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Connexin46 in the nucleus of cancer cells: a possible role as transcription modulator
(Springer Science and Business Media LLC, 2025-03-27)
Ainoa Fernández-Olivares
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Viviana P Orellana
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Jesús Llanquinao
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NUÑEZ VASQUEZ, GONZALO ESTEBAN
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Pablo Pérez-Moreno
Scopus© Citations 1 10
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Are there Effective Vegan-Friendly Supplements for Optimizing Health and Sports Performance? a Narrative Review
(Springer Science and Business Media LLC, 2025-03-12)
Álvaro Vergara A. Nieto
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Andrés Halabi Diaz
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Millaray Hernández
2Scopus© Citations 4
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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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A Simple Machine Learning-Based Quantitative Structure–Activity Relationship Model for Predicting pIC50 Inhibition Values of FLT3 Tyrosine Kinase
(MDPI AG, 2025-01-14)
ALCAZAR JIMENEZ, JACKSON JOSE
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Ignacio Sánchez
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Cristian Merino
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Bruno Monasterio
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Gaspar Sajuria
<jats:p>Background/Objectives: Acute myeloid leukemia (AML) presents significant therapeutic challenges, particularly in cases driven by mutations in the FLT3 tyrosine kinase. This study aimed to develop a robust and user-friendly machine learning-based quantitative structure–activity relationship (QSAR) model to predict the inhibitory potency (pIC50 values) of FLT3 inhibitors, addressing the limitations of previous models in dataset size, diversity, and predictive accuracy. Methods: Using a dataset which was 14 times larger than those employed in prior studies (1350 compounds with 1269 molecular descriptors), we trained a random forest regressor, chosen due to its superior predictive performance and resistance to overfitting. Rigorous internal validation via leave-one-out and 10-fold cross-validation yielded Q2 values of 0.926 and 0.922, respectively, while external validation on 270 independent compounds resulted in an R2 value of 0.941 with a standard deviation of 0.237. Results: Key molecular descriptors influencing the inhibitor potency were identified, thereby improving the interpretability of structural requirements. Additionally, a user-friendly computational tool was developed to enable rapid prediction of pIC50 values and facilitate ligand-based virtual screening, leading to the identification of promising FLT3 inhibitors. Conclusions: These results represent a significant advancement in the field of FLT3 inhibitor discovery, offering a reliable, practical, and efficient approach for early-stage drug development, potentially accelerating the creation of targeted therapies for AML.</jats:p>
Scopus© Citations 2 8
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The role of astrocytes in depression, its prevention, and treatment by targeting astroglial gliotransmitter release
(2024)
Yorley Duarte
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Daisy Quintana-Donoso
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Rodrigo Moraga-Amaro
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Ivanka Dinamarca
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Yordan Lemunao
<jats:p>The role of ventral hippocampus (vHipp) astroglial gliotransmission in depression was studied using chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS) rodent models. CRS increased Cx43 hemichannel activity and extracellular glutamate levels in the vHipp and blocking astroglial Cx43 hemichannel-dependent gliotransmission during CRS prevented the development of depression and glutamate buildup. Moreover, the acute blockade of Cx43 hemichannels induced antidepressant effects in rats previously subjected to CRS or CUMS. This antidepressant effect was prevented by coinjection of glutamate and D-serine. Furthermore, Cx43 hemichannel blockade decreased postsynaptic NMDAR currents in vHipp slices in a glutamate and D-serine-dependent manner. Notably, chronic microinfusion of glutamate and D-serine, L-serine, or the NMDAR agonist NMDA, into the vHipp induced depressive-like symptoms in nonstressed rats. We also identified a small molecule, cacotheline, which blocks Cx43 hemichannels and its systemic administration induced rapid antidepressant effects, preventing stress-induced increases in astroglial Cx43 hemichannel activity and extracellular glutamate in the vHipp, without sedative or locomotor side effects. In conclusion, chronic stress increases Cx43 hemichannel-dependent release of glutamate and D-/L-serine from astrocytes in the vHipp, overactivating postsynaptic NMDARs and triggering depressive-like symptoms. This study highlights the critical role of astroglial gliotransmitter release in chronic stress-induced depression and suggests it can be used as a target for the prevention and treatment of depression.</jats:p>
Scopus© Citations 5 8
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Reduction of nicotine and ethanol intake in alcohol-preferring (UChB) female rats by the α4β2 nicotinic acetylcholine receptor partial agonists 5-bromocytisine and cytisine
(2023)
María Elena Quintanilla
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Mario Rivera-Meza
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Pablo Berríos-Cárcamo
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Bruce K. Cassels
Scopus© Citations 2 2
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Spent coffee grounds extract: antimicrobial activity against Paenibacillus larvae and its effect on the expression of antimicrobial peptides in Apis mellifera
(2023)
Pablo Giménez-Martínez
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Fabián Zúñiga
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Sandra Medici
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Sandra Fuselli
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Jessica Martínez
1Scopus© Citations 4
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Mitochondria in oral cancer stem cells: Unraveling the potential drug targets for new and old drugs
(2023)
Ivonne Olmedo
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Daniela Martínez
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Javiera Carrasco-Rojas
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José A. Jara
1Scopus© Citations 19
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Integration of T‐cell clonality screening using <scp>TRBC</scp>‐1 in lymphoma suspect samples by flow cytometry
(2023)
Felipe Castillo
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Constanza Morales
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Biserka Spralja
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Joaquín Díaz‐Schmidt
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IRURETAGOYENA BRUCE, MIRENTXU INES
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The diagnosis of T‐cell non‐Hodgkin lymphomas (NHL) is challenging. The development of a monoclonal antibody specific for T‐cell receptor β constant region 1 (TRBC1) provides an alternative to discriminate clonal T cells. The aim of this study was to evaluate the diagnostic potential of an anti‐TRBC1 mAb for the identification of T‐NHL.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We performed a cross‐sectional diagnostic analytic study of samples tested for lymphoma. All samples sent for lymphoma screening were first evaluated using the standard Euroflow LST, to which a second additional custom‐designed T‐cell clonality assessment tube was added CD45/TRBC1/CD2/CD7/CD4/TCRγδ/CD3. Flow cytometry reports were compared with morphological and molecular tests.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Fifty‐nine patient samples were evaluated. Within the T‐cell population, cut‐off percentages in the CD4+ cells were from 29.4 to 54.6% and from 23.9 to 52.1% in CD8+ cells. Cut‐off ratios in CD4+ T cells were from 0.33 to 1.1, and in CD8+ cells between 0.22 and 1.0. Using predefined normal cut‐off values, 18 of 59 (30.5%) samples showed a restricted expression of TRBC1. A final diagnosis of a T‐NHL was confirmed clinically and/or by histopathological studies in 15 of the 18 cases (83.3%). There were no cases of T‐NHL by morphology/IHC with normal TRBC1 expression. Non‐neoplastic patient samples behaved between predefined TRBC1 cut‐off values.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Expression of TRBC1 provides a robust method for T‐cell clonality assessment, with very high sensitivity and good correlation with complementary methods. TRBC1 can be integrated into routine lymphoma screening strategies via flow cytometry.</jats:p></jats:sec>
Scopus© Citations 3 1
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Effects of a High-Fat Diet and Docosahexaenoic Acid during Pregnancy on Fatty Acid Composition in the Fetal Livers of Mice
(2023)
Daniela Álvarez
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Macarena Ortiz
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Gabriel Valdebenito
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Nicolás Crisosto
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Bárbara Echiburú
<jats:p>A high-fat diet (HFD) during pregnancy promotes fat accumulation and reduces docosahexaenoic acid (DHA) levels in the liver of the offspring at postnatal ages, which can depend on fetal sex. However, the prenatal mechanisms behind these associations are still unclear. Thus, we analyzed if an HFD alters DHA content and the expression of molecules related to fatty acid (FA) metabolism in the fetal liver. Female C57BL/6 mice were fed a control diet or HFD for 4–6 weeks before pregnancy until the gestational day (GD) 17.5. A subgroup of each diet received DHA (100 mg/Kg) orally from GD 6.5 until 16.5. On GD 17.5, maternal livers, placentas, and livers from male and female fetuses were collected for FA profiling with gas-chromatography and gene expression of molecules related to FA metabolism using qPCR. PPAR-α protein expression was evaluated using Western blot. The gene expression of placental FA transporters was also assessed. An HFD increased eicosapentaenoic acid (EPA) and decreased DHA levels and protein expression of PPAR-α in the fetal livers of both sexes. DHA increased the gene expression of Ppara, Cpt1, and Acsl1 in the livers of female fetuses. Therefore, an HFD reduces DHA levels and PPAR-α, a master regulator of gene expression, in the fetal liver. In turn, the livers of female fetuses seem to be more sensitive to DHA action.</jats:p>
Scopus© Citations 2

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