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Mohammad Reza Nourani1, Majid Ebrahimi1, Mehryar Habibi Roudkenar3, Ensieh Vahedi1, Mostafa Ghanei1, Abbas Ali Imani Fooladi21Chemical Injury Research Center; 2Microbial Product Research Center, Baqiyatallah University of Medical Sciences; 3Research Center, Iranian Blood Transfusion Organization, Tehran, IranBackground: Sulfur mustard can cause several long-term complications in the organs of individuals exposed to this toxic gas, and among these, pulmonary sequelae are the most important. More than 25 years after the Iran–Iraq war, thousands of Iranians are suffering from the chronic respiratory complications of sulfur mustard. Currently, based on several clinical findings, bronchiolitis obliterans is confirmed as the major diagnosis in these patients. Numerous studies have revealed that this disorder is strongly associated with oxidative stress due to excessive production of harmful reactive substances and decreased levels of endogenous antioxidants. Metallothioneins (MTs) are a group of low molecular weight sulfhydryl-rich intracellular proteins, and several isoforms have been identified in humans. MT-1A is an inducible and important MT isoform, which is transcriptionally activated by a variety of stress stimuli, such as free radicals.Methods: MT-1 mRNA expression and protein levels in endobronchial biopsy samples from 24 sulfur mustard-exposed patients and 15 unexposed control cases were evaluated by semiquantitative reverse transcriptase polymerase chain reaction, real-time reverse transcriptase polymerase chain reaction, and immunohistochemistry.Results: mRNA- MT-1A expression levels in sulfur mustard-exposed patients were upregulated compared with normal samples. Protein expression was also markedly higher in controls than in sulfur mustard-exposed patients.Conclusion: Upregulation of MT-1A mRNA in patients who have been exposed to sulfur mustard seems to be due to oxidative stress, which is induced in an attempt to ameliorate this harmful situation by reestablishment of homeostasis, but depletion of its protein might be due to secondary consequences of sulfur mustard toxicity, which are as yet not understood.Keywords: sulfur mustard, metallothionein-1A, airway, epithelial cells

Purpose: Due to the multilayered structure of the skin tissue, the architecture of its engineered scaffolds needs to be improved. In the present study, 45s5 bioglass nanoparticles were selected to induce fibroblast proliferation and their protein secretion, although cobalt ions were added to increase their potency., Methods: A 3-layer scaffold was designed as polyurethane (PU) - polycaprolactone (PCL)/ collagen/nanoparticles-PCL/collagen. The scaffolds examined by scanning electron microscopy (SEM), Fourier transform infrared (FTIR), tensile, surface hydrophilicity and weight loss. Biological tests were performed to assess cell survival, adhesion and the pattern of gene expression., Results: The mechanical assay showed the highest young modulus for the scaffold with the doped nanoparticles and the water contact angle of this scaffold after chemical crosslinking of collagen was reduced to 52.34±7.7°. In both assessments, the values were statistically compared to other groups. The weight loss of the corresponding scaffold was the highest value of 82.35±4.3 % due to the alkaline effect of metal ions and indicated significant relations in contrast to the scaffold with non-doped particles and bare one ( P value<0.05). Moreover, better cell expansion, greater cell confluence and a lower degree of toxicity were confirmed. The up-regulation of TGF β1 and VEGF genes introduced this scaffold as a better model for the fibroblasts commitment to a new skin tissue among bare and nondoped scaffold ( P value<0.05)., Conclusion: The 3-layered scaffold which is loaded with cobalt ions-bonded bioglass nanoparticles, is a better substrate for the culture of the fibroblasts., Competing Interests: All authors declare they have no conflict of interests and also, no concerned financial issues that could have influenced on this article., (©2024 The Authors.)

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., (© 2024. The Author(s).)

Aim: This study was conducted to investigate the effect of fibrin glue-CM11 antibacterial peptide mixture (FG-P) on the healing of infected wounds in vivo . Materials & methods: We formulated a mixture of FG-P and evaluated its antimicrobial activity in vitro against multidrug-resistant (MDR) bacteria involved in wound infection as well as its healing effect on wound infected by methicillin-resistant S. aureus (MRSA) in vivo . Results: The peptide had an MIC of 8 μg/ml against all bacteria isolates. Growth inhibition zones were evident for FG-P compared with FG. The in vivo study showed that the FG-P could be significantly effective in healing the MRSA-infected wound. Conclusion: The use of FG-P mixture is a very suitable option for treating infected wounds.

Objectives: Long-term potentiation (LTP) is a kind of synaptic plasticity and has a key role in learning and memory. Endocannabinoids and orexins are the endogenous systems that can modulate synaptic plasticity. Given that new studies have shown an interaction between cannabinoid and orexin systems in the brain, we decided to examine this interaction between the two systems on LTP induction in rat's hippocampus., Materials and Methods: Twenty-eight male Wistar rats were used for evaluating the effects of co-administrating of cannabinoid-1 receptor (CB1R) antagonist (AM251) and orexin-2 receptor (OX2R) antagonist (TCS OX2 29) on the induction of LTP in the Schaffer collateral-CA1 synapses of rat hippocampus. The drugs were microinjected into the CA1 area of rat hippocampus 30 min before inducing of LTP., Results: Results showed that sole administration of the antagonists inhibited LTP, with respect to the control group. Also, co-administrating of them reduced LTP as compared to the control group, but not significantly more than that when the antagonists were solely microinjected into the CA1. Nonetheless, the inhibitory effect of concurrent administration of the antagonists on LTP lasted until the end of the recording., Conclusion: These results propose that endogenous cannabinoids and orexins play a role in the expression of LTP, at least by CA1-CB1Rs and CA1-OX2Rs, respectively. Finally, there is no interaction between CB1R and OX2R on the induction of LTP in the Schaffer collateral-CA1 synapses; therefore, these two systems possibly act through common signaling pathways in the hippocampus's CA1 region., Competing Interests: All authors declare there are no conflicts of interest in this study.

Objective: The integration of nanomaterials and herbal medicine has led to the design of new nanocomposites, which are therapeutically more effective. The purpose of this study was to prepare different zinc oxide (ZnO)-based nanoparticles (NPs) via Mentha longifolia extract based on gauze linen fibre and study its effects on wound healing., Methods: The textural properties, morphology, thermal stability, purity, spectroscopic and phase structure of nanoparticles were investigated. Subsequently, male Wistar rats were subjected to wounds in six different treatment groups: Group I: control; group II: ZnO/W prepared in water (W); group III: ZnO/M synthesised with Mentha longifolia (M) extract; group IV: ZnO/copper(II) oxide (CuO)/M nanocomposite synthesised with M extract; group IV: treated with ZnO/silver (Ag)/M nanocomposite; group V: treated with ZnO/Ag/M nanocomposite; and finally, group VI: treated with ZnO/CuO/Ag/M nanocomposite. In all groups, the wounds were treated for 21 days with prepared samples. Every seven days, after measuring the decreasing rate of the wound size, tissue samples from each group were taken for histopathological analysis. The prepared tissue sections were assessed by haematoxylin and eosin staining for the formation of the epidermis, dermis and muscular tissue, and Masson's Trichrome staining for the formation of collagen fibres., Results: The results showed that the ZnO/CuO/Ag/M nanocomposite was a significantly more effective wound healing material in comparison with other samples (p<0.05)., Conclusion: In this study, the integration of ZnO/CuO/Ag nanocomposites with secondary metabolites of Mentha longifolia gave rise to a superior combination, which could support different phases of wound healing via the regulation of cytokines and growth factors in the course of healing.

Repairing of large bone injuries is an important problem in bone regeneration field. Thus, developing new therapeutic approaches such as tissue engineering using 3D scaffolds is necessary. Incorporation of some bioactive materials and trace elements can improve scaffold properties. We made chitosan/alginate/strontium-doped bioglass composite scaffolds with optimized properties for bone tissue engineering. Bioglass (BG) and Sr-doped bioglasses (Sr-BG) were synthesized using Sol-Gel method. Alginate-Chitosan (Alg/Cs) scaffold and scaffolds containing different ratio (10%, 20% and 30%) of BG (Alg/Cs/BG10, 20, 30) or Sr-BG (Alg/Cs/Sr-BG10, 20, 30) were fabricated using freeze drying method. Characterization of bioglasses/scaffolds was done using zeta sizer, FTIR, XRD, (FE) SEM and EDS. Also, mechanical strength, antibacterial effect degradation and swelling profile of scaffolds were evaluated. Bone differentiation efficiency and viability of MSCs on scaffolds were determined by Alizarin Red, ALP and MTT methods. Cell toxicity and antibacterial effect of bioglasses were determined using MTT, MIC and MBC methods. Incorporation of BG into Alg/Cs scaffolds amplified biomineralization and mechanical properties along with improved swelling ratio, degradation profile and cell differentiation. Mechanical strength and cell differentiation efficiency of Alg/Cs/BG20 scaffold was considerably higher than scaffolds with lower or higher BG concentrations. Alg/Cs/Sr-BG scaffolds had higher mechanical stability and more differentiation efficiency in comparison with Alg/Cs and Alg/Cs/BG scaffolds. Also, Mechanical strength and cell differentiation efficiency of Alg/Cs/Sr-BG20 scaffold was considerably higher than scaffolds with various Sr-BG concentrations. Biomineralization of Alg/Cs/BG scaffolds slightly was higher than Alg/Cs/Sr-BG scaffolds. Overall, we concluded that Alg/Cs/Sr-BG20 scaffolds are more suitable for repairing bone major injuries., (© 2022. The Author(s).)

The main purpose of neural tissue engineering and regenerative medicine is the development of biological substitutions to preserve, improve, and regenerate the damaged functions of tissues and organs. Three novel conduits, including polyurethane (PU), polyurethane/collagen (PU/C), and polyurethane/collagen/nano-bio glass (PU/C/NBG), were fabricated by the electrospinning technique. After confirming the suitability of conduits in the in-vitro environment, conduits were surgically sutured in a 10-mm gap in the sciatic nerve of a rat to evaluate their role in sciatic nerve reconstruction. After 4, 8, and 12 weeks of surgery, nerve regeneration was assessed by the hot plate test, sciatic functional index, electromyography, histology, and immunohistochemistry against S100, NF200, and CD31 antibodies. The results of various examinations revealed that the PU/C/NBG conduit is significantly more suitable than PU and PU/C conduits in terms of nerve regeneration. However, all three groups of conduits had the potential to be used for nerve regeneration. Overall, this study discovered that the PU/C/NBG conduit is a biocompatible neural conduit, which is a favorable candidate for peripheral nerve regeneration and axonal growth., (© 2021 Wiley Periodicals LLC.)

Peripheral nerve injury can significantly affect the daily life of individuals with impaired nerve function and permanent nerve deformity. One of the most common treatments is autograft transplantation. Tissue engineering is one of the efficient methods to regenerate injured nerves using scaffolds, cells, and growth factors. Conduits, which are produced by a variety of techniques, could be used as an alternative treatment for patients with damaged nerves. The electrospinning technique is one of the most important and widely used methods for generating nanofiber conduits from biocompatible polymers. In this study, using the electrospinning method, three different conduits, including polyurethane (PU), polyurethane/collagen (PU/C), and a new conduit based on polyurethane + collagen + nanobioglass (PU/C/NBG), were prepared. The characteristics of these three types of conduits were evaluated by SEM, XRD, and various experiments, including porosity, degradation, contact angle, DMTA, FTIR, MTT, and DAPI staining. The results of MTT and DAPI assays revealed the safety of conduits and proper cell attachment. Overall, the results obtained from various experiments showed that the novel PU/C/NBG conduit has better mechanical properties in terms of porosity, hydrophilicity, and biocompatibility in comparison with PU and PU/C conduits and could be a suitable candidate for peripheral nerve regeneration and axonal growth due to its repair potential.

Background: This study aimed to evaluate the amount of bone regeneration in critical defects of rabbit calvaria filled with magnesium- and strontium-doped bioactive glasses., Materials and Methods: In this rabbit critical-size calvarial defects study, 12 male New Zealand white rabbits were randomly divided into two groups. On the calvaria of each rabbit, four lesions (two lesions in the frontal bone and two lesions in the peritoneal bone) were created with a diameter of 8 mm spaced apart. Each lesion was filled in with (1) strontium-doped bioactive glass, (2) magnesium-doped bioactive glass, (3) 45S5 bioactive glass, and (4) empty lesion (control). Six rabbits were sacrificed at the end of 4 weeks, and six rabbits were randomly sacrificed at the end of 8 weeks. Bone sections with a 5-μ thickness of rabbit calvary bone were prepared, and the percentage of new bone, connective tissue, and residual material were calculated in microscopic images. Statistical analysis was performed by two-way ANOVA and Bonferroni additional tests, and the level of significance was set at P < 0.05 in all categories., Results: At 4 weeks, magnesium-doped bioactive glass showed the highest new bone formation with a mean of 11.66 ± 2.64, followed by the strontium-doped bioactive glass with the mean of 11.10 ± 1.69 ( P = 0.0001). While at week 8, the highest amount of new bone observed in the strontium-doped group with a mean of 28.22 ± 3.19, and then, the magnesium-doped bioactive glass with a mean of 22.55 ± 3.43 ( P = 0.0001)., Conclusion: Doping strontium and magnesium in the structure of bioactive glasses increases new bone regeneration in comparison with 45S5 bioactive glass., Competing Interests: The authors of this manuscript declare that they have no conflicts of interest, real or perceived, financial or nonfinancial in this article., (Copyright: © 2022 Dental Research Journal.)

The present study aimed to assess the effect of tissue hypoxia induced by sodium cyanide (NaCN) on male mice fertility and the protective role of ethyl pyruvate (EP). A number of 30 adult mice were assigned to three groups: 1) a control group, 2) a treatment group treated with 2 mg/kg of NaCN, and 3) a treatment group treated with 2 mg/kg of NaCN, along with 40 mg/kg EP (NaCN+EP). After 35 days, animals were anesthetized and serum, sperm, and tissue samples were taken. The results demonstrated a significant decrease in sperm quality, reproduction potency, and anti-oxidant potential, as well as an increase in lipid peroxidation in the NaCN group (p &lt;0.05). Moreover, the use of EP effectively restrained the disastrous effects of tissue hypoxia. It can be concluded that EP can moderate the complications resulting from tissue-hypoxia that is related to testes parameters., (Copyright © 2021, Author(s). Published by Kowsar.)

Background: The present study focused on burning as one of the main causes of mortality with detrimental economic and social effects in the world. The purpose of this study was to investigate the impact of collagen-chitosan gel extracted from Scomberomorus guttatus and shrimp skin in the treatment of second degree burn healing among rats., Materials & Method: To fulfill the purpose of the study, chitosan and collagen were extracted respectively from shrimp and Scomberomorus guttatus skin waste by the acid-based method and were evaluated by using Pico Tag, SDS-PAGE. The burn wound healing efficiency of marine collagen-chitosan gel was examined in vivo using rats. Three different ratios of collagen and chitosan blend (Col-CH, 1:3, 1:1 and 3:1) were prepared to obtain the most effective Col-CH gel for burn wound healing and were compared to the animals treated with silver sulfadiazine ointment. Healing burn wound was studied by measuring wound surface area with Image J and histopathologic examination was carried out based on the mean of epithelialization, fibroblastic cells, acute and chronic inflammatory cells, angiogenesis, structure collagen and the amount of collagen on days 15 and 25 post-burn., Results: The results of SDS-PAGE indicated that the extracted collagen was type I and it was composed of two α (α 1 and α 2 ) chains. Amino acid analysis showed a much higher glaycin content in extracted collagen which amounted to one-third of the total amino. The wound surface measurement showed a significant reduction in wound size in the group treated with Col-CH (3:1) compared to silver-sulfadiazine treated group on 15th and 25th days. Histopathological findings represented a high score in epithelialization, collagen, collagen structure, fibroblast cell and a decrease in inflammatory cells infiltration in Col-CH (3:1) treated group on 25th day. The most obvious finding of the present study is that chitosan-collagen gel (3:1) represented a better efficacy compared to sulfadiazine in burn wound healing on day 25 post-burn., Competing Interests: The authors declare that we have no conflict of interest., (© 2021 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Human amniotic membrane (AM) has been widely used for tissue engineering and regenerative medicine applications. AM has many favorable characteristics such as high biocompatibility, antibacterial activity, anti-scarring property, immunomodulatory effects, anti-cancer behavior and contains several growth factors that make it an excellent natural candidate for wound healing. To date, various methods have been developed to prepare, preserve, cross-link and sterilize the AM. These methods remarkably affect the morphological, physico-chemical and biological properties of AM. Optimization of an effective and safe method for preparation and preservation of AM for a specific application is critical. In this review, the isolation, different methods of preparation, preservation, cross-linking and sterilization as well as their effects on properties of AM are well discussed. For each section, at least one effective and safe protocol is described in detail., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

Wound healing has long been recognised as a major clinical challenge for which stablishing more effective wound therapies is necessary. The generation of metallic nanocomposites using biological compounds is emerging as a new promising strategy for this purpose. In this study, four metallic nanoparticles (NPs) with propolis extract (Ext) and one without propolis including ZnO/Ext, ZnO/Ag/Ext, ZnO/CuO/Ext, ZnO/Ag/CuO/Ext and ZnO/W were prepared by microwave method and assessed for their wound healing activity on excision experimental model of wounds in rats. The developed nanocomposites have been characterised by physico-chemical methods such as X-ray diffraction, scanning electron microscopy, diffuse reflectance UV-vis spectroscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis and Brunauer-Emmett-Teller analyses. The wounded animals treated with the NPs/Ext in five groups for 18 days. Every 6 days, for measuring wound closure rate, three samples of each group were examined for histopathological analysis. The prepared tissue sections were investigated by haematoxylin and Eosin stainings for the formation of epidermis, dermis and muscular and Masson's trichrome staining for the formation of collagen fibres. These findings toughly support the probability of using this new ZnO/Ag/Ext materials dressing for a wound care performance with significant effect compared to other NPs.

Pulmonary disease is a worldwide public health problem that reduces the life quality and increases the need for hospital admissions as well as the risk of premature death. A common problem is the significant shortage of lungs for transplantation as well as patients must also take immunosuppressive drugs for the rest of their lives to keep the immune system from attacking transplanted organs. Recently, a new strategy has been proposed in the cellular engineering of lung tissue as decellularization approaches. The main components for the lung tissue engineering are: (1) A suitable biological or synthetic three-dimensional (3D) scaffold, (2) source of stem cells or cells, (3) growth factors required to drive cell differentiation and proliferation, and (4) bioreactor, a system that supports a 3D composite biologically active. Although a number of synthetic as well biological 3D scaffold suggested for lung tissue engineering, the current favorite scaffold is decellularized extracellular matrix scaffold. There are a large number of commercial and academic made bioreactors, the favor has been, the one easy to sterilize, physiologically stimuli and support active cell growth as well as clinically translational. The challenges would be to develop a functional lung will depend on the endothelialized microvascular network and alveolar-capillary surface area to exchange gas. A critical review of the each components of lung tissue engineering is presented, following an appraisal of the literature in the last 5 years. This is a multibillion dollar industry and consider unmet clinical need., (© 2019 Wiley Periodicals, Inc.)

Background: Collagen is the main product in pharmaceutics and food industry with a high demand. Collagen can be extracted from several tissues such as skin, bone and tendon, etc. Collagen can be used in tissue engineering researches as a substrate of wound healing and nerve regeneration. Extraction methods of collagen are various with different purities. In this research, we aimed to extract collagen from human placenta with a modified method., Methods: This modified approach was used for extracting of collagen from human placenta with acetic acid and NaCl treatment using different concentrations., Results: SDS page showed three different bands that reflected two alpha-chains and one beta-chain with molecular weights of 102, 118 and 220 kDa, respectively. There was no significant difference between extracted collagen from human placenta and standard collagen in western blot analysis., Conclusion: It was concluded that human placenta can be an alternative source of collagen with high purity for biomedical applications such as tissue engineering, stem cell therapy and research., Competing Interests: The authors declare no conflict of interest.

Although pulmonary diseases account for a large number of deaths in the world, most have no treatment other than transplantation. New therapeutic methods for lung treatment include lung tissue engineering and regenerative medicine. Lung decellularization has been used to produce an appropriate scaffold for recellularization and implantation. We investigated 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS) with sodium dodecyl sulfate (SDS) and Triton X-100 detergents for effecting rat lung decellularization. We evaluated using conventional histology, immunofluorescence staining and SEM methods for removing nuclear material while leaving intact extracellular matrix proteins and three-dimensional architecture. We investigated different concentrations of CHAPS, SDS and Triton X-100 for different periods. We found that 2 mM CHAPS + 0/1% SDS for 48 h was the best among the treatments investigated. Our method can be used to produce an appropriate scaffold for recellularization by stem cells and for investigations ex vivo and in vivo.

An ultrahigh sensitive, simple and reliable Electrochemiluminescence (ECL) immunosensor for selective quantification of p53 protein was designed according to the enhancement effects of AuNPs on ECL emission of CdS nanocrystals (CdS NCs). CdS NCs were immobilized on the glassy carbon electrode and AuNPs introduced to the process through formation of a sandwich-type immunocomplex between first anti-p53/p53/ secondary anti-p53. ECL of CdS NCs firstly evoked the SPR of AuNPs which in return amplified the CdS NCs ECL intensity. By using graphene oxide in immunosensor fabrication procedure, and attaching more AuNPs on the surface of the electrode, the ECL intensity was further increased resulting in much higher sensitivity. After applying the optimum conditions, the linear range of the developed immunosensor was found between 20 and 1000 fg/ml with a calculated limit of detection of 4 fg/ml. Moreover, the interference, reproducibility and storage stability studies of the immunosensor were investigated. Finally, immunosensor's authenticity was evaluated by detecting the p53 protein in human spikes which offers it as a potential in early detection of cancer, monitoring the cancer progress and clinical prognosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Liposomes could improve the delivery of substances to sperm. This study was conducted to investigate the effect of the antioxidant ellagic acid and ellagic acid-loaded liposomes on post-thawed sperm quality in broiler breeder roosters. Semen was diluted in Beltsville extender containing ellagic acid or ellagic acid-loaded liposomes (ellagic acid at 0 (control), 0.5, 1, and 2 mM) and cryopreserved. Sperm quality was evaluated post-thawing: motility characteristics (Computer-Assisted Semen Analysis), membrane functionality (HOS test), abnormal morphology, mitochondrial activity (Rhodamine 123), apoptotic status (Annexin V/Propidium iodide), malondialdehyde, and antioxidant activities (glutathione peroxidase (GPx), superoxide dismutase (SOD), and total antioxidant capacity (TAC)). The results showed that 1 mM ellagic acid-loaded liposomes improved total motility, membrane functionality, and viability comparing to 0.5 and 2 mM ellagic acid, 2 mM ellagic acid-loaded liposomes, and control group. Mitochondrial activity was significantly higher for 1 mM ellagic acid-loaded liposomes compared to the rest of the treatments, except 1 mM ellagic acid. Ellagic acid at 1 mM in both forms significantly increased GPx and TAC after freeze-thawing (no significant variation for SOD), and also yielded the lower proportion of apoptotic and dead cells. In conclusion, ellagic acid improved post-thawed sperm quality in broiler breeder roosters. The use of liposomes could further enhance the effects of ellagic acid.

Bone defects remain a significant health issue and a major cause of morbidity in elderly patients. Composites based on collagen/calcium phosphate have been widely used for bone repair in clinical applications, owing to their comparability to bone extracellular matrix. This study aimed to evaluate the effects of a scaffold of collagen/calcium phosphate (COL/β-TCP) on bone formation to assess its potential use as a bone substitute to repair bone defects. Bilateral full-thickness critically sized calvarial defects (8 mm in diameter) were created in New Zealand white rabbits and treated with COL/β-TCP or COL scaffolds. One defect was also left unfilled as a control. Bone regeneration was assessed through histological evaluation using hematoxylin and eosin and Masson's trichrome staining after 4 and 8 weeks. Alizarin Red staining was also utilized to observe the mineralization process. Our findings indicated that COL/β-TCP implantation could better enhance bone regeneration than COL and exhibited both new bone growth and scaffold material degradation.

In recent years, for neurodegenerative diseases therapy, research has focused on the stem cells therapy. Due to promising findings in stem cell therapy, there are various sources of stem cells for transplantation in human. The aim of this study was to evaluate sciatic nerve regeneration in the rat after nerve transaction followed by human endometrial stem cells (hEnSCs) treatment into poly (e-caprolactone)/collagen/nanobioglass (PCL/collagen/NBG) nanofibrous conduits. After treatment of animals, the performance in motor and sensory tests, showed significant improvement in rats treated with hEnSCs as an autograft. H&E images provided from cross-sectional and, longitudinal-sections of the harvested regenerative nerve as well as immunohistochemistry results indicated that regenerative nerve fibres had been formed and accompanied with new blood vessels in the conduit cell group. Due to the advantage of high surface area for cell attachment, it is reported that this electrospun nerve conduit could find more application in cell therapy for nerve regeneration in future, to further improve the functional regeneration outcome, especially for longer nerve defect restoration. In conclusion, our results suggest that the PCL/collagen/NBG nanofibrous conduit filled with hEnSCs is a suitable strategy to improve nerve regeneration after a nerve transaction in rat.

Radiation-induced lung injury is one of the most prominent factors that interfere with chest cancer radiotherapy, and poses a great threat to patients exposed to total body irradiation. Upregulation of pro-oxidant enzymes is one of the main mechanisms through which the late effects of ionizing radiation on lung injury can be exerted. Interleukin (IL)-4 and IL-13 are two important cytokines that have been proposed to be involved in this process. Through stimulation of dual oxidase 1 and 2 (DUOX 1 & 2 ), they induce chronic oxidative stress in irradiated tissues. In this study, we evaluated the effects of curcumin treatment on the regulation of IL-4 and IL-13 , DUOX1 & 2 genes as well as the pathological changes developed by this treatment. Twenty male Wistar rats were divided into four groups: radiation only; curcumin only; radiation +curcumin; and control group with neither pharmacotherapy nor radiation. Curcumin was administered for 4 and 6 consecutive days before and after irradiation, respectively. Also, the chest area was irradiated with 15 Gy using a cobalt-60 gamma rays source. All rats were sacrificed 67 days after irradiation, followed by the assessment of the levels of IL-4 and IL-13; the expression of IL- 4 receptor-a1 ( IL4Ra1 ), IL13Ra2 , DUOX1 and DUOX2 , and finally the histopathological changes were evaluated. Radiation led to the increased level of IL-4, while the level of IL-13 showed no change. QPCR results showed the upregulation of IL4Ra1 , DUOX1 and DUOX2 following lung irradiation. Histopathological evaluation also showed a remarkable increase in pneumonitis and fibrosis. Treatment with curcumin downregulated the expression of IL-4 , IL4Ra1 , DUOX1 & 2 . Furthermore, it could mitigate pneumonitis and fibrosis following lung irradiation. The late effects of radiation- induced lung injury may be due to the upregulation of DUOX1 & 2 genes. Curcumin, through modulation of these genes, may contribute to the protection against ionizing radiation., Competing Interests: The authors report no conflict of interest.

Regenerative medicine (RM) is a promising new field of medicine that has mobilized several new tools to repair or replace lost or damaged cells or tissues by stimulating natural regenerative mechanisms nearby cell and tissue-based therapy approaches. However, mesenchymal stem cell (MSC) based therapy has been shown to be safe and effective to a certain degree in multiple clinical trial studies (CTSs) of several diseases, in most MSC CTSs the efficacy of treatment has been reported low. Therefore, researchers have focused on efficacy enhancing of MSC to improve migratory and homing, survival, stemness, differentiation and other therapeutic applicable properties by using different approaches. Gene therapy is one of the experimental technique tools that uses genes to change cells for therapeutic and investigation purposes. In this study has been focused on genetically modified MSCs for use in RM with an emphasis on CTSs. We highlight the basic concept of genetic modifications and also discuss recent clinical studies aspects. Recently reviewed studies show that MSC therapy with assistant gene therapy can be used in cancer therapy, heart diseases, Fanconi anemia and several other diseases.

Regeneration of peripheral nerve defects remained a remarkable clinical challenge. Engineered nerve conduits represent a promising strategy to improve functional recovery in peripheral nerve injury repair. However, nerve conduits require additional factors such as neurotrophic factors to create a more conducive microenvironment for nerve regeneration. Neurotrophic factors have well-demonstrated abilities to improve neurite outgrowth, making them great candidates for repairing of defected nerves. To this end, we examined the beneficial effects of repairing the transected rat sciatic nerve by loading of nerve growth factor (NGF) in nerve conduits. The PCL/Collagen/NBG conduits were interposed into the 10 mm right sciatic nerve defects. Twenty-four rats were randomly allocated into four groups: 1- nerve autograft group, 2- a nongrafted group with gap 10-mm, 3- conduit group and 4- the conduits loaded with NGF. Motor and sensory functional recovery, the evoked muscle action potential, and motor distal latency showed significant improvement in rats treated with NGF. The histology and immunohistochemistry studies revealed less fibrosis and a high level of expression of CD31 and NF-200 protein at the crush site in the Conduit + NGF group. In conclusion, the PCL/Collagen/NBG conduit loaded with NGF, which exhibited nanometer-scale features, neurotrophic activity, favorable mechanical properties and biocompatibility could improve sciatic nerve regeneration in rats.

We developed collagen (COL) and collagen/beta tricalcium phosphate (COL/β-TCP) scaffolds with a β-TCP/collagen weight ratio of 4 by freeze-drying. Mouse bone marrow-derived mesenchymal stem cells (BMMSCs) were cultured on these scaffolds for 14 days. Samples were characterized by physicochemical analyses and their biological properties such as cell viability and alkaline phosphatase (ALP) activity was, also, examined. Additionally, the vascularization potential of the prepared scaffolds was tested subcutaneously in Wistar rats. We observed a microporous structure with large porosity (∼95-98%) and appropriate pore size (120-200 µm). The COL/β-TCP scaffolds had a much higher compressive modulus (970 ± 1.20 KPa) than pure COL (0.8 ± 1.82 KPa). In vitro model of apatite formation was established by immersing the composite scaffold in simulated body fluid for 7 days. An ALP assay revealed that porous COL/β-TCP can effectively activate the differentiation of BMMSCs into osteoblasts. The composite scaffolds also promoted vascularization with good integration with the surrounding tissue. Thus, introduction of β-TCP powder into the porous collagen matrix effectively improved the mechanical and biological properties of the collagen scaffolds, making them potential bone substitutes for enhanced bone regeneration in orthopedic and dental applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 73-85, 2018., (© 2017 Wiley Periodicals, Inc.)

Background: Lung disease is the most common cause of death in the world. The last stage of pulmonary diseases is lung transplantation. Limitation and shortage of donor organs cause to appear tissue engineering field. Decellularization is a hope for producing intact ECM in the development of engineered organs., Aim: The goal of the decellularization process is to remove cellular and nuclear material while retaining lung three-dimensional and molecular proteins. Different concentration of detergents was used for finding the best approach in lung decellularization., Material and Methods: In this study, three-time approaches (24, 48 and 96 h) with four detergents (CHAPS, SDS, SDC and Triton X-100) were used for decellularizing rat lungs for maintaining of three-dimensional lung architecture and ECM protein composition which have significant roles in differentiation and migration of stem cells. This comparative study determined that variable decellularization approaches can cause significantly different effects on decellularized lungs., Results: Results showed that destruction was increased with increasing the detergent concentration. Single detergent showed a significant reduction in maintaining of three-dimensional of lung and ECM proteins (Collagen and Elastin). But, the best methods were mixed detergents of SDC and CHAPS in low concentration in 48 and 96 h decellularization., Conclusion: Decellularized lung tissue can be used in the laboratory to study various aspects of pulmonary biology and physiology and also, these results can be used in the continued improvement of engineered lung tissue.

Intervertebral disc degeneration is recognized to be the leading cause for chronic low-back pain. Injectable hydrogel is one of the great interests for tissue engineering and cell encapsulation specially for intervertebral (IVD) affecting rate of regeneration success, in this study we assessed viscoelastic properties of a Chitosan-β glycerophosphate-hyaluronic acid, Chondroitin-6-sulfate, type 2 of Collagen, gelatin, fibroin silk (Ch-β-GP-HA-CS-Col-Ge-FS) hydrogel which was named as NP hydrogel that is natural extracellular matrix of IVD. Chitosan-based hydrogel was made in the ratio of 1.5%: 7%: 1%:1%:1%-1.5%-1% (Ch: β-GP: HA-CS-Col-Ge-FS). Gelation time and other rheological properties were studied using amplitude sweep and frequency sweep tests. Also, the cytotoxicity of the hydrogel invitro assessed by MTT and trypan blue tests. Morphology of the hydrogel and attachment of NP cells were evaluated by SEM. Our result showed that NP hydrogel in 4°C is an injectable transparent solution. It started gelation in 37°C after about 30min. Gelation temperature of NP hydrogel was 37°C. Storage modulus (G') of this hydrogel at 37°C was almost constant over a wide range of strain. MTT and trypan blue tests showed hydrogel was cytocompatible. The obtained results suggest that this hydrogel would be a natural and cytocompatible choice as an injectable scaffold for using in vivo study of IVD regeneration., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Pulmonary diseases cusecs a large portion of mortality in the world. There is no more cure for pulmonary diseases and many approaches are needed for finding ways to cure. Nowadays, implantation and drugs are only ways for curing those people who are facing with these diseases. Tissue engineering and regenerative medicine have been appeared as multidisciplinary field and also, they presents new therapeutic approaches for pulmonary diseases. One of these therapeutic approaches is decellularization which removes cellular but leaves intact important extracellular matrix (ECM) proteins and three-dimensional (3D) architecture and also, this approach has been studied for in-vitro and ex-vivo. In this study, we aimed to investigate a comparison of different concentrations of Triton X-100 and Sodium dodecyl sulfate detergents in lung decellularization in order to evaluate the effects of different concentrations and times of mentioned detergents on three dimensional and ECM proteins lung. Two detergents (Triton-X100 and Sodium dodecyl sulfat) were used with different concentrations for decellularizing rat lungs for maintaining of three-dimensional lung architecture and ECM protein compositions which have significant roles in differentiation and migration of stem cells. Results showed that SDS 0.05%, 0.1% and Triton-X100 0.1% could maintain 3D, elastin and collagen better than other concentrations in 24 and 48 h- decellularization. We concluded that these approaches can help to achieve three-dimensional architecture and extracellular matrix of lung with minimum destruction for next step such as recellularization and in-vivo study.

Context: Mustard gas (e.g. sulfur mustard (SM)) has been used as a chemical agent in several battles and is still a potential worldwide menace. Besides local absorption, particularly in the skin, eyes and lungs, systemic spread of the agent also has detrimental effects on gonads, bone marrow and nervous system. Moreover, chronic exposure of SM to respiratory system causes death. Inducing oxidative stress, and disturbing DNA and tissue repair systems, inflammation and cell death signaling pathways have been introduced as molecular mechanisms of the injury., Methods: In this systematic review, more than 1200 (2000-2014) articles focusing on gross or molecular pathological reports in the acute phase of the respiratory injury after SM exposure were reviewed, followed by two different layers of gross and molecular pathological data (clinic and laboratory) integrated together in a spatio-temporal order. Role of epithelial, neutrophil and macrophage cells and three signaling pathways of inflammation, oxidative stress and cell death are covered in details., Results and Conclusion: Our results propose a critical role of interleukin-17 producing cells in acute and chronic inflammatory responses.

Introduction: Trauma is one of the causes of peripheral nerve injuries. Free radicals increase after tissue damage. Free radicals are usually scavenged and detoxified by antioxidants. In this study, we assessed the antioxidative role of the NGAL molecule in sciatic nerve repair in rats., Materials and Methods: The sciatic nerves of 40 rats were crushed and the total mRNA of samples from day 1 and 3 and week 1, 3, 5 post injury was extracted. The expression of the NGAL gene was confirmed by RT-PCR. For immunohistochemistry analysis, the samples were fixed in paraformaldehyde and cut in 20 micrometer slices by cryostat., Results: The expression of NGAL significantly upregulated in day 1, 3 and week 1 following the crushing of sciatic nerves in comparison with the intact nerves. Immunohistochemistry results also confirmed the protein expression of this gene., Discussion: The NGAL molecule showed upregulation in the degeneration process after nerve injury, so it may play an important role in nerve repair.

Human airway is generally destructed by inhaled factors and is the barrier to the external environment and has a crucial role in protection of the internal homeostasis of the lung. Sulfur mustard (SM) is a chemical warfare that capable of producing severe chemical injuries primarily in the lungs. Trefoil factor family (TFFs) plays major roles in epithelial repair and homeostasis, particularly in the lung. This study attempted to verify the role of TFFs in airway that induced by sulfur mustard. Fifteen patients exposed to SM and 10 non-exposed subjects were enrolled in this study. Bronchoscopy was carried out and endobronchial biopsy specimens were taken. The TFFs gene expressions were evaluated by RT-PCR. The results revealed that the TFF1 was overexpressed in exposed subjects in comparison to non-exposed subjects. In conclusion, TFF1 displays a distinct protein expression pattern in the developing of airway remodeling due to SM inhalation and plays an important role in maintaining the airway epithelium function.

Background: Mesenchymal stem cells (MSCs) have been recently received increasing attention for cell-based therapy, especially in regenerative medicine. However, the low survival rate of these cells restricts their therapeutic applications. It is hypothesized that autophagy might play an important role in cellular homeostasis and survival. This study aims to investigate the regenerative potentials of autophagy-modulated MSCs for the treatment of acute liver failure (ALF) in mice., Methods: ALF was induced in mice by intraperitoneal injection of 1.5 ml/kg carbon tetrachloride. Mice were intravenously infused with MSCs, which were suppressed in their autophagy pathway. Blood and liver samples were collected at different intervals (24, 48 and 72 h) after the transplantation of MSCs. Both the liver enzymes and tissue necrosis levels were evaluated using biochemical and histopathological assessments. The survival rate of the transplanted mice was also recorded during one week., Results: Biochemical and pathological results indicated that 1.5 ml/kg carbon tetrachloride induces ALF in mice. A significant reduction of liver enzymes and necrosis score were observed in autophagy-modulated MSC-transplanted mice compared to sham (with no cell therapy) after 24 h. After 72 h, liver enzymes reached their normal levels in mice transplanted with autophagy-suppressed MSCs. Interestingly, normal histology without necrosis was also observed., Conclusion: Autophagy suppression in MSCs ameliorates their liver regeneration potentials due to paracrine effects and might be suggested as a new strategy for the improvement of cell therapy in ALF.

Cell transplantation strategies have provided potential therapeutic approaches for treatment of neurodegenerative diseases. Mesenchymal stem cells from Wharton's jelly (WJMSCs) are abundant and available adult stem cells with low immunological incompatibility, which could be considered for cell replacement therapy in the future. However, MSC transplantation without any induction or support material causes poor control of cell viability and differentiation. In this study, we investigated the effect of the nanoscaffolds on WJMSCs differentiation into motor neuronal lineages in the presence of retinoic acid (RA) and sonic hedgehog (Shh). Surface properties of scaffolds have been shown to significantly influence cell behaviors such as adhesion, proliferation, and differentiation. Therefore, polycaprolactone (PCL) nanofibers were constructed via electrospinning, surface modified by plasma treatment, and grafted by collagen. Characterization of the scaffolds by means of ATR-FTIR, contact angel, and Bradford proved grafting of the collagen on the surface of the scaffolds. WJMSCs were seeded on nanofibrous and tissue culture plate (TCP) and viability of WJMSCs were measured by MTT assay and then induced to differentiate into motor neuron-like cells for 15 days. Differentiated cells were evaluated morphologically, and real-time PCR and immunocytochemistry methods were done to evaluate expression of motor neuron-like cell markers in mRNA and protein levels. Our results showed that obtained cells could express motor neuron biomarkers at both RNA and protein levels, but the survival and differentiation of WJMSCs into motor neuron-like cells on the PCL/collagen scaffold were higher than cultured cells in the TCP and PCL groups. Taken together, WJMSCs are an attractive stem cell source for inducing into motor neurons in vitro especially when grown on nanostructural scaffolds and PCL/collagen scaffolds can provide a suitable, three-dimensional situation for neuronal survival and differentiation that suggest their potential application towards nerve regeneration.

The most important property of stem cells from different sources is the capacity to differentiate into various cells and tissue types. However, problems including contamination, normal karyotype, and ethical issues cause many limitations in obtaining and using these cells from different sources. The cells in Wharton's jelly region of umbilical cord represent a pool source of primitive cells with properties of mesenchymal stem cells (MSCs). The aim of this study was to determine the potential of human Wharton's jelly-derived mesenchymal stem cells (WJMSCs) for differentiation to motor neuron cells. WJMSCs were induced to differentiate into motor neuron-like cells by using different signaling molecules and neurotrophic factors in vitro. Differentiated neurons were then characterized for expression of motor neuron markers including nestin, PAX6, NF-H, Islet 1, HB9, and choline acetyl transferase (ChAT) by quantitative reverse transcription PCR and immunocytochemistry. Our results showed that differentiated WJMSCs could significantly express motor neuron biomarkers in RNA and protein levels 15 d post induction. These results suggested that WJMSCs can differentiate to motor neuron-like cells and might provide a potential source in cell therapy for neurodegenerative disease.

Objective: In spite of accumulating information about pathological aspects of sulfur mustard (SM), the precise mechanism responsible for its effects is not well understood. Circulating microRNAs (miRNAs) are promising biomarkers for disease diagnosis and prognosis. Accurate normalization using appropriate reference genes, is a critical step in miRNA expression studies. In this study, we aimed to identify appropriate reference gene for microRNA quantification in serum samples of SM victims., Materials and Methods: In this case and control experimental study, using quantitative real-time polymerase chain reaction (qRT-PCR), we evaluated the suitability of a panel of small RNAs including SNORD38B, SNORD49A, U6, 5S rRNA, miR-423-3p, miR-191, miR-16 and miR-103 in sera of 28 SM-exposed veterans of Iran-Iraq war (1980-1988) and 15 matched control volunteers. Different statistical algorithms including geNorm, Normfinder, best-keeper and comparative delta-quantification cycle (Cq) method were employed to find the least variable reference gene., Results: miR-423-3p was identified as the most stably expressed reference gene, and miR- 103 and miR-16 ranked after that., Conclusion: We demonstrate that non-miRNA reference genes have the least stabil- ity in serum samples and that some house-keeping miRNAs may be used as more reliable reference genes for miRNAs in serum. In addition, using the geometric mean of two reference genes could increase the reliability of the normalizers.

Purpose: One of the advanced cancer therapy strategies is immune-stimulating compound based immunotherapy Staphylococcal enterotoxin B (SEB) is one of the potent superantigens, which can efficiently activate antitumor immune response to eradicate tumor growth and inhibit metastasis. Herein, we evaluated the effect of SEB on the expression of two master microRNAs, mir-335 and mir-10b, involved in metastasis., Methods: A metastatic breast cancer cell line MDA-MB231was treated with four different concentrations of SEB, including 10, 10(2), 10(3) and 10(4) ng/ml, for 24 and 48 hours. To identify the cytotoxic effect of SEB, treated cells were examined by MTT assay. The stem loop RT-PCR (TaqMan) was used to analyze the mir-335 and mir-10b expression., Results: RESULTS showed that SEB significantly increased the expression of mir-335 both after 24 and 48 hours (pv < 0.001 and pv < 0.05, respectively). No significant differences were found in the mir-10b expression., Conclusion: Moreover, our findings demonstrated no cytotoxic effect of SEB on the treated cells. Our results suggest that SEB probably induces its anti-metastatic effect via the expression regulation of the main genes which contributes to metastasis.

The aim of this study was to mimic the specific structure of bone and fabricate a biomimetic nano-hydroxyapatite (HA)/chitosan (Cs)/gelatin scaffolds using combination of particle leaching and freeze drying methods eliminating mold effects. To achieve an optimum structure, scaffolds with different gelatin/Cs weight ratio were fabricated. Morphological characterization of scaffolds by scanning electron microscopy method showed highly interconnected porous structures similar to cancellous bone with mean pore size ranging from 140 to 190 μm. Nano-HA crystals were dispersed homogeneously in the polymer matrix according to the energy-dispersive X-ray spectroscopy and transmission electron microscopy images. Fourier transform infrared and X-ray diffraction results disclosed that chemical interactions were formed between nano-HA, Cs, gelatin and crystallinity of each material decreased with blending. It was found that increasing the gelatin content significantly improved water uptake, degradation rate as well as attachment, infiltration and proliferation of Saos2 cells to the scaffolds. The presented results confirm that the designed biomimetic nano-HA /Cs/gelatin scaffolds can be used as promising substitutes for bone tissue engineering., (© 2014 Wiley Periodicals, Inc.)

Sulfur mustard (SM) is a blister-forming agent and can cause damages in various momentous human organs. Previous studies have demonstrated that chemical and mechanical injuries of epithelial cells cause to give rise the secretion of TGF-β1 and TGF-β2. These cytokines play a key role in respiratory remodeling due to SM. In this study, we investigated the impact of SM on the expression level of TGF-β isoforms and their receptors in vitro using reverse transcriptase polymerase chain reaction and western blotting. Our finding revealed the significant increase at concentrations of 25 μl/ml SM for 30 min and 60 min and also 100 μl/ml for 60 min for TGF-β1, 25, 50 and 100 μl/ml SM for 30 min for TGF-βr1 and after exposing with 100 μl/ml SM for both 30 and 60 min for TGF-β2 (p < 0.05). Data from western blotting showed the increase of TGF-β1 expression at the level of protein as the same pattern as the mRNA level. In vitro short-time exposure of fibroblast to SM can induce the expression of TGF-β1, TGF-β2 and TGF-βR1 denoting that over-expression of TGF-β isoforms and their receptors leads to differentiation and collagen production, causing in airway remodeling and fibrosis.

Sulfur mustard (SM) is a potent alkylating agent which reacts with nucleophilic groups on DNA, RNA and proteins. It is capable of inducing cellular toxicity and oxidative stress via production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The accumulation of high amounts of the reactive species causes harmful effects such as DNA damage, lipid peroxidation, protein oxidation, inflammation and apoptosis. Although SM (also known as mustard gas) and its derivatives are rapidly removed from the body, long-term damages are much more serious than the short-term effects and may be correlated with the subsequent changes occurred on the genome. In order to defend against oxidative properties of this toxic molecule, cells trigger several anti-oxidant pathways through up-regulating the corresponding genes. Enzymes like heme oxygenase-1, superoxide dismutase and glutathione-S-transferase are the examples of such genes. These enzymes produce anti-oxidant substances that are able to scavenge the reactive species, alleviate their noxious effects and protect the cells. Following SM gas exposure, gene transcription (mRNA levels) of these enzymes are ramped up to help detoxify the cells. Yet, some studies have reported that the up-regulated transcription does not necessarily translate into higher protein expression levels. The exact reason why this phenomenon happens is not clear. Creation of mutations in the genome sequence may lead to protein structure changes. Phosphorylation or other post-translational alterations of proteins upon SM exposure are also considered as possible causes. In addition, alterations in some microRNAs responsible for regulating post-translation events may inhibit the expression of the anti-oxidant proteins in the poisoned cells at translational level.

Aims: The present study aimed to compare the gene-expression profiling of CD133(+) and CD133(-) D10 cells., Materials & Methods: Cancer stem cell-like properties and gene-expression profiling of CD133(+) D10 cells versus CD133(-) cells were evaluated., Results: The CD133(+) D10 cells showed significantly higher clonogenic and spheroid forming potential, also higher expression of stemness genes NANOG and OCT4A compared with the CD133(-) cells. Gene-expression profiling of CD133(+) versus CD133(-) D10 cells revealed that 130 genes including ABC transporter superfamily (ABCC1, ABCG2 and ABCC6) were upregulated, while 61 genes including apoptosis modifying genes (CASP8 and TNFRSF4) were downregulated., Conclusion: We conclude that many genes involved in drug resistance and tumor aggressiveness are upregulated in CD133(+) D10 cells and targeting them might be an efficient strategy for treatment of melanoma.

There is much data about the acute effects of sulfur mustard gas on humans, animals and cells. But less is known regarding the molecular basics of chronic complications in humans. Basically, mustard gas, as an alkylating agent, causes several chronic problems in the eyes, skin and more importantly in the pulmonary system which is the main cause of death. Although recent proteomic research has been carried out on bronchoalveolar lavage (BAL) and serum, but high-throughput transcriptomics have not yet been applied to chronic airway remodeling. This is the first cDNA-microarray report on the chronic human mustard lung disease, 25 years after exposure during the Iran-Iraq war. Microarray transcriptional profiling indicated that a total of 122 genes were significantly dysregulated in tissues located in the airway of patients. These genes are associated with the extracellular matrix components, apoptosis, stress response, inflammation and mucus secretion.

Airway remodeling is a pathophysiologic process at the clinical, cellular, and molecular level relating to chronic obstructive airway diseases such as chronic obstructive pulmonary disease (COPD), asthma and mustard lung. These diseases are associated with the dysregulation of multiple molecular pathways in the airway cells. Little progress has so far been made in discovering the molecular causes of complex disease in a holistic systems manner. Therefore, pathway and network reconstruction is an essential part of a systems biology approach to solve this challenging problem. In this paper, multiple data sources were used to construct the molecular process of airway remodeling pathway in mustard lung as a model of airway disease. We first compiled a master list of genes that change with airway remodeling in the mustard lung disease and then reconstructed the pathway by generating and merging the protein-protein interaction and the gene regulatory networks. Experimental observations and literature mining were used to identify and validate the master list. The outcome of this paper can provide valuable information about closely related chronic obstructive airway diseases which are of great importance for biologists and their future research. Reconstructing the airway remodeling interactome provides a starting point and reference for the future experimental study of mustard lung, and further analysis and development of these maps will be critical to understanding airway diseases in patients.

Context: Sulfur mustard (SM) is an alkylating agent identified as a potent chemical warfare agent. More recently, SM was used in the Iraq conflict against Iranian troops and civilians. At present, there are many people suffering from chronic obstructive pulmonary disease (COPD) due to mustard gas in Iran. SM increases the endogenous production of reactive oxygen species (ROS). The oxidant/antioxidant imbalance present in the lungs of these patients also results from the impaired capacity of the antioxidant/detoxification enzymes to detoxify the harmful reactive oxygen metabolites., Objective: One of the major antioxidants in human airways is glutathione S-transferase. They facilitate the detoxification of various environmental of oxidative stress. In this study, we attempted to understand the significance different in expression of GSTs in airway wall of chemical patients and control., Materials and Methods: Seven normal and 20 SM induced COPD individuals were studied. Bronchoscopy was performed in all subjects and two specimens were taken from the main bronchus for mRNA extraction, PCR analysis and immunohistochemistry., Results: SM-induced COPD individuals showed expression of GSTA1 2.51 ± 0.83-, GSTM1 2.84 ± 1.71- and GSTP1 5.61 ± 2.59-folds higher than those of controls that revealed. GSTP1-immunoreactivity was strongly expressed in luminal border of normal samples. SM patient samples immunoreactivity for GSTP1 in the same area were negative., Discussion and Conclusion: According to these findings, we speculated that overexpression of GSTs mRNA in patients revealed that GSTs plays an important role in cellular protection against oxidative stress of MS in airway wall of patients.

Exosomes (EXO) are acellular vehicles used for cancer immunotherapy due to their immune inducing properties. To identify whether designed structure based on tumoral EXO have a cytotoxic effect together with a potent immunological property, we synthesized a novel structure based on EXO and staphylococcal entrotoxin B (SEB), two immune inducer substances, and surveyed its cytostatic effect on the breast cancer cell line. EXO were purified from tumor cells and SEB was anchored on it by protein transfer method. To determine the cytotoxic and apoptosis inducing effect of this structure, treated cells with different concentrations of EXO/SEB were examined by MTT assay and Hoechst staining method. In addition, the expression rate of bcl-2, bax, bak, fas, bcl-xl and the activity of caspase-3 and caspase-9 were assessed. We observed that EXO/SEB significantly decreased the cell proliferation and stimulated apoptosis (P < 0.001) at all concentration after 24 h (P < 0.001). Furthermore, EXO/SEB raised the expression rate of bax and bak (P < 0.001) but no impact on fas and bcl-xl after 48 h. We observed reducing effect of EXO/SEB on the mRNA expression of bcl-2. After 24 h of exposing the cell with the EXO/SEB, a significant increase was found in the activity of caspase at the concentration of 2.5, 5 and 10 μg/100 μl for caspase-9 and at all concentrations for caspase-3 (P < 0.001). Our designed structure, the EXO/SEB, is a novel model for apopto-immunotherapy being able to induce apoptosis in ER(-) breast cancer cells.

Peripheral nerves are exposed to physical injuries usually caused by trauma that may lead to a significant loss of sensory or motor functions and is considered as a serious health problem for societies today. This study was designed to develop a novel nano bioglass/gelatin conduit (BGGC) for the peripheral nerve regeneration. The bioglass nanoparticles were prepared by sol-gel technique and characterized using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction analysis. The interfacial bonding interaction between the nano-bioglass and gelatin in the developed conduits was assessed by FTIR. The surface morphology and pore size of the nanocomposite were investigated through scanning electron microscopy with the pore size of the conduits being 10-40 μm. Biocompatibility was assessed by MTT assay which indicated the BGGC to have good cytocompatibility. The guidance channel was examined and used to regenerate a 10 mm gap in the right sciatic nerve of a male Wistar rat. Twenty rats were randomly divided into two experimental groups, one with the BGGC and the other being normal rats. The gastrocnemius muscle contractility was also examined at one, two and three months post-surgery in all groups using electromyography (EMAP). Histological and functional evaluation and the results obtained from electromyography indicated that at three months, nerve regeneration of the BGGC group was statistically equivalent to the normal group (p > 0.05). Our result suggests that the BGGC can be a suitable candidate for peripheral nerve repair.

The prevalence of allergic diseases among infants is increasing particularly in developed countries. Although, the exact reason is not clear yet, one of the most probable explanations is reducing microbial exposure during early life and consequent alteration of gut microbiota. Various factors including delivery mode, infant`s diet, environment and antibiotics administration by mothers are involved in microbial colonization of infant`s intestine. Since the content of infant`gut microbiota plays a critical role in the maturation and development of the immune system, it determines the risk of immune diseases. Different studies confirmed the important role of vaginal delivery, due to transferring of useful bacteria to the neonatal's intestine, and breastfeeding, owing to the presence of exosomes and different kind of mediators in the milk which modify the pattern of intestinal microflora. As a result, it was proposed that both factors have remarkable effects on reducing allergic diseases. Furthermore, the consumption of probiotic productions by the mother during and after pregnancy possibly induces beneficial impacts on attenuating the allergic diseases.

Bioactive glass (BG) composites with a base of SiO2-Na2O-CaO-P2O5 are biocompatible biomaterials. The assessment of their abilities for medical applications has interested researchers. We produced a BG-containing SiO2-MgO-CaO-P2O5 by the sol-gel method. To determine the antibacterial effects, we analyzed the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) properties of this product on three microorganisms, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, known causative agents for biofilm formation on implant surfaces. In addition, we performed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to study the cytotoxic effects of our composite on animal cells. Our results demonstrated that our BG product inhibited the growth of bacteria in a concentration-dependent manner without any cytotoxic effects. Therefore, our BG product can be utilized as an appropriate implant for treating bone and tooth defects., (Copyright © 2012 Wiley Periodicals, Inc.)