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Background: Schizophrenia is a disease of the nervous system, and immune system disorders can affect its pathogenesis. Activation of microglia, proinflammatory cytokines, disruption of the blood-brain barrier due to inflammation, activation of autoreactive B cells, and consequently the production of autoantibodies against system antigens are among the immune processes involved in neurological diseases. Interleukin-32 (IL-32) is a proinflammatory cytokine that is essential in activating innate and adaptive immune responses. This study aimed to measure the serum level of IL-32 as well as the frequency of autoantibody positivity against several nervous system antigens in patients with schizophrenia. Material and Methods: This study was conducted on 40 patients with schizophrenia and 40 healthy individuals in the control group. Serum IL-32 levels were measured by ELISA. The frequency of autoantibodies against Hu, Ri, Yo, Tr, CV2, amphiphysin, SOX1, Zic4, ITPR1, CARP, glutamic acid decarboxylase GAD, recoverin, titin, and ganglioside antigens was measured by the indirect immunofluorescence method. Results: Serum IL-32 levels in patients with schizophrenia were significantly higher compared to the control group. The frequency of autoantibodies against GAD and RI antigens in patients with schizophrenia was significantly higher than in the control group. Autoantibodies were positive in 8 patients for GAD antigen and 5 patients for RI antigen. Autoantibodies were also positive in 2 patients for CV2, 1 patient for Hu, and 1 patient for CARP. Negative results were reported for other antigens. Conclusion: Our findings suggest that elevated the serum IL-32 level and autoantibodies against GAD and RI antigens may be a reflection of immune system dysregulation in patients with schizophrenia.

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.

Background: The profile of inflammatory and suppressing cytokines is important to contribute to the disruption of TH1/TH2 balance in Allergic rhinitis (AR). Objective: This study aimed to assess the expression levels of IL-6, IL-18, IL-21, IL-23, and TGF-β in nasal biopsies in AR patients and evaluate its correlation with the severity of AR.Material and method: The study included 30 patients with mild persistent allergic rhinitis (MPAR), patients with moderate-to-severe (M/S) PAR, and 30 healthy individuals. The biopsies of nasal inferior turbinate mucosa were collected from each participant. The expression of IL-6, IL-18, IL-21, IL-23, and TGF-β was evaluated by the quantitative real-time polymerasechain reaction. The degree of eosinophil infiltration into the nasal mucosa, blood eosinophils, and total serum IgE level were also measured. Result: The expression of IL-6, IL-18, and IL-23 in patients with AR significantly increased compared to the control group. Conversely, the gene expression of the TGF-β declined in the M/S PAR group rather than the AR- group. The data did not show a significant difference in the expression of the IL-21 gene between AR+ and AR- groups. Conclusion: We suggested that inflammatory cytokines including IL-6, IL-18, and IL-23 may be involved in the severity of AR and associated with markers of inflammation. Keywords: Allergic rhinitis; inflammation; interleukin-23; Nasal Mucosa.

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.

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.

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.

Aims The aim of this study was to present a new method for removing Sodium dodecyl sulfate (SDS) detergent from decellularized bovine pericardium using vacuum. Materials and Methods The cows’ pericardia were collected and decellularized. The samples were incubated with SDS1% for 48 h at 40 °C. To perform vacuum washing (VW: negative pressure was used to wash and remove detergents), every decellularized tissue was cut in 75mm diameter and fixed via a stainless-steel ring with 60mm diameter in the center of filtration Buchner Funnel which was connected to glass filtration flask The system was connected to a vacuum pump by a hose, and a negative pressure of -100 mmHg was applied for 15 min. Then, the samples were shaken and washed at 40-rpm in 100 ml of distilled water for 45 min. This process was repeated for samples of each group (6 times for sample VW6h, 12 times for sample VW12h, and 24 times for sample VW24h). At the end of every cycle, the effluent was collected to take a sample for SDS measurement. The normal washing (NW) group containing distilled water (NWd) and PBS (Phosphate buffered saline) (NWp) were used to wash and remove detergents. SDS measurements, MTT Assay, histological and tensile test, to compare two methods were used. Results The highest SDS in the effluent was in groups VW12h and VW24h (P ≤ 0.001) and the lowest residual SDS in scaffold was in two groups of VW12h and VW24h (P ≤ 0.001). MTT assay showed that cell survival in the VW12h and VW24h groups was higher than other groups and there' was no significant difference between cell survival in the VW12h and VW24h groups. Histological study showed destruction of tissue in the VW24h group. The results of the tensile test were shown that the native group had the highest module and the lowest amount was the VW24h sample which was reported with P ≤ 0.001 significance for all groups. Conclusion VW12h can be used as an effective method for SDS removal from decellularized pericardium which morphologically demonstrated a good structure in ECM.

Statement of the Problem The sphenoid sinus is a common target of paranasal surgery. Functional endoscopic sinus surgery is likely to endanger the anatomic variations of vital structures adjacent to the sphenoid sinus. Purpose The aim of this study was to determine the variations of sphenoid sinus and the related structures by using cone-beam computed tomography (CBCT). Materials and Method In this descriptive-analytic study, CBCT images of 103 patients aged above 20-years were selected (206 sides). Degree of pneumatization of sphenoid sinus, pneumatization of the anterior clinoid process, pterygoid process, protrusion of optic canal, vidian canal, and foramen rotundum, as well as prevalence of sinus septa were recorded. Examinations were performed using On-Demand software (Version 1); data were analyzed by using chi-square test. Results There was a statistically significant correlation between the pterygoid pneumatization and vidian canal protrusion (p< 0.001), and foramen rotundum protrusion (p< 0.001). The optic canal protrusion was found to be significantly associated with the anterior clinoid pneumatization and pterygoid process (p< 0.001). Statistically significant relationship was also observed between the carotid canal protrusion and pterygoid process pneumatization (p< 0.001). Conclusion The anatomical variations of the sphenoid sinus tend to give rise to a complexity of symptoms and potentially serious complications. This variability necessitates a comprehensive understanding of the regional sphenoid sinus anatomy by a detailed CBCT sinus examination.

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.