Publicaciones

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Proteus mirabilis biofilm expansion microscopy yields over 4-fold magnification for super-resolution of biofilm structure and subcellular DNA organization
Castagnini D, Palma K, Jara-Wilde J, Navarro N, González MJ, Toledo J, Canales-Huerta N, Scavone P and Härtel S
Bacterial biofilms form when bacteria attach to surfaces and generate an extracellular matrix that embeds and stabilizes a growing community. Detailed visualization and quantitative analysis of biofilm architecture by optical microscopy are limited by the law of diffraction. Expansion Microscopy (ExM) is a novel Super-Resolution technique where specimens are physically enlarged by a factor of ∼4, prior to observation by conventional fluorescence microscopy. ExM requires homogenization of rigid constituents of biological components by enzymatic digestion. We developed an ExM approach capable of expanding 48-h old Proteus mirabilis biofilms 4.3-fold (termed PmbExM), close to the theoretic maximum expansion factor without gross shape distortions. Our protocol, based on lytic and glycoside-hydrolase enzymatic treatments, degrades rigid components in bacteria and extracellular matrix. Our results prove PmbExM to be a versatile and easy-to-use Super-Resolution approach for enabling studies of P. mirabilis biofilm architecture, assembly, and even intracellular features, such as DNA organization.
Ophthalmology Optical Coherence Tomography Databases for Artificial Intelligence Algorithm: A Review
Restrepo D, Quion JM, Do Carmo Novaes F, Azevedo Costa ID, Vasquez C, Bautista AN, Quiminiano E, Lim PA, Mwavu R, Celi LA and Nakayama LF
Imaging plays a pivotal role in eye assessment. With the introduction of advanced machine learning and artificial intelligence (AI), the focus has shifted to imaging datasets in ophthalmology. While disparities and health inequalities hidden within data are well-documented, the ophthalmology field faces specific challenges to the creation and maintenance of datasets. Optical Coherence Tomography (OCT) is useful for the diagnosis and monitoring of retinal pathologies, making it valuable for AI applications. This review aims to identify and compare the landscape of publicly available optical coherence tomography databases for AI applications.
Topological insight of immune-vascular distribution in peri-implantitis lesions
Villalobos V, Silva I, Morales D, Canelo J, Garrido M, Carreño LJ, Cavalla F, Dutzan N and Caceres M
To characterize the distribution of macrophages, neutrophils, NK cells, and blood vessels in peri-implantitis compared to healthy aged gingiva samples.
Fluorescently labelled vedolizumab to visualise drug distribution and mucosal target cells in inflammatory bowel disease
Gabriëls RY, van der Waaij AM, Linssen MD, Dobosz M, Volkmer P, Jalal S, Robinson D, Hermoso MA, Lub-de Hooge MN, Festen EAM, Kats-Ugurlu G, Dijkstra G and Nagengast WB
Improving patient selection and development of biological therapies such as vedolizumab in IBD requires a thorough understanding of the mechanism of action and target binding, thereby providing individualised treatment strategies. We aimed to visualise the macroscopic and microscopic distribution of intravenous injected fluorescently labelled vedolizumab, vedo-800CW, and identify its target cells using fluorescence molecular imaging (FMI).
Viral shedding and viraemia of Andes virus during acute hantavirus infection: a prospective study
Ferrés M, Martínez-Valdebenito C, Henriquez C, Marco C, Angulo J, Barrera A, Palma C, Barriga Pinto G, Cuiza A, Ferreira L, Rioseco ML, Calvo M, Fritz R, Bravo S, Bruhn A, Graf J, Llancaqueo A, Rivera G, Cerda C, Tischler N, Valdivieso F, Vial P, Mertz G, Vial C and Le Corre N
Andes virus (ANDV) is a zoonotic Orthohantavirus leading to hantavirus cardiopulmonary syndrome. Although most transmissions occur through environmental exposure to rodent faeces and urine, rare person-to-person transmission has been documented, mainly for close contacts. This study investigates the presence and infectivity of ANDV in body fluids from confirmed cases and the duration of viraemia.
Supra-Threshold LS CE-Chirp Auditory Brainstem Response in the Elderly
Maass JC, Leiva A, Torrente M, Vergara R, Belkhiria C, Delgado C and Delano PH
Aging deteriorates peripheral and central auditory structures and functions. In elders, for an accurate audiological evaluation, it is important to explore beyond the cochlear receptor. Audiograms provide an estimation of hearing thresholds, while the amplitudes and latencies of supra-threshold auditory brainstem response (ABR) can offer noninvasive measures of the auditory pathways functioning. Regarding ABR, in young populations, level-specific chirp (LS CE-chirp) stimulus has been proposed as an alternative synchronizing method to obtain larger ABR responses than those evoked by clicks. However, the supra-threshold characteristics of chirp evoked ABR, and their association to hearing thresholds is relatively unknown in the elderly. The aim of this study was to evaluate supra-threshold LS CE-chirp ABRs in an aged population by comparing their features with click ABRs, and evaluating their relationship with audiometric hearing thresholds.
Co-Culture of . and . Synergistically Elevates IL-6 Expression via TLR4 Signaling in Oral Keratinocytes
Yáñez L, Soto C, Tapia H, Pacheco M, Tapia J, Osses G, Salinas D, Rojas-Celis V, Hoare A, Quest AFG, Díaz-Elizondo J, Pérez-Donoso JM and Bravo D
Periodontitis, characterized by persistent inflammation in the periodontium, is intricately connected to systemic diseases, including oral cancer. Bacteria, such as and , play a pivotal role in periodontitis development because they contribute to dysbiosis and tissue destruction. Thus, comprehending the interplay between these bacteria and their impacts on inflammation holds significant relevance in clinical understanding and treatment advancement. In the present work, we explored, for the first time, their impacts on the expressions of pro-inflammatory mediators after infecting oral keratinocytes (OKs) with a co-culture of pre-incubated and . Our results show that the co-culture increases IL-1β, IL-8, and TNF-α expressions, synergistically augments IL-6, and translocates NF-kB to the cell nucleus. These changes in pro-inflammatory mediators-associated with chronic inflammation and cancer-correlate with an increase in cell migration following infection with the co-cultured bacteria or alone. This effect depends on TLR4 because TLR4 knockdown notably impacts IL-6 expression and cell migration. Our study unveils, for the first time, crucial insights into the outcomes of their co-culture on virulence, unraveling the role of bacterial interactions in polymicrobial diseases and potential links to oral cancer.
Navigating beyond numbers: the clinical context and the role of high-sensitivity troponin on long-term outcomes of patients with suspected acute coronary syndrome
Gajardo AIJ, Lillo-Moya J and Llancaqueo M
IPR-Mediated Calcium Release Promotes Ferroptotic Death in SH-SY5Y Neuroblastoma Cells
Campos J, Gleitze S, Hidalgo C and Núñez MT
Ferroptosis is an iron-dependent cell death pathway that involves the depletion of intracellular glutathione (GSH) levels and iron-mediated lipid peroxidation. Ferroptosis is experimentally caused by the inhibition of the cystine/glutamate antiporter xCT, which depletes cells of GSH, or by inhibition of glutathione peroxidase 4 (GPx4), a key regulator of lipid peroxidation. The events that occur between GPx4 inhibition and the execution of ferroptotic cell death are currently a matter of active research. Previous work has shown that calcium release from the endoplasmic reticulum (ER) mediated by ryanodine receptor (RyR) channels contributes to ferroptosis-induced cell death in primary hippocampal neurons. Here, we used SH-SY5Y neuroblastoma cells, which do not express RyR channels, to test if calcium release mediated by the inositol 1,4,5-trisphosphate receptor (IPR) channel plays a role in this process. We show that treatment with RAS Selective Lethal Compound 3 (RSL3), a GPx4 inhibitor, enhanced reactive oxygen species (ROS) generation, increased cytoplasmic and mitochondrial calcium levels, increased lipid peroxidation, and caused cell death. The RSL3-induced calcium signals were inhibited by Xestospongin B, a specific inhibitor of the ER-resident IPR calcium channel, by decreasing IPR levels with carbachol and by IPR1 knockdown, which also prevented the changes in cell morphology toward roundness induced by RSL3. Intracellular calcium chelation by incubation with BAPTA-AM inhibited RSL3-induced calcium signals, which were not affected by extracellular calcium depletion. We propose that GPx4 inhibition activates IPR-mediated calcium release in SH-SY5Y cells, leading to increased cytoplasmic and mitochondrial calcium levels, which, in turn, stimulate ROS production and induce lipid peroxidation and cell death in a noxious positive feedback cycle.
Psychological factors are associated with pain extent in patients with carpal tunnel syndrome
Núñez-Cortés R, Carrasco JJ, Salazar-Méndez J, Torreblanca-Vargas S, Pérez-Alenda S, Calatayud J, Lluch E, Horment-Lara G, Cruz-Montecinos C and Cerda M
Widespread pain may be related to psychosocial aspects in several musculoskeletal conditions, but the literature on carpal tunnel syndrome (CTS) is scarce.
Science around the world
Gangrade N, Hidalgo C, Kanneganti TD and Lazennec G
Transcription levels of hes and their involvement in the biofilm formation of Shiga toxin-producing Escherichia coli O91
Vélez MV, Colello R, Nieto MV, Paz LE, Etcheverría AI, Vidal R and Padola NL
Shiga toxin-producing Escherichia coli (STEC) are recognized as being responsible for many cases of foodborne diseases worldwide. Cattle are the main reservoir of STEC, shedding the microorganisms in their feces. The serogroup STEC O91 has been associated with hemorrhagic colitis and hemolytic uremic syndrome. Locus of Adhesion and Autoaggregation (LAA) and its hes gene are related to the pathogenicity of STEC and the ability to form biofilms. Considering the frequent isolation of STEC O91, the biofilm-forming ability, and the possible role of hes in the pathogenicity of STEC, we propose to evaluate the ability of STEC to form biofilms and to evaluate the expression of hes before and after of biofilm formation. All strains were classified as strong biofilm-forming. The hes expression showed variability between strains before and after biofilm formation, and this may be due to other genes carried by each strain. This study is the first to report the relationship between biofilm formation, and hes expression and proposes that the analysis and diagnosis of LAA, especially hes as STEC O91 virulence factors, could elucidate these unknown mechanisms. Considering that there is no specific treatment for HUS, only supportive care, it is necessary to know the survival and virulence mechanisms of STEC O91.
Novel Strategies to Improve the Cardioprotective Effects of Cardioplegia
Osorio-Llanes E, Castellar-López J, Rosales-Rada W, Montoya Y, Bustamante J, Zalaquett R, Bravo-Sagua R, Riquelme JA, Sánchez G, Chiong M, Lavandero S and Mendoza-Torres E
The use of cardioprotective strategies as adjuvants of cardioplegic solutions has become an ideal alternative for the improvement of post-surgery heart recovery. The choice of the optimal cardioplegia, as well as its distribution mechanism, remains controversial in the field of cardiovascular surgery. There is still a need to search for new and better cardioprotective methods during cardioplegic procedures. New techniques for the management of cardiovascular complications during cardioplegia have evolved with new alternatives and additives, and each new strategy provides a tool to neutralize the damage after ischemia/reperfusion events. Researchers and clinicians have committed themselves to studying the effect of new strategies and adjuvant components with the potential to improve the cardioprotective effect of cardioplegic solutions in preventing myocardial ischemia/reperfusion-induced injury during cardiac surgery. The aim of this review is to explore the different types of cardioplegia, their protection mechanisms, and which strategies have been proposed to enhance the function of these solutions in hearts exposed to cardiovascular pathologies that require surgical alternatives for their corrective progression.
Author Correction: Neurocognitive correlates of semantic memory navigation in Parkinson's disease
Toro-Hernández FD, Migeot J, Marchant N, Olivares D, Ferrante F, González-Gómez R, González Campo C, Fittipaldi S, Rojas-Costa GM, Moguilner S, Slachevsky A, Chaná Cuevas P, Ibáñez A, Chaigneau S and García AM
Natural killer T cells in allergic asthma: implications for the development of novel immunotherapeutical strategies
Gutiérrez-Vera C, García-Betancourt R, Palacios PA, Müller M, Montero DA, Verdugo C, Ortiz F, Simon F, Kalergis AM, González PA, Saavedra-Avila NA, Porcelli SA and Carreño LJ
Allergic asthma has emerged as a prevalent allergic disease worldwide, affecting most prominently both young individuals and lower-income populations in developing and developed countries. To devise effective and curative immunotherapy, it is crucial to comprehend the intricate nature of this condition, characterized by an immune response imbalance that favors a proinflammatory profile orchestrated by diverse subsets of immune cells. Although the involvement of Natural Killer T (NKT) cells in asthma pathology is frequently implied, their specific contributions to disease onset and progression remain incompletely understood. Given their remarkable ability to modulate the immune response through the rapid secretion of various cytokines, NKT cells represent a promising target for the development of effective immunotherapy against allergic asthma. This review provides a comprehensive summary of the current understanding of NKT cells in the context of allergic asthma, along with novel therapeutic approaches that leverage the functional response of these cells.
Two centuries of vaccination: historical and conceptual approach and future perspectives
Montero DA, Vidal RM, Velasco J, Carreño LJ, Torres JP, Benachi O MA, Tovar-Rosero YY, Oñate AA and O'Ryan M
Over the past two centuries, vaccines have been critical for the prevention of infectious diseases and are considered milestones in the medical and public health history. The World Health Organization estimates that vaccination currently prevents approximately 3.5-5 million deaths annually, attributed to diseases such as diphtheria, tetanus, pertussis, influenza, and measles. Vaccination has been instrumental in eradicating important pathogens, including the smallpox virus and wild poliovirus types 2 and 3. This narrative review offers a detailed journey through the history and advancements in vaccinology, tailored for healthcare workers. It traces pivotal milestones, beginning with the variolation practices in the early 17th century, the development of the first smallpox vaccine, and the continuous evolution and innovation in vaccine development up to the present day. We also briefly review immunological principles underlying vaccination, as well as the main vaccine types, with a special mention of the recently introduced mRNA vaccine technology. Additionally, we discuss the broad benefits of vaccines, including their role in reducing morbidity and mortality, and in fostering socioeconomic development in communities. Finally, we address the issue of vaccine hesitancy and discuss effective strategies to promote vaccine acceptance. Research, collaboration, and the widespread acceptance and use of vaccines are imperative for the continued success of vaccination programs in controlling and ultimately eradicating infectious diseases.
Inhibition of NOX2 or NLRP3 inflammasome prevents cardiac remote ischemic preconditioning
Benavides S, Palavecino R, Riquelme JA, Montecinos L, Finkelstein JP, Donoso P and Sánchez G
Short episodes of ischemia-reperfusion (IR) in the heart (classical ischemic preconditioning, IPC) or in a limb (remote ischemic preconditioning, RIPC) before a prolonged ischemic episode, reduce the size of the infarct. It is unknown whether IPC and RIPC share common mechanisms of protection. Animals KO for NOX2, a superoxide-producing enzyme, or KO for NLRP3, a protein component of inflammasome, are not protected by IPC. The aim of this study was to investigate if NOX2 or NLRP3 inflammasome are involved in the protection induced by RIPC. We preconditioned rats using 4 × 5 min periods of IR in the limb with or without a NOX2 inhibitor (apocynin) or an NLRP3 inhibitor (Bay117082). In isolated hearts, we measured the infarct size after 30 min of ischemia and 60 min of reperfusion. In hearts from preconditioned rats we measured the activity of NOX2; the mRNA of Nrf2, gamma-glutamylcysteine ligase, glutathione dehydrogenase, thioredoxin reductase and sulfiredoxin by RT-qPCR; the content of glutathione; the activation of the NLRP3 inflammasome and the content of IL-1β and IL-10 in cardiac tissue. In exosomes isolated from plasma, we quantified NOX2 activity. The infarct size after IR decreased from 40% in controls to 9% of the heart volume after RIPC. This protective effect was lost in the presence of both inhibitors. RIPC increased NOX2 activity in the heart and exosomes, as indicated by the increased association of p47phox to the membrane and by the increased oxidation rate of NADPH. RIPC also increased the mRNA of Nrf2 and antioxidant enzymes. Also, RIPC increased the content of glutathione and the GSH/GSSG ratio. The inflammasome proteins NLRP3, procaspase-1, and caspase-1 were all increased in the hearts of RIPC rats. At the end of RIPC protocol, IL-1β increased in plasma but decreased in cardiac tissue. At the same time, IL-10 did not change in cardiac tissue but increased by 70% during the next 50 min of perfusion. RIPC activates NOX2 which upregulates the heart's antioxidant defenses and activates the NLRP3 inflammasome which stimulates a cardiac anti-inflammatory response. These changes may underlie the decrease in the infarct size induced by RIPC.
Cochlear dysfunction as an early biomarker of cognitive decline in normal hearing and mild hearing loss
Medel V, Delano PH, Belkhiria C, Leiva A, De Gatica C, Vidal V, Navarro CF, Martín SS, Martínez M, Gierke C, García X, Cerda M, Vergara R, Delgado C and Farías GA
Age-related hearing loss is an important risk factor for cognitive decline. However, audiogram thresholds are not good estimators of dementia risk in subjects with normal hearing or mild hearing loss. Here we propose to use distortion product otoacoustic emissions (DPOAEs) as an objective and sensitive tool to estimate the risk of cognitive decline in older adults with normal hearing or mild hearing loss.
Corrigendum: The role of cholesterol and mitochondrial bioenergetics in activation of the inflammasome in IBD
Astorga J, Gasaly N, Dubois-Camacho K, De la Fuente M, Landskron G, Faber KN, Urra FA and Hermoso MA
[This corrects the article DOI: 10.3389/fimmu.2022.1028953.].
Impact of the Pandemic Time on the Mental Health of People with Dementia and Their Family Caregivers in Brazil and Chile: One-Year Follow-Up
Olavarría L, Caramelli P, Lema J, Andrade CB, Pinto A, Azevedo LVDS, Thumala D, Vieira MCS, Rossetti AP, Generoso AB, Carmona KC, Sepúlveda-Loyola W, Pinto LAC, Barbosa MT and Slachevsky A
Previous studies reported the negative impact of social isolation on mental health in people with dementia (PwD) and their caregivers, butlongitudinal studies seem scarcer.