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Molecular Interplay Between Non-Coding RNAs and Connexins and Its Possible Role in Cancer
(MDPI AG, 2025-03-12)
Pablo Pérez-Moreno
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Juan P. Muñoz
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RETAMAL LUCERO, MAURICIO ANTONIO
Non-coding RNAs (ncRNAs) are sequences that do not encode for proteins and play key roles in different cellular processes, including cell proliferation and differentiation. On the other hand, connexins (Cxs) are transmembrane proteins that principally allow intercellular communication. In pathological conditions such as cancer, there is a deregulation in the expression and/or function of ncRNAs and Cxs, which in turn leads to an enhancement in the aggressive phenotype, such as a greater proliferative and invasive capacity. This suggests a plausible interplay between ncRNAs and Cxs. Based on that, this review aims to summarize the current knowledge regarding this relationship and to analyze how it may influence the development of aggressive traits in cancer cells and the clinicopathological features of cancer patients. Finally, we discuss the potential of ncRNAs and Cxs as promising clinical biomarkers for cancer diagnosis, prognosis, and therapeutic targeting.
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IL-10 and IL-6/IL-10 as predictive biomarkers for treatment response in non-infectious uveitis
(Frontiers Media SA, 2025-05-13)
Rodrigo A. Valenzuela
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Fabian Vega-Tapia
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Nathaly Elizalde
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Ivan Flores
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Felipe M. Rojas
Uveitis, a group of heterogeneous diseases causing ocular inflammation, is a major contributor to vision loss globally. While systemic corticosteroids (CS) are the mainstay treatment, identifying CS-refractory patients remains a significant challenge. This study aimed to explore cytokine expression and Glucocorticoid Receptor (GR) levels as biomarkers for the early detection of CS-refractory cases in non-infectious uveitis. We assayed blood samples from 19 patients with non-infectious uveitis, for the expression of IL-6, IL-17A, TNF-α, IL-10 and GRα. The cohort included 11 refractory and 8 sensitive patients, categorized based on their clinical response to corticosteroids (prednisone 1 mg/kg/day). Blood draws were conducted at three time points (at baseline, day 7- and day 14 after CS initiation), and peripheral blood mononuclear cells (PBMCs) were isolated to measure cytokine and GRα transcript levels via real-time PCR. The expression levels of GRα and cytokines IL-6, IL-17A and TNF-α did not show significant changes between CS-sensitive and CS-refractory patients on the different days of treatment. However, IL-10 expression levels as the day14-to-day7 ratio were significantly higher in patients sensitive to CS therapy. A higher day14-to-day7 ratio was also found for the IL-6/IL-10, IL-17A/IL-10 and GRα/IL-10 ratios. ROC curve analysis demonstrated a robust predictive performance of IL-10 mRNA expression and the IL-6/IL-10 ratio for identifying CS-refractory patients. In conclusion, the expression of IL-10 and the IL-6/IL-10 ratio hold promise as early predictive biomarkers for CS treatment refractoriness in patients with non-infectious uveitis. These findings offer valuable insights into personalized treatment strategies, potentially leading to improved clinical outcomes.
Scopus© Citations 6 1
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Methylated Reprimo Cell-Free DNA as a Non-Invasive Biomarker for Gastric Cancer
(MDPI AG, 2025-04-03)
María José Maturana
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Oslando Padilla
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Pablo M. Santoro
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Maria Alejandra Alarcón
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Wilda Olivares
Restrictions resulting from the COVID-19 pandemic abruptly reversed the slow decline of the diagnosis and mortality rates of gastric cancer (GC). This scenario highlights the importance of developing cost-effective methods for mass screening and evaluation of treatment response. In this study, we evaluated a non-invasive method based on the circulating methylated cell-free DNA (cfDNA) of Reprimo (RPRM), a tumor suppressor gene associated with the development of GC. Methylated RPRM cfDNA was analyzed in three de-identified cohorts: Cohort 1 comprised 81 participants with GC and 137 healthy donors (HDs); Cohort 2 comprised 27 participants with GC undergoing gastrectomy and/or chemotherapy analyzed at the beginning and after three months of treatment; and Cohort 3 comprised 1105 population-based participants in a secondary prevention program who underwent esophagogastroduodenal (EGD) endoscopy. This cohort includes 180 normal participants, 845 participants with premalignant conditions (692 with chronic atrophic gastritis [AG] and 153 with gastric intestinal metaplasia/low-grade dysplasia [GIM/LGD]), 21 with high-grade dysplasia/early GC [HGD/eGC], and 59 with advanced GC [aGC]). A nested case-control substudy was performed using a combination of methylated RPRM cfDNA and pepsinogens (PG)-I/II ratio. The dense CpG island of the promoter region of the RPRM gene was bisulfite sequenced and analyzed to develop a fluorescence-based real-time PCR assay (MethyLight). This assay allows the determination of the absolute number of copies of methylated RPRM cfDNA. A targeted sequence of PCR amplicon products confirmed the gastric origin of the plasma-isolated samples. In Cohort 1, the mean value of GCs (32,240.00 copies/mL) was higher than that of the HD controls (139.00 copies/mL) (p < 0.0001). After dividing this cohort into training–validation subcohorts, we identified an area under the curve of 0.764 (95% confidence interval (CI) = 0.683–0.845) in the training group. This resulted in a cut-off value of 87.37 copies/mL (sensitivity 70.0% and specificity 80.2%). The validation subcohort predicted a sensitivity of 66.67% and a specificity of 83.33%. In Cohort 2 (monitoring treatment response), RPRM levels significantly decreased in responders (p = 0.0042) compared to non-responders. In Cohort 3 (population-based participants), 18.9% %, 24.1%, 30.7%, 47.0%, and 71.2% of normal, AG, GIM/LGD, HGD/eGC, and aGC participants tested positive for methylated RPRM cfDNA, respectively. Overall sensitivity and specificity in distinguishing normal/premalignant conditions vs. GC were 65.0% (95% CI 53.52% to 75.33%) and 75.9% (95% CI 73.16% to 78.49%), respectively, with an accuracy of 75.11% (95% CI 72.45% to 77.64%). Logistic regression analyses revealed an OR of 1.85 (95% CI 1.11–3.07, p = 0.02) and an odds ratio (OR) of 3.9 (95% CI 1.53–9.93, p = 0.004) for the risk of developing GIM/LGD and HGD/eGC, respectively. The combined methylated RPRM cfDNA and PG-I/II ratio reached a sensitivity of 78.9% (95% CI 54.43% to 93.95%) and specificity of 63.04% (95% CI 52.34% to 72.88%) for detecting HGD/eGC vs. three to six age- and sex-matched participants with premalignant conditions. Our results demonstrate that methylated RPRM cfDNA should be considered a direct biomarker for the non-invasive detection of GC and a predictive biomarker for treatment response.
1Scopus© Citations 4
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Early high-sensitivity troponin elevation and short-term mortality in sepsis: a systematic review with meta-analysis
(Springer Science and Business Media LLC, 2025-02-14)
Abraham I. J. Gajardo
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Santiago Ferrière-Steinert
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Joaquín Valenzuela Jiménez
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Sebastián Heskia Araya
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Thomas Kouyoumdjian Carvajal
Abstract Background Serum cardiac troponin (cTn) elevation is a well-established phenomenon in sepsis. However, the clinical signifcance of this phenomenon with high-sensitivity (hs) assays and the current sepsis defnition needs to be settled. Research Question What is the association between early serum cTn levels measured by hs-assays and the risk of short-term mortality in septic patients? Study Design and Methods We conducted a systematic review using a comprehensive PubMed, Scopus, and Embase search. Studies were eligible if they reported association data on early hs-cTn and mortality in an adult sample with sepsis that met the Sepsis-3 defnition. For the synthesis of the efect of hs-cTn on mortality, we applied random efect models on the pooled unadjusted and adjusted odds ratio (OR and aOR, respectively) of elevated vs. normal hs-cTn serum values, and on the crude standardized mean diference (SMD) of hs-cTn between survivors and non-survivors. Results In total, 6242 patients from 17 studies were included, with short-term mortality rates ranging from 16.9% to 53.8%. Using a crude analysis, non-survivor patients showed higher hs-cTn than survivors (SMD of 0.87, 95%CI: 0.41–1.33). Elevated hs-cTn was associated with increased mortality (OR=1.78, 95% CI: 1.41–2.25). However, this prognostic efect was absent in studies that adjusted for diferent confounders (aOR=1.06, 95% CI: 0.99–1.14). Discussion and Conclusions Non-survivors of sepsis exhibited signifcantly elevated hs-cTn levels. While elevated hs-cTn levels are associated with an increased risk of mortality, they are not independently associated with this outcome in sepsis
1Scopus© Citations 19
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Gaps in biomedical research in frontotemporal dementia: A call for diversity and disparities focused research
(2024)
Karen Nuytemans
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Sanne Franzen
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Iris J. Broce
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Paulo Caramelli
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Ratnavalli Ellajosyula
<jats:title>Abstract</jats:title><jats:p>Frontotemporal dementia (FTD) is one of the leading causes of young‐onset dementia before age 65, typically manifesting as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). Although FTD affects all populations across the globe, knowledge regarding the pathophysiology and genetics derives primarily from studies conducted in North America and Western Europe. Globally, biomedical research for FTD is hindered by variable access to diagnosis, discussed in this group's earlier article, and by reduced access to expertise, funding, and infrastructure. This perspective paper was produced by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) and discusses the field's current status on the cross‐cultural aspects of basic and translational research in FTD (including that focused on epidemiology, genetics, biomarkers, and treatment). It subsequently provides a summary of gaps and needs to address the disparities and advance global FTD biomedical research.</jats:p>
Scopus© Citations 4
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Early high-sensitivity troponin elevation in predicting short-term mortality in sepsis: A protocol for a systematic review with meta-analysis
(2024)
Santiago Ferrière-Steinert
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Joaquín Valenzuela Jiménez
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Sebastián Heskia Araya
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Thomas Kouyoumdjian
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José Ramos-Rojas
<jats:sec id="sec001"> <jats:title>Background</jats:title> <jats:p>Sepsis is a common admission diagnosis in the intensive care unit (ICU). The Sepsis-3 consensus associates sepsis diagnosis with acute organ dysfunction. In these patients troponin elevation is a well-established phenomenon, but its clinical significance is not settled, as no systematic review has addressed the prognostic significance of the increasingly prevalent high-sensitivity troponin assays in acute organ dysfunction setting.</jats:p> <jats:p>This study aims to clarify the association between early serum troponin levels in high-sensitivity assays with short-term mortality risk in septic patients with acute organ dysfunction.</jats:p> </jats:sec> <jats:sec id="sec002"> <jats:title>Methods</jats:title> <jats:p>We will systematically search PubMed, Scopus and Embase for original articles; additionally, a manual search will be carried out through relevant literature. Generally, studies will be deemed eligible for inclusion if they evaluate the association between high-sensitivity troponin in the first 24 hours of admission and ICU, 30-days, or In-hospital mortality; in patients with septic shock or sepsis related to acute organ dysfunction. Two reviewers will independently select studies and extract the data. A meta-analysis for mortality outcome will be performed for comparative data regarding two effect measures: Odd ratios and Standardized Mean differences.</jats:p> </jats:sec> <jats:sec id="sec003"> <jats:title>Discussion</jats:title> <jats:p>This study will provide further evidence about the role of high-sensitivity troponin assays in predicting mortality in septic patients; potentially helping to guide further research and yielding valuable information for patient assessment.</jats:p> <jats:p>Conclusion about the certainty of evidence will be presented in a ´Summary of findings´ table.</jats:p> </jats:sec> <jats:sec id="sec004"> <jats:title>Trial registration</jats:title> <jats:p>PROSPERO registration:</jats:p> <jats:p>(<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024468883" xlink:type="simple">CRD42024468883</jats:ext-link>).</jats:p> </jats:sec>
8Scopus© Citations 3
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The Sicker the Patient the Higher the Lactate
(2013)
RICARDO ARNOLDO RONCO MACCHIAVELLO
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Andres Castillo
Scopus© Citations 1 1
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Association between maternal obesity, essential fatty acids and biomarkers of fetal liver function
(2023)
Macarena Ortiz
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Francisca Sánchez
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Daniela Álvarez
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Cristian Flores
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Francisca Salas-Pérez
7Scopus© Citations 5
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Assessing Pulmonary Epithelial Damage in Hantavirus Cardiopulmonary Syndrome: Challenging the Predominant Role of Vascular Endothelium through sRAGE as a Potential Biomarker
(2023)
Gabriela Meza-Fuentes
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LOPEZ HERNANDEZ, RENE RAMON
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RETAMAL LUCERO, MAURICIO ANTONIO
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CORTES SALINAS, LINA JIMENA
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VIAL COX, MARIA CECILIA
Hantavirus cardiopulmonary syndrome (HCPS) is a severe respiratory illness primarily associated with microvascular endothelial changes, particularly in the lungs. However, the role of the pulmonary epithelium in HCPS pathogenesis remains unclear. This study explores the potential of soluble Receptors for Advanced Glycation End-products (sRAGE) as a biomarker for assessing pulmonary epithelial damage in severe HCPS, challenging the prevailing view that endothelial dysfunction is the sole driver of this syndrome. We conducted a cross-sectional study on critically ill HCPS patients, categorizing them into mild HCPS, severe HCPS, and negative control groups. Plasma sRAGE levels were measured, revealing significant differences between the severe HCPS group and controls. Our findings suggest that sRAGE holds promise as an indicator of pulmonary epithelial injury in HCPS and may aid in tracking disease progression and guiding therapeutic strategies. This study brings clarity on the importance of investigating the pulmonary epithelium’s role in HCPS pathogenesis, offering potential avenues for enhanced diagnostic precision and support in this critical public health concern.
1
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Parámetros hematológicos y biomarcadores predictores de gravedad en Síndrome Inflamatorio Pediátrico Multisistémico asociado a SARS-CoV-2
(2021)
Patricia Verdugo
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Patricia Álvarez
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Patricia Aroca
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Vicente Enrique Montes-nogales
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POLI HARLOWE, MARIA CECILIA BERTA
<jats:p>El síndrome inflamatorio multisistémico pediátrico asociado a SARS-CoV-2 (MIS-C) se caracteriza por un estado hiperinflamatorio producto de una tormenta de citoquinas, evidenciado en alteraciones del laboratorio hematológico y proteínas de fase aguda.Objetivo: Describir las características clínicas y de laboratorio de pacientes hospitalizados por MIS-C e identificar marcadores predictores de gravedad.Pacientes y Método: Estudio retrospectivo de 32 pacientes. El grupo se dividió en crítico y no crítico según presentación clínica y tipo de terapia utilizada. En ellos se estudiaron aspectos clínicos y de laboratorio que incluyeron hemograma completo, pruebas de coagulación y biomarcadores. Resultados: 18/32 hombres, mediana de edad 6,8 años. Las manifestaciones más frecuentes fueron cardiovasculares (84,3%), digestivas (84%) y mucocutáneas (59%). El grupo de los críticos incluyó 15 pacientes, 12 hombres con mediana de edad de 8,9 años y los no críticos 17 pacientes; 6 hombres, con mediana de edad de 5,4 años. Los parámetros de laboratorio al ingreso en el grupo global mostraron aumento de la proteína C reactiva, dímero-D, leucocitos, neutrófilos, ferritina y fibrinógeno. La albúmina y la natremia en cambio se encontraban disminuidas. El grupo crítico se caracterizó por tener al ingreso: trombocitopenia, hipoalbuminemia, prolongación del tiempo de protrombina y elevación de la ferritina. Al deterioro hubo acentuación de la trombocitopenia, ascenso mayor de la proteína C reactiva junto a elevación de los neutrófilos.Conclusión: El hemograma, la proteína C reactiva y la albuminemia al ingreso resultaron ser de alto valor en la identificación de pacientes con riesgo de agravamiento clínico.</jats:p>
20Scopus© Citations 10

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