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1.
BMC Plant Biol ; 24(1): 98, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38331735

RESUMEN

Pine wilt disease (PWD) is a devastating forest disease caused by the pinewood nematode (PWN), Bursaphelenchus xylophilus, a migratory endoparasite that infects several coniferous species. During the last 20 years, advances have been made for understanding the molecular bases of PWN-host trees interactions. Major advances emerged from transcriptomic and genomic studies, which revealed some unique features related to PWN pathogenicity and constituted fundamental data that allowed the development of postgenomic studies. Here we review the proteomic approaches that were applied to study PWD and integrated the current knowledge on the molecular basis of the PWN pathogenicity. Proteomics has been useful for understanding cellular activities and protein functions involved in PWN-host trees interactions, shedding light into the mechanisms associated with PWN pathogenicity and being promising tools to better clarify host trees PWN resistance/susceptibility.


Asunto(s)
Pinus , Tylenchida , Animales , Proteómica , Virulencia , Pinus/genética , Pinus/parasitología , Enfermedades de las Plantas/parasitología
2.
Ann Surg ; 276(5): 868-874, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-35916378

RESUMEN

OBJECTIVE: To propose a new decision algorithm combining biomarkers measured in a tumor biopsy with clinical variables, to predict recurrence after liver transplantation (LT). BACKGROUND: Liver cancer is one of the most frequent causes of cancer-related mortality. LT is the best treatment for hepatocellular carcinoma (HCC) patients but the scarcity of organs makes patient selection a critical step. In addition, clinical criteria widely applied in patient eligibility decisions miss potentially curable patients while selecting patients that relapse after transplantation. METHODS: A literature systematic review singled out candidate biomarkers whose RNA levels were assessed by quantitative PCR in tumor tissue from 138 HCC patients submitted to LT (>5 years follow up, 32% beyond Milan criteria). The resulting 4 gene signature was combined with clinical variables to develop a decision algorithm using machine learning approaches. The method was named HepatoPredict. RESULTS: HepatoPredict identifies 99% disease-free patients (>5 year) from a retrospective cohort, including many outside clinical criteria (16%-24%), thus reducing the false negative rate. This increased sensitivity is accompanied by an increased positive predictive value (88.5%-94.4%) without any loss of long-term overall survival or recurrence rates for patients deemed eligible by HepatoPredict; those deemed ineligible display marked reduction of survival and increased recurrence in the short and long term. CONCLUSIONS: HepatoPredict outperforms conventional clinical-pathologic selection criteria (Milan, UCSF), providing superior prognostic information. Accurately identifying which patients most likely benefit from LT enables an objective stratification of waiting lists and information-based allocation of optimal versus suboptimal organs.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/cirugía , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Selección de Paciente , ARN , Estudios Retrospectivos , Factores de Riesgo , Transcriptoma
3.
Mar Drugs ; 19(12)2021 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-34940681

RESUMEN

Marine biofouling is a natural process that represents major economic, environmental, and health concerns. Some booster biocides have been used in biofouling control, however, they were found to accumulate in environmental compartments, showing negative effects on marine organisms. Therefore, it is urgent to develop new eco-friendly alternatives. Phenyl ketones, such as benzophenones and acetophenones, have been described as modulators of several biological activities, including antifouling activity (AF). In this work, acetophenones were combined with other chemical substrates through a 1,2,3-triazole ring, a strategy commonly used in Medicinal Chemistry. In our approach, a library of 14 new acetophenone-triazole hybrids was obtained through the copper(I)-catalyzed alkyne-azide cycloaddition "click" reaction. All of the synthesized compounds were evaluated against the settlement of a representative macrofouling species, Mytilus galloprovincialis, as well as on biofilm-forming marine microorganisms, including bacteria and fungi. The growth of the microalgae Navicula sp. was also evaluated after exposure to the most promising compounds. While compounds 6a, 7a, and 9a caused significant inhibition of the settlement of mussel larvae, compounds 3b, 4b, and 7b were able to inhibit Roseobacter litoralis bacterial biofilm growth. Interestingly, acetophenone 7a displayed activity against both mussel larvae and the microalgae Navicula sp., suggesting a complementary action of this compound against macro- and microfouling species. The most potent compounds (6a, 7a, and 9a) also showed to be less toxic to the non-target species Artemia salina than the biocide Econea®. Regarding both AF potency and ecotoxicity activity evaluation, acetophenones 7a and 9a were put forward in this work as promising eco-friendly AF agents.


Asunto(s)
Acetofenonas/farmacología , Incrustaciones Biológicas/prevención & control , Desinfectantes/farmacología , Triazoles/farmacología , Acetofenonas/química , Animales , Organismos Acuáticos , Biopelículas/efectos de los fármacos , Bivalvos/efectos de los fármacos , Desinfectantes/química , Larva/efectos de los fármacos , Microalgas/efectos de los fármacos , Relación Estructura-Actividad , Triazoles/química
4.
Molecules ; 25(24)2020 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-33322412

RESUMEN

The introduction of antifungals in clinical practice has an enormous impact on the provision of medical care, increasing the expectancy and quality of life mainly of immunocompromised patients. However, the emergence of pathogenic fungi that are resistant and multi-resistant to the existing antifungal therapy has culminated in fungal infections that are almost impossible to treat. Therefore, there is an urgent need to discover new strategies. The marine environment has proven to be a promising rich resource for the discovery and development of new antifungal compounds. Thus, this review summarizes more than one hundred marine natural products, or their derivatives, which are categorized according to their sources-sponges, bacteria, fungi, and sea cucumbers-as potential candidates as antifungal agents. In addition, this review focus on recent developments using marine antifungal compounds as new and effective approaches for the treatment of infections caused by resistant and multi-resistant pathogenic fungi and/or biofilm formation; other perspectives on antifungal marine products highlight new mechanisms of action, the combination of antifungal and non-antifungal agents, and the use of nanoparticles and anti-virulence therapy.


Asunto(s)
Antifúngicos/química , Productos Biológicos/química , Micosis/tratamiento farmacológico , Animales , Bacterias , Bioensayo , Química Farmacéutica , Farmacorresistencia Fúngica/efectos de los fármacos , Hongos , Humanos , Nanopartículas/química , Poríferos , Especies Reactivas de Oxígeno , Pepinos de Mar , Virulencia
5.
Front Sports Act Living ; 6: 1407848, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39184032

RESUMEN

Introduction: Video games have become increasingly popular worldwide, attracting billions of gamers across diverse demographics. While studies have highlighted their potential benefits, concerns about problematic gaming behaviors have also emerged. Conditions such as Internet Gaming Disorder (IGD) have been recognized by major health organizations, necessitating accurate diagnostic tools. However, existing methods, primarily reliant on self-report questionnaires, face challenges in accuracy and consistency. This paper proposes a novel technological approach to provide gaming behavior indicators, aiming to offer precise insights into gamer behavior and emotion regulation. Methods: To attain this objective, we investigate quantifiable gaming behavior metrics using automated, unobtrusive, and easily accessible methods. Our approach encompasses the analysis of behavioral telemetry data collected from online gaming platforms and incorporates automated extraction of gamer emotional states from face video recordings during gameplay. To illustrate the metrics and visualizations and demonstrate our method's application we collected data from two amateur and two professional gamers, all of whom played Counter-Strike2 on PC. Our approach offers objective insights into in-game gamer behavior, helping health professionals in the identification of patterns that may be difficult to discern through traditional assessment methods. Results: Preliminary assessments of the proposed methodology demonstrate its potential usefulness in providing valuable insights about gaming behavior and emotion regulation. By leveraging automated data collection and visualization analysis techniques, our approach offers a more comprehensive understanding of gamer behavior, which could enhance diagnostic accuracy and inform interventions for individuals at risk of problematic gaming behaviors. Conclusion: Our findings demonstrate the valuable insights obtainable from a tool that collects telemetry data, emotion regulation metrics, and gaming patterns. This tool, utilizing specific indicators, can support healthcare professionals in diagnosing IGD and tracking therapeutic progress, potentially addressing challenges linked to conventional IGD assessment methods. Furthermore, this initial data can provide therapists with detailed information on each player's problematic behaviors and gaming habits, enabling the development of personalized treatments tailored to individual needs. Future research endeavors will focus on refining the methodology and extending its application in clinical settings to facilitate more comprehensive diagnostic practices and tailored interventions for individuals at risk of problematic gaming behaviors.

6.
Front Sports Act Living ; 6: 1502895, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39469606

RESUMEN

[This corrects the article DOI: 10.3389/fspor.2024.1407848.].

7.
Port J Card Thorac Vasc Surg ; 31(2): 41-45, 2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38971990

RESUMEN

INTRODUCTION: Worldwide, there is an increase in scrutiny after surgical treatment of a vast array of pathologies. Doing so, a large body of evidence clearly supports centralisation, such as teaching hospitals, where a larger caseload enables optimal outcomes. These institutions have a strong presence of surgical residents seeking training in both technical and non-technical skills. Inevitably, as part of training, they will be involved in the surgical treatment of those patients, even as the primary operator. We sought to investigate the impact of trainee performed procedures in outcomes of common vascular procedures of different technical complexity. METHODS: A non-systematic MEDLINE and Scopus databases review on the outcomes of resident performed common vascular procedures was performed. RESULTS: Specific evidence in many procedures (venous disease, aortic aneurysms, peripheral artery disease) is lacking. After carotid endarterectomy (CEA), resident performed procedures seem to have similar cranial nerve palsy and stroke when compared to expert surgeons. Generally, resident-performed primary radiocephalic and elbow arteriovenous fistula (AVF) presents similar primary and secondary patency. As with CEA, AVF procedures performed by residents took longer. On aortic aneurysms, although no specific comparison has been performed, resident involvement (irrespective of surgeon or assistant) in these procedures does not seem associated with increased adverse events. CONCLUSION: In most vascular surgery procedures, little is known about resident performance and their impact on outcomes. Notwithstanding, resident-performed CEA and primary AVF seem free of major compromise to patients. Further research is warranted to clarify this topic.


Asunto(s)
Competencia Clínica , Internado y Residencia , Procedimientos Quirúrgicos Vasculares , Humanos , Procedimientos Quirúrgicos Vasculares/educación , Resultado del Tratamiento
8.
J Affect Disord ; 366: 226-233, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39216639

RESUMEN

The identification of psychopathological markers has been the focus of several scientific fields. The results were inconsistent due to lack of a clear nosology. Network analysis, focusing on the interactions between symptoms, provided important insights into the nosology of mental disorders. These interactions originate several topological properties that could constitute markers of psychopathology. One of these properties is network connectivity, which has been explored in recent years. However, the results have been inconsistent, and the topological properties of psychopathological networks remain largely unexplored and unknown. We compared several topological properties (i.e., connectivity, average path length, assortativity, average degree, modularity, global clustering) of psychopathological networks of healthy and disordered participants across depression (N = 2830), generalized anxiety (N = 13,463), social anxiety (N = 12,814), and obsessive-compulsive disorder (N = 16,426). Networks were estimated using Bayesian Gaussian Graphical Models. The Janson-Shannon measure of divergence was used to identify differences between the network properties. Network connectivity distinguished healthy and disordered participants' networks in all disorders. However, in depression and generalized anxiety, network connectivity was higher in healthy participants. The presence and number of motifs also distinguished the networks of healthy and disordered participants. Other topological properties (i.e., modularity, clustering, average path length and average degree) seem to be disorder-specific. The psychopathological significance of network connectivity must be clarified. Some topological properties of psychopathological networks are promising markers of psychopathology and may contribute to clarifying the nosology of mental disorders.


Asunto(s)
Trastornos de Ansiedad , Teorema de Bayes , Trastorno Obsesivo Compulsivo , Humanos , Femenino , Masculino , Adulto , Trastornos de Ansiedad/psicología , Trastornos de Ansiedad/fisiopatología , Trastorno Obsesivo Compulsivo/fisiopatología , Trastorno Obsesivo Compulsivo/psicología , Trastornos Mentales/psicología , Trastornos Mentales/fisiopatología , Persona de Mediana Edad , Trastorno Depresivo/psicología , Trastorno Depresivo/fisiopatología , Fobia Social/fisiopatología , Fobia Social/psicología , Psicopatología
9.
Front Public Health ; 12: 1362148, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39319300

RESUMEN

Background: Emotions can be regulated through several regulatory strategies that are involved in the development of psychopathological symptoms. Despite the well-established association between psychopathology and emotion dysregulation, little is known about the relationship between individual symptoms of depression and anxiety and emotion regulation strategies (ERS), as well as between ERS themselves. Method: We conducted a cross-sectional study and examined the interactions between six ERS (reappraisal, engagement, rumination, suppression, arousal control, and distraction) and assessed their distinctive association with the activation of specific symptoms of depression and anxiety in a community sample of 376 adults (80.4% female; Mage = 32.70; SDage = 11.80). The Regulation Emotion Systems Survey (RESS) was used to measure ERS. The Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) were used to assess psychological symptoms. An exploratory graph analysis was performed to examine the structural properties of the network of interactions between these behaviors. Additionally, to test the association of ERS with the activation of the depression symptoms network, an expected symptoms activity (ESA) was conducted. Results: Six communities were found that correspond to the six ERS. Rumination and suppression have a significant association with symptom activation (particularly low self-esteem), whereas reappraisal reduces symptomatic activation. The effect of arousal control, engagement, and distraction appears to depend on the remaining ERS rather than having much influence on their own. Conclusion: This study provides insight into how ERS interact with each other and with individual symptoms of depression and anxiety. Understanding the effects of these interactions on symptom activation and comorbidity can improve our understanding of psychopathology.


Asunto(s)
Ansiedad , Depresión , Regulación Emocional , Humanos , Femenino , Masculino , Estudios Transversales , Regulación Emocional/fisiología , Adulto , Depresión/psicología , Encuestas y Cuestionarios , Ansiedad/psicología , Persona de Mediana Edad , Trastornos de Ansiedad/psicología , Adulto Joven
10.
Pract Lab Med ; 39: e00365, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38371895

RESUMEN

Objectives: To verify the analytical performance of the HepatoPredict kit, a novel tool developed to stratify Hepatocellular Carcinoma (HCC) patients according to their risk of relapse after a Liver Transplantation (LT). Methods: The HepatoPredict tool combines clinical variables and a gene expression signature in an ensemble of machine-learning algorithms to forecast the benefit of a LT in HCC patients. To ensure the accuracy and reliability of this method, extensive analytical validation was conducted to verify its specificity and robustness. The experiments were designed following the guidelines for multi-target genomic assays such as ISO201395-2019, MIQE, CLSI-MM16, CLSI-MM17, and CLSI-EP17-A. The validation process included reproducibility between operators and between RNA extractions and RT-qPCR runs, and interference of input RNA levels or varying reagent levels. A recently retrained version of the HepatoPredict algorithms was also tested. Results: The validation process demonstrated that the HepatoPredict kit met the required standards for robustness (p > 0.05), analytical specificity (inclusivity of 95 %), and sensitivity (LoB, LoD, linear range, and amplification efficiency between 90 and 110 %). The operator, equipment, input RNA, and reagents used had no significant effect on the HepatoPredict results. Additionally, the testing of a recently retrained version of the HepatoPredict algorithm, showed that this new version further improved the accuracy of the kit and performed better than existing clinical criteria in accurately identifying HCC patients who are more likely to benefit LT. Conclusions: Even with the introduced variations in molecular and clinical variables, the HepatoPredict kit's prognostic information remains consistent. It can accurately identify HCC patients who are more likely to benefit from a LT. Its robust performance also confirms that it can be easily integrated into standard diagnostic laboratories.

11.
bioRxiv ; 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39463929

RESUMEN

Enteric neurons control gut physiology by regulating peristalsis, nutrient absorption, and secretion 1 . Disruptions in microbial communities caused by antibiotics or enteric infections result in the loss of enteric neurons and long-term motility disorders 2-5 . However, the signals and underlying mechanisms of this microbiota-neuron communication are unknown. We studied the effects of microbiota on the recovery of the enteric nervous system after microbial dysbiosis caused by antibiotics. We found that both enteric neurons and glia are lost after antibiotic exposure, but recover when the pre-treatment microbiota is restored. Using murine gnotobiotic models and fecal metabolomics, we identified neurogenic bacterial species and their derived metabolite succinate as sufficient to rescue enteric neurons and glia. Unbiased single-nuclei RNA-seq analysis uncovered a novel neural precursor-like population marked by the expression of the neuronal gene Nav2. Genetic fate-mapping showed that Plp1+ enteric glia differentiate into neurons following antibiotic exposure. In contrast, Nav2+ neurons expand upon succinate treatment and indicate an alternative mode of neuronal regeneration under recovery conditions. Our findings highlight specific microbial species, metabolites, and the underlying cellular mechanisms involved in neuronal regeneration, with potential therapeutic implications for peripheral neuropathies.

12.
Cureus ; 15(1): e34367, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36874659

RESUMEN

Cobicistat, used as a pharmacokinetic booster in therapeutic combination with human immunodeficiency virus (HIV) protease inhibitors and integrase inhibitors, is a strong inhibitor of cytochrome P450 3A4 (CYP3A4). Since most glucocorticoids are metabolized by the isoenzyme of the cytochrome P450 pathway, their plasma concentrations can be highly increased in the presence of cobicistat-boosted darunavir, with subsequent risk of iatrogenic Cushing's syndrome (ICS) and secondary adrenal insufficiency. We report a case of a 45-year-old man with HIV-hepatitis C virus co-infection treated with raltegravir and darunavir/cobicistat since 2019. In May 2021, he underwent a sleeve gastrectomy due to morbid obesity (BMI: 50.9 kg/m2) with multiple comorbidities. Four months after surgery, he was diagnosed with asthma and was started on inhaled budesonide, which was later changed to fluticasone propionate. At the 12-month postoperative visit, the patient referred proximal muscle weakness and asthenia, and suboptimal weight loss (excess weight loss of 39%) and high blood pressure were documented. Moon facies, buffalo hump, and abdominal large vinous striae were evident on physical examination. Laboratory studies showed impaired glucose metabolism and hypokalemia. Cushing's syndrome was suspected and further investigation confirmed its iatrogenic origin. The diagnosis of ICS and consequent secondary adrenal insufficiency due to an interaction between the darunavir/cobicistat combination and budesonide/fluticasone was established. Darunavir/cobicistat therapy was replaced by dolutegravir/doravirine dual therapy, inhaled corticoid was switched to beclomethasone, and glucocorticoid substitutive therapy was introduced. This is a particular case of overt ICS due to cobicistat-inhaled corticosteroid interaction in a superobese patient, developed after he underwent bariatric surgery. The presence of morbid obesity, combined with the rarity of this pharmacological complication in individuals taking cobicistat, made the correct diagnosis even more challenging. A meticulous review of pharmacologic habits and potential interactions is essential to avoid serious harm to patients.

13.
Eur J Case Rep Intern Med ; 10(6): 003813, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37304996

RESUMEN

Pseudopheochromocytoma is a pathological condition presenting with paroxysmal hypertension with normal or moderate elevation in catecholamines and metanephrine levels, but no evidence of a tumoural cause. Imaging studies and I-123 metaiodobenzylguanidine scintigraphy are essential for exclusion of pheocromocytoma. We describe a case of pseudopheochromocytoma related to levodopa in a patient with paroxysmal hypertension, headache, sweating, palpitations and increased plasmatic and urinary metanephrine levels, without adrenal or extra-adrenal tumour. The beginning of the patient's clinical symptoms coincided with the initiation of the levodopa treatment and the complete resolution of the symptoms occurred after the discontinuation of levodopa. LEARNING POINTS: Pseudopheochromocytoma and pheochromocytoma may have the same clinical and laboratorial presentation but different aetiologies.The diagnosis of pseudopheochromocytoma is based on paroxysmal hypertension with normal or increased plasma and urine levels of catecholamines or metanephrines after exclusion of a tumoural process.The pseudopheochromocytoma may be associated with levodopa, alone or in combination with other drugs that are likely to interfere with dopamine or catecholamine metabolism.

14.
Mol Med Rep ; 28(1)2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37232349

RESUMEN

Genetic testing for susceptibility genes through next­generation sequencing (NGS) has become a widely used technique. Using this, a number of genetic variants have been identified, several of which are variants of unknown significance (VUS). These VUS can either be pathogenic or benign. However, since their biological effect remains unclear, functional assays are required to classify their functional nature. As the use of NGS becomes more mainstream as a diagnostic tool in clinical practice, the number of VUS is expected to increase. This necessitates their biological and functional classification. In the present study, a VUS was identified in the BRCA1 gene (NM_007294.3:c.1067A>G) in two women at risk for breast cancer, for which no functional data has been reported. Therefore, peripheral lymphocytes were isolated from the two women and also from two women without the VUS. DNA from all samples were sequenced by NGS of a breast cancer clinical panel. Since the BRCA1 gene is involved in DNA repair and apoptosis, the functional assays chromosomal aberrations, cytokinesis­blocked micronucleus, comet, γH2AX, caspase and TUNEL assays were then conducted on these lymphocytes after a genotoxic challenge by ionizing radiation or doxorubicin to assess the functional role of this VUS. The micronucleus and TUNEL assays revealed a lower degree of DNA induced­damage in the VUS group compared with those without the VUS. The other assays showed no significant differences between the groups. These results suggested that this BRCA1 VUS is likely benign, since the VUS carriers were apparently protected from deleterious chromosomal rearrangements, subsequent genomic instability and activation of apoptosis.


Asunto(s)
Neoplasias de la Mama , Neoplasias Ováricas , Femenino , Humanos , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Pruebas Genéticas/métodos , Genes BRCA1 , Reparación del ADN , Daño del ADN/genética , Predisposición Genética a la Enfermedad , Neoplasias Ováricas/genética , Proteína BRCA2/genética
15.
Front Plant Sci ; 14: 1191923, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37342130

RESUMEN

The root-knot nematode (RKN) Meloidogyne luci presents a threat to the production of several important crops. This nematode species was added to the European Plant Protection Organization Alert list in 2017. The scarce availability of efficient nematicides to control RKN and the phasing out of nematicides from the market have intensified the search for alternatives, such as phytochemicals with bionematicidal properties. The nematicidal activity of 1,4-naphthoquinone (1,4-NTQ) against M. luci has been demonstrated; however, knowledge of the potential mode(s) of action of this compound is still scarce. In this study, the transcriptome profile of M. luci second-stage juveniles (J2), the infective stage, in response to 1,4-NTQ exposure was determined by RNA-seq to identify genes and pathways that might be involved in 1,4-NTQ's mode(s) of action. Control treatments, consisting of nematodes exposed to Tween® 80 (1,4-NTQ solvent) and to water, were included in the analysis. A large set of differentially expressed genes (DEGs) was found among the three tested conditions, and a high number of downregulated genes were found between 1,4-NTQ treatment and water control, reflecting the inhibitory effect of this compound on M. luci, with a great impact on processes related to translation (ribosome pathway). Several other nematode gene networks and metabolic pathways affected by 1,4-NTQ were also identified, clarifying the possible mode of action of this promising bionematicide.

16.
Sci Rep ; 12(1): 11512, 2022 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-35798798

RESUMEN

Hepatocellular carcinoma (HCC) is amongst the cancers with highest mortality rates and is the most common malignancy of the liver. Early detection is vital to provide the best treatment possible and liquid biopsies combined with analysis of circulating tumour DNA methylation show great promise as a non-invasive approach for early cancer diagnosis and monitoring with low false negative rates. To identify reliable diagnostic biomarkers of early HCC, we performed a systematic analysis of multiple hepatocellular studies and datasets comprising > 1500 genome-wide DNA methylation arrays, to define a methylation signature predictive of HCC in both tissue and cell-free DNA liquid biopsy samples. Our machine learning pipeline identified differentially methylated regions in HCC, some associated with transcriptional repression of genes related with cancer progression, that benchmarked positively against independent methylation signatures. Combining our signature of 38 DNA methylation regions, we derived a HCC detection score which confirmed the utility of our approach by identifying in an independent dataset 96% of HCC tissue samples with a precision of 98%, and most importantly successfully separated cfDNA of tumour samples from healthy controls. Notably, our risk score could identify cell-free DNA samples from patients with other tumours, including colorectal cancer. Taken together, we propose a comprehensive HCC DNA methylation fingerprint and an associated risk score for detection of HCC from tissue and liquid biopsies.


Asunto(s)
Carcinoma Hepatocelular , Ácidos Nucleicos Libres de Células , Neoplasias Hepáticas , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Ácidos Nucleicos Libres de Células/genética , Metilación de ADN/genética , Humanos , Biopsia Líquida , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología
17.
Antibiotics (Basel) ; 11(11)2022 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-36358143

RESUMEN

Fungal infections are one of the main causes of mortality and morbidity worldwide and taking into account the increasing incidence of strains resistant to classical antifungal drugs, the development of new agents has become an urgent clinical need. Considering that thioxanthones are bioisosteres of xanthones with known anti-infective actions, their scaffolds were selected for this study. A small library of synthesized aminothioxanthones (1-10) was evaluated for in vitro antifungal activity against Candida albicans, Aspergillus fumigatus, and Trichophyton rubrum; for the active compounds, the spectrum was further extended to other clinically relevant pathogenic fungi. The results showed that only compounds 1, 8, and 9 exhibited inhibitory and broad-spectrum antifungal effects. Given the greater antifungal potential presented, compound 1 was the subject of further investigations to study its anti-virulence activity and in an attempt to elucidate its mechanism of action; compound 1 seems to act predominantly on the cellular membrane of C. albicans ATCC 10231, altering its structural integrity, without binding to ergosterol, while inhibiting two important virulence factors-dimorphic transition and biofilm formation-frequently associated with C. albicans pathogenicity and resistance. In conclusion, the present work proved the usefulness of thioxanthones in antifungal therapy as new models for antifungal agents.

18.
Sci Rep ; 12(1): 16419, 2022 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-36180564

RESUMEN

Extended cut-off filtration by medium cut-off membranes (MCO) has been shown to be safe in maintenance hemodialysis (HD). The notion of using them for the control of chronic low-grade inflammation and positively influencing cellular immune aberrations seems tempting. We conducted an open label, multicenter, randomized, 90 day 2-phase cross over clinical trial (MCO- vs. high flux-HD). 46 patients underwent randomization of which 34 completed the study. Dialysate- or pre- and post-dialysis serum inflammatory mediators were assayed for each study visit. Ex vivo T cell activation was assessed from cryopreserved leucocytes by flow cytometry. Linear mixed models were used to compare treatment modalities, with difference in pre-dialysis serum MCP-1 levels after 3 months as the predefined primary endpoint. Filtration/dialysate concentrations of most mediators, including MCP-1 (mean ± SD: 10.5 ± 5.9 vs. 5.1 ± 3.8 pg/ml, P < 0.001) were significantly increased during MCO- versus high flux-HD. However, except for the largest mediator studied, i.e., YKL-40, this did not confer any advantages for single session elimination kinetics (post-HD mean ± SD: 360 ± 334 vs. 564 ± 422 pg/ml, P < 0.001). No sustained reduction of any of the studied mediators was found neither. Still, the long-term reduction of CD69+ (P = 0.01) and PD1+ (P = 0.02) activated CD4+ T cells was striking. Thus, MCO-HD does not induce reduction of a broad range of inflammatory mediators studied here. Long-term reduction over a 3-month period was not possible. Increased single session filtration, as evidenced by increased dialysate concentrations of inflammatory mediators during MCO-HD, might eventually be compensated for by compartment redistribution or increased production during dialysis session. Nevertheless, lasting effects on the T-cell phenotype were seen, which deserves further investigation.


Asunto(s)
Hemodiafiltración , Cefalosporinas , Proteína 1 Similar a Quitinasa-3 , Estudios Cruzados , Soluciones para Diálisis , Humanos , Inflamación , Mediadores de Inflamación , Membranas Artificiales , Fenotipo , Estudios Prospectivos , Diálisis Renal
19.
J Agric Food Chem ; 70(41): 13062-13070, 2022 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-35834180

RESUMEN

Gut microbiota modulation might constitute a mechanism mediating the effects of beer on health. In this randomized, double-blinded, two-arm parallel trial, 22 healthy men were recruited to drink 330 mL of nonalcoholic beer (0.0% v/v) or alcoholic beer (5.2% v/v) daily during a 4-week follow-up period. Blood and faecal samples were collected before and after the intervention period. Gut microbiota was analyzed by 16S rRNA gene sequencing. Drinking nonalcoholic or alcoholic beer daily for 4 weeks did not increase body weight and body fat mass and did not changed significantly serum cardiometabolic biomarkers. Nonalcoholic and alcoholic beer increased gut microbiota diversity which has been associated with positive health outcomes and tended to increase faecal alkaline phosphatase activity, a marker of intestinal barrier function. These results suggest the effects of beer on gut microbiota modulation are independent of alcohol and may be mediated by beer polyphenols.


Asunto(s)
Cerveza , Microbioma Gastrointestinal , Masculino , Humanos , Cerveza/análisis , ARN Ribosómico 16S/genética , Fosfatasa Alcalina , Biomarcadores
20.
Plants (Basel) ; 10(3)2021 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-33806880

RESUMEN

The root lesion Pratylenchus penetrans is an economically important pest affecting a wide range of plants. The morphometry of five P. penetrans isolates, parasitizing potato roots in Portugal, was compared and variability within and between isolates was observed. Of the 15 characters assessed, vulva position (V%) in females and the stylet length in both females/males showed the lowest coefficient of intra and inter-isolate variability. Moreover, DNA sequencing of the internal transcribed spacers (ITS) genomic region and cytochrome c oxidase subunit 1 (COI) gene was performed, in order to evaluate the intraspecific genetic variability of this species. ITS revealed higher isolate genetic diversity than the COI gene, with 15 and 7 different haplotypes from the 15 ITS and 14 COI sequences, respectively. Intra- and inter-isolate genetic diversity was found considering both genomic regions. The differentiation of these isolates was not related with their geographical origin. In spite of the high intraspecific variability, phylogenetic analyses revealed that both ITS region and COI gene separate P. penetrans from other related species. Our findings contribute to increasing the understanding of P. penetrans variability.

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