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1.
Neural Regen Res ; 20(5): 1293-1308, 2025 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38845223

RESUMEN

Spinal cord injuries have profound detrimental effects on individuals, regardless of whether they are caused by trauma or non-traumatic events. The compromised regeneration of the spinal cord is primarily attributed to damaged neurons, inhibitory molecules, dysfunctional immune response, and glial scarring. Unfortunately, currently, there are no effective treatments available that can fully repair the spinal cord and improve functional outcomes. Nevertheless, numerous pre-clinical approaches have been studied for spinal cord injury recovery, including using biomaterials, cells, drugs, or technological-based strategies. Combinatorial treatments, which target various aspects of spinal cord injury pathophysiology, have been extensively tested in the last decade. These approaches aim to synergistically enhance repair processes by addressing various obstacles faced during spinal cord regeneration. Thus, this review intends to provide scientists and clinicians with an overview of pre-clinical combinatorial approaches that have been developed toward the solution of spinal cord regeneration as well as update the current knowledge about spinal cord injury pathophysiology with an emphasis on the current clinical management.

2.
Nature ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39261725

RESUMEN

Layer 5 extratelencephalic (ET) neurons are present across neocortical areas and send axons to multiple subcortical targets1-6. Two cardinal subtypes exist7,8: (1) Slco2a1-expressing neurons (ETdist), which predominate in the motor cortex and project distally to the pons, medulla and spinal cord; and (2) Nprs1- or Hpgd-expressing neurons (ETprox), which predominate in the visual cortex and project more proximally to the pons and thalamus. An understanding of how area-specific ETdist and ETprox emerge during development is important because they are critical for fine motor skills and are susceptible to spinal cord injury and amyotrophic lateral sclerosis9-12. Here, using cross-areal mapping of axonal projections in the mouse neocortex, we identify the subtype-specific developmental dynamics of ET neurons. Whereas subsets of ETprox emerge by pruning of ETdist axons, others emerge de novo. We outline corresponding subtype-specific developmental transcriptional programs using single-nucleus sequencing. Leveraging these findings, we use postnatal in vivo knockdown of subtype-specific transcription factors to reprogram ET neuron connectivity towards more proximal targets. Together, these results show the functional transcriptional programs driving ET neuron diversity and uncover cell subtype-specific gene regulatory networks that can be manipulated to direct target specificity in motor corticofugal pathways.

3.
Int J Mol Sci ; 25(17)2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39273220

RESUMEN

Outer membrane vesicles (OMVs) are nanostructures derived from the outer membrane of Gram-negative bacteria. We previously demonstrated that vaccination with endotoxin-free OMVs isolated from an Acinetobacter baumannii strain lacking lipooligosaccharide (LOS) biosynthesis, due to a mutation in lpxD, provides full protection in a murine sepsis model. The present study characterizes the protein content of highly-purified OMVs isolated from LOS-replete and LOS-deficient strains. Four purification methods were evaluated to obtain highly purified OMV preparations: ultracentrifugation, size exclusion chromatography (SEC), ultracentrifugation followed by SEC, and Optiprep™. OMVs from each method were characterized using nanoparticle tracking analysis and electron microscopy. OMVs from LOS-deficient and LOS-replete strains purified using the Optiprep™ method were subjected to LC-MS/MS analysis to determine protein content. Significant differences in protein composition between OMVs from LOS-deficient and LOS-replete strains were found. Computational analyses using Bepipred 3.0 and SEMA 2.0 indicated that the lack of LOS led to the overexpression of immunogenic proteins found in LOS-containing OMVs and the presence of immune-stimulating proteins absent in LOS-replete OMVs. These findings have important implications for developing OMV-based vaccines against A. baumannii, using both LOS-containing and LOS-free OMVs preparations.


Asunto(s)
Acinetobacter baumannii , Proteínas de la Membrana Bacteriana Externa , Lipopolisacáridos , Acinetobacter baumannii/metabolismo , Acinetobacter baumannii/genética , Lipopolisacáridos/biosíntesis , Proteínas de la Membrana Bacteriana Externa/metabolismo , Proteínas de la Membrana Bacteriana Externa/genética , Infecciones por Acinetobacter/microbiología , Animales , Ratones , Espectrometría de Masas en Tándem , Membrana Externa Bacteriana/metabolismo
4.
Nutrients ; 16(17)2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39275340

RESUMEN

Chronic inflammation is a recognized risk factor for various cancers, including prostate cancer (PCa). We aim to explore the potential protective effects of aged black garlic extract (ABGE) against inflammation-induced prostate damage and its impact on prostate cancer cell lines. We used an ex vivo model of inflammation induced by Escherichia coli lipopolysaccharide (LPS) on C57BL/6 male mouse prostate specimens to investigate the anti-inflammatory properties of ABGE. The gene expression levels of pro-inflammatory biomarkers (COX-2, NF-κB, and TNF-α, IL-6) were measured. Additionally, we evaluated ABGE's therapeutic effects on the prostate cancer cell lines through in vitro functional assays, including colony formation, tumorsphere formation, migration assays, and phosphorylation arrays to assess the signaling pathways (MAPK, AKT, JAK/STAT, and TGF-ß). ABGE demonstrated significant anti-inflammatory and antioxidant effects in preclinical models, partly attributed to its polyphenolic content, notably catechin and gallic acid. In the ex vivo model, ABGE reduced the gene expression levels of COX-2, NF-κB, TNF-α, and IL-6. The in vitro studies showed that ABGE inhibited cell proliferation, colony and tumorsphere formation, and cell migration in the prostate cancer cells, suggesting its potential as a therapeutic agent. ABGE exhibits promising anti-inflammatory and anti-cancer properties, supporting further investigation into ABGE as a potential agent for managing inflammation and prostate cancer.


Asunto(s)
Antiinflamatorios , Ajo , Ratones Endogámicos C57BL , Extractos Vegetales , Próstata , Neoplasias de la Próstata , Masculino , Animales , Extractos Vegetales/farmacología , Ajo/química , Neoplasias de la Próstata/tratamiento farmacológico , Ratones , Antiinflamatorios/farmacología , Humanos , Próstata/efectos de los fármacos , Próstata/metabolismo , Próstata/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/prevención & control , Antioxidantes/farmacología , FN-kappa B/metabolismo , Lipopolisacáridos , Agua/química
5.
iScience ; 27(9): 110728, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39286494

RESUMEN

CombiVacS study has demonstrated a strong immune response of the heterologous ChAdOx1-S/BNT162b2 vaccine combination. The primary outcomes of the study were to assess the humoral immune response against SARS-CoV-2, 28 days after a third dose of a mRNA vaccine, in subjects that received a previous prime-boost scheme with ChAdOx1-S/BNT162b2. Secondary outcomes extended the study to 3 and 6 months. The third vaccine dose of mRNA-1273 in naive participants previously vaccinated with ChAdOx1-S/BNT162b2 regimen reached higher neutralizing antibodies titers against the variants of concern Delta and BA.1 lineage of Omicron compared with those receiving a third dose of BNT162b2 at day 28. These differences between BNT162b2 and mRNA-1273 arms were observed against the ancestral variant G614 at day 90. Suboptimal neutralizing response was observed against BQ.1.1, XBB.1.5/XBB.1.9, and JN.1 in a relevant proportion of individuals 180 days after the third dose, even after asymptomatic Omicron breakthrough infections. EudraCT (2021-001978-37); ClinicalTrials.gov (NCT04860739).

6.
PLoS Pathog ; 20(9): e1012529, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39241032

RESUMEN

Acinetobacter baumannii is an opportunistic nosocomial pathogen with high morbidity and mortality rates. Current treatment options for this pathogen are limited due to its increasing resistance to last-resort antibiotics. Despite A. baumannii's leading position in the World Health Organisations priority pathogens list, little is known about its virulence regulation. Through a high-throughput screening approach to identify novel biofilm regulators, we identified a previously uncharacterised predicted adenylate cyclase (AC), CavA, as a central regulator of this phenotype. cAMP is a crucial mediator of various aspects of bacterial physiology in other species but information about its role in A. baumannii is limited. We confirm that CavA AC is functional and synthesizes cAMP in A. baumannii. Using dRNA-seq, we verify that CavA is a negative biofilm formation regulator affecting Csu pili and exopolysaccharide production. We demonstrate for the first time that in A. baumannii, cAMP is atop of a hierarchical signalling cascade controlling inter- and intrabacterial signalling by modulating quorum sensing and cyclic di-GMP systems, ultimately governing virulence in vivo and adaptive antibiotic resistance. In contrast to the well-established paradigm in other bacteria where cAMP and cyclic di-GMP levels are inversely regulated, we uncover that the levels of these second messengers are directly proportional in A. baumannii. Overall, this study uncovers the central role of CavA and cAMP in the pathogenic success of A. baumannii and highlights this signalling cascade as a high potential target for novel therapeutic development.

7.
Atherosclerosis ; 398: 118589, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39277962

RESUMEN

BACKGROUND AND AIMS: Utilising real-world data, we quantified the burden of cardiovascular risk factors and long-term residual risk of atherothrombotic events among routine care cohorts with coronary (CAD) or peripheral (PAD) artery disease or ischemic stroke (IS) on guideline-recommended antiplatelet monotherapy (APMT). METHODS: Retrospective cohort study using data (2010-2020) from the United Kingdom Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics, including adults with CAD, PAD or IS who were first prescribed APMT (CAD/IS: aspirin; PAD: clopidogrel). Primary outcomes (recurrent events): major adverse cardiovascular events (MACE) for CAD/PAD/IS cohorts, major adverse limb events (MALE) for PAD. RESULTS: 266,478 CAD, 13,162 PAD, and 14,788 IS patients were included (mean age: 71 years; women 37.7%-47.5 %). Risk factor burden was high and attainment of recommended goals was low. There were 73,691, 3,121 and 7,137 MACE among CAD, PAD and IS patients, respectively (median follow-up: 89.9, 42.4 and 75.9 months, respectively), and 4,767 MALE among PAD patients. MACE incidence rate per 1000 person-years was higher in IS (268.7; 95%CI 265.3-272.0) than CAD (92.9; 95%CI 92.5-93.4) or PAD cohorts (97.2; 95%CI 94.6-99.8). MALE incidence rate was 195.9 (95%CI 192.2-199.6) per 1000 person-years. IS patients presented a lower rate of hospitalisations and longer time-to-first hospitalisation, but once hospitalised, they had a longer length-of-stay. PAD patients had the highest hospitalisation rate. CONCLUSIONS: Among a contemporary cohort with cardiovascular disease on APMT, long-term residual atherothrombotic risk remains high despite being on APMT. Greater attention to risk factor control and use of appropriate evidence-based therapy is required to reduce residual risk among this very high-risk population.

8.
Environ Res ; : 119989, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39278582

RESUMEN

Infancy is a period of continuous growth and development, where inadequate intake of essential elements and exposure to non-essential elements may have lifelong health consequences. Thus, the aim of this study is to evaluate the urine concentration of essential and non-essential elements as a proxy for internal exposure during the weaning period, from 3 to 18 months of age. The Nutrition in Early Life and Asthma (NELA) birth cohort generated the data for this study. Sociodemographic, dietary, and urine concentration of essential (Co, Cu, Mo, I, Fe, Mn, Se, Zn, and Ni) and non-essential elements (Al, V, As, Cd, Sb, Tl, and Pb) data were available for 490 participants at 3 months of age and 216 participants at 18 months of age. Paired urine samples at both time periods were available for 175 infants. At 3 months of age, exclusively breastfed infants had lower urine concentrations of Al, V, Fe, Co, Se, Sb, and Tl. Notably, the concentration of Mo had a median (IQR) of 0.60 (0.40-2.10) µg/L compared to a median (IQR) of 39.80 (25.00-56.40) µg/L observed in infants exclusively fed with formula. When we analyzed the change in urine elements concentrations between 3 and 18 months of age, we observed increased As (0.75 vs. 18.60 µg/L), Co (0.05 vs. 0.24 µg/L), Mo (1.98 vs. 50.0 µg/L), Pb (0.15 vs. 0.69 µg/L), Se (11.3 vs. 23.1 µg/L), Tl (0.02 vs. 0.11 µg/L), and V (0.05 vs. 0.11 µg/L). For Cu, lower urine concentrations were observed at 18 months of age in comparison with concentrations at 3 months (5.77 vs. 4.41 µg/L). Among the main food items identified as driving the changes in urine concentration between 3 and 18 months of age were white fish, rice and pasta, potato chips, custard, small blue fish, and legumes. Exclusively breastfed infants showed lower exposure to non-essential elements compared to those who were fed with a mixture or formula. With the introduction of solid foods, the exposure to some non-essential elements increased drastically, as in the case of As and Pb. In addition, exposure to the essential metal Mo also increased substantially with the introduction of solid food.

9.
Percept Mot Skills ; : 315125241278532, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39259972

RESUMEN

Perceptual-cognitive skills are crucial in successfully managing information and decision-making in sports, particularly in high-pressure environments. We examined 16 basketball referees' on-the-court visual search behavior by comparing referees of different experience levels (experienced, n = 8; and novice, n = 8) and different court positions. Participants' visual search behavior was analyzed during 20 live gameplay situations using eye-tracking technology. Dependent variables were the number of eye fixations, mean fixation time, and total fixation time on selected areas of interest; and independent variables were the referees' experience and visual angles (lead and trail referee positions). Experienced referees exhibited significantly lower total fixation time than novice referees (p = .009). Referees in the trail position showed more fixations of shorter duration and a greater focus on the basket than those in the lead position. Our findings suggest that the visual search behavior of basketball referees varies with their court position and experience. These data provide valuable insights into referees' complex visual search patterns in the real-game context, and they highlight the importance of considering viewing angle and experience in future research.

10.
Arch Med Res ; 56(1): 103073, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39260120

RESUMEN

BACKGROUND: The SARS-CoV-2 pandemic challenged health systems worldwide. In Mexico, the Public Health Incident Management Command (COISS) strategy was implemented to improve health care for patients with COVID-19 who required hospitalization. AIM: To evaluate the impact of the COISS strategy on case fatality rates (CFR) and years of life lost (YLL) in hospitalized patients with COVID-19. MATERIALS AND METHODS: The COISS strategy included eight actions implemented in states with high epidemic risk (COISS states). A secondary analysis of the public database from the Mexican Ministry of Health was performed considering patients with confirmed diagnoses of SARS-CoV-2 infection. The COISS strategy effectiveness was evaluated by its impact on in-hospital CFR and YLL at the beginning (T0) and end (T1) of the third wave, and at the end of the fourth wave (T2) and compared to states without intervention (non-COISS states). RESULTS: At T0, COISS states showed a higher CFR for hospitalized patients than non-COISS states, which decreased after the strategy implementation. After correction for baseline conditions, lower relative CFR at T1 and T2, compared to T0, and a protective effect in different age groups, especially in those ≥65 years, were found in hospitalized patients in COISS states. The COISS strategy was associated with lower CFR in hospitalized patients with COVID-19 at both T1 and T2. At T0, YLLs were higher in COISS states, but there were no significant differences at T1 and T2. CONCLUSIONS: COISS interventions effectively reduced CFR in hospitalized patients with COVID-19, providing protection to vulnerable patients and reducing the YLL gap.

11.
J Biol Chem ; : 107746, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39236875

RESUMEN

Mitochondria are central to cellular metabolism; hence, their dysfunction contributes to a wide array of human diseases. Cardiolipin, the signature phospholipid of the mitochondrion, affects proper cristae morphology, bioenergetic functions, and metabolic reactions carried out in mitochondrial membranes. To match tissue-specific metabolic demands, cardiolipin typically undergoes an acyl tail remodeling process with the final step carried out by the phospholipid-lysophospholipid transacylase tafazzin. Mutations in tafazzin are the primary cause of Barth syndrome. Here, we investigated how defects in cardiolipin biosynthesis and remodeling impacts metabolic flux through the TCA cycle and associated yeast pathways. Nuclear magnetic resonance was used to monitor in real-time the metabolic fate of 13C3-pyruvate in isolated mitochondria from three isogenic yeast strains. We compared mitochondria from a wild-type strain to mitochondria from a Δtaz1 strain that lacks tafazzin and contains lower amounts of unremodeled cardiolipin, and mitochondria from a Δcrd1 strain that lacks cardiolipin synthase and cannot synthesize cardiolipin. We found that the 13C-label from the pyruvate substrate was distributed through twelve metabolites. Several of the metabolites were specific to yeast pathways including branched chain amino acids and fusel alcohol synthesis. While most metabolites showed similar kinetics amongst the different strains, mevalonate concentrations were significantly increased in Δtaz1 mitochondria. Additionally, the kinetic profiles of α-ketoglutarate, as well as NAD+ and NADH measured in separate experiments, displayed significantly lower concentrations for Δtaz1 and Δcrd1 mitochondria at most time points. Taken together, the results show how cardiolipin remodeling influences pyruvate metabolism, tricarboxylic acid cycle flux, and the levels of mitochondrial nucleotides.

12.
Phys Rev Lett ; 133(8): 081401, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39241703

RESUMEN

We provide evidence for a correspondence between the formation of black holes and the stability of circular null geodesics around the collapsing perturbation. We first show that the critical threshold of the compaction function to form a black hole in radiation is well approximated by the critical threshold for the appearance of the first unstable circular orbit in a spherically symmetric background. We also show that the critical exponent in the scaling law of the primordial black hole mass close to the threshold is set by the inverse of the Lyapunov coefficient of the unstable orbits when a self-similar stage is developed close to criticality.

13.
Bioorg Chem ; 153: 107769, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39236582

RESUMEN

Promoting endogenous neurogenesis for brain repair is emerging as a promising strategy to mitigate the functional impairments associated with various neurological disorders characterized by neuronal death. Diterpenes featuring tigliane, ingenane, jatrophane and lathyrane skeletons, frequently found in Euphorbia plant species, are known protein kinase C (PKC) activators and exhibit a wide variety of pharmacological properties, including the stimulation of neurogenesis. Microbial transformation of these diterpenes represents a green and sustainable methodology that offers a hitherto little explored approach to obtaining novel derivatives and exploring structure-activity relationships. In the present study, we report the biotransformation of euphoboetirane A (4) and epoxyboetirane A (5), two lathyrane diterpenoids isolated from Euphorbia boetica, by Mucor circinelloides MC NRRL3631. Our findings revealed the production of nine biotransformation products (6-14), including jatrophane derivatives originated through an unprecedented rearrangement from the parent lathyranes. The chemical structures and absolute configurations of the new compounds were elucidated through comprehensive analysis using NMR and ECD spectroscopy, as well as MS. The study evaluated how principal metabolites and their derivatives affect TGFα and NRG1 release, as well as their potential to promote proliferation or differentiation in cultures of NSC isolated from the SVZ of adult mice. In order to shed some light on the mechanisms underlying the ability of 12 as a neurogenic compound, the interactions of selected compounds with PKC δ-C1B were analyzed through molecular docking and molecular dynamics. Based on these, it clearly appears that the ability of compound 12 to form both acceptor and donor hydrogen bonds with certain amino acid residues in the enzyme pocket leads to a higher affinity compound-PKC complex, which correlates with the observed biological activity.

14.
J Neuroeng Rehabil ; 21(1): 153, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39232831

RESUMEN

BACKGROUND: To overcome the application limitations of functional electrical stimulation (FES), such as fatigue or nonlinear muscle response, the combination of neuroprosthetic systems with robotic devices has been evaluated, resulting in hybrid systems that have promising potential. However, current technology shows a lack of flexibility to adapt to the needs of any application, context or individual. The main objective of this study is the development of a new modular neuroprosthetic system suitable for hybrid FES-robot applications to meet these needs. METHODS: In this study, we conducted an analysis of the requirements for developing hybrid FES-robot systems and reviewed existing literature on similar systems. Building upon these insights, we developed a novel modular neuroprosthetic system tailored for hybrid applications. The system was specifically adapted for gait assistance, and a technological personalization process based on clinical criteria was devised. This process was used to generate different system configurations adjusted to four individuals with spinal cord injury or stroke. The effect of each system configuration on gait kinematic metrics was analyzed by using repeated measures ANOVA or Friedman's test. RESULTS: A modular NP system has been developed that is distinguished by its flexibility, scalability and personalization capabilities. With excellent connection characteristics, it can be effectively integrated with robotic devices. Its 3D design facilitates fitting both as a stand-alone system and in combination with other robotic devices. In addition, it meets rigorous requirements for safe use by incorporating appropriate safety protocols, and features appropriate battery autonomy, weight and dimensions. Different technological configurations adapted to the needs of each patient were obtained, which demonstrated an impact on the kinematic gait pattern comparable to that of other devices reported in the literature. CONCLUSIONS: The system met the identified technical requirements, showcasing advancements compared to systems reported in the literature. In addition, it demonstrated its versatility and capacity to be combined with robotic devices forming hybrids, adapting well to the gait application. Moreover, the personalization procedure proved to be useful in obtaining various system configurations tailored to the diverse needs of individuals.


Asunto(s)
Robótica , Traumatismos de la Médula Espinal , Humanos , Robótica/instrumentación , Robótica/métodos , Traumatismos de la Médula Espinal/rehabilitación , Masculino , Rehabilitación de Accidente Cerebrovascular/instrumentación , Rehabilitación de Accidente Cerebrovascular/métodos , Fenómenos Biomecánicos , Terapia por Estimulación Eléctrica/instrumentación , Terapia por Estimulación Eléctrica/métodos , Marcha/fisiología , Persona de Mediana Edad , Femenino , Adulto , Prótesis Neurales , Diseño de Prótesis/métodos
15.
Artículo en Inglés | MEDLINE | ID: mdl-39252591

RESUMEN

BACKGROUND: Hemodynamic impact of commissural alignment (CA) with self-expandable transcatheter aortic valves (TAVR) has not been investigated yet. AIMS: To determine hemodynamic impact of CA with self-expandable TAVR. METHODS: Multicentric ambispective study comparing patients who underwent self-expandable TAVR in seven centers with the Evolut Pro/Pro+ (EP) (Medtronic) and Acurate neo2 (AN2) (Boston Scientific) with and without CA strategies. The degree of commissural misalignment (CMA) was assessed by computed tomography/angiography and 1-year transvalvular gradients/regurgitation evaluated by echocardiography. A matched comparison according to annular dimensions/eccentricity, prosthesis size/type, and baseline left ventricular function and gradients was performed. RESULTS: A total of 557 patients, mean age 80.7 ± 6.6 years, 61.4% men, and STS score of 4.3 ± 3.1% were analyzed. A CA technique was attempted in 215 patients (38.6%), including 113 patients with AN2 and 102 patients with EP. None/mild CMA was found in 158 (73.5% vs. 43.6% if no CA attempted, p < 0.001) with no differences between devices (AN2:75.2%; EP:71.6%, p = 0.545). Patients with moderate/severe CMA had a greater aortic peak gradient (22.3 ± 8.7 vs. 19.7 ± 8.5, p = 0.001), significantly greater progression of both peak (p = 0.002) and mean gradients (p = 0.001) after matching, and higher rate of central aortic regurgitation (1.2% vs. 0.4%, p = 0.005) at 1-year, but not a greater proportion of patients with mean gradient ≥ 10 mmHg. CONCLUSIONS: The use of CA strategies significantly reduced the rate of CMA for the self-expandable TAVR devices ACN2 and EP which was associated to lower transvalvular gradients and intra-prosthetic regurgitation progression at 1-year although no criteria of structural deterioration were met at this follow up. CLINICALTRIALS: org: NCT05097183.

16.
Eur J Pharm Sci ; 202: 106896, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39250981

RESUMEN

Recent advances in understanding Alzheimer's disease (AD) suggest the possibility of an infectious etiology, with Porphyromonas gingivalis emerging as a prime suspect in contributing to AD. P. gingivalis may invade systemic circulation via weakened oral/intestinal barriers and then cross the blood-brain barrier (BBB), reaching the brain and precipitating AD pathology. Based on the proposed links between P. gingivalis and AD, a prospective approach is the development of an oral nanovaccine containing P. gingivalis antigens for mucosal delivery. Targeting the gut-associated lymphoid tissue (GALT), the nanovaccine may elicit both mucosal and systemic immunity, thereby hampering P. gingivalis ability to breach the oral/intestinal barriers and the BBB, respectively. The present study describes the optimization, characterization, and in vitro evaluation of a candidate chitosan-coated poly(lactic-co-glycolic acid) (PLGA-CS) nanovaccine containing a P. gingivalis antigen extract. The nanocarrier was prepared using the double emulsion solvent evaporation method and optimized for selected experimental factors, e.g. PLGA amount, surfactant concentration, w1/o phase ratio, applying a d-optimal statistical design to target the desired physicochemical criteria for its intended application. After nanocarrier optimization, the nanovaccine was characterized in terms of particle size, polydispersity index (PdI), ζ-potential, encapsulation efficiency (EE), drug loading (DL), morphology, and in vitro release profile, as well as for mucoadhesivity, stability under simulated gastrointestinal conditions, antigen integrity, in vitro cytotoxicity and uptake using THP-1 macrophages. The candidate PLGA-CS nanovaccine demonstrated appropriate physicochemical, mucoadhesive, and antigen release properties for oral delivery, along with acceptable levels of EE (55.3 ± 3.5 %) and DL (1.84 ± 0.12 %). The integrity of the encapsulated antigens remained uncompromised throughout NPs production and simulated gastrointestinal exposure, as confirmed by SDS-PAGE and Western blotting analyses. Furthermore, the nanovaccine showed effective in vitro uptake, while exhibiting low cytotoxicity. Taken together, these findings underscore the potential of PLGA-CS NPs as carriers for adequate antigen mucosal delivery, paving the way for further investigations into their applicability as vaccine candidates against P. gingivalis.

17.
Artículo en Inglés | MEDLINE | ID: mdl-39259377

RESUMEN

This study investigates the postbiotic potential of extracellular products (ECPs) from Bacillus pumilus strains cultivated on microalgae-supplemented media. We assessed enzymatic and antimicrobial activities to select ECPs that enhance the digestive processes in gilthead seabream. Additionally, we explored the in vitro enzymatic capacity of the chosen postbiotics to hydrolyze macromolecules in microalgae. Finally, a feeding trial was conducted to determine the in vivo effects of the ECPs on Sparus aurata. In vitro enzymatic assays demonstrated diverse hydrolytic capacities among ECPs. All conditions exhibited antimicrobial activity against Photobacterium damselae subsp. piscicida, with variation in inhibitory effects against Vibrio harveyi and Tenacibaculum maritimum. Furthermore, in vitro assays revealed differences in protein hydrolysis and soluble protein concentration, influencing amino acid and reducing sugar release from microalgal biomass. These analyses facilitated a selection to test ECPs in vivo. Lastly, the in vivo experiment revealed no differences in the growth performance, nutrient utilization, and general metabolism of S. aurata fed the experimental diets. Dietary inclusion of postbiotics increased the activity of key digestive enzymes in fish compared to the control group, and particularly, values increased significantly when the fish were fed with the ECP-nanoparticulate-supplemented diet. In conclusion, the inclusion of microalgae in the culture media significantly influences the activity of extracellular products from B. pumilus strains, as evidenced in both in vitro and in vivo assays.

18.
Front Plant Sci ; 15: 1430695, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39114470

RESUMEN

Background: Seeds of woody plant species, such as those in the Acer genus like Norway maple (Acer platanoides L.) and sycamore (Acer pseudoplatanus L.), exhibit unique physiological traits and responses to environmental stress. Thioredoxins (Trxs) play a central role in the redox regulation of cells, interacting with other redox-active proteins such as peroxiredoxins (Prxs), and contributing to plant growth, development, and responses to biotic and abiotic stresses. However, there is limited understanding of potential variations in this system between seeds categorized as recalcitrant and orthodox, which could provide insights into adaptive strategies. Methods: Using proteomic analysis and DDA methods we investigated the Trx-h1 target proteins in seed axes. We complemented the results of the proteomic analysis with gene expression analysis of the Trx-h1, 1-Cys-Prx, and TrxR NTRA genes in the embryonic axes of maturing, mature, and stored seeds from two Acer species. Results and discussion: The expression of Trx-h1 and TrxR NTRA throughout seed maturation in both species was low. The expression of 1-Cys-Prx remained relatively stable throughout seed maturation. In stored seeds, the expression levels were minimal, with slightly higher levels in sycamore seeds, which may confirm that recalcitrant seeds remain metabolically active during storage. A library of 289 proteins interacting with Trx-h1 was constructed, comprising 68 from Norway maple and 221 from sycamore, with distinct profiles in each seed category. Recalcitrant seed axes displayed a wide array of metabolic, stress response, and signaling proteins, suggesting sustained metabolic activity during storage and the need to address oxidative stress. Conversely, the orthodox seed axes presented a protein profile, reflecting efficient metabolic shutdown, which contributes to their extended viability. The results of the study provide new insights into seed viability and storage longevity mechanisms. They enhance the understanding of seed biology and lay the foundation for further evolutionary research on seeds of different categories.

19.
Sci Technol Adv Mater ; 25(1): 2342232, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39104602

RESUMEN

FeMnAl steels are currently generating a lot of interest with potential applications for structural parts in armored vehicles due to their lower density and outstanding mechanical properties. Despite the extensive mechanical performance and heat treatment exploration of this alloy class, further weldability investigation is required for future large-scale deployment. In the present study, the liquation cracking of four heats of cast FeMnAl alloys was investigated by the spot-Varestraint technique. The study focuses primarily on the effect of the major elements of the FeMnAl system: C, Mn and Al. Optical and electron microscopy were employed to investigate the microstructural features, and CALPHAD was employed to aid the discussion regarding the alloy's composition differences and their effect on the liquation cracking susceptibility. The study was able to identify that compositions with the higher Mn, C, and lower Al presented the highest liquation cracking susceptibility. Conversely, composition presenting lower Mn, C, and Al showed the most resistant behavior. Furthermore, lower Al content promoted a fully-γ microstructure at low temperatures, which encouraged the appearance of longer cracks as a γ-matrix is more susceptible to HAZ cracking than a fully ferritic (α) or duplex (α + γ) microstructure.


The present manuscript indicates that FeMnAl steels are susceptible to liquation cracking for alloys with higher Mn, C, and lower Al.

20.
Ecol Evol ; 14(8): e70113, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39165544

RESUMEN

Mimicry, that is, the imitation of any unpalatable or defensive species by another, has been of central interest to evolutionary research since Darwin's lifetime. Two ant species, Camponotus guanchus Santschi, 1908 and Crematogaster alluaudi Emery, 1893, endemic to the Canary Islands, occur in two color-morphs: While the head of workers is always reddish and the gaster blackish, the mesosoma (inclusive waist) is either fully reddish or fully blackish. In addition to the obvious morphological and coloration similarities, we provide evidence of mimicry: (i) Ca. guanchus was found only within the area of Cr. alluaudi. (ii) Color morphs are geographically non-randomly distributed: Workers of both species from 16 localities of syntopic occurrences shared in eight cases a blackish and in eight cases a reddish mesosoma. Hence, Ca. guanchus mimics both local color-morphs of Cr. alluaudi. We consider a fascinating analogy with the Mediterranean mimicry system in Camponotus lateralis (Olivier, 1792) and its model species of the Crematogaster scutellaris (Olivier, 1792) group on an island scale. Additionally, we present two endemic bug species, Perenotus stysi (Ribes et al., 2008) and P. malobae Roca-Cusachs & Goula, 2016, as mimics of those Cr. alluaudi workers having a reddish mesosoma. Our distribution, coloration, frequency, and behavioral data as well as the analogy with Ca. lateralis and the Cr. scutellaris group suggest a Batesian-mimicry system in which Ca. guanchus, Perenotus stysi, and P. malobae mimic the unpalatable and aggressive Cr. alluaudi as an antipredator adaptation.

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