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A Bioinformatics Analysis Of Circulating Microrna Signatures As Novel Biomarkers For Predicting Chemotherapy Response Muttaqin, T. Amirul; Allen, Esther; Salazar, Beatriz
Journal of Multidisciplinary Sustainability Asean Vol. 2 No. 3 (2025)
Publisher : Yayasan Adra Karima Hubbi

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.70177/ijmsa.v2i3.2663

Abstract

Background. Chemotherapy response is highly variable, leading to ineffective treatment and toxicity. Reliable, non-invasive biomarkers to predict response a priori are urgently needed. Circulating microRNAs (miRNAs) are stable liquid biopsy candidates, but previous studies often lack robust validation. Purpose. This study aimed to identify and validate a novel, non-invasive circulating miRNA signature to accurately predict chemotherapy response using a large-scale bioinformatic approach. Method. A comprehensive in silico study was conducted. We aggregated and harmonized 948 patient samples from five public datasets (GEO, TCGA). A machine learning pipeline (LASSO + Random Forest) was applied to a Training Set (n=664) to discover a predictive signature. The signature was then validated in an Internal Testing Set (n=284) and a separate External Validation Cohort (n=120). Results. We aggregated and harmonized 948 patient samples from five public datasets (GEO, TCGA). A machine learning pipeline (LASSO + Random Forest) was applied to a Training Set (n=664) to discover a predictive signature. The signature was then validated in an Internal Testing Set (n=284) and a separate External Validation Cohort (n=120). We identified and validated a 7-miRNA circulating signature (c-miRSig). The model demonstrated high accuracy in both the internal (AUC 0.89) and external (AUC 0.86) validation sets. Conclusion. The signature was also a powerful prognostic tool, significantly stratifying patients for progression-free survival (p < 0.001). Functional analysis linked the signature to key chemoresistance pathways (PI3K-Akt, ABC transporters). The c-miRSig is a robust, non-invasive biomarker with dual predictive and prognostic power. This computationally validated signature provides a strong foundation for a clinically viable test to personalize chemotherapy, sparing non-responders from toxic, ineffective treatment.
AN INJECTABLE, THERMOSENSITIVE HYDROGEL AS A CELL DELIVERY VEHICLE FOR CARDIAC REGENERATIVE MEDICINE POST-MYOCARDIAL INFARCTION Muttaqin, T. Amirul; Som, Rit; Charalambous, Anna
Journal of Biomedical and Techno Nanomaterials Vol. 2 No. 4 (2025)
Publisher : Yayasan Adra Karima Hubbi

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.70177/jbtn.v2i4.2661

Abstract

Cell-based therapies for myocardial infarction (MI) are critically limited by poor acute cell retention and viability following direct injection. The harsh, ischemic microenvironment and mechanical washout result in massive cell death, neutralizing therapeutic potential and leading to failed clinical translation. This research aimed to design, synthesize, and evaluate a novel, injectable, thermosensitive hydrogel as a “pro-survival” cell delivery vehicle. The objective was to determine if this biomaterial could solve the critical failure points of retention and viability, thereby enhancing the therapeutic efficacy of mesenchymal stem cells (MSCs) post-MI. A composite hydrogel (Poloxamer/Hyaluronic Acid) was characterized in vitro for its rheological properties (LCST), mechanical stiffness, and cytoprotective capacity under ischemic stress. Its in vivo efficacy was then evaluated in a rat MI model (LAD ligation). The hydrogel+MSCs group (G5) was compared against controls (saline, MSCs-in-saline) via serial echocardiography and post-mortem histomorphometry. In vitro, the hydrogel confirmed ideal thermosensitivity (LCST 37.1°C) and cytoprotection (2.5-fold increase in ischemic cell survival). In vivo, the G5 (hydrogel+MSCs) group demonstrated significantly preserved cardiac function (LVEF 45.2%) compared to the MSCs-only group (G4: 34.1%) at 28 days. This was correlated with significantly reduced infarct size and enhanced border-zone angiogenesis. The thermosensitive hydrogel functions as an essential, enabling technology. It solves the critical failure points of acute retention and viability, demonstrating that an engineered “pro-survival” delivery vehicle is a prerequisite for the successful clinical translation of cardiac cell therapy.