismo
2.
Funct Plant Biol ; 512024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38266278

RESUMO

Flooding is a predominant abiotic stress for cultivated plants, including barley. This cereal crop shows a large adaptability to different environmental conditions, suggesting the presence of key traits to tolerate adverse conditions. During germination, genetic variations account for dissimilarities in flooding tolerance. However, differences in the seed microbiota may also contribute to tolerance/sensitivity during seedling establishment. This work investigated differences in microbiome among the grains of barley accessions. Two barley phenotypes were compared, each either tolerant or sensitive to a short submergence period followed by a recovery. The study used a metataxonomic analysis based on 16S ribosomal RNA gene sequencing and subsequent functional prediction. Our results support the hypothesis that bacterial microbiota inhabiting the barley seeds are different between sensitive and tolerant barley accessions, which harbour specific bacterial phyla and families. Finally, bacteria detected in tolerant barley accessions show a peculiar functional enrichment that suggests a possible connection with successful germination and seedling establishment.


Assuntos
Hordeum , Microbiota , Humanos , Hordeum/genética , Hordeum/microbiologia , Genótipo , Plântula/genética , Sementes/genética , Microbiota/genética , Bactérias/genética
3.
J Am Chem Soc ; 146(6): 3591-3597, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38295054

RESUMO

Here we present the discovery and development of a highly selective aromatic C-H amination reaction. This electrochemical strategy involves a cathodic reduction process that generates highly electrophilic dicationic N-centered radicals that can efficiently engage in aromatic C-H functionalization and channel the regioselectivity of the aromatic substitution. The nitrogen-radical cation-pi interaction with arenes used throughout nature leads to a charge transfer mechanism, with subsequent aromatic C-N bond formation. This electrochemical process generates aryl DABCOnium salts in excellent yields and regioselectivities (single regioisomer in most cases). The scope of the reaction on arene is broad where various functionalities such as aryl halides (bromides, chlorides, fluorides), carbonyls (ketones, esters, imides), sulfonamides, and heteroarenes (pyridines, bipyridines, and terpyridines) are well tolerated. Moreover, we disclose the synthetic utility of the aryl DABCOnium salt adducts leading to the direct access of diverse aryl piperazines and the chemoselective cleavage of the exocyclic aryl C(sp2)-N bond over electrophilic C(sp3)-N+ bonds via photoredox catalysis to afford synthetically useful aryl radicals that can engage in aryl C-C and C-P bond formation.

5.
J Exp Bot ; 74(14): 4277-4289, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37100757

RESUMO

Global climate change has dramatically increased flooding events, which have a strong impact on crop production. Barley (Hordeum vulgare) is one of the most important cereals and its cultivation includes a broad range of different environments. We tested the capacity to germinate of a large barley panel after a short period of submergence followed by a period of recovery. We demonstrate that sensitive barley varieties activate underwater secondary dormancy because of a lower permeability to oxygen dissolved in water. In sensitive barley accessions, secondary dormancy is removed by nitric oxide donors. The results of a genome-wide association study uncovered a Laccase gene located in a region of significant marker-trait association that is differently regulated during grain development and plays a key role in this process. Our findings will help breeders to improve the genetics of barley, thereby increasing the capacity of seeds to germinate after a short period of flooding.


Assuntos
Germinação , Hordeum , Germinação/genética , Hordeum/genética , Estudo de Associação Genômica Ampla , Sementes/genética , Grão Comestível/genética , Hipóxia
7.
Trends Plant Sci ; 28(5): 537-543, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36740490

RESUMO

Greenhouse gas (GHG) emissions have created a global climate crisis which requires immediate interventions to mitigate the negative effects on all aspects of life on this planet. As current agriculture and land use contributes up to 25% of total GHG emissions, plant scientists take center stage in finding possible solutions for a transition to sustainable agriculture and land use. In this article, the PlantACT! (Plants for climate ACTion!) initiative of plant scientists lays out a road map of how and in which areas plant scientists can contribute to finding immediate, mid-term, and long-term solutions, and what changes are necessary to implement these solutions at the personal, institutional, and funding levels.


Assuntos
Agricultura , Gases de Efeito Estufa , Gases de Efeito Estufa/análise , Plantas , Mudança Climática , Efeito Estufa
8.
Front Plant Sci ; 13: 908349, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35845658

RESUMO

Flooding events caused by severe rains and poor soil drainage can interfere with plant germination and seedling establishment. Rice is one of the cereal crops that has unique germination strategies under flooding. One of these strategies is based on the fast coleoptile elongation in order to reach the water surface and re-establish the contact with the air. Microorganisms can contribute to plant health via plant growth promoters and provide protection from abiotic stresses. To characterise the community composition of the microbiome in rice germination under submergence, a 16S rRNA gene profiling metagenomic analysis was performed of temperate japonica rice varieties Arborio and Lamone seedlings, which showed contrasting responses in terms of coleoptile length when submerged. This analysis showed a distinct microbiota composition of Arborio seeds under submergence, which are characterised by the development of a long coleoptile. To examine the potential function of microbial communities under submergence, culturable bacteria were isolated, identified and tested for plant growth-promoting activities. A subgroup of isolated bacteria showed the capacity to hydrolyse starch and produce indole-related compounds under hypoxia. Selected bacteria were inoculated in seeds to evaluate their effect on rice under submergence, showing a response that is dependent on the rice genotype. Our findings suggest that endophytic bacteria possess plant growth-promoting activities that can substantially contribute to rice seedling establishment under submergence.

9.
Plants (Basel) ; 11(3)2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35161441

RESUMO

Cereal crops can differ greatly in tolerance to oxygen shortage under germination and seedling establishment. Rice is able to germinate and elongate the coleoptile under submergence and anoxia. This capacity has been attributed to the successful use of starchy reserves through a molecular pathway activated by sugar starvation and low oxygen. This pathway culminates with the expression of α-amylases to provide sugars that fuel the sink organs. On the contrary, barley and wheat are unable to germinate under anoxia. The sensitivity of barley and wheat is likely due to the incapacity to use starch during germination. This review highlights what is currently known about the molecular mechanisms associated with cereal germination and seedling establishment under oxygen shortage with a special focus on barley and rice. Insights into the molecular mechanisms that support rice germination under low oxygen and into those that are associated with barley sensitivity may be of help for genetic improvement programs.

10.
Angew Chem Int Ed Engl ; 60(24): 13609-13613, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-33835680

RESUMO

We report a late-stage heteroarylation of aryl sulfonium salts through activation with α-amino alkyl radicals in a mechanistically distinct approach from previously reported halogen-atom transfer (XAT). The new mode of activation of aryl sulfonium salts proceeds in the absence of light and photoredox catalysts, engaging a wide range of hetarenes. Furthermore, we demonstrate the applicability of this methodology in synthetically useful cross-coupling transformations.

12.
Org Lett ; 22(14): 5671-5674, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32640160

RESUMO

We report a nucleophilic substitution reaction of five-membered hetarylsulfonium salts that results in a change of the substitution pattern on the arene. The products of these cine-substitutions are hard to access synthetically otherwise. The sulfonium salts that serve as starting materials are generated by a highly site-selective C-H functionalization reaction.

13.
Org Lett ; 22(12): 4593-4596, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32255644

RESUMO

Aryl sulfinates are precursors to a diverse number of sulfonyl-derived arenes, which are common motifs in pharmaceuticals and agrochemicals. Here, we report a site-selective two-step C-H sulfination sequence via aryl sulfonium salts to access aryl sulfonamides. Combined with site-selective aromatic thianthrenation, an operationally simple one-pot palladium-catalyzed protocol introduces the sulfonyl group using sodium hydroxymethylsulfinate (Rongalite) as a source of SO22-. The hydroxymethyl sulfone intermediate generated from the catalytic process can be employed as a synthetic handle to deliver a variety of sulfonyl-containing compounds.

16.
Chemistry ; 25(11): 2786-2792, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30520173

RESUMO

Radical carbofluorination reactions starting from arylhydrazines and nonactivated alkenes, in which the C-F bond is formed through the use of Selectfluor, can be improved through the addition of anisole. Because direct trapping products could be detected only in trace amounts, anisole does primarily act as a reversible scavenger for the highly reactive ammonium radical dication released from Selectfluor in the C-F bond-forming step. As shown for three diverse substitution patterns, the main role of anisole is to prevent, or at least reduce, the undesired addition of the ammonium radical dication to the alkene, which in turn leads to an unfavorable consumption of the arylhydrazine-derived precursors required for carbofluorination. Moreover, besides the remarkable polar effects in radical trapping, this study shows that the Selectfluor-derived nitrogen-centered radical dication may add directly to alkenes, which has not been described so far.

17.
Rev. lab. clín ; 6(1): 2-9, ene.-mar. 2013.
Artigo em Espanhol | IBECS | ID: ibc-110350

RESUMO

Introducción. La concentración sérica de 25-hidroxivitamina D (25[OH] vitamina D) es el parámetro que mejor refleja el estado de suficiencia de vitamina D de un individuo. El objetivo de este estudio fue comparar los resultados de 25-hidroxivitamina D obtenidos mediante 3 métodos automatizados comerciales utilizando muestras de pacientes y siguiendo el protocolo establecido en la guía CLSI (Clinical Laboratory Standards Institute) EP09-A2-IR. Material y métodos. Se determinaron las concentraciones de 25[OH] vitamina D en 40 muestras de suero mediante 3 inmunoensayos: LIAISON(R) (Diasorin), ARCHITECT (Abbot) y Elecsys Vitamin D total (Roche). Se siguió el protocolo EP09-A2-IR (2 edición 2010) del CLSI. Resultados. En el estudio de reproducibilidad ningún duplicado superó el límite de aceptabilidad y ninguno de los métodos presentó valores extremos. Los 3 métodos mostraron una alta correlación entre sí. Se observaron diferencias constantes y proporcionales entre los resultados de LIAISON(R) -ARCHITECT(R) y ARCHITECT -Elecsys, mientras que entre LIAISON(R) - Elecsys solo existieron diferencias constantes. La mediana del coeficiente de variación (CV) obtenido en el ARCHITECT fue significativamente inferior a la obtenida con el LIAISON(R) (p<0,01) pero no difirió significativamente de la del Elecsys (p=0,204). Tampoco existieron diferencias significativas entre las medianas del CV de LIAISON(R) respecto a Elecsys (p=0,308). Conclusión. Los 3 métodos presentan una buena reproducibilidad y una alta correlación entre sí, aunque los resultados de 25[OH] vitamina D obtenidos no son intercambiables. Todos parecen adecuados para su utilización, aunque deben ser valorados por cada laboratorio para seleccionar la metodología que más se ajuste a sus necesidades (AU)


Background. Serum concentration of 25-hydroxyvitamin D (25[OH]vitamin D) is the best parameter for assessing vitamin D status in patients. The aim of this study is to compare the results of vitamin D in patient samples using three different automated methods, following the CLSI (Clinical Laboratory Standards Institute) EP09-A2-IR (2nd edition 2010) guideline. Methods. Concentrations of 25-hydroxyvitamin D (25[OH]vitamin D) in 40 patient serum samples were determined, using three different immunoassays: LIAISON(R)(Diasorin), ARCHITECT (Abbot) and Elecsys Vitamin D total (Roche). The CLSI (Clinical Laboratory Standards Institute) EP09-A2-IR (2nd edition 2010) guideline was used. Results. In the reproducibility study no duplicate was outside the acceptability limit and there were no outliers in any of the methods. The three methods showed a good correlation with each other. Constant and proportional differences were observed between the results of LIAISON(R) -ARCHITECT(R) and ARCHITECT -Elecsys(R) , whereas only constant differences were observed between LIAISON(R) - Elecsys. The median CV obtained with ARCHITECT was significantly lower than with LIAISON(R) (P<.01), but was not significantly different from that of the Elecsys (P=.204). No significant difference between the median CV of LIAISON(R) and Elecsys (P=.308) was observed, either. Conclusion. The three methods show a good reproducibility and a good correlation between each other, although the results obtained are not interchangeable. All of them are appropriate for their use in clinical laboratories, although in each case an evaluation should be performed in order to choose the best method for the fulfilling of the laboratories requirements (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Vitamina D/análise , Vitamina D/sangue , Calcifediol/análise , Calcifediol/sangue , Espectrometria de Massas/métodos , Espectrometria de Massas , Medições Luminescentes/métodos , Medições Luminescentes , Técnicas de Laboratório Clínico/métodos , Técnicas de Laboratório Clínico , Manejo de Espécimes/métodos , Testes Laboratoriais/métodos , Calibragem/normas , Análise de Regressão , Intervalos de Confiança
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