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1.
Vet Res Commun ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38922387

RESUMEN

Fibropapillomatosis (FP) - tumour-associated chelonid alphaherpesvirus 5 (ChHV5; Scutavirus chelonidalpha5) - is a disease that affect marine turtles around the world, and characterized by the formation of cutaneous tumours that can appear anywhere on the body. We carried out a thorough literature search (from 1990 to 2024) in the feeding sites of North-western Mexico, a region that hosts important habitats for feeding, development, and reproduction for five of the seven existing sea turtle species. We found 18 reports recording a total of 32 cases of FP and/or ChHV5/Scutavirus chelonidalpha5 in coastal and insular areas of North-western Mexico. Baja California Sur resulted with the highest number of cases (75%). While the first case of ChHV5/Scutavirus chelonidalpha5 infection was reported in 2004, the presence of FP tumours was reported in 2014 and became more frequent between 2019 and 2024. The affected species were black, Chelonia mydas (50%), olive ridley, Lepidochelys olivacea (46.8%) and loggerhead turtles, Caretta caretta (3.2%). Tumours occurred mainly in anterior flippers (46.1%) and neck (22.5%), and most had a nodular and verrucous appearance with a rough surface. In the study region, there is a potential sign of the emergence of the ChHV5/Scutavirus chelonidalpha5 infections and FP disease during the last 20 years, with a rapid increase during the last 10 years. As long as infections by ChHV5/Scutavirus chelonidalpha5 and the prevalence of the FP disease may be potentially influenced by anthropogenic activities, a One Health approach is needed to understand and improve sea turtles' health.

2.
Cell Death Differ ; 31(7): 881-896, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38802657

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC), the most prevalent type of pancreatic cancer, is one of the deadliest forms of cancer with limited therapy options. Overexpression of the heat shock protein 70 (HSP70) is a hallmark of cancer that is strongly associated with aggressive disease and worse clinical outcomes. However, the underlying mechanisms by which HSP70 allows tumor cells to thrive under conditions of continuous stress have not been fully described. Here, we report that PDAC has the highest expression of HSP70 relative to normal tissue across all cancers analyzed. Furthermore, HSP70 expression is associated with tumor grade and is further enhanced in metastatic PDAC. We show that genetic or therapeutic ablation of HSP70 alters mitochondrial subcellular localization, impairs mitochondrial dynamics, and promotes mitochondrial swelling to induce apoptosis. Mechanistically, we find that targeting HSP70 suppresses the PTEN-induced kinase 1 (PINK1) mediated phosphorylation of dynamin-related protein 1 (DRP1). Treatment with the HSP70 inhibitor AP-4-139B was efficacious as a single agent in primary and metastatic mouse models of PDAC. In addition, we demonstrate that HSP70 inhibition promotes the AMP-activated protein kinase (AMPK) mediated phosphorylation of Beclin-1, a key regulator of autophagic flux. Accordingly, we find that the autophagy inhibitor hydroxychloroquine (HCQ) enhances the ability of AP-4-139B to mediate anti-tumor activity in vivo. Collectively, our results suggest that HSP70 is a multi-functional driver of tumorigenesis that orchestrates mitochondrial dynamics and autophagy. Moreover, these findings support the rationale for concurrent inhibition of HSP70 and autophagy as a novel therapeutic approach for HSP70-driven PDAC.


Asunto(s)
Autofagia , Carcinoma Ductal Pancreático , Proteínas HSP70 de Choque Térmico , Dinámicas Mitocondriales , Neoplasias Pancreáticas , Dinámicas Mitocondriales/efectos de los fármacos , Proteínas HSP70 de Choque Térmico/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Autofagia/efectos de los fármacos , Humanos , Animales , Ratones , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/tratamiento farmacológico , Línea Celular Tumoral , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Proteínas Quinasas/metabolismo
3.
bioRxiv ; 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38617240

RESUMEN

Regulatory T cells (Tregs) are promising cellular therapies to induce immune tolerance in organ transplantation and autoimmune disease. The success of chimeric antigen receptor (CAR) T-cell therapy for cancer has sparked interest in using CARs to generate antigen-specific Tregs. Here, we compared CAR with endogenous T cell receptor (TCR)/CD28 activation in human Tregs. Strikingly, CAR Tregs displayed increased cytotoxicity and diminished suppression of antigen-presenting cells and effector T (Teff) cells compared with TCR/CD28 activated Tregs. RNA sequencing revealed that CAR Tregs activate Teff cell gene programs. Indeed, CAR Tregs secreted high levels of inflammatory cytokines, with a subset of FOXP3+ CAR Tregs uniquely acquiring CD40L surface expression and producing IFNγ. Interestingly, decreasing CAR antigen affinity reduced Teff cell gene expression and inflammatory cytokine production by CAR Tregs. Our findings showcase the impact of engineered receptor activation on Treg biology and support tailoring CAR constructs to Tregs for maximal therapeutic efficacy.

4.
Mar Environ Res ; 198: 106491, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38657368

RESUMEN

Our study aimed to establish reference values for nesting females and compare them with those previously reported to understand olive ridley turtles' health status and contribute to long-term health assessment and monitoring in foraging and nesting areas from the state of Sinaloa, Mexico. In August and September 2018, morphometric data and biochemical profiles were collected from 33 nesting olive ridley turtles from Ceuta Beach Sanctuary (CBS) and 14 foraging female turtles captured at the foraging site, Navachiste Marine Area (NMA). Nesting turtles sampled had greater CCL (65.86 ± 1.70 cm) than those from the foraging area (61.54 ± 1.22) (p < 0.05). Regarding biochemical profiles, post-nesting turtles had higher packed cell volume (PCV), albumin, blood urea nitrogen (BUN), cholesterol, triglycerides, and calcium than turtles from the foraging area (p < 0.05). Phosphorus levels were higher in foraging turtles than in nesting turtles (p = 0.001), while the remaining parameters showed no significant differences. The present study describes for the first time the blood biochemical values of nesting turtles from the Ceuta Beach Sanctuary in southern Sinaloa, Mexico, similar to those of foraging turtles from the north of the state. The significant differences observed between the two analysis groups may be due to the energy reserves and reproductive and nesting activity of the nesting turtles, so the blood biochemistry values described in this study can be used as a standard reference blood value for the olive ridley turtle population of Sinaloa, Mexico.


Asunto(s)
Comportamiento de Nidificación , Tortugas , Animales , Tortugas/sangre , Tortugas/fisiología , México , Femenino , Monitoreo del Ambiente , Nitrógeno de la Urea Sanguínea , Valores de Referencia , Hematócrito
6.
Rev Neurol ; 78(8): 229-235, 2024 Apr 16.
Artículo en Español | MEDLINE | ID: mdl-38618670

RESUMEN

In pediatric patients, an acute altered mental status refers to a sudden and significant change in a child's brain function and level of consciousness. It may manifest as confusion, disorientation, agitation, lethargy or even a loss of consciousness. This condition is a medical emergency, and requires immediate evaluation and attention. There are several causes of acute altered mental status in children, including infections of the central nervous system such as meningitis or encephalitis, traumatic brain injury, metabolic disorders, seizures and poisoning, among others. The aim of this study was to analyse, prepare and classify the current literature in order to determine the best recommendations for the treatment of cases of acute altered mental status with various causes in pediatric patients. The study was based on opinions from experts in the field in order to classify the recommendations, and was submitted to the scientific committee of the Iberoamerican Academy of Pediatric Neurology for review. Our guide is an aid for the treatment of this non-specific symptom based on a basic and advanced approach, which can be applied by any pediatric neurologist.


TITLE: Guía de tratamiento de la alteración aguda del estado mental. Academia Iberoamericana de Neurología Pediátrica.La alteración aguda del estado mental en pediatría se refiere a un cambio repentino y significativo en la función cerebral y el nivel de conciencia de un niño. Puede manifestarse como confusión, desorientación, agitación, letargo o incluso pérdida de la conciencia. Esta condición es una emergencia médica, y requiere una evaluación y una atención inmediatas. Existen diversas causas de alteración aguda del estado mental en niños, algunas de las cuales incluyen infecciones del sistema nervioso central, como la meningitis o la encefalitis, los traumatismos craneoencefálicos, los trastornos metabólicos, las convulsiones o las intoxicaciones, entre otras. Este estudio tuvo como objetivo analizar, preparar y calificar la bibliografía actual para determinar las mejores recomendaciones sobre el tratamiento ante casos de alteración aguda del estado mental en pediatría de diferentes causas. El estudio se basó en la calificación de expertos en el campo para poder determinar la calificación de las recomendaciones, además de ser sometido a la revisión por parte del comité científico de la Academia Iberoamericana de Neurología Pediátrica. Nuestra guía representa una ayuda para el tratamiento de este síntoma inespecífico desde un enfoque básico y avanzado, aplicable por cualquier neurólogo pediatra.


Asunto(s)
Trastornos Mentales , Neurología , Humanos , Niño , Confusión , Sistema Nervioso Central , Neurólogos
7.
Cancer Res Commun ; 4(5): 1328-1343, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38687198

RESUMEN

Chronic lymphocytic leukemia (CLL) cell survival and growth is fueled by the induction of B-cell receptor (BCR) signaling within the tumor microenvironment (TME) driving activation of NFκB signaling and the unfolded protein response (UPR). Malignant cells have higher basal levels of UPR posing a unique therapeutic window to combat CLL cell growth using pharmacologic agents that induce accumulation of misfolded proteins. Frontline CLL therapeutics that directly target BCR signaling such as Bruton tyrosine kinase (BTK) inhibitors (e.g., ibrutinib) have enhanced patient survival. However, resistance mechanisms wherein tumor cells bypass BTK inhibition through acquired BTK mutations, and/or activation of alternative survival mechanisms have rendered ibrutinib ineffective, imposing the need for novel therapeutics. We evaluated SpiD3, a novel spirocyclic dimer, in CLL cell lines, patient-derived CLL samples, ibrutinib-resistant CLL cells, and in the Eµ-TCL1 mouse model. Our integrated multi-omics and functional analyses revealed BCR signaling, NFκB signaling, and endoplasmic reticulum stress among the top pathways modulated by SpiD3. This was accompanied by marked upregulation of the UPR and inhibition of global protein synthesis in CLL cell lines and patient-derived CLL cells. In ibrutinib-resistant CLL cells, SpiD3 retained its antileukemic effects, mirrored in reduced activation of key proliferative pathways (e.g., PRAS, ERK, MYC). Translationally, we observed reduced tumor burden in SpiD3-treated Eµ-TCL1 mice. Our findings reveal that SpiD3 exploits critical vulnerabilities in CLL cells including NFκB signaling and the UPR, culminating in profound antitumor properties independent of TME stimuli. SIGNIFICANCE: SpiD3 demonstrates cytotoxicity in CLL partially through inhibition of NFκB signaling independent of tumor-supportive stimuli. By inducing the accumulation of unfolded proteins, SpiD3 activates the UPR and hinders protein synthesis in CLL cells. Overall, SpiD3 exploits critical CLL vulnerabilities (i.e., the NFκB pathway and UPR) highlighting its use in drug-resistant CLL.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , Transducción de Señal , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/metabolismo , Leucemia Linfocítica Crónica de Células B/patología , Humanos , Animales , Ratones , Transducción de Señal/efectos de los fármacos , Piperidinas/farmacología , Piperidinas/uso terapéutico , Línea Celular Tumoral , Respuesta de Proteína Desplegada/efectos de los fármacos , Adenina/análogos & derivados , Adenina/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , FN-kappa B/metabolismo , Compuestos de Espiro/farmacología , Compuestos de Espiro/uso terapéutico , Supervivencia Celular/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacos , Receptores de Antígenos de Linfocitos B/metabolismo , Proliferación Celular/efectos de los fármacos
8.
Environ Sci Pollut Res Int ; 31(22): 31967-31977, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38642227

RESUMEN

Marine pollution by trace elements is a global concern due to potential toxicity to species and ecosystems. Copper is a fundamental trace element for many organisms; however, it becomes toxic at certain concentrations. The green turtle (Chelonia mydas) is a good sentinel species, due to its circumglobal distribution, long life cycle, coastal habits when juvenile, and is subject to environmental pollution. Quantifying and comparing copper levels makes it possible to understand the availability of this trace element in nature. During this research, comparisons were made between the levels of copper found in the liver, kidneys, and muscles of 35 turtles, from the United States (Hawaii and Texas), Brazil, and Japan. Copper was found in all specimens. In the liver, animals from Hawaii (91.08 µg g-1), Texas (46.11 µg g-1), and Japan (65.18 µg g-1) had statistically equal means, while those from Brazil (16. 79 µg g-1) had the lowest means. For the kidney, copper means were statistically equal for all Hawaii (3.71 µg g-1), Texas (4.83 µg g-1), Japan (2.47 µg g-1), and Brazil (1.89 µg g-1). In muscle, the means between Texas (0.75 µg g-1) and Japan (0.75 µg g-1) were the same, and the mean for Brazil (0.13 µg g-1) was the lowest. Among the organs, the highest levels of copper were found in the liver (28.33 µg g-1) followed by the kidney (2.25 µg g-1) and with the lowest levels in the muscle (0.33 µg g-1). This is the first study of copper levels among marine vertebrates in distant parts of the globe using similar comparative filters between different locations. Similar levels in turtles from such distant locations may indicate that there is a pantropical pattern of copper distribution in the biota, and that these animals are subject to the process of bioavailability of this metal in the environment and metabolic regulation.


Asunto(s)
Cobre , Tortugas , Contaminantes Químicos del Agua , Animales , Tortugas/metabolismo , Cobre/análisis , Océano Pacífico , Contaminantes Químicos del Agua/análisis , Océano Atlántico , Monitoreo del Ambiente , Brasil , Hígado/metabolismo , Hígado/química , Riñón/química , Japón , Texas
9.
ESMO Open ; 9(3): 102903, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38452436

RESUMEN

BACKGROUND: HER2DX, a multianalyte genomic test, has been clinically validated to predict breast cancer recurrence risk (relapse risk score), the probability of achieving pathological complete response post-neoadjuvant therapy (pCR likelihood score), and individual ERBB2 messenger RNA (mRNA) expression levels in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This study delves into the comprehensive analysis of HER2DX's analytical performance. MATERIALS AND METHODS: Precision and reproducibility of HER2DX risk, pCR, and ERBB2 mRNA scores were assessed within and between laboratories using formalin-fixed paraffin-embedded (FFPE) tumor tissues and purified RNA. Robustness was appraised by analyzing the impact of tumor cell content and protocol variations including different instruments, reagent lots, and different RNA extraction kits. Variability was evaluated across intratumor biopsies and genomic platforms [RNA sequencing (RNAseq) versus nCounter], and according to protocol variations. RESULTS: Precision analysis of 10 FFPE tumor samples yielded a maximal standard error of 0.94 across HER2DX scores (1-99 scale). High reproducibility of HER2DX scores across 29 FFPE tumors and 20 RNAs between laboratories was evident (correlation coefficients >0.98). The probability of identifying score differences >5 units was ≤5.2%. No significant variability emerged based on platform instruments, reagent lots, RNA extraction kits, or TagSet thaw/freeze cycles. Moreover, HER2DX displayed robustness at low tumor cell content (10%). Intratumor variability across 212 biopsies (106 tumors) was <4.0%. Concordance between HER2DX scores from 30 RNAs on RNAseq and nCounter platforms exceeded 90.0% (Cohen's κ coefficients >0.80). CONCLUSIONS: The HER2DX assay is highly reproducible and robust for the quantification of recurrence risk, pCR likelihood, and ERBB2 mRNA expression in early-stage HER2-positive breast cancer.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Reproducibilidad de los Resultados , Recurrencia Local de Neoplasia/genética , ARN/análisis , ARN Mensajero/genética
10.
Int J Environ Health Res ; : 1-10, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38351519

RESUMEN

Global environmental crises demand scaled-up investment in education about planetary health. We identified college and university programs in the United States that focus on the human-animal-ecosystem nexus by systematically searching the 2023-2024 catalogs of more than 1000 schools. We identified four frequently-used curricular models: (1) One Health programs offered by universities with veterinary and agriculture schools that emphasize zoonotic diseases, antimicrobial resistance, food safety, and wildlife conservation; (2) climate change and health (climate medicine) programs for graduate and professional students at large universities with medical and public health schools; (3) global environmental public health programs focused on pollution and other exposures; and (4) sustainability and health programs emphasizing food security, environmental justice, and other health issues that can be improved with ethical design and engineering. Highlighting the shared goals of these distinct academic models may help make planetary health a more visible area of teaching, research, and practice.

11.
Phys Rev Lett ; 132(6): 065102, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38394591

RESUMEN

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G_{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G_{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

13.
Artículo en Inglés | MEDLINE | ID: mdl-38184070

RESUMEN

AIM: To assess the radiopharmacist's role in a multidisciplinary team focused on the contraindications of regadenoson in order to ensure the safe use of pharmacologic vasodilator stress agents in patients undergoing SPECT-MPI. METHODS: We ambispectively studied its safe use in 1905 patients (54.1% female, mean age: 66.6±11.7 years, range: 20-95 years). Sex, age, medical history, medications, drug allergies, and contraindications for stress testing were registered together with recommendations for the nuclear physician in charge. RESULTS: Detected contraindications and corresponding recommendations were as follows: risk factors for QTc interval prolongation 7.5% - measurement of QTc interval previously to test and monitor ECG; prior stroke or TIA 4.2% - consider carotid stenosis assessment; salicylates/sulfonamides allergy 3.1% - use 99mTc-sestamibi; epilepsy or risk factors for seizures 2.4% - use of adenosine or reconsider test indication; systemic corticosteroid therapy for severe COPD 1.3% - reassessment of patient's condition; acute exacerbation of COPD 0.8% - defer test until acute episode is over; severe asthma 0.4% - do not perform test; methylxanthine ingestion 0.3% - avoid consumption previously; other 6.1% - evaluation of other contraindications. No contraindications were detected in 73.6% of patients. The test was canceled due to absolute contraindications in 2.9% of the requests. CONCLUSIONS: Working in a systematic way, the radiopharmacist was able to detect a high number of issues related to regadenoson, with one out of four patients presenting some clinical contraindication. The recommendations given by the radiopharmacist were well accepted by the nuclear physicians who changed their approach contributing to increase the safety of patients referred for MPI.


Asunto(s)
Imagen de Perfusión Miocárdica , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Vasodilatadores/efectos adversos , Imagen de Perfusión Miocárdica/métodos , Seguridad del Paciente , Tomografía Computarizada de Emisión de Fotón Único/métodos , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente
14.
Neurologia (Engl Ed) ; 39(3): 282-291, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37116688

RESUMEN

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease whose aetiology is unknown. It is characterised by upper and lower motor neuron degeneration. Approximately 90% of cases of ALS are sporadic, whereas the other 10% are familial. Regardless of whether the case is familial o sporadic, patients will develop progressive weakness, muscle atrophy with spasticity, and muscle contractures. Life expectancy of these patients is generally 2 to 5 years after diagnosis. DEVELOPMENT: In vivo models have helped to clarify the aetiology and pathogenesis of ALS, as well as the mechanisms of the disease. However, as these mechanisms are not yet fully understood, experimental models are essential to the continued study of the pathogenesis of ALS, as well as in the search for possible therapeutic targets. Although 90% of cases are sporadic, most of the models used to study ALS pathogenesis are based on genetic mutations associated with the familial form of the disease; the pathogenesis of sporadic ALS remains unknown. Therefore, it would be critical to establish models based on the sporadic form. CONCLUSIONS: This article reviews the main genetic and sporadic experimental models used in the study of this disease, focusing on those that have been developed using rodents.


Asunto(s)
Esclerosis Amiotrófica Lateral , Enfermedades Neurodegenerativas , Humanos , Animales , Ratones , Esclerosis Amiotrófica Lateral/patología , Proteínas de Unión al ADN/genética , Mutación
15.
Ecohealth ; 20(4): 390-401, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38110613

RESUMEN

Olive ridleys (Lepidochelys olivacea) are the most common sea turtle found in the Gulf of California. Unfortunately, the bacterial flora of nesting olive ridley turtles is still unknown. We conducted a study to identify, characterize, serotype, and determine the antibiotic resistance of potentially pathogenic bacteria isolated from olive ridley turtles nesting in northwestern Mexico. Bacteria were isolated and identified from the oral cavity and cloaca of 47 postnesting turtles. Escherichia coli and Vibrio parahaemolyticus were characterized, and antibiotic resistance testing was performed. One hundred bacteria belonging to 21 species were isolated, 53 from the oral cavity and 47 from the cloaca, the most prevalent being Pseudomonas aeruginosa, followed by Aeromonas hydrophila, Vibrio alginolyticus, Vibrio parahaemolyticus, Klebsiella pneumoniae, and E. coli, among others. Moreover, two to three different bacterial species were found co-colonizing both anatomical sites in some turtles. E. coli phylogroups B1, A, F, and unknown were identified as diarrheagenic E. coli (enteroaggregative and enteropathogenic E. coli). O1, O4, K8, K12, OUT, and KUT of V. parahaemolyticus serogroups were identified, also comprising pathogenic and nonpathogenic strains. Finally, 100% of the bacterial species tested were antibiotic resistant, and both MDR and XDR strains were found. In conclusion, olive ridley turtles are colonized by a diversity of bacterial species with a high rate of antibiotic resistance, some with pathogenic potential to turtles, representing a health risk factor for the species.


Asunto(s)
Tortugas , Animales , Bacterias , Escherichia coli , México , Pigmentación de la Piel
16.
Sci Rep ; 13(1): 15464, 2023 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-37726331

RESUMEN

The critically endangered black rhinoceros (Diceros bicornis; black rhino) experiences extinction threats from poaching in-situ. The ex-situ population, which serves as a genetic reservoir against impending extinction threats, experiences its own threats to survival related to several disease syndromes not typically observed among their wild counterparts. We performed an untargeted metabolomic analysis of serum from 30 ex-situ housed black rhinos (Eastern black rhino, EBR, n = 14 animals; Southern black rhino, SBR, n = 16 animals) and analyzed differences in metabolite profiles between subspecies, sex, and health status (healthy n = 13 vs. diseased n = 14). Of the 636 metabolites detected, several were differentially (fold change > 1.5; p < 0.05) expressed between EBR vs. SBR (40 metabolites), female vs. male (36 metabolites), and healthy vs. diseased (22 metabolites). Results suggest dysregulation of propanoate, amino acid metabolism, and bile acid biosynthesis in the subspecies and sex comparisons. Assessment of healthy versus diseased rhinos indicates involvement of arachidonic acid metabolism, bile acid biosynthesis, and the pentose phosphate pathway in animals exhibiting inflammatory disease syndromes. This study represents the first systematic characterization of the circulating serum metabolome in the black rhinoceros. Findings further implicate mitochondrial and immune dysfunction as key contributors for the diverse disease syndromes reported in ex-situ managed black rhinos.


Asunto(s)
Enfermedades del Sistema Inmune , Metabolómica , Femenino , Masculino , Animales , Síndrome , Perisodáctilos , Ácidos y Sales Biliares
17.
Nat Rev Nephrol ; 19(7): 440-450, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36973495

RESUMEN

Renal cell carcinoma (RCC) comprises a group of malignancies arising from the kidney with unique tumour-specific antigen (TSA) signatures that can trigger cytotoxic immunity. Two classes of TSAs are now considered potential drivers of immunogenicity in RCC: small-scale insertions and deletions (INDELs) that result in coding frameshift mutations, and activation of human endogenous retroviruses. The presence of neoantigen-specific T cells is a hallmark of solid tumours with a high mutagenic burden, which typically have abundant TSAs owing to non-synonymous single nucleotide variations within the genome. However, RCC exhibits high cytotoxic T cell reactivity despite only having an intermediate non-synonymous single nucleotide variation mutational burden. Instead, RCC tumours have a high pan-cancer proportion of INDEL frameshift mutations, and coding frameshift INDELs are associated with high immunogenicity. Moreover, cytotoxic T cells in RCC subtypes seem to recognize tumour-specific endogenous retrovirus epitopes, whose presence is associated with clinical responses to immune checkpoint blockade therapy. Here, we review the distinct molecular landscapes in RCC that promote immunogenic responses, discuss clinical opportunities for discovery of biomarkers that can inform therapeutic immune checkpoint blockade strategies, and identify gaps in knowledge for future investigations.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/patología , Antígenos de Neoplasias/genética , Inhibidores de Puntos de Control Inmunológico , Neoplasias Renales/patología , Nucleótidos
18.
Environ Sci Pollut Res Int ; 30(17): 50509-50519, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36795213

RESUMEN

Pollution is one of the biggest threats to marine life and trace elements are among the most toxic pollutants in this environment. Zn is an essential trace element for biota but becomes toxic at high concentrations. Sea turtles are good bioindicators of trace element pollution, due to their longevity and cosmopolitan distribution that allow bioaccumulation for years in their tissues. Determining and comparing Zn concentrations in sea turtles from faraway places is relevant for conservation due to the lack of knowledge of geographically broader distribution patterns of Zn in vertebrates. In this study, comparative analyses of bioaccumulation in the liver, kidney, and muscles of 35 C. mydas from Brazil, Hawaii, the USA (Texas), Japan, and Australia of statistically equal sizes were performed. Zn was found in all specimens, with the highest levels in the liver and kidneys. Specimens from Australia (30.58 µg g-1), Hawaii (31.91 µg g-1), Japan (29.99 µg g-1), and the USA (33.79 µg g-1) showed statistically equal means in the liver. Kidney levels were the same in Japan (35.09 µg g-1) and the USA (37.29 µg g-1) and the same in Australia (23.06 µg g-1) and Hawaii (23.31 µg/g). Specimens from Brazil had the lowest means in both organs (12.17 µg g-1 in the liver and 9.39 µg g-1 in the kidney). The pattern of equal Zn values for most specimens in the liver is an important finding, demonstrating that there are pantropical patterns in the distribution of this metal even in regions so far from each other. A possible explanation is due to the essential nature of this metal linked to metabolic regulation, in addition to the bioavailability for biological absorption in marine environments, such as RS in Brazil, with a lower standard bioavailability also found in other organisms. Therefore, factors such as metabolic regulation and bioavailability indicate that there is a pantropical distribution of Zn in marine biota and green turtles can be a useful model as a sentinel species.


Asunto(s)
Oligoelementos , Tortugas , Contaminantes Químicos del Agua , Animales , Zinc/análisis , Oligoelementos/análisis , Tortugas/metabolismo , Contaminantes Químicos del Agua/análisis , Hígado/metabolismo
19.
Zoonoses Public Health ; 70(4): 327-340, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36757053

RESUMEN

SARS-CoV-2 can infect pets under natural conditions, which raises questions about the risk factors related to the susceptibility of these animals to infection. The status of pet infection by SARS-CoV-2 in Mexico is not well-understood. We aimed to estimate the frequency of positive household cats and dogs to viral RNA and antibodies for SARS-CoV-2 during the second wave of human infections in Mexico, and to recognize the major risk factors related to host and pet ownership behaviour. We evaluated two study groups, cats and dogs from COVID-19-infected/-suspected households (n = 44) and those admitted for veterinary care for any reason at several veterinary hospitals in Puebla City, Mexico (n = 91). Using RT-PCR, we identified the presence of SARS-CoV-2 RNA in swabs of four dogs (18.18%) and zero cats in COVID-19-infected/-suspected households; within this group, 31.82% of dogs and 27.27% of cats were tested IgG ELISA-positive; and neutralizing antibodies were detected in one dog (4.55%) and two cats (9.09%). In the random group (pets evaluated at private clinics and veterinary teaching hospital), 25.00% of dogs and 43.59% of cats were ELISA-positive and only one cat showed neutralizing antibodies (2.56%). Older than 4-year-old, other pets at home, and daily cleaning of pet dish, were each associated with an increase in SARS-CoV-2 infection (p < 0.05). Allowing face lick, sharing bed/food with pets and owner tested positive or suspected COVID-19 were not significant risk factors, but more than 4 h the owner spent away from home during the lockdown for COVID-19 (OR = 0.37, p = 0.01), and outdoor pet food tray (OR = 0.32, p = 0.01) significantly decreased the risks of SARS-CoV-2 infection in pets, suggesting that time the owner spends with their pet is an important risk factor.


Asunto(s)
COVID-19 , Enfermedades de los Gatos , Enfermedades de los Perros , Animales , Gatos , Humanos , Perros , COVID-19/epidemiología , COVID-19/veterinaria , SARS-CoV-2 , Propiedad , México/epidemiología , Hospitales Veterinarios , ARN Viral , Control de Enfermedades Transmisibles , Hospitales de Enseñanza , Anticuerpos Neutralizantes , Factores de Riesgo , Mascotas , Enfermedades de los Gatos/epidemiología , Enfermedades de los Perros/epidemiología
20.
Artículo en Inglés | MEDLINE | ID: mdl-36758829

RESUMEN

AIM: To analyze a sample of pregnant patients who underwent pulmonary perfusion scintigraphy to rule out suspicion of pulmonary embolism (PE) during the acute COVID-19 infection hospitalization period in our hospital. MATERIAL AND METHODS: SPECT scintigraphy with a reduced dose (111MBq) of 99mTc-macroaggregated albumin was performed in all the patients (n=5). The images obtained were interpreted by comparing the findings with the radiological images according to the PISAPED criteria. RESULTS: Only one of the 5 patients was diagnosed with PE. Two patients showed pathological scintigraphy findings attributable to radiological alterations due to COVID-19 pneumonia, and the other two had normal pulmonary perfusion. CONCLUSION: Given the non-specific features of the clinical manifestations and d-dimer values ​​in COVID-19, as well as their similarity to those of PE, pulmonary perfusion scintigraphy plays a crucial role in the screening of PE in these patients due to its high sensitivity and lower irradiation compared to CT. Despite the limited number of patients, the results obtained have special relevance due to the absence of scientific publications in this group of patients within the exceptional context of the COVID-19 pandemic.


Asunto(s)
COVID-19 , Embolia Pulmonar , Embarazo , Humanos , Femenino , Mujeres Embarazadas , Pandemias , COVID-19/complicaciones , SARS-CoV-2 , Embolia Pulmonar/diagnóstico por imagen
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