Long-Term Effects of Hippocampal Low-Frequency Stimulation on Pro-Inflammatory Factors and Astrocytes Activity in Kindled Rats.

OBJECTIVE: Epilepsy is accompanied by inflammation, and the anti-inflammatory agents may have anti-seizure effects. In this investigation, the effect of deep brain stimulation, as a potential therapeutic approach in epileptic patients, was investigated on seizure-induced inflammatory factors. MATERIALS AND METHODS: In the present experimental study, rats were kindled by chronic administration of pentylenetetrazol (PTZ; 34 mg/Kg). The animals were divided into intact, sham, low-frequency deep brain stimulation (LFS), kindled, and kindled +LFS groups. In kindled+LFS and LFS groups, animals received four trains of intra-hippocampal low-frequency deep brain stimulation (LFS) at 20 minutes, 6, 24, and 30 hours after the last PTZ injection. Each train of LFS contained 200 pulses at 1 Hz, 200 µA, and 0.1 ms pulse width. One week after the last PTZ injection, the Y-maze test was run, and then the rats' brains were removed, and hippocampal samples were extracted for molecular assessments. The gene expression of two pro-inflammatory factors [interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)], and glial fibrillary acidic protein (GFAP) immunoreactivity (as a biological marker of astrocytes reactivation) were evaluated. RESULTS: Obtained results showed a significant increase in the expression of of interleukin-6 (IL-6), tumor necrosis factor (TNF)-α, and GFAP at one-week post kindling seizures. The application of LFS had a long-lasting effect and restored all of the measured changes toward normal values. These effects were gone along with the LFS improving the effect on working memory in kindled animals. CONCLUSION: The anti-inflammatory action of LFS may have a role in its long-lasting improving effects on seizure-induced cognitive disorders.

Neuroanatomical changes of the medial prefrontal cortex of male pups of Wistar rat after prenatal and postnatal noise stress.

Recent evidences showed that, noise stress causes abnormal changes in structure and function of central nervous system (CNS). The Current study was conducted to evaluate some stereological parameters of the medial prefrontal cortex (mPFC) of male pups of Wistar rat after prenatal and early postnatal noise stress. 18 pregnant Wistar rats were randomly divided into prenatal noise-exposed (NE) group, postnatal NE group, and controls. Male pups of NE groups were exposed to noise 100 dB at the frequency ranges of 500-8000 Hz, 4 h per day from gestational day one (GD1) to GD21 for the prenatal NE group, and from postnatal day one (PND1) to PND21 in the postnatal NE group. The Control group animals were maintained under standard condition without noise stimulation. Corticosterone level in plasma was measured using ELISA technique. Changes of the neurons and non-neurons cells number and volume of the mPFC were evaluated by stereological analysis. Tunnel assay was also used for detection of apoptotic cells. Increase in plasma corticosterone level, decrease in the number of neurons, and increase in the apoptotic cells number were observed in both NE groups. Decrease in volume of mPFC and also in non-neurons cells number was observed in the prenatal NE group. An increase in the non-neurons number was seen in the postnatal NE group. Data of the current comparative study showed that, noise stress during prenatal and early postnatal periods can induce the abnormal alteration in some stereological parameters of mPFC in male pups of Wistar rat. These negative alterations were more remarkable after prenatal noise stress.

Tacrolimus Improves the Implantation Rate in Patients with Elevated Th1/2 Helper Cell Ratio and Repeated Implantation Failure (RIF).

Introduction An abnormal endometrial immune response is involved in the pathogenesis of repeated implantation failure (RIF), so we investigated the effectiveness of tacrolimus treatment on the endometrium of RIF patients. Materials and Methods Ten RIF patients with elevated T-helper 1/T-helper 2 (Th1/Th2) cell ratios were recruited into a clinical study. The expression of p53, leukemia inhibitory factor (LIF), interleukin (IL)-4, IL-10, IL-17, and interferon gamma (IFN-γ) in the endometrium of patients with and without tacrolimus treatment and the association of these factors with assisted reproductive technology (ART) outcomes were investigated. Results Tacrolimus significantly increased the expression of LIF, IL-10, and IL-17 and decreased the expression of IL-4, IFN-γ, and the IFN-γ/IL-10 ratio in RIF patients. Tacrolimus treatment resulted in an implantation rate of 40%, a clinical pregnancy rate of 50%, and a live birth rate of 35% in RIF patients with elevated Th1/Th2 ratios who had previously failed to become pregnant despite at least three transfers of embryos. We also found a significant positive correlation between IL-10 levels and the implantation rate. Conclusions Our findings suggest that RIF patients with a higher Th1/Th2 ratio could be candidates for tacrolimus therapy and that this immunosuppressive drug could be acting through upregulation of LIF, IL-10, and IL-17.

Peripubertal stress following maternal immune activation sex-dependently alters depression-like behaviors in offspring.

There is an increasing evidence that maternal immune activation can render the offspring more vulnerable to the impacts of peripubertal stress on behavioral abnormalities in adulthood. The aim of this study was to investigate the combined effects of maternal immune activation and peripubertal stress on depression-related behaviors in male and female offspring. Pregnant mice were treated with lipopolysaccharides (LPS) or vehicle, and then offspring were subjected to stressful conditions or left unstressed during peripubertal period. Four behavioral tests including novelty-suppressed feeding test, sucrose preference test, tail suspension test, and forced swim test were used to measure depression-related behaviors in offspring. The activity of hypothalamic-pituitary-adrenal (HPA) or - gonadal (HPG) axes were also evaluated by measuring basal and stress-induced corticosterone, testosterone and estradiol levels in the serum of offspring. Our findings revealed that mild maternal immune activation and peripubertal stress interacted synergistically to induce depression-related symptoms and HPA axis hyperactivity in male offspring, whereas no significant changes were observed in female offspring. We also found that this combination of environmental factors significantly decreased serum testosterone and estradiol levels in adult male and female offspring respectively. There were also significant correlations between behavioral parameters and hormones. Taken together, these findings show that the combination of two environmental risk factors can predispose the male offspring to increased depression-related symptoms in adulthood as compared to the females. This study suggests that the combination of maternal immune activation and peripubertal stress can alter depression-related behaviors and HPA axis function in a sex-dependent manner.

The Effect of Prenatal Exposure to 2.4 GHz Radio Frequency on the Histology and Expression of the osteocalcin and RUNX2 Gene of the Forelimb in an NMRI Mouse.

Introduction: Today the use of electromagnetic waves has dramatically increased in modern industrial societies. This study aimed to investigate the effect of prenatal exposure to 2.4 GHz wireless frequency on forelimb development in an NMRI mouse in vivo. Methods: A total of 21 female mice weighing 25-30 g were included in the present study. They were randomly assigned to 3 groups, namely control (n=7), sham (n=7), and experimental (n=7). After mating, the experimental group was exposed to 2.4 GHz radio frequency at a distance of 20-30 cm from the device, 4 h/d until the delivery. The sham group was placed at a distance of 20-30 cm from the device every day without exposure to electromagnetic waves, and the control group had a pregnancy period without any stress and electromagnetic wave exposure. After giving birth, the forelimbs were isolated from the infants and examined by stereological studies and RT-PCR for the evaluation of osteocalcin and RUNX2 gene expression. Results: Although, at first glance, there was no macroscopic teratogen effect in forelimbs in all groups, via a stereological method, we showed that bone and cartilage volume decreased in the experimental group compared to the other groups. We also found that the experimental group had lower expression of the osteocalcin and RUNX2 gene than the control and sham groups did. However, there were no significant differences between the control and sham groups in terms of bone and cartilage volume and gene expression. Conclusion: Although teratogen effect of prenatal exposure to 2.4 GHz radio frequency on forelimbs was not demonstrated macroscopically, further studies showed negative effects on the forelimb bone, cartilage volume, and gene expression.

Curcumin protects purkinje neurons, ameliorates motor function and reduces cerebellar atrophy in rat model of cerebellar ataxia induced by 3-AP.

BACKGROUND: Cerebellar ataxias comprise a group of terminal illnesses with ataxia as the main symptom. Curcumin as a yellow polyphenol was extracted from the rhizome ofCurcuma longa. Owing to its antioxidant, anti-inflammatory, anti-fibrotic and anti-tumor features, curcumin is considered as a potential therapeutic agent. AIM: In this study, we aim to investigate the neuroprotective effects of oral administration of curcumin on a rat model of cerebellar ataxia induced by neurotoxin 3-acetylpyridine. METHODS: The animals were randomly separated into three groups (control, 3-acetylpyridine, and curcumin + 3-acetylpyridine). Next, motor performance and muscle electromyography activity were assessed. Then, in the molecular part of the study, the anti-apoptotic role of curcumin in cerebellar ataxia and its relationship to protection of Purkinje cells were investigated. RESULTS: Curcumin treatment improved motor coordination and muscular activity, reduced cleaved caspase-3, and increased glutathione level in 3-AP-lesioned rats as well as total volumes of cerebellar granular and molecular layers. CONCLUSION: the present study implies that curcumin might have neuroprotective effects to counteract neurotoxicity of 3-AP-induced ataxia.

Clinicopathologic Features of Colorectal Polyps in Shahid Beheshti University of Medical Sciences (SBMU).

Aim: This study was designed to report epidemiologic findings of polyps in Iranian patients, and predict histology of polyp regarding to demographic and colonoscopic findings. Background: Classification of colorectal polyps had been revised in the past two decades and there is a need for polyp categorization in the Iranian Health System. Patients and methods: In this retrospective study, the medical records of patients with colonoscopic diagnosis of polyp in pathology departments of SBMU affiliated teaching hospitals were reviewed. Patient's slides evaluated and demographics findings were assessed. The anatomical location, macroscopic appearance including size and histological assessment of all polyps were recorded. Results: From total number of 1106 polyps (detected in 862 patients), adenomatous polyps (638 [57.7%]) were the most prevalent findings, followed by colon mucosal tag (184[16.6%]), hyperplastic and serrated polyps (122[11%]), inflammatory polyps (110[9.9%]), hamartomatous (21[1.9%]), and malignant lesions (13[1.2%]). Multivariate logistic regression showed age (each one year increasing age; odds ratio [OR] = 1.026, 95%confidence interval [CI] = 1.016­1.036, p < 0.0001), location of polyp (right colon; OR = 1.905, 95%CI = 1.366­2.656, p < 0.0001), and polyp size of 5-10 mm (OR = 1.662, 95%CI = 1.214­2.276, p = 0.002), and polyp size of >10 mm (OR = 2.778, 95%CI = 1.750­4.411, p< 0.0001) were independently associated with neoplastic polyps. Also, polyp size of >10 mm (OR= 2.613, 95%CI= 1.083-6.307, p=0.033), tubulovillous pattern of polyp (OR= 3.508, 95%CI= 1.666-7.387, p=0.001) and villous pattern of polyp (OR= 10.444, 95%CI= 4.211-25.905, p<0.0001) were associated with high grade dysplasia in neoplastic polyps. Conclusion: Increased age, location of polyp (right colon), increased size of polyp and villous component of polyp could classify patients in high risk groups.

Sciatic nerve injury alters the spatial arrangement of neurons and glial cells in the anterior horn of the spinal cord.

The spatial arrangement of the cell is important and considered as underlying mechanism for mathematical modeling of cell to cell interaction. The ability of cells to take on the characteristics of other cells in an organism, it is important to understand the dynamical behavior of the cells. This method implements experimental parameters of the cell-cell interaction into the mathematical simulation of cell arrangement. The purpose of this research was to explore the three-dimensional spatial distribution of anterior horn cells in the rat spinal cord to examine differences after sciatic nerve injury. Sixteen Sprague-Dawley male rats were assigned to control and axotomy groups. Twelve weeks after surgery, the anterior horn was removed for first- and second-order stereological studies. Second-order stereological techniques were applied to estimate the pair correlation and cross-correlation functions using a dipole probe superimposed onto the spinal cord sections. The findings revealed 7% and 36% reductions in the mean volume and total number of motoneurons, respectively, and a 25% increase in the neuroglial cell number in the axotomized rats compared to the control rats. In contrast, the anterior horn volume remained unchanged. The results also indicated a broader gap in the pair correlation curve for the motoneurons and neuroglial cells in the axotomized rats compared to the control rats. This finding shows a negative correlation for the distribution of motoneurons and neuroglial cells in the axotomized rats. The cross-correlation curve shows a negative correlation between the motoneurons and neuroglial cells in the axotomized rats. These findings suggest that cellular structural and functional changes after sciatic nerve injury lead to the alterations in the spatial arrangement of motoneurons and neuroglial cells, finally affecting the normal function of the central nervous system. The experimental protocol was reviewed and approved by the Animal Ethics Committee of Shahid Beheshti University of Medical Sciences (approval No. IR.SBMU.MSP.REC1395.375) on October 17, 2016.

Effect of Artificial Oocyte Activation on Intra-Cytoplasmic Sperm Injection Outcomes in Patients with Lower Percentage of Sperm Containing Phospholipase Cζ: A Randomized Clinical Trial.

BACKGROUND: Artificial oocyte activation (AOA) is a specialized method in assisted reproductive technique (ART). According to increasing concern about using AOA, it is necessary to evaluate sperm-borne oocyte activating factors (SOAFs) including phospholipase C zeta (PLCζ). In this study, PLCζ before AOA was evaluated first and then the impact of AOA on pre-implantation embryo development was investigated. METHODS: This prospective clinical trial enrolled couples subjected to ICSI. By evaluating PLCζ, semen samples were categorized into two groups; I (Control) and II (PLCζ deficient). Retrieved oocytes from partners were put into three categories: control group (Injected with sperm from group I, n=113), group without AOA (Injected with sperm from group II and no exposure to AOA, n=106), and group AOA (Injected with sperm from group II and exposure to AOA, n=114). Finally, fertilization results were compared via Kruskal-Wallis followed by Dunn's multiple comparison test. The p<0.05 was considered statistically significant. RESULTS: Fertilization rate was significantly lower in the group without AOA compared to control group (41.9±6.3 vs. 78.1±4.7, p<0.001). AOA improved fertilization rate in group AOA compared to the group without AOA (69.5±3.9 vs. 41.9±6.3, p<0.01); however, cleavage (91.7±2.8, 90.9±4.6, and 95.2±3.4, respectively) and embryo quality (2.5±0.1, 2.3±0.2, and 2.4±0.2, respectively) scores were not substantially different between groups of control, with and without AOA. CONCLUSION: We showed that PLCζ can be considered as a good biomarker in evaluation of oocyte activation capability. Further studies are required to establish the best use of PLCζ as a biomarker in clinics.

Evaluation of PAWP and PLC? Expression in Infertile Men with Previous ICSI Fertilization Failure.

PURPOSE: The aim of this study was to evaluate postacrosomal sheet WW domain binding protein (PAWP) and phospholipase C ? (PLC?) protein expression in patients with fertilization failure. MATERIALS AND METHODS: Semen samples were collected from 15 fertile men (control group) and 15 patients with previous fertilization failure following ICSI (FF group) and were analyzed according to World Health Organization (WHO) criteria. The mean percentages of PAWP and PLC? positive sperm and the total level of PAWP and PLC? proteins were assessed using immunofluorescence staining. RESULTS: A significantly lower level and lower percentage of PAWP positive sperm in patients with fertilization failure was found compared to the control group (P = 0.01 and P = 0.03, respectively). The mean percentage ofPLC? positive sperm and level of PLC? protein were significantly lower in FF group compared to the control group (P = 0.0003 and P = 0.04, respectively). Significant positive correlations was observed between PAWP and PLC? positive sperms (r = 0.4, P = 0.008) and also total level of expression of PLC? and PAWP proteins (r = 0.4, P = 0.02) in all participants in the study. CONCLUSION: This is the first study that evaluates two main candidates for sperm-borne oocyte activating factors (SOAFs) simultaneously in patients with fertilization failure. Considering lower expression of PAWP and PLC? proteins in such patients, it seems like both factors might have the potential to be considered as SOAFs and diagnostic markers for the oocyte activation ability.

Oligoasthenoteratozoospermic (OAT) men display altered phospholipase C ζ (PLCζ) localization and a lower percentage of sperm cells expressing PLCζ and post-acrosomal sheath WW domain-binding protein (PAWP).

Oligoasthenoteratozoospermia (OAT) is demonstrated to be one of the most common causes of male subfertility. Phospholipase C ζ (PLCζ), a sperm-specific protein, is considered to be one of the sperm-borne oocyte activating factors (SOAFs), which play a vital role in fertilization. The post-acrosomal sheath WW domain-binding protein (PAWP) is another candidate for SOAF. The aim of this study was to compare the PLCζ localization patterns and percentage of PLCζ- and PAWP-positive sperm cells in patients with OAT and fertile men with normozoospermia. A total of 40 men included in this study were classified into two groups: OAT (n = 25) and control group (n = 15). Semen samples were collected and analyzed using conventional semen analysis according to the World Health Organization guidelines. The percentage of PLCζ- and PAWP-positive sperm cells and localization patterns of PLCζ were evaluated using immunofluorescence staining. The mean percentage of sperm cells expressing PAWP and PLCζ was significantly lower in OAT compared to control group (52.8 ± 4.2 vs. 76.8 ± 5 and 63.4 ± 3.5 vs. 86.7 ± 2.1, respectively). In addition, statistically significant differences were found with regard to the PLCζ localization patterns, including equatorial, acrosomal + equatorial, and equatorial + post-acrosomal pattern, between the two groups (p < 0.01). The present study showed a lower percentage of sperm cells expressing PLCζ and PAWP, as well as altered localization patterns of PLCζ in men with OAT. Given the role of PLCζ and PAWP in fertilization, as two major candidates for SOAFs, our findings indicate that PLCζ and PAWP impairments may be one of the possible etiologies of decreased fertility in OAT.

Phospholipase C zeta parameters in sperm from polymorphic teratozoospermic men.

Teratozoospermia is a disorder associated with high abnormal sperm morphology which affects fertility in males. In recent years, it has been described that biomarker-based sperm quality evaluation can alleviate male infertility treatment. Phospholipase C zeta (PLCζ) is a sperm-specific factor which appears to be a predicting biomarker for fertilization potential of males. Following fertilization, PLCζ enters into oocyte cytoplasm and induces oocyte activation, a fundamental stage in initiation of embryo development. Currently, PLCζ parameters, including localization patterns, the proportion of PLCζ-expressing sperm and the expression level, are not defined in polymorphic teratozoospermic men. This study aimed to evaluate PLCζ parameters in polymorphic teratozoospermic men, and compare these parameters with fertile normozoospermic men. Semen samples from thirteen normozoospermic fertile men and twenty-three polymorphic teratozoospermic men were included in this study and evaluated using western blotting and immunofluorescence analyses. Our data indicated significantly lower expression of PLCζ in polymorphic teratozoospermic men, as compared with control men; however, there was no significant difference in localization patterns and the proportion of PLCζ-expressing sperm between polymorphic teratozoospermic patients and control men. Collectively, findings from the present study demonstrated that polymorphic teratozoospermic men did not show abnormal localization patterns or the absence of PLCζ, as compared to the control men; nonetheless, lower expression of PLCζ, considering its role in oocyte activation, might be one of the possible causes of infertility in these patients.

Stimulation Effect of Low Level Laser Therapy on Sciatic Nerve Regeneration in Rat.

Introduction: Recent studies showed that low-level laser therapy (LLLT) accelerates the regeneration process of injured peripheral nerve tissue. The objective of this study was investigate the effect of LLLT (780 nm) on regeneration of injured right sciatic nerve of male Wistar rat. Methods: In this research work, the effect of LLLT (780 nm) on the regeneration process and reconstruction of injured peripheral right side sciatic nerve was investigated. Twelve adult male Wistar rats underwent surgery in aseptic conditions under general anesthesia to induce a lesion to their right side sciatic nerve according to standard protocol. Before suturing the location, only the experimental group was treated by laser. The damaged nerve was directly irradiated with (2 J, 100 mW, 40 seconds). The irradiation procedure was terminated in 21 days with little improvement (4 J, 200 mW, 40 seconds) across the skin surface of experimental group. Rats were selected randomly from each group to be sacrificed on different periods and histopathological examination was carried out on the extracted nerves. Results: Significant acceleration of revascularization and angiogenesis of the injury site was observed in the experimental group. Furthermore, a reduction of hemorrhages and increase in blood supply was observed. Also, Wallerian degeneration decreased while higher axonal density compared to the control rats was observed. Moreover, the cross-section analysis of the injured area on the 14th and 21st days as post-surgery showed that the nerve sheath diameter in the lesion area of the experimental group was reduced. While the ratio between thicknesses increased in the control group. Conclusion: The results of the current study suggest that laser phototherapy at 780 nm exactly could accelerate the regeneration process of injured peripheral nerves tissue.

Corrigendum to "Effect of Chronic Morphine Consumption on Synaptic Plasticity of Rat's Hippocampus: A Transmission Electron Microscopy Study".

[This corrects the article DOI: 10.1155/2013/290414.].

Erratum to: Evaluation of sHLA-G levels in serum of patients with prostate cancer identify as a potential of tumor marker.

[This corrects the article on p. 69 in vol. 50, PMID: 28417057.].

Spiritual Therapy in Coping with Cancer as a Complementary Medical Preventive Practice.

There are many of methods of treating cancer. However, the concept of curing the cancer is beyond our current knowledge. Some patients who have the cancer may seek an alternative manner of curing their disease. Alternative medicines, such as spiritual and complementary therapy, are able to cure the cancer and, at the least, are safe. Research on the importance of spirituality in cancer care has mainly been performed in geographically heterogeneous populations. The results are limited to these specific religious-cultural contexts and enlightened by contributions from ethnicity and religion. This article focused on the religiousness and spiritual support of cancer patients from diverse and heterogeneous groups around the globe. An electronic search of peer-reviewed articles was systematically performed to obtain the relevant literature with the CINAHL, PsycINFO, and PubMed databases. The keywords included religion, cancer, illness, psychotherapy, and spiritual and alternative treatment/therapies. The inclusion criteria for the reviews were that the documents were original quantitative research and published in English. Articles that were not directly relevant to the present objective were excluded. The present outcome of these review resources suggest that it may be helpful for clinicians to address spirituality, particularly with regard to prevention, healing, and survival of cancer patients. This article indicates that it may be useful for clinical oncologists to be informed of the prevalence of the use of spiritual medicine in their specialized field. In addition, patients should routinely be asked about the use of spiritual medicine as part of every cancer patient's evaluation.

Evaluation of sHLA-G levels in serum of patients with prostate cancer identify as a potential of tumor marker.

Prostate cancer is the most common cancer type in men and is the second cause of death, due to cancer, in patients over 50, after lung cancer. Prostate specific antigen (PSA) is a widely used tumor marker for prostate cancer. Recently, PSA is discovered in non-prostatic cancer tissues in men and women raising doubts about its specificity for prostatic tissues. PSA exists in low serum level in healthy men and in higher levels in many prostate disorders, including prostatitis and prostate cancer. Thus, a supplementary tumor marker is needed to accurately diagnose the cancer and to observe the patient after treatment. Recently, soluble human leukocyte antigen-G (sHLA-G) has been introduced as a new tumor marker for different cancer types, including colorectal, breast, lung, and ovary. The present descriptive-experimental study was carried out including patients with malignant prostate tumor, patients with benign prostate tumor, and a group of health men as the control group, as judged by an oncologist as well as a pathologist. After sterile blood sampling, sHLA-G was measured by enzyme-linked immunosorbent assay in each group. The data was then analyzed using one-way ANOVA. P≤0.05 was considered as statistically significant. The results showed that the mean of sHLA-G level was high in patients. Also, it was found that there was a significant difference in sHLA serum level between the three groups. The data revealed that sHLA-G can be a novel supplementary tumor marker in addition to PSA to diagnose prostate cancer.

Ultrastructural maturation of human bone marrow mesenchymal stem cells-derived cardiomyocytes under alternative induction of 5-azacytidine.

Adult cardiomyocytes lack the ability to proliferate and are unable to repair damaged heart tissue, therefore differentiation of stem cells to cardiomyocytes represents an exceptional opportunity to study cardiomyocytes in vitro and potentially provides a valuable source for replacing damaged tissue. However, characteristic maturity of the in vitro differentiated cardiomyocytes and methods to achieve it are yet to be optimized. In this study, differentiation of human bone marrow-mesenchymal stem cells (hBM-MSCs) into cardiomyocytes is accomplished and the process investigated ultrastructurally. The hBM-MSCs were alternatively treated with 5 µM of 5-azacytidine (5-aza) for 8 weeks resulting in differentiation to cardiomyocytes. Expressions of cardiomyocyte-specific genes [cardiac α-actinin, cardiac ß-myosin heavy chain (MHC) and connexin-43] and proteins (cardiac α-actinin, cardiac troponin and connexin-43) were confirmed in a time-dependent manner from the first to the fifth weeks post-induction. Ultrastructural maturation of hBM-MSCs-derived cardiomyocyte (MSCs-CM) corresponded with increase in number and organization of myofilaments in cells over time. Starting from week five, organized myofibrils along with developing sarcomeres were detectable. Later on, MSCs-CM were characterized by the presence of sarcoplasmic reticulum, T-tubules and diads as cardiomyocytes connected to each other by intercalated disc-like structures. Here, we showed the potential of hBM-MSCs as a source for the production of cardiomyocytes and confirmed mature ultrastructural characteristics of these cells using our alternative incubation method.

Expression of Glycogen synthase kinase 3-ß (GSK3-ß) gene in azoospermic men.

BACKGROUND: The Wnt/ß- The Wnt/ß-catenin signaling pathway is involved in many developmental processes in both fetal and adult life; its abnormalities can lead to disorders including several types of cancers and malfunction of specific cells and tissues in both animals and humans. Its role in reproductive processes has been proven. OBJECTIVE: This study was designed to evaluate the expression of the key regulator of this signaling pathway GSK3-ß and its presumed role in azoospermia. MATERIALS AND METHODS: WNT3a protein concentration and GSK3-ß gene expression levels were measured and compared between two groups of infertile men. The test groups consisted of 10 patients with obstructive and 10 non-obstructive azoospermia. The control group was selected among healthy men after vasectomies that were willing to conceive a child using a testicular biopsy technique. Samples were obtained by testicular biopsy and screened for the most common mutations (84, 86 and 255) in the SRY region before analyzing. GSK3-ß gene expression was assessed quantitatively by real time-PCR. RESULTS: The WNT3a protein concentration had no significant difference between the two test groups and controls. Expression of GSK3-ß was down-regulated in non-obstructive azoospermia (3.10±0.19) compared with normal (7.12±0.39) and obstructive azoospermia (6.32±0.42) groups (p=0.001). CONCLUSION: Down-regulation of GSK-3ß may cause to non-obstructive azoospermia. Regulation and modification of GSK-3ß gene expression by drugs could be used as a therapeutic solution.

The effect of high level natural ionizing radiation on expression of PSA, CA19-9 and CEA tumor markers in blood serum of inhabitants of Ramsar, Iran.

Since several high level natural radiation areas (HLNRAs) exist on our planet, considerable attention has been drawn to health issues that may develop as the result of visiting or living in such places. City of Ramsar in Iran is an HNLRA, and is a tourist attraction mainly due to its hot spas. However, the growing awareness over its natural radiation sources has prompted widespread scientific investigation at national level. In this study, using an ELISA method, the level of expression of three tumor markers known as carcinoembryonic antigen (CEA), prostate-specific antigen (PSA) and carcino antigen 19-9 (CA19-9) in blood serum of 40 local men of Ramsar (subject group) was investigated and compared to 40 men from the city of Noshahr (control group). Noshahr was previously identified as a normal level natural radiation area (NLNRA) that is some 85 km far from Ramsar. According to statistical analysis, there was a significant difference in the levels of PSA and CA19-9 markers between the two groups (p < 0.001) with those of Ramsar being considerably higher. CEA level did not show any difference. Although some of the volunteers tested positive to the markers, they were in good health as confirmed by the physician. Moreover, the high number of positive markers in Noshahr was considerable. Therefore, future study is needed to further validate this result and to determine the level of positivity to tumor markers in both cities.