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1.
Polymers (Basel) ; 16(14)2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39065323

RESUMEN

This study explores a method that has the potential to be cost effective in inhibiting biofilm formation on metallic prostheses, thereby preventing rejection or the requirement for replacement. A cost-effective metal alloy used in biomedical implants was chosen as the substrate, and ibuprofen (Ibu), a well-known anti-inflammatory drug, was selected for drug release tests for its widespread availability and accessibility. Multilayer coatings consisting of cellulose acetate (CA), polycaprolactone (PCL), and chitosan (CHI), with or without ibuprofen (Ibu) content, were applied onto medical-grade stainless steel (SS-316 type) through electrospinning, electrospray, or blow spinning. The adhesion of the CA, PCL, and layered CA/PCL membranes, with thicknesses ranging from 20 to 100 µm, to SS substrates varied between 0.15 N and 0.22 N without CHI, which increased to 0.21 and 0.74 N, respectively, when a CHI interlayer was introduced by electrospraying between the SS and the coatings. Although drug release in a simulated body fluid (SBF) medium is predominantly governed by diffusion-driven mechanisms in all single- and multilayer coatings, a delayed release was noted in CA coatings containing Ibu when overlaid with a PCL coating produced by blow spinning. This suggests avenues for further investigations into combinations of multilayer coatings, both with and without drug-imbued layers.

2.
Plants (Basel) ; 13(14)2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39065488

RESUMEN

Zinc enrichment of edible food products, through the soil and/or foliar application of fertilizers, is a strategy that can increase the contents of some nutrients, namely Zn. In this context, a workflow for agronomic enrichment with zinc was carried out on irrigated Vitis vinifera cv. Syrah, aiming to evaluate the mobilization of photoassimilates to the winegrapes and the consequences of this for winemaking. During three productive cycles, foliar applications were performed with ZnSO4 or ZnO, at concentrations ranging between 150 and 1350 g.ha-1. The normal vegetation index as well as some photosynthetic parameters indicated that the threshold of Zn toxicity was not reached; it is even worth noting that with ZnSO4, a significant increase in several cases was observed in net photosynthesis (Pn). At harvest, Zn biofortification reached a 1.2 to 2.3-fold increase with ZnSO4 and ZnO, respectively (being significant relative to the control, in two consecutive years, with ZnO at a concentration of 1350 g.ha-1). Total soluble sugars revealed higher values with grapes submitted to ZnSO4 and ZnO foliar applications, which can be advantageous for winemaking. It was concluded that foliar spraying was efficient with ZnO and ZnSO4, showing potential benefits for wine quality without evidencing negative impacts.

3.
J Autoimmun ; 148: 103279, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38972102

RESUMEN

B cells of people with multiple sclerosis (MS) are more responsive to IFN-γ, corresponding to their brain-homing potential. We studied how a coding single nucleotide polymorphism (SNP) in IFNGR2 (rs9808753) co-operates with Epstein-Barr virus (EBV) infection as MS risk factors to affect the IFN-γ signaling pathway in human B cells. In both cell lines and primary cells, EBV infection positively associated with IFN-γ receptor expression and STAT1 phosphorylation. The IFNGR2 risk SNP selectively promoted downstream signaling via STAT1, particularly in transitional B cells. Altogether, EBV and the IFNGR2 risk SNP independently amplify IFN-γ signaling, potentially driving B cells to enter the MS brain.

4.
Cureus ; 16(6): e61670, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38966477

RESUMEN

Angioimmunoblastic T-cell lymphoma (AITL) is a rare type of non-Hodgkin lymphoma (NHL). We present a case of a 60-year-old female who attended the emergency department (ED) with fatigue, recurrent fever, weight loss, and adenopathy for six months. Laboratory findings showed anemia, lymphocytosis, eosinophilia, thrombocytosis, cholestasis, hypoproteinemia, and hypoalbuminemia. Abdominopelvic computed tomography (CT) revealed multiple adenopathies. A lymph node biopsy yielded inconclusive results in the outpatient clinic. Later, during admission, the patient underwent a positron emission tomography-computed tomography (PET-CT), revealing a cervical adenopathy cluster that was excised en bloc. Histology confirmed the diagnosis of AITL. The medical team initiated chemotherapy but opted for exclusive symptomatic treatment due to disease progression. The patient died six months after diagnosis. The fluctuating and nonspecific presentation of AITL can hinder and delay definitive diagnosis, therefore impacting treatment and prognosis.

5.
Sci Data ; 11(1): 669, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38909064

RESUMEN

Species phenology - the timing of key life events - is being altered by ongoing climate changes with yet underappreciated consequences for ecosystem stability. While flowering is generally occurring earlier, we know much less about other key processes such as the time of fruit ripening, largely due to the lack of comprehensive long-term datasets. Here we provide information on the exact date and site where seeds of 4,462 taxa were collected for the Index Seminum (seed exchange catalogue) of the Botanic Garden of the University of Coimbra, between 1926 and 2013. Seeds were collected from spontaneous and cultivated individuals across Portugal, including both native and introduced taxa. The database consists of 127,747 curated records with information on the species, or infraspecific taxa (including authority), and the day and site where seeds were collected. All records are georeferenced and provided with a confidence interval for the collection site. Taxonomy was first curated manually by in-house botanists and then harmonized according to the GBIF backbone taxonomy.


Asunto(s)
Frutas , Plantas , Cambio Climático , Ecosistema , Plantas/clasificación , Portugal , Semillas
6.
Int J Mol Sci ; 25(11)2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38892146

RESUMEN

Advanced oxidation processes, including photocatalysis, have been proven effective at organic dye degradation. Tailored porous materials with regulated pore size, shape, and morphology offer a sustainable solution to the water pollution problem by acting as support materials to grafted photocatalytic nanoparticles (NPs). This research investigated the influence of pore and particle sizes of photocatalytic MICROSCAFS® on the degradation of methyl orange (MO) in aqueous solution (10 mg/L). Photocatalytic MICROSCAFS® are made of binder-less supported P25 TiO2 NPs within MICROSCAFS®, which are silica-titania microspheres with a controlled size and interconnected macroporosity, synthesized by an adapted sol-gel method that involves a polymerization-induced phase separation process. Photocatalytic experiments were performed both in batch and flow reactors, with this latter one targeting a proof of concept for continuous transformation processes and real-life conditions. Photocatalytic degradation of 87% in 2 h (batch) was achieved, using a calibrated solar light simulator (1 sun) and a photocatalyst/pollutant mass ratio of 23. This study introduces a novel flow kinetic model which provides the modeling and simulation of the photocatalytic MICROSCAFS® performance. A scavenger study was performed, enabling an in-depth mechanistic understanding. Finally, the transformation products resulting from the MO photocatalytic degradation were elucidated by high-resolution mass spectrometry experiments and subjected to an in silico toxicity assessment.


Asunto(s)
Compuestos Azo , Luz Solar , Titanio , Contaminantes Químicos del Agua , Purificación del Agua , Catálisis , Purificación del Agua/métodos , Titanio/química , Contaminantes Químicos del Agua/química , Porosidad , Compuestos Azo/química , Microesferas , Dióxido de Silicio/química , Fotólisis , Cinética , Procesos Fotoquímicos
7.
Acta Odontol Latinoam ; 37(1): 68-78, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38920128

RESUMEN

Language disorders may interfere with social integration and affectpersonal development. Beca-use the balance of the stomatognathic system can interfere with language, it is important for speech therapy and dentistry to work together, providing multidisciplinar y Healthcare. AIM: To analyze the 100 most frequently cited articles on language disorders in children and adolescents and assess the interplay with dentistry by means of a bibliometric analysis. MATERIALS AND METHOD: A search of the 100 most frequently cited articles up to December 2021 on language disorders was performed in the Web of Science Core Collection database. Four researchers extracted the data on number of citations, title, authors, country, year of publication, journals, study design, prevalent clinical conditions, and area of expertise. The analyses were performed using VOSviewer and Excel. RESULTS: The total number of citations ranged from 251 to 1,431. Four articles were cited more than 1,000 times. Bishop DVM (10 articles; 3,653 citations) and Tomblin JD (10 articles; 4,261 citations) were the most frequently cited authors. The institutions with the largest number of publications were the University of Oxford/England (11%) and the University of Kansas/USA (8%). Observational study design was the most frequent (77%). Autism spectrum disorder (18%) and dyslexia (14%) were the most broadly investigated clinical conditions. Speech-language pathology (32%) was the area of expertise with the largest number of articles, and none of the top 100 studies showed interplay with dentistry. CONCLUSION: The 100 most widely cited articles on language disorders are mostly observational, mainly address autism spectrum disorder, and are in the field of speech-language pathology No study reported interplay with dentistry.


Os disturbios de linguagem podem interferir na integrando social e afetar o desenvolvimento dos individuos. O trabalho multidisciplinar entre fonoaudiologia e odontologia é muito importante para a promogdo da saúde. O equilibrio do sistema estomatognático interfere na linguagem. OBJETIVO: Analisar os100 artigos mais citados sobre distúrbios de linguagem em criannas e adolescentes e verificar a interando com a odontologia por meio de análise bibliométrica. MATERIAL E MÉTODO: Foi realizada uma busca pelos 100 artigos mais citados sobre distúrbios de linguagem na base de dados Web of Science Core Collection até dezembro de 2021. Quatro pesquisadores extrairam os dados referentes a número de citanoes, titulo, autores, país, ano de publicando, periódicos, desenho de estudo, condinoes clínicas prevalentes e área de especializando. As análises foram realizadas utilizando VOSviewer e Excel. RESULTADOS: O número total de citanoes variou de 251 a 1.431. Quatro artigos foram citados mais de 1.000 vezes. Bishop DVM (10 artigos; 3.653 citanoes) e Tomblin JD (10 artigos; 4.261 citanoes) foram os autores mais frequentemente citados. As instituinoes com maior número de publicanoes foram a Universidade de Oxford/Inglaterra (11%) e a Universidade de Kansas/EUA (8%). O desenho de estudo observacional foi o mais frequente (77%). O transtorno do espectro autista (18%) e a dislexia (14%) foram as condinoes clínicas mais amplamente investigadas. A Fonoaudiologia (32%) foi a área de atuando com maior número de artigos e nenhum estudo, entre os top100, mostrou interando com a Odontologia. CONCLUSÃO: Os 100 artigos mais citados sobre distúrbios de linguagem sdo em sua maioria observacionais, abordam principalmente transtornos do espectro do autismo e estdo na área de fonoaudiologia. Nenhum estudo apresentou interando com a odontologia.


Asunto(s)
Bibliometría , Humanos , Niño , Adolescente , Trastornos del Desarrollo del Lenguaje , Odontología
8.
Mov Disord ; 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38850081

RESUMEN

BACKGROUND: Among the different types of pain related to Parkinson's disease (PD), parkinsonian central pain (PCP) is the most disabling. OBJECTIVES: We investigated the analgesic efficacy of two therapeutic strategies (opioid with oxycodone- prolonged-release (PR) and higher dose of levodopa/benserazide) compared with placebo in patients with PCP. METHODS: OXYDOPA was a randomized, double-blind, double-dummy, placebo-controlled, multicenter parallel-group trial run at 15 centers within the French NS-Park network. PD patients with PCP (≥30 on the Visual Analogue Scale [VAS]) were randomly assigned to receive oxycodone-PR (up to 40 mg/day), levodopa/benserazide (up to 200 mg/day) or matching placebo three times a day (tid) for 8 weeks at a stable dose, in add-on to their current dopaminergic therapy. The primary endpoint was the change in average pain intensity over the previous week rated on VAS from baseline to week-10 based on modified intention-to-treat analyses. RESULTS: Between May 2016 and August 2020, 66 patients were randomized to oxycodone-PR (n = 23), levodopa/benserazide (n = 20) or placebo (n = 23). The mean change in pain intensity was -17 ± 18.5 on oxycodone-PR, -8.3 ± 11.1 on levodopa/benserazide, and -14.3 ± 18.9 in the placebo groups. The absolute difference versus placebo was -1.54 (97.5% confidence interval [CI], -17.0 to 13.90; P = 0.8) on oxycodone-PR and +7.79 (97.5% CI, -4.99 to 20.58; P = 0.2) on levodopa/benserazide. Similar proportions of patients in each group experienced all-cause adverse events. Those leading to study discontinuation were most frequently observed with oxycodone-PR (39%) than levodopa/benserazide (5%) or placebo (15%). CONCLUSIONS: The present trial failed to demonstrate the superiority of oxycodone-PR or a higher dose of levodopa in patients with PCP, while oxycodone-PR was poorly tolerated. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

10.
Front Immunol ; 15: 1391949, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38765015

RESUMEN

Dimethyl fumarate (DMF, Tecfidera) is an oral drug utilized to treat relapsing-remitting multiple sclerosis (MS). DMF treatment reduces disease activity in MS. Gastrointestinal discomfort is a common adverse effect of the treatment with DMF. This study aimed to investigate the effect of DMF administration in the gut draining lymph nodes cells of C57BL6/J female mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We have demonstrated that the treatment with DMF (7.5 mg/kg) significantly reduces the severity of EAE. This reduction of the severity is accompanied by the increase of both proinflammatory and anti-inflammatory mechanisms at the beginning of the treatment. As the treatment progressed, we observed an increasing number of regulatory Foxp3 negative CD4 T cells (Tr1), and anti-inflammatory cytokines such as IL-27, as well as the reduction of PGE2 level in the mesenteric lymph nodes of mice with EAE. We provide evidence that DMF induces a gradual anti-inflammatory response in the gut draining lymph nodes, which might contribute to the reduction of both intestinal discomfort and the inflammatory response of EAE. These findings indicate that the gut is the first microenvironment of action of DMF, which may contribute to its effects of reducing disease severity in MS patients.


Asunto(s)
Dimetilfumarato , Encefalomielitis Autoinmune Experimental , Ganglios Linfáticos , Ratones Endogámicos C57BL , Linfocitos T Reguladores , Animales , Dimetilfumarato/farmacología , Dimetilfumarato/uso terapéutico , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/inmunología , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/efectos de los fármacos , Ratones , Femenino , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Mesenterio , Citocinas/metabolismo , Inmunosupresores/farmacología , Inmunosupresores/uso terapéutico , Modelos Animales de Enfermedad
11.
Gels ; 10(5)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38786224

RESUMEN

Nanostructured lipid carriers (NLCs) have the potential to increase the bioavailability and reduce the side effects of docetaxel (DTX). However, only a small fraction of nanoparticles given intravenously can reach a solid tumor. In situ-forming gels combined with nanoparticles facilitate local administration and promote drug retention at the tumor site. Injectable hydrogels based on poloxamer 407 are excellent candidates for this hybrid nanoparticle-hydrogel system because of their thermoresponsive behavior and biocompatibility. Therefore, this work aimed to develop injectable poloxamer hydrogels containing NLCs for intratumoral delivery of DTX. To ensure sterility, the obtained hydrogels were autoclaved (121 °C for 15 min) after preparation. Then, the incorporation of NLCs into the poloxamer hydrogels and the impact of steam sterilization on the nanocomposite hydrogels were evaluated concerning sol-gel transition, injectability, and physicochemical stability. All formulations were extruded through the tested syringe-needle systems with acceptable force (2.2-13.4 N) and work (49.5-317.7 N·mm) of injection. Following steam sterilization, injection became easier in most cases, and the physicochemical properties of all hydrogels remained practically unchanged according to the spectroscopical and thermal analysis. The rheological evaluation revealed that the nanocomposite hydrogels were liquid at 25 °C and underwent rapid gelation at 37 °C. However, their sterilized counterparts gelled at 1-2 °C above body temperature, suggesting that the autoclaving conditions employed had rendered these nanocomposite hydrogels unsuitable for local drug delivery.

12.
Polymers (Basel) ; 16(9)2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38732695

RESUMEN

Nanocelluloses have gained significant attention in recent years due to their singular properties (good biocompatibility, high optical transparency and mechanical strength, large specific surface area, and good film-forming ability) and wide-ranging applications (paper, food packaging, textiles, electronics, and biomedical). This article is a comprehensive review of the applications of nanocelluloses (cellulose nanocrystals, cellulose nanofibrils, and bacterial nanocellulose) in the conservation and restoration of historical paper documents, including their preparation methods and main properties. The novelty lies in the information collected about nanocelluloses as renewable, environmentally friendly, and sustainable materials in the field of cultural heritage preservation as an alternative to conventional methods. Several studies have demonstrated that nanocelluloses, with or without other particles, may impart to the paper documents excellent optical and mechanical properties, very good stability against temperature and humidity aging, higher antibacterial and antifungal activity, high protection from UV light, and may be applied without requiring additional adhesive.

13.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38732157

RESUMEN

Autism Spectrum Disorder (ASD) is an early onset neurodevelopmental disorder characterized by impaired social interaction and communication, and repetitive patterns of behavior. Family studies show that ASD is highly heritable, and hundreds of genes have previously been implicated in the disorder; however, the etiology is still not fully clear. Brain imaging and electroencephalography (EEG) are key techniques that study alterations in brain structure and function. Combined with genetic analysis, these techniques have the potential to help in the clarification of the neurobiological mechanisms contributing to ASD and help in defining novel therapeutic targets. To further understand what is known today regarding the impact of genetic variants in the brain alterations observed in individuals with ASD, a systematic review was carried out using Pubmed and EBSCO databases and following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review shows that specific genetic variants and altered patterns of gene expression in individuals with ASD may have an effect on brain circuits associated with face processing and social cognition, and contribute to excitation-inhibition imbalances and to anomalies in brain volumes.


Asunto(s)
Trastorno del Espectro Autista , Encéfalo , Neuroimagen , Humanos , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/diagnóstico por imagen , Neuroimagen/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/metabolismo , Electroencefalografía , Predisposición Genética a la Enfermedad
14.
ACS Appl Polym Mater ; 6(10): 5618-5629, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38807950

RESUMEN

This work introduces the encapsulation of hexamethylene diisocyanate derivatives (HDI, TriHDI, and PHDI) with the biodegradable polymer poly(butylene adipate-co-terephthalate) (PBAT) through a solvent evaporation method. These microcapsules (MCs) were then employed in adhesive formulations for footwear. Moreover, MCs containing PHDI were produced in a closed vessel, demonstrating the potential for recovering and reusing organic solvents for the first time. The MCs were achieved with an isocyanate payload reaching up to 68 wt %, displaying a spherical shape, a core-shell structure, and thin walls without holes or cracks. The application of MCs as cross-linking agents for adhesives was evaluated following industry standards. The adhesives' strength surpassed the minimum requirement by a significant margin. Creep tests demonstrated that the formulation with MCs exhibits superior thermostability. Furthermore, the formulation with MCs-PHDI presented the best results reported to date for this type of system, as no displacement was observed in the bonded substrates. Environmental assessment indicates that adhesives with MCs have higher global warming potential (+16.2%) and energy consumption (+10.8%) than the standard commercial adhesives, but under alternative realistic scenarios, the differences can be insignificant. Therefore, adhesive formulations incorporating MCs promise to be on par with traditional adhesive systems regarding environmental impacts while providing benefits such as improved and safe handling of isocyanates and excellent bonding effectiveness.

15.
Oecologia ; 205(1): 135-147, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38739168

RESUMEN

Animal personality can shape individual's fitness. Yet, the mechanistic relationship by which individual's personality traits lead to variations in fitness remains largely underexplored. Here, we used novel object tests to measure boldness of chick-provisioning Cory's shearwaters (Calonectris borealis) from a coastal colony off west Portugal, and deployed GPS loggers to study their at-sea behaviour and distribution. We then tested whether boldness predicts individual differences in adult's trophic ecology and variations in chick growth, to assess potential implications of personality-specific foraging behaviours. Foraging effort was higher for shyer than for bolder individuals, which, during short forays, exhibited larger foraging ranges, and foraged in regions of higher and more variable bathymetry. This suggests that nearby the colony bolder individuals expanded their foraging area to maximize resource acquisition and increase the probability of foraging success. When endeavouring to longer distances, bolder individuals exhibited comparably shorter foraging ranges and targeted low bathymetry regions, likely with enhanced prey availability, while shyer individuals exhibited much larger foraging ranges indicating greater flexibility when foraging in oceanic realms. Despite such differences between bolder and shyer individuals their isotopic niches were similar. Yet, chicks raised by bolder parents grew at a faster rate than those raised by shyer parents. Together, our results suggest that differences in resource acquisition strategies could play a key role through which individual's boldness may influence breeding performance, even when individuals have similar isotopic preferences.


Asunto(s)
Ecosistema , Animales , Aves , Portugal , Conducta Alimentaria , Conducta Predatoria
16.
Sci Rep ; 14(1): 12267, 2024 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-38806574

RESUMEN

Extracellular vesicles (EVs) are lipid-membrane enclosed structures that are associated with several diseases, including those of genitourinary tract. Urine contains EVs derived from urinary tract cells. Owing to its non-invasive collection, urine represents a promising source of biomarkers for genitourinary disorders, including cancer. The most used method for urinary EVs separation is differential ultracentrifugation (UC), but current protocols lead to a significant loss of EVs hampering its efficiency. Moreover, UC protocols are labor-intensive, further limiting clinical application. Herein, we sought to optimize an UC protocol, reducing the time spent and improving small EVs (SEVs) yield. By testing different ultracentrifugation times at 200,000g to pellet SEVs, we found that 48 min and 60 min enabled increased SEVs recovery compared to 25 min. A step for pelleting large EVs (LEVs) was also evaluated and compared with filtering of the urine supernatant. We found that urine supernatant filtering resulted in a 1.7-fold increase on SEVs recovery, whereas washing steps resulted in a 0.5 fold-decrease on SEVs yield. Globally, the optimized UC protocol was shown to be more time efficient, recovering higher numbers of SEVs than Exoquick-TC (EXO). Furthermore, the optimized UC protocol preserved RNA quality and quantity, while reducing SEVs separation time.


Asunto(s)
Vesículas Extracelulares , Ultracentrifugación , Ultracentrifugación/métodos , Humanos , Vesículas Extracelulares/metabolismo , Biomarcadores/orina , Orina/citología , Orina/química , Femenino
18.
Biomolecules ; 14(5)2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38785933

RESUMEN

The problem of antimicrobial resistance is becoming a daunting challenge for human society and healthcare systems around the world. Hence, there is a constant need to develop new antibiotics to fight resistant bacteria, among other important social and economic measures. In this regard, murepavadin is a cyclic antibacterial peptide in development. The synthesis of murepavadin was undertaken in order to optimize the preparative protocol and scale-up, in particular, the use of new activation reagents. In our hands, classical approaches using carbodiimide/hydroxybenzotriazole rendered low yields. The use of novel carbodiimide and reagents based on OxymaPure® and Oxy-B is discussed together with the proper use of chromatographic conditions for the adequate characterization of peptide crudes. Higher yields and purities were obtained. Finally, the antimicrobial activity of different synthetic batches was tested in three Pseudomonas aeruginosa strains, including highly resistant ones. All murepavadin batches yielded the same highly active MIC values and proved that the chiral integrity of the molecule was preserved throughout the whole synthetic procedure.


Asunto(s)
Antibacterianos , Pruebas de Sensibilidad Microbiana , Péptidos Cíclicos , Pseudomonas aeruginosa , Pseudomonas aeruginosa/efectos de los fármacos , Péptidos Cíclicos/química , Péptidos Cíclicos/síntesis química , Péptidos Cíclicos/farmacología , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/síntesis química , Péptidos Antimicrobianos/farmacología , Carbodiimidas/química , Humanos
19.
Mol Cell ; 84(9): 1667-1683.e10, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38599210

RESUMEN

The nucleus is composed of functionally distinct membraneless compartments that undergo phase separation (PS). However, whether different subnuclear compartments are connected remains elusive. We identified a type of nuclear body with PS features composed of BAZ2A that associates with active chromatin. BAZ2A bodies depend on RNA transcription and BAZ2A non-disordered RNA-binding TAM domain. Although BAZ2A and H3K27me3 occupancies anticorrelate in the linear genome, in the nuclear space, BAZ2A bodies contact H3K27me3 bodies. BAZ2A-body disruption promotes BAZ2A invasion into H3K27me3 domains, causing H3K27me3-body loss and gene upregulation. Weak BAZ2A-RNA interactions, such as with nascent transcripts, promote BAZ2A bodies, whereas the strong binder long non-coding RNA (lncRNA) Malat1 impairs them while mediating BAZ2A association to chromatin at nuclear speckles. In addition to unraveling a direct connection between nuclear active and repressive compartments through PS mechanisms, the results also showed that the strength of RNA-protein interactions regulates this process, contributing to nuclear organization and the regulation of chromatin and gene expression.


Asunto(s)
Cromatina , Histonas , ARN Largo no Codificante , Cromatina/metabolismo , Cromatina/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Humanos , Histonas/metabolismo , Histonas/genética , Núcleo Celular/metabolismo , Núcleo Celular/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Células HeLa , Transcripción Genética , ARN/metabolismo , ARN/genética , Animales , Regulación de la Expresión Génica
20.
J Neural Transm (Vienna) ; 131(7): 799-811, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38578434

RESUMEN

OBJECTIVE: To assess amantadine use and associated factors in the patients with Parkinson's disease (PD). BACKGROUND: Immediate-release amantadine is approved for the treatment of PD and is largely used in clinical practice to treat "levodopa-induced dyskinesia (LIDs). Its use varies according to countries and PD stages. The prospective NS-Park cohort collects features of PD patients followed by 26 French PD Expert Centres. METHODS: Variables used for the analyses included demographics, motor and non-motor PD symptoms and motor complications [motor fluctuations (MFs), LIDs)], antiparkinsonian pharmacological classes and levodopa equivalent daily dose (LEDD). We evaluated: (i) prevalence of amantadine use and compared clinical features of amantadine users vs. non-users (cross-sectional analysis); (ii) factors associated with amantadine initiation (longitudinal analysis); (iii) amantadine effect on LIDs, MFs, apathy, impulse control disorders and freezing of gait (Fog) (longitudinal analysis). RESULTS: Amantadine use prevalence was 12.6% (1,585/12,542, median dose = 200 mg). Amantadine users were significantly younger, with longer and more severe PD symptoms, greater LEDD and more frequent use of device-aided/surgical treatment. Factors independently associated with amantadine initiation were younger age, longer PD duration, more frequent LIDs, MFs and FoG, higher LEDD and better cognitive function. 9 of the 658 patients on amantadine had stopped it at the following visit, after 12-18 months (1.3%). New users of amantadine presented a higher improvement in LIDs and MF compared to amantadine never users. CONCLUSIONS: About 12% of PD patients within the French NS-Park cohort used amantadine, mostly those with younger age and more severe PD. Amantadine initiation was associated with a subsequent reduction in LIDs and MFs.


Asunto(s)
Amantadina , Antiparkinsonianos , Enfermedad de Parkinson , Amantadina/uso terapéutico , Amantadina/efectos adversos , Humanos , Masculino , Femenino , Francia/epidemiología , Anciano , Antiparkinsonianos/efectos adversos , Antiparkinsonianos/uso terapéutico , Antiparkinsonianos/administración & dosificación , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/epidemiología , Persona de Mediana Edad , Estudios Prospectivos , Discinesia Inducida por Medicamentos/epidemiología , Discinesia Inducida por Medicamentos/etiología , Estudios Transversales , Levodopa/efectos adversos , Levodopa/administración & dosificación , Estudios Longitudinales , Estudios de Cohortes
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