mohammad ahmadvand

Blocking of inhibitory receptors such as NK group-2 member-A (NKG2A) enhances tumor immunity of natural killer (NK) cells. Additionally, antibody-dependent cellular cytotoxicity (ADCC) is an important cytotoxic modality of action of NK cells, which act as a functional bridge between innate and adaptive immunity. Here, we investigated the safety and feasibility of anti-NKG2A antibody-pretreated NK cells combined with IgG1 antibody (cetuximab) in patients with advanced gastric adenocarcinoma (GAC).

In this pilot study, treatment was initiated with cetuximab-based chemotherapy, followed by three times adoptive administration of anti-NKG2A pretreated NK cells (at doses 7×108 cells/injection) at 5-day intervals in three unresectable and locally advanced GAC patients who enrolled regarding vital signs and clinical characteristics. The clinical signs, laboratory parameters, and CTCAE (Common Terminology Criteria for Adverse Events) were documented for a safety and feasibility assessment.

The expanded cells were confirmed to be enriched in NK cells with high expression of CD56 (88.1%) and low expression of NKG2A (0.22%). The combination NK cell therapy was well tolerated, with transient adverse events. All patients were alive at the last follow-up (24 weeks). All patients showed overall decreases in tumor size and CA 19–9 level 4 weeks after combination therapy. However, two patients showed progressive disease (PD) after 12 weeks and the level of CA19-9 was increased in all three patients after 24 weeks.

In conclusion, this study demonstrated the safety and feasibility of infusing high doses of anti-NKG2A pretreated NK cells combined with cetuximab in patients with GAC.

Growing evidence supports that changes in the expression of the suppressor of cytokine signaling 3 (SOCS3) protein contribute to the pathogenesis of types of inflammatory bowel diseases (IBDs), including ulcerative colitis (UC). Despite the importance of the currently known genetic risk map, an increasing number of observations reveal that epigenetic modifications, including DNA methylation, are considered as or even more important for IBD pathogenesis than genetic predisposition. We investigated the hypothesis that alterations in DNA methylation status at the promoter region within the SOCS3 gene in colorectal tissue specimens may be involved in the susceptibility to UC.

We studied extracted DNA from colorectal biopsies of 15 ulcerative colitis cases and 15 age—and sex-matched healthy controls and performed genotype analyses of the promoter methylation status of the SOCS3 gene, using the real-time quantitative multiplex methylation-specific PCR (QM-MSP) assay to show evidence of differential methylation between cases of ulcerative colitis and healthy controls.

Based on methylation assay data profiling, we found that the mean CpG island methylation levels at the SOCS3 gene promoter region in colorectal mucosa of patients with UC was significantly higher than mucosa from healthy controls (ulcerative colitis vs. healthy controls; 0.00007±0.0018 vs. 0.07±0.142, p<0.000).

Our data provide an important insight into the influence of epigenetic aberrances in the SOCS3 gene such that the inactivation of the SOCS3 gene by promoter hypermethylation might be a risk factor for inflamed mucosa of UC. It might also fundamentally contribute to the initiation of the inflammatory process and development of UC.

 The activities and functions of natural killer (NK) cells are regulated by a limited repertoire of activating and inhibitory receptors. Thus, we provided a study of inhibition of the NKG2A using monoclonal antibodies (mAbs), and as a primary endpoint, we evaluated whether it can be translated to enhance adoptive NK cell immunotherapy, as the secondary endpoint, we investigated safety and feasibility.

 In this study, we investigated the safety of anti-NKG2A-pretreated NK cells in improving ADCC function to manage hepatocellular carcinoma (HCC). After a conditioning regimen, we initiated a pilot study of expanded donor haploidentical NK cell infusion. Patients received a fludarabine/cyclophosphamide conditioning followed by adoptive immunotherapy with IL2–activated haploidentical NK cells. Anti-NKG2A pretreated NK cells were infused on days 0,+5, and+10 post-conditioning regimens at a dose of 7×108 cells (n=3). The median follow-up was 4 months for all patients.

 Although all patients were alive at the last follow-up, two of them showed progressive disease and an increase in tumor size. In addition, all patients showed a relative decrease in alpha-fetoprotein (AFP) expression levels after one month.

 This study demonstrated the safety and feasibility of infusing high doses of ex vivo expanded NK cells after conditioning with transient side effects.

Context: 

Adoptive T-cell therapy with chimeric antigen receptor (CAR) has shown tremendous progress in hematological cancers. However, some obstacles, such as high price tag, cytokine release syndrome, inability to penetrate solid tumors, and manufacturing complexity limit the wide application of this therapy. Natural killer (NK) cells can kill target cells via mechanisms similar to those of CD8+ cytotoxic T cells; therefore, CAR-NK cell therapy is a promising strategy for cancer treatment.

Evidence Acquisition:

 In this manuscript, all articles published in English regarding CAR-NKs and their application for the treatment of different types of cancers were collected from several databases, including PubMed, Scopus, and Google Scholar, using related keywords such as "Cancer, CAR construction, NK cells, and CAR-NK cells".

Compared with CAR-T cells, CAR-NK cells have several advantages, including less toxicity, a high potential opportunity for universal off-the-shelf manufacturing, increased infiltration into solid tumors, overcoming resistant tumor microenvironment, and absence of graft-versus-host disease (GVHD).

In this review, we discuss NK cell biology, the source of CAR-NK cells, CAR structure, advances, challenges, and ways to overcome these challenges in CAR-NK cell therapy. Furthermore, we have summarized and highlighted some preclinical and clinical studies in this field.

Despite substantial efforts to leverage natural killer (NK) cells in cancer immunotherapy, challenges associated with limited cell numbers and sources persist. In this study, our objective is to differentiate NK cells from cord blood hematopoietic stem cells (CB-HSCs) and assess their anti-tumor effects.

Cord blood samples were obtained from pregnant women undergoing normal delivery. Mononuclear cells (MNC) were isolated by gradient centrifugation. Subsequently, HSCs were isolated using the MACs cell separation kit. The isolated HSCs were cultured in NK cell differentiation and expansion media for 21 days and 7 days, respectively. The NK cells were examined for expression of activating markers, cytokine secretion and cytolytic effects by flow cytometry, ELISA and XTT tests, respectively.

High-purity HSCs and NK cells were obtained in this study. The CB-HSCs-derived NK cells exhibited significantly higher expression of NKG2D, NKp30, NKp44 and NKp46 receptors (at day 28 of treatment) after treatment by IL-15 and IL-2, compared to the early differentiated NK cells (day 21). NK cells derived from CB-HSCs treated with the combination of IL-15 and IL-2 could robustly lyse breast cancer MCF-7 and K562 cells. Also, the obtained NK cells were able to release higher amounts of TNF-α and IFN-γ cytokines in response to tumor cell experiences.

Our findings showed that functionally active CB-HSCs-derived NK cells can be successfully generated ex vivo using a cytokine cocktail without a need for stroma for potential use in the cancer immunotherapy.

Changes in the expression of nucleotide-binding oligomerization domain containing 2 (NOD2) play an important role in the pathogenesis of a variety of autoimmune diseases including inflammatory bowel diseases (IBDs). Epigenetic modifications, including DNA methylation, are considered an important mechanism in the suppression of gene activity. In this study, we investigated the relationship between DNA methylation patterns of the promoter region of the NOD2 gene and the pathogenesis of Crohn’s disease (CD).

Colonic mucosa samples were obtained from 15 Iranian patients with IBD and 15 age- and sex-matched healthy controls with no history of autoimmune disease. After the bisulfite conversion of genomic DNA, the DNA methylation status of three CpG sites in the promoter region of the NOD2 gene was determined by the real-time quantitative multiplex methylation-specific PCR (QM-MSP) assay.

Using this approach, we identified that IBD patients showed a decreased level of methylation of the NOD2 promoter in the colonic mucosa than did the healthy controls. (Unmethylated DNA in Crohn's disease vs. healthy controls; 0.128±0.093 vs. 0.025±0.016, P<0.000).

According to our findings, promoter hypomethylation of the NOD2 gene in the colonic mucosa might contribute to the development and severity of CD. Furthermore, aberrant DNA methylation levels are expected to serve as a clinically useful risk marker.

Gastric cancer is one of the most commonly known malignancies and is the fifth cancer-related death globally. Whereas natural killer (NK) cells play a critical role in tumor elimination; therefore, adoptive NK cell therapy has become a promising approach in cancer cytotherapy. Hence, this study investigated the chemoimmune cell therapy in MKN-45 derived xenograft gastric cancer model.

Three groups of animals have received the following treatments separately: activated NK cells, capecitabine, the combination of capecitabine and activated NK cells, and one was considered as the control group. Morphometric properties of tumor samples were evaluated at the end of the study. NK cells infiltration was evaluated by immunohistochemistry (IHC) of hCD56. Mitotic count and treatment response was assessed by hematoxylin and eosin (H&E) staining. The proliferation ratio to apoptosis was determined by IHC assessment of Ki67 and caspase 3.

The results indicated that the NK cell therapy could effectively decrease the mitotic count in pathology assessment, but the tumor was not completely eradicated. In combination with metronomic chemotherapy (MC) of capecitabine, NK cell therapy demonstrated a significant difference in tumor morphometric properties compared to the control group. The proliferation ratio to apoptosis was also in line with pathology data.

Although NK cell therapy could effectively decrease the mitotic count in vivo, the obtained findings indicated lesser potency than MC despite ex vivo activation. In order to enhance NK cell therapy effectiveness, suppressive features of the tumor microenvironment and inhibitory immune checkpoints blockade should be considered.

Changes in the expression of nucleotide-binding oligomerization domain containing 2 (NOD2) play an important role in the pathogenesis of several autoimmune diseases, such as inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). It seems that epigenetic modifications, including DNA methylation, have an important role in the suppression of gene activity. In this study, the relationship between DNA methylation patterns of the promoter region of the NOD2 gene and the pathogenesis of CD was assessed. Colonic mucosal samples were obtained from 15 Iranian patients with CD and 15 matched healthy controls with no history of autoimmune diseases. After bisulfite conversion of genomic DNA, the DNA methylation status of three CpG sites in the promoter region of the NOD2 gene was determined by the real-time quantitative multiplex methylation-specific PCR assay. Using this approach, we identified a decreased level of methylation of the NOD2 promoter in the colonic mucosa of patients with CD (0.128±0.093 vs. 0.025±0.016, unmethylated DNA in CD vs. healthy controls, respectively, P<0.000). According to our findings, promoter hypomethylation of the NOD2 gene in the colonic mucosa might contribute to the development and severity of CD.

Ulcerative colitis (UC) is an idiopathic chronic inflammatory disease of the colon with evidence addressing the role of epigenetic changes. The intention of this study was to detect the association of DNA methylation levels of NOD2 gene with UC and to evaluate whether any of these changes might be a useful biomarker for detecting patients with UC.

The methylation status of the promoter CpG islands (CGIs) of NOD2 gene was examined in the colonic mucosae of 15 cancer-free patients with UC and 15 age- and sex-matched healthy controls by the real-time quantitative multiplex-methylation specific PCR (QM-MSP) assay. Methylation-specific melting curve analysis (MS-MCA) was used to analyze the data.

The median unmethylated DNA index was significantly higher in cases compared to controls, and hypormethylation of NOD2 gene was significantly correlated with UC (Unmethylated DNA in UC vs. HC; 0.102±0.055 vs. 0.025±0.016, P = 0.000).

The NOD2 gene that was differentially methylated in UC patients, provides new insights into the pathogenesis of UC, with a view to making steps toward the development of accurate biomarkers for diagnostic tools in UC.

Although Imatinib has revolutionized the treatment of chronic myeloid leukemia (CML), not all patients reach complete remission and a considerable proportion of the patients develop resistance to Imatinib.

In an attempt to increase the tail on the survival curve, we conducted a Phase I/II study of PR1/BCR-ABL multipeptides vaccination trial in CML patients with at least 15 months of Imatinib treatment and 5 months of persistent molecular residual disease.

One month after the completion of the vaccinations, 4 patients nearly developed a 1-log fall in their BCR-ABL transcript level, with 4 patients achieving a major molecular response (MMR). Nine patients were followed for more than a period of 7 years. The vaccinations were associated with a MMR in five patients and a complete molecular response (CMR) in one patient. The removal of Imatinib in two patients who achieved MMR after the vaccinations led to a resurgence of the leukemia population and relapse.

Our study suggests that a combination of immunotherapy with Imatinib targeted therapy keeps the leukemia population under control, improving the long-lasting clinical and molecular response of CML patients, for at least 7 years.

Climate and the required parameters for agricultural products are the important factors of production. We can determine potential facilities in different areas and consider the maximum tapping through agricultural meteorology. Due to drylands potentials in Hamedan province, we conducted a comprehensive survey based on 20 years (1995-1995) climatic elements of 9 main and supplementary synoptic stations. Thus, according to wheat phenological conditions and matching those with climatic conditions requirements in Hamedan province, we surveyed effective indices in grow crops. Finally, using geographic information systems (GIS) we implemented climatic elements zoning and weighting. Then the appropriate and inappropriate areas of the province for dryland wheat were determined. Results indicated among the climatic elements, annual rainfall and its distribution during the growing season, also the grow degree day (GDD) are important factors in process of dryland wheat. Based on maps extracted from the GIS, about 18 percent of the areas of province which are located in west, south west including Nahavand, Tuiserkan and Asadabad cities, enjoy very potentials and 46percent medium, 34percent good and 2 percent of Ghahavand city of Hamedan city functions lacks the necessary talent. with no potentials.

Optimization using radial basis functions as an interpolation tool in trust-region (ORBIT), is a derivative-free framework based on fully linear models to solve unconstrained local optimization, especially when the function evaluations are computationally expensive. This algorithm stores the interpolation points and function values to using at subsequent iterations. Despite the comparatively advanced management used for interpolation points, we maintain that ORBIT ignores sorting the interpolation points based on the function values. In this paper, we propose an improved version SORT-ORBIT by sorting the interpolation points and selecting a point as the trust-region center in which the objective function reaches its minimum value. Numerical results indicate the efficiency of the improved version compared with the original version. In addition, to estimate high-accuracy solutions, we equip the ORBIT with a new gradient-free convergence test.

Growing evidence supports that changes in the methylation state of Inflammatory Bowel Disease (IBD)-associated genes could significantly alter levels of gene expression, potentially contributing to disease onset and progression. We supposed that alterations in DNA methylation status at promoter region within the suppressor of cytokine signaling 3 (SOCS3) gene in intestinal tissues may be involved in the susceptibility to Crohn's Disease (CD).

DNA methylation status in the promoter region of the human SOCS3 gene of intestinal tissues from 15 patients with CD and 15 age- and sex-matched healthy controls were profiled using the real-time Quantitative Multiplex Methylation Specific PCR (QM-MSP) assay.

Based on methylation assay data profiling, we found that patients with CD showed a higher degree of methylation of the SOCS3 gene promoter region than did the healthy controls (unmethylated DNA in CD vs. healthy controls; 0.00048±0.0011 vs. 0.07±0.142, p<0.000).

The data presented here demonstrate that aberrant methylation of the CpG islands within promoter regions of SOCS3 gene in colonic mucosa of CD was associated with mucosal inflammatory status, providing insights into the involvement of methylation could contribute to the initiation of the inflammatory process and development of CD.

The problem of the present research is to explain the position of women in the thought and practice of contemporary Salafi currents. The method of the study is a causal and library-based one. The problem of this research can be solved with regard to three points: 1. a study of the court Salafi that regulates its jurisprudential views with the strategies of the government, industrial jurisprudence and expediency, that is the precedence of political expediency over religious rules; 2. a study of the jihadist Salafi movement, which, with its uncommon fatawa, while criticizing the official Salafism, has a jurisprudentially centrifugal view on the issue of women and 3.  a study of the reformative Salafism which jurisprudentially viewed, its rules are in accordance to the taste of Sharichr('39')a and relies on fiqhi maqasidi, purpose-based jurisprudence. This view remains faithful to Sharichr('39')a and refrains from extremist and inhumanistic views in the field. The findings of the study emphasize the categorization of these views according to the validity of the type of jurisprudential view. In such a way that, despite their being common in the principles of epistemology, ontology and anthropology, in fiqhi maqasidi and fiqhi sana`ti, technical jurisprudence, different views towards women have been formed, influenced by socio-cultural status and historical geographical destiny.
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‎ORBIT is a derivative-free trust-region framework that employs a radial basis function (RBF) interpolation to solve the computationally expensive optimization problems‎. ‎The accuracy and stability of RBF interpolation depend on a so-called shape parameter‎, ‎the type of RBF and the number of data points‎. ‎So it is more appropriate to determine these parameters properly‎. ‎In this paper‎, ‎we evaluate the performance of the ORBIT algorithm by different types of RBF‎, ‎different numbers of data points and different shape parameter values‎. ‎We utilize Dolan-More performance profile and More-Wild data profile to investigate the performance of algorithms‎. ‎Finally‎, ‎based on this numerical study we proposed some recommendations for the type of RBF‎, ‎the number of data points and the shape parameter value‎.

Endometrial receptivity plays a key role in pregnancy success in assisted reproduction cycles. Recent evidence suggests that seminal plasma (SP) and follicular fluid (FF) influence the uterine endometrium to improve implantation of the embryo and the establishment of pregnancy. In this study, we attempt to assess the influence of FF and SP on the expression levels of main endometrial receptivity genes (HOXA10, HOXA11, ITGAV, ITGB3 and LIF) in endometrial stromal cells.

In this experimental study, SP and FF were collected from 15 healthy fertile men and 15 healthy fertile women, respectively. Tissue specimens of the endometrium were obtained from 12 women undergoing hysterectomy for benign conditions. After endometrial stromal cell isolation and culture, dose- and time-dependent cytotoxic effects of pooled FF and SP on 3D-cultured endometrial cells were evaluated. A second independent set of 12 endometrium samples was treated under determined optimum conditions and evaluated for gene expression analysis using quantitative real-time polymerase chain reaction (qRT–PCR).

The results of this study indicated that exposure of endometrial stromal cells to FF resulted in the elevated expression of HOXA10 (fold change=2.6, P=0.02), HOXA11 (fold change=3.3, P=0.002), LIF (fold change=4.6, P=0.0003), ITGB3 (fold change=3.5, P=0.012), and ITGAV (fold change=2.8, P=0.001) compared to untreated cells. In addition, we found that SP-treated endometrial cells showed increased mRNA levels of only the LIF gene (fold change=2.5, P=0.008) compared to untreated cells.

Human SP and FF may modulate the endometrial receptivity and improve the implantation rate in assisted reproduction cycles through the up-regulation of endometrial receptivity genes.

The current research is about the relationship between spirituality and political power strategies. Therefore, this article examines this relationship in the form of three traditional, modern and postmodern discourses. In the traditional era, spirituality is not an independent and distinct reality of religions, and political power in this discourse has it’s perfectly legitimacy to apply the rules of religion. In the modern age, following the secularization processes, not only spirituality but also religions have lost their place as sources of action and the legitimacy of political power. Even under the modern formulation, militant secularism does not only eradicate religion from the political and social point of view, but also militant It as exemplified by the policy of communist governments towards religions. In the postmodern era, spiritual poverty has led to a social decline and psychological crisis on one hand, and it has become a concern for capitalism, production and accumulation of capital on the other hand. This has led power strategies to encourage and disseminate some spiritualties that are more in line with the form and purpose of political power.

The present paper relates to this question, what are the characteristics of the language of mysticism in the 7th and 8th centuries, during the rule of the Ilkhanites. Using the Whittsteinnean linguistic theories and Foucault's power/ knowledge theory, this study tries to explain the characteristics of the language of mysticism in this age. From the perspective of this paper, although the mystical concepts comes from the inner experience of human and is not related to the senses, but the works of mystics are expressed in the common language of mankind. Examining the main characteristics of the language of mysticism such as antirationality, removing established habits, breaking the taboo and being secret…we try to explain the relationship between each of this elements with political power.

Kleefstra Syndrome is characterized by severe mental retardation, brachycephaly, microcephaly, epileptic seizures, distinct facial features, and infantile weak muscle tone and heart defects. Deletion of EHMT1 is the main player in 75% of cases. Because of blurriness in genotype-phenotype correlation through clinical and molecular features of both 9q34.3 microdeletion patients and those with an intragenic EHMT1 mutation in Kleefstra Syndrome, genetic characterization of patients with clinical symptoms of such spectrum is desirable. We report the first Kleefstra Syndrome patient in Iran characterized through genetic approaches. Our report could improve KS diagnosis in Iran and prepare PND and PGs options for involved families.

Mucopolysaccharidosis VI (MPS-VI) is an infrequent autosomal recessive disorder caused by mutations in ARSB gene and deficiency in lysosomal enzyyme ARSB activities subsequently. This enzyme is essential for the breaking of glycosaminoglycans (GAGs) such as dermatan sulfate and chondroitin sulfate. ARSB dysfunction results in imperfect breakdown of GAGs and their accumulation in urine. Mutations in ARSB gene are the main players in MPS-VI disease and its clinical consequences. Most reported mutations are point mutations but there are some other examples in literature. Here we report a novel missense mutation in ARSB gene that is inherited as an autosomal recessive mode and probably explain the clinical status of the proband. This mutation replaces the threonine 92 by proline and alters ARSB structure. This is the most feasible scenario for clinical condition we described here. This novel mutation should be remarked for PND and PGD to improve the health and management of such families.

Ataxia-telangiectasia is a rare disorder with neurological manifestations and caused by mutations in ATM gene. This gene produce a serine/threonine protein kinase, an activator of the DNA damage response in the face of DNA DSBs, which phosphorylates downstream substrates integrating with DNA repair procedure. Most ATM mutations are private mutations and, there is no mutational hotspots in the ATM gene. We unveiled a new mutation in this gene in an 8 years old A-T patient. This mutation led to fundamental alterations in ATM protein structure and representation of AT lastly.

Cornelia de Lange (CDLs) is a rare syndrome, which is characterized by multiple congenital anomalies including microcephaly, mental retardation, delayed growth and development, hypertrichosis, and defects in heart, gastrointestinal, renal and upper limbs. The syndrome prevalence is 1 per 30,000 to 50,000 live births. The diagnosis is mainly based on clinical manifestations. It can be inheritated in Autosomal dominant or X-linked forms through mutations in at least five genes NIPBL, SMC1A, HDAC8, RAD21 and SMC3. This article introduces a case of Cornelia De Lange syndrome.
Case: This study reports a 40 week boy with Cornelia de Lange syndrome, which has been diagnosed by Ultrasonography. The clinical manifestations were left lip and plate, cardiomegaly, cryptorchidism, deformities in both arms from elbows to fingers and existing only one finger. He passed away after 3 days of birth.
An increased awareness about this syndrome may result in an early diagnosis and a decrease in morbidity.

Signal transducers and activators of transcription (STATs) are cytoplasmic transcriptionfactors that have a key role in cell fate. STATs, a protein family comprised ofseven members, are proteins which are latent cytoplasmic transcription factors thatconvey signals from the cell surface to the nucleus through activation by cytokinesand growth factors. The signaling pathways have diverse biological functions thatinclude roles in cell differentiation, proliferation, development, apoptosis, and inflammationwhich place them at the center of a very active area of research. In this reviewwe explain Janus kinase (JAK)/STAT signaling and focus on STAT3, which istransient from cytoplasm to nucleus after phosphorylation. This procedure controlsfundamental biological processes by regulating nuclear genes controlling cell proliferation,survival, and development. In some hematopoietic disorders and cancers,overexpression and activation of STAT3 result in high proliferation, suppression ofcell differentiation and inhibition of cell maturation. This article focuses on STAT3and its role in malignancy, in addition to the role of microRNAs (miRNAs) on STAT3activation in certain cancers.

Background and the present study has been carried out aiming at designing an education system evaluation model in Police University, determining the indicators and criteria for each of the education evaluation dimensions, determining the indicators and criteria for empowerment evaluation, the results and consequences of the system, and also determining the weight, importance, and the relationship of each dimension, indicators, and the evaluation criteria of this system. this study is of an implicational type and the qualitative and quantitative methods are also employed in this research. In order to collect qualitative data, we got benefit of the viewpoints of 21 Police University administrators and faculty members who are expert in the field of police education and training (ideological-political, counterintelligence-security, military-disciplinary, physical fitness and psychological studies). In order to collect quantitative data, 151 professors were selected out of 249 professors and they answered the questionnaire. The validity of this model was obtained using the experts’ ideas and the reliability was obtained using Cronbach Alpha Coefficient.Findings and the results showed that the model has a satisfactory validity and reliability. The obtained model is formed of three dimensions of empowerment instruments, results, and consequences and also two internal and external dimensions and each of these dimensions is composed of some factors, criteria, and indicators. According to the 900-point model, each of the dimensions of empowerment instruments, results, and consequences have 400, 200, and 300 points, respectively. In addition, the internal dimension of empowerment instruments has devoted 60% (240 points) and the external dimension of empowerment instruments has devoted 40% (160 points) of all the points related to the empowerment instruments to themselves. Among the four factors related to the internal dimension of empowerment instruments (development and learning, capacity and power, internal process and budget), most of the points was for the factor of development and learning containing 89 points. The external dimension of empowerment instruments is also composed of two factors that 83 points of that are devoted to rules and regulations and 77 points of that are devoted to policies and strategies. 104 out of 200 points related to the dimension of results are devoted to the training factor and 96 points are devoted to education. The consequences dimension is composed of four factors. The 96 points out of 300 points of consequences are devoted to internal stakeholders’ satisfaction, 84 points are devoted to external stakeholders’ satisfaction, 57 points are devoted to the inside excel and 63 points are devoted to outside excel. At the end, according to the obtained results, it can be said that the formulated model has a satisfactory validity and reliability and it can be used for evaluating educational and training system in Police University.

Β-thalassemia considers worldwide public health disorders. Novel fetal hemoglobin inducer agents such as thalidomide and sodium butyrate have been attended for ameliorating clinical complications of such disorders.We used thalidomide and sodium butyrate for increasing the level of fetal hemoglobin in erythroid progenitors. Briefly, after isolation of CD133+ stem cells from umbilical cord blood and differentiation into erythroid lineage, erythroid progenitors were treated with thalidomide and sodium butyraye as single and combination. H3K4 histone methylation was evaluated following fetal hemoglobin induction using chromatin immuno percipitation (ChIP) technique. The results of this study showed that the effect of thalidomide on increasing of H3K4 methylation was highest compared to sodium butyrate and combination of both agents (p<0.05). Consequently, our study of the epigenetic modification of the γ-globin suggests that histone H3K4 dimethylation are significant for the regulation of developmental stage-specific expression of the γ-globin genes.