Resistive gas sensors for the detection of NH3gas based on 2D WS2, WSe2, MoS2, and MoSe2: a review.

Transition metal dichalcogenides (TMDs) with a two-dimensional (2D) structure and semiconducting features are highly favorable for the production of NH3gas sensors. Among the TMD family, WS2, WSe2, MoS2, and MoSe2exhibit high conductivity and a high surface area, along with high availability, reasons for which they are favored in gas-sensing studies. In this review, we have discussed the structure, synthesis, and NH3sensing characteristics of pristine, decorated, doped, and composite-based WS2, WSe2, MoS2, and MoSe2gas sensors. Both experimental and theoretical studies are considered. Furthermore, both room temperature and higher temperature gas sensors are discussed. We also emphasized the gas-sensing mechanism. Thus, this review provides a reference for researchers working in the field of 2D TMD gas sensors.

Recent advances in enhances peripheral nerve orientation: the synergy of micro or nano patterns with therapeutic tactics.

Several studies suggest that topographical patterns influence nerve cell fate. Efforts have been made to improve nerve cell functionality through this approach, focusing on therapeutic strategies that enhance nerve cell function and support structures. However, inadequate nerve cell orientation can impede long-term efficiency, affecting nerve tissue repair. Therefore, enhancing neurites/axons directional growth and cell orientation is crucial for better therapeutic outcomes, reducing nerve coiling, and ensuring accurate nerve fiber connections. Conflicting results exist regarding the effects of micro- or nano-patterns on nerve cell migration, directional growth, immunogenic response, and angiogenesis, complicating their clinical use. Nevertheless, advances in lithography, electrospinning, casting, and molding techniques to intentionally control the fate and neuronal cells orientation are being explored to rapidly and sustainably improve nerve tissue efficiency. It appears that this can be accomplished by combining micro- and nano-patterns with nanomaterials, biological gradients, and electrical stimulation. Despite promising outcomes, the unclear mechanism of action, the presence of growth cones in various directions, and the restriction of outcomes to morphological and functional nerve cell markers have presented challenges in utilizing this method. This review seeks to clarify how micro- or nano-patterns affect nerve cell morphology and function, highlighting the potential benefits of cell orientation, especially in combined approaches.

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.

Magnesium-oxide-enhanced bone regeneration: 3D-printing of gelatin-coated composite scaffolds with sustained Rosuvastatin release.

Critical-size bone defects are one of the main challenges in bone tissue regeneration that determines the need to use angiogenic and osteogenic agents. Rosuvastatin (RSV) is a class of cholesterol-lowering drugs with osteogenic potential. Magnesium oxide (MgO) is an angiogenesis component affecting apatite formation. This study aims to evaluate 3D-printed Polycaprolactone/ß-tricalcium phosphate/nano-hydroxyapatite/ MgO (PCL/ß-TCP/nHA/MgO) scaffolds as a carrier for MgO and RSV in bone regeneration. For this purpose, PCL/ß-TCP/nHA/MgO scaffolds were fabricated with a 3D-printing method and coated with gelatin and RSV. The biocompatibility and osteogenicity of scaffolds were examined with MTT, ALP, and Alizarin red staining. Finally, the scaffolds were implanted in a bone defect of rat's calvaria, and tissue regeneration was investigated after 3 months. Our results showed that the simultaneous presence of RSV and MgO improved biocompatibility, wettability, degradation rate, and ALP activity but decreased mechanical strength. PCL/ß-TCP/nHA/MgO/gelatin-RSV scaffolds produced sustained release of MgO and RSV within 30 days. CT images showed that PCL/ß-TCP/nHA/MgO/gelatin-RSV scaffolds filled approximately 86.83 + 4.9 % of the defects within 3 months and improved angiogenesis, woven bone, and osteogenic genes expression. These results indicate the potential of PCL/ß-TCP/nHA/MgO/gelatin-RSV scaffolds as a promising tool for bone regeneration and clinical trials.

Fabrication of Rosuvastatin-Incorporated Polycaprolactone -Gelatin Scaffold for Bone Repair: A Preliminary In Vitro Study.

OBJECTIVE: Rosuvastatin (RSV) is a hydrophilic, effective statin with a long half-life that stimulates bone regeneration. The present study aims to develop a new scaffold and controlled release system for RSV with favourable properties for bone tissue engineering (BTE). MATERIALS AND METHODS: In this experimental study, high porous polycaprolactone (PCL)-gelatin scaffolds that contained different concentrations of RSV (0 mg/10 ml, 0.1 mg/10 ml, 0.5 mg/10 ml, 2.5 mg/10 ml, 12.5 mg/10 ml, and 62.5 mg/10 ml) were fabricated by the thermally-induced phase separation (TIPS) method. Mechanical and biological properties of the scaffolds were evaluated by Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), compressive strength, porosity, MTT, alkaline phosphatase (ALP) activity, water contact angle, degradation rate, pH alteration, blood clotting index (BCI), and hemocompatibility. RESULTS: SEM analysis confirmed that the porous structure of the scaffolds contained interconnected pores. FTIR results showed that the RSV structure was maintained during the scaffold's fabrication. RSV (up to 62.5 mg/10 ml) increased compressive strength (16.342 ± 1.79 MPa), wettability (70.2), and degradation rate of the scaffolds. Scaffolds that contained 2.5 mg/10 ml RSV had the best effect on the human umbilical cord mesenchymal stem cell (HUC-MSCs) survival, hemocompatibility, and BCI. As a sustained release system, only 31.68 ± 0.1% of RSV was released from the PCL-Gelatin-2.5 mg/10 ml RSV scaffold over 30 days. In addition, the results of ALP activity showed that RSV increased the osteogenic differentiation potential of the scaffolds. CONCLUSION: PCL-Gelatin-2.5 mg/10 ml RSV scaffolds have favorable mechanical, physical, and osteogenic properties for bone tissue and provide a favorable release system for RSV. They can mentioned as a a promising strategy for bone regeneration that should be further assessed in animals and clinical studies.

Biological study of skin wound treated with Alginate/Carboxymethyl cellulose/chorion membrane, diopside nanoparticles, and Botox A.

A hydrogel-based wound dressing with desirable properties is necessary for achieving functional skin integrity post-injury. This study focuses on preparing a hydrogel using Alginate/Carboxymethyl cellulose (Alg/CMC) as a base material. To evaluate its regenerative effects on full-thickness wounds, diopside nanoparticles and Botulinum toxin A (BTX-A) were incorporated into the hydrogel along with chorion membrane. The diopside nanoparticles (DNPs) act as a proangiogenic factor, promoting proliferation and regulating inflammation, while the chorion membrane facilitates these processes. Additionally, BTX-A prevents scar formation and aids in wound closure. The nanoparticles and hydrogel were characterized using various techniques, and their cytocompatibility was assessed. In vivo studies and quantitative polymerase chain reaction analysis showed that wound area reduction was significant after two weeks of treatment with the Alg/CMC/ChNPs/DNPs/BTX-A hydrogel. Overall, this scaffold demonstrated potential for promoting tissue regeneration and new epithelization formation, making it a promising candidate for enhancing skin restoration in wound treatments.

Comparison of the protective effects of CS/TPP and CS/HPMCP nanoparticles containing berberine in ethanol-induced hepatotoxicity in rat.

BACKGROUND: Alcoholic liver disease (ALD) is a globally critical condition with no available efficient treatments. METHODS: Herein, we generated chitosan (CS) nanoparticles cross-linked with two different agents, hydroxypropyl methylcellulose phthalate (HPMCP; termed as CS/HPMCP) and tripolyphosphate (TPP; termed as CS/TPP), and loaded them with berberine (BBr; referred to as CS/HPMCP/BBr and CS/TPP/BBr, respectively). Alongside the encapsulation efficiency (EE) and loading capacity (LC), the releasing activity of the nanoparticles was also measured in stimulated gastric fluid (SGF) and stimulated intestinal fluid (SIF) conditions. The effects of the prepared nanoparticles on the viability of mesenchymal stem cells (MSCs) were also evaluated. Ultimately, the protective effects of the nanoparticles were investigated in ALD mouse models. RESULTS: SEM images demonstrated that CS/HPMCP and CS/TPP nanoparticles had an average size of 235.5 ± 42 and 172 ± 21 nm, respectively. The LC and EE for CS/HPMCP/BBr were calculated as 79.78% and 75.79%, respectively; while the LC and EE for CS/TPP/BBr were 84.26% and 80.05%, respectively. pH was a determining factor for releasing BBr from CS/HPMCP nanoparticles as a higher cargo-releasing rate was observed in a less acidic environment. Both the BBr-loaded nanoparticles increased the viability of MSCs in comparison with their BBr-free counterparts. In vivo results demonstrated CS/HPMCP/BBr and CS/TPP/BBr nanoparticles protected enzymatic liver functionality against ethanol-induced damage. They also prevented histopathological ethanol-induced damage. CONCLUSIONS: Crosslinking CS nanoparticles with HPMCP can mediate controlled drug release in the intestine improving the bioavailability of BBr.

Preparation, Characterization, and Anticancer Activity Assessment of Chitosan/TPP Nanoparticles Loaded with Echis carinatus Venom.

AIMS AND BACKGROUND: Echis carinatus venom is a toxic substance naturally produced by special glands in this snake species. Alongside various toxic properties, this venom has been used for its therapeutic effects, which are applicable in treating various cancers (liver, breast, etc.). OBJECTIVE: Nanotechnology-based drug delivery systems are suitable for protecting Echis carinatus venom against destruction and unwanted absorption. They can manage its controlled transfer and absorption, significantly reducing side effects. METHODS: In the present study, chitosan nanoparticles were prepared using the ionotropic gelation method with emulsion cross-linking. The venom's encapsulation efficiency, loading capacity, and release rate were calculated at certain time points. Moreover, the nanoparticles' optimal formulation and cytotoxic effects were determined using the MTT assay. RESULTS: The optimized nanoparticle formulation increases cell death induction in various cancerous cell lines. Moreover, chitosan nanoparticles loaded with Echis carinatus venom had a significant rate of cytotoxicity against cancer cells. CONCLUSION: It is proposed that this formulation may act as a suitable candidate for more extensive assessments of cancer treatment using nanotechnology-based drug delivery systems.

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.

Recent advances on 3D-printed PCL-based composite scaffolds for bone tissue engineering.

Population ageing and various diseases have increased the demand for bone grafts in recent decades. Bone tissue engineering (BTE) using a three-dimensional (3D) scaffold helps to create a suitable microenvironment for cell proliferation and regeneration of damaged tissues or organs. The 3D printing technique is a beneficial tool in BTE scaffold fabrication with appropriate features such as spatial control of microarchitecture and scaffold composition, high efficiency, and high precision. Various biomaterials could be used in BTE applications. PCL, as a thermoplastic and linear aliphatic polyester, is one of the most widely used polymers in bone scaffold fabrication. High biocompatibility, low cost, easy processing, non-carcinogenicity, low immunogenicity, and a slow degradation rate make this semi-crystalline polymer suitable for use in load-bearing bones. Combining PCL with other biomaterials, drugs, growth factors, and cells has improved its properties and helped heal bone lesions. The integration of PCL composites with the new 3D printing method has made it a promising approach for the effective treatment of bone injuries. The purpose of this review is give a comprehensive overview of the role of printed PCL composite scaffolds in bone repair and the path ahead to enter the clinic. This study will investigate the types of 3D printing methods for making PCL composites and the optimal compounds for making PCL composites to accelerate bone healing.

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.

Exploring the Physicochemical, Electroactive, and Biodelivery Properties of Metal Nanoparticles on Peripheral Nerve Regeneration.

Despite the advances in the regeneration/rehabilitation field of damaged tissues, the functional recovery of peripheral nerves (PNs), especially in a long gap injury, is considered a great medical challenge. Recent progress in nanomedicine has provided great hope for PN regeneration through the strategy of controlling cell behavior by metal nanoparticles individually or loaded on scaffolds/conduits. Despite the confirmed toxicity of metal nanoparticles due to long-term accumulation in nontarget tissues, they play a role in the damaged PN regeneration based on the topography modification of scaffolds/conduits, enhancing neurotrophic factor secretion, the ion flow improvement, and the regulation of electrical signals. Determining the fate of neural progenitor cells would be a major achievement in PN regeneration, which seems to be achievable by metal nanoparticles through altering cell vital approaches and controlling their functions. Therefore, in this literature, an attempt was made to provide an overview of the effective activities of metal nanoparticles on the PN regeneration, until the vital clues of the PN regeneration and how they are changed by metal nanoparticles are revealed to the researcher.

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.

Cell loaded hydrogel containing Ag-doped bioactive glass-ceramic nanoparticles as skin substitute: Antibacterial properties, immune response, and scarless cutaneous wound regeneration.

An ideal tissue-engineered dermal substitute should possess angiogenesis potential to promote wound healing, antibacterial activity to relieve the bacterial burden on skin, as well as sufficient porosity for air and moisture exchange. In light of this, a glass-ceramic (GC) has been incorporated into chitosan and gelatin electrospun nanofibers (240-360 nm), which MEFs were loaded on it for healing acceleration. The GC was doped with silver to improve the antibacterial activity. The bioactive nanofibrous scaffolds demonstrated antibacterial and superior antibiofilm activities against Gram-negative and Gram-positive bacteria. The nanofibrous scaffolds were biocompatible, hemocompatible, and promoted cell attachment and proliferation. Nanofibrous skin substitutes with or without Ag-doped GC nanoparticles did not induce an inflammatory response and attenuated LPS-induced interleukin-6 release by dendritic cells. The rate of biodegradation of the nanocomposite was similar to the rate of skin regeneration under in vivo conditions. Histopathological evaluation of full-thickness excisional wounds in BALB/c mice treated with mouse embryonic fibroblasts-loaded nanofibrous scaffolds showed enhanced angiogenesis, and collagen synthesis as well as regeneration of the sebaceous glands and hair follicles in vivo.

In silico design of a multi-epitope vaccine against HPV16/18.

BACKGROUND: Cervical cancer is the fourth most common cancer affecting women and is caused by human Papillomavirus (HPV) infections that are sexually transmitted. There are currently commercially available prophylactic vaccines that have been shown to protect vaccinated individuals against HPV infections, however, these vaccines have no therapeutic effects for those who are previously infected with the virus. The current study's aim was to use immunoinformatics to develop a multi-epitope vaccine with therapeutic potential against cervical cancer. RESULTS: In this study, T-cell epitopes from E5 and E7 proteins of HPV16/18 were predicted. These epitopes were evaluated and chosen based on their antigenicity, allergenicity, toxicity, and induction of IFN-γ production (only in helper T lymphocytes). Then, the selected epitopes were sequentially linked by appropriate linkers. In addition, a C-terminal fragment of Mycobacterium tuberculosis heat shock protein 70 (HSP70) was used as an adjuvant for the vaccine construct. The physicochemical parameters of the vaccine construct were acceptable. Furthermore, the vaccine was soluble, highly antigenic, and non-allergenic. The vaccine's 3D model was predicted, and the structural improvement after refinement was confirmed using the Ramachandran plot and ProSA-web. The vaccine's B-cell epitopes were predicted. Molecular docking analysis showed that the vaccine's refined 3D model had a strong interaction with the Toll-like receptor 4. The structural stability of the vaccine construct was confirmed by molecular dynamics simulation. Codon adaptation was performed in order to achieve efficient vaccine expression in Escherichia coli strain K12 (E. coli). Subsequently, in silico cloning of the multi-epitope vaccine was conducted into pET-28a ( +) expression vector. CONCLUSIONS: According to the results of bioinformatics analyses, the multi-epitope vaccine is structurally stable, as well as a non-allergic and non-toxic antigen. However, in vitro and in vivo studies are needed to validate the vaccine's efficacy and safety. If satisfactory results are obtained from in vitro and in vivo studies, the vaccine designed in this study may be effective as a therapeutic vaccine against cervical cancer.

Criteria, Challenges, and Opportunities for Acellularized Allogeneic/Xenogeneic Bone Grafts in Bone Repairing.

As bone grafts become more commonly needed by patients and as donors become scarcer, acellularized bone grafts (ABGs) are becoming more popular for restorative purposes. While autogeneic grafts are reliable as a gold standard, allogeneic and xenogeneic ABGs have been shown to be of particular interest due to the limited availability of autogeneic resources and reduced patient well-being in long-term surgeries. Because of the complete similarity of their structures with native bone, excellent mechanical properties, high biocompatibility, and similarities of biological behaviors (osteoinductive and osteoconductive) with local bones, successful outcomes of allogeneic and xenogeneic ABGs in both in vitro and in vivo research have raised hopes of repairing patients' bone injuries in clinical applications. However, clinical trials have been delayed due to a lack of standardized protocols pertaining to acellularization, cell seeding, maintenance, and diversity of ABG evaluation criteria. This study sought to uncover these factors by exploring the bone structures, ossification properties of ABGs, sources, benefits, and challenges of acellularization approaches (physical, chemical, and enzymatic), cell loading, and type of cells used and effects of each of the above items on the regenerative technologies. To gain a perspective on the repair and commercialization of products before implementing new research activities, this study describes the differences between ABGs created by various techniques and methods applied to them. With a comprehensive understanding of ABG behavior, future research focused on treating bone defects could provide a better way to combine the treatment approaches needed to treat bone defects.

Designing a novel multi­epitope vaccine against Ebola virus using reverse vaccinology approach.

Ebola virus (EBOV) is a dangerous zoonotic infectious disease. To date, more than 25 EBOV outbreaks have been documented, the majority of which have occurred in Central Africa. The rVSVG-ZEBOV-GP vaccine (ERVEBO), a live attenuated vaccine, has been approved by the US Food and Drug Administration (FDA) to combat EBOV. Because of the several drawbacks of live attenuated vaccines, multi-epitope vaccines probably appear to be safer than live attenuated vaccines. In this work, we employed immunoinformatics tools to design a multi-epitope vaccine against EBOV. We collected sequences of VP35, VP24, VP30, VP40, GP, and NP proteins from the NCBI database. T-cell and linear B-cell epitopes from target proteins were identified and tested for antigenicity, toxicity, allergenicity, and conservancy. The selected epitopes were then linked together in the vaccine's primary structure using appropriate linkers, and the 50S ribosomal L7/L12 (Locus RL7 MYCTU) sequence was added as an adjuvant to the vaccine construct's N-terminal. The physicochemical, antigenicity, and allergenicity parameters of the vaccine were all found to be satisfactory. The 3D model of the vaccine was predicted, refined, and validated. The vaccine construct had a stable and strong interaction with toll-like receptor 4 (TLR4) based on molecular docking and molecular dynamic simulation (MD) analysis. The results of codon optimization and in silico cloning revealed that the proposed vaccine was highly expressed in Escherichia coli (E. coli). The findings of this study are promising; however, experimental validations should be carried out to confirm these findings.

A comparative study of the effects of crab derived exosomes and doxorubicin in 2 & 3-dimensional in vivo models of breast cancer.

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.