Purpose: A substantial proportion of children with high risk Neuroblastoma die within the first 5 years post-diagnosis despite the complex treatment applied. In the recent years, tumor environment has been revealed as key factor for cancer treatment efficacy. In this sense, non-tumorigenic Neural Crest progenitor cells from high risk patients, have been described as part of Neuroblastoma stroma, promoting tumor growth and contributing to mesenchyme formation.
View Article and Find Full Text PDFThe human CMP-sialic acid transporter (hCST) is a mammalian highly conserved type III antiporter that translocates CMP-sialic acid into the Golgi lumen, supporting sialylation. Although different works have focused on elucidating structure-function relationships in the hCST, this is the first study to address them in an alternatively spliced isoform. We have previously reported the expression of a functional human del177 isoform that has skipping of exon 6, resulting in a loss of 59 amino acids, without change in the open reading frame and conserving its C-terminal region.
View Article and Find Full Text PDFHere, we explored the vast potential of microbiome-based interventions in preventing and managing non-communicable diseases including obesity, diabetes, allergies, celiac disease, inflammatory bowel diseases, malnutrition, and cardiovascular diseases across different life stages. We discuss the intricate relationship between microbiome and non-communicable diseases, emphasizing on the "window of opportunity" for microbe-host interactions during the first years after birth. Specific biotics and also live biotherapeutics including fecal microbiota transplantation emerge as pivotal tools for precision medicine, acknowledging the "one size doesn't' fit all" aspect.
View Article and Find Full Text PDFLight chain amyloidosis is a conformational disease caused by the abnormal proliferation and deposition of antibody light chains as amyloid fibers in organs and tissues. The effect of Cu(II) binding to the model recombinant protein 6aJL2-R24G was previously characterized in our group, and we found an acceleration of the aggregation kinetics of the protein. In this study, in order to confirm the Cu(II) binding sites, histidine variants of 6aJL2-R24G were prepared and the effects of their interaction with Cu(II) were analyzed by circular dichroism, fluorescence spectroscopy, isothermal calorimetry titrations, and molecular dynamics simulations.
View Article and Find Full Text PDFcatalase-peroxidase (-KatG) is a bifunctional heme-dependent enzyme that has been shown to activate isoniazid (INH), the widely used antibiotic against tuberculosis (TB). The L333V-KatG variant has been associated with INH resistance in clinical isolates from Mexico. To understand better the mechanisms of INH activation, its catalytic properties (catalase, peroxidase, and IN-NAD formation) and crystal structure were compared with those of the wild-type enzyme (WT-KatG).
View Article and Find Full Text PDFThe mechanism by which glycoside hydrolases control the reaction specificity through hydrolysis or transglycosylation is a key element embedded in their chemical structures. The determinants of reaction specificity seem to be complex. We looked for structural differences in domain B between the 4-α-glucanotransferase from Thermotoga maritima (TmGTase) and the α-amylase from Thermotoga petrophila (TpAmylase) and found a longer loop in the former that extends towards the active site carrying a W residue at its tip.
View Article and Find Full Text PDFTools for radiation exposure reconstruction are required to support the medical management of radiation victims in radiological or nuclear incidents. Different biological and physical dosimetry assays can be used for various exposure scenarios to estimate the dose of ionizing radiation a person has absorbed. Regular validation of the techniques through inter-laboratory comparisons (ILC) is essential to guarantee high quality results.
View Article and Find Full Text PDFAs the rate of discovery of new antibacterial compounds for multidrug-resistant bacteria is declining, there is an urge for the search for molecules that could revert this tendency. has emerged as a highly virulent Gram-negative bacterium that has acquired multiple resistance mechanisms against antibiotics and is considered of critical priority. In this work, we developed a quantitative structure-property relationship (QSPR) model with 592 compounds for the identification of structural parameters related to their property as antibacterial agents against .
View Article and Find Full Text PDFBackground: Due to the complexities of advanced illnesses and their treatments, it can be difficult for patients in palliative care to maintain their quality of life. Telemedicine interventions in chronic disease management engage patients in their care, provide continuous follow-up by their health care providers, identify symptoms earlier, and allow a quick response to illness-related decline.
Objective: We aimed to detail and reflect on the design of an app and evaluate its feasibility to monitor the clinical situation of patients with advanced illnesses.
Background: Center-based cardiac rehabilitation programs (CRPs) reduce morbidity and mortality after an ischemic cardiac event; however, they are widely underused. Home-based CRP has emerged as an alternative to improve patient adherence; however, its safety and efficacy remain unclear, especially for older patients and female patients.
Objective: This study aimed to develop a holistic home-based CRP for patients with ischemic heart disease and evaluate its safety and impact on functional capacity, adherence to a healthy lifestyle, and quality of life.
After large-scale radiation accidents where many individuals are suspected to be exposed to ionizing radiation, biological and physical retrospective dosimetry assays are important tools to aid clinical decision making by categorizing individuals into unexposed/minimally, moderately or highly exposed groups. Quality-controlled inter-laboratory comparisons of simulated accident scenarios are regularly performed in the frame of the European legal association RENEB (Running the European Network of Biological and Physical retrospective Dosimetry) to optimize international networking and emergency readiness in case of large-scale radiation events. In total 33 laboratories from 22 countries around the world participated in the current RENEB inter-laboratory comparison 2021 for the dicentric chromosome assay.
View Article and Find Full Text PDFObjective: This study aims to contribute to the recovery of Indigenous evolutionary history in the Southern Pampas region of Argentina through an analysis of ancient complete mitochondrial genomes.
Materials And Methods: We generated DNA data for nine complete mitogenomes from the Southern Pampas, dated to between 2531 and 723 cal BP. In combination with previously published ancient mitogenomes from the region and from throughout South America, we documented instances of extra-regional lineage-sharing, and estimated coalescent ages for local lineages using a Bayesian method with tip calibrations in a phylogenetic analysis.
Light chain amyloidosis is the most common form of systemic amyloidosis. This disease is caused by the formation and deposition of amyloid fibers made from immunoglobulin light chains. Environmental conditions such as pH and temperature can affect protein structure and induce the development of these fibers.
View Article and Find Full Text PDFJ Mark Access Health Policy
December 2022
Background: Clinician's choice of hypoallergenic formulas in the first-line management of cow's milk protein allergy (CMPA) should be informed by evidence on clinical efficacy and cost-effectiveness.
Objective: We compare the cost-effectiveness of amino acid-based formula (AAF), extensively hydrolyzed casein formula with Lactobacillus rhamnosus Gorbach Goldin (EHCF+LGG), extensively hydrolyzed whey formula (EHWF), and rice hydrolyzed formula (RHF) in non-breastfed children in France.
Methods: Immunotolerance and atopic manifestations' prevalence were based on a prospective non-randomized study with a 36-month follow-up.
The presence of AMR bacteria in the human-animal-environmental interface is a clear example of the One Health medicine. Several studies evidence the presence of resistant bacteria in wildlife, which can be used as a good indicator of anthropization level on the ecosystem. The fast increase in AMR in the environment in the last decade has been led by several factors as globalization and migration.
View Article and Find Full Text PDFBackground: Depression and frailty are closely related, but the mechanisms by which depressed older adults are at an increased risk of becoming frail are still not well understood.
Aim: To assess socioeconomic and depression-related risk factors for frailty in older adults with depression.
Methods: Observational and prospective cohort study, with 12-month follow-up, of nonfrail community-dwelling subjects aged ≥70 years old with depression.
We recently screened a series of new aziridines β-D-galactopyranoside derivatives for selective anticancer activity and identified 2-methyl-2,3-[(4-methylbenzenesulfonyl)imino]propyl 2,3-di-O-benzyl-4,6-O-(S)-benzylidene-β-D-galactopyranoside (AzGalp) as the most promising compound. In this article, we explore the possible mechanisms involved in the cytotoxicity of this aziridine and evaluate its selective anticancer activity using cancer cells and normal cells from a variety of tissues. Our data show that AzGalp induces DNA damage (comet assay).
View Article and Find Full Text PDFElastography is a sonographic technique that provides a noninvasive evaluation of the stiffness of a lesion. The objective of this work was to evaluate the accuracy of strain elastography, the most accessible modality in clinical practice, to discriminate between different histological types of malignant mammary neoplasms in the canine species, which can provide complementary information in real time to the diagnosis and thus help in the choice of surgical technique. A total of 34 females with 56 mammary carcinomas were selected and classified into three histological groups according to their aggressiveness.
View Article and Find Full Text PDFThe high incidence of colorectal cancer (CRC) in developed countries indicates a predominant role of the environment as a causative factor. Natural gut microbiota provides multiple benefits to humans. Dysbiosis is characterized by an unbalanced microbiota and causes intestinal damage and inflammation.
View Article and Find Full Text PDFIn the Patagonian region, is the most diverse and abundant genus of ectomycorrhizal fungi with at least 250 species. Sequestrate forms were until recently documented within the genus , a genus now known to be polyphyletic, and many were consequently transferred to . Original descriptions were mostly available in German and Spanish and interpretations of morphological structures outdated.
View Article and Find Full Text PDFThe Colombian scorpion produces a venom considered of low toxicity. Nevertheless, there are known cases of envenomation resulting in cardiovascular disorders, probably due to venom components that target ion channels. Among them, the gene (hERG1) potassium channels are critical for cardiac action potential repolarization and alteration in its functionality are associated with cardiac disorders.
View Article and Find Full Text PDFJ Clin Immunol
October 2021
J Clin Immunol
August 2021
Mutations in recombinase activating genes 1 and 2 (RAG1/2) result in human severe combined immunodeficiency (SCID). The products of these genes are essential for V(D)J rearrangement of the antigen receptors during lymphocyte development. Mutations resulting in null-recombination activity in RAG1 or RAG2 are associated with the most severe clinical and immunological phenotypes, whereas patients with hypomorphic mutations may develop leaky SCID, including Omenn syndrome (OS).
View Article and Find Full Text PDFObjective: There is a two-way relationship between frailty and depression, but the mechanisms by which one may influence the other are not well understood. The objective of this study was to evaluate the relationship between psychosocial factors and frailty in community-dwelling aged populations with depression.
Design: Observational cross-sectional study.