In this paper, a novel series of imidazole-based heme oxygenase-1 (HO-1) inhibitors is reported. These compounds were obtained by modifications of previously described high potent and selective arylethanolimidazoles. In particular, simplification of the central linker and repositioning of the hydrophobic portion were carried out. Results indicate that a hydroxyl group in the central region is crucial for the potency as well as the spatial distribution of the hydrophobic portion. Docking studies revealed a similar interaction of the classical HO-1 inhibitors with the active site of the protein. The most potent and selective compound (5a) was tested for its potential cytotoxic activity against hormone-sensitive and hormone-resistant breast cancer cell lines (MCF-7 and MDA-MB-231).

Background: Inflammatory bowel disease (IBD) comprises a group of disorders that manifest through chronic inflammation of the colon and small intestine. Although the exact cause of IBD is still unclear, dysfunctional immunoregulation involving overproduction of inflammatory cytokines such as TNF‐α, and IL‐6 have been implicated in pathogenesis. Current therapy relies on immunosuppression, cytotoxic drugs, and monoclonal antibodies against TNF‐α. These classes of drugs have severe side‐effects, especially when used for long duration. Our previous work with raloxifene, a selective estrogen receptor modulator, has shown that the drug, and to a greater extent its micellar formulation, has a significant suppressive effect on NF‐κB, an essential immune‐regulator. This finding directed the current work towards testing the anti‐inflammatory and immunomodulatory effects of raloxifene using cell lines, as well as testing the potential use of the styrene maleic acid (SMA) micelles loaded with raloxifene (SMA‐Ral) against dextran sulfate sodium (DSS) induced colitis in an in vivo model of IBD.Results: Treatment of MCF‐7 cells with TNF‐α was shown to protect the cells from the cytotoxic effect of raloxifene (42 vs. 10% cell death, with TNF‐α. Treating CaCo‐2 cells with both free and SMA‐Ral improved cell survival after exposure to 2% DDS with significantly higher protection with SMA‐Ral. Treatment of U‐937 with SMA‐Ral and free‐Ral resulted in down‐regulation of TNF‐α, IL‐1β, IL‐6, and MIP1α, with greater inhibition of the SMA‐Ral, compared to free Ral. Balb/c mice treated with raloxifene and SMA‐Ral showed weight gain at 14 days, compared to the control group (122, and 115% respectively). Treatment with raloxifene prevented DSS‐induced diarrhea in 6/6 of free raloxifene treated mice and in 5/6 mice treated with SMA‐Ral. Control group of DSS‐treated mice showed average colon length of 7.4 cm compared to 13 cm in the control group. The average colon length was 12.3 and 11.5 cm for raloxifene and SMA‐Ral treated groups, respectively. Furthermore, inflammatory cytokines such as IL‐6 and TNF‐α were reduced in serum of animals treated with free‐Ral and SMA‐Ral.Conclusions: Raloxifene and its micellar formulation warrants further studies to understand their effect on the treatment of colitis.

Sepsis is a life-threatening condition characterized by dysregulated immune responses to infection. To elucidate early transcriptional changes in sepsis, we conducted a case–control study profiling gene expression in whole blood from 20 early-stage sepsis patients and 9 healthy controls. Using Affymetrix Clariom D Human Arrays and robust preprocessing, we identified differentially expressed genes (DEGs) using standard bioinformatic pipelines. A total of 344 genes were significantly upregulated, while 9703 were significantly downregulated in sepsis patients (|log2FC| > 1, adjusted p < 0.05). Pathway enrichment and Gene Ontology analysis revealed activation of innate immune pathways, neutrophil degranulation, and cytokine signaling, alongside suppression of lymphocyte differentiation and antigen presentation. These results suggest a shift toward an innately driven inflammatory state in early sepsis. Our findings provide transcriptomic insights that may support the development of early diagnostic biomarkers and therapeutic targets.

Sickle cell disease (SCD) is the most common hemoglobinopathy, caused by a mutation in the β-globin gene of hemoglobin. It predisposes patients to painful Vaso-occlusive crises (VOC) and multi-organ dysfunctions. The disease exhibits significant phenotypic variability, making it challenging to predict severity and outcomes. This study aimed to characterize the whole blood gene expression profile of Bahraini SCD patients, identifying differentially expressed genes during steady-state (n = 10) and VOC (n = 10) compared to healthy controls (n = 8). Analysis revealed 2073 and 3363 dysregulated genes during steady-state and VOC, respectively, compared to controls, with 1078 genes differentially expressed during VOC versus steady-state. Gene Ontology (GO) enrichment analysis highlighted significant deregulation in immune and hematopoietic pathways, including down-regulation of critical genes for immune modulation and hematopoietic balance. Notably, the transcription factor RUNX3, involved in immune cell differentiation and inflammation, was among the 668 down-regulated genes. RUNX3 was four-fold down-regulated in microarray analysis, three-fold in PCR, and showed a mean protein concentration of 11.13 pg/mL during VOC compared to 457.93 pg/mL during steady-state (p < 0.01). These findings suggest that RUNX3 may serve as a potential biomarker for VOC. Future large-scale validation, additional proteomic studies, and functional investigations are recommended to confirm its clinical utility and significance.

This study investigates the effects of copper nanoparticles (CuNPs) on KRT19 gene expression in four breast cancer cell lines (MDA-MB-231, MDA-MB-468, MCF7, and T47D), representing triple-negative and luminal subtypes. Using cytotoxicity assays, quantitative RT-PCR, and bioinformatics tools (STRING, g:Profiler), we demonstrate subtype-specific, dose-dependent KRT19 suppression, with epithelial-like cell lines showing greater sensitivity. CuNPs, characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM) with a mean size of 179 ± 15 nm, exhibited dose-dependent cytotoxicity. Bioinformatics analyses suggest KRT19′s potential as a biomarker for CuNP-based therapies, pending in vivo and clinical validation. These findings highlight CuNPs’ therapeutic potential and the need for further studies to optimize their application in personalized breast cancer treatment.

Glioblastoma (GBM), a devastating brain malignancy, resists conventional therapies due to molecular heterogeneity and the blood–brain barrier’s significant restriction on drug delivery. Cannabinoids like WIN 55,212-2 show promise but are limited by poor solubility and systemic toxicity. To address these challenges, we evaluated styrene–maleic acid (SMA) micellar encapsulation of WIN 55,212-2 (SMA-WIN) against free WIN in epithelial (LN18) and mesenchymal (A172) GBM cell lines, targeting cytotoxicity and receptor modulation (CB1, CB2, TRPV1, PPAR-γ). SMA-WIN exhibited significantly enhanced cytotoxicity, achieving IC50 values of 12.48 µM (LN18) and 16.72 µM (A172) compared to 20.97 µM and 30.9 µM for free WIN, suggesting improved cellular uptake via micellar delivery. In LN18 cells, both formulations upregulated CB1 and CB2, promoting apoptosis. Notably, SMA-WIN uniquely increased PPAR-γ expression by 2.3-fold in A172 cells, revealing a mesenchymal-specific mechanism absent in free WIN, which primarily modulated CB1/CB2. These findings position SMA-WIN as a promising candidate for precision GBM therapy, particularly for resistant mesenchymal subtypes, paving the way for in vivo validation to confirm blood–brain barrier penetration and clinical translation.