Biology subjects

Rashidi, H.

Publications and source records attributed to Rashidi, H..

3 recordsLinked to original sources

bioRxiv2025

Unveiling Novel Molecular Drivers in Breast Cancer Brain Metastasis: Multi-Omics Integration Identifies Downregulation of VCAN and Emerging Roles of ASCL2/GRAMD1A as Prognostic Biomarkers and Therapeutic Vulnerabilities

PurposeBreast cancer brain metastasis (BCBM) presents a major clinical challenge, driven by molecular mechanisms that remain poorly characterized. Patients and methodsThree RNA-seq datasets (GSE110590, GSE193103, GSE209998) were analyzed to identify BCBM-associated genes. Survival outcomes (2,976 primary tumors) were assessed via Kaplan-Meier (KM Plotter), genetic alterations via cBioPortal, pathways/networks via GeneMANIA/SIGNOR, and miRNA-mRNA interactions via miRNet. Drug candidates were prioritized using the CTD. ResultsTNFRSF9 and VCAN were downregulated (log2FC: -1.18 to -2.63), while GRAMD1A, ASCL2, TACC3, and PFKFB4 were upregulated (log2FC: +1.02 to +1.70). High PFKFB4 (HR=1.71) and TACC3 (HR=1.46) predicted poor survival, with VCAN suppression (Fold change (Fc) =0.24) and GRAMD1A elevation (Fc=1.31) confirmed in metastases. Pathways included ECM remodeling (VCAN), metabolic rewiring (PFKFB4), and mitotic instability (TACC3). miR-210-3p (hypoxia) and miR-27a-3p (angiogenesis) drove BCBM, countered by miR-335/34a. Drug candidates: Valproic Acid (TACC3/ASCL2), Vorinostat (VCAN), and CDK4/6 inhibitors. ConclusionThis study identifies TNFRSF9, VCAN, GRAMD1A, ASCL2, TACC3, and PFKFB4 as key drivers of BCBM, with dysregulation linked to immune evasion, metabolic adaptation, and mitotic instability. Prioritized miRNAs (e.g., miR-210-3p) and repurposed drugs (e.g., Valproic Acid, Vorinostat) offer actionable therapeutic strategies. These findings advance precision approaches for BCBM, pending preclinical validation to translate targets into clinical practice.

genetics↗

bioRxiv2024

Localized Delivery of Growth Factors from Microparticles Modulate Osteogenic and Chondrogenic Gene Expression in Growth Factor-dependent Manner in an ex vivo Chick Embryonic Bone Model.

AbstractGrowth factors play a crucial role in regulating various cellular functions, including proliferation and differentiation. Consequently, the biomaterial-based delivery of exogenous growth factors presents a promising strategy in regenerative medicine to manage the healing process and restore tissue function. For effective therapeutic applications, it is essential that these active compounds are precisely targeted to the site of regeneration, with release kinetics that align with the slow pace of tissue growth. We have developed an ex vivo model utilizing a developing embryonic chick bone, and using PLGA based microparticles as controlled-release systems, allowing for the investigation of spatiotemporal effects of growth factor delivery on cell differentiation and tissue formation. Our findings demonstrate that BMP2 and FGF2 can significantly alter cell morphology and zonally pattern collagen deposition within the model, but only when the growth factor presentation rate is carefully regulated. Furthermore, the growth factor-dependent responses observed underscore the potential of this model to explore the interactions between cells and the growth factors released from biomaterials in an approach which can be applied for bone tissue engineering.

bioengineering↗

bioRxiv2024

The safety and efficacy of Ultrasound Histotripsy and human pluripotent stem cell-derived hepatic spheroid implantation as a potential therapy for treatment of congenital metabolic liver disease: assessment in an immunocompetent rodent model.

BackgroundLiver disease secondary to an inborn or genetic error of metabolism is a rare group of conditions often associated with chronic ill health and reduced survival. Curative treatment is mainly limited to liver transplantation with major long-term risks. Cell therapy is a promising alternative, but current approaches are ineffective. AimTo develop histotripsy, a non-invasive high intensity ultrasound procedure for liver tissue mechanical ablation, combined with hepatocyte stem cell implantation as a novel method of reversing liver failure from genetic disease. This study assessed the safety and feasibility of this approach in healthy rodents. MethodsUnder general anaesthesia, adult rats (n=12) underwent laparotomy and ultrasound histotripsy to the exposed liver. Around 1 million cells were injected into a single histotripsy cavity in each animal under direct vision (n=10) with two receiving only histotripsy without cell injection. On completion of cell implant haemostasis was secured, laparotomy incision closed, and the animals recovered. Groups of animals were terminated immediately and after 4 hrs, 8 hrs, 24hrs, 4 days and 7 days. Liver and vital organs were assessed for procedure related injuries and evidence of viable implanted cells by histology and immunohistochemistry. ResultsAll animals successfully recovered, and no complication was observed throughout the study. Created cavities were successfully identified in histological analysis of rat. The presence of human cells was verified using anti-human nuclei antibody confirming successful implantation of liver organoids into decellularized cavities. ConclusionsIn this feasibility study, we demonstrated suitability of histotripsy to create decellularized cavities in liver parenchyma. In addition, feasibility of direct transplantation of undissociated liver organoids into the created cavities was demonstrated as a potential approach to treat inborn liver disease by creating nodules of healthy cells capable of performing loss metabolic function. Therapeutic efficacy of this approach will be evaluated in an upcoming study.

bioengineering↗