Artículos Medicina y Ciencias de la Salud

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A Natural deep eutectic solvent as an effective material for dual debridement and antibiofilm effects in chronic wound treatment
(2024) Map, Christina; Ezquer, Fernando; Mamani, Sigde; Campodónico, Paola; Cárcamo, Constanza; Martinez, Fabián; Aburto, Isabel; Ezquer, Marcelo; Morales, Bernardo; Olivares, Belén
In chronic wound treatment, the debridement of devitalized tissue and the eradication of the biofilm must balance aggressiveness with care to protect regenerating tissues. In this study, urea, a potent chaotropic molecule, was modulated through the formation of a Natural Deep Eutectic Solvent (NADES) with betaine to develop a new debriding material (BU) suitable for application into injured dermal tissues. To evaluate BU's debriding capacity, along with its antibiofilm effect and biocompatibility, pre-clinical to clinical methods were employed. In vitro determinations using artificial and clinical slough samples indicate that BU has a high debriding capacity. Additionally, BU's de-structuring effects lead to a strong antibiofilm capability, demonstrated by a reduced bacterial load compared to the antiseptic PHMB-Betaine or medical honey, evaluated in artificial slough and ex vivo human skin. Furthermore, BU's efficacy was evaluated in a murine model of diabetic wound, demonstrating significant effects on debriding and antibiofilm capacity, similar to those observed in PHMB-Betaine and medical honey-treated animals. Finally, BU was clinically evaluated in leg ulcers, showing superiority in reduction of bacterial load and wound area compared to honey, with no adverse effects. Thus, BU represents a simple and non-biocidal option that could contributes to chronic wound care.
Beyond tobacco: genomic disparities in lung cancer between smokers and never-smokers
(2024) Garrido, Javiera; Bernal, Yanara; González, Evelin; Blanco, Alejandro; Sepúlveda, Gonzalo; Freire, Matías; Oróstica, Karen; Rivas, Solange; Marcelain, Katherine; Owen, Gareth; Ibañez, Carolina; Corvalan, Alejandro; Garrido, Marcelo; Assar, Rodrigo; Lizana, Rodrigo; Cáceres, Javier; Ampuero, Diego; Ramos, Liliana; Pérez, Paola; Aren, Osvaldo; Chernilo, Sara; Fernández, Cristina; Spencer, María; Flores, Jacqueline; Bernal, Giuliano; Ahumada, Mónica; Rasse, Germán; Sánchez, Carolina; De Amorim, Maria; Bartelli, Thais; Noronha, Diana; Dias, Emmanuel; Freitas, Helano; Armisén, Ricardo
Background: Tobacco use is one of the main risk factors for Lung Cancer (LC) development. However, about 10-20% of those diagnosed with the disease are never-smokers. For Non-Small Cell Lung Cancer (NSCLC) there are clear differences in both the clinical presentation and the tumor genomic profiles between smokers and never-smokers. For example, the Lung Adenocarcinoma (LUAD) histological subtype in never-smokers is predominately found in young women of European, North American, and Asian descent. While the clinical presentation and tumor genomic profiles of smokers have been widely examined, never-smokers are usually underrepresented, especially those of a Latin American (LA) background. In this work, we characterize, for the first time, the difference in the genomic profiles between smokers and never-smokers LC patients from Chile. Methods: We conduct a comparison by smoking status in the frequencies of genomic alterations (GAs) including somatic mutations and structural variants (fusions) in a total of 10 clinically relevant genes, including the eight most common actionable genes for LC (EGFR, KRAS, ALK, MET, BRAF, RET, ERBB2, and ROS1) and two established driver genes for malignancies other than LC (PIK3CA and MAP2K1). Study participants were grouped as either smokers (current and former, n = 473) or never-smokers (n = 200) according to self-report tobacco use at enrollment. Results: Our findings indicate a higher overall GA frequency for never-smokers compared to smokers (58 vs. 45.7, p-value < 0.01) with the genes EGFR, KRAS, and PIK3CA displaying the highest prevalence while ERBB2, RET, and ROS1 the lowest. Never-smokers present higher frequencies in seven out of the 10 genes; however, smokers harbor a more complex genomic profile. The clearest differences between groups are seen for EGFR (15.6 vs. 21.5, p-value: < 0.01), PIK3CA (6.8 vs 9.5) and ALK (3.2 vs 7.5) in favor of never-smokers, and KRAS (16.3 vs. 11.5) and MAP2K1 (6.6 vs. 3.5) in favor of smokers. Alterations in these genes are comprised almost exclusively by somatic mutations in EGFR and mainly by fusions in ALK, and only by mutations in PIK3CA, KRAS and MAP2K1. Conclusions: We found clear differences in the genomic landscape by smoking status in LUAD patients from Chile, with potential implications for clinical management in these limited-resource settings.
Adequate housing as a social determinant of the health of international migrants and locals in Chile between 2013 and 2022
(2024) Blukacz, Alice; Oyarte, Marcela; Cabieses, Báltica
Background: Adequate housing is a fundamental right and a social determinant of health. It also represents a historically contentious topic in Latin America. Migratory flows to Chile have become increasingly precarious in the past few years, limiting opportunities for adequate housing, with potential repercussions on the health of international migrants and the general population. This study aims to analyse adequate housing as a social determinant of health among international migrants and locals between 2013 and 2022 in Chile. Methods: Observational cross-sectional study based on repeated versions of the nationally representative Socioeconomic Characterization Survey in Chile. Adequate housing indicators adapted from the United Nations Housing Rights Programme guidelines were analyzed with relation to individual health, distinguishing between the local and international migrant populations. Logistic regression models were fitted for housing indicators with migration as the main independent variable and for short-term and long-term healthcare needs in locals and immigrants with housing as the main dependent variables. Models were adjusted for sociodemographic variables and considered the complex sample design. Results: Descriptive findings indicated higher availability of services and infrastructure among international migrants, and a disadvantage for habitability, location, and affordability by quintiles compared to locals. Logistic regression models, adjusting for demographic variables, revealed significant associations between migration status and overcrowding (OR 6.14, 2022), poor housing materiality (OR 5.65, 2022) and proximity to healthcare centres (OR 1.4, 2022) compared to locals. Experiencing hazardous situations consistently predicted short-term healthcare needs in both migrants (OR = 1.4, 2022) and locals (OR = 2.8, 2022). Overcrowding predicted both long and short-term healthcare needs among locals across the years and long term needs among migrants in 2013 and 2015. Conclusions: We found significant inequities in adequate housing between migrant populations and locals in Chile, and some inequities among both populations based on structural socioeconomic deprivation. Experiencing hazardous situations emerged as a social determinant of health among international migrants in 2022, potentially suggesting growing challenges related to social exclusion in urban areas. However, limitations such as exclusion criteria of the survey and sample sizes for data on the migrant population potentially suggest that housing challenges and their impact on health are underestimated.
Migración e Interculturalidad en el Currículum: Ideas de planificación docente
(2024) Pavez-Soto, Iskra; Poblete Godoy, Daniela; Alfaro Contreras, Carmen; Dufraix, Iciar; Brevis Arratia, Katherine
A pesar de garantizarse el derecho a la educación en Chile, todavía e evidencia una debilidad en las políticas públicas educativas y curriculares que promuevan una genuina inclusión de la población estudiantil migrante. Por tal motivo, el objetivo de este artículo es analizar los tópicos vinculados a migración e interculturalidad presentes en el currículo chileno a fin de proponer estrategias pedagógicas que permitan abordar la creciente diversidad cultural en las aulas, en particular, la presencia de estudiantes migrantes. Para ello, se llevó a cabo un análisis documental que examinó las Bases Curriculares de Historia, Geografía y Ciencias Sociales identificando los contenidos relacionados a migración e interculturalidad. Los resultados revelan nudos temáticos presentes en cada una de las áreas de aprendizaje (asignaturas), a partir de esto, se entregan ideas de planificación docente para realizar talleres en la Enseñanza Básica y Media. Se concluye sobre la oportunidad de implementar un currículo adaptado a las necesidades del profesorado y desde la perspectiva de la interculturalidad en contextos de alta migración.
Youth and Social Outburst in Chile: Collective and Territorial Identities in Dispute*
(2024) Pavez-Soto, Iskra; González-Pavez, Matías; Ortíz-López, Juan; Poblete-Godoy, Daniela
This article aims to characterize collective and territorial identity disputes among young participants in the 2019 Social Outburst in Chile. It highlights the crisis of representativeness that the country has been experiencing for years and focuses on the youth subject as a protagonist of social movements. A mixed methodology was designed, which resulted in an online questionnaire applied to a sample of 41 young people and students between 15 and 24 years old, residents of communities in the Metropolitan Region. It is concluded that distrust towards political institutions persists. Still, new collective-territorial identities emerge through the resignification of public spaces, various mass demonstrations, and a militant symbology.
Recommendations for Implementing the INTERACT3 CareBundle for Intracerebral Hemorrhagein Latin America: Results of a Delphi Method
(2024) Allende, María Ignacia; Munoz Venturelli, Paula; González, Francisca; Bascur, Francisca; Craig S., Anderson; Ouyang, Menglu; Cabieses, Báltica; Obach, Alexandra; Cano-Nigenda, Vanessa; Arauz, Antonio; LATAM INTERACT3 Consensus Statement Panel
Introduction: The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT3) showed that the implementation of a care bundle improves outcomes after acute intracerebral hemorrhage (ICH). We aimed to establish consensus-based recommendations for the broader integration of the care bundle across Latin American countries (LAC). Methods: A 3-phase Delphi study allowed a panel of 32 healthcare workers from 14 LAC to sequentially rank statements relevant to 7 domains (training, resources/infrastructure, patient education, blood pressure, temperature, glycemic control, and anticoagulation reversal). The pre-defined consensus threshold was 75%. Results: A total of 43 statements reached consensus by the third round, with 12 new statements emerging through rounds. The highest-ranked statements in each domain emphasized critical aspects, but successful implementation requires appropriate resourcing. Key priorities were continuous training of all healthcare workers in ICH management, establishing protocols aligned with available resources, and collaborative interdisciplinary care supported by institutional networks. Statements related to anticoagulation reversal had the highest priority. Conclusions: Consensus statements are provided to facilitate integration of the INTERACT3 care bundle to reduce disparities in ICH outcomes in LAC.
International migration, food insecurity, and mental health: A scoping review protocol
(2024) Blukacz, Alice; Cabieses, Báltica; Huerta, Catalina; Lake, Amelia A.; Smith, Jo; Giles, Emma L.; Deane, Faye
INTRODUCTION Food insecurity is a global priority that has been found to negatively impact mental health, increasing the risk of mental disorders and severe mental illness. International migrants may face food insecurity throughout their migratory cycle due to a range of risk factors, such as poor transit conditions, precarious employment, financial pressure, discrimination, and lack of availability and access to culturally relevant food, among others. Although there are multiple reviews on migration, food insecurity, and health in general, no scoping review has been conducted on food insecurity among international migrants focusing on mental health. OBJECTIVE To investigate the available evidence on food insecurity and mental health among international migrants. METHODS A search of scientific literature in English, Spanish, French, Italian, and Portuguese published since 2013 will be performed in the Web of Science, PubMed, Medline, APA PsycArticles, Cinahl, and ASSIA databases, including grey literature available in Google Scholar. Two authors will independently review titles, abstracts, and full texts before extracting data from publications complying with the eligibility criteria. Extracted data will be descriptively mapped according to emerging thematic categories. EXPECTED RESULTS The review will contribute to identifying what is known about international migration, food insecurity, and mental health, gaps in the literature, opportunities for specific research subtopics, and how food insecurity and mental health can be linked in the existing literature.
ADAR-Mediated A>I(G) RNA Editing in the Genotoxic Drug Response of Breast Cancer
(2024) Bernal, Yanara; Durán, Eduardo; Solar, Isidora; Sagredo, Eduardo; Armisén, Ricardo
Epitranscriptomics is a field that delves into post-transcriptional changes. Among these modifications, the conversion of adenosine to inosine, traduced as guanosine (A>I(G)), is one of the known RNA-editing mechanisms, catalyzed by ADARs. This type of RNA editing is the most common type of editing in mammals and contributes to biological diversity. Disruption in the A>I(G) RNA-editing balance has been linked to diseases, including several types of cancer. Drug resistance in patients with cancer represents a significant public health concern, contributing to increased mortality rates resulting from therapy non-responsiveness and disease progression, representing the greatest challenge for researchers in this field. The A>I(G) RNA editing is involved in several mechanisms over the immunotherapy and genotoxic drug response and drug resistance. This review investigates the relationship between ADAR1 and specific A>I(G) RNA-edited sites, focusing particularly on breast cancer, and the impact of these sites on DNA damage repair and the immune response over anti-cancer therapy. We address the underlying mechanisms, bioinformatics, and in vitro strategies for the identification and validation of A>I(G) RNA-edited sites. We gathered databases related to A>I(G) RNA editing and cancer and discussed the potential clinical and research implications of understanding A>I(G) RNA-editing patterns. Understanding the intricate role of ADAR1-mediated A>I(G) RNA editing in breast cancer holds significant promise for the development of personalized treatment approaches tailored to individual patients' A>I(G) RNA-editing profiles.
Lactadherin immunoblockade in small extracellular vesicles inhibits sEV-mediated increase of pro-metastatic capacities
(2024) Durán, Eduardo; Del Campo, Matías; Gutiérrez, Valentina; Wichmann, Ignacio; Trigo, César; Ezquer, Marcelo; Lobos, Lorena
Background: Tumor-derived small extracellular vesicles (sEVs) can promote tumorigenic and metastatic capacities in less aggressive recipient cells mainly through the biomolecules in their cargo. However, despite recent advances, the specific molecules orchestrating these changes are not completely defined. Lactadherin is a secreted glycoprotein typically found in the milk fat globule membrane. Its overexpression has been associated with increased tumorigenesis and metastasis in breast cancer (BC) and other tumors. However, neither its presence in sEVs secreted by BC cells, nor its role in sEV-mediated intercellular communication have been described. The present study focused on the role of lactadherin-containing sEVs from metastatic MDA-MB-231 triple-negative BC (TNBC) cells (sEV-MDA231) in the promotion of pro-metastatic capacities in non-tumorigenic and non-metastatic recipient cells in vitro, as well as their pro-metastatic role in a murine model of peritoneal carcinomatosis. Results: We show that lactadherin is present in sEVs secreted by BC cells and it is higher in sEV-MDA231 compared with the other BC cell-secreted sEVs measured through ELISA. Incubation of non-metastatic recipient cells with sEV-MDA231 increases their migration and, to some extent, their tumoroid formation capacity but not their anchorage-independent growth. Remarkably, lactadherin blockade in sEV-MDA231 results in a significant decrease of those sEV-mediated changes in vitro. Similarly, intraperitoneally treatment of mice with MDA-MB-231 BC cells and sEV-MDA231 greatly increase the formation of malignant ascites and tumor micronodules, effects that were significantly inhibited when lactadherin was previously blocked in those sEV-MDA231. Conclusions: As to our knowledge, our study provides the first evidence on the role of lactadherin in metastatic BC cell-secreted sEVs as promoter of: (i) metastatic capacities in less aggressive recipient cells, and ii) the formation of malignant ascites and metastatic tumor nodules. These results increase our understanding on the role of lactadherin in sEVs as promoter of metastatic capacities which can be used as a therapeutic option for BC and other malignancies.
Iron-Reduced Graphene Oxide Core-Shell Micromotors Designed for Magnetic Guidance and Photothermal Therapy under Second Near-Infrared Light
(2024) Donoso, Orlando; Riveros, Ana; Marco, José; Venegas, Diego; Paredes, Verónica; Olguín, Camila; Mayorga, Cristina; Lobos, Lorena; Franco, Felipe; Wang, Joseph; Kogan, Marcelo; Bollo, Soledad; Yañez, Claudia; Báez, Daniela
Core-shell micro/nanomotors have garnered significant interest in biomedicine owing to their versatile task-performing capabilities. However, their effectiveness for photothermal therapy (PTT) still faces challenges because of their poor tumor accumulation, lower light-to-heat conversion, and due to the limited penetration of near-infrared (NIR) light. In this study, we present a novel core-shell micromotor that combines magnetic and photothermal properties. It is synthesized via the template-assisted electrodeposition of iron (Fe) and reduced graphene oxide (rGO) on a microtubular pore-shaped membrane. The resulting Fe-rGO micromotor consists of a core of oval-shaped zero-valent iron nanoparticles with large magnetization. At the same time, the outer layer has a uniform reduced graphene oxide (rGO) topography. Combined, these Fe-rGO core-shell micromotors respond to magnetic forces and near-infrared (NIR) light (1064 nm), achieving a remarkable photothermal conversion efficiency of 78% at a concentration of 434 µg mL-1. They can also carry doxorubicin (DOX) and rapidly release it upon NIR irradiation. Additionally, preliminary results regarding the biocompatibility of these micromotors through in vitro tests on a 3D breast cancer model demonstrate low cytotoxicity and strong accumulation. These promising results suggest that such Fe-rGO core-shell micromotors could hold great potential for combined photothermal therapy.
Analysis of the Behavior of Deep Eutectic Solvents upon Addition of Water: Its Effects over a Catalytic Reaction
(2024) Campodónico, Paola; Alarcón, Jazmín; Alcázar, Jackson; Olivares, Belén; Suárez, Cristian
This study presents the potential role of deep eutectic solvents (DESs) in a lipase-catalyzed hydrolysis reaction as a co-solvent in an aqueous solution given by a phosphate buffer. Ammonium salts, such as choline chloride, were paired with hydrogen bond donors, such as urea, 1,2,3-propanetriol, and 1,2 propanediol. The hydrolysis of p-nitrophenyl laureate was carried out with the lipase Candida antarctica Lipase B (CALB) as a reaction model to evaluate the solvent effect and tested in different DES/buffer phosphate mixtures at different % w/w. The results showed that two mixtures of different DES at 25 % w/w were the most promising solvents, as this percentage enhanced the activities of CALB, as evidenced by its higher catalytic efficiency (kcatKM). The solvent analysis shows that the enzymatic reaction requires a reaction media rich in water molecules to enable hydrogen-bond formation from the reaction media toward the enzymatic reaction, suggesting a better interaction between the substrate and the enzyme-active site. This interaction could be attributed to high degrees of freedom influencing the enzyme conformation given by the reaction media, suggesting that CALB acquires a more restrictive structure in the presence of DES or the stabilized network given by the hydrogen bond from water molecules in the mixture improves the enzymatic activity, conferring conformational stability by solvent effects. This study offers a promising approach for applications and further perspectives on genuinely green industrial solvents.
Distinct Driver Pathway Enrichments and a High Prevalence of TSC2 Mutations in Right Colon Cancer in Chile: A Preliminary Comparative Analysis
(2024) Tapia, Camilo; Valenzuela, Guillermo; González, Evelin; Maureira, Ignacio; Toro, Jessica; Freire, Matías; Sepúlveda, Gonzalo; Ampuero, Diego; Blanco, Alejandro; Gallegos, Iván; Morales, Fernanda; Erices, José; Barajas, Olga; Ahumada, Mónica; Contreras, Héctor; González, Jaime; Armisén, Ricardo; Marcelain, Katherine
Colorectal cancer (CRC) is the second leading cause of cancer deaths globally. While ethnic differences in driver gene mutations have been documented, the South American population remains understudied at the genomic level, despite facing a rising burden of CRC. We analyzed tumors of 40 Chilean CRC patients (Chp) using next-generation sequencing and compared them to data from mainly Caucasian cohorts (TCGA and MSK-IMPACT). We identified 388 mutations in 96 out of 135 genes, with TP53 (45%), KRAS (30%), PIK3CA (22.5%), ATM (20%), and POLE (20%) being the most frequently mutated. TSC2 mutations were associated with right colon cancer (44.44% in RCRC vs. 6.45% in LCRC, p-value = 0.016), and overall frequency was higher compared to TCGA (p-value = 1.847 × 10-5) and MSK-IMPACT cohorts (p-value = 3.062 × 10-2). Limited sample size restricts definitive conclusions, but our data suggest potential differences in driver mutations for Chilean patients, being that the RTK-RAS oncogenic pathway is less affected and the PI3K pathway is more altered in Chp compared to TCGA (45% vs. 25.56%, respectively). The prevalence of actionable pathways and driver mutations can guide therapeutic choices, but can also impact treatment effectiveness. Thus, these findings warrant further investigation in larger Chilean cohorts to confirm these initial observations. Understanding population-specific driver mutations can guide the development of precision medicine programs for CRC patients.
A Comprehensive Analysis of the Effect of A>I(G) RNA-Editing Sites on Genotoxic Drug Response and Progression in Breast Cancer
(2024) Bernal, Yanara; Blanco, Alejandro; Sagredo, Eduardo; Oróstica, Karen; Alfaro, Ivan; Marcelain, Katherine; Armisén, Ricardo
Dysregulated A>I(G) RNA editing, which is mainly catalyzed by ADAR1 and is a type of post-transcriptional modification, has been linked to cancer. A low response to therapy in breast cancer (BC) is a significant contributor to mortality. However, it remains unclear if there is an association between A>I(G) RNA-edited sites and sensitivity to genotoxic drugs. To address this issue, we employed a stringent bioinformatics approach to identify differentially RNA-edited sites (DESs) associated with low or high sensitivity (FDR 0.1, log2 fold change 2.5) according to the IC50 of PARP inhibitors, anthracyclines, and alkylating agents using WGS/RNA-seq data in BC cell lines. We then validated these findings in patients with basal subtype BC. These DESs are mainly located in non-coding regions, but a lesser proportion in coding regions showed predicted deleterious consequences. Notably, some of these DESs are previously reported as oncogenic variants, and in genes related to DNA damage repair, drug metabolism, gene regulation, the cell cycle, and immune response. In patients with BC, we uncovered DESs predominantly in immune response genes, and a subset with a significant association (log-rank test p < 0.05) between RNA editing level in LSR, SMPDL3B, HTRA4, and LL22NC03-80A10.6 genes, and progression-free survival. Our findings provide a landscape of RNA-edited sites that may be involved in drug response mechanisms, highlighting the value of A>I(G) RNA editing in clinical outcomes for BC.
Challenges for gene therapy in the financial sustainability of health systems: a scoping review
(2024) Ossandon, Hugo; Armijo, Nicolás; Vargas, Constanza; Repetto, Gabriela; Espinoza, Manuel
Aim: To review the available evidence about the strategies implemented or proposed for coverage or reimbursement for currently approved gene therapies. Methods: A scoping review was conducted to analyze the evidence published during the years 2016 to 2023. The main search criteria were coverage or reimbursement of gene therapy by healthcare systems. The eligible articles were those that described or proposed a financing model used to provide coverage in the various systems around the world. Results: The study identified 279 publications, and after removing duplicates and screening for eligibility, 10 were included in the study. The results show that various financing models have been proposed, including subscription-based payment models, outcome-based payment models, and amortization strategies. However, several barriers to implementing these models were identified, such as deficiencies in informatics systems for data collection, changes in laws or regulations, the lack of accessible clinical endpoints and administrative costs. Conclusion: This scoping review provides an overview of financing strategies for gene therapies. Gene therapies can cure rare or previously intractable diseases, but their high cost can make access difficult. Publishing experiences with these models can help evaluate their use and gather more evidence for their effectiveness.
Aloe vera peel-derived nanovesicles display anti-inflammatory properties and prevent myofibroblast differentiation
(2024) Ramírez, Orlando; Pomareda, Florencia; Olivares, Belén; Huang, Ya-Lin; Zavala, Gabriela; Carrasco, Javiera; Álvarez, Simón; Leiva, Camila; Hidalgo, Valeria; Romo, Pablo; Sánchez, Matías; Vargas, Ayleen; Martínez, Jessica; Aguayo, Sebastian; Schuh, Christina
Background: Aloe vera (AV) is a medicinal plant, most known for its beneficial effects on a variety of skin conditions. Its known active compounds include carbohydrates and flavonoids such as quercetin and kaempferol, among others. In the past decade, plant nanovesicles (NVs) have gained considerable interest as interkingdom communicators, presenting an opportunity for clinical standardization of natural products. In this study, we aimed to assess the potential of AVpNVs for the treatment of burn wounds. Methods: AVpNVs were isolated and characterized regarding vesicle yield (nanoparticle tracking analysis) and structure (transmission electron microscopy and atomic force microscopy), as well as their protein content with proteomics. We assessed key characteristics for treating burn wounds in vitro, such as the anti-inflammatory potential in LPS-stimulated macrophages and keratinocytes, and the effect of AVpNVs on myofibroblast differentiation and contraction. Key findings: AVpNVs presented a homogenous NV population, vesicular shape, and NV-associated protein markers. AVpNVs significantly decreased the secretion of pro-inflammatory cytokines TNFα, IL-1β, and IL-6. Furthermore, AVpNVs inhibited myofibroblast differentiation and significantly decreased their contractile potential in collagen matrices. Observed effects were linked to proteins identified in the isolates through proteomics analysis. Conclusion: AVpNVs displayed characteristics as an inflammatory modulator, while simultaneously diminishing myofibroblast differentiation and contraction. Novel strategies for burn wound treatment seek to decrease scarring on a cellular and molecular level in the early stages of wound healing, which makes AVpNVs a promising candidate for future plant-vesicle-based treatments.
Pannexin-1 expression in tumor cells correlates with colon cancer progression and survival
(2024) Fierro, Aaron; Landskron, Glauben; Camhi, Ilan; Basterrechea, Benjamín; Parada, Daniela; Lobos-González, Lorena; Dubois, Karen; Araneda, Catalina; Romero, Camila; Domínguez, Antonia; Vásquez, Gonzalo; López, Francisco; Alvarez, Karin; González, Carlos; Hager, Carolina; Balboa, Elisa; Eugenin, Eliseo; Hermoso, Marcela; De la Fuente, Marjorie
Aims: Pannexin-1 (PANX1) is a hemichannel that releases ATP upon opening, initiating inflammation, cell proliferation, and migration. However, the role of PANX1 channels in colon cancer remains poorly understood, thus constituting the focus of this study. Main methods: PANX1 mRNA expression was analyzed using multiple cancer databases. PANX1 protein expression and distribution were evaluated by immunohistochemistry on primary tumor tissue and non-tumor colonic mucosa from colon cancer patients. PANX1 inhibitors (probenecid or 10Panx) were used to assess colon cancer cell lines viability. To study the role of PANX1 in vivo, a subcutaneous xenograft model using HCT116 cells was performed in BALB/c NOD/SCID immunodeficient mice to evaluate tumor growth under PANX1 inhibition using probenecid. Key findings: PANX1 mRNA was upregulated in colon cancer tissue compared to non-tumor colonic mucosa. Elevated PANX1 mRNA expression in tumors correlated with worse disease-free survival. PANX1 protein abundance was increased on tumor cells compared to epithelial cells in paired samples, in a cancer stage-dependent manner. In vitro and in vivo experiments indicated that blocking PANX1 reduced cell viability and tumor growth. Significance: PANX1 can be used as a biomarker of colon cancer progression and blocking PANX1 channel opening could be used as a potential therapeutic strategy against this disease.
Borders and liminality in the right to health of migrants in transit: The case of Colchane in Chile and Necoclí in Colombia
(2024) Jaramillo Contreras, Andrea Carolina; Cabieses, Báltica; Knipper, Michael; Rocha Jiménez, Teresita
The absence of the right to health of migrants in transit has evolved into a significant global health concern, particularly in the border regions thus, this study aims to improve knowledge in this area by exploring the effects of the spatio-temporal liminal characteristics at borders in the achievement of the right to health of migrants in transit moving across two of the most transited and dangerous borders in Latin America: Colchane (Chile-Bolivia) and the Dari´en Gap (Colombia-Panamá). Through a qualitative descriptive multi-case study, we implemented 50 semi-structured interviews (n = 30 in Chile and n = 20 in the Dari´en/Necoclí) involving national, regional, and local stakeholders. The findings highlight that the fulfilment of the right to health of migrants in transit is hindered by liminal dynamics at the borders. These dynamics include closure of borders, (in)securities, uncer tainty and waiting, lack of economic resources, lack of protection to all, liminal politics, and humanitarian in terventions. These findings surface how the borders’ liminality exacerbates the segregation of migrants in transit by placing them in a temporospatial limbo that undermines their right to health. Our study concludes that not just the politics but also the everyday practices, relationships and social infrastructure at borders impedes the enjoyment of the right to health of distressed migrants in transit. The short-term humanitarian response; illicit dynamics at borders; migratory regulations; and border and cross-border political structures are some of the most significant determinants of health at these borderlands.
Editorial: SLC6A1: the past, present and future
(2023) Johannesen, Katrine M.; Pérez Palma, Eduardo; Rubboli, Guido
Controlled Release of the Anticancer Drug Cyclophosphamide from a Superparamagnetic β‑Cyclodextrin Nanosponge by Local Hyperthermia Generated by an Alternating Magnetic Field
(2024) SALAZAR SANDOVAL, SEBASTIAN ANDRES; Díaz-Saldívar, Patricia; Araya, Ingrid; Celis, Freddy; Cortés-Arriagada, Diego; Riveros, Ana; Rojas-Romo, Carlos; Jullian, Carolina; Silva, Nataly; Yutronic, Nicolás; Kogan, Marcelo J.; Jara, Paul
β-cyclodextrin (β-CD) nanosponge (NS) was synthesized using diphenyl carbonate (DPC) as a cross-linker to encapsulate the antitumor drug cyclophosphamide (CYC), thus obtaining the NSs-CYC system. The formulation was then associated with magnetite nanoparticles (MNPs) to develop the MNPs-NSs-CYC ternary system. The formulations mentioned above were characterized to confirm the deposition of the MNPs onto the organic matrix and that the superparamagnetic nature of the MNPs was preserved upon association. The association of the MNPs with the NSs-drug complex was confirmed through field emission scanning electron microscopy, energy dispersive spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, dynamic light scattering, ζ-potential, atomic absorption spectroscopy, X-ray powder diffraction, selected area electron diffraction, and vibrating-sample magnetometer. The superparamagnetic properties of the ternary system allowed the release of CYC by utilizing magnetic hyperthermia upon the exposure of an alternating magnetic field (AMF). The drug release experiments were carried out at different frequencies and intensities of the magnetic field, complying with the “Atkinson−Brezovich criterion”. The assays in AMF showed the feasibility of release by controlling hyperthermia of the drug, finding that the most efficient conditions were F = 280 kHz, H = 15 mT, and a concentration of MNPs of 5 mg/mL. CYC release was temperature-dependent, facilitated by local heat generation through magnetic hyperthermia. This phenomenon was confirmed by DFT calculations. Furthermore, the ternary systems outperformed the formulations without MNPs regarding the amount of released drug. The MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assays demonstrated that including CYC within the magnetic NS cavities reduced the effects on mitochondrial activity compared to those observed with the free drug. Finally, the magnetic hyperthermia assays showed that the tertiary system allows the generation of apoptosis in HeLa cells, demonstrating that the MNPs embedded maintain their properties to generate hyperthermia. These results suggest that using NSs associated with MNPs could be a potential tool for a controlled drug delivery in tumor therapy since the materials are efficient and potentially nontoxic.
High-resolution manometry thresholds and motor patterns among asymptomatic individuals.
(2022) Rengarajan, Arvind; Rogers, Benjamin D.; Wong, Zhiqin; Tolone, Salvatore; Sifrim, Daniel; Serra, Jordi; Savarino, Edoardo; Roman, Sabine; Remes-Troche, Jose M.; Ramos, Rosa; Perez de la Serna, Julio; Pauwels, Ans; Leguizamo, Ana Maria; Yeh Lee, Yeong; Kawamura, Osamu; Hayat, Jamal; Hani, Albis; Gonlachanvit, Sutep; Cisternas, Daniel; Cisternas, Daniel; Carlson, Dustin; Bor, Serhat; Bhatia, Shobna; Abrahao, Luiz; Pandolfino, John; Gyawali, C. Prakash
Objective: High-resolution manometry (HRM) is the current standard for characterization of esophageal body and esophagogastric junction (EGJ) function. We aimed to examine the prevalence of abnormal esophageal motor patterns in health, and to determine optimal thresholds for software metrics across HRM systems. Design: Manometry studies from asymptomatic adults were solicited from motility centers worldwide, and were manually analyzed using integrated relaxation pressure (IRP), distal latency (DL), and distal contractile integral (DCI) in standardized fashion. Normative thresholds were assessed using fifth and/or 95th percentile values. Chicago Classification v3.0 criteria were applied to determine motor patterns across HRM systems, study positions (upright vs supine), ages, and genders. Results: Of 469 unique HRM studies (median age 28.0, range 18-79 years). 74.6% had a normal HRM pattern; none had achalasia. Ineffective esophageal motility (IEM) was the most frequent motor pattern identified (15.1% overall), followed by EGJ outflow obstruction (5.3%). Proportions with IEM were lower using stringent criteria (10.0%), especially in supine studies (7.1%-8.5%). Other motor patterns were rare (0.2%-4.1% overall) and did not vary by age or gender. DL thresholds were close to current norms across HRM systems, while IRP thresholds varied by HRM system and study position. Both fifth and 95th percentile DCI values were lower than current thresholds, both in upright and supine positions. Conclusions: Motor abnormalities are infrequent in healthy individuals and consist mainly of IEM, proportions of which are lower when using stringent criteria in the supine position. Thresholds for HRM metrics vary by HRM system and study position.

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