Combinatorial therapeutic strategies using siRNA and small molecules to eradicate tumors are emerging. Targeting multiple signaling pathways decreases the chances of cancer cells switching and adapting new signaling processes that may occur when using a single therapeutic modality. Aberrant functioning of Notch-1, Wnt/β-catenin, and STAT3 proteins and their crosstalk signaling pathways have been found to be involved in tumor survival, drug resistance, and relapse. In the current study, we describe a therapeutic potential of single and combinations of siRNA designed for silencing Notch-1, Wnt/β-catenin, and STAT3 in MCF7_DoxS (wild type) and MCF7_DoxR (doxorubicin resistant) breast cancer cells. The MCF7_DoxR cells were developed through treatment with a gradual increase in doxorubicin concentration, the expression of targeted genes was investigated, and the expression profiling of CD44/CD24 of the MCF7_DoxS and MCF7_DoxR cells were detected by flow cytometry. Both MCF7_DoxS and MCF7_DoxR breast cancer cells were treated with single and combinations of siRNA to investigate synergism and were analyzed for their effect on cell proliferation with and without doxorubicin treatment. The finding of this study showed the overexpression of targeted genes and the enrichment of the CD44⁻/CD24⁺ phenotype in MCF7_DoxR cells when compared to MCF7_DoxS cells. In both cell lines, the gene silencing efficacy showed a synergistic effect when combining STAT3/Notch-1 and STAT3/Notch-1/β-catenin siRNA. Interestingly, the chemosensitivity of MCF7_DoxS and MCF7_DoxR cells to doxorubicin was increased when combined with siRNA treatment. Our study shows the possibility of using single and combinations of siRNA to enhance the chemosensitivity of cancer cells to conventional antitumor chemotherapy.

Angiogenesis is one of cancer hallmarks that are required for both cancer progression and metastasis. In this study we examined the antiangiogenic properties of the ethanolic crude extracts of four Salvia species grown in Jordan.

The wide diversity of microbiota at the genera and species levels across sites and individuals is related to various causes and the observed differences between individuals. Efforts are underway to further understand and characterize the human-associated microbiota and its microbiome. Using 16S rDNA as a genetic marker for bacterial identification improved the detection and profiling of qualitative and quantitative changes within a bacterial population. In this light, this review provides a comprehensive overview of the basic concepts and clinical applications of the respiratory microbiome, alongside an in-depth explanation of the molecular targets and the potential relationship between the respiratory microbiome and respiratory disease pathogenesis. The paucity of robust evidence supporting the correlation between the respiratory microbiome and disease pathogenesis is currently the main challenge for not considering the microbiome as a novel druggable target for therapeutic intervention. Therefore, further studies are needed, especially prospective studies, to identify other drivers of microbiome diversity and to better understand the changes in the lung microbiome along with the potential association with disease and medications. Thus, finding a therapeutic target and unfolding its clinical significance would be crucial.

This study aimed at fabricating gold (Au), iron (Fe) and selenium (Se) nanoparticles (NPs) using various natural plant extracts from the Fertile Crescent area and evaluating their potential application as antioxidant and biocompatible agents to be used in the pharmaceutical field, especially in drug delivery. The Au-NPs were synthesized using Ephedra alata and Pistacia lentiscus extracts, whereas the Fe-NPs and Se-NPs were synthesized using peel, fruit and seed extracts of Punica granatum. The phytofabricated NPs were characterized by the UV-visible spectroscopy, scanning electron microscope, Fourier transform infrared spectroscopy, X-ray diffraction (XRD) and energy-dispersive X-ray (EDS) spectroscopy. Scanning electron microscope technique showed that the synthesized NPs surface was spherical, and the particle size analysis confirmed a particle size of 50 nm. The crystalline nature of the NPs was confirmed by the XRD analysis. All synthesized NPs were found to be biocompatible in the fibroblast and human erythroleukemic cell lines. Se-NPs showed a dose-dependent antitumor activity as evidenced from the experimental results with breast cancer (MCF-7) cells. A dose-dependent, free-radical scavenging effect of the Au-NPs and Se-NPs was observed in the DPPH (2,2-Diphenyl-1-picrylhydrazyl) assay, with the highest effect recorded for Au-NPs.

Background: Breast cancer is the most common type of cancer among females. Hypoxia mediates cancer hallmarks and results from reduced oxygen level due to irregularities in tumor vascularization or when the tumor size prevents oxygen diffusion and triggers angiogenesis to compensate for low oxygen. Cancer stem cells (CSCs) are a rare subpopulation, able to self-renew and to give rise to tumor-initiating cells. It is proposed that CSCs’ secretions help to recruit endothelial cells via angiogenic factors to establish tumor vascularization. In the tumor microenvironment, the effect of hypoxia on CSCs and the impact of their secretions on triggering angiogenesis and tumor vascularization remain questionable. In this study, three-dimensional (3D) CSCs derived from MCF-7 were directly exposed to repetitive long-term cycles of hypoxia to assess its effect on CSCs and then to evaluate the role of the hypoxic CSCs’ (CSCs^HYP) secretions in angiogenesis using (HUVECs) as a model for tumor neovascularization response. Methods: CSCs derived from MCF-7 cell-line were expanded under repetitive, strictly optimized, long-term/continuous and intermittent hypoxic shots for almost four months to assess hypoxic effect on CSCs, sorted based on CD44⁺/CD24⁻ biomarkers. Hypoxic phenotype of CSCs^HYP was evaluated by assessing the acquired chemoresistance using MTT assay and elevated stemness properties were assessed by flow cytometry. To evaluate the effect of the secretions from CSCs^HYP on angiogenesis, HUVECs were exposed to CSCs^HYP conditioned-medium (CdM)—in which CSCs had been previously grown—to mimic the tumor microenvironment and to assess the effect of the secretions from CSCs^HYP on the HUVECs’ capability of tube formation, migration and wound healing. Additionally, co-culture of CSCs^HYP with HUVECs was performed. Results: CSCs^HYP acquired higher chemoresistance, increased stemness properties and obtained greater propagation, migration, and wound healing capacities, when compared to CSCs in normoxic condition (CSCs^NOR). HUVECs’ tube formation and migration abilities were mediated by hypoxic (CSCs) conditioned media (CdM). Discussion: This study demonstrates that chemoresistant and migrational properties of CSCs are enhanced under hypoxia to a certain extent. The microenvironment of CSCs^HYP contributes to tumor angiogenesis and migration. Hypoxia is a key player in tumor angiogenesis mediated by CSCs.