Decellularized tissues as platforms for digestive system cancer models.

The extracellular matrix (ECM) is a multifunctional network of macromolecules that regulate various cellular functions and physically support the tissues. Besides physiological conditions, the ECM also changes during pathological conditions such as cancer. As tumor cells proliferate, notable changes occur in the quantity and makeup of the surrounding ECM. Therefore, the role of this noncellular component of tissues in studies of tumor microenvironments should be considered. So far, many attempts have been made to create 2-dimensional (2D) or 3-dimensional (3D) models that can replicate the intricate connections within the tumor microenvironment. Decellularized tissues are proper scaffolds that imitate the complex nature of native ECM. This review aims to summarize 3D models of digestive system cancers based on decellularized ECMs. These ECM-based scaffolds will enable us to study the interactive communication between cells and their surrounding environment which brings new potential for a better understanding of the pathophysiology of cancer.

Isolation and Characterization of Extracellular Vesicles of Chick Embryo Blood.

Exosomes from plants or animals are a cheap, available, and promising option in medicine, which can be used for the detection or treatment of various diseases. This study aims to evaluate the antitoxic and antioxidant properties of Extracellular vesicle (EVs) extracted from chicken embryo blood using a fibroblast cell line (NIH/3T3). EVs from chick embryos were extracted in this experimental investigation using the sedimentation method and examined using dynamic light scattering (DLS) and field emission electron microscopy (FE-SEM). The protein concentration and overall antioxidant capacity of the EVs were determined using bicinchoninic acid (BCA) and antioxidant capacity (FRAP). EVs were added to NIH/3T3 cells at varying concentrations (1, 2, and 10 mg/ml), and the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay test was used to measure cell survival. The size of the isolated EVs was confirmed to be less than 100 nm by electron microscopy and DLS. The quantity of protein in these EVs was 3200 µg/ml, and their total antioxidant capacities were 3130.17, 1914.122, and 976.9 µMol/L. The MTT test findings demonstrated that NIH/3T3 cells survived treatment with EVs (P ≤ 0.001) compared to the control group. Antioxidant-rich and protein-rich exosomes in chicken embryos may be valuable in managing oxidative stress.

Decellularized kidney capsule as a three-dimensional scaffold for tissue regeneration.

Tissue regeneration is thought to have considerable promise with the use of scaffolds designed for tissue engineering. Although polymer-based scaffolds for tissue engineering have been used extensively and developed quickly, their ability to mimic the in-vivo milieu, overcome immunogenicity, and have comparable mechanical or biochemical properties has limited their capability for repair. Fortunately, there is a compelling method to get around these challenges thanks to the development of extracellular matrix (ECM) scaffolds made from decellularized tissues. We used ECM decellularized sheep kidney capsule tissue in our research. Using detergents such as Triton-X100 and sodium dodecyl sulfate (SDS), these scaffolds were decellularized. DNA content, histology, mechanical properties analysis, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), biocompatibility, hemocompatibility and scanning electron microscope (SEM) imaging were measured. The results showed that the three-dimensional (3D) structure of the ECM remained largely intact. The scaffolds mentioned above had several hydrophilic properties. The best biocompatibility and blood compatibility properties were reported in the SDS method of 0.5%. The best decellularization scaffold was introduced with 0.5% SDS. Therefore, it can be proposed as a scaffold that has ECM like natural tissue, for tissue engineering applications.

Exosome-loaded decellularized tissue: Opening a new window for regenerative medicine.

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.

A novel cell-free therapy using exosomes in the inner ear regeneration.

Cellular and molecular alterations associated with hearing loss are now better understood with advances in molecular biology. These changes indicate the participation of distinct damage and stress pathways that are unlikely to be fully addressed by conventional pharmaceutical treatment. Sensorineural hearing loss is a common and debilitating condition for which comprehensive pharmacologic intervention is not available. The complex and diverse molecular pathology that underlies hearing loss currently limits our ability to intervene with small molecules. The present review focuses on the potential for the use of extracellular vesicles in otology. It examines a variety of inner ear diseases and hearing loss that may be treatable using exosomes (EXOs). The role of EXOs as carriers for the treatment of diseases related to the inner ear as well as EXOs as biomarkers for the recognition of diseases related to the ear is discussed.

Tissue Engineering Scaffolds Loaded With a Variety of Plant Extracts: Novel Model in Breast Cancer Therapy.

Despite recent improvements in detecting and managing breast cancer (BC), it continues to be a major worldwide health concern that annually affects millions of people. Exploring the anti-BC potentials of natural compounds has received a lot of scientific attention due to their multi-target mode of action and good safety profiles because of these unmet needs. Drugs made from herbs are secure and have a lot fewer negative effects than those made from synthetic materials. Early stage patients benefit from breast-conserving surgery, but the risk of local recurrence remains, necessitating implanted scaffolds. These scaffolds provide residual cancer cell killing and tailored drug delivery. This review looks at plant extract-infused tissue engineering scaffolds, which provide a novel approach to treating BC. By offering patient individualized, safer treatments, these scaffolds could completely change how BC is treated.

Resveratrol-loaded decellularized ovine pericardium: ECM introduced for tissue engineering.

An ideal scaffold for skin tissue engineering should have a suitable potential for antibacterial activity, no hemolysis, sufficient porosity for air exchange, water retention capacity, and a suitable swelling rate to maintain tissue moisture. Considering this issue, our study used decellularized ovine pericardial tissue's extracellular matrix (ECM). These scaffolds were decellularized with sodium dodecyl sulfate (SDS) and sodium deoxycholate (SD) detergents along with vacuum methods. Following imaging with scanning electron microscopy (SEM), analysis of the mechanical properties, and the measurement of the amount of DNA, collagen, and glycosaminoglycan (GAG), our study observed that the three-dimensional (3D) structure of ECM was largely preserved. Resveratrol (RES) 400 µg/µL was loaded into the above scaffold, and analysis revealed that scaffolds containing RES and with vacuum reported higher antibacterial properties, a higher swelling rate, and increased water retention capacity. The biocompatibility and hemocompatibility properties of the above scaffolds also reported a significant difference between methods of decellularization.

Prospects of plant-derived exosome-like nanocarriers in oncology and tissue engineering.

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.

Accelerated wound healing with resveratrol-loaded decellularized pericardium in mice model.

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.

The Decellularized Calf Testis: Introducing Suitable Scaffolds for Spermatogenesis Studies.

BACKGROUND: Men's infertility and lack of production of healthy and active sperm are concerns of recent years in most countries. Studies on the preparation of extracellular matrix (ECM) from decellularization of testis tissue and spermatogenesis could provide proper results to solve some of the men's infertility problems. This study aims to decellularize calf testis by different methods to reach a suitable scaffold and introduce it in spermatogenesis studies. MATERIALS AND METHODS: In this experimental study, calf testis were decellularized by a freeze-de freeze, 1% sodium deoxycholate (SD), 0.1% sodium dodecyl sulfate (SDS), 0.1% SDS-vacuum, 1% SDS, 1% SDS-vacuum, and Triton- X100 methods. The content of DNA, collagen, and glycosaminoglycan (GAG) was analyzed using the kit and staining with Hematoxylin-Eosin, Masson's trichrome, Alcian blue, and Orcein methods. The morphology of the scaffolds was analyzed with a scanning electron microscope (SEM). RESULTS: Methods of 1% SDS, 1% SDS-vacuum, and 1% SD completely removed the cells. The preservation of collagen and GAG was confirmed using the staining kit and methods. The use of a vacuum showed greater porosity in the SEM images. Toxicity and hemolysis were not observed in the scaffolds. CONCLUSION: Testis decellularization with 1% SDS and 1% SD, in addition to cell removal, could maintain the ECM structure to a large extent without having cytotoxic and hemolysis effects.

Nerve regeneration using decellularized tissues: challenges and opportunities.

In tissue engineering, the decellularization of organs and tissues as a biological scaffold plays a critical role in the repair of neurodegenerative diseases. Various protocols for cell removal can distinguish the effects of treatment ability, tissue structure, and extracellular matrix (ECM) ability. Despite considerable progress in nerve regeneration and functional recovery, the slow regeneration and recovery potential of the central nervous system (CNS) remains a challenge. The success of neural tissue engineering is primarily influenced by composition, microstructure, and mechanical properties. The primary objective of restorative techniques is to guide existing axons properly toward the distal end of the damaged nerve and the target organs. However, due to the limitations of nerve autografts, researchers are seeking alternative methods with high therapeutic efficiency and without the limitations of autograft transplantation. Decellularization scaffolds, due to their lack of immunogenicity and the preservation of essential factors in the ECM and high angiogenic ability, provide a suitable three-dimensional (3D) substrate for the adhesion and growth of axons being repaired toward the target organs. This study focuses on mentioning the types of scaffolds used in nerve regeneration, and the methods of tissue decellularization, and specifically explores the use of decellularized nerve tissues (DNT) for nerve transplantation.

Stem cells and exosomes: as biological agents in the diagnosis and treatment of polycystic ovary syndrome (PCOS).

A typical condition of the female reproductive system is polycystic ovary syndrome (PCOS). Hyperinsulinemia, insulin resistance, obesity, and hyperandrogenism are just a few of the metabolic abnormalities linked to this disease. Type 2 diabetes, hypertension, and cardiovascular disease are further issues related to PCOS. One consequence of this syndrome for which numerous treatment procedures have been developed is infertility. Metformin and clomiphene, two common allopathic medications used to treat PCOS, both have drawbacks and are ineffective. It is vital to seek novel therapeutic modalities to address these constraints. Exosomes (EXOs) are a particular class of extracellular vesicles that cells release, and they are known to play a significant role in mediating intercellular communication. A wide range of cargo, including lipids, proteins, mRNA, miRNAs, and numerous other noncoding RNAs, are contained in the nanoscale lipid bilayer exosomes. The cytokine effects of stem cells and EXOs derived from them enable the defense against metabolic diseases like PCOS. Moreover, EXO microRNAs can potentially be employed as biomarkers in the detection and management of PCOS. In this study, the potential of stem cells and exosomes are specifically investigated in the diagnosis and treatment of PCOS as one of the diseases of the female reproductive system.

The Emerging Role of Exosomal miRNAs as Biomarkers for Early Cancer Detection: A Comprehensive Literature Review.

A significant number of cancer-related deaths are recorded globally each year, despite attempts to cure this illness. Medical science is working to develop new medication therapies as well as to find ways to identify this illness as early as possible, even using noninvasive techniques. Early detection of cancer can greatly aid its treatment. Studies into cancer diagnosis and therapy have recently shifted their focus to exosome (EXO) biomarkers, which comprise numerous RNA and proteins. EXOs are minuscule goblet vesicles that have a width of 30 to 140 nm and are released by a variety of cells, including immune, stem, and tumor cells, as well as bodily fluids. According to a growing body of research, EXOs, and cancer appear to be related. EXOs from tumors play a role in the genetic information transfer between tumor and basal cells, which controls angiogenesis and fosters tumor development and spread. To identify malignant activities early on, microRNAs (miRNAs) from cancers can be extracted from circulatory system EXOs. Specific markers can be used to identify cancer-derived EXOs containing miRNAs, which may be more reliable and precise for early detection. Conventional solid biopsy has become increasingly limited as precision and personalized medicine has advanced, while liquid biopsy offers a viable platform for noninvasive diagnosis and prognosis. Therefore, the use of body fluids such as serum, plasma, urine, and salivary secretions can help find cancer biomarkers using technologies related to EXOs.

Resveratrol: Targeting cancer stem cells and ncRNAs to overcome cancer drug resistance.

A major challenge in treating cancer is the development of drug resistance, which can result in treatment failure and tumor recurrence. Targeting cancer stem cells (CSCs) and non-coding RNAs (ncRNAs) with a polyphenolic substance called resveratrol has the ability to combat this problem by lowering cancer resistance to drugs and opening up new therapeutic options. Resveratrol alters the expression of genes related to self-renewal, modulating important signaling pathways involved in cancer initiation and CSC control. Additionally, resveratrol affects non-coding RNAs (ncRNAs), including Micro-RNAs (miRNAs) and long non-coding RNAs (lncRNAs which are essential for stemness, drug resistance, and other cancer-related activities. Numerous studies have shown that resveratrol has the potential to be an effective anticancer drug when used in combination therapy, but issues with absorption and pharmacokinetics still need to be resolved before it can be used in clinical applications. Reducing chemotherapy resistance by better understanding the intricate mechanisms by which resveratrol affects cancer cells and CSCs, as well as its impact on ncRNA expression, could eventually contribute to more effective cancer treatments. To completely understand these pathways and optimize the utilization of resveratrol in combination treatments, additional study is necessary.

The Relationship between Body Mass Index, Metal Elements, and Antioxidant Capacity of Semen on The Human Sperm Chromatin.

BACKGROUND: Sperm chromatin abnormalities are defects in nuclear maturation and DNA integrity. These defects originated from defective spermatogenesis due to a lack of DNA repair during chromatin remodeling. Changes in semen elements can cause damage to chromatin. There is little information about the relationship between changes in trace metal elements and total antioxidant capacity (TAC) with sperm chromatin damage. The present study was conducted to determine the relationship between Selenium (Se), Iron (Fe), Zinc (Zn), Copper (Cu) and the TAC of semen with the status of human sperm chromatin. MATERIALS AND METHODS: In this experimental study, semen samples (n=30) were collected from healthy men referred to Kermanshah Motazadi Hospital and stored in liquid nitrogen; after thawing and centrifugation, sperm were separated. The atomic absorption method was used to measure the concentration of metal elements. The TAC was evaluated using the ferric-reducing antioxidant capacity of the plasma method. Furthermore, the integrity of sperm chromatin was measured using the sperm DNA fragmentation (SDF) method. RESULTS: The status of sperm chromatin had a non-significant correlation with body mass index (BMI, P=0.25, r=0.21) and a non-significant negative correlation with sperm count (P=0.71, r=-0.71) and motility (P=0.75, r=0.61). In addition, there was no significant relationship between sperm chromatin and the TAC of semen (P=0.92, r=0.01). Additionally, there was no significant correlation between Se, Zn, or Cu concentration (P>0.05) and Fe concentration, which had a partially positive relationship with the chromatin state of sperm (P=0.24, r=0.20). CONCLUSION: The trace metal elements in the seminal fluid did not play a significant role in the status of sperm chromatin.

Exosome-loaded scaffolds for regenerative medicine in hard tissues.

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.

The effect of marine algae-derived exosomes on breast cancer cells: Hypothesis on a new treatment for cancer.

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.

Advantages of Material Biofunctionalization Using Nucleic Acid Aptamers in Tissue Engineering and Regenerative Medicine.

Material engineering is a fundamental issue in the applications of materials in the medical field. One of the aspects of material engineering is incorporating recognition sites on the surface of biomaterials, which plays an essential role in increasing the efficiency of tissue engineering scaffolds in various aspects. The application of peptides and antibodies to establish the recognition and adhesion sites has limitations, such as fragility and instability under physical and chemical processes. Therefore, synthetic ligands such as nucleic acid aptamers have received much attention for easy synthesis, minimal immunogenicity, high specificity, and stability under processing. Due to the effective role of these ligands in increasing the efficiency of engineered constructs in this study, the advantages of nucleic acid aptamers in tissue engineering will be reviewed. Aptamer-functionalized biomaterials can attract endogenous stem cells to wounded areas and organize their actions to facilitate tissue regeneration. This approach harnesses the body's inherent regeneration potential to treat many diseases. Also, increased efficacy in controlled release, slow and targeted drug delivery are important issues in drug delivery for tissue engineering approaches which can be achieved by incorporating aptamers in drug delivery systems. Aptamer-functionalized scaffolds have very applications, such as diagnosis of cancer, hematological infections, narcotics, heavy metals, toxins, controlled release from the scaffolds, and in vivo cell tracing. Aptasensors, as a result of many advantages over other traditional assay methods, can replace older methods. Furthermore, their unique targeting mechanism also targets compounds with no particular receptors. Targeting cell homing, local and targeted drug delivery, cell adhesion efficacy, cytocompatibility and bioactivity of scaffolds, aptamer-based biosensor, and aptamer-functionalized scaffolds are the topics that will be examined in this review study.

Mortality and disability-adjusted life years for smoking-attributed cancers from 1990 to 2019 in the north Africa and middle east countries: a systematic analysis for the global burden of disease study 2019.

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.

Exosomes and exosome-loaded scaffolds: Characterization and application in modern regenerative medicine.

Exosomes (EXOs) are extracellular vesicles derived from the endosome. These heterogeneous nanoparticles (30-150 nm) are secreted from various cells and play important biological roles in intercellular communication. EXOs have received much attention for application in regenerative therapies and tissue repair due to their stability, biosafety, and functional versatility. However, in their free forms, "EXOs have poor bioavailability" at the site of action and are devoid of controlled-release mechanisms. These issues have been largely remedied by scaffolding EXOs with appropriate biomaterials such as hydrogels to create EXOs -loaded scaffold (ELS). These biomaterial-based scaffolds can be rationally designed and functionalized to enhance various aspects of ELS including bioavailability, biocompatibility, and loading/release control. Additionally, the ELS are superior to free EXOs due to reduced injection-related side effects. This review article provides a comprehensive and updated account of EXOs and ELS isolation, characterization, and application in regenerative medicine with a focus on soft tissue repair. We also offer insights into the advantages of ELS therapy compared to stem cell therapy towards application in wound healing, cardiac and bone repair. ELS promotes cell migration to the scaffold and will cause better homing of exosomes. Different types of scaffolds are made and each one can be modified based on the repair in the target tissues so that the reactions between the scaffold and exosome take place properly and effective signals are created for tissue repair.