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1.
Proc Natl Acad Sci U S A ; 120(7): e2208509120, 2023 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-36745791

RESUMEN

Antigenic peptides derived from introns are presented on major histocompatibility (MHC) class I molecules, but how these peptides are produced is poorly understood. Here, we show that an MHC class I epitope (SL8) sequence inserted in the second intron of the ß-globin gene in a C57BL/6 mouse (HBB) generates immune tolerance. Introduction of SL8-specific CD8+ T cells derived from OT-1 transgenic mice resulted in a threefold increase in OT-1 T cell proliferation in HBB animals, as compared to wild-type animals. The growth of MCA sarcoma cells expressing the intron-derived SL8 epitope was suppressed in wild-type animals compared to HBB mice. The ß-globin pre-mRNA was detected in the light polysomal fraction, and introducing stop codons identified a non-AUG initiation site between +228 and +255 nts upstream of the SL8. Isolation of ribosome footprints confirmed translation initiation within this 27 nt sequence. Furthermore, treatment with splicing inhibitor shifts the translation of the pre-mRNA to monosomal fractions and results in an increase of intron-derived peptide substrate as shown by polysome profiling and cell imaging. These results show that non-AUG-initiated translation of pre-mRNAs generates peptides for MHC class I immune tolerance and helps explain why alternative tissue-specific splicing is tolerated by the immune system.


Asunto(s)
Antígenos de Histocompatibilidad Clase I , Precursores del ARN , Animales , Ratones , Antígenos de Histocompatibilidad Clase I/genética , Precursores del ARN/genética , Linfocitos T CD8-positivos , Biosíntesis de Proteínas , Presentación de Antígeno , Ratones Endogámicos C57BL , Péptidos/metabolismo , Tolerancia Inmunológica/genética , Epítopos , Antígenos de Histocompatibilidad Clase II/genética
2.
Appl Microbiol Biotechnol ; 108(1): 241, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38413482

RESUMEN

The present work aimed to develop, characterize, and evaluate the antibacterial and antibiofilm activity of two nanoemulsions (NEs) containing 500 µg/mL of curcumin from Curcuma longa (CUR). These NEs, produced with heating, contain olive oil (5%) and the surfactants tween 80 (5%) and span 80 (2.5%), water q.s. 100 mL, and were stable for 120 days. NE-2-CUR presented Ø of 165.40 ± 2.56 nm, PDI of 0.254, ζ of - 33.20 ± 1.35 mV, pH of 6.49, and Entrapment Drug Efficiency (EE) of 99%. The NE-4-CUR showed a Ø of 105.70 ± 4.13 nm, PDI of 0.459, ζ of - 32.10 ± 1.45 mV, pH of 6.40 and EE of 99.29%. Structural characterization was performed using DRX and FTIR, thermal characterization using DSC and TG, and morphological characterization using SEM, suggesting that there is no significant change in the CUR present in the NEs and that they remain stable. The MIC was performed by the broth microdilution method for nine gram-positive and gram-negative bacteria, as well as Klebsiella pneumoniae clinical isolates resistant to antibiotics and biofilm and efflux pump producers. The NEs mostly showed a bacteriostatic profile. The MIC varied between 125 and 250 µg/mL. The most sensitive bacteria were Staphylococcus aureus and Enterococcus faecalis, for which NE-2-CUR showed a MIC of 125 µg/mL. The NEs and ceftazidime (CAZ) interaction was also evaluated against the K. pneumoniae resistant clinical isolates using the Checkerboard method. NE-2-CUR and NE-4-CUR showed a synergistic or additive profile; there was a reduction in CAZ MICs between 256 times (K26-A2) and 2 times (K29-A2). Furthermore, the NEs inhibited these isolates biofilms formation. The NEs showed a MBIC ranging from 15.625 to 250 µg/mL. Thus, the NEs showed physicochemical characteristics suitable for future clinical trials, enhancing the CAZ antibacterial and antibiofilm activity, thus becoming a promising strategy for the treatment of bacterial infections caused by multidrug-resistant K. pneumoniae. KEY POINTS: • The NEs showed physicochemical characteristics suitable for future clinical trials. • The NEs showed a synergistic/additive profile, when associated with ceftazidime. • The NEs inhibited biofilm formation of clinical isolates.


Asunto(s)
Antiinfecciosos , Curcumina , Antibacterianos/farmacología , Ceftazidima/farmacología , Curcumina/farmacología , Curcumina/química , Aceite de Oliva/farmacología , Bacterias Grampositivas , Bacterias Gramnegativas , Antiinfecciosos/farmacología , Klebsiella pneumoniae , Pruebas de Sensibilidad Microbiana
3.
Nucleic Acids Res ; 50(20): 11799-11819, 2022 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-36350639

RESUMEN

The oncogenic Epstein-Barr virus (EBV) evades the immune system but has an Achilles heel: its genome maintenance protein EBNA1. Indeed, EBNA1 is essential for viral genome maintenance but is also highly antigenic. Hence, EBV seemingly evolved a system in which the glycine-alanine repeat (GAr) of EBNA1 limits the translation of its own mRNA to the minimal level to ensure its essential function, thereby, at the same time, minimizing immune recognition. Therefore, defining intervention points at which to interfere with GAr-based inhibition of translation is an important step to trigger an immune response against EBV-carrying cancers. The host protein nucleolin (NCL) plays a critical role in this process via a direct interaction with G-quadruplexes (G4) formed in the GAr-encoding sequence of the viral EBNA1 mRNA. Here we show that the C-terminal arginine-glycine-rich (RGG) motif of NCL is crucial for its role in GAr-based inhibition of translation by mediating interaction of NCL with G4 of EBNA1 mRNA. We also show that this interaction depends on the type I arginine methyltransferase family, notably PRMT1 and PRMT3: drugs or small interfering RNA that target these enzymes prevent efficient binding of NCL on G4 of EBNA1 mRNA and relieve GAr-based inhibition of translation and of antigen presentation. Hence, this work defines type I arginine methyltransferases as therapeutic targets to interfere with EBNA1 and EBV immune evasion.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Infecciones Tumorales por Virus , Humanos , Infecciones por Virus de Epstein-Barr/genética , Antígenos Nucleares del Virus de Epstein-Barr/genética , Antígenos Nucleares del Virus de Epstein-Barr/metabolismo , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Sistema Inmunológico/metabolismo , Virus Oncogénicos/genética , Virus Oncogénicos/metabolismo , Proteína-Arginina N-Metiltransferasas , Proteínas Represoras , ARN Mensajero/metabolismo , Infecciones Tumorales por Virus/tratamiento farmacológico , Infecciones Tumorales por Virus/metabolismo
4.
Lasers Med Sci ; 39(1): 120, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38695965

RESUMEN

Cellulite, a perceived alteration in skin topography, is predominantly found in adipose tissue-rich body regions such as the hips, buttocks, thighs, and abdomen. Contrary to common belief, the etiology and pathophysiology of cellulite are not well-established or universally agreed upon. This lack of understanding about the actual etiology of cellulite directly influences the selection of suitable treatments that can address both the aesthetic and inflammatory aspects of the condition. Various treatment methods, including electrophysical agents like electric currents, radiofrequency, ultrasound, and photobiomodulation, have been tested. However, the questionable methodological quality of many studies complicates the determination of effective treatments for cellulite. In this study, we conducted a systematic review of clinical studies that utilized electrophysical agents in cellulite treatment. METHODS: We employed the PICO (population, intervention, control, and outcome) process to develop our search strategy and establish inclusion/exclusion criteria. We searched five databases: Medline, Central, Scopus, Lilacs, and PEDro, for studies conducted between 2001 and July 2021 that involved cellulite treatment with electrophysical agents. To ensure systematicity and guide study selection, we adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. RESULTS: Our initial search yielded 556 articles: 379 from Medline, 159 from Central, and 18 from Lilacs. After applying our inclusion criteria, only 32 studies remained. Of these, only two (6.2%) were evaluated as having strong and good methodology via the QualSyst tool. CONCLUSIONS: Our findings indicate that the quality of evidence from clinical studies on the use of electrophysical agents for cellulite treatment remains subpar. Further studies with robust experimental designs and more precise assessment techniques are necessary. While our study does not refute the effectiveness of the techniques used for cellulite treatment, it underscores the need for additional well-designed trials.


Asunto(s)
Celulitis , Humanos , Celulitis/terapia , Terapia por Estimulación Eléctrica/métodos , Terapia por Luz de Baja Intensidad/métodos , Ensayos Clínicos como Asunto , Terapia por Radiofrecuencia/métodos
5.
Lasers Med Sci ; 39(1): 88, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38453765

RESUMEN

The objective of the study was to investigate the impact of photobiomodulation (PBM) on the paretic upper limb in post-stroke patients with spastic hemiparesis and to understand the potential of PBM as a long-term non-invasive therapy for reducing the side effects caused by spasticity in the hemiparetic upper limb after a stroke. This is a double-blind randomized clinical trial constituted of 27 participants, being Control group (CG = 12 healthy individuals) and PBM group (PBMG = 15 post-stroke individuals). In the CG, the baseline blood lactate (BL) was evaluated, followed by the evaluation of the IC torque of the biceps and triceps muscles, with the isokinetic dynamometer associated with surface electromyography (EMG) and, subsequently, a new measurement of BL. The PBMG received 10 sessions of treatment with PBM (780 nm, Power: 100 mV, Power Density: 3.18 W/cm2, Energy: 4 J, Fluency: 127.4 J/cm2, Time: 40 s per point and 1.280 s total, Spot: 0.0314 cm2, 32 Points: 16 points (brachial biceps) and 16 points (brachial triceps) applied with contact at 90°, Total Energy: 64 J), which in the pre-treatment evaluation measured BL, the visual analogue scale (VAS) of pain; torque and EMG of the same muscles in the IC, subsequently, a new measurement of VAS and BL, and measurement of range of motion (ROM) during the reaching movement. At the conclusion of the ten sessions, all participants underwent a reassessment, wherein all tests originally administered during the initial evaluation were repeated. Subsequently, the data were analyzed using the Shapiro-Wilk normality test. For related data, the paired t-test was used for normal distributions and the Wilcoxon test for non-normal data. For unrelated data, the t test was used for normal distributions and the Mann-Whitney test for non-normal data. Muscle torque was higher for the CG, with a significant difference (CGxPBMG = p < 0.0001). There was no significant difference between the EMG values of the CG in relation to the Pre-PBM phase and with the Post-PBM phase of the PBMG (p > 0.05). On the other hand, there was a 38% reduction in pain reported by hemiparetic patients (p = 0.0127) and a decrease in BL in the PBMG. Post-PBM ROM increased by 46.1% in the elbow extension of the paretic limb. In conclusion, Photobiomodulation (PBM) demonstrated significant improvements in muscle performance, reducing fatigue and pain levels, and enhancing range of motion in post-stroke patients with spastic hemiparesis. These findings support the potential integration of PBM into rehabilitation protocols, but further research and clinical trials are needed to validate and expand upon these promising outcomes.


Asunto(s)
Terapia por Luz de Baja Intensidad , Accidente Cerebrovascular , Humanos , Espasticidad Muscular/etiología , Espasticidad Muscular/radioterapia , Ácido Láctico , Torque , Terapia por Luz de Baja Intensidad/métodos , Músculo Esquelético , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/radioterapia , Electromiografía , Extremidad Superior , Rango del Movimiento Articular , Dolor/complicaciones , Paresia/radioterapia , Paresia/complicaciones
6.
Neurochem Res ; 48(1): 117-130, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36018438

RESUMEN

Adenosine, a purine nucleoside with neuromodulatory actions, is part of the purinergic signaling system (PSS). Caenorhabditis elegans is a free-living nematode found in soil, used in biological research for its advantages as an alternative experimental model. Since there is a lack of evidence of adenosine's direct actions and the PSS's participation in this animal, such an investigation is necessary. In this research, we aimed to test the effects of acute and chronic adenosine at 1, 5, and 10 mM on nematode's behaviors, morphology, survival after stress conditions, and on pathways related to the response to oxidative stress (DAF-16/FOXO and SKN-1) and genes products downstream these pathways (SOD-3, HSP-16.2, and GCS-1). Acute or chronic adenosine did not alter the worms' morphology analyzed by the worms' length, width, and area, nor interfered with reproductive behavior. On the other hand, acute and chronic adenosine modulated the defecation rate, pharyngeal pumping rate, and locomotion, in addition, to interacting with stress response pathways in C. elegans. Adenosine interfered in the speed and mobility of the worms analyzed. In addition, both acute and chronic adenosine presented modulatory effects on oxidative stress response signaling. Acute adenosine prevented the heat-induced-increase of DAF-16 activation and SOD-3 levels, while chronic adenosine per se induced DAF-16 activation and prevented heat-induced-increase of HSP-16.2 and SKN-1 levels. Together, these results indicate that exogenous adenosine has physiological and biochemical effects on C. elegans and describes possible purinergic signaling in worms.


Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animales , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Adenosina/farmacología , Adenosina/metabolismo , Estrés Oxidativo , Superóxido Dismutasa/metabolismo , Longevidad , Factores de Transcripción Forkhead/metabolismo
7.
Analyst ; 148(17): 4053-4063, 2023 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-37529888

RESUMEN

Early and accurate detection of infection by pathogenic microorganisms, such as Plasmodium, the causative agent of malaria, is critical for clinical diagnosis and ultimately determines the patient's outcome. We have combined a polystyrene-based microfluidic device with an immunoassay which utilises Surface-Enhanced Raman Spectroscopy (SERS) to detect malaria. The method can be easily translated to a point-of-care testing format and shows excellent sensitivity and specificity, when compared to the gold standard for laboratorial detection of Plasmodium infections. The device can be fabricated in less than 30 min by direct patterning on shrinkable polystyrene sheets of adaptable three-dimensional microfluidic chips. To validate the microfluidic system, samples of P. falciparum-infected red blood cell cultures were used. The SERS-based immunoassay enabled the detection of 0.0012 ± 0.0001% parasitaemia in a P. falciparum-infected red blood cell culture supernatant, an ∼7-fold higher sensitivity than that attained by most rapid diagnostic tests. Our approach successfully overcomes the main challenges of the current Plasmodium detection methods, including increased reproducibility, sensitivity, and specificity. Furthermore, our system can be easily adapted for detection of other pathogens and has excellent properties for early diagnosis of infectious diseases, a decisive step towards lowering their high burden on healthcare systems worldwide.


Asunto(s)
Malaria Falciparum , Malaria , Parásitos , Plasmodium , Humanos , Animales , Poliestirenos , Plasmodium falciparum , Reproducibilidad de los Resultados , Malaria/diagnóstico , Malaria Falciparum/diagnóstico , Sensibilidad y Especificidad , Dispositivos Laboratorio en un Chip
8.
Lasers Med Sci ; 38(1): 249, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37910318

RESUMEN

The objective of this study was to evaluate the effects of cardiorespiratory rehabilitation (CR) and transcranial photobiomodulation (tPBM) on exercise tolerance (ET), heart rate variability (HRV), and peripheral muscle activity in individuals with spasticity. Fifteen participants with spasticity were randomly assigned to two groups: the tPBM group (tPBMG) consisted of eight volunteers who underwent tPBM (on mode) and CR, while the control group (CG) consisted of seven volunteers who underwent simulated tPBM (off mode) and CR. The CR program included 12 weeks of treatment, twice a week for one hour, involving aerobic exercises and lower limb strengthening. For tPBM, a cluster with three lasers (λ = 680 nm, 808 nm), with a power of 100 mW/laser and energy of 36 J, applied to the F7, F8, and Fpz points. The following parameters were evaluated after 8 and 12 weeks: ET, HRV, and surface electromyography (EMG) of the rectus femoris muscle during orthostasis (ORT), isometric squatting (ISOM), and isotonic squatting (ISOT). Both groups showed a 40% increase in ET for the CG and a 30% increase for the tPBMG. The CG had more pronounced parasympathetic modulation alterations during post-exercise effort and recovery compared to the tPBMG. The EMG results showed that the tPBMG exhibited progressive improvement in muscle activity during ISOM and ISOT, as well as a decrease in the interlimb difference. In conclusion, both CR and tPBMG demonstrated improvements in ET. However, tPBMG specifically showed promising effects on HRV modulation and peripheral muscle electrical activity, providing additional benefits compared to CR alone.


Asunto(s)
Terapia por Luz de Baja Intensidad , Espasticidad Muscular , Humanos , Espasticidad Muscular/radioterapia , Terapia por Luz de Baja Intensidad/métodos , Electromiografía , Extremidad Inferior , Músculo Cuádriceps
9.
Lasers Med Sci ; 38(1): 278, 2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-38017192

RESUMEN

The dysfunctions of the female pelvic floor have a great influence on the quality of life of women, in all areas, social, psychological, and sexual. Stress urinary incontinence is the clinical condition in which the woman involuntarily loses urine to efforts, such as coughing and sneezing, causing great embarrassment and affecting her quality of life. The physiotherapeutic treatments include muscle strengthening; however, muscle fatigue is present when performing the exercises. Here we investigate the effects of photobiomodulation to prevent muscle fatigue in the pelvic floor in the treatment of stress urinary incontinence, associated with a muscle strengthening exercise protocol. We used an infrared laser (808 nm, 100 mW) and 3 J/point and fluence of 107.1 J/cm2. The application was performed at 3 points on the vaginal introits and at another 3 points inside the vaginal canal cavity for the treatment of stress urinary incontinence associated with strengthening exercises with vaginal cones. Twenty-two volunteers participated in the study, divided into two groups: group 1 (laser therapy + strengthening) and group 2 (placebo laser + strengthening). In the group 1 quality of life score, the assessment (11.63 ± 4.33) was the highest score at 17 and in the reevaluation (7.81 ± 5.14) the lowest was 0 (p < 0.05). The muscular strength increased considerably (p < 0.05) for group 1, where the vast majority of patients gained more than twice the strength in the pelvic apparatus (8.36 ± 6.65 before X 13.81 ± 8.92 after). The volunteers acquired an increase in the contraction of the muscles of the pelvic apparatus (p < 0.05) (3.45 ± 1.07); after laser application, this number increased considerably (4.27 ± 0.61). Endurance had an increase of almost 50% compared to placebo, demonstrating the resistance gain in the perineal muscles (3.90 ± 2.35 X 5 ± 1.90). We concluded that photobiomodulation treatment showed significant efficacy in relation to muscle fatigue in the pelvic apparatus right after a strengthening program in women with stress urinary incontinence.


Asunto(s)
Incontinencia Urinaria de Esfuerzo , Incontinencia Urinaria , Humanos , Femenino , Incontinencia Urinaria de Esfuerzo/radioterapia , Diafragma Pélvico , Calidad de Vida , Terapia por Ejercicio/métodos , Resultado del Tratamiento
10.
Reprod Domest Anim ; 58 Suppl 2: 4-14, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37133304

RESUMEN

The mammary gland (MG) of ruminants is essential for assuring the immune protection and nutrition of the suckling youngs. The domestication of these species aimed at increasing milk production for human consumption enhanced udder susceptibility to infections and in this context, a better understanding of the MG immune defences has become a cornerstone for the success of dairy farming. In this review, we explore constitutive and inducible immune mechanisms of the mammary gland and briefly discuss the knowledge gaps that remain to be elucidated for the implementation of strategies focused on boosting mammary immune responses.


Asunto(s)
Enfermedades de los Bovinos , Glándulas Mamarias Humanas , Mastitis Bovina , Animales , Humanos , Bovinos , Femenino , Leche , Rumiantes , Inmunidad Innata , Glándulas Mamarias Animales
11.
Sensors (Basel) ; 23(10)2023 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-37430841

RESUMEN

Microfluidic-based platforms have become a hallmark for chemical and biological assays, empowering micro- and nano-reaction vessels. The fusion of microfluidic technologies (digital microfluidics, continuous-flow microfluidics, and droplet microfluidics, just to name a few) presents great potential for overcoming the inherent limitations of each approach, while also elevating their respective strengths. This work exploits the combination of digital microfluidics (DMF) and droplet microfluidics (DrMF) on a single substrate, where DMF enables droplet mixing and further acts as a controlled liquid supplier for a high-throughput nano-liter droplet generator. Droplet generation is performed at a flow-focusing region, operating on dual pressure: negative pressure applied to the aqueous phase and positive pressure applied to the oil phase. We evaluate the droplets produced with our hybrid DMF-DrMF devices in terms of droplet volume, speed, and production frequency and further compare them with standalone DrMF devices. Both types of devices enable customizable droplet production (various volumes and circulation speeds), yet hybrid DMF-DrMF devices yield more controlled droplet production while achieving throughputs that are similar to standalone DrMF devices. These hybrid devices enable the production of up to four droplets per second, which reach a maximum circulation speed close to 1540 µm/s and volumes as low as 0.5 nL.


Asunto(s)
Microfluídica , Ácidos Nucleicos , Bioensayo , Dispositivos Laboratorio en un Chip , Tecnología
12.
Nano Lett ; 22(7): 2780-2785, 2022 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-35343708

RESUMEN

Here, we report an exceptional feature of the one-dimensional threadlike assemblies of a four-monolayer colloidal CdSe nanoplatelet (NPL)-based thin-film transistor. A series of different lengths of threads (200-1200 nm) was used as an active n channel in thin-film transistors (TFTs) to understand the change in mobility with the length of the threads. The film with the longest threads shows the highest conductivity of ∼12 S/cm and electron mobility of ∼14.3 cm2 V-1 s-1 for an applied gate voltage of 2 V. The mobility trends with the length seem to be driven mostly by the lower defects in threads, where the loss of electron hopping is less. Furthermore, our results show the mobility trends in stacking-dependent CdSe NPL threads and provide a new insight into fabricating high-mobility TFTs with the use of colloidal CdSe NPLs.

13.
Nano Lett ; 22(22): 9020-9026, 2022 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-36367392

RESUMEN

Halide perovskites have been widely explored for numerous optoelectronic applications among which phototransistors have appeared as one of the most promising light signal detectors. However, it is still a great challenge to endow halide perovskites with both mobility and high photosensitivity because of their high sensitivity to moisture in ambient atmosphere. Here, we explore an FAPbBr3 perovskite quantum dot (QD) phototransistor with bandlike charge transport and measure a dark hole mobility of 14.2 cm2 V-1 s-1 at ambient atmosphere. Attaining both high mobility and good optical figures of merit, a detectivity of ∼1016 Jones is achieved, which is a record for halide perovskite nanocrystals. Simple A-site salt (FABr) treatments offer a mechanism for connecting between perovskite QDs for better charge transfer in high-quality devices. All of these important properties are superior to most advanced inorganic semiconductor phototransistors, indicating a promising future in optoelectronic applications.

14.
Genet Mol Biol ; 46(1): e20210345, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36734368

RESUMEN

Austrodiplostomum Szidat & Nani, 1951 is a genus of parasitic digenetic trematodes widely distributed in the Neotropical region. Infects a wide variety of species, families and requests for freshwater fish. We identify samples of Austrodiplostomum sp, based on metacercariae isolates from eyes of tambaqui (Colossoma macropomum), a fish of high commercial importance in Brazil, and widely consumed by the population of the northern region. The sequences obtained clustered with A. compactum. This is the first report of the occurrence of diplostomids in farmed tambaqui in Amazonia.

15.
Development ; 146(16)2019 08 21.
Artículo en Inglés | MEDLINE | ID: mdl-31405994

RESUMEN

Retinal ganglion cell (RGC) degeneration is a hallmark of glaucoma, the most prevalent cause of irreversible blindness. Thus, therapeutic strategies are needed to protect and replace these projection neurons. One innovative approach is to promote de novo genesis of RGCs via manipulation of endogenous cell sources. Here, we demonstrate that the pluripotency regulator gene Krüppel-like factor 4 (Klf4) is sufficient to change the potency of lineage-restricted retinal progenitor cells to generate RGCs in vivo Transcriptome analysis disclosed that the overexpression of Klf4 induces crucial regulators of RGC competence and specification, including Atoh7 and Eya2 In contrast, loss-of-function studies in mice and zebrafish demonstrated that Klf4 is not essential for generation or differentiation of RGCs during retinogenesis. Nevertheless, induced RGCs (iRGCs) generated upon Klf4 overexpression migrate to the proper layer and project axons aligned with endogenous fascicles that reach the optic nerve head. Notably, iRGCs survive for up to 30 days after in vivo generation. We identified Klf4 as a promising candidate for reprogramming retinal cells and regenerating RGCs in the retina.This article has an associated 'The people behind the papers' interview.


Asunto(s)
Factores de Transcripción de Tipo Kruppel/fisiología , Neurogénesis , Células Ganglionares de la Retina/fisiología , Animales , Ciclo Celular , Femenino , Proteínas de Homeodominio/metabolismo , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Regeneración Nerviosa , Células-Madre Neurales/fisiología , Ratas , Factor de Transcripción Brn-3A/metabolismo , Factor de Transcripción Brn-3B/metabolismo , Pez Cebra , Proteínas de Pez Cebra/fisiología
16.
Cell Immunol ; 374: 104484, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35247713

RESUMEN

The accumulation of protein aggregates is toxic and linked to different diseases such as neurodegenerative disorders, but the role of the immune system to target and destroy aggregate-carrying cells is still relatively unknown. Here we show a substrate-specific presentation of antigenic peptides to the direct MHC class I pathway via autophagy. We observed no difference in presentation of peptides derived from the viral EBNA1 protein following suppression of autophagy by knocking down Atg5 and Atg12. However, the same knock down treatment suppressed the presentation from ovalbumin. Fusing the aggregate-prone poly-glutamine (PolyQ) to the ovalbumin had no effect on antigen presentation via autophagy. Interestingly, fusing the EBNA1-derived gly-ala repeat (GAr) sequence to ovalbumin rendered the presentation Atg5/12 independent. We also demonstrate that the relative levels of protein expression did not affect autophagy-mediated antigen presentation. These data suggest a substrate-dependent presentation of antigenic peptides for the MHC class I pathway via autophagy and indicate that the GAr of the EBNA1 illustrates a novel virus-mediated mechanism for immune evasion of autophagy-dependent antigen presentation.


Asunto(s)
Presentación de Antígeno , Antígenos de Histocompatibilidad Clase I , Antígenos , Autofagia , Antígenos de Histocompatibilidad Clase II/metabolismo , Evasión Inmune , Ovalbúmina
17.
Cell Mol Neurobiol ; 42(6): 1875-1886, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33704604

RESUMEN

Recent evidences have shown the therapeutic potential of transcranial photobiomodulation on traumatic brain injury and Alzheimer's disease. Despite the promising benefits in the brain, little is known about the laser's effects in the absence of pathological conditions. We submitted young (4 months old) and aged (20 months old) rats to transcranial low-level laser and evaluated their exploratory activity and habituation in open field, anxiety in elevated plus maze, spatial memory in Barnes maze, and aversive memory in a step-down inhibitory avoidance task. Additionally, the levels of a panel of inflammatory cytokines and chemokines were quantified in two different brain regions: the cerebral cortex and the hippocampus. Young and aged rats submitted to transcranial laser exhibited better cognitive performance in Barnes maze than did control rats. Transcranial laser therapy decreased cortical levels of GM-CSF, IL-10, MCP-1, LIX, and TNFα in young rats and IL-5 in aged rats. High levels of IL-6, IL-10, and TNF-alpha were found in the cerebral cortex of aged rats submitted to transcranial laser. In the hippocampus, a decrease in IP-10 and fractalkine levels was observed in the aged rats from the laser group when compared to the aged rats from the control group. Our data indicate that transcranial photobiomodulation improves spatial learning and memory and alters the neuroinflammatory profile of young and aged rats' brains.


Asunto(s)
Terapia por Luz de Baja Intensidad , Memoria Espacial , Animales , Ansiedad , Hipocampo , Interleucina-10 , Aprendizaje por Laberinto , Ratas
18.
Clin Rehabil ; 36(10): 1281-1291, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35918813

RESUMEN

OBJECTIVES: To investigate the effect of prolonged low-level laser therapy application combined with exercise on pain and disability in patients with osteoarthritis of the knee. DESIGN: A randomized controlled trial. SETTING: Special rehabilitation services. SUBJECTS: Forty-three participants with knee osteoarthritis. INTERVENTION: Following initial assessment, participants were randomly allocated to the Laser group (n = 22, 44 knees) and received low-level laser therapy while the Placebo group (n = 21, 42 knees) received placebo therapy three times a week for 3 weeks. Both groups then received low-level laser therapy combined with exercise three times a week for the following 8 weeks. MAIN OUTCOME MEASURES: The primary outcome was change in knee pain and disability (Lequesne). Secondary outcomes included change in mobility (Timed Up and Go test), range of motion (goniometer), muscular strength (dynamometer), activity (Western Ontario and McMaster Universities Osteoarthritis questionnaire), and medication intake and relief. RESULTS: Mean (SD) age of participants was 63.02 (9.9) years. Pain scores at baseline, 3 weeks, 11 weeks, and 6 months follow-up were 9.1 (1.3), 2.6 (2.3), 0.2 (0.9), and 0.2 (0.8) for the Laser group and 9.5 (8.0), 7.7 (5.3), 5.6 (2.4), and 7.4 (5.0) for the Placebo group, respectively. Disability scores at baseline, 3 weeks, 11 weeks, and 6 months follow-up were 14.9 (4.7), 7.6 (4.8), 3.9 (4.2), and 3.5 (4.1) for the Laser group and 17.8 (14.7), 15.2 (11.5), 11.6 (6.4), and 15.8 (11.9) for the Placebo Group, respectively. CONCLUSION: In participants with osteoarthritis of the knee, the isolated application of low-level laser therapy in the initial 3 weeks and combined with exercises in the final 8 weeks reduced pain, disability, and intake of medication over a 6-month period.


Asunto(s)
Terapia por Luz de Baja Intensidad , Osteoartritis de la Rodilla , Método Doble Ciego , Terapia por Ejercicio , Humanos , Persona de Mediana Edad , Dolor , Dimensión del Dolor , Equilibrio Postural , Estudios de Tiempo y Movimiento , Resultado del Tratamiento
19.
Lasers Med Sci ; 37(6): 2639-2644, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35237888

RESUMEN

Cellulite is a morphological alteration of the tegument tissue, directly interfering in self-esteem with etiology and pathophysiology far from being a consensus. Although the visual diagnosis of cellulitis is well known, it does not represent the real pathological condition of the subcutaneous tissue. The aim of the study was to investigate the hypothesis that the more heterogeneous tissue pattern analyzed by infrared thermography, the more severe is the cellulite grade. Forty female participants were selected and 60 thighs were analyzed by clinical anamnesis and infrared thermography. Classical visual analysis was correlated to the tissue heterogeneity measured by thermography. R Spearman's correlation between visual evaluation and thermography was 0.92. Phototype presented a negative significant correlation of 0.67 with classical visual analysis. In the present study, we presented a simple method based on infrared thermography that can be adopted in any esthetics office with a correlation of 0.92 with the visual classic evaluation, but, besides, may be very helpful to the clinician to decide which treatment will be adopted, i.e., an aggressive and inflammatory approach such as the radiofrequency of shockwave therapy or an anti-inflammatory approach such as photobiomodulation, depending on the inflammatory status of cellulite.


Asunto(s)
Celulitis , Lipodistrofia , Celulitis/tratamiento farmacológico , Celulitis/terapia , Femenino , Humanos , Lipodistrofia/diagnóstico , Lipodistrofia/patología , Grasa Subcutánea , Termografía , Muslo
20.
Mikrochim Acta ; 190(1): 40, 2022 12 30.
Artículo en Inglés | MEDLINE | ID: mdl-36585475

RESUMEN

Laser-induced graphene (LIG) is as a promising material for flexible microsupercapacitors (MSCs) due to its simple and cost-effective processing. However, LIG-MSC research and production has been centered on non-sustainable polymeric substrates, such as polyimide. In this work, it is presented a cost-effective, reproducible, and robust approach for the preparation of LIG structures via a one-step laser direct writing on chromatography paper. The developed strategy relies on soaking the paper in a 0.1 M sodium tetraborate solution (borax) prior to the laser processing. Borax acts as a fire-retardant agent, thus allowing the laser processing of sensitive substrates that other way would be easily destroyed under the high-energy beam. LIG on paper exhibiting low sheet resistance (30 Ω sq-1) and improved electrode/electrolyte interface was obtained by the proposed method. When used as microsupercapacitor electrodes, this laser-induced graphene resulted in specific capacitances of 4.6 mF cm-2 (0.015 mA cm-2). Furthermore, the devices exhibit excellent cycling stability (> 10,000 cycles at 0.5 mA cm-2) and good mechanical properties. By connecting the devices in series and parallel, it was also possible to control the voltage and energy delivered by the system. Thus, paper-based LIG-MSC can be used as energy storage devices for flexible, low-cost, and portable electronics. Additionally, due to their flexible design and architecture, they can be easily adapted to other circuits and applications with different power requirements.


Asunto(s)
Grafito , Capacidad Eléctrica , Electrodos , Rayos Láser
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