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30 result(s) for "Vakhshiteh, Faezeh"
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Mesenchymal stem cell exosomes: a two-edged sword in cancer therapy
Mesenchymal stem cells (MSCs) are multipotent stromal cells present in various adult tissues. Several studies suggest that MSCs secrete exosomes that perform as mediators in the tumor niche and play several roles in tumorigenesis, angiogenesis, and metastasis. In contrast, there are other studies supporting the tumor-suppressing effects of MSC-derived exosomes. Therefore, the exact association of MSC exosomes and tumor cells remains open to debate. This review aimed to demonstrate the present knowledge of MSC-derived exosomes in cancer research and to illustrate current approaches to make use of modified exosomes as a platform in therapeutic strategies in cancer.
Dual functions of the ΔNp63-miR-141-3p-YAP1 regulatory axis in cervical cancer progression are dependent on histological subtype
Cervical cancer (CC) poses a significant global health challenge, necessitating the development of novel therapeutic strategies. The interplay between the p63 isoform (ΔNp63), microRNA-141-3p (miR-141-3p), and Yes-associated protein 1 (YAP1) has emerged as a potential area of interest in cancer progression. This study aimed to investigate the functional relationship between the between the p63 isoform (ΔNp63), miR-141-3p and YAP1 in modulating migration, invasion, and epithelial–mesenchymal transition (EMT) in two CC cell lines, CaSki, and HeLa, which are human cervical squamous cell carcinoma (SCC) and adenocarcinoma (ADC) cells, respectively. The Gene Expression Omnibus (GEO) datasets, were utilized to assess the expression profiles of TP63 and YAP1 in the cervical SCC and ADC samples by using the GEO2R tool. The prediction software (miRDIP, miRmap, and TargetScan), and RT-qPCR were used to determine the relationship between genes. Different assays were performed for proliferative, migratory and invasive abilities of cells. The results were confirmed by western blot analysis. The ΔNp63-miR-141-3p-YAP1 axis exhibited distinct, cell-line-specific functions. In HeLa cells, this axis promoted a prometastatic phenotype by upregulating YAP1, leading to increased proliferation, migration, invasion, and EMT. Conversely, in CaSki cells, the same axis demonstrated an antimetastatic function by downregulating YAP1. YAP1 expression was significantly higher in HeLa cells compared to CaSki cells. In HeLa cells, YAP1 expression appeared to be regulated not solely by the upstream ΔNp63-miR-141-3p axis, suggesting its role as a key oncogene in HeLa cell progression. MiR-141-3p demonstrated context-dependent effects, exhibiting both pro- and anti-metastatic activities depending on the specific cell line. These findings highlight the complex and subtype-specific functions of the ΔNp63-miR-141-3p-YAP1 regulatory network in cervical cancer progression. In summary, our data highlights the different functions of ΔNp63-miR-141-3p-YAP1 axis in regulating proliferation, migration and invasion as well as EMT of different cervical cancer cells.
Reactive oxygen species from non-thermal gas plasma (CAP): implication for targeting cancer stem cells
Cancer remains a major global health challenge, with the persistence of cancer stem cells (CSCs) contributing to treatment resistance and relapse. Despite advancements in cancer therapy, targeting CSCs presents a significant hurdle. Non-thermal gas plasma, also known as CAP, represents an innovative cancer treatment. It has recently gained attention for its often found to be selective, immunogenic, and potent anti-cancer properties. CAP is composed of a collection of transient, high-energy, and physically and chemically active entities, such as reactive oxygen species (ROS). It is acknowledged that the latter are responsible for a major portion of biomedical CAP effects. The dynamic interplay of CAP-derived ROS and other components contributes to the unique and versatile properties of CAP, enabling it to interact with biological systems and elicit various therapeutic effects, including its potential in cancer treatment. While CAP has shown promise in various cancer types, its application against CSCs is relatively unexplored. This review assesses the potential of CAP as a therapeutic strategy for targeting CSCs, focusing on its ability to regulate cellular states and achieve redox homeostasis. This is done by providing an overview of CSC characteristics and demonstrating recent findings on CAP’s efficacy in targeting these cells. By contributing insights into the unique attributes of CSCs and the potential of CAP, this work contributes to an advanced understanding of innovative oncology strategies.
Heterotypic tumor spheroids: a platform for nanomedicine evaluation
Nanomedicine has emerged as a promising therapeutic approach, but its translation to the clinic has been hindered by the lack of cellular models to anticipate how tumor cells will respond to therapy. Three-dimensional (3D) cell culture models are thought to more accurately recapitulate key features of primary tumors than two-dimensional (2D) cultures. Heterotypic 3D tumor spheroids, composed of multiple cell types, have become more popular than homotypic spheroids, which consist of a single cell type, as a superior model for mimicking in vivo tumor heterogeneity and physiology. The stromal interactions demonstrated in heterotypic 3D tumor spheroids can affect various aspects, including response to therapy, cancer progression, nanomedicine penetration, and drug resistance. Accordingly, to design more effective anticancer nanomedicinal therapeutics, not only tumor cells but also stromal cells (e.g., fibroblasts and immune cells) should be considered to create a more physiologically relevant in vivo microenvironment. This review aims to demonstrate current knowledge of heterotypic 3D tumor spheroids in cancer research, to illustrate current advances in utilizing these tumor models as a novel and versatile platform for in vitro evaluation of nanomedicine-based therapeutics in cancer research, and to discuss challenges, guidelines, and future directions in this field. Graphical Abstract
Exosomal circRNAs: new players in colorectal cancer
Colorectal cancer (CRC) is one of the most malignant cancer types, characterized by elevated mortality rate and treatment resistance. Despite the progress achieved in the explanation of the molecular basis of the disease as well as introducing potential biomarkers in the clinical practice, further investigation is essential to identify innovative molecules that contribute to colorectal carcinogenesis. Circular RNAs (circRNAs) are a novel and unexplored RNA type, associated with various human pathological conditions. Recently, circRNAs have been identified to be enriched and stable in exosomes and can exert their functions when exosomes reach neighboring or distant cells. Increasing evidence indicates that these so called exosomal circRNAs (exo-circRNAs) act as signaling molecules to regulate cancer proliferation, metastasis, and sensitivity to radio- and chemotherapy. This review aims to discuss the latest progress in exo-circRNAs studies in CRC with an emphasis on their potential as promising diagnostic molecular markers and therapeutic targets.
Molecular and phenotypic characterization of 5-FU resistant colorectal cancer cells: toward enrichment of cancer stem cells
Cancer stem cells (CSCs) as a subgroup of cells within a tumor capable of self-renewal, thereby driving tumor initiation and spread. Addressing treatment failures in cancer, linked to CSCs and their resistance mechanisms, requires effective preclinical models for testing targeted therapies. Caco2- and HT-29-resistant cells were generated by repeated treatment of cells with growing concentrations of 5-fluorouracil (5-FU) anticancer drug for an extended time. The sensitivity of 5-FU-resistant cells was evaluated by cytotoxicity assay. Stemness, epithelial-mesenchymal transition (EMT), migration and drug resistance characteristics were assessed through gene expression investigation by real-time PCR. The expression of CD44, CD133, and CD66 were evaluated by flow cytometry. To end, the bioinformatic analysis estimated the molecular function and biological pathways considering the differential expression of selected genes and proteins. 5-FU-exposed cells displayed increased resistance to 5-FU. The gene expression analysis showed an upregulation of stemness genes ( KLF4 , SOX2 , OCT4 , C-MYC ), enhanced scavenging system, and elevated expression of CSC surface markers (CD44 and CD133) compared to parental cells. Additionally, pro-EMT genes ( TWIST1 , SNAIL1 , ZEB1 , Vimentin , and N-cadherin ) were significantly upregulated compared to parental cells, with the downregulation of E-cadherin as an EMT suppressor gene reflected in increased migration capacity. Moreover, increased expression of ABC transporter genes ( ABCB1 , ABCC1 ) was observed, correlating with enhanced drug resistance. The bioinformatic analysis highlighted pathways related to microRNAs in cancer, cells pluripotency, and proteoglycans. Methods of drug exposure take priority over spheroid formation, particularly due to their enhanced efficacy in stemness, EMT, and surface markers. This positions them as a promising protocol for establishing experimental models of CSCs.
In vitro assessment of Pediococcus acidilactici Kp10 for its potential use in the food industry
Background Selection of a microbial strain for the incorporation into food products requires in vitro and in vivo evaluations. A bacteriocin-producing lactic acid bacterium (LAB), Pediococcus acidilactici Kp10, isolated from a traditional dried curd was assessed in vitro for its beneficial properties as a potential probiotic and starter culture. The inhibitory spectra of the bacterial strain against different gram-positive and gram-negative bacteria, its cell surface hydrophobicity and resistance to phenol, its haemolytic, amylolytic and proteolytic activities, ability to produce acid and coagulate milk together with its enzymatic characteristics and adhesion property were all evaluated in vitro. Results P. acidilactici Kp10 was moderately tolerant to phenol and adhere to mammalian epithelial cells (Vero cells and ileal mucosal epithelium). The bacterium also exhibited antimicrobial activity against several gram-positive and gram-negative food-spoilage and food-borne pathogens such as Listeria monocytgenes ATCC 15313, Salmonella enterica ATCC 13311, Shigella sonnei ATCC 9290, Klebsiella oxytoca ATCC 13182, Enterobacter cloaca ATCC 35030 and Streptococcus pyogenes ATCC 12378. The absence of haemolytic activity and proteinase (trypsin) and the presence of a strong peptidase (leucine-arylamidase) and esterase-lipase (C4 and C8) were observed in this LAB strain. P. acidilactici Kp10 also produced acid, coagulated milk and has demonstrated proteolytic and amylolactic activities. Conclusion The properties exhibited by P. acidilactici Kp10 suggested its potential application as probiotic and starter culture in the food industry.
Oxytocin protective effects on zebrafish larvae models of autism-like spectrum disorder
Autism is a complicated neurodevelopmental disorder characterized by social interaction deficiencies, hyperactivity, anxiety, communication disorders, and a limited range of interests. The zebrafish ( ) is a social vertebrate used as a biomedical research model to understand social behavior mechanisms. After spawning, the eggs were exposed to sodium valproate for 48 hr, after which the eggs were divided into eight groups. Except for the positive and control groups, there were six treatment groups based on oxytocin concentration (25, 50, and 100 μM) and time point (24 and 48 hr). Treatment was performed on days 6 and 7, examined by labeling oxytocin with fluorescein-5-isothiocyanate (FITC) and imaging with confocal microscopy and the expression levels of potential genes associated with the qPCR technique. Behavioral studies, including light-dark background preference test, shoaling behavior, mirror test, and social preference, were performed on 10, 11, 12, and 13 days post fertilization (dpf), respectively. The results showed that the most significant effect of oxytocin was at the concentration of 50 μM and the time point of 48 hr. Increased expression of , , and genes was also significant at this oxytocin concentration. Light-dark background preference results showed that oxytocin in the concentration of 50 µM significantly increased the number of crosses between dark and light areas compared with valproic acid (positive group). Also, oxytocin showed an increase in the frequency and time of contact between the two larvae. We showed a decrease in the distance in the larval group and an increase in time spent at a distance of one centimeter from the mirror. Our findings showed that the increased gene expression of , , and improved autistic behavior. Based on this study some indications showed that oxytocin administration in the larval stage could significantly improve the autism-like spectrum.