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1.
Foods ; 13(17)2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39272607

RESUMEN

Meat products containing Vitamin D3 (VD3) are an innovative option that could contribute to reducing deficiencies in this micronutrient. Designing nanoemulsions that carry VD3 is the first step in developing functional meat products. Thereby, this study investigated the impact of food components on the nanoemulsion properties. A central composite design was used to study the effects of pea protein (PP, 0.5-2.5%), safflower oil (SO, 5-15%), and salt (0-0.5%) on the nanoemulsion stability (ζ-potential and particle size) and the VD3 retention. Also, the optimized nanoemulsion carrying VD3 was incorporated into a meat matrix to study its retention after cooking. The combination of food components in the optimized nanoemulsion were SO = 9.12%, PP = 1.54%, and salt content = 0.4%, resulting in the predicted values of ζ-potential, particle size, and VD3 retention of -37.76 mV, 485 nm, and 55.1%, respectively. The VD3 that was nanoencapsulated and included in a meat product remained more stable after cooking than the VD3 that was not encapsulated. If a meat product is formulated with 5 or 10% safflower oil, the stability of the nanoencapsulated VD3 is reduced. This research contributes to developing functional meat products carrying nanoencapsulated vitamin D3 in natural food-grade components.

2.
Pharmaceutics ; 16(8)2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39204362

RESUMEN

Over the last decade, scientists have shifted their focus to the development of smart carriers for the delivery of chemotherapeutics in order to overcome the problems associated with traditional chemotherapy, such as poor aqueous solubility and bioavailability, low selectivity and targeting specificity, off-target drug side effects, and damage to surrounding healthy tissues. Nanofiber-based drug delivery systems have recently emerged as a promising drug delivery system in cancer therapy owing to their unique structural and functional properties, including tunable interconnected porosity, a high surface-to-volume ratio associated with high entrapment efficiency and drug loading capacity, and high mass transport properties, which allow for controlled and targeted drug delivery. In addition, they are biocompatible, biodegradable, and capable of surface functionalization, allowing for target-specific delivery and drug release. One of the most common fiber production methods is electrospinning, even though the relatively two-dimensional (2D) tightly packed fiber structures and low production rates have limited its performance. Forcespinning is an alternative spinning technology that generates high-throughput, continuous polymeric nanofibers with 3D structures. Unlike electrospinning, forcespinning generates fibers by centrifugal forces rather than electrostatic forces, resulting in significantly higher fiber production. The functionalization of nanocarriers on nanofibers can result in smart nanofibers with anticancer capabilities that can be activated by external stimuli, such as light. This review addresses current trends and potential applications of light-responsive and dual-stimuli-responsive electro- and forcespun smart nanofibers in cancer therapy, with a particular emphasis on functionalizing nanofiber surfaces and developing nano-in-nanofiber emerging delivery systems for dual-controlled drug release and high-precision tumor targeting. In addition, the progress and prospective diagnostic and therapeutic applications of light-responsive and dual-stimuli-responsive smart nanofibers are discussed in the context of combination cancer therapy.

3.
Sensors (Basel) ; 24(5)2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38474967

RESUMEN

This paper presents the integration of a sensing layer over interdigitated electrodes and an electronic circuit on the same flexible printed circuit board. This integration provides an effective technique to use this design as a wearable gas measuring system in a target application, exhibiting high performance, low power consumption, and being lightweight for on-site monitoring. The wearable system proves the concept of using an NFC tag combined with a chemoresistive gas sensor as a cumulative gas sensor, having the possibility of holding the data for a working day, and completely capturing the exposure of a person to NO2 concentrations. Three different types of sensors were tested, depositing the sensing layers on gold electrodes over Kapton substrate: bare graphene, graphene decorated with 5 wt.% zinc oxide nanoflowers, or nanopillars. The deposited layers were characterized using FESEM, EDX, XRD, and Raman spectroscopy to determine their crystalline structure, morphological and chemical compositions. The gas sensing performance of the sensors was analyzed against NO2 (dry and humid conditions) and other interfering species (dry conditions) to check their sensitivity and selectivity. The resultant-built wearable NFC tag system accumulates the data in a non-volatile memory every minute and has an average low power consumption of 24.9 µW in dynamic operation. Also, it can be easily attached to a work vest.

4.
Molecules ; 29(3)2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38338380

RESUMEN

In recent years, nanocarriers have played an ever-increasing role in clinical and biomedical applications owing to their unique physicochemical properties and surface functionalities. Lately, much effort has been directed towards the development of smart, stimuli-responsive nanocarriers that are capable of releasing their cargos in response to specific stimuli. These intelligent-responsive nanocarriers can be further surface-functionalized so as to achieve active tumor targeting in a sequential manner, which can be simply modulated by the stimuli. By applying this methodological approach, these intelligent-responsive nanocarriers can be directed to different target-specific organs, tissues, or cells and exhibit on-demand controlled drug release that may enhance therapeutic effectiveness and reduce systemic toxicity. Light, an external stimulus, is one of the most promising triggers for use in nanomedicine to stimulate on-demand drug release from nanocarriers. Light-triggered drug release can be achieved through light irradiation at different wavelengths, either in the UV, visible, or even NIR region, depending on the photophysical properties of the photo-responsive molecule embedded in the nanocarrier system, the structural characteristics, and the material composition of the nanocarrier system. In this review, we highlighted the emerging functional role of light in nanocarriers, with an emphasis on light-responsive liposomes and dual-targeted stimuli-responsive liposomes. Moreover, we provided the most up-to-date photo-triggered targeting strategies and mechanisms of light-triggered drug release from liposomes and NIR-responsive nanocarriers. Lastly, we addressed the current challenges, advances, and future perspectives for the deployment of light-responsive liposomes in targeted drug delivery and therapy.


Asunto(s)
Nanopartículas , Neoplasias , Humanos , Liposomas/uso terapéutico , Portadores de Fármacos/química , Nanopartículas/química , Sistemas de Liberación de Medicamentos , Neoplasias/tratamiento farmacológico
5.
Nat Commun ; 14(1): 8070, 2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38057312

RESUMEN

Dung removal by macrofauna such as dung beetles is an important process for nutrient cycling in pasturelands. Intensification of farming practices generally reduces species and functional diversity of terrestrial invertebrates, which may negatively affect ecosystem services. Here, we investigate the effects of cattle-grazing intensification on dung removal by dung beetles in field experiments replicated in 38 pastures around the world. Within each study site, we measured dung removal in pastures managed with low- and high-intensity regimes to assess between-regime differences in dung beetle diversity and dung removal, whilst also considering climate and regional variations. The impacts of intensification were heterogeneous, either diminishing or increasing dung beetle species richness, functional diversity, and dung removal rates. The effects of beetle diversity on dung removal were more variable across sites than within sites. Dung removal increased with species richness across sites, while functional diversity consistently enhanced dung removal within sites, independently of cattle grazing intensity or climate. Our findings indicate that, despite intensified cattle stocking rates, ecosystem services related to decomposition and nutrient cycling can be maintained when a functionally diverse dung beetle community inhabits the human-modified landscape.


Asunto(s)
Escarabajos , Ecosistema , Animales , Bovinos , Biodiversidad , Clima , Granjas , Heces
6.
Front Oncol ; 13: 1155244, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37588099

RESUMEN

Background and objective: Neoadjuvant chemotherapy (NAC) followed by cystectomy is the standard of care in muscle-invasive bladder cancer (MIBC). Pathological response has been associated with longer survival, but no currently available clinicopathological variables can identify patients likely to respond, highlighting the need for predictive biomarkers. We sought to identify a predictive signature of response to NAC integrating clinical score, taxonomic subtype, and gene expression. Material and methods: From 1994 to 2014, pre-treatment tumor samples were collected from MIBC patients (stage T2-4N0/+M0) at two Spanish hospitals. A clinical score was determined based on stage, hydronephrosis and histology. Taxonomic subtypes (BASQ, luminal, and mixed) were identified by immunohistochemistry. A custom set of 41 genes involved in DNA damage repair and immune response was analyzed in 84 patients with the NanoString nCounter platform. Genes related to pathological response were identified by LASSO penalized logistic regression. NAC consisted of cisplatin/methotrexate/vinblastine until 2000, after which most patients received cisplatin/gemcitabine. The capacity of the integrated signature to predict pathological response was assessed with AUC. Overall survival (OS) and disease-specific survival (DSS) were analyzed with the Kaplan-Meier method. Results: LASSO selected eight genes to be included in the signature (RAD51, IFNγ, CHEK1, CXCL9, c-MET, KRT14, HERC2, FOXA1). The highest predictive accuracy was observed with the inclusion in the model of only three genes (RAD51, IFNɣ, CHEK1). The integrated clinical-taxonomic-gene expression signature including these three genes had a higher predictive ability (AUC=0.71) than only clinical score plus taxonomic subtype (AUC=0.58) or clinical score alone (AUC=0.56). This integrated signature was also significantly associated with OS (p=0.02) and DSS (p=0.02). Conclusions: We have identified a predictive signature for response to NAC in MIBC patients that integrates the expression of three genes with clinicopathological characteristics and taxonomic subtypes. Prospective studies to validate these results are ongoing.

8.
Microorganisms ; 11(6)2023 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-37375052

RESUMEN

Tar spot disease in corn, caused by Phyllachora maydis, can reduce grain yield by limiting the total photosynthetic area in leaves. Stromata of P. maydis are long-term survival structures that can germinate and release spores in a gelatinous matrix in the spring, which are thought to serve as inoculum in newly planted fields. In this study, overwintered stromata in corn leaves were collected in Central Illinois, surface sterilized, and caged on water agar medium. Fungi and bacteria were collected from the surface of stromata that did not germinate and showed microbial growth. Twenty-two Alternaria isolates and three Cladosporium isolates were collected. Eighteen bacteria, most frequently Pseudomonas and Pantoea species, were also isolated. Spores of Alternaria, Cladosporium, and Gliocladium catenulatum (formulated as a commercial biofungicide) reduced the number of stromata that germinated compared to control untreated stromata. These data suggest that fungi collected from overwintered tar spot stromata can serve as biological control organisms against tar spot disease.

9.
Pathogens ; 12(2)2023 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-36839564

RESUMEN

Chagas disease, caused by Trypanosoma cruzi infections, is included in the group of neglected diseases, and efforts to develop new therapeutic or immunoprevention approaches have not been successful. After the publication of the T. cruzi genome, the number of molecular and biochemical studies on this parasite has increased considerably, many of which are focused on families of variant surface proteins, especially trans-sialidases, mucins, and mucin-associated proteins. The disperse gene protein 1 family (DGF-1) is one of the most abundant families in the T. cruzi genome; however, the large gene size, high copy numbers, and low antibody titers detected in infected humans make it an unattractive study target. However, here we argue that given the ubiquitous presence in all T. cruzi species, and physicochemical characteristics, the DGF-1 gene family may play and important role in host-parasite interactions.

10.
ACS Infect Dis ; 9(3): 582-592, 2023 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-36780430

RESUMEN

The oral transmission of Chagas disease (oCD) in Venezuela announced its appearance in 2007. Different from other populations affected by oCD and despite close supervision during treatment with nitroheterocyclic drugs, the result was treatment failure. We studied genetic features of natural bloodstream parasite populations and populations after treatment of nine patients of this outbreak. In total, we studied six hemoculture isolates, eight Pre-Tx blood samples, and 17 samples collected at two or three Post-Tx time-points between 2007 and 2015. Parasitic loads were determined by quantitative polymerase chain reaction (qPCR), and discrete typing units (DTU), minicircle signatures, and Tcntr-1 gene sequences were searched from blood samples and hemocultures. Half-maximal inhibitory concentration (IC50) values were measured from the hemocultures. All patients were infected by TcI. Significant decrease in parasitic loads was observed between Pre-Tx and Post-Tx samples, suggesting the evolution from acute to chronic phase of Chagas disease. 60% of intra-DTU-I variability was observed between Pre-Tx and Post-Tx minicircle signatures in the general population, and 43 single-nucleotide polymorphisms (SNPs) were detected in a total of 12 Tcntr-1 gene sequences, indicative of a polyclonal source of infection. SNPs in three post-Tx samples produced stop codons giving rise to putative truncated proteins or displaced open reading frames, which would render resistance genes. IC50 values varied from 5.301 ± 1.973 to 104.731 ± 4.556 µM, demonstrating a wide range of susceptibility. The poor drug response in the Pre-Tx parasite populations may be associated with the presence of naturally resistant parasite clones. Therefore, any information that can be obtained on drug susceptibility from in vitro assays, in vivo assays, or molecular characterization of natural populations of Trypanosoma cruzi becomes essential when therapeutic guidelines are designed in a given geographical area.


Asunto(s)
Enfermedad de Chagas , Trypanosoma cruzi , Humanos , Trypanosoma cruzi/genética , Venezuela/epidemiología , Genotipo , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/epidemiología , Enfermedad de Chagas/parasitología , Brotes de Enfermedades , Inmunidad Innata
11.
Cytokine ; 162: 156104, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36493630

RESUMEN

AIMS: Cigarette smoke often induces pulmonary and systemic inflammation. In animal models, mesenchymal stem cells (MSC) tend to ameliorate these effects. We aimed to explore the local and systemic expression of cytokines in guinea pigs chronically exposed to cigarette smoke, and their modifications by MSC. MAIN METHODS: Concentrations of IL-1ß, IL-6, IL-8, IL-12, TNF-α, INF-É£, TSG-6, MMP-9, TIMP-1, and/or TIMP-2 in serum and bronchoalveolar lavage (BALF) from animals exposed to tobacco smoke (20 cigarettes/day, 5 days/week for 10 weeks) were determined, and mRNA expression of some of them was measured in lung tissue. Intratracheal instillation of allogeneic bone marrow MSC (5x106 cells in 1 ml) was done at week 2. KEY FINDINGS: After cigarette smoke, IL-6 and IFN-γ increased in serum and BALF, while IL-1ß and IL-12 decreased in serum, and TSG-6 and TIMP-2 increased in BALF. IL-1ß had a paradoxical increase in BALF. MSC had an almost null effect in unexposed animals. The intratracheal administration of MSC in guinea pigs exposed to cigarette smoke was associated with a statistically significant decrease of IL-12 and TSG-6 in serum, as well as a decrease of IL-1ß and IFN-γ and an increase in TIMP-1 in BALF. Concerning mRNA expression in lung tissue, cigarette smoke did not modify the relative amount of the studied transcripts, but even so, MSC decreased the IL-12 mRNA and increased the TIMP-1 mRNA. SIGNIFICANCE: A single intratracheal instillation of MSC reduces the pulmonary and systemic proinflammatory pattern induced by chronic exposure to cigarette smoke in guinea pigs. TRIAL REGISTRATION: Not applicable.


Asunto(s)
Fumar Cigarrillos , Células Madre Mesenquimatosas , Cobayas , Animales , Citocinas/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Inhibidor Tisular de Metaloproteinasa-2 , Interleucina-6/farmacología , Fumar Cigarrillos/efectos adversos , Pulmón/metabolismo , Interleucina-12/farmacología , ARN Mensajero , Células Madre Mesenquimatosas/metabolismo , Líquido del Lavado Bronquioalveolar
12.
Clin Biochem ; 109-110: 98-101, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36130631

RESUMEN

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a multisystem and progressive neurodegenerative mitochondrial disease, caused by point nucleotide changes in the mtDNA where 80 % of cases have the mutation m.3243A>G in the MT-TL1 gene. In this work, we described the clinical, biochemical and molecular analysis of three Venezuelan patients affected with MELAS syndrome. All cases showed lactic acidosis, cortical cerebral atrophy on magnetic resonance imaging and muscular system deficit, and in two of the cases alteration of urine organic acid levels was also registered. A screening for the mutation m.3243A>G in different patients' body samples confirmed the presence of this mutation with variable degrees of heteroplasmy (blood = 7-41 %, buccal mucosa = 14-53 %, urine = 58-94 %). The mitochondrial haplogroups for the three patients were different (H, C1b, and A2), indicating an independent origin for the mutation.


Asunto(s)
Acidosis Láctica , Síndrome MELAS , Humanos , ADN Mitocondrial/genética , Síndrome MELAS/genética , Síndrome MELAS/diagnóstico , Mutación , Venezuela
13.
Life Sci Alliance ; 5(12)2022 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-36171140

RESUMEN

Synthetic directed evolution via localized sequence diversification and the simultaneous application of selection pressure is a promising method for producing new, beneficial alleles that affect traits of interest in diverse species; however, this technique has rarely been applied in plants. Here, we designed, built, and tested a chimeric fusion of T7 RNA Polymerase (RNAP) and deaminase to enable the localized sequence diversification of a target sequence of interest. We tested our T7 RNAP-DNA base editor in <i>Nicotiana benthamiana</i> transient assays to target a transgene expressing <i>GFP</i> under the control of the T7 promoter and observed C-to-T conversions. We then targeted the T7 promoter-driven <i>acetolactate synthase</i> sequence that had been stably integrated in the rice genome and generated C-to-T and G-to-A transitions. We used herbicide treatment as selection pressure for the evolution of the <i>acetolactate synthase</i> sequence, resulting in the enrichment of herbicide-responsive residues. We then validated these herbicide-responsive regions in the transgenic rice plants. Thus, our system could be used for the continuous synthetic evolution of gene functions to produce variants with improved herbicide resistance.


Asunto(s)
Acetolactato Sintasa , Herbicidas , Oryza , Acetolactato Sintasa/genética , ADN , ARN Polimerasas Dirigidas por ADN , Resistencia a los Herbicidas/genética , Herbicidas/farmacología , Oryza/genética , Proteínas Virales
14.
J Anim Sci Technol ; 64(2): 274-290, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35530412

RESUMEN

This study was conducted to evaluate the effect of ferulic acid (FA) and clinoptilolite (CTL) supplementation on the growth performance, carcass characteristics, and meat quality of hair-breed lambs. Twenty-eight Kathadin male lambs (33.72 ± 3.4 kg) were randomly allocated to one of the four diets (n=7) under a 2 × 2 factorial arrangement to evaluate the effect of FA (0 or 300 ppm) and CTL (0% or 1%) during the last 40 days of the finishing phase. No interaction between additives was shown for growth performance, carcass characteristics and meat quality, with exception of the fatty acid profile (p < 0.05). FA reduced feed intake and carcass conformation (p < 0.05). Wholesale cuts were not affected by FA or CTL (p > 0.05). The L*, a*, and C* color parameters and some intramuscular fatty acids of the longissimus thoracis muscle were positively modified by CTL supplementation (p < 0.05). While there was no FA × CTL interaction, each additive could be used individually in animal nutrition to improve the feedlot performance and meat quality of the lambs.

15.
Anal Chem ; 94(6): 2785-2793, 2022 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-35102738

RESUMEN

Imaging techniques based on mass spectrometry or spectroscopy methods inform in situ about the chemical composition of biological tissues or organisms, but they are sometimes limited by their specificity, sensitivity, or spatial resolution. Multimodal imaging addresses these limitations by combining several imaging modalities; however, measuring the same sample with the same preparation using multiple imaging techniques is still uncommon due to the incompatibility between substrates, sample preparation protocols, and data formats. We present a multimodal imaging approach that employs a gold-coated nanostructured silicon substrate to couple surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) and surface-enhanced Raman spectroscopy (SERS). Our approach integrates both imaging modalities by using the same substrate, sample preparation, and data analysis software on the same sample, allowing the coregistration of both images. We transferred molecules from clean fingertips and fingertips covered with plasticine modeling clay onto our nanostructure and analyzed their chemical composition and distribution by SALDI-MS and SERS. Multimodal analysis located the traces of plasticine on fingermarks and provided chemical information on the composition of the clay. Our multimodal approach effectively combines the advantages of mass spectrometry and vibrational spectroscopy with the signal enhancing abilities of our nanostructured substrate.


Asunto(s)
Nanoestructuras , Oro , Silicio/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Análisis Espectral
16.
Neurol Sci ; 43(6): 3923-3928, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35067827

RESUMEN

INTRODUCTION: Twenty percent of patients with Guillain-Barré syndrome (GBS) have poor outcomes despite proper management. The aim of the study was to characterize electrophysiological factors related to poor outcome in patients with GBS. METHODS: We conducted an observational study from a prospective cohort of 91 patients with GBS in a tertiary healthcare center in Mexico, from 2017 to 2019. Demographics and nerve conduction studies were performed on admission, and a 3-month follow-up for GBS disability score was ensued, allocating patients in good (GBS disability score ≤ 2) and poor outcome (GBS disability score ≥ 3) groups. A logistic regression analysis for independent walk at 3 months was performed. Kaplan-Meier estimator curves for independent walk in very low (< 20% LLN) and low-normal ( ≥20% LLN) peroneal nerve CMAPs are presented. RESULTS: From the 91 GBS patients included, 37 (40.6%) did not regain independent walk at 3 months. Axonal variants were more common in the poor outcome group (31.4% vs 59.4%, p = 0.01) as well as AIDP variants with motor conduction block (6.6% vs 42.4%, p = 0.018). Univariable analysis was statistically significant for very low median, ulnar, tibial, and peroneal CMAP amplitudes in poor outcome patients; however, multivariable analysis was only significant for very low peroneal nerve CMAP amplitude (OR 3.6 [1.1-11.5, p = 0.024]). Conversely, a greater proportion of GBS patients with low-normal CMAPs recovered independent walk at 90 days (75% vs 30%, p < 0.001). CONCLUSION: Severe axonal injury of the peroneal nerve, axonal, and AIDP with motor conduction block variants predicts worse functional outcome regarding independent walk at 3 months.


Asunto(s)
Síndrome de Guillain-Barré , Nervio Peroneo , Potenciales de Acción , Humanos , Músculos , Conducción Nerviosa/fisiología , Estudios Prospectivos
17.
Biology (Basel) ; 11(1)2022 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-35053067

RESUMEN

The aim was to determine if players with a prior hamstring strain injury (HSI) exhibit bilateral deficits in knee flexor eccentric strength and hamstring muscle volume and differences in sprinting performance compared with players without a history of HSIs. Forty-six male professional soccer players participated in this study. Eccentric knee flexor strength, hamstring muscle volume (MRI), and a 20-m running sprint test (5- and 10-m split time) were assessed at the start of the preseason. Eccentric knee strength of the previously injured limbs of injured players was greater (ES: 1.18-1.36) than the uninjured limbs in uninjured players. Previously injured limbs showed possibly larger biceps femoris short heads (BFSh) and likely semitendinosus (ST) muscle volumes than the contralateral uninjured limbs among the injured players (ES: 0.36) and the limbs of the uninjured players (ES: 0.56), respectively. Players who had experienced a previous HSI were possibly slower in the 5-m (small ES: 0.46), while unclear differences were found in both the 10-m and 20-m times. Players with a prior HSI displayed greater eccentric knee flexor strength, possibly relatively hypertrophied ST and BFSh muscles, and possibly reduced 5-m sprinting performances than previously uninjured players. This can have implication for the design of secondary hamstring muscle injury prevention strategies.

18.
Cancers (Basel) ; 13(24)2021 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-34944855

RESUMEN

In the phase II MAJA trial, maintenance therapy with vinflunine resulted in longer progression-free survival compared to best supportive care in advanced urothelial cell carcinoma (aUCC) patients who did not progress after first-line platinum-based chemotherapy. However, despite an initial benefit observed in some patients, unequivocal resistance appears which underlying mechanisms are presently unknown. We have performed gene expression and functional enrichment analyses to shed light on the discovery of these underlying resistance mechanisms. Differential gene expression profile of eight patients with poor outcome and nine with good outcome to vinflunine administered in the MAJA trial were analyzed. RNA was isolated from tumor tissue and gene expression was assessed by microarray. Differential expression was determined with linear models for microarray data. Gene Set Enrichment Analysis (GSEA) was used for the functional classification of the genes. In vitro functional studies were performed using UCC cell lines. Hierarchical clustering showed a differential gene expression pattern between patients with good and poor outcome to vinflunine treatment. GSEA identified epithelial-to-mesenchymal transition (EMT) as the top negatively enriched hallmark in patients with good outcome. In vitro analyses showed that the polyphenol curcumin downregulated EMT markers and sensitized UCC cells to vinflunine. We conclude that EMT mediates resistance to vinflunine and suggest that the reversion of this process could enhance the effect of vinflunine in aUCC patients.

19.
Rev. biol. trop ; 69(4)dic. 2021.
Artículo en Español | LILACS, SaludCR | ID: biblio-1387689

RESUMEN

Resumen Introducción: Para incrementar el número de crías de tortugas marinas, es necesario mejorar estrategias de conservación, como incubación de nidos, en condiciones de vivero que contrarresten los efectos de las condiciones climáticas extremas. Objetivo: Comparar cinco parámetros de éxito reproductivo (éxito de eclosión, huevos sin desarrollo aparente, crías muertas, mortalidad embrionaria y período de incubación) de la tortuga marina Lepidochelys olivacea. Métodos: Se evaluó la incubación de nidos bajo dos períodos de reubicación de nidos (P1 ~28.8 °C agosto-septiembre y P2 ~27.1 °C octubre-noviembre, temperatura ambiental promedio, bajo condiciones de vivero, en el 2018 en Guerrero, México. Resultados: Se encontraron diferencias significativas en el éxito de eclosión y la mortalidad embrionaria entre los períodos de reubicación de nidos (P < 0.001). En P1, se observaron valores más bajos de éxito de eclosión (77.0 % P1 vs 88.6 % P2) y valores más altos de mortalidad embrionaria (13.7 % P1 vs 3.3 % P2) comparados con los de P2. Es importante señalar que, en el presente estudio la mortalidad embrionaria se presentó en una etapa tardía de desarrollo, es decir, en embriones casi completamente desarrollados. No se encontraron diferencias entre periodos respecto a los parámetros de huevos sin desarrollo aparente, crías muertas y período de incubación. Conclusiones: Las diferencias entre las condiciones ambientales durante el primer período de reubicación de nidos en comparación con el segundo período parecen afectar el éxito de eclosión y mortalidad embrionaria de L. olivacea. Por lo tanto, es importante tomar medidas al respecto durante esta etapa de incubación para tratar de mejorar la incubación de nidos bajo condiciones de vivero.


Abstract Introduction: In order to increase the number of sea turtle hatchlings, it is necessary to improve conservation strategies, such as nest incubation in hatchery conditions that counteract the effects of extreme climatic conditions. Objective: To compare five reproductive success parameters (hatching success, eggs with no apparent embryonic development, dead hatchlings, embryonic mortality, and incubation period) of the sea turtle Lepidochelys olivacea. Methods: The incubation of nests was evaluated under two periods of nest relocation, P1 ~28.8 °C (August and September) and P2 ~27.1 °C (October and November), average ambient temperature, under hatchery condition, in 2018 in Guerrero, Mexico. Results: Significant differences were found in hatching success and embryonic mortality between nest relocation periods (P < 0.001). In P1, lower values of hatching success (77.0 % P1 vs 88.6 % P2) and higher values of embryonic mortality (13.7 % P1 vs 3.3 % P2) were observed compared to those of P2. It's important pointing that, in the present study, embryonic mortality occurred at a late stage of development, that is, in almost fully developed embryos. No differences were found between periods regarding the parameters eggs with no apparent embryonic development, dead hatchlings and incubation period. Conclusions: The differences between the environmental conditions during the first period of nest relocation compared to the second period, respectively, seem to affect the hatching success and embryonic mortality of L. olivacea. Therefore, it is important to take action on this issue during this incubation stage to try to improve the incubation of nests under hatchery conditions.


Asunto(s)
Animales , Reproducción , Tortugas
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