The therapeutic effect of MSCs and their extracellular vesicles on neuroblastoma.

Neuroblastoma is a common inflammatory-related cancer during infancy. Standard treatment modalities including surgical interventions, high-dose chemotherapy, radiotherapy, and immunotherapy are not able to increase survival rate and reduce tumor relapse in high-risk patients. Mesenchymal stem cells (MSCs) are known for their tumor-targeting and immunomodulating properties. MSCs could be engineered to express anticancer agents (i.e., growth factors, cytokines, pro-apoptotic agents) or deliver oncolytic viruses in the tumor microenvironment. As many functions of MSCs are mediated through their secretome, researchers have tried to use extracellular vesicles (EVs) from MSCs for targeted therapy of neuroblastoma. Here, we reviewed the studies to figure out whether the use of MSCs could be worthwhile in neuroblastoma therapy or not. Native MSCs have shown a promoting or inhibiting role in cancers including neuroblastoma. Therefore, MSCs are proposed as a vehicle to deliver anticancer agents such as oncolytic viruses to the neuroblastoma tumor microenvironment. Although modified MSCs or their EVs have been shown to suppress the tumorigenesis of neuroblastoma, further pre-clinical and clinical studies are required to come to a conclusion.

Roles of Mesenchymal Stem Cells in Breast Cancer Therapy: Engineered Stem Cells and Exosomal Cell-Free Based Therapy.

Breast cancer has a high prevalence among women, with a high mortality rate. The number of people who suffer from breast cancer disease is increasing, whereas metastatic cancers are mostly incurable, and existing therapies have unfavorable side effects. For an extended duration, scientists have dedicated their efforts to exploring the potential of mesenchymal stem cells (MSCs) for the treatment of metastatic cancers, including breast cancer. MSCs could be genetically engineered to boost their anticancer potency. Furthermore, MSCs can transport oncolytic viruses, suicide genes, and anticancer medicines to tumors. Extracellular vesicles (EVs) are MSC products that have attracted scientist's attention as a cell-free treatment. This study narratively reviews the current state of knowledge on engineered MSCs and their EVs as promising treatments for breast cancer.

Fabrication and characterization of metformin-loaded PLGA/Collagen nanofibers for modulation of macrophage polarization for tissue engineering and regenerative medicine.

In tissue engineering (TE) and regenerative medicine, the accessibility of engineered scaffolds that modulate inflammatory states is extremely necessary. The aim of the current work was to assess the efficacy of metformin (MET) incorporated in PLGA/Collagen nanofibers (Met-PLGA/Col NFs) to modulate RAW264.7 macrophage phenotype from pro-inflammatory status (M1) to anti-inflammatory status (M2). Given this, MET-PLGA/Col NFs were fabricated using an electrospinning technique. Structural characterization such as morphology, chemical and mechanical properties, and drug discharge pattern were assessed. MTT assay test exposed that MET-PLGA/Col NFs remarkably had increased cell survival in comparison with pure PLGA/Collagen NFs and control (p < 0.05) 72 h after incubation. Based on the qPCR assay, a reduction in the expression of iNOS-2 and SOCS3 was found in the cells seeded on MET-PLGA/Col NFs, demonstrating the substantial modulation of the M1 phenotype to the M2 phenotype. Moreover, it was determined a main decrease in the pro-inflammatory cytokines and mediator's expression but the growth factors amount related to anti-inflammatory M2 were meaningfully upregulated. Finally, MET-PLGA/Col NFs possibly will ensure a beneficial potential for effective variation of the macrophage response from an inflammatory phase (M1) to a pro-regenerative (M2) phase.

Resveratrol inhibits glioblastoma cells and chemoresistance progression through blockade P-glycoprotein and targeting AKT/PTEN signaling pathway.

Malignant gliomas have been categorized as a debilitating class of brain tumors that are resistant to radiation and chemotherapeutic drugs, and have a poor prognosis. Hyper-activation of PI3K/AKT pathway and overexpression of p-glycoprotein transporter contributes to enhanced glioblastoma survival and chemoresistance. Resveratrol which possibly inhibits PI3K pathway, has been thus investigated for a potential therapeutic role in glioma. In the present study, the effect of resveratrol on human U87MG and doxorubicin-resistant glioblastoma cells (U87MG/DOX) survival evaluated by MTT. The ability of resveratrol to overcome doxorubicin resistance in glioblastoma cells was also explored with Rhodamines 123 uptake and ELISA assays. Resveratrol reduced cell survival in a PTEN and P53-dependent manner which was an effect associated with the inhibition of PI3K signaling pathway and via the activation of P-glycoprotein. Our finding showed that resveratrol, as a glioblastoma cell growth inhibitor and chemosensitizer, could be promising if used in the treatment of brain cancer. Resveratrol inhibits the progression of glioblastoma cells and reverses chemoresistance by upregulating PTEN, and suppressing AKT and P-glycoprotein. Targeting PTEN with resveratrol may offer a novel therapeutic approach for the chemo-sensitization of glioblastoma cells.

The expression of miR-181b, CYLD, CBX-7, BCL2, and p53 in osteosarcoma patients and correlation with clinicopathological factors.

Osteosarcoma is a common human malignancy with a high mortality rate worldwide. Recent studies have been focused on understanding the involvement of microRNA (miRNAs) in the pathogenesis of osteosarcoma. Therefore, the present study aimed to measure the expression levels of miR-181a, cylindromatosis (CYLD), chromo box homolog 7 (CBX7), B-cell lymphoma 2 (BCL2), and tumor protein p53 in tumor tissue and adjacent normal tissues in patients with osteosarcoma and its relationship with clinicopathological factors. The expression levels of miR-181a, CYLD, CBX7, BCL2, and p53 were measured in 60 patients with osteosarcoma using quantitative real-time polymerase chain reaction. Finally, we compared the relationship between these gene levels and clinicopathological factors in tumor and healthy tissues. Our results showed that the expression levels of miR-181a, BCL2, and p53 were significantly higher in osteosarcoma tissue in comparison with normal tissues (p < .05). On the contrary, CYLD and CBX7 were downregulated in osteosarcoma tumor tissues compared to adjacent healthy tissues (p < .05). In addition, the expression levels of miR-181a in tumor tissues were strongly correlated with patients' age, tumor size, clinical stage, cancer grade, and lymph node metastasis (p < .05). Our findings highlight new insights into understanding the role of miR-181a in the pathogenesis of osteosarcoma. However, further studies are needed to elucidate miRNA as therapeutic targets for osteosarcoma.

The modulatory effects of two bioflavonoids, quercetin and thymoquinone on the expression levels of DNA damage and repair genes in human breast, lung and prostate cancer cell lines.

BACKGROUND: The recent decade has witnessed the increasing potential of various flavonoids such as quercetin and thymoquinone in inhibiting cancer cells proliferation and growth and their therapeutic effects in various cancers. Therefore, in the current study, we aim to evaluate the expression levels of key factors of DNA damage response in human breast, lung and prostate cancer cell lines in response to treatment with quercetin and thymoquinone. METHODS: MTT assay was applied to assess the effects of quercetin and thymoquinone on the viability of MCF-7, A549, and PC3 cancer cells. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to evaluate the expression levels of p53, RAD51, Ku70, XRCC1, and H2AX in treated cells. In addition, the expression rate of 8-hydroxy-deoxyguanosine (8-OH-dG) was assessed by ELISA kit. RESULTS: The quercetin and thymoquinone induce cytotoxicity in breast, lung, and prostate cancer cells effectively; MCF-7 cells were the most sensitive cells to quercetin with an IC50 value of 50 µM and PC3 cells were more sensitive to thymoquinone with an IC50 value of 20 µM. The expression levels of DNA damage markers, H2AX, and 8-OH-dG were significantly increased in all cancer cells treated with quercetin and thymoquinone (p < 0.05). Moreover, both flavonoids significantly decreased the expression levels of DNA repair mediators, RAD51, Ku70, XRCC1, in cell lines. P53 was also increased in MCF-7 and A549 cells. CONCLUSION: We concluded that quercetin and thymoquinone may exert their effects through modulation of DNA damage response, increasing DNA damage, and suppressing DNA repair genes.

Synthetic electrospun nanofibers as a supportive matrix in osteogenic differentiation of induced pluripotent stem cells.

Continuous remodeling is not able to repair large bone defects. Bone tissue engineering is aimed to repair these defects by creating bone grafts. To do this, several technologies and biomaterials have been employed to fabricate an in vivo-like supportive matrix. Electrospinning is a versatile technique to fabricate porous matrices with interconnected pores and high surface area, replicating in vivo microenvironment. Electrospun scaffolds have been used in a large number of studies to provide a matrix for bone regeneration and osteogenic differentiation of stem cells such as induced pluripotent stem cells (iPSCs). Electrospinning uses both natural and synthetic polymers, either alone or in combination, to fabricate scaffolds. Among them, synthetic polymers have had a great promise in bone regeneration and repair. They allow the fabrication of biocompatible and biodegradable scaffolds with high mechanical properties, suitable for bone engineering. Furthermore, several attempts have done to increase the osteogenic properties of these scaffolds. This paper reviewed the potential of synthetic electrospun scaffolds in osteogenic differentiation of iPSCs. In addition, the approaches to improve the osteogenic differentiation of these scaffolds are addressed.