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Osteosarcoma (OS), as the most common primary bone cancer, has a high invasiveness and metastatic potential, therefore, it has a poor prognosis. This study identified early diagnostic biomarkers using miRNA expression profiles associated with osteosarcoma metastasis. In the first step, we used RNA-seq and online microarray data from osteosarcoma tissues and cell lines to identify differentially expressed miRNAs. Then, using seven feature selection algorithms for ranking, the first-ranked miRNAs were selected as input for five machine learning systems. Using network analysis and machine learning algorithms, we developed new diagnostic models that successfully differentiated metastatic osteosarcoma from non-metastatic samples based on newly discovered miRNA signatures. The results showed that miR-34c-3p and miR-154-3p act as the most promising models in the diagnosis of metastatic osteosarcoma. Validation for this model by RT-qPCR in benign tissue and osteosarcoma biopsies confirmed the lower expression of miR-34c-3p and miR-154-3p in OS samples. In addition, a direct correlation between miR-34c-3p expression, miR-154-3p expression and tumor grade was discovered. The combined values of miR-34c-3p and miR-154-3p showed 90 % diagnostic power (AUC = 0.90) for osteosarcoma samples and 85 % (AUC = 0.85) for metastatic osteosarcoma. Adhesion junction and focal adhesion pathways, as well as epithelial-to-mesenchymal transition (EMT) GO terms, were identified as the most significant KEGG and GO terms for the top miRNAs. The findings of this study highlight the potential use of novel miRNA expression signatures for early detection of metastatic osteosarcoma. These findings may help in determining therapeutic approaches with a quantitative and faster method of metastasis detection and also be used in the development of targeted molecular therapy for this aggressive cancer. Further research is needed to confirm the clinical utility of miR-34c-3p and miR-154-3p as diagnostic biomarkers for metastatic osteosarcoma.
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Neoplasias Ósseas , Regulação Neoplásica da Expressão Gênica , Aprendizado de Máquina , MicroRNAs , Osteossarcoma , Osteossarcoma/genética , Osteossarcoma/patologia , Osteossarcoma/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Neoplasias Ósseas/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Metástase Neoplásica , Linhagem Celular Tumoral , Masculino , Feminino , Perfilação da Expressão Gênica , Transição Epitelial-Mesenquimal/genéticaRESUMO
INTRODUCTION: Mesenchymal stromal cell (MSC)-based therapy has generated great hope for the treatment of various diseases such as myocardial infarction and stroke. Unfortunately, MSC-based therapy faces major hurdles in its translation to clinical practice. To address these issues, preconditioning and genetic modification strategies have been developed. Through preconditioning, MSCs are cultured under sub-lethal conditions of environmental stresses or treated with specific drugs, biomolecules, and growth factors. Genetic modification is a procedure in which specific genetic sequences are transferred into the MSCs via viral vectors or CRISP/Cas9 in order to alter the expression of distinctive genes. AREAS COVERED: In this article, a comprehensive review on preconditioning and gene modification inducers, mechanisms of action, and their impacts were discussed. In addition, clinical trials that used preconditioned and genetic modified MSCs are debated. EXPERT OPINION: Numerous preclinical investigations have demonstrated that preconditioning and genetic modifications considerably enhance MSC's therapeutic capacity through improving their survival rate, antioxidant activity, growth factor secretion, immunomodulation, homing efficiency, and angiogenesis. For MSC preconditioning and genetic modification to achieve clinical translation, remarkable outcomes in clinical trials are of pivotal importance.
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Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Humanos , Transdução de Sinais , Antioxidantes , Fatores Imunológicos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Transplante de Células-Tronco Mesenquimais/métodosRESUMO
OBJECTIVE: Surgery and chemotherapy are the most common therapeutic strategies proposed for oral squamous cell carcinoma (OSCC). However, some of the disadvantages associated with the current methods like unwanted side effects and poor drug response lead the scientist to seek for novel modalities and delivery approaches to enhance the efficacy of treatments. The study aimed to assess the effectiveness of disulfiram (DSF)-loaded Niosomes on cancerous phenotypes of the OSCC cells. MATERIALS AND METHODS: In this experimental study, an optimum formulation of DSF-loaded Niosomes was developed for the treatment of OSCC cells to reduce drug doses and improve the poor stability of DSF in the OSCC environment. The design expert software was utilized to optimize the particles in terms of size, polydispersity index (PDI), and entrapment efficacy (EE). RESULTS: Acidic pH increased the release rate of DSF from these formulations. The size, PDI, and EE of Niosomes were more stable at 4°C compared to 25°C. The results indicated that DSF-loaded Niosomes could induce apoptosis (P=0.019) in the OSCC cells compared to the control group. Moreover, it could reduce colony formation ability (P=0.0046) and also migration capacity of OSCC cells (P=0.0015). CONCLUSION: Our findings indicated that the application of proper dose of DSF-loaded Niosomes (12.5 µg/ml) increases apoptosis, decreases colony formation capacity and declines the migration ability of OSCC cells.
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Gastric cancer (GC) is known as a deadly malignancy all over the world, yet none of the current therapeutic regimens have achieved efficacy. this current study has aimed to optimize and reduce treatment doses and overcome multidrug resistance in GC by developing optimum niosomal formulation for the delivery of doxorubicin (DXR), paclitaxel (PTX), and their co-delivery. The particles' size, polydispersity index (PDI), and entrapment efficacy (EE%) were optimized using statistical techniques, i.e., Box-Behnken and Central Composite Design. In contrast to soluble drug formulations, the release rate of medicines from nanoparticles were higher in physiological and acidic pH. Niosomes were more stable at 4 °C, compared to 25 °C. The MTT assay revealed that the IC50 of drug-loaded niosomes was the lowest among all developed formulations. The apoptosis-related genes (CASPASE-3, CASPASE-8, and CASPASE-9) and tumor suppressor genes (BAX, BCL2) were evaluated in cancer cells before and after treatment. In comparison to control cells and cells treated with soluble forms of DXR and PTX, while the expression of BCL2 decreased, the expression of BAX, CASPASE-3, CASPASE-8, and CASPASE-9 was enhanced in cells treated with drug-loaded niosomes. Drug-loaded niosomes inhibited colony formation capacity and increased apoptosis in human AGS gastric cancer cells. Our results indicate that co-delivery of DXR and PTX-loaded niosomes may be an effective and innovative therapeutic approach to gastric cancer.
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Nanopartículas , Neoplasias Gástricas , Humanos , Paclitaxel/farmacologia , Caspase 3 , Caspase 9 , Caspase 8 , Lipossomos , Neoplasias Gástricas/tratamento farmacológico , Proteína X Associada a bcl-2 , Liberação Controlada de Fármacos , Doxorrubicina/farmacologiaRESUMO
Introduction: Autoimmune thyroiditis (AIT) is an autoimmune disorder that is characterized by thyroid gland dysfunction. Low-level laser therapy (LLLT), as a safe and non-invasive intervention, has gained much attention in many clinical applications including pain relief, regenerative medicine, and autoimmune. Methods: In this review, we discuss the effect of LLLT on cellular responses and its application in the treatment of AIT. Such keywords as "low-level laser therapy", "photobiomodulation" and "autoimmune thyroiditis" were used to find studies related to laser therapy in AIT in Google Scholar, PubMed and Medline databases. Results: LLLT reduced thyroid gland inflammation and inhibited immune cell trafficking. LLLT modulated inflammatory responses and improved thyroid gland regeneration. Conclusion: Investigations indicated that besides current treatment strategies, LLLT could be a promising therapeutic approach for the treatment of AIT.
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Introduction: Rheumatoid arthritis (RA) is an inflammatory and autoimmune disorder that is characterized by joint inflammation, pain, physical disability, and morning stiffness. In the present study, the effect of low-level laser therapy (LLLT) on RA was reviewed. Methods: "Low-level laser therapy", "rheumatoid arthritis disease", and "photobiomodulation" keywords were searched in Google Scholar, PubMed, and Medline. Results: A literature survey led to a discussion about the immunology of the RA, laser therapy, mechanism of LLLT action, and anti-inflammatory and immunomodulatory properties of LLLT. Conclusion: It was concluded that LLLT could improve RA patients' quality of life, reduce pain, and enhance physical movement.
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Introduction: Multiple sclerosis (MS) is an autoimmune disease. Inflammatory cells, cytokines and chemokines play a major role in the pathogenesis of the disease. Low-level laser therapy (LLLT) as a photobiostimulation approach could affect a wide range of cellular responses. LLLT inhibits the inflammatory signaling pathway, improves cell viability, inhibits apoptosis, modulates immune responses and induces the production of growth factors. Methods: In this review, we discuss the effect of LLLT on cellular responses and its application in the treatment of MS. Such keywords as "low-level laser therapy", "photobiomodulation" and "multiple sclerosis" were used to find studies related to laser therapy in MS in Google scholar, PubMed and Medline databases. Results: LLLT reduced the inflammatory immune cells and mediators. It also enhanced the regeneration of neurons. Conclusion: Investigations showed that besides current treatment strategies, LLLT could be a promising therapeutic approach for the treatment of MS.
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Recent developments in bone tissue engineering have paved the way for more efficient and cost-effective strategies. Additionally, utilization of autologous sources has been considered very desirable and is increasingly growing. Recently, activated platelet rich plasma (PRP) has been widely used in the field of bone tissue engineering, since it harbours a huge number of growth factors that can enhance osteogenesis and bone regeneration. In the present study, the osteogenic effects of PRP coated nanofibrous PES/PVA scaffolds on adipose-derived mesenchymal stem cells have been investigated. Common osteogenic markers were assayed by real time PCR. Alkaline phosphate activity, calcium deposition and Alizarin red staining assays were performed as well. The results revealed that the highest osteogenic differentiation occurred when cells were cultured on PRP coated PES/PVA scaffolds. Interestingly, direct application of PRP to culture media had no additive effects on osteogenesis of cells cultured on PRP coated PES/PVA scaffolds or those receiving typical osteogenic factors. The highest osteogenic effects were achieved by the simplest and most cost-effective method, i.e. merely by using PRP coated scaffolds. PRP coated PES/PVA scaffolds can maximally induce osteogenesis with no need for extrinsic factors. The major contribution of this paper to the current researches on bone regeneration is to suggest an easy, cost-effective approach to enhance osteogenesis via PRP coated scaffolds, with no additional external growth factors.