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1.
Mar Environ Res ; 202: 106751, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39303653

RESUMEN

The structure and functioning of ecosystems are largely determined by the interactions between species within a biological community. Among these interactions, species exhibiting similar vertical and spatial prey preferences can be identified, thereby belonging to the same trophic guild. Our study explored some trophic characteristics of a diverse megafaunal community (cetaceans, tunas, seabirds) in the Bay of Biscay (BoB). Using stable isotope analysis (SIA), we explored the dietary habits and niche overlap among predators. The degree of isotopic niche overlap was generally low, but with certain species exhibiting large and narrow isotopic niche areas (long-finned pilot whales and Balearic shearwaters, respectively). Our results revealed a diversity of dietary preferences leading to the identification of three distinct trophic guilds based on prey functional groups and spatial preferences: cephalopod feeders (e.g. long-finned pilot whales, Cuvier's beaked whales, striped dolphins), crustacean feeders (e.g. fin whales, albacores), and piscivores (e.g. common dolphins, harbour porpoises, bottlenose dolphins, Atlantic bluefin tunas, Balearic shearwaters). Our findings showed resource partitioning and niche differentiation among the megafaunal community, highlighting the complexity of BoB's marine ecosystem. The insights derived from this study hold important implications for ecosystem management and the implementation of conservation initiatives.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39306579

RESUMEN

BACKGROUND AND OBJECTIVES: Stem cell mobilization is a well-known procedure to harvest hematopoietic stem cells for autologous stem cell transplantation in certain hematologic diseases. Numerous studies have been conducted to identify risk factors for poor mobilization but there are no studies that identify good mobilizers. In our hospital, we decided to explore good mobilizers, defining them as those with ≥40 CD34+ cells/µL on Day +4 in order to start early apheresis. MATERIAL AND METHODS: A descriptive retrospective study was performed at Hospital Universitari Son Espases. A total of 198 patients mobilized with doses of around 10 µg/kg of granulocyte colony-stimulating factor (G-CSF) every 12 h were analyzed for autologous collection between January 2015 and September 2022. Fifty patients who had ≥40 CD34+ cells/µL on Day +4 started early apheresis; the rest continued mobilization as planned. Success was defined as obtaining over 2.5 × 106 CD34+ cells/kg in a single apheresis. RESULTS: The necessary number of CD34+ cells/kg to perform an autologous stem cell transplantation was reached in a single apheresis session in 62 % of patients with ≥40 CD34+ cells/µL in peripheral blood. A cutoff of 102 CD34+ cells/µL on Day +4 was shown to have the best success rate (94 %). In an analysis of success, age, previously failed mobilization and having one or more adverse factors for bad mobilization were statistically significant. CONCLUSION: Patients considered as good mobilizers were matched with our factors of poor mobilization, revealing that most patients (79 %) had none or only one risk factor for poor mobilization. Apheresis on Day +4 in good mobilizers was shown to be an effective alternative to reduce mobilization duration and decrease the amount of granulocyte-colony stimulating factor administered.

3.
Sci Rep ; 14(1): 20728, 2024 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-39237611

RESUMEN

The characteristics of the host are crucial in the final outcome of COVID-19. Herein, the influence of genetic and clinical variants in COVID-19 severity was investigated in a total of 1350 patients. Twenty-one single nucleotide polymorphisms of genes involved in SARS-CoV-2 sensing as Toll-like-Receptor 7, antiviral immunity as the type I interferon signalling pathway (TYK2, STAT1, STAT4, OAS1, SOCS) and the vasoactive intestinal peptide and its receptors (VIP/VIPR1,2) were studied. To analyse the association between polymorphisms and severity, a model adjusted by age, sex and different comorbidities was generated by ordinal logistic regression. The genotypes rs8108236-AA (OR 0.12 [95% CI 0.02-0.53]; p = 0.007) and rs280519-AG (OR 0.74 [95% CI 0.56-0.99]; p = 0.03) in TYK2, and rs688136-CC (OR 0.7 [95% CI 0.5-0.99]; p = 0.046) in VIP, were associated with lower severity; in contrast, rs3853839-GG in TLR7 (OR 1.44 [95% CI 1.07-1.94]; p = 0.016), rs280500-AG (OR 1.33 [95% CI 0.97-1.82]; p = 0.078) in TYK2 and rs1131454-AA in OAS1 (OR 1.29 [95% CI 0.95-1.75]; p = 0.110) were associated with higher severity. Therefore, these variants could influence the risk of severe COVID-19.


Asunto(s)
COVID-19 , Polimorfismo de Nucleótido Simple , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Humanos , COVID-19/genética , COVID-19/inmunología , COVID-19/virología , Masculino , Femenino , Persona de Mediana Edad , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Anciano , Adulto , Receptor Toll-Like 7/genética , TYK2 Quinasa/genética , Genotipo , Predisposición Genética a la Enfermedad , 2',5'-Oligoadenilato Sintetasa/genética
4.
Front Oncol ; 14: 1448213, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39319059

RESUMEN

Human Papillomavirus (HPV) related Multiphenotypic Sinonasal Carcinoma (HMSC) is a rare tumor with features of both atypical squamous cell and adenoid cystic carcinoma, making diagnosis challenging. Approximately 80% of HMSC cases carries HPV type 33 followed by type 35. We present a patient with HMSC. Pathological classification was aided by immunohistochemistry (IHC). The presence of HPV-DNA was tested using PCR and HPV E6/E7 expression by RNA in situ hybridization (RNA ISH). Whole exome sequencing (WES) was used to identify somatic gene mutations and copy number alterations. A 55-year-old male presented with an HMSC in the right nostril. Histological examination showed a solid basaloid subtype with mucinous spaces and ductal structures. IHC showed positive staining for SOX-10, SMA, p40, p63, PanCK, CK8 and MYB. Diffuse positive staining for p16 was observed and PCR and RNA ISH indicated the presence of HPV type 35. The patient was treated with endoscopic surgery and radiotherapy and is currently alive and recurrence-free after 16 months of follow-up. WES revealed 38 somatic sequence variants and several chromosomal regions with copy number alterations, including a copy number gain at 6q23 where MYB is located. EP300, ZNF22, ZNF609 and LRIG3 are some of the genes whose mutations were indicated as probably pathogenic. We did not find mutations predictive for drug response according to the ESMO Scale for Clinical Actionability of Molecular Targets database. This is the first report of WES analysis of an HMSC, in this case associated with HPV type 35. The detected mutation in EP300 and the overexpression of MYB may serve as molecular targets for personalized therapy.

5.
Biochim Biophys Acta Rev Cancer ; 1879(5): 189173, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39154967

RESUMEN

Gap junctions, membrane-based channels comprised of connexin proteins (Cxs), facilitate direct communication among neighbouring cells and between cells and the extracellular space through their hemichannels. The normal human breast expresses various Cxs family proteins, such as Cx43, Cx30, Cx32, Cx46, and Cx26, crucial for proper tissue development and function. These proteins play a significant role in breast cancer development, progression, and therapy response. In primary tumours, there is often a reduction and cytoplasmic mislocalization of Cx43 and Cx26, while metastatic lesions show an upregulation of these and other Cxs. Although existing research predominantly supports the tumour-suppressing role of Cxs in primary carcinomas through channel-dependent and independent functions, controversies persist regarding their involvement in the metastatic process. This review aims to provide an updated perspective on Cxs in human breast cancer, with a specific focus on intrinsic subtypes due to the heterogeneous nature of this disease. Additionally, the manuscript will explore the role of Cxs in immune interactions and novel forms of intercellular communication, such as tunneling nanotubes and extracellular vesicles, within the breast tumour context and tumour microenvironment. Recent findings suggest that Cxs hold potential as therapeutic targets for mitigating metastasis and drug resistance. Furthermore, they may serve as novel biomarkers for cancer prognosis, offering promising avenues for future research and clinical applications.


Asunto(s)
Neoplasias de la Mama , Comunicación Celular , Conexinas , Humanos , Conexinas/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Uniones Comunicantes/metabolismo , Microambiente Tumoral , Animales , Transducción de Señal
6.
Clin Neurol Neurosurg ; 245: 108511, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39180812

RESUMEN

INTRODUCTION: Surgery of lesions in the posterior wall of the third ventricle requires great expertise due to its deep location and important surrounding structures. This region has been traditionally reached through a supracerebellar infratentorial approach, but new options have emerged, especially with the development of neuroendoscopy. METHODS: One formalin-fixed cadaver human head was dissected. Five different endoscopic approaches were performed: interhemispheric transcallosal transchoroidal, frontal transforaminal transchoroidal, supraorbital subfrontal translamina terminalis, expanded endonasal, and supracerebellar infratentorial. An anatomical description of the different approaches was conducted and quantitative measurements (craniocaudal and latero-lateral distances) were taken using the StealthStation ® workstation after performing a CT scan of the specimen. RESULTS: The interhemispheric transcallosal transchoroidal, frontal transforaminal transchoroidal, and supraorbital subfrontal translamina terminalis approaches provided great view of all the structures of the posterior wall of the third ventricle. Maximum craniocaudal distance was obtained through the supraorbital subfrontal translamina terminalis approach (10.6 mm), with great difference from the expanded endonasal approach (5.2 mm). The widest latero-lateral distance from inside the third ventricle was achieved through the interhemispheric transcallosal transchoroidal approach (4.6 mm), similar to the expanded endonasal (4.1 mm), and differing from the supraorbital subfrontal translamina terminalis (2.4 mm). CONCLUSIONS: The endoscopic approaches provided an adequate alternative to more traditional microsurgical approaches to the posterior wall of the third ventricle, with a great view of all its structures. The selection of the approach must be taken under consideration in each case.


Asunto(s)
Cadáver , Neuroendoscopía , Tercer Ventrículo , Humanos , Tercer Ventrículo/cirugía , Tercer Ventrículo/diagnóstico por imagen , Tercer Ventrículo/anatomía & histología , Neuroendoscopía/métodos , Endoscopía/métodos , Procedimientos Neuroquirúrgicos/métodos
7.
Nat Biotechnol ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39169264

RESUMEN

T cell alloreactivity against minor histocompatibility antigens (mHAgs)-polymorphic peptides resulting from donor-recipient (D-R) disparity at sites of genetic polymorphisms-is at the core of the therapeutic effect of allogeneic hematopoietic cell transplantation (allo-HCT). Despite the crucial role of mHAgs in graft-versus-leukemia (GvL) and graft-versus-host disease (GvHD) reactions, it remains challenging to consistently link patient-specific mHAg repertoires to clinical outcomes. Here we devise an analytic framework to systematically identify mHAgs, including their detection on HLA class I ligandomes and functional verification of their immunogenicity. The method relies on the integration of polymorphism detection by whole-exome sequencing of germline DNA from D-R pairs with organ-specific transcriptional- and proteome-level expression. Application of this pipeline to 220 HLA-matched allo-HCT D-R pairs demonstrated that total and organ-specific mHAg load could independently predict the occurrence of acute GvHD and chronic pulmonary GvHD, respectively, and defined promising GvL targets, confirmed in a validation cohort of 58 D-R pairs, for the prevention or treatment of post-transplant disease recurrence.

8.
Artículo en Inglés | MEDLINE | ID: mdl-39148250

RESUMEN

OBJECTIVE: The aim of the present study was to identify the risk factors for severe maternal outcomes (SMO) of women with suspected or confirmed infections using the data from the WHO global maternal sepsis study (GLOSS). METHODS: We conducted a secondary analysis of the GLOSS cohort study, which involved pregnant or recently pregnant women with suspected or confirmed infection around 713 health facilities in 52 low- and middle-income countries, and high-income countries. A nested case-control study was conducted within the GLOSS cohort. Cases included infection-related maternal deaths or near misses, while controls represented non-SMO. Logistic mixed models, adjusting for country variations, were employed. Using univariate analysis, we calculated crude odds ratios (crude OR) and their 95% confidence interval (95% CI). Variables were identified with less than 16% missing data, and P values less than 0.20 were used to perform the multivariate logistic model multilevel. RESULTS: A total of 2558 women were included in the analysis. As for the cases, 134 patients were found in the pregnant in labor or not in labor group and 246 patients in the postpartum or postabortion group. Pregnant women with prior childbirths faced a 64% increased risk of SMO. Ante- or intrapartum hemorrhage increased risk by 4.45 times, while trauma during pregnancy increased it by 4.81 times. Pre-existing medical conditions elevated risk five-fold, while hospital-acquired infections increased it by 53%. Secondary infections raised risk six-fold. Postpartum/postabortion women with prior childbirths had a 45% elevated risk, and pre-existing medical conditions raised it by 2.84 times. Hospital-acquired infections increased risk by 93%. Postpartum hemorrhage increased risk approximately five-fold, while abortion-related bleeding doubled it. Previous cesarean, abortion, and stillbirth also elevated risk. CONCLUSIONS: Key risk factors for SMO include prior childbirths, hemorrhage, trauma, pre-existing conditions, and hospital-acquired or secondary infections. Implementing effective alert systems and targeted interventions is essential to mitigate these risks and improve maternal health outcomes, especially in resource-limited settings.

9.
Proc Natl Acad Sci U S A ; 121(32): e2402068121, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39088395

RESUMEN

Linguistic communication is an intrinsically social activity that enables us to share thoughts across minds. Many complex social uses of language can be captured by domain-general representations of other minds (i.e., mentalistic representations) that externally modulate linguistic meaning through Gricean reasoning. However, here we show that representations of others' attention are embedded within language itself. Across ten languages, we show that demonstratives-basic grammatical words (e.g., "this"/"that") which are evolutionarily ancient, learned early in life, and documented in all known languages-are intrinsic attention tools. Beyond their spatial meanings, demonstratives encode both joint attention and the direction in which the listener must turn to establish it. Crucially, the frequency of the spatial and attentional uses of demonstratives varies across languages, suggesting that both spatial and mentalistic representations are part of their conventional meaning. Using computational modeling, we show that mentalistic representations of others' attention are internally encoded in demonstratives, with their effect further boosted by Gricean reasoning. Yet, speakers are largely unaware of this, incorrectly reporting that they primarily capture spatial representations. Our findings show that representations of other people's cognitive states (namely, their attention) are embedded in language and suggest that the most basic building blocks of the linguistic system crucially rely on social cognition.


Asunto(s)
Atención , Lenguaje , Humanos , Atención/fisiología , Cognición/fisiología , Lingüística , Comunicación , Femenino , Masculino
10.
J Crit Care ; 84: 154867, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39024823

RESUMEN

Hantaviruses, members of the Bunyaviridae family, can cause two patterns of disease in humans, hantavirus hemorrhagic fever with renal syndrome (HFRS) and cardiopulmonary syndrome (HCPS), being the latter hegemonic on the American continent. Andesvirus is one of the strains that can cause HCPS and is endemic in Chile. Its transmission occurs through direct or indirect contact with infected rodents' urine, saliva, or feces and inhalation of aerosol particles containing the virus. HCPS rapidly evolves into acute but reversible multiorgan dysfunction. The hemodynamic pattern of HCPS is not identical to that of cardiogenic or septic shock, being characterized by hypovolemia, systolic dysfunction, and pulmonary edema secondary to increased permeability. Given the lack of specific effective therapies to treat this viral infection, the focus of treatment lies in the timely provision of intensive care, specifically hemodynamic and respiratory support, which often requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO). This narrative review aims to provide insights into specific ICU management of HCPS based on the available evidence and gathered experience in Chile and South America including perspectives of pathophysiology, organ dysfunction kinetics, timely life support provision, safe patient transportation, and key challenges for the future.


Asunto(s)
Cuidados Críticos , Síndrome Pulmonar por Hantavirus , Humanos , Cuidados Críticos/métodos , Síndrome Pulmonar por Hantavirus/terapia , Síndrome Pulmonar por Hantavirus/diagnóstico , Síndrome Pulmonar por Hantavirus/fisiopatología , Síndrome Pulmonar por Hantavirus/epidemiología , Oxigenación por Membrana Extracorpórea/métodos , Chile/epidemiología , Orthohantavirus/fisiología
11.
Support Care Cancer ; 32(8): 540, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39044016

RESUMEN

BACKGROUND: Breast cancer-related lymphedema in the upper limb remains one of the most distressful complications of breast cancer treatment. YouTube is considered a potential digital resource for population health and decision making. However, access to inadequate information or misinformation could have undesirable impacts. This cross-sectional study aimed to evaluate the reliability, quality and content of YouTube videos on lymphedema as an information source for Spanish-speaking breast cancer survivors. METHODS: A search of YouTube was conducted in January 2023 using the key words "breast cancer lymphedema" and "lymphedema arm breast cancer." Reliability and quality of the videos were evaluated using the Discern tool, content, source of production, number of likes, comments, views, duration, Video Power Index, likes ratio, view ratio and age on the platform. RESULTS: Amongst the 300 Spanish language videos identified on YouTube, 35 were selected for analysis based on the inclusion and exclusion criteria. Of the 35 selected videos, 82.9% (n = 29) were developed by healthcare or academic professionals and 17.1% (n = 9) by others. Reliability (p < 0.017) and quality (p < 0.03) were higher in the videos made by professionals. The Discern total score (r = 0.476; p = 0.004), reliability (r = 0.472; p = 0.004) and quality (r = 0.469; p = 0.004) were positively correlated with the duration of the videos. CONCLUSIONS: Our findings provide a strong rationale for educating breast cancer survivors seeking lymphedema information to select videos made by healthcare or academic professionals. Standardised evaluation prior to video publication is needed to ensure that the end-users receive accurate and quality information from YouTube.


Asunto(s)
Neoplasias de la Mama , Supervivientes de Cáncer , Medios de Comunicación Sociales , Grabación en Video , Humanos , Estudios Transversales , Femenino , Neoplasias de la Mama/complicaciones , Reproducibilidad de los Resultados , Linfedema/etiología , Información de Salud al Consumidor/normas , Información de Salud al Consumidor/métodos , Persona de Mediana Edad , Difusión de la Información/métodos , Adulto , Fuentes de Información
12.
Plants (Basel) ; 13(14)2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39065525

RESUMEN

Leaf senescence is a complex trait which becomes crucial for grain filling because photoassimilates are translocated to the seeds. Therefore, a correct sync between leaf senescence and phenological stages is necessary to obtain increasing yields. In this study, we evaluated the performance of five deep machine-learning methods for the evaluation of the phenological stages of sunflowers using images taken with cell phones in the field. From the analysis, we found that the method based on the pre-trained network resnet50 outperformed the other methods, both in terms of accuracy and velocity. Finally, the model generated, Sunpheno, was used to evaluate the phenological stages of two contrasting lines, B481_6 and R453, during senescence. We observed clear differences in phenological stages, confirming the results obtained in previous studies. A database with 5000 images was generated and was classified by an expert. This is important to end the subjectivity involved in decision making regarding the progression of this trait in the field and could be correlated with performance and senescence parameters that are highly associated with yield increase.

13.
Food Chem ; 455: 139761, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-38850975

RESUMEN

Xylooligosaccharides (XOs) have shown high potential as prebiotics with nutritional and health benefits. In this work, XOs were obtained from highly purified, carboxy-reduced glucuronoarabinoxylans by treatment with Driselase®. The mixtures were fractionated, and the structures were elucidated by methylation analysis and NMR spectroscopy. Antioxidant activity was determined by the methods of DPPH and ß-carotene/linoleic acid. It was found that the most active oligosaccharides (P3 and G3) comprised 4 or 5 xylose units, plus two arabinoses and one 4-O-methylglucose as side chains, their sequence of units was determined. The optimal concentration for their use as antioxidants was 2 mg/mL. The synthetic antioxidant butylated hydroxytoluene (BHT, 0.2 mg/mL) showed a percentage of inhibition 15% higher than P3. Although its concentration was ∼10 times higher, P3 is non-toxic, and could have great advantages as food additive. These results show that pure XOs exert significant antioxidant activity, only due to their carbohydrate nature.


Asunto(s)
Antioxidantes , Oligosacáridos , Antioxidantes/química , Antioxidantes/farmacología , Oligosacáridos/química , Xilanos/química , Glucuronatos/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Relación Estructura-Actividad , Brotes de la Planta/química
14.
Infect Dis (Lond) ; 56(7): 575-580, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38743059

RESUMEN

OBJECTIVE: To study the effect of plitidepsin antiviral treatment in immunocompromised COVID-19 patients with underlying haematological malignancies or solid tumours, particularly those who have undergone anti-CD20 therapies. DESIGN: We conducted a retrospective observational study, involving 54 adults treated with plitidepsin on compassionate use as an antiviral drug. Our analysis compared outcomes between patients with solid tumours and those with haematological malignancies, and a cohort of cases treated or not with anti-CD20 monoclonal antibodies. RESULTS: Patients with a history of anti-CD20 therapies showed a prolonged time-to-negative RT-PCR for SARS-CoV-2 infection compared to non-treated patients (33 d (28;75) vs 15 (11;25); p = .002). Similar results were observed in patients with solid tumours in comparison to those with haematological malignancies (13 (10;16) vs 26 (17;50); p < .001). No serious adverse events were documented. CONCLUSIONS: Patients with haematological malignancies appear to be at a heightened risk for delayed SARS-CoV-2 clearance and subsequent clinical complications. These findings support plitidepsin as a well-tolerated treatment in this high-risk group. A phase II clinical trial (NCT05705167) is ongoing to evaluate plitidepsin as an antiviral drug in this population.KEY POINTSHaematological patients face an increased risk for severe COVID-19.Anti-CD20 therapies could increase fatal outcomes in COVID-19 patients.Persistent viral replication is increased in immunocompromised patients.Plitidepsin does not lead to new serious adverse events in immunocompromised patients.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , COVID-19 , Depsipéptidos , Neoplasias Hematológicas , Neoplasias , Péptidos Cíclicos , SARS-CoV-2 , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/complicaciones , Anciano , Depsipéptidos/uso terapéutico , Depsipéptidos/efectos adversos , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Péptidos Cíclicos/uso terapéutico , Antivirales/uso terapéutico , Resultado del Tratamiento , Adulto , Ensayos de Uso Compasivo , Huésped Inmunocomprometido , Antígenos CD20/inmunología , Anciano de 80 o más Años
15.
Polymers (Basel) ; 16(10)2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38794619

RESUMEN

Nervous system traumatic injuries are prevalent in our society, with a significant socioeconomic impact. Due to the highly complex structure of the neural tissue, the treatment of these injuries is still a challenge. Recently, 3D printing has emerged as a promising alternative for producing biomimetic scaffolds, which can lead to the restoration of neural tissue function. The objective of this work was to compare different biomaterials for generating 3D-printed scaffolds for use in neural tissue engineering. For this purpose, four thermoplastic biomaterials, ((polylactic acid) (PLA), polycaprolactone (PCL), Filaflex (FF) (assessed here for the first time for biomedical purposes), and Flexdym (FD)) and gelatin methacrylate (GelMA) hydrogel were subjected to printability and mechanical tests, in vitro cell-biomaterial interaction analyses, and in vivo biocompatibility assessment. The thermoplastics showed superior printing results in terms of resolution and shape fidelity, whereas FD and GelMA revealed great viscoelastic properties. GelMA demonstrated a greater cell viability index after 7 days of in vitro cell culture. Moreover, all groups displayed connective tissue encapsulation, with some inflammatory cells around the scaffolds after 10 days of in vivo implantation. Future studies will determine the usefulness and in vivo therapeutic efficacy of novel neural substitutes based on the use of these 3D-printed scaffolds.

16.
Gels ; 10(4)2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38667671

RESUMEN

Neural Invasion (NI) is a key pathological feature of cancer in the colonization of distant tissues, and its underlying biological mechanisms are still scarcely known. The complex interactions between nerve and tumor cells, along with the stroma, make it difficult to reproduce this pathology in effective study models, which in turn has limited the understanding of NI pathogenesis. In this study, we have designed a three-dimensional model of NI squamous cell carcinoma combining human epidermoid carcinoma cells (hECCs) with a complete peripheral nerve segment encapsulated in a fibrine-agarose hydrogel. We recreated two vital processes of NI: a pre-invasive NI model in which hECCs were seeded on the top of the nerve-enriched stroma, and an invasive NI model in which cancer cells were immersed with the nerve in the hydrogel. Histological, histochemical and immunohistochemical analyses were performed to validate the model. Results showed that the integration of fibrin-agarose advanced hydrogel with a complete nerve structure and hECCs successfully generated an environment in which tumor cells and nerve components coexisted. Moreover, this model correctly preserved components of the neural extracellular matrix as well as allowing the proliferation and migration of cells embedded in hydrogel. All these results suggest the suitability of the model for the study of the mechanisms underlaying NI.

17.
Int J Pharm ; 657: 124139, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38677396

RESUMEN

Mesenchymal stem cell (MSC) therapy shows promise in regenerative medicine. For osteoarthritis (OA), MSCs delivered to the joint have a temporal window in which they can secrete growth factors and extracellular matrix molecules, contributing to cartilage regeneration and cell proliferation. However, upon injection in the non-vascularized joint, MSCs lacking energy supply, starve and die too quickly to efficiently deliver enough of these factors. To feed injected MSCs, we developed a hyaluronic acid (HA) derivative, where glucose is covalently bound to hyaluronic acid. To achieve this, the glucose moiety in 4-aminophenyl-ß-D-glucopyranoside was linked to the HA backbone through amidation. The hydrogel was able to deliver glucose in a controlled manner using a trigger system based on hydrolysis catalyzed by endogenous ß-glucosidase. This led to glucose release from the hyaluronic acid backbone inside the cell. Indeed, our hydrogel proved to rescue starvation and cell mortality in a glucose-free medium. Our approach of adding a nutrient to the polymer backbone in hydrogels opens new avenues to deliver stem cells in poorly vascularized, nutrient-deficient environments, such as osteoarthritic joints, and for other regenerative therapies.


Asunto(s)
Glucosa , Ácido Hialurónico , Hidrogeles , Células Madre Mesenquimatosas , Osteoartritis , Ácido Hialurónico/química , Glucosa/metabolismo , Osteoartritis/terapia , Hidrogeles/química , Humanos , Trasplante de Células Madre Mesenquimatosas/métodos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , beta-Glucosidasa/metabolismo , Animales
18.
Exp Hematol Oncol ; 13(1): 38, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38581035

RESUMEN

Rhabdomyosarcoma (RMS), such as other childhood tumors, has witnessed treatment advancements in recent years. However, high-risk patients continue to face poor survival rates, often attributed to the presence of the PAX3/7-FOXO1 fusion proteins, which has been associated with metastasis and treatment resistance. Despite efforts to directly target these chimeric proteins, clinical success remains elusive. In this study, the main aim was to address this challenge by investigating regulators of FOXO1. Specifically, we focused on TRIB3, a potential regulator of the fusion protein in RMS. Our findings revealed a prominent TRIB3 expression in RMS tumors, highlighting its correlation with the presence of fusion protein. By conducting TRIB3 genetic inhibition experiments, we observed an impairment on cell proliferation. Notably, the knockdown of TRIB3 led to a decrease in PAX3-FOXO1 and its target genes at protein level, accompanied by a reduction in the activity of the Akt signaling pathway. Additionally, inducible silencing of TRIB3 significantly delayed tumor growth and improved overall survival in vivo. Based on our analysis, we propose that TRIB3 holds therapeutic potential for treating the most aggressive subtype of RMS. The findings herein reported contribute to our understanding of the underlying molecular mechanisms driving RMS progression and provide novel insights into the potential use of TRIB3 as a therapeutic intervention for high-risk RMS patients.

19.
Glob Chang Biol ; 30(3): e17186, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38450925

RESUMEN

The Arctic is a global warming 'hot-spot' that is experiencing rapid increases in air and ocean temperatures and concomitant decreases in sea ice cover. These environmental changes are having major consequences on Arctic ecosystems. All Arctic endemic marine mammals are highly dependent on ice-associated ecosystems for at least part of their life cycle and thus are sensitive to the changes occurring in their habitats. Understanding the biological consequences of changes in these environments is essential for ecosystem management and conservation. However, our ability to study climate change impacts on Arctic marine mammals is generally limited by the lack of sufficiently long data time series. In this study, we took advantage of a unique dataset on hooded seal (Cystophora cristata) movements (and serum samples) that spans more than 30 years in the Northwest Atlantic to (i) investigate foraging (distribution and habitat use) and dietary (trophic level of prey and location) habits over the last three decades and (ii) predict future locations of suitable habitat given a projected global warming scenario. We found that, despite a change in isotopic signatures that might suggest prey changes over the 30-year period, hooded seals from the Northwest Atlantic appeared to target similar oceanographic characteristics throughout the study period. However, over decades, they have moved northward to find food. Somewhat surprisingly, foraging habits differed between seals breeding in the Gulf of St Lawrence vs those breeding at the "Front" (off Newfoundland). Seals from the Gulf favoured colder waters while Front seals favoured warmer waters. We predict that foraging habitats for hooded seals will continue to shift northwards and that Front seals are likely to have the greatest resilience. This study shows how hooded seals are responding to rapid environmental change and provides an indication of future trends for the species-information essential for effective ecosystem management and conservation.


Asunto(s)
Caniformia , Phocidae , Animales , Ecosistema , Calentamiento Global , Hábitos
20.
Lancet Reg Health Am ; 31: 100705, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38445021

RESUMEN

Background: Reducing maternal mortality ratio (MMR) remains a paramount goal for low- and middle-income countries (LMICs), especially after COVID-19's devastating impact on maternal health indicators. We describe our experience implementing the Hospital Padrino Strategy (HPS), a collaborative model between a high-complexity hospital (Fundación Valle del Lili) and 43 medium- and low-complexity hospitals in one Colombian department (an administrative and territorial division) from 2021 to 2022, to sustain the trend towards reducing MMR. The study aimed to assess the effects of implementing HPS on both hospital performance and maternal health indicators in Valle del Cauca department (VCD). Methods: A mixed-methods study was conducted, comprising two phases. In the first phase, we investigated a cohort of hospitals through prospective follow-up to assess the outcomes of HPS implementation on hospital performance and maternal health indicators in VCD. In the second phase, qualitative data were collected through focus groups with 131 health workers from 33 hospitals to explore the implications of the HPS implementation on healthcare personnel. All data were obtained from records within the HPS implementation and from the Health Secretary of VCD. Findings: Evidence shows that in the context of HPS, 51 workshops involved 980 healthcare workers, covering the entire territory. Substantial improvements were observed in hospital conditions and healthcare personnel's technical competencies when providing obstetric care. Seven hundred eighty-five pregnant women with obstetric or perinatal emergencies received care through telehealth systems, with a progressive increase in technology adoption. Nine percent required Intensive Care Unit (ICU) admission, and none died. The MMR decreased from 78.8 in 2021 to 12.0 cases per 100,000 live births by 2022. Improvements in indicators and conducted training sessions instilled confidence and empowerment among the healthcare teams in the sponsored hospitals, as evidenced in focus groups derived from a sample of 131 healthcare workers from 33 hospitals. Interpretation: Implementing the Hospital Padrino Strategy led to a significant MMR reduction, and consolidated a model of social healthcare innovation replicable in LMICs. Funding: The Hospital Padrino Strategy was funded by the Fundación Valle del Lili and the Health Secretary of Valle del Cauca. Furthermore, this study received funding from a general grant for research from Tecnoquimicas S.A.

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