Facultad de Medicina

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    Atmospheric Pollutants Affect Physical Performance: A Natural Experiment in Horse Racing Studied by Principal Component Analysis
    (05-2022) Araneda Valenzuela, Oscar Florencio
    The impact of some atmospheric pollutants (PM10, PM2.5, O3, NO2, NO, SO2, CO), humidity and temperature were studied on the performance of thoroughbred racehorses. The study included 162 official handicap races held in 2012 in Santiago de Chile, at distances of 1000, 1100 and 1200 m, on a track in good condition, with a layout that included a bend, during the summer and winter months. The environmental variables were measured at the time of the race and were obtained from a monitoring station located 470 m from the equestrian center. The environmental variables showed an autocorrelation of variables, so they were reduced using principal component analysis. Subsequently, the principal components were correlated with running speed using Pearson’s method. Totals of 60.17 and 23.29% of the total variability of the data was explained by principal components 1 and 2 (PC1 and PC2), respectively. PC1 was mainly determined by NO, NO2, and CO (loadings~0.90) and secondarily by PM10, PM2.5, and SO2 (loadings~0.6), with which the data showed inverse associations, while with temperature and O3 it showed direct associations (loadings~0.7). In addition, this component correlated negatively with running speed (r = −0.50), while PC2 was not associated with this variable. In conclusion, using the principal component analysis strategy, it was determined that running speed is affected by air pollutants.
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    El ácido estearidónico: Un ácido graso omega-3 de origen vegetal con gran potencialidad en salud y nutrición
    (09-2015) Valenzuela B., Alfonso
    Los beneficios para la salud de los ácidos grasos poliinsaturados omega-3 eicosapentaenoico (20:5,EPA) y docosahexaenoico (22:6, DHA) son ampliamente conocidos y están disponibles principalmente en alimentos de origen marino como el pescado. Sin embargo, en función de las recomendaciones internacionales acerca del consumo de pescado, éste es muy reducido en muchos países, incluido Chile. Por ello, la industria de alimentos está mostrando un interés creciente por el ácido estearidónico (18:4, SDA), un ácido graso omega-3 de 18 carbonos presente en los aceites de semilla de ciertas especies vegetales y que actúa como precursor del EPA y DHA en el metabolismo humano. La tasa de conversión de SDA en EPA resulta ser mucho más elevada que la del ácido α-linolénico (18:3, ALA), que es el principal ácido graso omega-3 en fuentes vegetales terrestres. La suplementación con SDA aporta una variedad de efectos beneficiosos para la salud humana según los estudios realizados. En el presente artículo se discuten algunos efectos en la salud derivados del SDA y la potencialidad de algunas plantas de origen silvestre para convertirse en aportadoras de SDA.
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    Las microalgas: Una fuente renovable para la obtención de ácidos grasos omega-3 de cadena larga para la nutrición humana y animal
    (09-2015) Valenzuela B., Alfonso
    Los ácidos grasos polinsaturados omega-3 de cadena larga (AGPICL omega-3) EPA y DHA, son considerados actualmente de gran importancia nutricional debido a los numerosos efectos positivos en la salud observados a partir de su administración tanto en la nutrición humana como animal, por lo cual se sugiere su suplementación. Sin embargo, las fuentes para aportarlos como suplemento no son muchas, siendo principalmente el aceite de pescado, en el caso de los humanos, y la harina y el aceite de pescado en el caso de los animales, la principal fuente de suplementación de AGPICL omega-3. Tanto el aceite de pescado como la harina de pescado son productos que han comenzado han disminuir su disponibilidad debido, principalmente, a la sobreexplotación del recurso pesquero, con lo cual ambos productos tienen actualmente alto valor. Algunos aceites de origen vegetal contienen ácido alfa linolénico, el cual es un ácido graso omega-3 y el precursor de los AGPICL omega-3, pero que no remplaza en sus efectos nutricionales al EPA y DHA. Más recientemente, las microalgas han surgido como una alternativa renovable para la obtención de AGPICL omega-3, principalmente por su aporte de EPA y/o DHA y buen rendimiento de extracción. Estos microorganismos pueden ser cultivados artificialmente a escala industrial y debidamente procesados (liofilizados, microencapsulados, etc.) o el aceite y/o los fosfolípidos extraídos de ellos (consumidos como tal o microencapsulados), puede ser utilizados para adicionarse a una variedad de alimentos tanto para humanos como para animales (mascotas, animales de engorda, peces en cultivo, entre otros). Este trabajo analiza la potencialidad del uso de las microalgas en la nutrición humana y animal como fuentes de AGPICL omega-3.
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    Pediatría social
    (09-2015) Castro, Daniela
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    Antimicrobial activity of mesenchymal stem cells: Current status and new perspectives of antimicrobial peptide-based therapies
    (30-03-2017) Alcayaga-Miranda, Francisca; Cuenca, Jimena; Khoury, Maroun
    While mesenchymal stem cells (MSCs)-based therapy appears to be promising, there are concerns regarding possible side effects related to the unwanted suppression of antimicrobial immunity leading to an increased risk of infection. Conversely, recent data show that MSCs exert strong antimicrobial effects through indirect and direct mechanisms, partially mediated by the secretion of antimicrobial peptides and proteins (AMPs). In fact, MSCs have been reported to increase bacterial clearance in preclinical models of sepsis, acute respiratory distress syndrome, and cystic fibrosis-related infections. This article reviews the current evidence regarding the direct antimicrobial effector function of MSCs, focusing mainly on the role of MSCs-derived AMPs. The strategies that might modulate the expression and secretion of these AMPs, leading to enhanced antimicrobial effect, are highlighted. Furthermore, studies evaluating the presence of AMPs in the cargo of extracellular vesicles (EVs) are underlined as perspective opportunities to develop new drug delivery tools. The antimicrobial potential of MSCs-derived EVs can also be heightened through cell conditioning and/or drug loading. Finally, improving the pharmacokinetics and delivery, in addition to deciphering the multi-target drug status of AMPs, should synergistically lead to key advances against infections caused by drug-resistant strains.
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    La innovación en la industria de alimentos: Historia de algunas innovaciones y de sus innovadores
    (2015) Valenzuela B., Alfonso
    La innovación es un tema actualmente presente en todas las áreas del desarrollo, particularmente en la industria de los alimentos. La innovación requiere esfuerzo creativo, audacia, habilidades tecnológicas y/o comerciales. En la evolución de los alimentos y de los procesos asociados han existido muchos fracasos pero también muchas innovaciones e innovadores exitosos. Este trabajo describe algunos casos de innovaciones exitosas que finalmente se transformaron en productos que diariamente son de consumo masivo.
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    Ectasia ductal mamaria en niños, a propósito de un caso clínico
    (2015) Vial Letelier, Verónica
    Introducción. La telorragia es un síntoma poco frecuente en pacientes pediátricos, la causa más frecuente en esta población es la ectasia ductal mamaria (EDM), que es una afección benigna y autolimitada, caracterizada por la dilatación del conducto mamario, fibrosis e inflamación periductal. Objetivo. Presentar un caso de EDM, para facilitar el rápido reconocimiento por parte de los médicos, y evitar estudios y tratamientos agresivos. Caso clínico. Lactante de sexo masculino de 6 meses de edad, sano, alimentado por lactancia materna exclusiva; consultó por un nódulo retroareolar derecho y telorragia unilateral. Se realizó una ecografía Doppler que mostró una lesión multiquística, sugerente de una EDM. Se planteó tratamiento expectante y acudió a control a los 6 meses con excelente evolución. Conclusiones. La EDM es la principal causa de telorragia en niños, corresponde a una afección benigna, y la resolución generalmente es espontánea, antes de los 9 meses. Por lo que su conocimiento es de gran relevancia para el adecuado diagnóstico y manejo de estos pacientes.
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    Bioética aplicada en Atención Primaria
    (2021) Nadal Agost, Carmen
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    Maternal stress during pregnancy alters circulating small extracellular vesicles and enhances their targeting to the placenta and fetus
    (Biological Research, 2024-12) Sánchez Rubio, Mario; Abarzúa Catalán, Lorena; Del Valle, Ana; Méndez Ruette, Maxs; Salazar, Natalia; Sigala, Jacinta; Sandoval, Soledad; Luarte, Alejandro; Monteiro, Lara J.; Wyneken, Úrsula; Illanes, Sebastián E.; Bátiz, Luis Federico
    Background: Maternal psychological distress during pregnancy can negatively impact fetal development, resulting in long-lasting consequences for the offspring. These effects show a sex bias. The mechanisms whereby prenatal stress induces functional and/or structural changes in the placental-fetal unit remain poorly understood. Maternal circulating small extracellular vesicles (sEVs) are good candidates to act as “stress signals” in mother-to-fetus communication. Using a repetitive restraint-based rat model of prenatal stress, we examined circulating maternal sEVs under stress conditions and tested whether they could target placental-fetal tissues. Results: Our mild chronic maternal stress during pregnancy paradigm induced anhedonic-like behavior in pregnant dams and led to intrauterine growth restriction (IUGR), particularly in male fetuses and placentas. The concentration and cargo of maternal circulating sEVs changed under stress conditions. Specifically, there was a significant reduction in neuron-enriched proteins and a significant increase in astrocyte-enriched proteins in blood-borne sEVs from stressed dams. To study the effect of repetitive restraint stress on the biodistribution of maternal circulating sEVs in the fetoplacental unit, sEVs from pregnant dams exposed to stress or control protocol were labeled with DiR fluorescent die and injected into pregnant females previously exposed to control or stress protocol. Remarkably, maternal circulating sEVs target placental/fetal tissues and, under stress conditions, fetal tissues are more receptive to sEVs. Conclusion: Our results suggest that maternal circulating sEVs can act as novel mediators/modulators of mother-to-fetus stress communication. Further studies are needed to identify placental/fetal cellular targets of maternal sEVs and characterize their contribution to stress-induced sex-specific placental and fetal changes.
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    Survival advantage of native and engineered T cells is acquired by mitochondrial transfer from mesenchymal stem cells
    (Journal of Translational Medicine, 2024-12) Court, Angela C.; Parra Crisóstomo, Eliseo; Castro Córdova, Pablo; Lorca, Rocío; Figueroa, Fernando E.; Khoury, Maroun
    Background: Apoptosis, a form of programmed cell death, is critical for the development and homeostasis of the immune system. Chimeric antigen receptor T (CAR-T) cell therapy, approved for hematologic cancers, retains several limitations and challenges associated with ex vivo manipulation, including CAR T-cell susceptibility to apoptosis. Therefore, strategies to improve T-cell survival and persistence are required. Mesenchymal stem/stromal cells (MSCs) exhibit immunoregulatory and tissue-restoring potential. We have previously shown that the transfer of umbilical cord MSC (UC-MSC)-derived mitochondrial (MitoT) prompts the genetic reprogramming of CD3+ T cells towards a Treg cell lineage. The potency of T cells plays an important role in effective immunotherapy, underscoring the need for improving their metabolic fitness. In the present work, we evaluate the effect of MitoT on apoptotis of native T lymphocytes and engineered CAR-T cells. Methods: We used a cell-free approach using artificial MitoT (Mitoception) of UC-MSC derived MT to peripheral blood mononuclear cells (PBMCs) followed by RNA-seq analysis of CD3+ MitoTpos and MitoTneg sorted cells. Target cell apoptosis was induced with Staurosporine (STS), and cell viability was evaluated with Annexin V/7AAD and TUNEL assays. Changes in apoptotic regulators were assessed by flow cytometry, western blot, and qRT-PCR. The effect of MitoT on 19BBz CAR T-cell apoptosis in response to electroporation with a non-viral transposon-based vector was assessed with Annexin V/7AAD. Results: Gene expression related to apoptosis, cell death and/or responses to different stimuli was modified in CD3+ T cells after Mitoception. CD3+MitoTpos cells were resistant to STS-induced apoptosis compared to MitoTneg cells, showing a decreased percentage in apoptotic T cells as well as in TUNEL+ cells. Additionally, MitoT prevented the STS-induced collapse of the mitochondrial membrane potential (MMP) levels, decreased caspase-3 cleavage, increased BCL2 transcript levels and BCL-2-related BARD1 expression in FACS-sorted CD3+ T cells. Furthermore, UC-MSC-derived MitoT reduced both early and late apoptosis in CAR-T cells following electroporation, and exhibited an increasing trend in cytotoxic activity levels. Conclusions: Artificial MitoT prevents STS-induced apoptosis of human CD3+ T cells by interfering with the caspase pathway. Furthermore, we observed that MitoT confers protection to apoptosis induced by electroporation in MitoTpos CAR T-engineered cells, potentially improving their metabolic fitness and resistance to environmental stress. These results widen the physiological perspective of organelle-based therapies in immune conditions while offering potential avenues to enhance CAR-T treatment outcomes where their viability is compromised.
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    Impact of KDM6B mosaic brain knockout on synaptic function and behavior
    (Scientific Reports, 2024-12) Nardocci, Gino
    Autism spectrum disorders (ASD) are complex neurodevelopmental conditions characterized by impairments in social communication, repetitive behaviors, and restricted interests. Epigenetic modifications serve as critical regulators of gene expression playing a crucial role in controlling brain function and behavior. Lysine (K)-specific demethylase 6B (KDM6B), a stress-inducible H3K27me3 demethylase, has emerged as one of the highest ASD risk genes, but the precise effects of KDM6B mutations on neuronal activity and behavioral function remain elusive. Here we show the impact of KDM6B mosaic brain knockout on the manifestation of different autistic-like phenotypes including repetitive behaviors, social interaction, and significant cognitive deficits. Moreover, KDM6B mosaic knockout display abnormalities in hippocampal excitatory synaptic transmission decreasing NMDA receptor mediated synaptic transmission and plasticity. Understanding the intricate interplay between epigenetic modifications and neuronal function may provide novel insights into the pathophysiology of ASD and potentially inform the development of targeted therapeutic interventions.
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    How to enhance MSCs therapeutic properties? An insight on potentiation methods
    (Stem Cell Research and Therapy, 2024-12) García Guerrero, Cynthia; Araya, María Jesús; Luz Crawford, Patricia
    Mesenchymal stem/stromal cells (MSCs) have emerged as a promising tool in the field of regenerative medicine due to their unique therapeutic properties as they can differentiate into multiple cell types and exert paracrine effects. However, despite encouraging results obtained in preclinical studies, clinical trials have not achieved the same levels of efficacy. To improve the therapeutic properties of MSCs, several strategies have been explored. Therefore, in this review, the therapeutic properties of MSCs will be analyzed, and an update and overview of the most prominent approaches used to enhance their therapeutic capabilities will be provided. These approaches include using drugs, molecules, strategies based on biomaterials, and modification parameters in culture. The strategy described shows several common factors among those affected by these strategies that lead to an enhancement of the MSCs therapeutic properties such as the activation of the PI3K/AKT pathway and the increased expression of Heat Shock Proteins and Hypoxia-Inducible Factor. The combined effect of these elements shift MSCs towards a glycolytic state, suggesting this shift is essential for their enhancement.
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    Human papillomaviruses in hand squamous cell carcinomas from Chilean patients
    (Infectious Agents and Cancer, 2024-12) Gubelin, Hans; Gubelin, Walter
    Introduction: Cutaneous squamous cell carcinoma (SCC) accounts for 20% of all skin cancers and its incidence continues to increase globally. It represents 75% of non-melanoma skin cancer (NMSC) mortality. Risk factors include ultraviolet radiation (UVR) exposure, advanced age, chemical exposure, fair skin types, and immunosuppression. While most human papillomavirus (HPV) infections are associated with the development of warts, a subgroup is potentially implicated in the development of cutaneous SCC. The prevalence of alpha, beta, and gamma-HPV in Chilean patients with hand SCCs has not been previously addressed. The objective of this study was to evaluate the presence of HPV and genotyping in hand SCC from Chilean patients. Materials and methods: An observational, cross-sectional, descriptive study was conducted. Alpha (α), beta (β) and gamma (γ)-HPV detection was performed by conventional polymerase chain reaction (PCR) in paraffin-embedded tissue samples from 52 patients diagnosed with hand SCC from Santiago, Chile. HPV genotyping was carried out via direct amplicon sequencing by Sanger method. Results: The most frequent carcinoma site was the dorsum of the hands (52.5%). α-HPV was not detected in these specimens, whereas β-HPV and γ-HPV were detected in 25% of the analyzed samples. The most frequent genotypes found were β-HPV 100 (38%) and γ-HPV 178 (15%). Additionally, γ-HPV 101, 162, HPV-mSK_016, HPV-mSK_083, HPV-mSK_213 and HPV-mSK249nr genotypes were detected, none of which had been previously described in cutaneous SCC. Conclusion: β-HPV and γ-HPV are detectable in 25% of hand SCCs from Chilean patients. It is important to conduct prospective studies to better elucidate the role of these viruses in the development of this disease.
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    Enfermedad pulmonar difusa (EPD)
    (Alarcón, Paula) Alarcón, Paula
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    Bronquiectasias
    (Alarcón, Paula) Alarcón, Paula
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    Cáncer hepático
    (Alarcón, Paula) Alarcón, Paula
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    Coagulopatías
    (Alarcón, Paula) Alarcón, Paula
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    Enfermedad reumática
    (Alarcón, Paula) Alarcón, Paula
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    Trastornos plaquetarios
    (Alarcón, Paula) Alarcón, Paula