Comparison of the Characteristics of Breast Milk-derived Stem Cells with the Stem Cells Derived from the Other Sources: A Comparative Review.

Breast milk (BrM) is not only a nutrition supply but also contains a diverse population of cells. It has been estimated that up to 6% of the cells in human milk possess the characteristics of mesenchymal stem cells (MSC). Available data also indicate that these cells are multipotent and capable of self-renewal and differentiation to other cells. In this review, we have compared different characteristics such as CD markers, differentiation capacity, and morphology of stem cells derived from human breast milk (hBr-MSC) with human bone marrow (hBMSC), Wharton's jelly (WJMSC), and human adipose tissue (hADMSC). The literature review revealed that human breast milk-derived stem cells specifically express a group of cell surface markers, including CD14, CD31, CD45, and CD86. Importantly, a group of markers, CD13, CD29, CD44, CD105, CD106, CD146, and CD166, were identified which were common in the four sources of stem cells. WJMSC, hBMSC, hADMSC, and hBr-MSC are potently able to differentiate into the mesoderm, ectoderm, and endoderm cell lineages. The ability of hBr-MSCs in differentiation into the neural stem cells, neurons, adipocyte, hepatocyte, chondrocyte, osteocyte, and cardiomyocytes has made these cells a promising source of stem cells in regenerative medicine, while isolation of stem cells from the commonly used sources, such as bone marrow, requires invasive procedures. Although autologous breast milk-derived stem cells are an accessible source for women who are in the lactation period, breast milk can be considered a source of stem cells with high differentiation potential without any ethical concern.

Thymoquinone loading into hydroxyapatite/alginate scaffolds accelerated the osteogenic differentiation of the mesenchymal stem cells.

BACKGROUND: Phytochemical agents such as thymoquinone (TQ) have osteogenic property. This study aimed to investigate the synergic impact of TQ and hydroxyapatite on mesenchymal stem cell differentiation. Alginate was also used as drug vehicle. METHODS: HA scaffolds were fabricated by casting into polyurethane foam and sintering at 800 °C, and then, 1250 °C and impregnated by TQ containing alginate. The adipose-derived stem cells were aliquoted into 4 groups: control, osteogenic induced-, TQ and osteogenic induced- and TQ-treated cultures. Adipose derived-mesenchymal stem cells were mixed with alginate and loaded into the scaffolds RESULTS: The results showed that impregnation of HA scaffold with alginate decelerated the degradation rate and reinforced the mechanical strength. TQ loading in alginate/HA had no significant influence on physical and mechanical properties. Real-time RT-PCR showed significant elevation in collagen, osteopontin, and osteocalcin expression at early phase of differentiation. TQ also led to an increase in alkaline phosphatase activity. At long term, TQ administration had no impact on calcium deposition and proliferation rate as well as bone-marker expression. CONCLUSION: TQ accelerates the differentiation of the stem cells into the osteoblasts, without changing the physical and mechanical properties of the scaffolds. TQ also showed a synergic influence on differentiation potential of mesenchymal stem cells.

Crosstalk of Long Non-coding RNAs and EMT: Searching the Missing Pieces of an Incomplete Puzzle for Lung Cancer Therapy.

BACKGROUND: Lung cancer has the first place among cancer-related deaths worldwide and demands novel strategies in the treatment of this life-threatening disorder. The aim of this review is to explore the regulation of epithelial-to-mesenchymal transition (EMT) by long non-coding RNAs (lncRNAs) in lung cancer. INTRODUCTION: LncRNAs can be considered as potential factors for targeting in cancer therapy, since they regulate a bunch of biological processes, e.g. cell proliferation, differentiation and apoptosis. The abnormal expression of lncRNAs occurs in different cancer cells. On the other hand, epithelial-to-mesenchymal transition (EMT) is a critical mechanism participating in migration and metastasis of cancer cells. METHODS: Different databases, including Google Scholar, Pubmed and Science direct, were searched for collecting articles using keywords such as "LncRNA", "EMT", and "Lung cancer". RESULTS: There are tumor-suppressing lncRNAs that can suppress EMT and metastasis of lung cancer cells. Expression of such lncRNAs undergoes down-regulation in lung cancer progression and restoring their expression is of importance in suppressing lung cancer migration. There are tumor- promoting lncRNAs triggering EMT in lung cancer and enhancing their migration. CONCLUSION: LncRNAs are potential regulators of EMT in lung cancer, and targeting them, both pharmacologically and genetically, can be of importance in controlling the migration of lung cancer cells.

Toward Regulatory Effects of Curcumin on Transforming Growth Factor-Beta Across Different Diseases: A Review.

Immune response, proliferation, migration and angiogenesis are juts a few of cellular events that are regulated by transforming growth factor-ß (TGF-ß) in cells. A number of studies have documented that TGF-ß undergoes abnormal expression in different diseases, e.g., diabetes, cancer, fibrosis, asthma, arthritis, among others. This has led to great fascination into this signaling pathway and developing agents with modulatory impact on TGF-ß. Curcumin, a natural-based compound, is obtained from rhizome and roots of turmeric plant. It has a number of pharmacological activities including antioxidant, anti-inflammatory, anti-tumor, anti-diabetes and so on. Noteworthy, it has been demonstrated that curcumin affects different molecular signaling pathways such as Wnt/ß-catenin, Nrf2, AMPK, mitogen-activated protein kinase and so on. In the present review, we evaluate the potential of curcumin in regulation of TGF-ß signaling pathway to corelate it with therapeutic impacts of curcumin. By modulation of TGF-ß (both upregulation and down-regulation), curcumin ameliorates fibrosis, neurological disorders, liver disease, diabetes and asthma. Besides, curcumin targets TGF-ß signaling pathway which is capable of suppressing proliferation of tumor cells and invading cancer cells.

Progress in Delivery of siRNA-Based Therapeutics Employing Nano-Vehicles for Treatment of Prostate Cancer.

Prostate cancer (PCa) accounts for a high number of deaths in males with no available curative treatments. Patients with PCa are commonly diagnosed in advanced stages due to the lack of symptoms in the early stages. Recently, the research focus was directed toward gene editing in cancer therapy. Small interfering RNA (siRNA) intervention is considered as a powerful tool for gene silencing (knockdown), enabling the suppression of oncogene factors in cancer. This strategy is applied to the treatment of various cancers including PCa. The siRNA can inhibit proliferation and invasion of PCa cells and is able to promote the anti-tumor activity of chemotherapeutic agents. However, the off-target effects of siRNA therapy remarkably reduce its efficacy in PCa therapy. To date, various carriers were designed to improve the delivery of siRNA and, among them, nanoparticles are of importance. Nanoparticles enable the targeted delivery of siRNAs and enhance their potential in the downregulation of target genes of interest. Additionally, nanoparticles can provide a platform for the co-delivery of siRNAs and anti-tumor drugs, resulting in decreased growth and migration of PCa cells. The efficacy, specificity, and delivery of siRNAs are comprehensively discussed in this review to direct further studies toward using siRNAs and their nanoscale-delivery systems in PCa therapy and perhaps other cancer types.

MicroRNAs and Their Influence on the ZEB Family: Mechanistic Aspects and Therapeutic Applications in Cancer Therapy.

Molecular signaling pathways involved in cancer have been intensively studied due to their crucial role in cancer cell growth and dissemination. Among them, zinc finger E-box binding homeobox-1 (ZEB1) and -2 (ZEB2) are molecules that play vital roles in signaling pathways to ensure the survival of tumor cells, particularly through enhancing cell proliferation, promoting cell migration and invasion, and triggering drug resistance. Importantly, ZEB proteins are regulated by microRNAs (miRs). In this review, we demonstrate the impact that miRs have on cancer therapy, through their targeting of ZEB proteins. MiRs are able to act as onco-suppressor factors and inhibit the malignancy of tumor cells through ZEB1/2 down-regulation. This can lead to an inhibition of epithelial-mesenchymal transition (EMT) mechanism, therefore reducing metastasis. Additionally, miRs are able to inhibit ZEB1/2-mediated drug resistance and immunosuppression. Additionally, we explore the upstream modulators of miRs such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), as these regulators can influence the inhibitory effect of miRs on ZEB proteins and cancer progression.

STAT3 Pathway in Gastric Cancer: Signaling, Therapeutic Targeting and Future Prospects.

Molecular signaling pathways play a significant role in the regulation of biological mechanisms, and their abnormal expression can provide the conditions for cancer development. The signal transducer and activator of transcription 3 (STAT3) is a key member of the STAT proteins and its oncogene role in cancer has been shown. STAT3 is able to promote the proliferation and invasion of cancer cells and induces chemoresistance. Different downstream targets of STAT3 have been identified in cancer and it has also been shown that microRNA (miR), long non-coding RNA (lncRNA) and other molecular pathways are able to function as upstream mediators of STAT3 in cancer. In the present review, we focus on the role and regulation of STAT3 in gastric cancer (GC). miRs and lncRNAs are considered as potential upstream mediators of STAT3 and they are able to affect STAT3 expression in exerting their oncogene or onco-suppressor role in GC cells. Anti-tumor compounds suppress the STAT3 signaling pathway to restrict the proliferation and malignant behavior of GC cells. Other molecular pathways, such as sirtuin, stathmin and so on, can act as upstream mediators of STAT3 in GC. Notably, the components of the tumor microenvironment that are capable of targeting STAT3 in GC, such as fibroblasts and macrophages, are discussed in this review. Finally, we demonstrate that STAT3 can target oncogene factors to enhance the proliferation and metastasis of GC cells.

PD-1/PD-L1 axis regulation in cancer therapy: The role of long non-coding RNAs and microRNAs.

Cancer immunotherapy is a growing field nowadays. Among different molecular pathways, PD-1/PD-L1 signaling pathway plays a significant role in the regulation of immune responses. It has been reported that stimulation of PD-1/PD-L1 axis is correlated with T cell exhaustion, T cell apoptosis, and their reduced capability in proliferation. PD-1/PD-L1 axis provides a condition for immune evasion of cancer cells and interferes with anti-tumor immunity. Much attention has been directed towards targeting PD-1/PD-L1 axis in cancer immunotherapy. It seems that identification of upstream modulators of this axis can broaden our understanding to develop novel anti-tumor drugs for cancer immunotherapy. MicroRNAs (miRs) and long non-coding RNAs (lncRNAs) are key subcategories of non-coding RNAs, since they can regulate various biological processes by targeting different molecular pathways. In this review, we demonstrate that onco-suppressor miRs and lncRNAs inhibit PD-1/PD-L1 axis to provide anti-tumor immunity and in this way, other molecular pathways such as STAT, ZEB, PI3K/Akt and so on may be targeted. In contrast, oncogene miRs and lncRNAs induce PD-1/PD-L1 axis. Identification of miR/PD-1 and lncRNA/PD-1 signaling pathways can help us in finding an effective drug for cancer immunotherapy, and can direct us towards genetic manipulation of the aforementioned pathways.