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Background: Regular moderate exercise and endogenous cannabinoid activity have independently been shown to alleviate seizure (SE) attacks. Objectives: This study aimed to investigate the effect of physical activity on the expression levels of cannabinoid CB1 and CB2 receptors in the brains Methods: Male Wistar rats were divided into five groups: Sham, SE, physical activity (PA), PA + SE, and PA before SE. Epileptic SEs were induced by administering pentylenetetrazol (PTZ; intraperitoneally, 35 mg/kg) every other day for four weeks in the SE, PA + SE, and PA before SE groups. Animals in the PA, PA + SE, and PA before SE groups participated in treadmill running (30 minutes per day, five days a week). The mean number of cortical and hippocampal (CA1, CA3) CB1 and CB2 receptors was assessed using immunohistochemistry. Results: The study data revealed a significant reduction of CB1 and CB2 receptors in the CA1, CA3, and cortex of the SE group compared to the sham group. A significant increase in CB1 receptors was observed in the PA and PA before SE groups compared to the SE group in both cortical and hippocampal areas. Physical activity significantly increased hippocampal and cortical CB2 receptor distribution in the PA, PA + SE, and PA before SE groups compared to the SE group. Conclusions: These findings suggest that exercise modulates the expression of hippocampal and cortical cannabinoid receptors in epileptic rats, highlighting the involvement of the endocannabinoid pathway in the anti-epileptic effects of exercise. [ABSTRACT FROM AUTHOR]

Introduction: Strategies of Schwann cell (SC) transplantation for regeneration of peripheral nerve injury involve many limitations. Stem cells can be used as alternative cell source for differentiation into Schwann cells. Given the high potential of neural crest-derived stem cells for the generation of multiple cell lineages, in this research, we considered whether olfactory ectomesenchymal stem cells (OE-MSCs) derived from neural crest can spontaneously differentiate into SC lineage Methods: OE-MSCs were isolated from human nasal mucosa and characterized by the mesenchymal and neural crest markers. The cells were cultured in glial growth factors-free medium and further investigated in terms of the phenotypic and functional properties. Results: Immunocytochemical staining and real-time PCR analysis indicated that the cultured OE-MSCs expressed SCs markers, SOX10, p75, S100, GFAP and MBP, differentiation indicative. It was found that the cells could secrete neurotrophic factors, including brainderived neurotrophic factor (BDNF) and nerve growth factor (NGF). Furthermore, after cocultured with PC12, the mean neurite length was enhanced by OE-MSCs. Conclusion: The findings indicated that OE-MSCs could be differentiated spontaneously into SC-like phenotypes, suggesting their applications for transplantation in peripheral nerve injuries. [ABSTRACT FROM AUTHOR]

Strategies of Schwann cell (SC) transplantation for regeneration of peripheral nerve injury involve many limitations. Stem cells can be used as alternative cell source for differentiation into Schwann cells. Given the high potential of neural crest-derived stem cells for the generation of multiple cell lineages, in this research, we considered whether olfactory ectomesenchymal stem cells (OE-MSCs) derived from neural crest can spontaneously differentiate into SC lineage. OE-MSCs were isolated from human nasal mucosa and characterized by the mesenchymal and neural crest markers. The cells were cultured in glial growth factors-free medium and further investigated in terms of the phenotypic and functional properties. Immunocytochemical staining and real-time PCR analysis indicated that the cultured OE-MSCs expressed SCs markers, SOX10, p75, S100, GFAP and MBP, differentiation indicative. It was found that the cells could secrete neurotrophic factors, including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Furthermore, after co-cultured with PC12, the mean neurite length was enhanced by OE-MSCs. The findings indicated that OE-MSCs could be differentiated spontaneously into SC-like phenotypes, suggesting their applications for transplantation in peripheral nerve injuries. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder diagnosed by anovulation hyperandrogenism. Hyperandrogenism increases apoptosis, which will eventually disturb follicular growth in PCOS patients. Since mitochondria regulate apoptosis, they might be affected by high incidence of follicular atresia. This may cause infertility. Since vitamin D3 has been shown to improve the PCOS symptoms, the aim of study was to investigate the effects vitamin D3 on mtDNA copy number, mitochondrial biogenesis, and membrane integrity of granulosa cells a PCOS-induced mouse model. Materials and Methods: In this experimental study, the PCOS mouse model was induced by dehydroepiandrosterone (DHEA). Granulosa cells after identification by follicle-stimulating hormone receptor (FSHR) were cultured in three groups: 1. granulosa cells treated with vitamin D3 (100 nM for 24 hours), 2. granulosa cells without any treatments, 3. Non-PCOS granulosa cells (control group). Mitochondrial biogenesis gene (TFAM) expression was compared between different groups using real-time PCR. mtDNA copy number was also investigated by qPCR. The mitochondrial structure was evaluated by transmission electron microscopy (TEM). Hormonal levels were measured by enzymelinked immunosorbent assay (ELISA) kit. Results: The numbers of pre-antral and antral follicles increased in PCOS group in comparison with the non-PCOS group. Mitochondrial biogenesis genes were downregulated in granulosa cells of PCOS mice when compared to the non-PCOS granulosa cells. However, treatment with vitamin D3 increased mtDNA expression levels of these genes compared to PCOS granulosa cells with no treatments. Most of the mitochondria in the PCOS group were spherical with almost no cristae. Our results showed that in the PCOS group treated with vitamin D3, the mtDNA copy number increased significantly in comparison to PCOS granulosa cells with no treatments. Conclusion: According to this study, we can conclude, vitamin D3 improves mitochondrial biogenesis and membrane integrity, mtDNA copy number in granulosa cells of PCOS mice which might improve follicular development and subsequently oocyte quality. [ABSTRACT FROM AUTHOR]

Background: The Rosemary extract (RE) possesses various antioxidant, cytoprotective and cognition-improving bioactivities. In this study, we postulated which doses of RE have a more effect on the hippocampus of middle-aged rats. Methods: In this experimental study, thirty-two middle-aged male Wistar rats were fed by different doses (50,100 and 200 mg/kg/day) of RE (containing 40% carnosic acid) or distilled water for 12 weeks. The effects of different RE doses on learning and spatial memory scores, hippocampal neuronal survival, antioxidant enzymes and lipid peroxidation amount were evaluated by one and two way analysis of variance (ANOVA). Results: It seemed that RE (100mg/kg) could recover the spatial memory retrieval score (p< 0.05). The amount of activity of SOD, GPx and CAT enzymes in the hippocampus of animals of the RE (100mg/kg) group showed a significant increase compared to the normal group (p< 0.01), (p< 0.01) and (p< 0.05), respectively. Also, the amount of activity of GPx in the RE (50 mg/kg) group of animals showed a significant increase compared to the normal group (p< 0.05). No significant difference was found between the groups in the MDA level. Conclusion: The results revealed that rosemary extract (40% carnosic acid) may improve the memory score and oxidative stress activity in middle aged rats in a dose dependent manner, especially in 100mg/kg. [ABSTRACT FROM AUTHOR]

Objective(s): Morphine dependence (MD) potently protects heart against ischemia reperfusion (IR) injury through specific signaling mechanisms, which are different from the pathways involved in acute morphine treatment or classical preconditioning. Since opioid receptor density changes post cerebral ischemia strongly correlated with brain histological damage, in the present study, we tried to elucidate the possible role of opioid receptors in IR injury among morphine-dependent mice. Materials and Methods: Accordingly, incremental doses (10 mg/kg/day to 30 mg/kg/day) of morphine sulphate were subcutaneously administered for 5 days before global brain ischemia induction through bilateral common carotid artery occlusion. Animals were received naloxone (5 mg/kg) or L-NAME (20 mg/kg) 30 min after the last morphine dose. Twenty four hr after the ischemia induction, Retention trial of passive avoidance test and western blot analysis were done. histological analysis (TUNEL and NISSL staining) performed 72 hr after ischemia. Results: MD improved post ischemia memory performance (P<0.01) and neuronal survival (P<0.001) and decreased apoptosis (P<0.05) in region I of hippocampus (CA1 region) in mouse. Treatment with naloxone or L-NAME abolished all MD aforementioned effects. Conclusion: Results of the present study suggested that opioid receptors activation in the early hr post ischemia is crucial for MD-induced hippocampus tolerance against IR injury. Opioid receptordependent balance of NO production was another key factor in MD-induced protection. Further studies are required to determine the effect of MD on opioid receptor changes after ischemia and its correlation with MD-induced protection. [ABSTRACT FROM AUTHOR]

Objective(s): Spinal cord injury (SCI) is one of the most serious clinical diseases and its treatment has been a subject of interest to researchers. There are two important therapeutic strategies in the treatment of SCI: replacing lost tissue cells through cells implantation and scar elimination. Therefore, in this study we used human adipose-derived stem cells (hADSCs) implantation and injection of Chondroitinase ABC. Aim of present study was to answer to this question: which one is more efficient for Improvement of locomotor recovery after SCI in rat? Transplantation of hADSCs or injection of ChABC. Materials and Methods: The spinal cord of rats was injured by contusion using a weight-drop at the level of T8-9, the hADSCs and Chondroitinase ABC were infused in to the spinal cord tissue after injury. BBB test was performed and recorded for each animal weekly for 8 weeks. After the 8th weeks, Serial crosssections were stained with cresyl violet and examined under a light microscope and area of cavity in the spinal cord was measured. Results: At 8th weeks after injection, hADSCs and ChABC significantly promote locomotor function (P<0.01) and spinal cords of hADSCs and ChABC group had cavities much smaller than those of the control group (P<0.001). Conclusion: Results of the present study shows dealing with inappropriate neuro-inhibitory environment and glial scar by ChABC have equal role compare to cell therapy (with hADSCs) for improving motor function after SCI and this result in adoption of proper therapeutic strategies for SCI intervention is important. [ABSTRACT FROM AUTHOR]

Background: Adenosine is an endogenous purine nucleoside that has a neuromodulatory role in the central nervous system. The amphetamine derivative (±)-3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a synthetic amphetamine analogue used recreationally to obtain an enhanced affiliated emotional response. MDMA is a potent monoaminergic neurotoxin with the potential of damage to brain neurons. The NF-kB family of proteins are ubiquitously expressed and are inducible transcription factors that regulate the expression of genes involved in disparate processes such as immunity and in-growth, development and cell-death regulation. In this study we investigated the effects of the A2a adenosine receptor (A2a-R) agonist (CGS) and antagonist (SCH) on NF-kB expression after MDMA administration. Methods: Sixty three male Sprague-Dawley rats were injected to MDMA (10 and 20mg/kg) followed by intraperitoneal CGS (0.03 mg/kg) or SCH (0.03mg/kg) injection. The cerebellum were then removed forcresyl-violet staining, western blot and RT-PCR analyses. MDMA significantly elevated NF-kB expression. Our results showed that MDMA increased the number of cerebellar dark neurons. Results: We observed that administration of CGS following MDMA, significantly elevated the NF-kB expression both at mRNA and protein levels. By contrast, administration of the A2a-R antagonist SCH resulted in a decrease in the NF-kB levels. Conclusion: These results indicated that, co-administration of A2a agonist (CGS) can protect against MDMA neurotoxic effects by increasing NF-kB expression levels; suggesting a potential application for protection against the neurotoxic effects observed in MDMA users. [ABSTRACT FROM AUTHOR]

Introduction: Stress is defined as any environmental change that disturbs the maintenance of brain homeostasis. Stress leads to production of pro-inflammatory cytokines that provoke neurodegenerative disorders. In the present study, we investigated the effects of dalteparin on hippocampal neuronal death induced by chronic stress in rats. Methods: the study was carried out on 60 adult male wistar rats, weighing 200- 250 gr. The rats were randomly divided into three groups: control, stress and stress + dalteparin (SD) groups. Animals in the stress and stress + dalteparin group were exposed to chronic stress for 4 weeks. Animals in the stress + dalteparin (SD) group received dalteparin (70,100 and 140 IU/kg/days i.p.) during the stress period. After the last stressor animals were sacrificed and concentration of IL-6 in serum was measured using ELISA. All animals were reperfused and their brains were processed for histological analysis through Nissl analysis. Results: We found that the serum concentration of IL-6 was significantly higher in the CMS (Chronic Mild Stress) exposure group than in the control group (p<0.05). Moreover, dalteparin, dose dependently decreased IL-6 concentration in the SD groups. Chronic stress also resulted in significant cell loss in hippocampal CA1, CA3 and hilus. Dalteparin markedly inhibited the decreases in number of hippocamoal CA1 and CA3 (p<0.01) and hilus (p<0.05) neurons caused by chronic stress. Discussion: chronic stress damages hippocampal CA1, CA3 and hilus neurons, and dalteparin protects hippocampus from damage induced by chronic stress. [ABSTRACT FROM AUTHOR]

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Objective: Tumor necrosis factor-alpha (TNF-α), checkpoint inhibitors, and interleukin-17 (IL-17) are critical targets in inflammation and autoimmune diseases. Monoclonal antibodies (mAbs) have a successful portfolio in the treatment of chronic diseases. With the current progress in stem cells and gene therapy technologies, there is the promise of replacing costly mAbs production in bioreactors with a more direct and cost-effective production method inside the patient's cells. In this paper we examine the results of an investigational assessment of secukinumab gene therapy. Materials and Methods: In this experimental study, the DNA sequence of the heavy and light chains of secukinumab antibodies were cloned in a lentiviral vector. Human chorionic villous mesenchymal stem cells (CMSCs) were isolated and characterized. After lentiviral packaging and titration, part of the recombinant viruses was used for transduction of the CMSCs and the other part were applied for systemic gene therapy. The engineered stem cells and recombinant viruses were applied for ex vivo and in vivo gene therapy, respectively, in different groups of rat models. In vitro and in vivo secukinumab expression was confirmed with quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and ELISA by considering the approved secukinumab as the standard reference. Results: Cell differentiation assays and flow cytometry of standard biomarkers confirmed the multipotency of the CMSCs. Western blot and qRT-PCR confirmed in vitro gene expression of secukinumab at both the mRNA and protein level. ELISA testing of serum from treated rat models confirmed mAb overexpression for both in vivo and ex vivo gene therapies. Conclusion: In this study, a lentiviral-mediated ex vivo and in vivo gene therapy was developed to provide a moderate dose of secukinumab in rat models. Biosimilar gene therapy is an attractive approach for the treatment of autoimmune disorders, cancers and other chronic diseases. [ABSTRACT FROM AUTHOR]

Human umbilical cord matrix (hUCM) is considered as a promising source of mesenchymal stem cells (MSCs) due to several advantages over other tissues. The potential of neural differentiation of hUCM-MSCs is of great interest in the context of treating neurodegenerative diseases. In recent years, considerable efforts have been made to establish in vitro conditions for improving the differentiation of hUCM-MSCs toward neuronal cells. In the present study, we evaluated the neural differentiation potential of hUCM-MSCs in the presence of cAMP-elevating agents forskolin and 3-isobutyl-1-methylxanthine (IBMX). hUCM-MSCs were isolated from fetal umbilical cord and characterized by flow cytometry analysis for mesenchymal specific markers. Mesodermal differentiation potential was assessed through selective media with lineage-specific induction factors. For assessment of neural differentiation, cells were cultured in the presence of cAMP-elevating agents for 8 and 24 h. The neuronal differentiated MSCs were characterized for neuronal specific markers by immunocytochemistry and western blotting. Isolated hUCM-MSCs were found positive for mesenchymal markers (CD73, CD90, and CD105) while negative for hematopoietic markers (CD34 and CD45) .Following neural induction, most cells represented neural-like cells morphology. Neural markers including β-tubulin III (Tuj-1), neuron-specific enolase (NSE), microtubule-associated protein-2 (MAP-2) and nestin were expressed in treated cells with respect to control group. The astrocyte specific marker, glial fibrillary acidic protein (GFAP) was also shown by immunofluorescence in treated cells. ( These findings demonstrate that hUCM-MSCs have the ability to rapidly differentiate into neural cell types of neuron-like cells and astrocytes by cAMP-elevating agents without the presence of growth factors.

Objective: Skin wound healing is a serious clinical problem especially after surgery and severe injury of the skin. Cell therapy is an innovative technique that can be applied to wound healing. One appropriate source of stem cells for therapeutic use is stem cells from the adult bulge of hair follicles. This study examined the effects of adult bulge hair follicle stem cells (HFSC) in wound healing., Materials and Methods: Hair follicle stem cells were obtained from rat vibrissa and labeled with DiI (Invitrogen, Carlsbad, CA), then special markers were detected using flow cytometry. A full-thickness excisional wound model was created and DiI-labeled HFSC were injected around the wound bed. Wound healing was recorded with digital photographs. Animals were sacrificed at 3, 7, or 14 days after surgery, and were used for the following histological analyses., Results: Flow cytometry analysis showed that HFSC were CD34 positive and nestin positive, but K15 negative. Morphological analysis of HFSC-treated wounds exhibited accelerated wound closure. Histological analysis of hematoxylin and eosin stained and Masson's trichrome-stained photomicrographs showed significantly more re-epithelialization and dermal structural regeneration in HFSC-treated wounds than in the control group. Immunohistochemical analysis of CD31 protein-positive cells showed angiogenesis was also more significant in HFSC-treated wounds than in the control group., Conclusion: Hair follicle stem cells accelerate skin wound healing. Isolating HFSC from a small skin biopsy could repair less-extensive full-thickness skin wounds by autologous stem cells and overcome major challenges regarding the use of stem cells in clinical application, while avoiding immune rejection and ethical concerns.