Introduction. Oxidative stress and inflammation are hallmarks of neurodegenerative diseases, including a reduced repair capacity. Neural progenitor cells (NPCs) from the subventricular zone (SVZ), the dentate gyrus and the olfactory bulb can migrate and differentiate into neurons or glial cells. CXCL12 chemokine binds to CXCR4 and this axis contributes to neuroinflammation. Following CNS insult, chemokines recruit stem cells for repair while the aberrant CXCR4 activation promotes cell death. In fact, NPCs, endothelial cells, neurons (and glia) express CXCR4, which enhance the homing of stem cells for neuronal repair. CXCL12 attracts neuroblasts and it is also secreted at sites of injury.

Aim. This study evaluated whether cerebrolysin (brain porcine peptide) or recombinant chemokines may protect cortical neurons at 7 DIV against staurosporine-induced cell death or LPS-induced inflammation in a N2a cell line. For this purpose, extracts from cortical neurons or N2a cells were isolated and several inflammatory markers were quantified by pCR (IL-1 beta and CXCR4/SDF1 alpha). Staurosporine or LPS treatment were added during 6 hours in the medium and cerebrolysin or recombinant proteins were o/n added in the presence of these treatments.

Results. The antiapoptotic role of chemokines and/or cerebrolysin was demonstrated in staurosporine-treated cortical neurons at 7 DIV using an XTT assay. Cerebrolysin prevented staurosporine-induced apoptosis in the N2A cell line and decreased Il-1 beta leveles in a N2a cell line exposed to LPS during 6 h.

Conclusion. The observed correlation between cerebrolysin and the neuroprotective effect of chemokines against apoptosis suggests that CXCR4 chemokine receptor activation by cerebrolysin prevented staurosporine-induced cell death in cortical neurons from rats and also reduced IL-1 beta levels in a N2a murine cell line exposed to LPS (lipopolysaccharide)). Although the clinic efficacy of cerebrolysin against dementia requires more clinical evidences, some clinical trials have confirmed its efficacy against neurological diseases.

Background: Variations in drug responses are related to inherited characteristics of the genome that cause a wide variability in individual responses to drugs. Pharmacogenetics or pharmacogenomics analyses help us to understand DNA variations that are related to drug action (pharmacodynamics) and drug disposition (pharmacokinetics). Using a pharmacogenomics (PGx) approach, we studied different CYP450 genes that are associated with drug metabolism, along with their genomic variants, thus strengthening our understanding of personalized medicines.

Methods: We downloaded the PGx database from the FDA website and collated the data utilizing various evolutionary tools and software. We also provided an overview of current progress in computational approaches for the prediction of drug metabolism and toxicity using a combination of knowledge graph- and AI-based approaches. Utilizing ethnicity data from published sources, we also correlated the clinical implications of drug metabolism and toxicity variability in different population cohorts.

Results: We observed that 42 unique drugs catering to nine different therapeutic areas are associated with six CYP450 (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A5) genes/biomarkers and 32 unique variants/SNPs. The allelic frequencies (AFs) of the 32 variants were also studied in different population ethnicity groups (from a published database). We observed unique combinations of drugs, biomarkers and variant associations that highlight how the metabolism of a drug is controlled/regulated/metabolized by the genetic basis of an individual. We observed 32 unique combinations where the same CYP biomarker and its variant are shared by different drugs associated with different therapeutic areas.

Conclusions: PGx studies should be inclusive, and policy makers/drug regulators should include such approaches for better understanding the genetic basis of drug-metabolizing genes for better drug response. The PGx approach also highlights a significant association between Precision Medicine and Pharmacovigilance by understanding drug metabolism and toxicity in accordance with an individual’s genetic makeup.

Breast cancer is a leading cause of cancer-related deaths worldwide. While significant progress has been made in its diagnosis and treatment, it remains a major public health concern. This study aimed to investigate the transcriptomic effects of Mebendazole, an antiparasitic drug, on SUM159 cell lines, a model for triple-negative breast cancer (TNBC). RNA-Seq analysis was conducted to identify differentially expressed genes (DEGs) between untreated and Mebendazole-treated cells. Our analysis revealed significant transcriptional alterations in Mebendazole-treated SUM159 cells, with data collected from the NCBI GEO database. The GALAXY server NGS data analysis frame work was used, followed by FASTQC, FASTP, HISAT2, SAMTOOL_Sort, SAMTOOLs_Dataset, the Uploading GTF for Humans standard file from UCSC, Hiseq-Count and analysis in R-reported DEGs. The list of 820 DEGs were analysed for enrichment using EnrichR, David tools, to understand the involvement of DEGs in biological processes. DEGs were enriched in pathways related to cell cycle regulation, apoptosis, survival signaling, and metabolism, suggesting that Mebendazole exerts its effects through multiple mechanisms. Notably, the identified DEGs were associated with various diseases, including breast cancer and neurodegenerative disorders. The downregulated genes from the analysis reported to be involved in liver cirrhosis, atherosclerosis, neurological disorder, cellular adhesion, the extracellular matrix, the transcription factor, and the assembly of collagens in humans, whereas the upregulated genes were more involved in pathways of breast cancer, ovarian cancer, the cell cycle and the cell division process. These findings highlight the potential for Mebendazole to be repurposed as a therapeutic agent beyond its traditional use in parasitic infections. Further research is needed to validate these in vitro findings in vivo and explore the clinical implications of Mebendazole for cellular mechanisms, the signal cascade, TNBC and neurodegenerative diseases.

Introduction: RUNX1, a transcription factor crucial for hematopoiesis and frequently mutated in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), has recently been implicated in solid tumors. This study investigates the role of RUNX1 mutations in stomach adenocarcinoma and their impact on the tumor immune microenvironment.

Methods: Bioinformatic approaches using GEPIA (Gene Expression Profiling Interactive Analysis) and TIMER (Tumor Immune Estimation Resource) were used to analyze gene expression data and immune cell infiltration in stomach adenocarcinoma samples with and without RUNX1 mutations.

Results: Stomach adenocarcinomas harboring RUNX1 mutations exhibited significantly higher levels of macrophage infiltration compared to wild-type tumors. Gene expression analysis revealed upregulation of key inflammatory mediators, including IFNG, TNF, IL1B, and NLRP3, in RUNX1-mutated samples. These findings suggest a strong association between RUNX1 mutations and an enhanced inflammatory tumor microenvironment.

Conclusions: This study establishes a potential link between RUNX1 mutations, increased immune cell recruitment, and elevated expression of pro-inflammatory genes in stomach adenocarcinoma. This altered immune landscape may have important implications for disease progression and the development of targeted therapeutic approaches. Furthermore, these findings extend our understanding of RUNX1's role beyond hematological malignancies, highlighting its significance in solid tumors and opening new avenues for research and potential therapeutic interventions.

Introduction:
Cancer poses a global challenge due to aggressive metastasis, treatment resistance, and relapse, often driven by cancer stem cells (CSCs). CSCs evade conventional therapies, emphasizing the need for CSC-targeted strategies. The Iroquois homeobox (IRX) gene family is linked to cancer stemness, but the exact roles and therapeutic potential of IRX genes in CSC promotion remain unclear.

Methods:
Normalized gene expression data from all six IRX genes were downloaded from publicly available databases. A comparison of IRX expression with cancer stages and drug sensitivity was conducted. All data processing and analysis were performed using GraphPad Prism (10.0.2). A Student t-test was used to compare difference between two groups and a one-way ANOVA test was applied to compare multiple groups. The functional role of these IRXs in CSC regulation will be assessed using in vitro and in vivo models.

Results:
In silico analyses revealed an elevated expression of Iroquois homeobox 3 (IRX3) and Iroquois homeobox 5 (IRX5) in castration-resistant prostate cancer (PCa) patient samples and patient-derived xenografts (PDXs) compared to primary tumours, with further upregulation after enzalutamide treatment. Gene set enrichment analysis identified significant enrichment of stemness-associated gene signatures in PCa patients with high IRX3 expression. Additionally, expression data revealed IRX5 upregulation with therapy resistance in several breast cancer (BCa) cell lines. Future studies will explore the roles of IRX3 and IRX5 in CSC maintenance, tumour progression, metastasis, and therapeutic resistance in PCa and BCa models.

Conclusions:
Given the link between CSCs, therapy resistance, and metastasis, we hypothesize that elevated IRX3 and IRX5 expression contributes to CSC maintenance in PCa and BCa. If validated, these IRXs could serve as novel therapeutic targets, inhibiting CSC-driven tumour growth and progression. This would represent a significant advancement, as no therapies currently target CSCs and ultimately preventing metastasis, drug resistance, and relapse in PCa and BCa patients.