Cell Journal (Yakhteh)
Volume:17 Issue: 2, Summer 2015

Population-based genetic association studies have proven to be a powerful tool in identifying genes implicated in many complex human diseases that have a huge impact on public health. An essential quality control step in such studies is to undertake Hardy-Weinberg equilibrium (HWE) calculations. Deviations from HWE in the control group may reflect important problems including selection bias, population stratification and genotyping errors. If HWE is violated, the inferences of these studies may thus be biased. We therefore aimed to examine the extent to which HWE calculations are reported in genetic association studies published in Cell Journal(Yakhteh) (Cell J). Using keywords pertaining to genetic association studies, eleven relevant articles were identified of which ten provided full genotypic data. The genotype distribution of 16 single nucleotide polymorphisms (SNPs) was re-analyzed for HWE by using three different methods where appropriate. HWE was not reported in 60% of all articles investigated. Among those reporting, only one article provided calculations correctly and in detail. Therefore, 90% of articles analyzed failed to provide sufficient HWE data. Interestingly, three articles had significant HWE deviation in their control groups of which one highly deviated from HWE expectations (P= 9.8×10-12). We thus show that HWE calculations are under-reported in genetic association studies published in this journal. Furthermore, the conclusions of the three studies showing significant HWE in their control groups should be treated cautiously as they may be potentially misleading. We therefore recommend that reporting of detailed HWE calculations should become mandatory for such studies in the future.

β-thalassemia is the most common single gene disorder worldwide, in which hemoglobin β-chain production is decreased. Today, the life expectancy of thalassemic patients is increased because of a variety of treatment methods; however treatment related complications have also increased. The most common side effect is osteoporosis, which usually occurs in early adulthood as a consequence of increased bone resorption. Increased bone resorption mainly results from factors such as delayed puberty, diabetes mellitus, hypothyroidism, ineffective hematopoiesis as well as hyperplasia of the bone marrow, parathyroid gland dysfunction, toxic effect of iron on osteoblasts, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) deficiency. These factors disrupt the balance between osteoblasts and osteoclasts by interfering with various molecular mechanisms and result in decreased bone density. Given the high prevalence of osteopenia and osteoporosis in thalassemic patients and complexity of their development process, the goal of this review is to evaluate the molecular aspects involved in osteopenia and osteoporosis in thalassemic patients, which may be useful for therapeutic purposes.

Hematopoietic stem cells (HSCs) transplantation using umbilical cord blood (UCB) has improved during the last decade. Because of cell limitations, several studies focused on the ex vivo expansion of HSCs. Numerous investigations were performed to introduce the best cytokine cocktails for HSC expansion The majority used the Fms-related tyrosine kinase 3 ligand (FLT3-L) as a critical component. According to FLT3-L biology, in this study we have investigated the hypothesis that FLT3-L only effectively induces HSCs expansion in the presence of a mesenchymal stem cell (MSC) feeder. In this experimental study, HSCs and MSCs were isolated from UCB and placenta, respectively. HSCs were cultured in different culture conditions in the presence and absence of MSC feeder and cytokines. After ten days of culture, total nucleated cell count (TNC), cluster of differentiation 34+ (CD34+) cell count, colony forming unit assay (CFU), long-term culture initiating cell (LTC-IC), homeobox protein B4 (HoxB4) mRNA and surface CD49d expression were evaluated. The fold increase for some culture conditions was compared by the t test. HSCs expanded in the presence of cytokines and MSCs feeder. The rate of expansion in the co-culture condition was two-fold more than culture with cytokines (P<0.05). FLT3-L could expand HSCs in the co-culture condition at a level of 20-fold equal to the presence of stem cell factor (SCF), thrombopoietin (TPO) and FLT3-L without feeder cells. The number of extracted colonies from LTC-IC and CD49d expression compared with a cytokine cocktail condition meaningfully increased (P<0.05). FLT3-L co-culture with MSCs can induce high yield expansion of HSCs and be a substitute for the universal cocktail of SCF, TPO and FLT3-L in feeder-free culture.

Pancreatic stroma plays an important role in the induction of pancreatic cells by the use of close range signaling. In this respect, we presume that pancreatic mesenchymal cells (PMCs) as a fundamental factor of the stromal niche may have an effective role in differentiation of umbilical cord blood cluster of differentiation 133+ (UCB-CD133+) cells into newly-formed β-cells in vitro. This study is an experimental research. The UCB-CD133+ cells were purified by magnetic activated cell sorting (MACS) and differentiated into insulin producing cells (IPCs) in co-culture, both directly and indirectly with rat PMCs. Immunocytochemistry and enzyme linked immune sorbent assay (ELISA) were used to determine expression and production of insulin and C-peptide at the protein level. Our results demonstrated that UCB-CD133+ differentiated into IPCs. Cells in islet-like clusters with (out) co-cultured with rat pancreatic stromal cells produced insulin and C-peptide and released them into the culture medium at the end of the induction protocol. However they did not respond well to glucose challenges. Rat PMCs possibly affect differentiation of UCB-CD133+ cells into IPCs by increasing the number of immature β-cells.

Superparamagnetic iron oxide nanoparticles (SPIONs) have been used to label mammalian cells and to monitor their fate in vivo using magnetic resonance imaging (MRI). However, the effectiveness of phenotype of labeled cells by SPIONs is still a matter of question. The aim of this study was to investigate the efficiency and biological effects of labeled mouse embryonic stem cells (mESCs) using ferumoxide- protamine sulfate complex. In an experimental study, undifferentiated mESCs, C571 line, a generous gift of Stem Cell Technology Company, were cultured on gelatin-coated flasks. The proliferation and viability of SPION-labeled cells were compared with control. ESCs and embryoid bodies (EBs) derived from differentiated hematopoietic stem cells (HSCs) were analyzed for stage-specific cell surface markers using fluorescence-activated cell sorting (FACS). Our observations showed that SPIONs have no effect on the self-renewal ability of mESCs. Reverse microscopic observations and prussian blue staining revealed 100% of cells were labeled with iron particles. SPION-labeled mESCs did not significantly alter cell viability and proliferation activity. Furthermore, labeling did not alter expression of representative surface phenotypic markers such as stage-specific embryonic antigen 1 (SSEA1) and cluster of differentiation 117 (CD117) on undifferentiated ESC and CD34, CD38 on HSCs, as measured by flowcytometry. According to the results of the present study, SPIONs-labeling method as MRI agents in mESCs has no negative effects on growth, morphology, viability, proliferation and differentiation that can be monitored in vivo, noninvasively. Noninvasive cell tracking methods are considered as new perspectives in cell therapy for clinical use and as an easy method for evaluating the placement of stem cells after transplantation.

Type I diabetes is an immunologically-mediated devastation of insulin producing cells (IPCs) in the pancreatic islet. Stem cells that produce β-cells are a new promising tool. Adult stem cells such as mesenchymal stem cells (MSCs) are self renewing multi potent cells showing capabilities to differentiate into ectodermal, mesodermal and endodermal tissues. Pancreatic and duodenal homeobox factor 1 (PDX1) is a master regulator gene required for embryonic development of the pancreas and is crucial for normal pancreatic islets activities in adults. We induced the over-expression of the PDX1 gene in human bone marrow MSCs (BM-MSCs) by Lenti-PDX1 in order to generate IPCs. Next, we examine the ability of the cells by measuring insulin/c-peptide production and INSULIN and PDX1 gene expressions. After transduction, MSCs changed their morphology at day 5 and gradually differentiated into IPCs. INSULIN and PDX1 expressions were confirmed by real time polymerase chain reaction (RT-PCR) and immunostaining. IPC secreted insulin and C-peptide in the media that contained different glucose concentrations. MSCs differentiated into IPCs by genetic manipulation. Our result showed that lentiviral vectors could deliver PDX1 gene to MSCs and induce pancreatic differentiation.

Distraction osteogenesis (DO) is a surgical procedure used to generate large volumes of new bone for limb lengthening. In this animal experimental study, a 30% lengthening of the left tibia (mean distraction distance: 60.8 mm) was performed in ten adult male dogs by callus distraction after osteotomy and application of an Ilizarov fixator. Distraction was started on postoperative day seven with a distraction rate of 0.5 mm twice per day and carried out at a rate of 1.5 mm per day until the end of the study. Autologous bone marrow mesenchymal stem cells (BM-MSCs) and platelet-rich plasma (PRP) as the treatment group (n=5) or PRP alone (control group, n=5) were injected into the distracted callus at the middle and end of the distraction period. At the end of the consolidation period, the dogs were sacrificed after which computerized tomography (CT) and histomorphometric evaluations were performed. Radiographic evaluationsrevealed that the amount and quality of callus formations were significantly higher in the treatment group (P<0.05). As measured by CT scan, the healing parametersin dogs of the treatment group were significantly greater (P<0.05). New bone formation in the treatment group was significantly higher (P<0.05). The present study showed that the transplantation of BM-MSCs positively affects early bony consolidation in DO. The use of MSCs might allow a shortened period of consolidation and therefore permit earlier device removal.

Perivitelline fluid (PVF) of the horseshoe crab embryo has been reported to possess an important role during embryogenesis by promoting cell proliferation. This study aims to evaluate the effect of PVF on the proliferation, chromosome aberration (CA) and mutagenicity of the dental pulp stem cells (DPSCs). This is an in vitro experimental study. PVF samples were collected from horseshoe crabs from beaches in Malaysia and the crude extract was prepared. DPSCs were treated with different concentrations of PVF crude extract in an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay (cytotoxicity test). We choose two inhibitory concentrations (IC50 and IC25) and two PVF concentrations which produced more cell viability compared to a negative control (100%) for further tests. Quantitative analysis of the proliferation activity of PVF was studied using the AlamarBlue® assay for 10 days. Population doubling times (PDTs) of the treatment groups were calculated from this assay. Genotoxicity was evaluated based on the CA and Ames tests. Statistical analysis was carried out using independent t test to calculate significant differences in the PDT and mitotic indices in the CA test between the treatment and negative control groups. Significant differences in the data were P<0.05. A total of four PVF concentrations retrieved from the MTT assay were 26.887 mg/ml (IC50), 14.093 mg/ml (IC25), 0.278 mg/ml (102% cell viability) and 0.019 mg/ml (102.5% cell viability). According to the AlamarBlue® assay, these PVF groups produced comparable proliferation activities compared to the negative (untreated) control. PDTs between PVF groups and the negative control were insignificantly different (P>0.05). No significant aberrations in chromosomes were observed in the PVF groups and the Ames test on the PVF showed the absence of significant positive results. PVF from horseshoe crabs produced insignificant proliferative activity on treated DPSCs. The PVF was non-genotoxic based on the CA and Ames tests.

In order to retain an undifferentiated pluripotent state, embryonic stem (ES) cells have to be cultured on feeder cell layers. However, use of feeder layers limits stem cell research, since experimental data may result from a combined ES cell and feeder cell response to various stimuli. In this experimental study, a buffalo ES cell line was established from in vitro derived blastocysts and characterized by the Alkaline phosphatase (AP) and immunoflourescence staining of various pluripotency markers. We examined the effect of various factors like fibroblast growth factor 2 (FGF-2), leukemia inhibitory factor (LIF) and Y-27632 to support the growth and maintenance of bubaline ES cells on gelatin coated dishes, in order to establish feeder free culture systems. We also analyzed the effect of feeder-conditioned media on stem cell growth in gelatin based cultures both in the presence as well as in the absence of the growth factors. The results showed that Y-27632, in the presence of FGF-2 and LIF, resulted in higher colony growth and increased expression of Nanog gene. Feeder-Conditioned Medium resulted in a significant increase in growth of buffalo ES cells on gelatin coated plates, however, feeder layer based cultures produced better results than gelatin based cultures. Feeder layers from buffalo fetal fibroblast cells can support buffalo ES cells for more than two years. We developed a feeder free culture system that can maintain buffalo ES cells in the short term, as well as feeder layer based culture that can support the long term maintenance of buffalo ES cells.

Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, is resistant to anticancer drugs. Angiogenesis is a major cause of tumor resistance to chemotherapy, and vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. The purpose of this study is to investigate the impact of small-interfering RNA targeting VEGF gene (VEGF-siRNA) on chemosensitivity of HCC cells in vitro. In this experimental study, transfection was performed on Hep3B cells. After transfection with siRNAs, VEGF mRNA and protein levels were examined. Cell proliferation, apoptosis and anti-apoptotic gene expression were also analyzed after treatment with VEGF-siRNA in combination with doxorubicin in Hep3B cells. Transfection of VEGF-siRNA into Hep3B cells significantly reduced the expression of VEGF at both mRNA and protein levels. Combination therapy with VEGF-siRNA and doxorubicin more effectively suppressed cell proliferation and induced apoptosis than the respective monotherapies. This could be explained by the significant downregulation of B-cell lymphoma 2 (BCL-2) and SURVIVIN. VEGF-siRNA enhanced the chemosensitivity of doxorubicin in Hep3B cells at least in part by suppressing the expression of anti-apoptotic genes. Therefore, the downregulation of VEGF by siRNA combined with doxorubicin treatment has been shown to yield promising results for eradicating HCC cells.

Embryonic germ (EG) cells are the results of reprogramming primordial germ cells (PGC) in vitro. Studying these cells can be of benefit in determining the mechanism by which specialized cells acquire pluripotency. Therefore in the current study we have tried to derive rat EG cells with inhibition of transforming growth factor-β (TGFβ) and mitogen-activated protein kinase kinase (MEK) signaling pathways. In this experimental study, rat PGCs were cultured under feeder free condition with two small molecules that inhibited the above mentioned pathways. Under this condition only two-day presence of stem cell factor (SCF) as a survival factor was applied for PGC reprogramming. Pluripotency of the resultant EG cells were further confirmed by immunofluorescent staining, directed differentiation ability to neural and cardiac cells, and their contribution to teratoma formation as well. Moreover, chromosomal stability of two different EG cells were assessed through Gbanding technique. Formerly, derivation of rat EG cells were observed solely in the presence of glycogen synthase kinase-3 (GSK3β) and MEK pathway inhibitors. Due to some drawbacks of inhibiting GSK3β molecules such as increases in chromosomal aberrations, in the present study we have attempted to assess a feeder-free protocol that derives EG cells by the simultaneous suppression of TGFβ signaling and the MEK pathway. We have shown that rat EG cells could be generated in the presence of two inhibitors that suppressed the above mentioned pathways. Of note, inhibition of TGFβ instead of GSK3β significantly maintained chromosomal integrity. The resultant EG cells demonstrated the hallmarks of pluripotency in protein expression level and also showed in vivo and in vitro differentiation capacities. Rat EG cells with higher karyotype stability establish from PGCs by inhibiting TGFβ and MEK signaling pathways.

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

Due to the restricted potential of neural stem cells for regeneration of central nervous system (CNS) after injury, providing an alternative source for neural stem cells is essential. Adipose derived stem cells (ADSCs) are multipotent cells with properties suitable for tissue engineering. In addition, alginate hydrogel is a biocompatible polysaccharide polymer that has been used to encapsulate many types of cells. The aim of this study was to assess the proliferation rate and level of expression of neural markers; NESTIN, glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP2) in encapsulated human ADSCs (hADSCs) 10 and14 days after neural induction. In this experimental study, ADSCs isolated from human were cultured in neural induction media and seeded into alginate hydrogel. The rate of proliferation and differentiation of encapsulated cells were evaluated by 3-[4, 5-dimethylthiazol- 2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay, immunocytoflourescent and realtime reverse transcriptase polymerase chain reaction (RT-PCR) analyzes 10 and 14 days after induction. The rate of proliferation of encapsulated cells was not significantly changed with time passage. The expression of NESTIN and GFAP significantly decreased on day 14 relative to day 10 (P<0.001) but MAP2 expression was increased. Alginate hydrogel can promote the neural differentiation of encapsulated hADSCs with time passage.

To explore the cumulative genotoxic damage to glioblastoma (GBM) cells, grown as multicellular spheroids, following exposure to 6 MV X-rays (2 Gy, 22 Gy) with or without, 2- methoxy estradiol (2ME2), iododeoxyuridine (IUDR) or topotecan (TPT), using the Picogreen assay. The U87MG cells cultured as spheroids were treated with 6 MV X-ray using linear accelerator. Specimens were divided into five groups and irradiated using X-ray giving the dose of 2 Gy after sequentially incubated with one of the following three drug combinations: TPT, 2-ME2/TPT, IUDR/TPT or 2ME2/IUDR/ TPT. One specimen was used as the irradiated only sample (R). The last group was also irradiated with total dose of 22 Gy (each time 2 Gy) of 6 MV X-ray in 11 fractions and treated for three times. DNA damage was evaluated using the Picogreen method in the experimental study. R/TPT treated group had more DNA damage [double strand break (DSB)/single strand break (SSB)] compared with the untreated group (P<0.05). Moreover the R/ TPT group treated with 2ME2 followed by IUDR had maximum DNA damage in spheroid GBM indicating an augmented genotoxicity in the cells. The DNA damage was induced after seven fractionated irradiation and two sequential treatments with 2ME2/IUDR/TPT. To ensure accuracy of the slope of dose response curve the fractionated radiation was calculated as 7.36 Gy with respect to α/β ratio based on biologically effective dose (BED) formulae. Cells treated with 2ME2/IUDR showed more sensitivity to radiation and accumulative DNA damage. DNA damage was significantly increased when GBM cells treated with TPT ceased at S phase due to the inhibition of topoisomerase enzyme and phosphorylation of Chk1 enzyme. These results suggest that R/TPTtreated cells increase sensitivity to 2ME2 and IUDR especially when they are used together. Therefore, due to an increase in the level of DNA damage (SSB vs. DSB) and impairment of DNA repair machinery, more cell death will occur. This in turn may improve the treatment of GBM.

In today’s world, 2.45-GHz radio-frequency radiation (RFR) from industrial, scientific, medical, military and domestic applications is the main part of indoor-outdoor electromagnetic field exposure. Long-term effects of 2.45-GHz Wi-Fi radiation on male reproductive system was not known completely. Therefore, this study aimed to investigate the major cause of male infertility during short- and long-term exposure of Wi-Fi radiation. This is an animal experimental study, which was conducted in the Department of Anatomical Sciences, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, IRAN, from June to August 2014. Three-month-old male Wistar rats (n=27) were exposed to the 2.45 GHz radiation in a chamber with two Wi-Fi antennas on opposite walls. Animals were divided into the three following groups: I. control group (n=9) including healthy animals without any exposure to the antenna, II. 1-hour group (n=9) exposed to the 2.45 GHz Wi-Fi radiation for 1 hour per day during two months and III.7-hour group (n=9) exposed to the 2.45 GHz Wi-Fi radiation for 7 hours per day during 2 months. Sperm parameters, caspase-3 concentrations, histomorphometric changes of testis in addition to the apoptotic indexes were evaluated in the exposed and control animals. Both 1-hour and 7-hour groups showed a decrease in sperm parameters in a time dependent pattern. In parallel, the number of apoptosis-positive cells and caspase-3 activity increased in the seminiferous tubules of exposed rats. The seminal vesicle weight reduced significantly in both1-hour or 7-hour groups in comparison to the control group. Regarding to the progressive privilege of 2.45 GHz wireless networks in our environment, we concluded that there should be a major concern regarding the timedependent exposure of whole-body to the higher frequencies of Wi-Fi networks existing in the vicinity of our living places.

This study was conducted to assess survival of follicles, their oocyte maturation and fertilization potential as well as expression of early embryo developmental genes in in vitro cultured pre-antral follicles derived from vitrified-warmed mouse ovary. In this experimental study, ovaries of 12-day old Naval Medical Research Institute (NMRI) female mice were placed into non-vitrified and vitrifiedwarmed groups. Isolated preantral follicles from experimental groups were cultured in vitro for 12 days. On the 12th day of culture, oocyte maturation was induced and then matured oocytes were in vitro fertilized. The rates of oocyte maturation and two-cell stage embryo formation were assessed. Relative expression of Mater and Zar1 was evaluated on days 1, 6, 10 and 12 of culture. Data analysis was performed by t test and two-way ANOVA (P<0.05). Our data showed no significant difference between the control and vitrification groups in the rate of follicular survival, oocyte maturation and two-cell stage embryo formation. The level of gene expression was higher on the 6th and 10th days of culture for Mater and Zar1 in vitrified-warmed group compared with non-vitrified group, however, there was no significant difference between the two groups. It seems that the applied vitrification method did not reveal any negative effect on maturation and developmental competence of oocytes surrounded in preantral follicles and therefore could preserve follicular reserves efficiently.

To investigate the transdifferentiation relationship between eight types of liver cell during rat liver regeneration (LR). 114 healthy Sprague-Dawley (SD) rats were used in this experimental study. Eight types of liver cell were isolated and purified with percoll density gradient centrifugation and immunomagentic bead methods. Marker genes for eight types of cell were obtained by retrieving the relevant references and databases. Expression changes of markers for each cell of the eight cell types were measured using microarray. The relationships between the expression profiles of marker genes and transdifferentiation among liver cells were analyzed using bioinformatics. Liver cell transdifferentiation was predicted by comparing expression profiles of marker genes in different liver cells. During LR hepatocytes (HCs) not only express hepatic oval cells (HOC) markers (including PROM1, KRT14 and LY6E), but also express biliary epithelial cell (BEC) markers (including KRT7 and KRT19); BECs express both HOC markers (including GABRP, PCNA and THY1) and HC markers such as CPS1, TAT, KRT8 and KRT18; both HC markers (KRT18, KRT8 and WT1) and BEC markers (KRT7 and KRT19) were detected in HOCs. Additionally, some HC markers were also significantly upregulated in hepatic stellate cells (HSCs), sinusoidal endothelial cells (SECs), Kupffer cells (KCs) and dendritic cells (DCs), mainly at 6-72 hours post partial hepatectomy (PH). Our findings indicate that there is a mutual transdifferentiation relationship between HC, BEC and HOC during LR, and a tendency for HSCs, SECs, KCs and DCs to transdifferentiate into HCs.

Oxidative stress down regulates antioxidant enzymes including superoxide dismutase (SOD) and contributes to the development of cardiac hypertrophy. N-Acetyl cysteine (NAC) can enhance the SOD activity, so the aim of this study is to highlight the inhibitory role of NAC against endothelin-1 (ET-1)-induced cardiac hypertrophy. In this experimental study at QAU from January, 2013 to March, 2013. ET-1 (50 μg/kg) and NAC (50 mg/kg) were given intraperitoneally to 6-day old neonatal rats in combination or alone. All rats were sacrificed 15 days after the final injection. Histological analysis was carried out to observe the effects caused by both drugs. Reactive oxygen species (ROS) analysis and SOD assay were also carried out. Expression level of hypertrophic marker, brain natriuretic peptide (BNP), was detected by western blotting. Our findings showed that ET-1-induced cardiac hypertrophy leading towards heart failure was due to the imbalance of different parameters including free radical-induced oxidative stress and antioxidative enzymes such as SOD. Furthermore NAC acted as an antioxidant and played inhibitory role against ROS-dependent hypertrophy via regulatory role of SOD as a result of oxidative response associated with hypertrophy. ET-1-induced hypertrophic response is associated with increased ROS production and decreased SOD level, while NAC plays a role against free radicals-induced oxidative stress via SOD regulation.

Chlorpyrifos (CP) as an organophosphorus pesticide is thought to induce oxidative stress in human cells via producing reactive oxygen species (ROS) that leads to the presence of pathologic conditions due to apoptosis along with acetylcholinesterase (AChE) inhibition.This study aimed to evaluate the apoptotic effects of CP and to assess the protective potential of CeO2 nanoparticle (CNP) and sodium selenite (SSe) by measuring cascades of apoptosis, oxidative stress, inflammation, and AChE inhibition in human isolated lymphocytes. In the present experimental study, we examined the anti-oxidative and AChE activating potential of CNP and SSe in CP-treated human lymphocytes. Therefore, the lymphocytes were isolated and exposed to CP, CP+CNP, CP+SSe, and CP+CNP+SSe after a three-day incubation. Then tumor necrosis factor-alpha (TNF-α) release, myeloperoxidase (MPO) activity, thiobarbituric acid-reactive substances (TBARS) levels as inflammatory/oxidative stress indices along with AChE activity were assessed. In addition, the apoptotic process was measured by flow cytometry. Results showed a significant reduction in the mortality rate, TNF-α, MPO activity, TBARS, and apoptosis rate in cells treated with CNP, SSe and their combination. Interestingly, both CNP and SSe were able to activate AChE which is inhibited by CP. The results supported the synergistic effect of CNP/SSe combination in the prevention of apoptosis along with oxidative stress and inflammatory cascade. CP induces apoptosis in isolated human lymphocytes via oxidative stress and inflammatory mediators. CP firstly produces ROS, which leads to membrane phospholipid damage. The beneficial effects of CNP and SSe in reduction of CP-induced.

In recent years emphasis has been placed on evaluation studies and the publication of scientific papers in national and international journals. In this regard the publication of scientific papers in journals in the Institute for Scientific Information (ISI) database is highly recommended. The evaluation of scientific output via articles in journals indexed in the ISI database will enable the Iranian research authorities to allocate and organize research budgets and human resources in a way that maximises efficient science production. The purpose of the present paper is to publish a general and valid view of science production in the field of stem cells. In this research, outputs in the field of stem cell research are evaluated by survey research, the method of science assessment called Scientometrics in this branch of science. A total of 1528 documents was extracted from the ISI database and analysed using descriptive statistics software in Excel. The results of this research showed that 1528 papers in the stem cell field in the Web of Knowledge database were produced by Iranian researchers. The top ten Iranian researchers in this field have produced 936 of these papers, equivalent to 61.3% of the total. Among the top ten, Soleimani M. has occupied the first place with 181 papers. Regarding international scientific participation, Iranian researchers have cooperated to publish papers with researchers from 50 countries. Nearly 32% (452 papers) of the total research output in this field has been published in the top 10 journals. These results show that a small number of researchers have published the majority of papers in the stem cell field. International participation in this field of research unacceptably low. Such participation provides the opportunity to import modern science and international experience into Iran. This not only causes scientific growth, but also improves the research and enhances opportunities for employment and professional development. Iranian scientific outputs from stem cell research should not be limited to only a few specific journals.

Thallium acetate (TI) is a cumulative poison intimately accompanied by an increase in reactive oxygen species (ROS) formation that represents an important risk factor for tissue injury and malfunction. This study aims to determine the possible hepatoprotective and antioxidant effects of diallyl sulfide (DAS) from garlic and curcumin from turmeric against TI-induced liver injury and oxidative stress (OS) in rats. This in vivo animal study divided rats into six groups of 8 rats per group. The first group received saline and served as the control group. The second and third groups received DAS or curcumin only at a dose of 200 mg/kg. The fourth group received TI at a dose of 6.4 mg/kg for 5 consecutive days. The fifth and sixth groups received DAS or curcumin orally 1 hour before TI intoxication at the same dose as the second and third groups. Liver integrity serum enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and γ-glutamyltransferase (γ-GT) were evaluated. Serum and liver tissue homogenate lipid peroxidation and OS biomarkers were measured. The data were analyzed by one-way ANOVA followed by Duncan’s multiple range test for post hoc analysis using SPSS version 16. TI induced marked oxidative liver damage as shown by significantly (P≤0.05) elevated serum AST, ALT, ALP, LDH and γ-GT levels. There were significant (P≤0.05) increases in serum and hepatic malondialdehyde (MDA) and serum nitric oxide (NO) as well as decreased hepatic glutathione (GSH) and catalase (CAT) activities. There were significantly (P≤0.05) less serum and hepatic superoxide dismutase (SOD) and total antioxidant capacity (TAC). Pre-treatment with DAS or curcumin ameliorated the changes in most studied biochemical parameters. DAS and curcumin effectively reduced TI-induced liver toxicity.

Cerebral palsy (CP) is a non progressive, demyelinating disorder that affects a child’s development and posture and may be associated with sensation, cognition, communication and perception abnormalities. In CP, cerebral white matter is injured resulting in the loss of oligodendrocytes. This causes damage to the myelin and disruption of nerve conduction. Cell therapy is being explored as an alternate therapeutic strategy as there is no treatment currently available for CP. To study the benefits of this treatment we have administered autologous bone marrow mononuclear cells (BMMNCs) to a 12-year-old CP case. He was clinically re-evaluated after six months and found to demonstrate positive clinical and functional outcomes. His trunk strength, upper limb control, hand functions, walking stability, balance, posture and coordination improved. His ability to perform activities of daily living improved. On repeating the Functional Independence Measure (FIM), the score increased from 90 to 113. A repeat positron emission tomography- computed tomography (PET-CT) scan of the brain six months after intervention showed progression of the mean standard deviation values towards normalization which correlated to the functional changes. At one year, all clinical improvements have remained. This indicated that cell transplantation may improve quality of life and have a potential for treatment of CP.