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Chronic kidney disease (CKD) has emerged as a significant global public health concern. Recent epidemiological studies have highlighted the link between exposure to fine particulate matter (PM2.5) and a decline in renal function. PM2.5 exerts harmful effects on various organs through oxidative stress and inflammation. Acute kidney injury (AKI) resulting from ischaemia-reperfusion injury (IRI) involves biological processes similar to those involved in PM2.5 toxicity and is a known risk factor for CKD. The objective of this study was to investigate the impact of PM2.5 exposure on IRI-induced AKI. Through a unique environmentally controlled setup, mice were exposed to urban PM2.5 or filtered air for 12 weeks before IRI followed by euthanasia 48 h after surgery. Animals exposed to PM2.5 and IRI exhibited reduced glomerular filtration, impaired urine concentration ability, and significant tubular damage. Further, PM2.5 aggravated local innate immune responses and mitochondrial dysfunction, as well as enhancing cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway activation. This increased renal senescence and suppressed the anti-ageing protein klotho, leading to early fibrotic changes. In vitro studies using proximal tubular epithelial cells exposed to PM2.5 and hypoxia/reoxygenation revealed heightened activation of the STING pathway triggered by cytoplasmic mitochondrial DNA, resulting in increased tubular damage and a pro-inflammatory phenotype. In summary, our findings imply a role for PM2.5 in sensitising proximal tubular epithelial cells to IRI-induced damage, suggesting a plausible association between PM2.5 exposure and heightened susceptibility to CKD in individuals experiencing AKI. Strategies aimed at reducing PM2.5 concentrations and implementing preventive measures may improve outcomes for AKI patients and mitigate the progression from AKI to CKD. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Lesión Renal Aguda , Ratones Endogámicos C57BL , Material Particulado , Daño por Reperfusión , Animales , Lesión Renal Aguda/patología , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/etiología , Lesión Renal Aguda/metabolismo , Daño por Reperfusión/patología , Material Particulado/efectos adversos , Material Particulado/toxicidad , Ratones , Masculino , Contaminación del Aire/efectos adversos , Modelos Animales de Enfermedad , Riñón/patología , Riñón/metabolismo , Transducción de Señal , Tasa de Filtración GlomerularRESUMEN
Breast cancer is one of the most common malignancies worldwide and the most common form of cancer in women. A large proportion of patients begin with localized disease and undergo treatment with curative intent, while another large proportion of patients debuts with disseminated metastatic disease. In the last subgroup of patients, the prognosis in recent years has changed radically, given the existence of different targeted therapies thanks to the discovery of different biomarkers. Serological, histological, and genetic biomarkers have demonstrated their usefulness in the initial diagnosis, in the follow-up to detect relapses, to guide targeted treatment, and to stratify the prognosis of the most aggressive tumors in those with breast cancer. Molecular markers are currently the basis for the diagnosis of metastatic disease, given the wide variety of chemotherapy regions and existing therapies. These markers have been a real revolution in the therapeutic arsenal for breast cancer, and their diagnostic validity allows the classification of tumors with higher rates of relapse, aggressiveness, and mortality. In this sense, the existence of therapies targeting different molecular alterations causes a series of changes in tumor biology that can be assessed throughout the course of the disease to provide information on the underlying pathophysiology of metastatic disease, which allows us to broaden our knowledge of the different mechanisms of tissue invasion. Therefore, the aim of the present article is to review the clinical, diagnostic, predictive, prognostic utility and limitations of the main biomarkers available and under development in metastatic breast cancer.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Biomarcadores de Tumor/genética , Recurrencia Local de NeoplasiaRESUMEN
BACKGROUND: In Mexico, there is a paucity of evidence on the magnitude of prenatal exposure to metals. OBJECTIVE: To estimate the concentration of arsenic, cadmium, manganese and lead in umbilical cord blood (UCB) and its association with maternal blood concentrations during pregnancy and delivery. MATERIAL AND METHODS: Metal concentration in maternal blood was analyzed during pregnancy (n = 901), delivery (n = 732) and in UCB (n = 512) from participants of the PROGRESS cohort residing in Mexico City. The association between concentrations in UCB and maternal biomarkers was analyzed using generalized linear models, adjusted for relevant covariates. RESULTS: Mean concentrations (µg/L) of lead, arsenic and manganese in UCB were 27.14 (25.28-29.14), 0.77 (0.71-0.84) and 42.60 (40.45-44.83), respectively. Cadmium concentration could not be estimated because 86.2% of measurements were below the detection limit. Lead and manganese concentrations in UCB were significantly associated with maternal biomarkers during pregnancy and delivery; at delivery, association was only observed with arsenic. CONCLUSIONS: Prenatal exposure to toxic metals in sensitive periods of organogenesis shows a neglected public health problem. Biomonitoring of the population and establishment of regulations aimed at providing care to vulnerable populations is required.
ANTECEDENTES: En México es exigua la evidencia sobre la exposición prenatal a metales. OBJETIVO: Estimar la concentración de arsénico, cadmio, manganeso y plomo en sangre de cordón umbilical (SCU), y su asociación con las concentraciones en sangre materna durante el embarazo y parto. MATERIAL Y MÉTODOS: Se analizó la concentración de los metales en sangre materna durante el embarazo (n = 901), parto (n = 732) y en la SCU (n = 512) de participantes de la cohorte PROGRESS, residentes en la Ciudad de México. Se estimó la asociación entre la concentración en SCU y los biomarcadores maternos mediante modelos lineales generalizados, ajustados por covariables relevantes. RESULTADOS: La media (µg/L) de plomo, arsénico y manganeso en SCU fue 27.14 (25.28-29.14), 0.77 (0.71-0.84) y 42.60 (40.45-44.83), respectivamente. El valor del cadmio no se pudo estimar porque 86.2 % de las mediciones fueron inferiores al límite de detección. Las concentraciones de plomo y manganeso en SCU se asociaron significativamente a los biomarcadores maternos durante el embarazo y el parto; solo se observó asociación con arsénico en el parto. CONCLUSIONES: La exposición prenatal a metales tóxicos en periodos sensibles de la organogénesis evidencia un problema de salud pública desatendido. Se requiere un biomonitoreo poblacional y establecer regulación dirigida a proveer atención a población vulnerable.
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Arsénico , Efectos Tardíos de la Exposición Prenatal , Embarazo , Femenino , Humanos , Cadmio , Manganeso , Exposición Materna , Sangre Fetal , México , MetalesRESUMEN
BACKGROUND/OBJECTIVE: The objective of this study was to describe the molecular sensitization profile of mite allergy in an area with a high environmental exposure of house dust mites (HDM) and storage mites. METHODS: Skin prick tests were performed with standardized extracts (DIATER, Madrid, Spain). A specific commercial molecular panel (MADx) for Dermatophagoides pteronyssinus (Dpt), Dermatophagoides farinae (Dfar), Lepidoglyphus destructor (Ldt), Tyrophagus putrescentiae (Tput), and Blomia tropicalis (Blot) was correlated with clinical parameters in Galician (northwestern of Spain) HDM allergic patients. RESULTS: Fifty patients (60% female) met the inclusion and exclusion criteria. All of the patient's present rhinitis (50), 28% (14) rhinitis and asthma, and 18% (9) atopic dermatitis (AD). Hundred patients had a positive prick test for Dpt, followed by Dfar (92%), Ldt and Tput (74%), and Blot (68%). More than 50% recognized specific IgE for Der p 1, Der p 2, reaching 86% in the case of Der p 23. No statistically significant differences in IgE levels were found between patients with/without asthma and those with mild or moderate-severe rhinitis. Der p 7 was higher among rhinitis patients (p value 0.05). AD relative risk (RR) was increased in patients sensitized to Der f 2, Der p 2, and Der p 23. Der p 10 decreases the risk to have AD (RR 0.80). CONCLUSION: The evaluation of IgE results in a comprehensive panel of allergens allows differentiation of serological reactivity profiles with their clinical expression, to perform an optimal management. Improvements in component resolved diagnosis and more research on the clinical relevance of mite allergens are needed to achieve a genuine diagnosis leading to specific immunotherapy.
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Asma , Dermatitis Atópica , Rinitis , Alérgenos , Animales , Antígenos Dermatofagoides , Dermatitis Atópica/inducido químicamente , Femenino , Humanos , Inmunoglobulina E , Masculino , Técnicas de Diagnóstico Molecular , Piridinolcarbamato , Pyroglyphidae , Rinitis/diagnóstico , Pruebas CutáneasRESUMEN
The effects of drought on soil dynamics after fire are poorly known, particularly its long-term (i.e., years) legacy effects once rainfall returns to normal. Understanding this is particularly important for nutrient-poor soils in semi-arid regions affected by fire, in which rainfall is projected to decrease with climate change. Here, we studied the effects of post-fire drought and its legacy on soil microbial community structure and functionality in a Cistus-Erica shrubland (Spain). Rainfall total and patterns were experimentally modified to produce an unburned control (natural rainfall) and four burned treatments: control (natural rainfall), historical control (long-term average rainfall), moderate drought (percentile 8 historical rainfall, 5 months of drought per year), and severe drought (percentile 2, 7 months of drought). Soil nutrients and microbial community composition (ester-linked fatty acid approach) and functionality (enzyme activities and C mineralization rate) were monitored during the first 4 years after fire under rainfall treatments, plus two additional ones without them (six post-fire years). We found that the recovery of burned soils was lower under drought. Post-fire drought increased nitrate in the short term and reduced available phosphorus, exchangeable potassium, soil organic matter, enzyme activities, and carbon mineralization rate. Moreover, drought decreased soil total microbial biomass and fungi, with bacteria becoming relatively more abundant. Two years after discontinuing the drought treatments, the drought legacy was significant for available phosphorus and enzyme activities. Although microbial biomass did not show any drought legacy effect, the proportion of fungi and bacteria (mainly gram-positive) did, being lower and higher, respectively, in former drought-treated plots. We show that drought has an important impact on soil processes, and that some of its effects persist for at least 2 years after the drought ended. Therefore, drought and its legacy effects can be important for modeling biogeochemical processes in burned soils under future climate change.
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OBJECTIVE: To estimate the prevalence of elevated (≥5.0µg /dL) blood lead levels (BLL) and its association with the use of lead glazed ceramics (LGC). MATERIALS AND METHODS: In 2018, we measured capillary BLL in a representative sample of children 1 to 4 years old residing in Mexican localities under 100 000 inhabitants (Ensanut 100k). We inquired about use of LGC for food preparation and consumption. To estimate its association with BLL, multinomial logit models stratified by region were generated. RESULTS: The prevalence of elevated BLL levels was 21.8%. For the North, Central and South regions, the prevalence were 9.8, 20.7 and 25.8%, respectively. The association with use and frequency of LGC was highly significant and differential by region. CONCLUSIONS: Lead exposure remains a public health problem in Mexico, particularly in the Central and South regions, and is strongly associated with the use of LGC.
OBJETIVO: Estimar la prevalencia de niveles elevados (≥5.0µg/dL) de plomo en sangre (PbS) y su asociación con el uso de loza de barro vidriado con plomo (LBVPb). MATERIAL Y MÉTODOS: En 2018 se midió PbS capilar en una muestra represen- tativa de niños de 1 a 4 años de edad residentes en localidades de México menores de 100 000 habitantes (Ensanut 100k). Se indagó sobre uso de LBVPb para consumo de alimentos. Para estimar su asociación con PbS, se generaron modelos logit multinomial estratificados por región. RESULTADOS: La prevalencia de niveles elevados de PbS fue de 21.8%. En las regiones Norte, Centro y Sur las prevalencias fueron 9.8, 20.7 y 25.8%, respectivamente. La asociación con uso y frecuencia de LBVPb fue altamente significativa y diferencial por región. CONCLUSIONES: La exposición a plomo permanece como un problema de salud pública en México, particularmente en el Centro y Sur, y está fuertemente asociada con el uso de LBVPb.
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Cerámica , Utensilios de Comida y Culinaria , Plomo/sangre , Cerámica/química , Preescolar , Utensilios de Comida y Culinaria/estadística & datos numéricos , Estudios Transversales , Femenino , Humanos , Lactante , Plomo/análisis , Masculino , México , Poblaciones VulnerablesRESUMEN
Fire is a major factor controlling global carbon (C) and nitrogen (N) cycling. While direct C and N losses caused by combustion have been comparably well established, important knowledge gaps remain on postfire N losses. Here, we quantified both direct C and N combustion losses as well as postfire gaseous losses (N2 O, NO and N2 ) and N leaching after a high-intensity experimental fire in an old shrubland in central Spain. Combustion losses of C and N were 9.4 Mg C/ha and 129 kg N/ha, respectively, representing 66% and 58% of initial aboveground vegetation and litter stocks. Moreover, fire strongly increased soil mineral N concentrations by several magnitudes to a maximum of 44 kg N/ha 2 months after the fire, with N largely originating from dead soil microbes. Postfire soil emissions increased from 5.4 to 10.1 kg N ha-1 year-1 for N2 , from 1.1 to 1.9 kg N ha-1 year-1 for NO and from 0.05 to 0.2 kg N ha-1 year-1 for N2 O. Maximal leaching losses occurred 2 months after peak soil mineral N concentrations, but remained with 0.1 kg N ha-1 year-1 of minor importance for the postfire N mass balance. 15 N stable isotope labelling revealed that 33% of the mineral N produced by fire was incorporated in stable soil N pools, while the remainder was lost. Overall, our work reveals significant postfire N losses dominated by emissions of N2 that need to be considered when assessing fire effects on ecosystem N cycling and mass balance. We propose indirect N gas emissions factors for the first postfire year, equalling to 7.7% (N2 -N), 2.7% (NO-N) and 5.0% (N2 O-N) of the direct fire combustion losses of the respective N gas species.
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Incendios , Nitrógeno/análisis , Suelo/química , Ecosistema , Bosques , Gases , Región Mediterránea , Minerales/análisis , EspañaRESUMEN
Connectomics data from animal models provide an invaluable opportunity to reveal the complex interplay between structure and function in the mammalian brain. In this work, we investigate the relationship between structural and functional connectivity in the rat brain cortex using a directed anatomical network generated from a carefully curated meta-analysis of published tracing data, along with resting-state functional MRI data obtained from a group of 14 anesthetized Wistar rats. We found a high correspondence between the strength of functional connections, measured as blood oxygen level dependent (BOLD) signal correlations between cortical regions, and the weight of the corresponding anatomical links in the connectome graph (maximum Spearman rank-order correlation ρ=0.48). At the network-level, regions belonging to the same functionally defined community tend to form more mutual weighted connections between each other compared to regions located in different communities. We further found that functional communities in resting-state networks are enriched in densely connected anatomical motifs. Importantly, these higher-order structural subgraphs cannot be explained by lower-order topological properties, suggesting that dense structural patterns support functional associations in the resting brain. Simulations of brain-wide resting-state activity based on neural mass models implemented on the empirical rat anatomical connectome demonstrated high correlation between the simulated and the measured functional connectivity (maximum Pearson correlation ρ=0.53), further suggesting that the topology of structural connections plays an important role in shaping functional cortical networks.
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Corteza Cerebral/anatomía & histología , Corteza Cerebral/fisiología , Vías Nerviosas/anatomía & histología , Vías Nerviosas/fisiología , Animales , Conectoma , Imagen por Resonancia Magnética , Ratas , Ratas WistarRESUMEN
Understanding how drought affects seeder and resprouter plants during post-fire regeneration is important for the anticipation of Mediterranean vegetation vulnerability in a context of increasing drought and fire caused by climate change. A Mediterranean shrubland was subjected to various drought treatments (including 45% rainfall reduction, 7 months drought yr-1 ), before and after experimental burning, by means of a rainout-shelter system with an irrigation facility. Predawn shoot water potential (Ψpd ), relative growth rate (RGR), specific leaf area (SLA) and bulk leaf carbon isotopic composition (δ13 C) were monitored in the main woody species during the first 3 yr after fire. Cistus ladanifer seedlings showed higher Ψpd , RGR and SLA, and lower δ13 C, than unburned plants during the first two post-fire years. Seedlings under drought maintained relatively high Ψpd , but suffered a decrease in Ψpd and RGR, and an increase in δ13 C, relative to control treatments. Erica arborea, E. scoparia and Phillyrea angustifolia resprouts had higher Ψpd and RGR than unburned plants during the first post-fire year. Resprouters were largely unaffected by drought. Overall, despite marked differences between the two functional groups, post-fire environments were favourable for plant functioning of both seeder and resprouter shrubs, even under the most severe drought conditions implemented.
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Sequías , Incendios , Plantas/metabolismo , Análisis de Varianza , Isótopos de Carbono/metabolismo , Gases/metabolismo , Humedad , Región Mediterránea , Análisis Multivariante , Hojas de la Planta/anatomía & histología , Hojas de la Planta/fisiología , Brotes de la Planta/fisiología , Análisis de Componente Principal , Lluvia , Estaciones del Año , Suelo/química , Especificidad de la Especie , Luz Solar , Presión de Vapor , AguaRESUMEN
In critically ill patients, overweight and obesity are associated with acute respiratory distress syndrome and acute kidney injury (AKI). However, the effect of obesity on ischemia-reperfusion injury (IRI)-induced AKI is unknown. We hypothesized that obesity would aggravate renal IRI in mice. We fed mice a standard or high-fat diet for eight weeks. The mice were divided into four groups and submitted to sham surgery or IRI: obese, normal, normal + IRI, obese, and obese + IRI. All studies were performed 48 h after the procedures. Serum glucose, cholesterol, and creatinine clearance did not differ among the groups. Survival and urinary osmolality were lower in the obese + IRI group than in the normal + IRI group, whereas urinary neutrophil gelatinase-associated lipocalin levels, tubular injury scores, and caspase 3 expression were higher. Proliferating cell nuclear antigen expression was highest in the obese + IRI group, as were the levels of oxidative stress (urinary levels of thiobarbituric acid-reactive substances and renal heme oxygenase-1 protein expression), whereas renal Klotho protein expression was lowest in that group. Expression of glutathione peroxidase 4 and peroxiredoxin 6, proteins that induce lipid peroxidation, a hallmark of ferroptosis, was lower in the obese + IRI group. Notably, among the mice not induced to AKI, macrophage infiltration was greater in the obese group. In conclusion, greater oxidative stress and ferroptosis might aggravate IRI in obese individuals, and Klotho could be a therapeutic target in those with AKI.
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Lesión Renal Aguda , Obesidad , Estrés Oxidativo , Daño por Reperfusión , Animales , Lesión Renal Aguda/etiología , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Daño por Reperfusión/complicaciones , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Obesidad/complicaciones , Obesidad/metabolismo , Ratones , Masculino , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Glucuronidasa/metabolismo , Riñón/metabolismo , Riñón/patologíaRESUMEN
Odontology, as a scientific discipline, continuously collaborates with biomaterials engineering to enhance treatment characteristics and patients' satisfaction. Endodontics, a specialized field of dentistry, focuses on the study, diagnosis, prevention, and treatment of dental disorders affecting the dental pulp, root, and surrounding tissues. A critical aspect of endodontic treatment involves the careful selection of an appropriate endodontic sealer for clinical use, as it significantly influences treatment outcomes. Traditional sealers, such as zinc oxide-eugenol, fatty acid, salicylate, epoxy resin, silicone, and methacrylate resin systems, have been extensively used for decades. However, advancements in endodontics have given rise to bioceramic-based sealers, offering improved properties and addressing new challenges in endodontic therapy. In this review, a classification of these materials and their ideal properties are presented to provide evidence-based guidance to clinicians. Physicochemical properties, including sealing ability, stability over time and space, as well as biological properties such as biocompatibility and antibacterial characteristics, along with cost-effectiveness, are essential factors influencing clinicians' decisions based on individual patient evaluations.
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Materiales Biocompatibles , Materiales de Obturación del Conducto Radicular , Humanos , Materiales de Obturación del Conducto Radicular/química , Ensayo de Materiales , Resinas Epoxi/química , Cemento de Óxido de Zinc-EugenolRESUMEN
Functional magnetic resonance imaging (fMRI) provides insights into cognitive processes with significant clinical potential. However, delays in brain region communication and dynamic variations are often overlooked in functional network studies. We demonstrate that networks extracted from fMRI cross-correlation matrices, considering time lags between signals, show remarkable reliability when focusing on statistical distributions of network properties. This reveals a robust brain functional connectivity pattern, featuring a sparse backbone of strong 0-lag correlations and weaker links capturing coordination at various time delays. This dynamic yet stable network architecture is consistent across rats, marmosets, and humans, as well as in electroencephalogram (EEG) data, indicating potential universality in brain dynamics. Second-order properties of the dynamic functional network reveal a remarkably stable hierarchy of functional correlations in both group-level comparisons and test-retest analyses. Validation using alcohol use disorder fMRI data uncovers broader shifts in network properties than previously reported, demonstrating the potential of this method for identifying disease biomarkers.
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Encéfalo , Electroencefalografía , Imagen por Resonancia Magnética , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Animales , Humanos , Ratas , Electroencefalografía/métodos , Masculino , Red Nerviosa/fisiología , Red Nerviosa/diagnóstico por imagen , Mapeo Encefálico/métodos , Callithrix/fisiología , AdultoRESUMEN
The PD-1/PD-L1 axis is a complex signaling pathway that has an important role in the immune system cells. Programmed cell death protein 1 (PD-1) acts as an immune checkpoint on the T lymphocytes, B lymphocytes, natural killer (NK), macrophages, dendritic cells (DCs), monocytes, and myeloid cells. Its ligand, the programmed cell death 1 ligand (PD-L1), is expressed in the surface of the antigen-presenting cells (APCs). The binding of both promotes the downregulation of the T cell response to ensure the activation to prevent the onset of chronic immune inflammation. This axis in the tumor microenvironment (TME) performs a crucial role in the tumor progression and the escape of the tumor by neutralizing the immune system, the engagement of PD-L1 with PD-1 in the T cell causes dysfunctions, neutralization, and exhaustion, providing the tumor mass production. This review will provide a comprehensive overview of the functions of the PD-1/PD-L1 system in immune function, cancer, and the potential therapeutic implications of the PD-1/PD-L1 pathway for cancer management.
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Antígeno B7-H1 , Neoplasias , Receptor de Muerte Celular Programada 1 , Microambiente Tumoral , Humanos , Neoplasias/inmunología , Neoplasias/metabolismo , Neoplasias/patología , Antígeno B7-H1/metabolismo , Antígeno B7-H1/inmunología , Receptor de Muerte Celular Programada 1/metabolismo , Receptor de Muerte Celular Programada 1/inmunología , Animales , Microambiente Tumoral/inmunología , Transducción de Señal , Progresión de la Enfermedad , Inmunomodulación , Investigación Biomédica TraslacionalRESUMEN
Extreme drought events during post-fire regeneration are becoming increasingly frequent in Mediterranean-type ecosystems. Understanding how plants with different traits and origins respond to such conditions during early life stages is therefore critical for assessing the effect of climate change. Here, seedlings of three Cistus (semi-deciduous malacophylls from the Mediterranean Basin) and three Ceanothus (evergreen sclerophylls from California) species, two post-fire seeder genera with contrasting leaf traits, were subjected to complete water deprivation for 3 months in a common garden experiment. The leaf and plant structure and plant tissue water relations were characterized before the drought, and the functional responses (water availability, gas exchange and fluorescence) were monitored during the drought. Both genera exhibited contrasting leaf structure and tissue water relations traits, with higher leaf area and specific leaf area as well as higher osmotic potential at maximum turgor and turgor loss point in Cistus than Ceanothus. During drought, Ceanothus showed a more conservative use of water than Cistus, with a water potential less sensitive to decreasing soil moisture and a strong decline in photosynthesis and stomatal conductance in response to water deficit, but also a level of fluorescence more responsive to drought than Cistus. However, we could not find a different degree of drought resistance between the genera. This was particularly clear between Cistus ladanifer L. and Ceanothus pauciflorus DC., the two most functionally contrasting species, but at the same time, the two most drought-resistant. Our findings demonstrate that species with different leaf traits and functional responses to water stress may not differ in their degree of drought resistance, at least during the seedling stage. This underlines the need to take general categorizations by genus or functional types with caution and to deepen our knowledge about the Mediterranean-type species ecophysiology, especially during early life stages, in order to anticipate their vulnerability to climate change.
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Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity and accounts for >90% of all oral cancers. Despite advances in diagnostic procedures and therapeutic interventions, overall survival has not improved significantly in recent decades, primarily due to late diagnosis, locoregional recurrence and treatment resistance. Identifying reliable biomarkers for early detection, prognosis evaluation and treatment response prediction is critical for improving clinical outcomes in patients with OSCC. In the present review, the prognostic and predictive utility of circulating biomarkers, such as circulating tumour cells, serological biomarkers and histological and genetic biomarkers, were explored in the context of OSCC. In addition, the potential role of immune checkpoints in the treatment of OSCC was highlighted and the rapidly evolving field of liquid biopsy and its potential to revolutionize diagnosis, prognosis evaluation and treatment were examined. The existing evidence for the clinical utility of these biomarkers was critically evaluated and the challenges and limitations associated with their introduction into routine clinical practice were addressed. In conclusion, the present review highlights the promising role of biomarkers in improving the current understanding of the pathogenesis of OSCC and offers potential avenues for improving patient care through personalized medicine approaches.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/genética , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/terapia , Neoplasias de la Boca/genética , Biomarcadores de Tumor/genética , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/patología , PronósticoRESUMEN
Alcohol use disorder (AUD) is a complex condition representing a leading risk factor for death, disease and disability. Its high prevalence and severe health consequences make necessary a better understanding of the brain network alterations to improve diagnosis and treatment. The purpose of this study was to evaluate the potential of resting-state fMRI 3D texture features as a novel source of biomarkers to identify AUD brain network alterations following a radiomics approach. A longitudinal study was conducted in Marchigian Sardinian alcohol-preferring msP rats (N = 36) who underwent resting-state functional and structural MRI before and after 30 days of alcohol or water consumption. A cross-sectional human study was also conducted among 33 healthy controls and 35 AUD patients. The preprocessed functional data corresponding to control and alcohol conditions were used to perform a probabilistic independent component analysis, identifying seven independent components as resting-state networks. Forty-three radiomic features extracted from each network were compared using a Wilcoxon signed-rank test with Holm correction to identify the network most affected by alcohol consumption. Features extracted from this network were then used in the machine learning process, evaluating two feature selection methods and six predictive models within a nested cross-validation structure. The classification was evaluated by computing the area under the ROC curve. Images were quantized using different numbers of gray-levels to test their influence on the results. The influence of ageing, data preprocessing, and brain iron accumulation were also analyzed. The methodology was validated using structural scans. The striatal network in alcohol-exposed msP rats presented the most significant number of altered features. The radiomics approach supported this result achieving good classification performance in animals (AUC = 0.915 ± 0.100, with 12 features) and humans (AUC = 0.724 ± 0.117, with 9 features) using a random forest model. Using the structural scans, high accuracy was achieved with a multilayer perceptron in both species (animals: AUC > 0.95 with 2 features, humans: AUC > 0.82 with 18 features). The best results were obtained using a feature selection method based on the p-value. The proposed radiomics approach is able to identify AUD patients and alcohol-exposed rats with good accuracy, employing a subset of 3D features extracted from fMRI. Furthermore, it can help identify relevant networks in drug addiction.
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Alcoholismo , Humanos , Animales , Ratas , Alcoholismo/diagnóstico por imagen , Estudios Longitudinales , Estudios Transversales , Imagen por Resonancia Magnética/métodos , Modelos Animales , Estudios RetrospectivosRESUMEN
Macrophages are a type of immune cell distributed throughout all tissues of an organism. Allograft inflammatory factor 1 (AIF1) is a calcium-binding protein linked to the activation of macrophages. AIF1 is a key intracellular signaling molecule that participates in phagocytosis, membrane ruffling and F-actin polymerization. Moreover, it has several cell type-specific functions. AIF1 plays important roles in the development of several diseases: kidney disease, rheumatoid arthritis, cancer, cardiovascular diseases, metabolic diseases and neurological disorders, and in transplants. In this review, we present a comprehensive review of the known structure, functions and role of AIF1 in inflammatory diseases.
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Chronic venous disease (CVD) is a common condition that affects the veins in the lower limbs, resulting in a variety of symptoms, such as swelling, pain, and varicose veins (VVs). The plenty hormonal, hemodynamic and mechanical changes occurred in pregnancy make women especially vulnerable to suffer from this condition in this period. Previous works have identified that CVD is associated with an increased inflammatory milieu and significant damage in maternofetal tissues, such as the umbilical cord. However, the inflammatory status of this structure in these patients has not been studied yet. Thus, the aim of the present study was to examine gene and protein expression of a set of inflammatory markers-Allograft inflammatory factor 1 (AIF-1), the proinflammatory cytokines interleukin 12A (IL-12A) and IL-18 and the anti-inflammatory product IL-10-in the umbilical cord of women with CVD during pregnancy (N = 62) and healthy pregnant women (HC; N = 52) by the use of real time qPCR and immunohistochemistry (IHC). Our results demonstrate that the umbilical cord tissue from CVD women exhibit an increased expression of AIF-1, IL-12A and IL-18 along with a decrease in IL-10. Therefore, our study suggests an inflammatory status of this structure related to CVD. Further studies should be conducted to evaluate the expression of other inflammatory markers, as well as to analyze the maternofetal impact of these findings.
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Global warming is projected to increase the frequency and intensity of droughts in the Mediterranean region, as well as the occurrence of large fires. Understanding the interactions between drought, fire and plant responses is therefore important. In this study, we present an experiment in which rainfall patterns were modified to simulate various levels of drought in a Mediterranean shrubland of central Spain dominated by Cistus ladanifer, Erica arborea and Phillyrea angustifolia. A system composed of automatic rainout shelters with an irrigation facility was used. It was designed to be applied in vegetation 2 m tall, treat relatively large areas (36 m2), and be quickly dismantled to perform experimental burning and reassembled back again. Twenty plots were subjected to four rainfall treatments from early spring: natural rainfall, long-term average rainfall (2 months drought), moderate drought (25% reduction from long-term rainfall, 5 months drought) and severe drought (45% reduction, 7 months drought). The plots were burned in late summer, without interfering with rainfall manipulations. Results indicated that rainfall manipulations caused differences in soil moisture among treatments, leading to reduced water availability and growth of C. ladanifer and E. arborea in the drought treatments. However, P. angustifolia was not affected by the manipulations. Rainout shelters had a negligible impact on plot microenvironment. Experimental burns were of high fire intensity, without differences among treatments. Our system provides a tool to study the combined effects of drought and fire on vegetation, which is important to assess the threats posed by climate change in Mediterranean environments.
Asunto(s)
Clima , Sequías/estadística & datos numéricos , Incendios/estadística & datos numéricos , Bosques , Desarrollo de la Planta/fisiología , Lluvia , Monitoreo del Ambiente/estadística & datos numéricos , Islas del Mediterráneo , EspañaRESUMEN
Beta diversity, and its components of turnover and nestedness, reflects the processes governing community assembly, such as dispersal limitation or biotic interactions, but it is unclear how they operate at the local scale and how their role changes along postfire succession. Here, we analyzed the patterns of beta diversity and its components in a herbaceous plant community after fire, and in relation to dispersal ability, in Central Spain. We calculated multiple-site beta diversity (ßSOR) and its components of turnover (ßSIM) and nestedness (ßSNE) of all herbaceous plants, or grouped by dispersal syndrome (autochory, anemochory, and zoochory), during the first 3 years after wildfire. We evaluated the relationship between pairwise beta diversity (ßsor), and its components (ßsim, ßsne), and spatial distance or differences in woody plant cover, a proxy of biotic interactions. We found high multiple-site beta diversity dominated by the turnover component. Community dissimilarity increased with spatial distance, driven mostly by the turnover component. Species with less dispersal ability (i.e., autochory) showed a stronger spatial pattern of dissimilarity. Biotic interactions with woody plants contributed less to community dissimilarity, which tended to occur through the nestedness component. These results suggest that dispersal limitation prevails over biotic interactions with woody plants as a driver of local community assembly, even for species with high dispersal ability. These results contribute to our understanding of postfire community assembly and vegetation dynamics.