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Collagen, a naturally occurring fibrous protein, is a potential resource of biological materials for tissue engineering and regenerative medicine because it is structurally biocompatible, has low immunogenicity, is biodegradable, and is biomimetic. Numerous studies have documented in the literature how Collagen nanofibers exhibit limited cell adhesion, poor viscosity, and no interior fibril structure. The biomedical industry is using Poly Glycerol Sebacate prepolymer(PGSp), a biodegradable and biocompatible polyester with high adhesion and very viscous appearance, more often. Here, unique electrospun Collagen/PGSp/ZnO/NPs blend nanofibers for skin tissue application were developed and described with varied PGSp percent. Additionally, when ternary blends of Collagen, PGSp, and Zink Oxide Nanoparticles (ZnO NPs) are used, the antibacterial properties of the scaffolds are improved. The bead-free electrospun nanofibers were produced by raising the PGSp concentration to 30%w/w. SEM, EDS, tensile, MTT, FTIR, SDS-page, swelling test, contact-angle, antimicrobial, biodegradation, XRD, and cell attachment procedures were used to characterize the crosslinked nanofibers. The ternary blend nanofibers with a weight ratio of Collagen/PGSp 30%/ZnONPs 1% had higher stress/strain strength (0.25 mm/mm), porosity (563), cell survival, and degradation time. Moreover, after applying for wound healing in diabetic rats, Collagen/PGSp 30%/could be show improving wound healing significantly compared to other groups.

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

Irisin is a myokine secreted mostly by muscles after exercise, and its secretion level changes in metabolic disorders. The aim of present study was to investigate the effect of metformin on changes in the levels of plasma irisin, blood glucose and insulin resistance in male Sprague-Dawley rats receiving a high-fat emulsion diet. Twenty-four rats were divided into a normal control group (n = 8) and a high-fat diet group (n = 16). Then, high-fat diet group was divided into two subgroups, including high-fat diet control group (n = 8) and metformin group (n = 8). The normal control group received a standard diet. The high-fat diet control group received a high-fat emulsion diet containing corn oil by gavage on a daily basis for six weeks, and the metformin group received a high-fat emulsion diet with metformin (250 mg/kg/daily). At the end of the six-week period, factors such as glucose, insulin, irisin, Adiponectin, insulin resistance, liver enzymes, tumor necrosis factor α (TNF-α), serum lipid profile, lipid profile and lipid peroxidation in liver were measured and PGC-1α gene expression were examined in adipose tissue by Real-time PCR method. Liver histological tests with hematoxylin-eosin staining were performed to evaluate fat accumulation in liver tissue. Blood glucose level, insulin resistance, adiponectin, serum irisin level and liver lipid profile in the group receiving high-fat diet compared to the normal control group increased significantly (P

Abstract Infection with human immunodeficiency virus (HIV)‐1 causes immunological disorders and death worldwide which needs to be further assisted by novel anti‐retroviral drug delivery systems. Consequently, finding newer anti‐retroviral pharmaceuticals by using biocompatible, biodegradable nanomaterials comprising a nanoparticle as core and a therapeutic agent is of high global interest. In this experiment, a second generation of a negatively charged nano‐biopolymer linear globular G2 dendrimer was carefully conjugated and loaded with well‐known anti‐HIV drugs lamivudine and efavirenz, respectively. They were characterised by a variety of analytical methods such as Zetasizer, Fourier‐transform infrared spectroscopy, elemental analysis and liquid chromatography‐mass spectroscopy. Additionally, conjugated lamivudine and loaded efazirenz with globular PEGylated G2 dendrimer were tested on an HEK293 T cell infected by single‐cycle replicable HIV‐1 virion and evaluated using XTT test and HIV‐1 P24 protein load. The results showed that lamivudine‐conjugated G2 significantly decreased retroviral activity without any cell toxicity. This effect was more or less observed by efavirenz‐loaded G2. These nano‐constructs are strongly suggested for further in vivo anti‐HIV assays.

Objective: Numerous evidence indicates that microRNAs (miRNAs) are critical regulators in the spermatogenesis process. The aim of this study was to investigate Mir-106b cluster regulates primordial germ cells (PGCs) differentiation from human mesenchymal stem cells (MSCs). Materials and Methods: In this experimental study, samples containing male adipose (n: 9 samples- age: 25-40 years) were obtained from cosmetic surgeries performed for the liposuction in Imam Khomeini Hospital. The differentiation of MSCs into PGCs was accomplished by transfection of a lentivector expressing miR-106b. The transfection of miR- 106b was also confirmed by the detection of a clear green fluorescent protein (GFP) signal in MSCs. MSCs were treated with bone morphogenic factor 4 (BMP4) protein, as a putative inducer of PGCs differentiation, to induce the differentiation of MSCs into PGCs (positive control). After 4 days of transfection, the expression of miR-106b, STELLA, and FRAGILIS genes was evaluated by real-time polymerase chain reaction (PCR). Also, the levels of thymocyte differentiation antigen 1 (Thy1) protein was assessed by the western blot analysis. The cell surface expression of CD90 was also determined by immunocytochemistry method. The cytotoxicity of miR-106b was examined in MSCs after 24, 48, and 72 hours using the MTT assay. Results: MSCs treated with BMP4 or transfected by miR-106b were successfully differentiated into PGCs. The results of this study also showed that the expression of miR-106b was significantly increased after 48 hours from transfection. Also, we showed STELLA, FARGILIS, as well as the protein expression of Thy1, was significantly higher in MSCs transfected by lentivector expressing miR-106b in comparison with MSCs treated with BMP4 (P≤0.05). MTT assay showed miR-106b was no toxic during 72 hours in 1 μg/ml dose, that this amount could elevated germ cells marker significantly higher than other experimental groups (P≤0.05). Conclusion: According to this findings, it appears that miR-106b plays an essential role in the differentiation of MSCs into PGCs.

Résumé Contexte La ferroptose est une mort cellulaire dépendante du fer qui est distincte de l’apoptose. Sur la base de quantités excessives de fer et d’espèces réactives de l’oxygène chez les rats varicocèles (VCL), nous avons fait l’hypothèse que la ferroptose pourrait être impliquée dans la VCL. Comme l’acide alpha-lipoïque (ALA) s’est avéré avoir des activités antioxydante et anti-ferroptotique nous avons dans ce travail testé le statut ferroptose dans notre modèle de rats VCL et évalué l’effet protecteur de ALA. Dans ce but, 70 rats mâles Wistar ont été divisés en plusieurs groupes: témoin, fictif et groupes varicocèle qui ont été initialement sacrifiés deux mois après l’opération pour vérifier l’induction de la varicocèle. Un deuxième lot des 3 mêmes groupes a été sacrifié 4 mois après l’induction de la varicocèle pour évaluer l’effet de la supplémentation en ALA. Les paramètres mesurés étaient l’intégrité de la chromatine (via les tests au bleu d’aniline et à l’orange acridine), la peroxydation lipidique (via le test BODIPY), la morphométrie testiculaire et la teneur en fer. De plus, les marqueurs redox (GSH et NADPH) et ferroptotique (Nrf2, Slc7a11, P53 et p-Jnk) ont été évalués 2 et 4 mois après l’opération. Résultats L’altération des paramètres spermatiques a permis de vérifier l’induction de la VCL. Le fer s’est bien accumulé dans les testicules pendant la VCL et a diminué de manière significative après le traitement ALA. Les marqueurs moléculaires ferroptotiques n’ont pas été modifiés de manière significative que ce soit en quantité d’ARNm et de protéines. La supplémentation en ALA n’a pas modifié la teneur en NADPH, mais a augmenté les niveaux de GSH. Conclusions Malgré l’accumulation accrue de fer dans les testicules 2 et 4 mois après l’induction chirurgicale de la VCL, les investigations au niveau moléculaire n’ont pas clairement démontré l’implication de la ferroptose. Cela pourrait s’expliquer par la nature mosaïque de la VCL qui affecte certains tubules séminifères et pas d’autres, ce qui pourrait atténuer les évaluations réalisées sur organe entier. En parallèle, notre étude confirme que l’ALA stimule la voie NRF2 stimulant la réponse anti-oxydante.

Objective: The aim of the present study was to evaluate the effects of lysophosphatidic acid (LPA) supplementation of human ovarian tissue culture media on tissue survival, follicular development and expression of apoptotic genes following xenotransplantation. Materials and Methods: In this experimental study, human ovarian tissue was collected from eight normal female to male transsexual individuals and cut into small fragments. These fragments were vitrified-warmed and cultured for 24 hours in the presence or absence of LPA, then xenografted into back muscles of γ-irradiated mice. Two weeks post-transplantation the morphology of the recovered tissues were evaluated by hematoxylin and eosin staining. The expression of genes related to apoptosis (BAX and BCL2) were analyzed by real time revers transcription polymerase chain reaction (RT-PCR) and detection of BAX protein was done by immunohistochemical staining. Results: The percent of normal and growing follicles were significantly increased in both grafted groups in comparison to the non-grafted groups, however, these rates were higher in the LPA-treated group than the non-treated group (P

Background: One of the important factor associated with male infertility is high production of reactive oxygen species(ROS). The main function of Nuclear factor erythroid 2-related factor 2 (NRF 2) is to activate the cellular antioxidantresponse by inducing the transcription of a wide array of genes that can combat the harmful effects of factorssuch as oxidative stress. The purpose of this study was to evaluate the effect of N-acetyl-L-cysteine (NAC), as anantioxidant drug, on NRF 2 Gene Expression in Asthenoteratozoospermia Men.Materials and Methods: In this randomized, blinded clinical trial study, included 50 infertile men with asthenoteratozoospermia,who received NAC (600 mg, three times daily). Sperm parameters analyzed according to the world health organization(WHO; 2010). Sperm DNA fragmentation, relative NRF 2 expression, and seminal plasma level of antioxidant enzymeswere measured by TUNEL assay, reverse transcription polymerase chain reaction (RT-PCR) and ELISA test, respectively.Results: After NAC treatment, findings showed a significant increase in sperm concentration and motility comparedto pre-treatment status, whereas the percentage of abnormal morphology and DNA fragmentation was significantlydecreased (p

Objective The embryonic cerebrospinal fluid (e-CSF) contains various growth factors and morphogens. Recent studies showed that e-CSF plays significant roles in embryonic brain development. Adipose tissue-derived stem cells (ADSCs) have a mesodermal origin that can be differentiated into mesodermal and ectodermal lineages. This study aimed to evaluate the effects of e-CSF on the proliferation, viability, and neural differentiation of ADSCs in rats. Materials And Methods In this experimental study, adipose tissue was dissected out from the inguinal region of adult male rats. Then, ADSCs were isolated by enzymatic digestion from adipose tissues and mesenchymal cells were confirmed using the flow cytometry analysis that measured the cell surface markers including CD90, CD44, CD73, CD105, CD34, CD45, and CD11b. The multi-potential characteristics of ADSCs were assessed by osteogenic and adipogenic potentials of these cells. Under suitable in vitro conditions, ADSCs were cultured in DMEM supplemented with and without additional 10% e-CSF. These fluids were collected from Wistar rats at the E17, E18, and E19 gestational ages. Cellular proliferation and viability were determined using the MTT assay. Immunocytochemistry was used to study the expression of β-III tubulin in ADSCs. The neurite outgrowth of cultured cells was assessed using the ImageJ software. Results The results of the present study demonstrated that the viability of ADSCs in cell culture conditioned with E17 and E18 e-CSF were significantly increased in comparison with controls. Cultured cells treated with e-CSF from E18 and E19 established neuronal-like cells bearing long process, whereas no process was observed in the control groups or cultured cells treated with E17 e-CSF. Conclusion This study showed that e-CSF has the ability to induce neuronal differentiation and viability in ADSCs. Our data support a significant role of e-CSF as a therapeutic strategy for the treatment of neurodegenerative diseases.

Objective(s): Breast cancer is a devastating disease related to women. The anticancer properties of 8-hydroxyquinoline (8HQ) and the increasing use of graphene oxide (GO), as a drug delivery system with anti-cancerous properties, led us to investigate the toxicity and apoptosis-induction capability of 8HQ-coated GO on breast cancer cells compared with normal breast cells.Materials and Methods: Breast cancer (MCF-7) and normal breast (MCF-10) cell lines were treated with several doses of 8-HQ-coated GO for 12, 24, and 48 hr. The toxicity of the nanocomposite was measured using MTT assay and the effect of the nanocomposite on cell apoptosis was determined by examining the expression of P53, P21, Bax, and BCL2 genes, as well as Annexin-V /PI apoptosis assay.Results: There were significantly increased cell deaths in nanocomposite-treated MCF-7 breast cancer cells, compared with treated normal breast cells. Significantly increased expression of P53, P21, and Bax genes and reduced expression of BCL2 gene were found in the treated breast cancer cell line compared with the normal cell line. Annexin-V/PI assay also illustrated significant induction of apoptosis in MCF-7 following nanocomposite treatment.Conclusion: Overall, 8HQ-coated GO has toxicity for breast cancer cell lines and one of the mechanisms through which this nanocomposite can induce cell death is the induction of apoptosis. With complementary in vitro and in vivo studies, this nanocomposite can be suggested as a nano-drug with anti-cancer properties.

Introduction: Transforming growth factor-beta (TGF-β) is known as standard chondrogenic differentiation agent, even though it comes with undesirable side effects such as early hypertrophic maturation, mineralization, and secretion of inflammatory/angiogenic factors. On the other hand, platelet-rich plasma (PRP) is found to have a chondrogenic impact on mesenchymal stem cell proliferation and differentiation, with no considerable side effects. Therefore, we compared chondrogenic impact of TGF-β and PRP on adipose-derived stem cells (ADSCs), to see if PRP could be introduced as an alternative to TGF-β. Methods: Differentiation of ADSCs was monitored using a couple of methods including glycosaminoglycan production, miRNAs expression, vascular endothelial growth factor (VEGF)/tumor necrosis factor alpha (TNFα) secretion, alkaline phosphatase (ALP) and calcium content assays. Results: Accordingly, the treatment of differentiating cells with 5% (v/v) PRP resulted in higher glycosaminoglycan production, enhanced SOX9 transcription, and lowered TNFα and VEGF secretion compared to the control and TGF-β groups. Besides, the application of PRP to the media up-regulated miR-146a and miR-199a in early and late stages of chondrogenesis, respectively. Conclusion: PRP induces in vitro chondrogenesis, as well as TGF-β with lesser inflammatory and hypertrophic side effects.

Abstract Background Infertile men have higher levels of semen reactive oxygen species (ROS) than fertile men. High levels of semen ROS can cause sperm dysfunction, sperm DNA damage and reduced male reproductive potential. This study investigated the effects of supplementation with N-acetyl-cysteine (NAC) on the sperm quality, chromatin integrity and levels of oxidative stress in infertile men. Methods The study was carried out in the unit of ACECR Infertility Research Center, Qom, Iran. The patients consisted of 50 infertile men with asthenoteratozoospermia who received NAC (600 mg/d) orally for 3 months, after which they were compared with pre-treatment status. Semen was analyzed according to WHO (2010), followed by the assessment of protamine content [chromomycin A3 (CMA3)] and DNA integrity [terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)]. Oxidative stress markers, i.e. total antioxidant capacity (TAC) and malondialdehyde (MDA), as well as hormonal profile (LH, FSH, Testosterone and Prolactin) were determined by ELISA kit. Results After NAC treatment, patients’ sperm count and motility increased significantly whereas abnormal morphology, DNA fragmentation and protamine deficiency showed significant decreases compared to pre-treatment levels (P

Background: Iron oxide nanoparticles are commonly used for various purposes, such as biomedical, medical, and cosmetic services and research. However, there is a little information about the effects of the nanoparticles on human health. The current investigation was conducted to evaluate the adverse effects of iron oxide nanoparticles (FeNP) on the reproductive organs of mice, such as the testicular tissue and sperm cells. Methods: Twenty-eight male NMRI mice were randomly divided in four groups (N=7). The control group received only a regular diet. The experimental groups were administered FeNP in doses of 50, 150 and 300 mg/Kg intraperitoneally (IP), over four days. Epididymal sperm parameters, such as sperm number and motility were assessed by computer-assisted sperm analysis (CASA). Stereological analysis was also conducted on the histological sections. Results: The results demonstrated that FeNP (300 mg/Kg/day) caused a significant decrease in the sperm parameters, such as motility, spermatogonia, primary spermatocytes, spermatid, Sertoli, Leydig cells, total length of seminiferous tubules, and testicular interstitial tissue volumes. Conclusion: In summary, FeNP affected several reproductive tissue and cellular parameters at the administered dosage. Further research is required to examine the mechanism of action of FeNP the mice reproductive system.

Objective(s): Bacterial cellulose (BC) has applications in medical science, it is easily synthesized, economic and purer compared to plant cellulose. The present study aimed to evaluate BC, a biocompatible natural polymer, as a scaffold for the bone marrow mesenchymal stem cells (BMSCs) loaded with fisetin, a phytoestrogen.Materials and Methods: BC hydrogel scaffold was prepared from Gluconaceter xylinus and characterized through scanning electron microscopy (SEM). Biocompatibility of BC was measured by MTT assay, BMSCs were obtained from femur of rat and the osteogenic potential of the BC scaffold cultured with BMSCs and loaded with fisetin, was investigated by measuring the alkaline phosphatase (ALP) activity, alizarin red staining (ARS) and real-time PCR in terms of osteoblast-specific marker, osteocalcin (OCN) and osteopontin (OPN). Results: Biocompatibility results did not show any toxic effects of BC scaffold on BMSCs, while it increased cell viability. The data showed that BC loaded fisetin differentiated BMSCs into osteoblasts as demonstrated by ALP activity assays and ARS in vitro. Moreover, results from gene expression assay showed the expression of OCN and OPN genes was increased in cells that were seeded on the BC scaffold loaded with fisetin.Conclusion: According to the results of the present study, BC loaded with fisetin is an effective strategy to promote osteogenic differentiation and a proper localized delivery system, which could be a potential candidate in bone tissue engineering.

Background DNA methylation is one the epigenetic mechanisms, which is critically involved in gene expression. This phenomenon is mediated by DNA methyl-transferases and is affected by environmental stress, including in vitro maturation (IVM) of oocytes. Melatonin, as an antioxidant, may theoretically be involved in epigenetic regulation via reductions of reactive oxygen species. This study was performed to investigate DNA methylation and the possibility of goat oocyte development after treatment with different concentrations of melatonin. Materials and Methods This experimental study was performed to investigate DNA methylation and the possibility of goat oocyte development after treatment with different concentrations of melatonin. For this purpose, oocytes with granulated cytoplasm were selected and co-cultured with at least two layers of cumulus cells in maturation medium with 10-6M, 10-9M, 10-12M and 0-M (as control group) of melatonin. Nucleus status, glutathione content and devel- opmental competence of the oocytes in each experimental group were assessed. Also, expression of genes associated with DNA methylation, including DNA methyltransferase 1 (DNMT1), DNA methyltransferase 3b (DNMT3b) and DNA methyltransferase 3a (DNMT3a) was evaluated by quantitative real time-polymerase chain reaction (RT-PCR). Results According to our findings, the percentage of oocytes that reached the M-II stage significantly increased in the 10-12 M group (P < 0.05). Also, a significant elevation of glutathione content was observed in melatonin-treated oocytes (P < 0.05). Analysis of blastocyst formation revealed that developmental competence of the oocytes was higher than the control group (P < 0.05). It was observed that melatonin treatment decreased expression levels of DNA meth- yltransferases (DNMTs) and global DNA methylation (P < 0.05). In addition, the expression of melatonin receptor1A (MTNR1A) was detected in both cumulus and oocyte by RT-PCR. Conclusion The results suggested that in goat model melatonin affects DNA methylation pattern, leading to an im- provement in the developmental competence of the oocytes.

Background Saffron (Crocus sativus L.) has been traditionally used as a spice for coloring and flavoring in some countries cuisine. One of the main components of saffron is Crocin. Recent research have shown that crocin has various pharmacological effects. The aim of this study was to assess the effects of crocin on the Pituitary-Gonadal axis and Kiss-1 gene expression in hypothalamus and ovarian tissue organization in female Wistar rats. Materials and Methods In this experimental study, 18 adult female Wistar rats were randomly divided into three groups. Control group received normal saline and experimental groups received two different doses of crocin (100 and 200 mg/kg) every two days for 30 days. After the treatment period, blood samples were obtained from the heart and centrifuged. Next, the serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), estrogen and progesterone hormones were measured by ELISA assay. The ovarian tissues were removed and fixed for histological investigation. The hypothalamic Kiss-1 gene expression was measured using real-time polymerase chain reaction (PCR). All data were analyzed using one-way ANOVA. Results A significant reduction (P=0.038) in the number of atretic graafian follicles (0.5 ± 0.31) was observed in rats treated with 200 mg/kg crocin. In addition, estrogen concentration in experimental groups (35.04 ± 0.85 and 36.18 ± 0.69 in crocin 100 and 200 mg/kg groups, respectively) compared to control group (38.35 ± 0.64) and progesterone concentration in rats treated with crocin 200 mg/kg (2.06 ± 0.07) compared to control group (2.16 ± 0.04), significantly decreased. Interestingly, relative expressions of Kiss-1 mRNA significantly decreased in experimental groups (0.00053 ± 0.00051 and 0.0011 ± 0.00066 in crocin 100 and 200 mg/kg groups, respectively) (P=0.000) compared to control group (1 ± 0). Conclusion Crocin, at hypothalamic level, reduces Kiss-1 gene expression and it can prevent follicular atresia and reduce serum levels of estrogen and progesterone.

Introdution: One of the major challengs in ovarian tissue transplantation is overcomeing ischemia/ reperfusion injuries. During ischemia–reperfusion processes, oxygen free radicals constitute the most important component that induces damage of the grafted tissues. The aim of this study was to investigate the effect of L-Carnitine (LC) as an antioxidant on heterotopic transplantation of mouse ovarian tissue. Methods: In this laboratory experimental study, 5- week old female NMRI mice were divided into four groups: control, transplanted without administration (autograft), sham group (autograft+ saline) and LC group (autograft+ L- carnitine). Left ovarian tissues were transplanted into the Gluteal muscle for 3 weeks. After this time, ovarian tissues from all groups were removed and fixed in formalin for histological studies. Furthermore, rate of Caspase- 3 was assessed by immunohistochemistry test. Lipid peroxidation was assessed by measuring malondialdehyde (MDA). One-way ANOVA and Tudey test was used to analyze the data using the spss 16 software. Significance was defined as P≤0.0. Results: The study results indicated that total follicular count in transplantedwithout administration and sham groups was significantly lower than the control group (p

Of different types of bio-compatible nano‌particles, iron oxide nanoparticle has attracted attention for its applications especially in medicine and magnetic resonance imaging (MRI). We decided to study histological changes in testis and spermatogenesis in mature male mice that are affected by ironoxide nanoparticles (Fe2O3) during fetal period. In this study, the mice were divided into three experimental and two control and sham groups. Iron oxide at do-ses of 10, 30, 50 mg/kg were injected into pregnant mice during 10th, 12th and 14th days of the critical period of fetus testis development. After the maturation of the mice which were born, slices with the thickness of 0.06 µm were prep-ared from adult male testis and epididymis, stained with hematoxylin and eosin. The cells were counted, then the obta-ined data was analyzed with one-way ANONA and Tukey testes. The results showed that the number of epididymis sp-erms at the doses of 10 and 30 mg/kg, testis weight at the dose of 30 mg/kg, primary spermatocytes at the dose 10mg/kg had increased, while the testis diameter in all the three experimental groups and the volume of the testis at the dose of 50 mg/kg had decreased. Disorganization and vacuolization were observed at high doses. Passing through the cell me-mbrane, and considering its oxidation and reduction potentials, it was observed that Iron oxide nanoparticle acts as anti-oxidant at low doses and shows toxicity at high doses. The fact obtained in the paper reflects the dual potential of the ir-on oxide nanoparticle.

Background and purpose: Glycyrrhiza glabra is a perennial plant with some major food and medicinal compounds that has received attention by food and pharmaceutical industries. The aim of this study was to investigate the effect of licorice on in vitro maturation of immature oocytes on NMRI mice. Materials and methods: In this experimental study, the animals were randomly divided into five groups: a control, a sham and three experimental groups. The mice were injected intraperitoneally with 7.5 IU PMSG to stimulate ovulation. The control group, received only water and food. The sham animals were gavaged with 200 ml of distilled water for 7 days. The three experimental groups were given daily injection of 100, 200, and 500 μL licorice by oral gavage for 7 days. The mice were sacrificed on day 8, the ovaries were then removed and investigated for oocytes reaching metaphase II (MII) within 24 hours. The oocytes were fertilized by the sperm of male mice and investigated after 24 and 48 hours after in vitro fertilization (IVF). Results: Compared with the control group, consumption of licorice extract in experimental groups (II and III) was found to have a positive effect on the number of follicles, oocytes, and number of 2 and 4 cell embryos. Conclusion: This study showed the beneficial effects of licorice extract due to its Phyto-estrogenic properties on oocyte maturation and infertility.

Background Polycystic ovary syndrome (PCOS) is a common but complex endocrine disorder and is the major cause of anovulation and consequent subfertility. In this study the effect of grape seed extract (GSE) on triglyceride (TG), total cholesterol (TC), highdensity lipoprotein-cholestrol (HDL-C), low-density lipoprotein-cholestrol (LDL-C) and interleukin-6 (IL-6) in PCOS Wistar rats were assessed. Materials and Methods In this experimental study, 84 adult female Wistar rats were divided into 7 groups (n=12) including control (intact), Sham (estradiol valerate solvent injection), control PCOS and 4 experimental PCOS groups. To induce the syndrome, a single subcutaneous injection of 2 mg estradiol valerate was applied. In experimental groups, PCOS rats were treated with different doses of 50, 75, 100 and 200 mg/kg body weight (BW) GSE by intraperitoneal injection for 10 consecutive days. After harvesting blood serum, TG was measured by Glycerol-3-phosphate Oxidase-Peoxidase (GPO- PAP), TC by Cholesterol Oxidase-Peroxidase (CHOD-PAP), and HDL-C by sedimentation method, LDL-C by Friedwald calculation and IL-6 by ELISA method. The serum values of each parameter were analyzed using one-way ANOVA at P≤0.05. Results In all experimental groups significant decrease of visceral fat was obvious as compared with control PCOS group. LDL-C, TC and IL-6 levels in experimental groups, particularly at dose of 50 mg/kg of GSE, were significantly decreased as compared with PCOS group. However, HDL-C levels were not significantly changed. Conclusion : According to the findings of this study, it can be concluded that GSE with its effects on serum TC, LDL-C and IL-6 could reduce the effects of dyslipidemia and inflammation in PCOS rats and improve systemic symptoms of PCOS.

Nowadays, with the applications of titanium dioxide nanoparticles (TiO2-NPs) in pharmacy, food industry, cosmetics, toothpaste and sunscreens, pregnant women are exposed to nanoparticles. Since tooth development is vuln-erable to environmental impacts and mandibular first molar bud develops before maxillary first molar bud, in this ex-perimental study the effects of TiO2-NPs on the development of first mandibular molar bud in NMRI mouse was inve-stigated. Twenty five female NMRI mice were randomly divided into five groups (N=5); Control group (pregnant mice without any treatment), sham group (treated with distilled water), experimental groups 1, 2 and 3 (treated with 50, 150 and 500 mg/kg BW TiO2-NPs, respectively, via gavage from embryonic days 10.5-14.5). On E14.5, embryos heads were prepared for histological examination and dental tissues were evaluated. Data were analyzed by ANOVA and post hoc test (Tukey). Microscopic observation showed tissue disorganization in experimental groups. Findings showed that in experimental groups 1 and 2, the diameter of bud and dental papilla and the length of dental bud decreased sign-ificantly. In experimental group 2, decrease in the diameter of dental follicle, dental bud and dental papilla and the le-ngth of dental bud was significant. On the other hand, in experimental group 3, only the decrease in the length of dental bud was significant. These findings showed that nano titanium dioxide can reduce the size of dental buds and is capable of preventing tooth development.

Background & aim: Liraglutide has used for treatment of obesity and type 2 diabetes, which are main factors of infertility. Regarding that, uterus as the most important organ reproductive system is under vulnerable, particularly by chemical drugs, in this research the effects of Liraglutide on uterine tissue changes and Estradiol and FSH hormones in NMRI mice in In vivo condition has been investigated. Methods: This experimental study has been done on 28 adult female NMRI mice (8 to 12 weeks) that have been selected with body weight between 25 and 30 grams. Female mice were randomly divided into four groups (including 7 mice): control, sham and two experimental groups. Control mice received no treatment, experimental and sham groups were injected Liraglutide with 0.6 and 1.8 mg/kg density and solution for 30 days respectively. All injection were daily and subcutaneously. After 30 days injection, the mice were deeply anesthetized and in addition to blood sampling, mice’s uterus was removed and the one-third of right middle part of the uterus has been investigated as tissue studies. Following histochemical staining, the samples were studied using light and transmission electron microcopies. The collected data were analyzed using one-way analyses (ANOVA) and Tukey test. Results: The results of using Liraglutide has been shown mice’s weight of experimental groups (1 and 2), compared with sham and control groups, have marked decrease (p

Chemical pesticides possess toxic and destructive impacts on the reproductive system and disrupt endocrine function. In this experimental study, the effect of movento, as a chemical pesticide, was investigated in comparison with chitosan, a biological pesticide, on the female reproductive system in vivo. In this study, 56 mice were randomly dived into 7 groups including control and experimental groups treated with movento and chitosan. After a 21-day treatment, mice were killed and their ovaries and blood being collected. In addition, the samples were fixed and stained with H & E method. The results exhibited that treatment with 2.5 and 5 mg/kg chitosan had no significant effect on the number and diameter of primary, secondary and antral follicles, while these items were significantly reduced in 10 mg/kg ch-itosan group and all movento-treated groups as well. In addition, the level of sexual hormones, such as estradiol, FSH and LH, was decreased in 10 mg/kg chitosan group and all movento-treated groups in comparison with the control gr-oup. The findings showed that movento affected the sexual hormone levels, ovary and ovarian follicle structure and in-duced abnormality in female reproductive system, while chitosan, as a biological pesticide, should be used due to its minimum effects on female reproductive system

Objective(s): Pesticides has wide range of infertility in female reproductive. This study was done to evaluate the effect of movento pesticide on development of granulosa cells and ovarian follicles and FoxO1 and Vnn1 gene expression in BALB/c mice. Materials and Methods: In this study 40 healthy BALB/c mice 5-6 weeks age were used. Animals were randomly allocated into four groups. Control (without any intervention), three experimental groups received 25, 50 and 100 mg/kg movento dissolved in PBS by gavage for 21 days. Animals scarified after three weeks. For determining the effects of movento on granulosa cells in culture, treatments were conducted to movento (125, 250, 500 μg/ml) for 24 hr. We surveyed the expression of the FoxO1 and Vnn1 in granulosa cells in vitro, and its relation to cell death by flowcytometer and DAPI. Levels of FoxO1 and Vnn1 were analyzed by real-time PCR. Results: Exposure to movento significantly decreased ovarian weight and the number of primary, secondary and antral follicles. Further, treatment with different concentration of movento induced apoptosis on granulosa cells. Gene expression analysis showed the transcriptional expression of FoxO1 and vnn1 in granulosa cells. Level of Vnn1 mRNA in granulosa cells was decreased in granulosa cells and expression of FoxO1 significantly increased in treated groups in compare to controls (P-value

Silencing of gene expression by siRNA (small interfering RNA) is a powerful approach used to study the genetic analysis and functional roles of mammalian genes. There is at present no report about the effects of mammalian two-hybrid system plasmids delivery of sense and antisense strands. The leishmania pteridine reductase 1 (PTR1) gene was cloned as sense and antisense strands into mammalian two hybrid system plasmids. The constructs were transfected into human blood macrophages on the basis of eight experimental groups. (Antisense strand ± LPS, sense strand ± LPS, dsRNA ± LPS, negative control ± LPS). After 24 hours, cytokines production was assessed with ELISA. Transfection of sense and antisense strand RNA into monocyte-derived macrophages (MDM) was confirmed by RT-PCR. Single strands RNA expressed IL-8, IL-12, IL-1β inflammatory cytokines and dsRNA induced IL-8, IL-12 and TNF-α production in MDM. In contrast, random uptake from a mixture of two plasmids was downregulated IL-8, IL-12, IFN-γ cytokines, with a significant difference of p

Objective: The label and detection of cells injected into target tissues is an area of focus for researchers. Iron oxide nanoparticles can be used to label cells as they have special characteristics. The purpose of this study is to examine the effects of iron oxide nanoparticles on human-derived amniotic membrane stem cell (hAMCs) survival and to investigate the magnetic properties of these nanoparticles with increased contrast in magnetic resonance imaging (MRI). Materials and Methods: In this experimental study, we initially isolated mesenchymal stem cells from amniotic membranes and analyzed them by flow cytometry. In addition, we synthesized superparamagnetic iron oxide nanoparticles (SPIONs) and characterized them by various methods. The SPIONs were incubated with hAMCs at concentrations of 25-800 μg/mL. The cytotoxicity of nanoparticles on hAMCs was measured by the MTT assay. Next, we evaluated the effectiveness of the magnetic nanoparticles as MRI contrast agents. Solutions of SPION were prepared in water at different iron concentrations for relaxivity measurements by a 1.5 Tesla clinical MRI instrument. Results: The isolated cells showed an adherent spindle shaped morphology. Polyethylene glycol (PEG)-coated SPIONs exhibited a spherical morphology. The average particle size was 20 nm and magnetic saturation was 60 emu/g. Data analysis showed no significant reduction in the percentage of viable cells (97.86 ± 0.41%) after 72 hours at the 125 μg/ml concentration compared with the control. The relaxometry results of this SPION showed a transverse relaxivity of 6.966 (μg/ml.s)-1 Conclusion: SPIONs coated with PEG used in this study at suitable concentrations had excellent labeling efficiency and biocompatibility for hAMCs.

Background and Aim: Iron oxide nanoparticles are used in fields related to nanotechnology including ecology, magnetic storage, imaging and medicinal purposes. Iron nanoparticles produce reactive oxygen species (Ros). These materials are able to cross the placenta. The aim of this study was to investigate toxic effect of iron oxide nanoparticles on fetal lung in mice. Methods: In this study, at day 14 of pregnancy, fetal lungs were removed and transferred to the Cell culture medium. The lungs were divided into 5 groups, including control, sham and experimental groups of 1, 2 and 3 (received respectively 10, 30 and 50 mg/kg nano iron oxide) and then they were incubated for 24 hours. For histopathological evaluation, lung tissues were stained with Hematoxylin-Eosin and the results were evaluated. Results: Mean number of bronchioles and the diameter of blood vessels in exprimental groups showed no significant difference compared with control and sham groups. Mean number of blood vessels in experimental groups 1 and 2 showed no significant difference compared to control and sham groups, while in the experimental group 3, mean number of blood vessels showed significant decrease compared to sham and control groups (p

The underlying mechanisms of how nicotine affects cord umbilical cells remain largely elusive. Nicotine rapidly crosses the blood-brain barrier (10 to 20 s) and binds to nicotinic acetylcholine receptors (nAChRs). Nicotine considered as a major compound found in cigarette smoke and the mechanism of nicotine action in immune response is not well understood. Cigarette smoke well known by activation of toll like receptors (TLRs) especially TLR4 and 9 which stimulates the immune response by induction of releases of cytokines mainly CXCL-8 which in turn triggers lungs reactions specially induction of neutrophils recruitments. In this study we isolated human umbilical mononuclear cells (UCBMC) from umbilical cord blood and exposed to the nicotine for detection any cytokines and TLRs modulation. We have found that nicotine (at concentration 0.01µM) induced release of TNF-a and IL-6 but not CXCL-8 production. Besides we have shown that nicotine did not effect on TLR4 surface expression however up-regulated the TLR2 surface expression. Moreover expression of CD11a and CXCR4 after nicotine incubation was upregulated as demonstrated by flow cytometry analysis, These data indicated that nicotine by stimulation of inflammatory cytokines induces immune response. The present study provides evidence that nicotine selectively regulates the release of cytokines and expression of TLRs. Further studies are needed to exploring details of its effects and signaling.

Background Quantum dots (QDs) are new types of fluorescent materials for biological labeling. QDs toxicity study is an essential requirement for future clinical applications. Therefore, this study aimed to evaluate cytotoxic effects of CdSe: ZnS QDs on male reproductive system. Materials and Methods In this experimental study, the different concentrations of CdSe: ZnS QDs (10, 20 and 40 mg/kg) were injected to 32 male mice (adult group) and 24 pregnant mice (embryo group) on day 8 of gestation. The histological changes of testis and epididymis were studied by a light microscopy, and the number of seminiferous tubules between two groups was compared. One-way analysis of variance (one-way Anova) using the Statistical Package for the Social Sciences (SPSS, SPSS Inc., USA) version 16 were performed for statistical analysis. Results In adult group, histological studies of testis tissues showed a high toxicity of CdSe: ZnS in 40 mg/kg dose followed by a decrease in lamina propria; destruction in interstitial tissue; deformation of seminiferous tubules; and a reduction in number of spermatogonia, spermatocytes, and spermatids. However, there was an interesting result in fetal testis development, meaning there was no significant effect on morphology and structure of the seminiferous tubules and number of sperm stem cells. Also histological study of epididymis tissues in both groups (adult and embryo groups) showed no significant effect on morphology and structure of tubule and epithelial cells, but there was a considerable reduction in number of spermatozoa in the lumen of the epididymal duct in 40 mg/kg dose of adult group. Conclusion The toxicity of QDs on testicular tissue of the mice embryo and adult are different before and after puberty. Due to lack of research in this field, this study can be an introduction to evaluate the toxicity of QDs on male reproduction system in different stages of development.

Objective(s):Medicinal benefits of quantum dots have been proved in recent years but there is little known about their toxicity especially in vivo toxicity. In order to use quantum dots in medical applications, studies ontheir in vivo toxicity is important. Materials and Methods: CdSe:ZnS quantum dots were injected in 10, 20, and 40 mg/kg doses to male mice10 days later, mice were sacrificed and five micron slides were prepared structural and optical properties of quantum dots were evaluated using XRD. Results: Histological studies of testis tissue showed high toxic effect of CdSe:ZnS in 40 mg/kg group. Histological studies of epididymis did not show any effect of quantum dots in terms of morphology and tube structure. Mean concentration of LH and testosterone and testis weight showed considerable changes in mice injected with 40 mg/kg dose of CdSe:ZnS compared to control group. However, FSH and body weight did not show any difference with control group. Conclusion: Although it has been reported that CdSe is highly protected from the environment by its shell, but this study showed high toxicity for CdSe:ZnS when it is used in vivo which could be suggested that shell could contribute to increased toxicity of quantum dots. Considering lack of any previous study on this subject, our study could potentially be used as an basis for further extensive studies investigating the effects of quantum dots toxicity on development of male sexual system.

Background: Marine natural products contain a wide range of bioactive compounds with therapeutic properties that have revealed crucial properties in the treatment of some diseases. Some of these compounds have recently received considerable attention for drug discovery. In this study we examined the anti-angiogenic effect of saponin isolated from Holothuria leucospilota (sea cucumber) through evaluation of vascular endothelial growth factor D (VEGF-D) and transforming growth factor-β (TGFβ) expression in a breast cancer cell line. Methods: To investigate the effect of SCS on VEGF-D and TGF-β expression in breast cancer cells, the cells were treated with various concentrations of sample. After 48 h the viability of the cells was evaluated by trypan blue staining, and VEGF-D and TGFβ mRNA expression was were evaluated by real time-PCR. Results: Our results revealed that SCS can suppress cell viability and VEGF-D and TGFβ mRNA expression in breast cancer cells. Sea cucumber saponin at a concentration of 12 μg/ml inhibited VEGF-D and TGFβ expression more than 90% compared with controls. Conclusion: Findings suggest that SCS could inhibit tumor growth via inhibition of angiogenesis

Objective: Oximes are important materials in organic chemistry. Synparamethyl benzaldehyde oxime (toloaldoxime) is structurally similar to other oximes, hence we have studied its effects on the neonatal and adult female Balb/c mice reproductive systems in order to provide a platform for future studies on the production of female contraceptive drugs. Materials and Methods: In experimental study, we studied the effects of toloaldoxime on ovary growth and gonadal hormones of neonatal and adult Balb/c mice. A regression model for prediction was presented. Results: The effects of toloaldoxime on neonatal mice were more than adult mice. The greatest effect was on the number of Graafian follicles (59.6% in adult mice and 31.83% in neonatal mice). The least effect was on ovary weight, and blood serum levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH). Conclusion: According to the data obtained, toloaldoxime can be considered an antipregnancy substance.

Background: Different investigation showed that 5-methoxypsoralen and 8- methoxypsoralen reduce birth rates in the rats. Objective: In this study we worked out the effect of methoxsalen together with ultraviolent A (UVA) radiation on mature Balb/C mice spermatogenesis. Materials and Methods: The LD50 standard was determined 160 mg/kg and the UVA dose which causes erythema was calculated 0.046 J/cm2. A sub-lethal dose of 80 mg/kg of methoxsalen solution was injected intrapritoneally to mature mice and after one hour they were exposed to UVA radiation for 20 minutes. Experiments applied included methoxsalen alone, methoxsalen with UVA, UVA alone, sham group (a group received Tween 80), and control group (N=6). In all experimental groups except UVA alone group, injections were carried out, during two consecutive weeks. Serial cross sections (5 µm thickness) were prepared for morphological and histological studies. Tunica albuginea diameter, and number of type A and type B spermatogonia and histological investigation of the testes were measured. Results: Microscopical and statistical analyses showed significant anomalies among the experimental groups compared to control and sham group. These anomalies included decrease the body weight; increase the relative testis weight; and decrease the number of spermapogonia (type A and B), primary spermatocytes, spermatids and sperms in experimental groups I and II compared to control group. Our results showed the number of spermatozoa in experimental group I was 22.6±2.12, in experimental group II was 33.6±2.05 and in control group was 44.3±2.77 (p

Objective: There is a wide application of titanium dioxide (TiO2) nanoparticles (NPs) in industry. These particles are used in various products, and they also has biological effects on cells and organs through direct contact. Materials and Methods: In this experimental research, the effect of TiO2 on chondrogenesis of forelimb buds of mice embryos was assessed in in vivo condition. Concentrations of 30, 150 and 500 mg/kg body weight (BW) TiO2 NPs (20 nm size) dissolved in distilled water were injected intraperitoneally to Naval Medical Research Institute (NMRI) mice on day 11.5 of gestation. On day 15, limb buds were amputated from the embryos and skeletogeneis of limb buds were studied. Results: TiO2 NPs caused the significant changes in chondrocytes in the following developmental stages: resting, proliferating, hypertrophy, degenerating, perichondrium and mesenchymal cells. Decreased number of mesenchymal cells and increased level of chondrocytes were observed after the injection of different concentrations of TiO2, which proves the unpredictable effects of TiO2 on limb buds. Conclusion: Results of the present study showed TiO2 NPs accelerated the chondrogenesis of limb buds, but further studies are recommended to predict TiO2 toxicity effects on organogenesis.

Objective: There are several factors, like environmental agents, neurotrophic factors, serotonin and some hormones such as estrogen, affecting neurogenesis and neural differentiation. Regarding to importance of proliferation and regeneration in central nervous system, and a progressive increase in neurodegenerative diseases, cell therapy is an attractive approach in neuroscience. The aim of the present study was to investigate the effects of sex steroid hormones and basic fibroblast growth factor (bFGF) on neuronal differentiation of mouse bone marrow-derived mesenchymal stem cells (BM-MSCs). Materials and Methods: This experimental study was established in Kharazmi University. BM was isolated from the bones of femur and tibia of 4-6-week old Naval Medical Research Institute (NMRI) mice, and the cells were cultured. The cells were divided into following 4 groups based on the applied treatments: I. control (no treatment), II. steroid hormones (β-estradiol, progesterone and testosterone), III. bFGF and IV. combination of steroid hormones and bFGF. Immunocytochemistry and flow cytometery analyses were applied for beta III-tubulin (β-III tubulin) and microtubule-associated proteins-2 (MAP-2) in 4 days of treatment for all groups. Results: The cells treated with combination of bFGF and steroid hormones represented more expressions of neural markers as compared to control and to other two groups treated with either bFGF or steroid hormones. Conclusion: This study showed that BM-MSCs can express specific neural markers after receiving bFGF pretreatment that was followed by sex steroid hormones treatment. More investigations are necessary to specify whether steroid hormones and bFGF can be considered for treatment of CNS diseases and disorders.

Objective(s):Marine organisms are known as a potential source of natural products, which contain bioactive substances with therapeutic properties. Sea cucumbers are prominent among marine organisms because of their dietary and therapeutic applications. In addition, they have capacity of synthesizing saponins molecules and other metabolites with therapeutic properties such as antitumor, antimicrobial, anti-inflammatory and antioxidant activities. The aim of this study was to evaluate the antioxidant and pro-apoptotic effects of sea cucumber saponins (SCS) isolated from Holothuria leucospilota species. Materials and Methods: Evaluation of antioxidant activity of SCS was carried out by DPPH (1, 1-diphenyl-2-picrylhydrazyl), ABTS (azino-bis-3-ethylbenzothiazoline-6-sulfonic acid), power reducing and total antioxidant assays. The anti-proliferative effect was studied by МТТ (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. Mechanisms leading to apoptosis were also evaluated byfluorescence microscopy, flow cytometry and real time PCR. Results: The results showed that the DPPH and ABTS activities increased in a dose dependent manner. The reducing capacity enhanced with increasing concentration of the saponin extract (0 to 2 mg/ml). The SCS exhibited moderate total antioxidant activity. Evaluation of anti-proliferative effect revealed that SCS with IC50 of about 6 μg/ml, can display a good cytotoxic activity in a dose dependent manner. Further apoptosis induction was confirmed by fluorescence microscopy and flow cytometry. Sea cucumber saponin was also found to exert a pro-apoptotic effect by increasing the expression of Bax and decreasing the expression of Bcl2. Conclusion: These results indicate that the SCS may act as a natural antioxidant and antitumor agent.

ABSTRACT Nanotubes with their unique properties have diversified mechanical and biological applications. Due to similarity of dimensions with extracellular matrix (ECM) elements, these materials are used in designing scaffolds. In this research, Carboxylated Single-Wall Carbon Nanotubes in optimization of decellularized scaffold of bovine articular cartilage was used. At first, the articular cartilage was decellularized. Then the scaffolds were analyzed in: (i) decellularized scaffolds, and (ii) scaffolds plunged into homogenous suspension of nanotubes in distilled water, were smeared with Carboxylated-SWCNT. The tissue rings derived from the rabbit's ear were assembled with reinforced scaffolds and they were placed in a culture media for 15 days. The scaffolds in two groups and the assembled scaffolds underwent histologic and electron microscopy. Scanning electron microscopy showed that the structure of ECM of articular cartilage has been maintained well after decellularization. Fourier transform infrared analysis showed that the contents of ECM have not been changed under treatment process. Atomic force microscopy analysis showed the difference in surface topography and roughness of group (ii) scaffolds in comparison with group (i). Transmission electron microscopy studies showed the Carboxylated-SWCNT bond with the surface of decellularized scaffold and no penetration of these compounds into the scaffold. The porosity percentage with median rate of 91.04 in group (i) scaffolds did not have significant difference with group (ii) scaffolds. The electron microscopy observations confirmed migration and penetration of the blastema cells into the group (ii) assembled scaffolds. This research presents a technique for provision of nanocomposite scaffolds for cartilage engineering applications.

Objective(s): Mesenchyme is a type of undifferentiated loose connective tissue that is derived mostly from mesoderm. Recently, mesenchymal stem cells (MSCs), as adult stem cells (ASCs) able to divide into a variety of different cells, are of utmost importance for stem cell research. In this research, ability of the liver extract to induce differentiation of rat derived omentum tissue mesenchymal stem cells (rOT-MSCs) into hepatocyte cells (HCs) was investigated. Materials and Methods: After isolation and confirmation of rOT-MSCs they were co-cultured with liver extract and hepatogenic differentiation was monitored. Expressions of mesenchymal stem cell markers were also analyzed via flow cytometry. Moreover, expressions of octamer-binding transcription factor-4 (Oct-4), Wilm's tumor suppressor gene-1 (WT-1), albumin (ALB), alpha fetoprotein (AFP), cytokeratin-18 (CK-18), and mRNAs were analyzed using RT-PCR on days 16, 18 and 21. ALB production was analyzed by immunocytochemistry and western blot. Furthermore, glycogen and urea production were determined via periodic acid-Schiff (PAS) staining and colorimetric assays respectively. Results:The phenotypic characterization revealed the positive expressions of CD90, CD44 and negative expression of CD45 inrOT-MSCs. These cells also expressed mRNA of Oct-4 and WT-1 as markers of omentum tissue. Differentiated rOT-MSCs in presence of 6 µg/ml liver extract expressed ALB, AFP, CK-18, glycogen and urea as specific markers of HCs. Conclusion: These observations suggest that liver extract is potentially able to induce differentiation of MSCs into hepatocyte lineage and can be considered an available source for imposing tissue healing on the damaged liver.

Induced pluripotent cells have been considered as one of the most recent and best cell sources for the cell therapy. In this study, the differentiation potency of human iPS cells, cultured on scaffolds, which can differentiate into definitive endodermal cells as precursor for hepatocytes, pancreatic and lung cells, was studied. Embryoid bodies composed of pluripotent cells, were seeded on electrospinning nanofiber scaffold. The cells were differentiated into definitive endoderm using IDE1. Expression of definitive endoderm markers including Sox17, FoxA2 and GSC were confirmed by immunocytochemistry staining and qRT-PCR analysis. In the present study, morphology and viability of cells were evaluated by utilizing a scanning electron microscopy and MTT assay, respectively. The results demonstrated the positive effect of 3D cultures, using suitable factors, on definitive endoderm differentiation.

Background: Holothuroids (sea cucumbers) are members of the phylum echinodermata, which produce saponins. Saponins exhibit a wide spectrum of pharmacological and biological activities. In this study, we isolated the crude saponins from the body wall of the dominant Iranian species of sea cucumber, Holothuria leucospilota (H. leucospilota). The purpose of this study was to confirm the presence of saponins in the Persian Gulf H. leucospilota and study the hemolytic and cytotoxic activities of these compounds. Methods: The body wall of sea cucumber was dried and powdered and the crude saponins were isolated using various solvents. The crude saponins were further purified by column chromatography using HP-20 resin. The foam test, Thin Layer Chromatography (TLC), hemolytic assay, and Fourier Transform Infrared Spectroscopy (FTIR) confirmed the presence of saponins. Cytotoxicity was analyzed using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay on A549 cells, a human lung cancer cell line. Results: The foam test, hemolytic assay, and TLC supported the presence of saponin compounds in the 80% ethanol fraction of H. leucospilota. The infrared (IR) spectrum of the extract showed hydroxyl (-OH), alkyl (C-H), ether (C-O) and ester (–C=O) absorption characteristic of teriterpenoid saponins. The C-O-C absorption indicated glycoside linkages to the sapogenins. The crude saponin extracted from sea cucumber was cytotoxic to A549 cells. Conclusion: The 80% ethanol fraction of saponin isolated from H. leucospilota exhibited hemolytic activity and offers promise as an anti-cancer candidate.

Objective: Human induced pluripotent stem cells (iPSCs) have been shown to have promising capacity for stem cell therapy and tissue engineering applications. Therefore, it is essential to compare the ability of these cells with the commonly used mesenchymal stem cells (MSC) for bone tissue engineering in vitro. Materials and Methods: In this experimental study, the biological behavior and osteogenic capacity of the iPSCs were compared with MSCs isolated from human adipose tissue (AT-MSCs) using 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Alizarin red staining, alkaline phosphatase (ALP) activity measurements, calcium content assay and common osteogenic-related genes. Data were reported as the mean ± SD. One-way analysis of variance (ANOVA) was used to compare the results. A p value of less than 0.05 was considered statistically significant. Results: There was a significant difference between the rate of proliferation of the two types of stem cells; iPSCs showed increased proliferation compared to AT-MSCs. During osteogenic differentiation, ALP activity and mineralization were demonstrated to be significantly higher in iPSCs. Although AT-MSCs expressed higher levels of Runx2, iPSCs expressed higher levels of osteonection and osteocalcin during differentiation. Conclusion: iPSCs showed a higher capacity for osteogenic differentiation and hold promising potential for bone tissue engineering and cell therapy applications.

Background: The goals of the study are evaluation the effects of food deprivation and isolation situation as a social stress on fertility; and in the following, investigation of the improving effect of melatonin as an antioxidant component. Materials and Methods: In this experimental study, We investigated histopathological and serological effects of melatonin and social stress (food deprivation and isolation) on different features of sperm and testicular tissue among 42 male rats in 7 groups including control, sham, melatonin received (M), food deprivation (FD), Food deprivation and melatonin treatment (FDM), Food deprivation and isolation situation (FDi), and Food deprivation and melatonin treatment and isolation situation (FDMi) groups. Epididymal sperms of all rats were also counted. Histopathological evaluation of the testes was done under a light microscopy to determine the number of spermiogenic cells. Serological evaluation of testosterone, corticosterone, and melatonin was performed, as well. For statistical analysis, oneway ANOVA and Tukey’s post hoc test were used, and the value of p≤0.05 was considered statistically significance. Results: The result showed that food deprivation increased the number of abnormal, immotile, and dead sperms, while decreased the number of normal sperms (p < 0.05). Isolation could improve sperm motility and viability, while enhanced the number of sper- matogenic cells. Melatonin had a protective effect on sperm count, motility, and viability, while reduced sperm abnormality. Conclusion Our results demonstrated that melatonin treatment and isolation situation improve the parameters related to epididymal sperms and spermatogenic cells after food deprivation.

Background: Amniotic membrane derived stem cells (AMSCs) have considerable advantages to use in regenerative medicine and their anti- inflammatory effects, growth factor secretion and differentiation potential make them suitable candidates for stem cell therapy of nervous system. The developing and neonatal brain contains a spectrum of growth factors to direct development of endogenous and donor cells. Using an in vitro model system, we investigated the plasticity and potential of mouse AMSCs to differentiate into neural cells in response to neonatal mice brain extracted medium. Methods: Mouse amniotic membrane stem cells were isolated from embryos, cultured in presence of medium derived from neonatal mouse brain medium and immunohistochemistry and flow cytometry analyses were used to explore the neural differentiation of them. Results: Isolated amnion membrane stem cells showed high rate of viability and proliferation and presented neural characters in the presence of neonatal brain extracted medium such morphological changes and Nestin and Map-2 expression. Conclusion: In conclusion, results from this study showed that amnion membrane derives stem cells are potent stem cells to respond to environmental signals promoting them to neural fate.

Objective(s): The adverse effects of pyridaben on reproductive system in male animals are not well established. This study was designed to elucidate how pyridaben can effects the histomorphometric, hormonal alternations and reproductive functions of BALB/c mice . Materials and Methods : For this study, 80 adult and apparently healthy male BALB/c mice were divided into three groups Viz, control, test group 1 and test group 2. Test groups 1 and 2 were received the toxin at doses of 53 mg/kg. BW, and 212 mg/kg. BW, respectively. The experiment period for both groups was 10, 25 and 45 days. Results : The levels of FSH, LH and testosterone were significantly (P

Introduction: Bone marrow (BM) is a known source of mesenchymal stem cells (MSCs) that are used for cell therapy. This study attempts to identify if the Wharton’s Jelly (WJ) is a suitable substitute for BM as a source for MSCs. Materials and Methods: A population of human WJ and BM stem cells were isolated and incubated with fluorescein conjugated antibodies for five specific MSC markers. Cell populations were subsequently analyzed by flow cytometry. Results: Most of the stem cells isolated from WJ and BM were positive for MSC markers. No significant differences existed between the expression of typical markers of MSCs in WJ isolated cells and that of BM. Conclusion: WJ is a potential replacement for BM as a source of MSCs and can be used for cell therapy in clinical applications.

Introduction: Salep tubers have been used in traditional medicine as a drug for improving sexual function and vigor. We did not find sufficient scientific evidence to support it. The present study was designed to evaluate the effect of Salep tuber extract on the structure of testis and sexual hormones in adult male mice. Materials and Methods: In this experimental study, we used 18 adult male mice (mean age of 4 weeks) and randomly divided them into three groups: the control group did not receive anything, the placebo group received only 200 µl deionized water, and the experimental group received 40 mg salep extract/200µl deionized water intraperitoneally for 7 days. Two weeks after the last injection, we took blood sample for biochemical analysis of LH, FSH and Testosterone and removed the testis of animals for histopathological study. Results: The results showed a significant increase in LH (ng/ml) in the experimental group (0.6 ± 0.09) compared to the placebo (0.39 ± 0.006) and control (0.38 ± 0.007) groups (p

Objective: Embryonic cerebrospinal fluid (e-CSF) has an important role in development of embryonic and adult brain. Proteomic analysis suggests that this fluid has many morphogenes and cytokines that alter in time and space throughout embryonic life. The aim of this study was to evaluate the developmental effect of embryonic CSF on proliferation and differentiation of neuroprogenitor cells in different gestational age.Materials and Methods: In this In this experimental study, we examined the role of e-CSF on proliferation and differentiation of neuroprogenitor cells using neurosphere culture method. Neurospheres size analysis and MTT assay were used to assess cell proliferation after four days in vitro. Glial differentiation study was carried out by immunocytochemistry. Neurospheres size and percentage of glial fibrialy acidic protein (GFAP) positive cells were measured by image analyzer (image J). The data were analyzed by one-way ANOVA, followed by the Tukey’s post hoc test. Data were expressed as mean ± SEM, and differences were considered significant when p

Background: Pyridaben, a pyridazinone derivative, is a new acaricide and insecticide for control of mites and some insects such as white flies, aphids and thrips. Objective: This study was designed to elucidate how pyridaben can affect the sperms' morphological parameters, its DNA integrity, and to estimate the effect of various quantities of pyridaben on in vitro fertilization rate. Materials and Methods: In this study, 80 adult male Balb/C strain mice were used. Animals were divided into control and two test groups. Control group received distilled water. The test group was divided into two subgroups, viz, high dose (212 mg/kg/day) and low dose (53 mg/kg/day) and they received the pyridaben, orally for duration of 45 days. The spermatozoa were obtained from caudae epididymides on day 45 in all groups. Sperm viability, protamin compression (nuclear maturity), DNA double-strand breaks, and in vitro fertilizing (IVF) ability were examined. Results: The pyridaben treatment provoked a significant decrease in sperm population and viability in epididymides. The data obtained from this experiment revealed that, the pyridaben brings about negative impact on the sperm maturation and DNA integrity in a time-dependent manner, which consequently caused a significant (p

Objective: Methoxsalen is a natural photoactive compound which is found in many seed plants. A number of epidermal proliferative disorders can be treated by methoxsalen along with long wave ultraviolet A (UVA).Materials and Methods: In an experimental study, we aimed to demonstrate the effect of methoxsalen, UVA and their combination on oogenesis Balb/C mice. There were two experimental groups and a control group. The experimental groups were composed of i. a short term group with treatment duration of 15 days and ii. a long term group with treatment duration of 5 weeks. Both the long term and short term experimental groups were further subdivided into a UVA group, a methoxsalen group and a methoxsalen plus UVA group. After treatment, mature females in prosterus phase of ovarian cycle were scarified with ether, while their ovaries were removed and prepared for histological studies.Results: Both macro and microscopic studies showed significant anomalies (p