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1.
Mol Biol Rep ; 51(1): 675, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38787484

ABSTRACT

BACKGROUND: Bioscaffolds and cells are two main components in the regeneration of damaged tissues via cell therapy. Umbilical cord stem cells are among the most well-known cell types for this purpose. The main objective of the present study was to evaluate the effect of the pretreatment of the foreskin acellular matrix (FAM) by monophosphoryl lipid A (MPLA) and Lactobacillus casei supernatant (LCS) on the attraction of human umbilical cord mesenchymal stem cells (hucMSC). METHODS AND RESULTS: The expression of certain cell migration genes was studied using qRT-PCR. In addition to cell migration, transdifferentiation of these cells to the epidermal-like cells was evaluated via immunohistochemistry (IHC) and immunocytochemistry (ICC) of cytokeratin 19 (CK19). The hucMSC showed more tissue tropism in the presence of MPLA and LCS pretreated FAM compared to the untreated control group. We confirmed this result by scanning electron microscopy (SEM) analysis, glycosaminoglycan (GAG), collagen, and DNA content. Furthermore, IHC and ICC data demonstrated that both treatments increase the protein expression level of CK19. CONCLUSION: Pretreatment of acellular bioscaffolds by MPLA or LCS can increase the migration rate of cells and also transdifferentiation of hucMSC to epidermal-like cells without growth factors. This strategy suggests a new approach in regenerative medicine.


Subject(s)
Lacticaseibacillus casei , Lipid A , Mesenchymal Stem Cells , Humans , Mesenchymal Stem Cells/metabolism , Lacticaseibacillus casei/metabolism , Lipid A/metabolism , Lipid A/analogs & derivatives , Cell Movement/drug effects , Skin/metabolism , Tissue Scaffolds/chemistry , Male , Umbilical Cord/cytology , Umbilical Cord/metabolism , Foreskin/cytology , Cell Transdifferentiation/drug effects , Tissue Engineering/methods , Extracellular Matrix/metabolism , Keratin-19/metabolism , Keratin-19/genetics
2.
J Tissue Viability ; 33(2): 332-344, 2024 May.
Article in English | MEDLINE | ID: mdl-38594147

ABSTRACT

Mesenchymal stem cell-derived exosomes (MSCs-EXO) have received a lot of interest recently as a potential therapeutic tool in regenerative medicine. Extracellular vesicles (EVs) known as exosomes (EXOs) are crucial for cell-cell communication throughout a variety of activities including stress response, aging, angiogenesis, and cell differentiation. Exploration of the potential use of EXOs as essential therapeutic effectors of MSCs to encourage tissue regeneration was motivated by success in the field of regenerative medicine. EXOs have been administered to target tissues using a variety of methods, including direct, intravenous, intraperitoneal injection, oral delivery, and hydrogel-based encapsulation, in various disease models. Despite the significant advances in EXO therapy, various methods are still being researched to optimize the therapeutic applications of these nanoparticles, and it is not completely clear which approach to EXO administration will have the greatest effects. Here, we will review emerging developments in the applications of EXOs loaded into decellularized tissues as therapeutic agents for use in regenerative medicine in various tissues.


Subject(s)
Exosomes , Regenerative Medicine , Regenerative Medicine/methods , Regenerative Medicine/trends , Exosomes/physiology , Humans , Animals , Mesenchymal Stem Cells/physiology
3.
Hum Cell ; 37(1): 121-138, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37878214

ABSTRACT

Almost all cell types, either in vivo or in vitro, create extracellular vesicles (EVs). Among them are exosomes (EXOs), i.e., tiny nanovesicles containing a lipid bilayer, proteins, and RNAs that are actively involved in cellular communication, indicating that they may be exploited as both diagnostics and therapeutics for conditions like cancer. These nanoparticles can also be used as nanocarriers in many types of research to carry agents such as drugs. Plant-derived exosome-like nanoparticles (PENs) are currently under investigation as a substitute for EXOs formed from mammalian cells, allowing researchers to get beyond the technical constraints of mammalian vesicles. Because of their physiological, chemical, and biological properties, PENs have a lot of promise for use as nanocarriers in drug delivery systems that can deliver various dosages, especially when it comes to large-scale repeatability. The present study has looked at the origins and isolation techniques of PENs, their anticancer properties, their usage as nanocarriers in the treatment of different illnesses, and their antioxidant properties. These nanoparticles can aid in the achievement of therapeutic objectives, as they have benign, non-immunogenic side effects and can pass biological barriers. Time-consuming and perhaps damaging PEN separation techniques is used. For the current PEN separation techniques to be used in commercial and therapeutic settings, they must be altered. In this regard, the concurrent application of biological sciences can be beneficial for improving PEN separation techniques. PENs' innate metabolic properties provide them a great deal of promise for application in drug delivery systems. However, there could be a risk to both the loaded medications and the intrinsic bioactive components if these particles are heavily armed with drugs. Therefore, to prevent these side effects, more studies are needed to devise sophisticated drug-loading procedures and to learn more about the physiology of PENs.


Subject(s)
Exosomes , Extracellular Vesicles , Neoplasms , Animals , Exosomes/metabolism , Tissue Engineering , Drug Delivery Systems , Neoplasms/drug therapy , Neoplasms/metabolism , Mammals
4.
Cell Tissue Bank ; 25(1): 245-253, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37917229

ABSTRACT

One of the key objectives of regenerative medicine is the design of skin tissue engineering scaffolds to promote wound healing. These scaffolds provide a fresh viewpoint on skin injury repair by emulating body tissues in their structure. A suitable platform for cellular processes can be provided by natural scaffolds made from decellularized tissues while retaining the primary components. Resveratrol (RES), which has qualities like angiogenesis, antioxidant, antibacterial, and anti-inflammatory, is also useful in the healing of wounds. In this investigation, RES-loaded decellularized sheep pericardium scaffolds were created and tested on full-thickness wounds in a mouse model. According to the in vivo findings, the groups in which the wound was treated with decellularized pericardium (DP) had better wound healing than the control group and showed more production of angiogenic and anti-inflammatory substances. The secretion of these factors was greater in RES-loaded decellularized pericardium (DP-RES) than in the scaffold without RES, and the macroscopic and histological data supported this. Therefore, the use of decellularization scaffolds with substances like RES for the regeneration of skin wounds can be further researched and evaluated in the preclinical stages.


Subject(s)
Skin , Wound Healing , Mice , Animals , Sheep , Resveratrol/pharmacology , Skin/injuries , Tissue Scaffolds/chemistry , Disease Models, Animal , Anti-Inflammatory Agents , Pericardium
5.
Tissue Cell ; 82: 102102, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37178527

ABSTRACT

Tissue engineering can be used to repair tissue by employing bioscaffolds that provide better spatial control, porosity, and a three-dimensional (3D) environment like the human body. Optimization of injectability, biocompatibility, bioactivity, and controlled drug release are also features of such scaffolds. The 3D shape of the scaffold can control cell interaction and improve cell migration, proliferation, and differentiation. Exosomes (EXOs) are nanovesicles that can regulate osteoblast activity and proliferation using a complex composition of lipids, proteins, and nucleic acids in their vesicles. Due to their excellent biocompatibility and efficient cellular internalization, EXOs have enormous potential as desirable drug/gene delivery vectors in the field of regenerative medicine. They can cross the biological barrier with minimal immunogenicity and side effects. Scaffolds that contain EXOs have been studied extensively in both basic and preclinical settings for the regeneration and repair of both hard (bone, cartilage) and soft (skin, heart, liver, kidney) tissue. Cell motility, proliferation, phenotype, and maturation can all be controlled by EXOs. The angiogenic and anti-inflammatory properties of EXOs significantly influence tissue healing. The current study focused on the use of EXO-loaded scaffolds in hard tissue regeneration.


Subject(s)
Exosomes , Regenerative Medicine , Humans , Tissue Scaffolds , Osteogenesis , Exosomes/metabolism , Tissue Engineering/methods
6.
J Cancer Res Ther ; 19(2): 218-220, 2023.
Article in English | MEDLINE | ID: mdl-37006061

ABSTRACT

Breast cancer is one of the most common cancers among women worldwide. Therefore, further research in this area remains necessary. In pursuit of cancer treatment, the use of aquatic and marine resources has been considered in recent years. Marine algae create a wide variety of metabolites with different biological activities, and their anticancer properties have been reported in several studies. With particles ranging in size between 30 and 100 nm in size, exosomes are a class of cell-released extracellular vesicles that contain DNA, RNA, and proteins. Nontoxic properties and lack of an immune response are critical considerations in the medical use of exosome nanoparticles. Studies have demonstrated that exosomes are used for cancer therapy and in several drug delivery trials; however, no study so far has been done on exosomes derived from marine algae. Research has shown that three-dimensional (3D) models of cancer are advantageous for studying drug effects. This hypothesis aims to design a 3D model of breast cancer in vitro and evaluate cell growth after treatment with a marine algae-derived exosome.


Subject(s)
Breast Neoplasms , Exosomes , Female , Humans , Exosomes/metabolism , Breast Neoplasms/genetics , Cell Line, Tumor
7.
BMC Cancer ; 23(1): 80, 2023 Jan 24.
Article in English | MEDLINE | ID: mdl-36694168

ABSTRACT

AIM AND BACKGROUND: Smoking is a modifiable risk factor for cancers. The aim of the study is to estimate the trend of mortality and DALYs of smoking-attributed cancers in the North Africa and Middle East (NAME) countries. METHODS: In this study, estimates from the Global Burden of Disease 2019 (GBD-2019) study were used to report the mortality and DALYs for 16 smoking-attributed cancers. The mortality and DALYs rates from smoking-attributed cancers were evaluated by age, sex, and the 21 countries of the NAME countries from 1990 to 2019. RESULTS: Age standardized mortality rates (ASMR) for the 29 smoking-attributed cancers in the NAME countries in 1990 and 2019 were estimated to be 24.7 (95% Uncertainty Interval: 21.5, 27.8) and 22.4 (95%UI: 19.8, 25.4) respectively, which shows a 9.2% decrease in the three decades. DALYs/100,000 for smoking-attributed cancers was, also, estimated to be 600.3 (95%UI: 521.6, 682.6) and 515.6 (95%UI: 454.9, 585.4) respectively, which indicates a 14.1% decreased in these three decades. In the last three decades, the percentage changes in DALYs/100,000 for smoking-attributed cancers in males and females were - 0.16 and - 0.03, respectively. Plus, The percentage changes in ASMR in males and females were - 12% and 8%, respectively. Furthermore, The highest ASMR and DALYs were observed in Lebanon, Turkey, and Palestine in 2019. CONCLUSION: The mortality rates of cancers from smoking have increased substantially among females, in most countries of the NAME region, in recent years. The burden caused by smoking can be reduced through modifying lifestyle and applying strict laws on smoking by governments and policymakers.


Subject(s)
Global Burden of Disease , Neoplasms , Male , Female , Humans , Disability-Adjusted Life Years , Neoplasms/epidemiology , Risk Factors , Smoking/adverse effects , Smoking/epidemiology , Lebanon , Quality-Adjusted Life Years , Global Health
8.
Cell Tissue Bank ; 24(2): 495-501, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36434168

ABSTRACT

A decellularized amniotic membrane matrix is an ideal scaffolding system. This study compared the effectiveness of amniotic membrane and amniotic membrane pretreated with monophosphoryl lipid A (MPLA) for repairing the fascia of the abdomen with tension sutures. A total of 24 rats were randomly divided into three groups of eight each. In the control group, the fascia was repaired only with non-absorbable monofilament yarn under tension. In the second and third groups, in addition to the control treatment, acellular amniotic membrane was used and MPLA pretreated amniotic membrane was used, respectively. At 3, 7 and 14 days after treatment, the fascia repair was examined macroscopically and microscopically in all groups. Macroscopic examination showed that the use of MPLA pretreated significantly different from the other groups only in the fibrin exudate. Changes in the fascia rupture pressure showed significant differences between groups. Group three, which was sutured with MPLA pretreated acellular membrane, showed greater amounts of collagen, monocytes and neovascularization, especially at days 7 and 14. The results show that MPLA pretreated acellular amniotic membrane helped to repair abdominal fascia to some extent.


Subject(s)
Amnion , Lipid A , Humans , Rats , Animals , Fascia , Collagen
9.
Med Oncol ; 40(1): 31, 2022 Dec 02.
Article in English | MEDLINE | ID: mdl-36460860

ABSTRACT

Chemotherapy drugs are the first line of cancer treatment, but problems such as low intratumoral delivery, poor bioavailability, and off-site toxicity must be addressed. Cancer-specific drug delivery techniques could improve the therapeutic outcome in terms of patient survival. The current study investigated the loading of chemotherapy drugs loaded into exosomes for cancer treatment. Exosomes are the smallest extracellular vesicles found in body fluids and can be used to transfer information by moving biomolecules from cell to cell. This makes them useful as carriers. As the membranes of these nanoparticles are similar to cell membranes, they can be easily transported to carry different components. As most chemotherapy drugs are not easily soluble in liquid, loading them into exosomes can be a suitable solution to this problem. This cancer treatment could avert the injection of high doses of drugs and provide a more appropriate release mechanism.


Subject(s)
Antineoplastic Agents , Exosomes , Extracellular Vesicles , Nanoparticles , Neoplasms , Humans , Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use
10.
Cell J ; 24(9): 506-514, 2022 Sep 12.
Article in English | MEDLINE | ID: mdl-36274203

ABSTRACT

OBJECTIVE: Acellular matrices of different allogeneic or xenogeneic origins are widely used as structural scaffolds in regenerative medicine. The main goal of this research was to optimize a method for decellularization of foreskin for skin regeneration in small wounds. MATERIALS AND METHODS: In this experimental study, the dermal layers of foreskin were divided into two sections and subjected to two different decellularization methods: the sodium dodecyl sulfate method (SDS-M), and our optimized foreskin decellularization method (OFD-M). A combination of non-ionic detergents and SDS were used to decellularize the foreskin in OFD-M. The histological, morphological, and biomechanical properties of both methods were compared. In addition, human umbilical cord mesenchymal stem cells (hucMSCs) were isolated, and the biocompatibility and recellularization of both scaffolds by hucMSC were subsequently determined. RESULTS: We observed that OFD-M is an appropriate approach for successful removal of cellular components from the foreskin tissue, without physical disturbance to the acellular matrix. In comparison to SDS-M, this new bioscaffold possesses a fine network containing a high amount of collagen fibers and glycosaminoglycans (GAG) (P≤0.03), is biocompatible and harmless for hucMSC (viability 91.7%), and exhibits a relatively high tensile strength. CONCLUSION: We found that the extracellular matrix (ECM) structural integrity, the main ECM components, and the mechanical properties of the foreskin are well maintained after applying the OFD-M decellularization technique, indicating that the resulting scaffold would be a suitable platform for culturing MSC for skin grafting in small wounds.

11.
Chem Phys Lipids ; 243: 105179, 2022 03.
Article in English | MEDLINE | ID: mdl-35150707

ABSTRACT

INTRODUCTION: Using tissue engineering and modifying the tumor microenvironment, three-dimensional (3D) in vitro and in vivo cancer modeling can be performed with appropriate similarity to native. Exosomes derived from different sources have recently been used in cancer studies due to their anticancer effects. In this study, the effect of crab derived exosomes in 2 & 3-dimensional (2& 3D) in vivo models of breast cancer (BC) were investigated and compared with the doxorubicin (DOX). METHODS: 2D and 3D models of BC were induced using the chitosan/ß-glycerol phosphate hydrogel (Ch/ß-GP) and 1 × 106 4T1 cells in the female mice aged 6-8 weeks. 1 mg/ml exosome and 5 mg/kg DOX were injected by intratumoral (IT), intravenous (IV), and intraperitoneal (IP) methods into mice on day 9, 13, and 17 with and without hydrogel as a drug delivery system. After 21 days, the mice were sacrificed, and the tissues (lung, liver, and tumor) were removed. The weight and size of the tumor were measured. Real-time PCR assessed changes of VEGF, Bcl2, and P53 genes expression levels. Nitric oxide (NO) secretion from the cancer 3D model was evaluated by Griess assay. RESULTS AND CONCLUSION: Based on the results, the size and weight of tumors in treated groups with exosomes and DOX were reduced significantly (P ≤ 0.001, P ≤ 0.002, P ≤ 0.02) in 2D and 3D models. Changes in VEGF, Bcl2 and P53 gene expression levels were less in the 3D model than in the 2D model. Drug delivery with hydrogel increased tumor inhibition compared to drug injection without hydrogel. Decreased NO secretion was observed in all treatment groups compared to the control group (untreated). Crab exosomes showed anti cancer effects on 2&3D models of BC. 3D model of BC showed greater drug resistance than the 2D model after treating with crab derived exosomes and DOX. 3D model of BC mimics native tumor better than 2D and can be used in cancer studies and for drug screening with greater confidence than 2D model. Also, the use of slow release drug delivery system reduced drug resistance in both models.


Subject(s)
Brachyura , Breast Neoplasms , Exosomes , Animals , Breast Neoplasms/metabolism , Cell Line, Tumor , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Exosomes/metabolism , Female , Humans , Hydrogels/metabolism , Mice , Proto-Oncogene Proteins c-bcl-2/metabolism , Proto-Oncogene Proteins c-bcl-2/therapeutic use , Tumor Microenvironment , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/therapeutic use
12.
Cell Tissue Bank ; 23(3): 407-415, 2022 Sep.
Article in English | MEDLINE | ID: mdl-34806123

ABSTRACT

Numbers of women worldwide face infertility, which will have a significant impact on a couple's life. As a result, assisting with the treatment of these individuals is seen as a critical step. Successful births following uterus and ovary donation have been reported in recent. When immunosuppressive drugs are used in patients who receive donated tissues, there are always problems with the drugs' side effects. In recent years, tissue engineering has mainly been successful in treating infertility using decellularization techniques. Engineered uterus and ovary prevent immunological reactions and do not require immunosuppressive drugs. The most important aspect of using decellularized tissue is its proper function after transplantation. These tissues must be able to produce follicles, secrete hormones and cause pregnancy. This study aimed to investigate research on decellularized tissues and transplanted into the female reproductive system. In this study, just tissues that, after transplantation, have the proper function for fertility were investigated.


Subject(s)
Infertility , Ovary , Female , Fertility , Humans , Infertility/therapy , Ovary/transplantation , Pregnancy , Tissue Engineering/methods , Tissue Scaffolds , Uterus/transplantation
13.
Life Sci ; 278: 119525, 2021 Aug 01.
Article in English | MEDLINE | ID: mdl-33894272

ABSTRACT

AIMS: Despite many attempts to treat ovarian cancer, 13,940 individuals perish annually due to this disease worldwide. Chemotherapy is the main approach to ovarian cancer treatment, but the development of drug resistance is a major obstacle to the successful treatment. Oleuropein is a phenolic ingredient with anticancer characteristics. This study was aimed at investigating the effect of oleuropein on cell viability, cisplatin resistance, and apoptosis, as well as the expression levels of miR-34a, miR-125b, miR16, miR-21, and some of their potential target genes in ovarian cancer cells. MAIN METHODS: A2780S and A2780/CP cell lines were exposed to different concentrations of oleuropein alone or in combination with cisplatin for 48 h and 72 h. After that, the cell viability and apoptosis were evaluated using MTT assay and flow cytometry, respectively. Bioinformatics analyses were conducted using STRING database and Cytoscape software. The effect of oleuropein and/or cisplatin on the expression of miRNAs and target genes was assessed via Real-time PCR. KEY FINDINGS: Upon treatment with oleuropein, the expression of P21, P53, and TNFRSF10B increased while that of Bcl-2 and Mcl1 decreased. Moreover, this is the 1st report of a significant decrease in the expression of miR-21 and increase in the expression of miR-34a, miR-125b, and miR16 by oleuropein and/or cisplatin in ovarian cancer cells. SIGNIFICANCE: Altogether, these data revealed that oleuropein regulated the expression of the above-mentioned miRNAs in ovarian cancer cells, which potentially resulted in apoptosis induction, cell proliferation inhibition, and cisplatin resistance decline in ovarian cancer cells. To confirm the results of this study, it is suggested that similar experiments be performed in animal models of ovarian cancer.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis , Cisplatin/pharmacology , Drug Resistance, Neoplasm , Iridoid Glucosides/pharmacology , Ovarian Neoplasms/drug therapy , Carcinoma, Ovarian Epithelial/drug therapy , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival , Computational Biology , Female , Gene Expression Regulation, Neoplastic , Humans , Inhibitory Concentration 50 , MicroRNAs/metabolism , Phenol/chemistry , Time Factors
14.
Chem Phys Lipids ; 234: 105009, 2021 01.
Article in English | MEDLINE | ID: mdl-33189639

ABSTRACT

There are no commercially available effective antiviral medications or vaccines to deal with novel coronavirus disease (COVID-19). Hence there is a substantial unmet medical need for new and efficacious treatment options for COVID-19. Most COVID-19 deaths result from acute respiratory distress syndrome (ARDS). This virus induces excessive and aberrant inflammation so it is important to control the inflammation as soon as possible. To date, results of numerous studies have been shown that mesenchymal stem cells and their derivatives can suppress inflammation. Exosomes function as intercellular communication vehicles to transfer bioactive molecules (based on their origins), between cells. In this review, the recent exosome-based clinical trials for the treatment of COVID-19 are presented. Potential therapy may include the following items: First, using mesenchymal stem cells secretome. Second, incorporating specific miRNAs and mRNAs into exosomes and last, using exosomes as carriers to deliver drugs.


Subject(s)
COVID-19/therapy , Drug Delivery Systems/methods , Exosomes/transplantation , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells , SARS-CoV-2 , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , COVID-19/immunology , Clinical Trials as Topic , Exosomes/chemistry , Humans , Mesenchymal Stem Cell Transplantation/adverse effects , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Treatment Outcome , COVID-19 Drug Treatment
15.
Eur J Pharmacol ; 886: 173509, 2020 Nov 05.
Article in English | MEDLINE | ID: mdl-32889065

ABSTRACT

In spite of advancements in breast cancer therapy, this disease is still one of the significant causes of women fatalities globally. Dysregulation of miRNA plays a pivotal role in the initiation and progression of cancer. Therefore, the administration of herbal compounds with anticancer effects through controlling microRNA expression can be considered as a promising therapy for cancer. Oleuropein is the most prevalent phenolic compound in olive. Given its domestic consumption, low cost, and nontoxicity for human beings, oleuropein can be used in combination with the standard chemotherapy drugs. To this end, we examined the effect of oleuropein on two breast cancer cell lines (MCF7 and MDA-MB-231). Our findings revealed that oleuropein significantly decreased cell viability in a dose- and time-dependent manner, while it increased the apoptosis in MCF7 and MDA-MB-231 cells. In the presence of oleuropein, the expression levels of miR-125b, miR-16, miR-34a, p53, p21, and TNFRS10B increased, while that of bcl-2, mcl1, miR-221, miR-29a and miR-21 decreased. The findings pointed out that oeluropein may induce apoptosis via not only increasing the expression of pro-apoptotic genes and tumor suppressor miRNAs, but also decreasing the expression of anti-apoptotic genes and oncomiR. Consequently, oleuropein can be regarded as a suitable herbal medication for cancer therapy.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis Regulatory Proteins/drug effects , Apoptosis/drug effects , Breast Neoplasms/drug therapy , Iridoid Glucosides/pharmacology , Signal Transduction/drug effects , Antineoplastic Agents, Phytogenic/therapeutic use , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Computational Biology , Dose-Response Relationship, Drug , Female , Gene Expression Regulation, Neoplastic , Genes, Tumor Suppressor/drug effects , Humans , Iridoid Glucosides/therapeutic use , MicroRNAs/biosynthesis , MicroRNAs/genetics
16.
Mol Biol Rep ; 47(8): 5851-5864, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32691274

ABSTRACT

Cell-based wound therapy is faced with some limiting factors that decrease the therapeutic efficacy of transplanted cells. In this study, we aimed to genetically modify fibroblast cells with anti-apoptotic Survivin gene (Birc5) before cell transplantation. In vitro, pIRES2-eGFP-Survivin plasmid was transfected into the fibroblast cells and the growth curve was evaluated for transfected and normal cells performing MTT assay. In vivo, two 6-diameter cutaneous wounds were created at mice dorsal skin. Fibrin clot was used as a delivery vehicle to transfer cells into the wound bed. The effects of four treatment groups including (a) Cell-SVV-Clot (b) Cell-GFP-Clot, (c) Normal cell-Clot and, (d) Clot alone were evaluated. After 1,2,3,7 and 14 days post-transplantation, the wounds were photographed for evaluating the wound closure rate and wound samples were obtained. Angiogenesis and formation of granulated tissue were assessed via H&E staining for wound samples. The expression levels of Survivin, VEGF, and bFGF genes were also determined using qRT-PCR. The MTT assay showed similar proliferation potential of transfected cells with normal cells verifying that Survivin had no detrimental effect. Compared to the Normal cell-Clot group, the Survivin overexpression was seen for 3 days in the Cell-SVV-Clot group verifying the cell survival during the early stage of wound healing. The Survivin further upregulated VEGF and bFGF expressions resulting in more angiogenesis and formation of granulated tissue by day 3 and 14. The treated wounds with Cell-SVV-Clot were regenerated with a higher wound closure rate by day 7 compared to Normal cell-Clot and Clot groups. Survivin enhanced wound healing through induction of VEGF and bFGF at particular times post-wounding that led to a more structured-epidermis with higher angiogenesis and granulation tissue formation rate.


Subject(s)
Cell- and Tissue-Based Therapy/methods , Fibroblasts/transplantation , Survivin/biosynthesis , Wound Healing/physiology , Animals , Disease Models, Animal , Female , Fibroblasts/metabolism , Green Fluorescent Proteins/metabolism , Mice , Mice, Inbred BALB C , Regeneration/physiology , Survivin/genetics , Survivin/metabolism , Transfection/methods
17.
Chem Phys Lipids ; 226: 104836, 2020 01.
Article in English | MEDLINE | ID: mdl-31678051

ABSTRACT

Exosomes are cup-shaped structures, made of two lipid layers. Their size is in the range of 30-150 nm. Exosomes are excreted to the extracellular space and function in local and systemic cellular communication. Based on their primary origins, they can contain substantial amounts of RNA, protein, and miRNA; the horizontal transfer of these contents significantly determines the exosome's biological effects. The endosomal origins of exosomes can be deduced based on their surface protein markers. The use of exosomes as a diagnostic biomarker and therapeutic tool, has numerous advantages because they do not pose risks such as aneuploidy and transplant rejection. This - overview highlights the recent findings in exosome development and current knowledge in exosome-based therapies.


Subject(s)
Exosomes/metabolism , Animals , Biomarkers/metabolism , Humans
18.
Wound Repair Regen ; 27(6): 661-671, 2019 11.
Article in English | MEDLINE | ID: mdl-31298446

ABSTRACT

Mesenchymal stem cells (MSCs) accelerate wound healing but the harsh environment of wound site limits the engraftment, retention, and survival rate of transplanted cells. There are multiple approaches that amplify the therapeutic potential of MSCs. The MSCs derived from medical waste material, provide comparable regenerative abilities compared to traditional sources. The application of different scaffolds increases MSC delivery and migration into the wound. The spheroid culture of MSC increases the paracrine effects of the entrapped cells and the secretion of pro-angiogenic and anti-inflammatory cytokines. The MSC pretreating and preconditioning enhances the cell migration, proliferation, and survival rate, which lead to higher angiogenesis, re-epithelialization, wound closure, and granulation tissue formation. Moreover, genetic modification has been performed in order to increase MSC angiogenesis, differentiation potential, as well as the cell life span. Herein, we review the results of aforementioned approaches and provide information accommodating to the continued development of MSC-based wound therapy in the future.


Subject(s)
Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/cytology , Neovascularization, Physiologic , Wound Healing/physiology , Wounds and Injuries/therapy , Animals , Cell Differentiation/physiology , Cell Movement/physiology , Cell Proliferation , Humans , Treatment Outcome , Wounds and Injuries/pathology
19.
Med J Islam Repub Iran ; 31: 136, 2017.
Article in English | MEDLINE | ID: mdl-29951436

ABSTRACT

Background: Different studies have investigated the association between p53 codon 72 Arg>Pro polymorphism and cancer risk. Because of the lack of consensus of the results in individual studies, we conducted this meta-analysis by pooling all currently available case-control studies to estimate the effect of p53 codon 72 Arg/Pro polymorphism on cancer susceptibility in Iranian population. Methods: A comprehensive search was undertaken and primary data from all peer-reviewed journals indexed in PubMed, Google Scholar, Scopus, Magiran, Scientific Information Databank (SID), Iran Medex, and CAB abstract electronic were used to conduct this meta-analysis. We considered some exclusion and inclusion criteria to select the articles. Statistical heterogeneity was explored using the I-square. Publication bias was assessed graphically and statistically by Begg's funnel plot and Egger test. All statistical analyses were performed using StatsDirect software and a two- tailed test. P-value less than 0.05 was considered statistically significant for any test. Results: Our dataset, which included 35 case-control studies, consisted of 2426 cancer cases and 2928 controls. Pooled OR and 95%CI indicated that codon 72 Arg>Pro polymorphism was not associated with odds of developing cancer among Iranian population in the dominant model (Pro/Pro+Arg/Pro vs. Arg/Arg: OR= 0.96, 95%CI= 0.74 to 1.24 chi2= 0.06, p= 0.8). Moreover, no significant association was detected in variant allele (Pro vs Arg: OR= 1.075, 95%CI= 0.91 to 1.25), homozygous (Pro/Pro vs Arg/Arg: OR=0.911 95%CI= 0.66 to 1.25), and heterozygous (Arg/Pro vs Arg/Arg: OR= 0.84, 95%CI= 0.7 to 1). Conclusion: Our study revealed that p53 codon 72 Arg>Pro polymorphism was not associated with overall cancer odds in Iranian population.

20.
Med Oncol ; 31(5): 955, 2014 May.
Article in English | MEDLINE | ID: mdl-24729159

ABSTRACT

As the second most frequent cause of cancer death, gastric cancer is a common disease worldwide. Most of the patients are being diagnosed in the stage that conventional treatments are not effective, and invasion and metastases lead to death. So, identification of novel molecular markers to improve early diagnosis, prognosis and treatment of the gastric cancer is a necessity. EYA1 is a member of EYA family which their deregulation has been demonstrated in several types of cancer. The aim of this study was to assess EYA1 gene expression in tissues of the gastric cancer patients and to investigate its correlation with clinicopathological parameters. A total of 60 tumor and non-tumor gastric specimens were evaluated for EYA1 gene expression using quantitative real-time PCR. The EYA1 expression decreased significantly in gastric tumor tissues compared with adjacent normal tissues. We further showed that there was a negative correlation between the EYA1 gene expression levels, tumor size, lymphatic invasion and distant metastasis. In conclusion, EYA1 might be used as a potential biomarker for monitoring gastric carcinoma progression rate. Further studies to determine the mechanism of action of EYA1 is needed to unravel the role of this gene in gastric cancer pathogenesis.


Subject(s)
Adenocarcinoma/genetics , Biomarkers, Tumor/genetics , Gastric Mucosa/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Nuclear Proteins/genetics , Protein Tyrosine Phosphatases/genetics , Stomach Neoplasms/genetics , Adenocarcinoma/secondary , Aged , Disease Progression , Female , Follow-Up Studies , Humans , Male , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Staging , Prognosis , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Stomach Neoplasms/pathology
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