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Question

Tainá Miotto de Souza replied to the topic "Questions"

Publication: DNA methylation profile in pediatric patients with germ cell tumors

Thanks for your amazing talk and results! I have some questions, as follows: 1) Did you identify subtype-specific methylation patterns (e.g., yolk sac vs dysgerminoma vs immature teratoma), and if so, do these overlap with known methylation “imprints” in primordial germ cell development or pluripotency pathways? 2) Since resistance to cisplatin is a major clinical issue, have you explored whether methylation changes in DNA repair genes (e.g., MGMT, MLH1, or other repair-associated promoters) correlate with high-risk or resistant cases in your cohort? 3) Considering the reliance on tumor markers and histopathology in GCT diagnosis, do you envision that DNA methylation profiling could be translated into a minimally invasive diagnostic approach (for instance, via circulating tumor DNA methylation in plasma) and how would you address challenges of sensitivity and specificity in children? Thanks and congrats again!
08/28/2025
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Question

Tainá Miotto de Souza replied to the topic "Implications of DNA methylation in tumor biology"

Publication: DNA methylation profile in pediatric patients with germ cell tumors

Congratulations on your work, it's so complex and well-developed! I work with gliomas, which are brain tumors, and there's much discussion about methylation changes. Some gliomas even present a hypermethylator profile, so this is a very promising study. I just have two questions regarding your work: 1. Your methylation data from 13 pediatric GCT samples are very interesting. Considering the small sample size and tumor heterogeneity, have you thought about ways to validate whether these patterns are consistent across a larger patient population or other tumor subtypes? 2. Have you considered complementing this with RNA-seq or proteomics to explore how these methylation changes might influence gene expression or tumor behavior? Again, congrats for your project!
08/28/2025
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Question

Paulo Henrique dos Santos Bento replied to the topic "Impact of NS5A on oxidative stress and oncogenic pathways"

Publication: The role of the NS5A protein of the hepatitis C virus (HCV) in cellular signaling pathways associated with hepatocellular carcinoma in the presence of oxidative stress

Congratulations for your work, it's very interesting! I'm currently studying the NS5 protein in gliomas, so I found your study extremely relevant and engaging. I have two questions about your work: First, how might the upregulation of GRB2 by NS5A contribute to the establishment of a pro-oncogenic microenvironment in hepatocytes? And given that NS5A expression protected cells from H2O2-induced loss of viability, what additional experiments would you propose to clarify whether this protective effect is mediated primarily through oxidative stress modulation or through alterations in survival signaling pathways?
08/28/2025
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Question

Anna Gabriele Prado dos Santos replied to the topic "Questions"

Publication: CIRSIMARIN MODULATES A549 LUNG CANCER CELL MIGRATION IN 2D AND 3D CULTURES VIA TRANSCRIPTIONAL REGULATION OF METALLOPROTEINASES

Thanks for your amazing talk and results! I have some questions, as follows: 1) You demonstrated the downregulation of MMP2/9/11 transcripts after cirsimarin exposure, so I wonder if these transcript changes translate into reduced proteolytic activity in the extracellular milieu, for instance, and have you measured their active vs. pro-forms (e.g., by zymography or activity assays)? 2) There is a notable difference in effective concentrations between your 2D (1–40 μM) and 3D (160 μM) assays. How do you interpret this in terms of compound diffusion, binding to ECM components, local aggregation/solubility, or compound stability within spheroids? 3) Which upstream signalling pathways do you hypothesize link cirsimarin to MMP transcriptional repression — for example, FAK/ERK, NF-κB, or TGF-β/EMT regulators?
08/28/2025
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Question

Letícia Santiago da Silva Ferreira replied to the topic "Questions"

Publication: Decoding the epigenetic response to early stress: SLC6A4 methylation trajectories in preterm newborns

Thanks for your amazing talk and results! I have some questions, as follows: 1) Given the temporal changes in CpG methylation you observed, have you assessed whether these epigenetic modifications also happen at the transcriptional or protein level of SLC6A4 to establish functional consequences beyond methylation signatures? In addition, did you explore whether the CpG-specific methylation differences cluster within known transcription factor binding sites or regulatory motifs of the SLC6A4 promoter, and could these site-specific changes differentially impact serotonin transporter regulation? 2) How do you distinguished methylation changes due to prematurity itself from those potentially driven by external perinatal stressors (e.g., oxygen therapy, corticosteroids, NICU handling, maternal stress), and have you controlled for these in your analyses? 3) From a translational perspective, do you envision that SLC6A4 methylation profiling at birth could serve as a biomarker for identifying preterm infants at higher risk of later neurodevelopmental disorders, and what are the ethical implications of early-life epigenetic risk stratification in neonatology? Thanks and congrats again!  
08/28/2025
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Question

Gabrielly Alexandria replied to the topic "Questions"

Publication: Regulatory LncRNAs analysis in leukocytes of patients with Parkinson’s disease reveals distinct molecular patterns in each clinical phenotype

Thanks for your amazing talk and results! I have some questions, as follows: 1) Since HOTTIP and FIRRE are overexpressed across all phenotypes, do you hypothesize they act as general PD-related neuroinflammatory regulators, and have you explored whether their upregulation correlates with circulating cytokine levels or immune cell activation markers? 2) From a translational perspective, do you foresee lncRNA-based blood signatures serving as reliable liquid biopsy biomarkers for PD diagnosis and subtyping in clinical practice, considering challenges of specificity (neurodegeneration vs systemic inflammation) and stability of circulating lncRNAs? Thanks and congrats again!
08/28/2025
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Question

Nathália Reis dos Santos replied to the topic "Questions"

Publication: INVESTIGATION OF THE ROLE OF NOCTURNIN PHOSPHATASE IN THE METABOLISM OF GLIOMAS WITH ISOCITRATE DEHYDROGENASE MUTATIONS

Thanks for your amazing talk and results! I have some questions, as follows: 1) You propose that mtIDH compensates for LDH loss under hypoxia by providing an alternative NAD⁺ regeneration pathway, so I wonder whether you have quantified intracellular NAD⁺/NADH and NADP⁺/NADPH ratios in mtIDH-expressing vs LDH-deficient glioma cells, and how do these values compare to in vivo glioma samples from TCGA or patient-derived xenografts? 2) How do you comprehend the observed inverse correlation between mtIDH and LDH expression with the well-established “Warburg effect” in gliomas? Could mtIDH tumors represent a distinct metabolic subtype that preferentially uses glutamine or alternative substrates under hypoxia, and have isotope-tracing experiments been performed to map carbon flux? 3) In your hypoxia survival assays, have you examined whether mtIDH expression impacts HIF1α stabilization or transcriptional activity, given that α-KG and 2-HG differentially regulate prolyl hydroxylases?   Thanks and congrats again!
08/27/2025
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