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Bladder cancer (BC) is one of the most prevalent cancers around the world and, if not treated well, has high morbidity and mortality. Many studies have indicated that there may be various roles for the aryl hydrocarbon receptor (AHR) in the immune system. The aim of this study was to determine the frequency of Foxp3(+) regulatory T (Treg) and T helper 17 cells (Th17) in BC tissue in comparison with controls and determine the relationship between AHR, Foxp3(+) Treg and Th17 cells in BC. A total of 40 patients with BC were enrolled in this study. The control group was selected from non‐tumoural parts of bladder tissues from the patients who have undergone cystoscopy. The percentage of regulatory T cells (Foxp3(+)/CD4(+)) and Th17 (IL‐17(+)/CD4(+)), as well as AHR(+) cells in BC tissues and controls, were determined by immunohistochemistry. The results of this study showed that the number of Foxp3(+) Treg and Th17 is significantly higher in bladder tumour tissues in comparison with non‐tumoural tissues. Also, the percentage of AHR(+) lymphocytes and AHR(+) cells was increased significantly in bladder tumour tissues rather than non‐tumoural tissues. This study also found a relation between AHR and Foxp3(+)/CD4(+) T lymphocytes ratio cells in BC. The percentage of Foxp3(+) Tregs and AHR(+) cells were significantly correlated with the grade and stage of BC. An increase in the percentage of Foxp3(+) Treg and Th17 cells may play an important role in tumour immunity; and determining the relationship between AHR and differentiation of Th17/Foxp3(+)Treg in BC can lead to a potential cancer therapeutic possibility.

This study aims to investigate the neuroprotective effect of wild lowbush blueberry on CIRI in rats. Accordingly, CIRI and reperfusion were induced in rats for 60 min and 24 h, respectively. Then, the mechanisms of the neuroprotective effects of BBE were investigated in the injury through evaluating miR-146a, miR-21, and their targets in a CIRI rat model. After that, the BBE (30, 60, and 120 mg/kg b.wt) was intraperitoneally injected for 14 days, then CIRI was induced by BCCAO for 60 min for ischemic stroke and reperfusion for 24 h. Several parameters including the oxidative stress levels in the hippocampus and serum were measured 24 h after the CIRI. The findings showed that the BBE significantly decreased the levels of malondialdehyde (MDA) and nitric oxide (NO) and increased ferric ion reducing antioxidant power (FRAP) levels in the hippocampus and serum following the stroke. The BBE also maximized the miR-146a and miR-21 expressions and moderated iNOS and TNF-α expressions in the hippocampus. Likewise, the BBE enlarged the CA1 and CA3 domains of the post-stroke pyramidal cell layers of the hippocampus. Overall, the results revealed that BBE had potent neuroprotective efficacy against CIRI via the effective modulation of neuroinflammatory cascades and protected neurons against ischemic death.

Articular cartilage has weak intrinsic self-healing capacity. Tissue engineering is an appropriate option for cartilage regeneration. This research was designed to evaluate the effects of pore size in scaffolds on mechanical properties and chondrocyte-scaffold interactions. PCL scaffolds were fabricated with large, medium, and small pore sizes. The constructs were analyzed by SEM, swelling tests, mechanical tests, MTT assay, and H&E staining after chondrocyte seeding. Mechanical features of the scaffolds were near to human articular cartilage. Our findings suggest that the PCL scaffold with medium pore sizes provides suitable mechanical strength and better chondrocyte-scaffold interactions simultaneously for application in cartilage.

The aim of present study is to investigate pretreatment with hydroalcoholic extract of Alpinia officinarum rhizome on the severity of epilepsy and memory impairment in rat. In this experimental study, rats were randomly assigned to seven groups. Control group and negative control group were intraperitoneally injected with normal saline and PTZ, respectively, for 10 days. The intervention groups received A. officinarum extract at different doses (50, 100 and 150 mg/kg) 30 minutes before PTZ injection. A. officinarum extract treatment in rats with PTZ-induced kindling exerted significant increase in seizure latency and significant decrease in the frequency of total body seizure, frequent spinning, and jumping. Flumazenil significantly inhibited the antiepileptic effects of A. officinarum extract in the rat receiving the extract at 150 mg/kg. A. officinarum extract can inhibit PTZ-induced seizure and memory impairment, and therefore can be considered as a potent agent which warranted further research to clarify its effects.

Background Cyclophosphamide (CP) is an anti-neoplastic alkylating agent that is extensively used in different chemotherapy regimens. Adverse effects on the reproductive system, especially spermatogenesis, are one of the most important side effects of this drug. It is medically essential to use complementary and alternative drugs. Herbal drugs have long been used as a complementary treatment. Our purpose was to study the effect of hydroalcoholic Allium atroviolaceum L. extract on spermatogenesis in CP-treated mice. Results CP affected a significant decrease in sperm count, motility, viability, and morphology. Sperm count was significantly higher in the all extract groups than in the group of control (ppppppp Conclusion A. atroviolaceum extract treatment significantly improved CP-induced reproductive toxicity.

Early life stress is associated with various complications. Auraptene has significant antioxidant and anti-inflammatory effects. This study aimed to assess the probable underlying mechanisms that mediate changes in the behavior, hippocampus, heart and serum in the mouse model of maternal separation (MS) stress. We evaluated the possible protective effects of auraptene in these changes focusing on inflammatory response and oxidative state. Mice were treated with auraptene (5, 10, and 50 mg/kg). In addition, anxiety-like behaviors were evaluated using behavioral tests; including open field test (OFT) and elevated plus maze (EPM). Hippocampus and heart samples were assessed histopathologically. Levels of malondialdehyde (MDA) and antioxidant capacity, as well as nitrite levels, were measured in serum, heart, and hippocampal tissues. Moreover, gene expression of inflammatory markers (Il-1β and Tlr-4) was evaluated in the heart and hippocampus. Results showed that auraptene reversed the negative effects of MS on behavior (increased time spent in central zone of the OFT and time and entries to the open arms of the EPM). Auraptene mitigated adverse effects of MS on the hippocampus (increased diameter and decreased percentage of dark neurons in the CA3 area). Accordingly, auraptene decreased MDA and nitrite levels and increased the antioxidant capacity in serum, and hippocampal samples. However, we observed different effects for different doses of auraptene in the heart samples. We concluded that MS is associated with anxiety-like behavior and cellular/molecular modifications in the heart, hippocampus and serum. We found that auraptene exerted protective effects against these negative effects of MS in mouse.

Background and Aim. Rutin is a flavonol with neuroprotective activity. The aim of the present study is to investigate the role of the glutamatergic system in the antidepressant-like effect of rutin in a mouse model of maternal separation (MS) stress focusing on histological changes in the CA3 area of the hippocampus. Methods. Mouse neonates were exposed to MS paradigm 3 hours daily from postnatal days (PND) 2 to 14. The control and MS mice were divided separately into 16 groups (n=8) (8 groups for each set) including mice that received normal saline, mice that received rutin at doses of 10, 50, and 100 mg/kg, mice that received NMDA at a dose of 150 mg/kg, mice that received ketamine (NMDA antagonist) at a dose of 0.25 mg/kg, mice that received NMDA antagonist plus a subeffective dose of rutin, and mice that received NMDA plus an effective dose of rutin. Forced swimming test (FST) was performed. Afterwards, the hippocampus was evaluated in cases of histopathological changes as well as expression of NR2A and NR2B genes. Results. Rutin significantly reduced immobility time in the FST. The expression of NR2A and NR2B subunits of NMDA receptor in MS mice was significantly higher than that in the control group. Rutin significantly decreased the expression of NR2B and NR2A subunits in the hippocampus. The CA3 diameter and percentage of dark neurons in the hippocampus of MS mice significantly decreased and increased, respectively, which partially reversed following rutin administration. Conclusion. Rutin, partially, through a neuroprotective effect on the hippocampus exerted antidepressant-like effect. We concluded that NMDA receptors, at least in part, mediated the beneficial effect of rutin.

Increasing use of cell-phone is one of the most important risk factors for population health. We designed an experimental study aimed at evaluating the effects of cell-phone radiofrequency (RF) waves exposure on fertilization in mice. Two hundred male and female NMRI-mice were used. One hundred males divided in five groups (n = 20) as control and exposed groups. Those irradiated with cell-phone RF in “Standby-mode” 1, 5 and 10 h daily named groups II, III and IV; respectively. Group V irradiated with cell-phone on “Active-mode” one hour daily. After 30 days irradiation, 50 males and 50 females were kept 24 h to assess their embryos. Fifty males were scarified to evaluate both in vitro and in vivo parameters, and 50 females received PMSG & HCG for both quantitative and qualitative evaluation. Comparing groups III, IV and V with control-group showed significantly decreased in the number of two-cell embryos (p = .000); however, a significant increase was found in the number of dead embryos (p = .000). Furthermore, 5 h daily irradiation significantly decreased grade-A embryos (p = .015); while, it significantly increased grade-B, C and D embryos (p-values = 0.026, 0.007, 0.006; respectively). Moreover, comparing groups IV and V to control-group, significant increase was found in pregnancy duration (p = .005, p = .009; respectively). However, in the mentioned groups a significant decrease was seen in number of newborn mice (p = .001, p = .004; respectively). In conclusion our findings showed that the cell-phone radiation can affect development of embryos as well as the number of newborn and pregnancy duration in NMRI-mouse, which might be a significant cause of reproductive failure. Keywords: Fertility, IVF, RF, Cell-phone, Embryo

Background The most important side effects of Cyclophosphamide, as an anticancer broad-spectrum drug, are the negative effects on the reproduction and fertility because of oxidative stress. Considering the antioxidant properties of medicinal plants, especially those of the Allium genus, this paper studied the effect of hydroalcoholic extract of Allium atroviolaceum L. on the pathology of testicular tissue in CP-treated mice. Methods Groups of this experimental study consisted of normal saline recipients; three groups receiving A. atroviolaceum extract at 50, 100, 200 mg/kg; three groups receiving A. atroviolaceum extract at 50, 100, and 200 mg/g and 6.6 mg/kg of Cyclophosphamide; and a group given Cyclophosphamide at 1.6 mg/kg. All injections were performed intra-peritoneally. After 30 days, the testicular histological profile as well as the number of spermatozoa, the number of primary and round spermatocytes, and the number of spermatogonia were investigated. Results Cyclophosphamide treatment significantly reduced the lumen diameter, the seminiferous tubule diameter, the epithelial thickness, as well as decreased the quantity of spermatozoa and round and primary spermatocytes compared to the control group. Cyclophosphamide groups treated with A. atroviolaceum extract at 50, 100 and 200 mg/kg in a significant manner improved these variables (P < 0.001). Conclusion A. atroviolaceum extract can significantly improve Cyclophosphamide-induced toxicity and pathological process on testicular tissue. It seems that this plant, with high antioxidant capacity, can be considered a complementary therapy for Cyclophosphamide to prevent undesirable effects on the reproductive system.

INTRODUCTION Today, the use of electromagnetic waves in medical diagnostic devices, such as magnetic resonance imaging (MRI), has increased, and many of its biological effects have been reported. The aim of the present study was to assess the biological effects of 1.5 Tesla (T) magnetic resonance imaging (MRI) on fertility and reproductive parameters. METHODS Eighty adult male and female NMRI mice (NMRI: Naval Medical Research Institute) of age 6-8 weeks were studied and randomly divided into two study and control groups. After confirmation of pregnancy, the mice in the study group were exposed to the MRI (1.5 T) machine's waves over the next three weeks, once a week for 36 minutes. One day and thirty-five days after the last radiation, the mice were killed in order to do the in vitro fertilization (IVF) by neck beads' displacement and the impact on the evolution of embryos, and its quality was studied. Data were analyzed using SPSS version 20 and the significance level of less than 0.05 was considered. RESULTS Embryo morphometry showed that the total diameter and the cytoplasm diameter of the study group embryos suffered significant reduction compared to the control group, 1 day after the last irradiation (p < 0.05), but the diameter of the perivitelline space of this group's embryos had a significant increase (p < 0.05). The qualitative results during 35 days after irradiation showed that morphologically parameters of the embryos in the study group had no significant differences from the control group. CONCLUSION Exposure to MRI irradiation can transiently disturb the development of mouse embryos and fertility, but these effects are reversible 35 days after the last irradiation.

It is well known that diabetes is associated with impairment of testicular function. The present study aimed to investigate the effect of Semilil, an herbal medicine with angiogenic action, on testicular germ cell apoptosis in streptozotocin (STZ)-induced chronic diabetic rats.

Understanding neuroectoderm formation and its subsequent diversification to functional neural subtypes remains elusive. We have shown here for the first time that embryonic stem cells (ESCs) can differentiate into neurons and motor neurons (MNs) by using a coculture embryonic notochord model in vitro. Mouse ESCs were induced to form neural precursors via timed exposure to retinoic acid (RA) using the 4-/4+ RA protocol. These cells were then cocultured with alginate bead-encapsulated notochords isolated from Hamburger and Hamilton stage 6-10 chick embryos. The use of notochord alone was not able to induce neural differentiation from ESCs, and, therefore, notochord does not possess neural inducing activity. Hence, the most successful neuronal cells and MN differentiation was only observed following the coculture of RA-pretreated ESCs with notochord. This resulted in a significantly greater number of cells expressing microtubule-associated protein-2 (MAP2), HB9, choline acetyltransferase (ChAT) and MN-specific genes. While further characterization of these differentiated cells will be essential before transplantation studies commence, these data illustrate the effectiveness of embryonic notochord coculture in providing valuable molecular cues for directed differentiation of ESCs toward an MN lineage.

Context Connective tissue cells include fibroblasts, chondrocytes, adipocyte, and osteocytes. These cells are specialized for the secretion of collagenous extracellular matrix and are responsible for the architectural framework of the human body. Evidence Acquisition Connective tissue cells play a central role in supporting as well as repairing tissues and organs. Fibroblast cell therapy could be used for the treatment of burn wounds, scars, diabetic foot ulcers, acne scars and skin aging. This review focused on biology of fibroblasts and their role in cell therapy of recessive dystrophic epidermolysis bullosa (RDEB). Results Fibroblasts are known to play a pivotal role in skin structure and integrity, and dermal fibroblasts are believed to promote skin regeneration and rejuvenation via collagen production. Conclusions Fibroblasts can be used in transplantations to ameliorate an immune system response, in order to reduce antigen production. Human fibroblasts suppress ongoing mixed lymphocyte reactions (MLRs) between lymphocyte cells from two individuals, and supernatant materials from fibroblast cultures suppress MLRs.

Context Stem cell therapy, especially in the segment of mesenchymal stem cells (MSCs), is one of the most promising areas of regenerative medicine. Evidence Acquisition According to research conducted by various researchers, Wharton’s Jelly mesenchymal stem cells (WJMSCs) have several advantages compared to others sources, in regenerative medicine: WJMSCs are more primary cells; WJMSCs can be easily isolated and without invasive procedures; WJMSCs have no ethical problems; WJMSCs are more cost effective than other sources of MSCs. Also, WJMSCs were demonstrated to express stem cell mesenchymal markers. Results Similar to bone marrow MSCs, WJMSCs express major histocompatibility complex (MHC) class I molecules. Conclusions Although the aforementioned challenges must still be addressed, the potential of WJMSCs in skin regenerative clinical treatments is promising.

Context Burn wounds of the skin require a long period to healing, which very often is incomplete, with functional and esthetic consequences for the patients. Stem cells in the traumatized tissue represent the promoters of the healing process and are a primary focus for regenerative medicine, which aims to find and use the triggers for the activation of stem cells of sin tissue. Evidence Acquisition At present, tissue engineering, composite epithelial autografts, multipotent stem cells and combined gene delivery with stem cell therapy are the approaches used in regenerative medicine. Alongside, the development of 3D scaffolds or matrices is a promising adjunct, as studies investigate the multiple uses of these supports for wound repair. Results Application of cells to the burn wound could be performed, either by the bedside, as a non-invasive procedure, or in the operating room, with the use of a matrix, scaffold or dermal substitute. Cell spraying, although under use in clinical setting, is not yet supported by conclusive data. Magnetic resonance imaging, optical imaging and positron emission tomography are currently used to assess the viability and location of stem cells, after transplantation. Conclusions Stem cell therapies in wound care may lessen the morbidities associated with wound healing. An ideal method for the effective administration of stem cells for burn patients has not yet been elucidated. Further comparison of the local and systemic effects in burn patients, associated with each route of stem cell delivery, needs to be performed.