alireza abdanipour

In most developed countries, accreditation programs are implemented based on standards to evaluate and improve medical education. This study aims to evaluate the quality and quantity of the educational system in universities and faculties located in the sixth macro-region of Iran to improve the existing conditions according to society's expectations of higher education.

In this study , by convergent-parallel approach, the effects of institutional accreditation in universities and faculties in the sixth macro-region were examined in 2019 based on the national accreditation project including 66 standards and 351 indicators in 8 areas. A field visit to educational-research facilities and a documentation study were conducted based on the eight areas. After collecting and reviewing the data, the accreditation results were presented. 

Considering the educational-research facilities as well as the achievement of necessary and preferred standards, we saw a significant growth in medical universities and faculties in the region.

Medical universities and faculties in the sixth macro-region should provide the necessary infrastructure to reach the optimal level in all necessary standards and improve the quality of medical education. In addition, familiarizing all university staff with the accreditation standards can help improve the quality of services.

The effect of selegiline as an oxidase inhibitor on cell differentiation into neuron-like cells has been demonstrated by altering gene expression. Based on the results of studies on the role of statins in neurotrophin regulation, in this study, we examined the effect of lovastatin (HMG-CoA reductase inhibitor) on the differentiation of bone marrow mesenchymal cells (BMSCs) into neuron-like cells. Selegiline isanirreversible inhibitor of monoamineoxidase(MAO)typeB. Sincedopaminein thehumanbrain is metabolized primarily by MAO-B, selegiline increases dopamine levels in the central nervous system. In addition to inhibiting MAO-B, selegiline also inhibits the uptake of dopamine and norepinephrine into presynaptic nerves and increases dopamine turnover.

Bone marrow mesenchymal cells were collected from 28-day-old rats and cultured under standard conditions on the medium. The experimental groups in this study were as follows: BMSCs (control); BMSCs induced with 20Mselegiline for 24 hours (experiment 1); BMSCs induced with 6 Mlovastatin for 24 hours (experiment 2); BMSCs were induced with 20 Mselegiline for 24 hours and 6 M lovastatin for the next 24 hours (experiment 3). Real-time RT-PCR was performed to determine the mRNA levels of the nestin and NF-68 genes.

Real-time RT-PCR results showed that nestin and NF-68 mRNA levels were significantly increased in the co-treatment group (experiment 3) compared to the other experimental groups (P < 0.05).

Based on the increased expression of nestin and NF-68 genes, the presence of lovastatin has a synergistic effect on neuronal differentiation and optimization of stem cell therapeutic approaches.

Uncontrolled stress affects hippocampal-dependent memory through altering the morphology and the proliferation rate of the hippocampal progenitor cells.

In this experimental study, neural stem cells (NSCs) derived from rat hippocampus were extracted and cultured to produce neutrospheres in a serum-free environment. Nestin antibody was used to identification the induced NSCs. Cell proliferation and cytotoxicity due to the effect of norepinephrine were measured by MTT assay. NSCs were assigned in the following experimental groups: Control (untreated), NE (treated with norepinephrine), Pro (pretreated with beta-blocker propranolol then norepinephrine), Pra (pretreated with alfa-blocker prazosin then norepinephrine), and Syn (pretreated with propranolol and prazosin then norepinephrine). Real-time RT-PCR was conducted to quantify mRNA levels of the Stk4, Caspase-3 and Sox2.

The flow cytometry analysis revealed that NSCs were nestin positive. Real-time RT-PCR results showed that gene expression levels of Sox2 mRNA was increased via norepinephrine. Also, gene expression levels of Stk4 and Caspase-3 were increased in the group that pretreated with prazosin.

Taken together, the effect of norepinephrine on hippocampus-derived neural stem cells is receptor-dependent and, increase of norepinephrine under chronic stress can lead to the either proliferation or apoptosis in the NSCs, as a double-edged sword.

Institutional accreditation is a type of quality assurance in medical education to achieve quality standards in higher education institutions. The present study aimed at internal evaluation of the faculties affiliated to Zanjan University of Medical Sciences based on the institutional accreditation standards.

This study was conducted based on a descriptive cross-sectional design. The research samples included all the faculties affiliated to Zanjan University of Medical Sciences. This study was performed based on the national institutional accreditation standards (IA), including 66 standards and 351 measures in eight evaluation domains, approved by the Ministry of Health and Medical Education. In order to conduct an internal evaluation based on institutional accreditation standards, the experts in the fields of institutional accreditation were initially provided with the necessary training. Upon the collection of documents, the data was evaluated by the research group based on the accreditation standards. In the next step, to confirm the documents and complete the internal evaluation, a field visit was conducted to the educational and research facilities of the faculties based on the accreditation standards. Finally, the faculty officials and senior managers of Zanjan University of Medical Sciences were provided with feedback on the results of the internal evaluation in the two sections of mandatory and developmental standards.

As evidenced by the obtained results, Zanjan University of Medical Sciences showed significant improvement in the achievement of accreditation standards in field evaluations. The highest and lowest percentages of compliance with the standards were observed in the faculties of nursing-midwifery and health-paramedicine, respectively.

In order to reach an ideal level in all necessary standards and improve the quality of medical education, in addition to the provision of necessary infrastructure, managers, professors, and experts in the field of education need to be thoroughly familiar with institutional accreditation standards.

Adipose-derived stem cells (ADSCs) are one of the most well-known and accessible sources of stem cells that can be used for the treatment of neurodegenerative diseases. On the other hand, previous studies have suggested that selegiline, as an irreversible inhibitor of monoamine oxidase, affects stem cells’ differentiation into neurons. This study was conducted to investigate the involvement in phosphatidylinositol-bisphosphate 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in ADSCs differentiation to neuron-like cells using selegiline as inducer.

ADSCs were isolated from male rats, cultured in DMEM and then treated with selegiline (10-7 M) for 24h. Real-time PCR for nestin and neurofilament-68 (NF-68) was performed from the negative control (ADSCs at the 3rd passage), positive control (ADSCs were treated with 10-7 M selegeline for 24h, PI3AKT inhibitor (ADSCs were pretreated with treated with 10µM LY294002 for 3h, then10-7 M selegeline for the next 24h, and MAPK inhibitor (ADSCs were pretreated with treated with 10µM PD98059 for 3h, then10-7 M selegeline for the next 24h).

Nestin and NF-68 genes have been over-expressed in the selegiline-treated ADSCs. The PD98059 and LY294002 significantly down-regulated the selegiline-induced over-expression of nestin and NF-68; however, PI3K inhibition did not return the genes expression to control level. ADSCs were immunoreactivefor nestin and NF-68 about 98% and 95% respectively.

According to the results, selegilinecan induce the gene expression of neural stem cell biomarkers in ADSCs through MAPK pathway activating and so differentiating them into neuron-like cells.

After primary tissue damage as a result of spinal cord injury (SCI), there is a period of secondary damage, which includes several cellular and inflammatory biochemical cascades. As a novel pro-apoptotic kinase, Mst1 (serine/threonine kinase 4) promotes programmed cell death in an inflammatory disease model. This study aimed to evaluate Mst1 gene expression levels in rats with spinal cord injury treated with L- deprenyl.  The rats were divided into control (contusion), laminectomy, sham-operated (contused rats received 1 ml normal saline intraperitoneal), and treatment (contused rats received 5 mg/kg of L-deprenyl intraperitoneal; once a day for 7 days). The BBB (Basso, Beattie, and Bresnahan) scales were performed to assess motor function following SCI. Rats were sacrificed 28 days after SCI and the spinal cord lesion area was removed. Apoptosis and cavity formation in the spinal cord were determined by H&E staining and TUNEL assay, respectively. The mRNA levels of the Mst1, Nrf2, Bcl-2, and PGC1α genes were analyzed using real-time quantitative PCR. The results showed significant improvement in motor function in the L- deprenyl group compared with the untreated group. Histological analysis showed a significant reduction in the number of tunnel-positive cells after injection of L-deprenyl, as well as a decrease in the volume of the cavity. In addition, L-deprenyl treatment increased the expression of the Nrf2, Bcl-2, and PGC1α genes, while reducing the expression of the Mst1 gene in the spinal nerves.  These results suggest that L-deprenyl is a promising treatment for spinal cord injury.

 The neuroprotective potential of 1,8-Cineole (CIN) has recently been documented in vitro. Here we studied potential beneficial therapeutic effects of CIN, using the temporal lobe epilepsy (TLE) pilocarpine rat model through up-regulation of Bcl-2, as an anti-apoptotic gene.

A total of 32 (n=8 per group) male Wistar rats were divided into 4 groups as follows:  i) normal rats (received CIN (50 mg/kg)). ii) Non-treated epileptic rats. iii) Vehicle epileptic rats treated with 10% Polysorbate 20 (Tween 20). iv) TLE-treated rats with CIN once daily (50 mg/kg), three days after the first seizure and up to 28 days, four days a week (treatment group).
For the analysis, based on the Racine scale, the score of 4 and 5 was chosen. Rats were sacrificed and primed 28 days after the first seizure for both histopathological and quantitative real time PCR (qRT-PCR) analysis.

 The findings showed that CIN prevents cell death caused by Pilocarpine, via regulatory effect on apoptotic and anti-apoptotic gene expression. QRT-PCR results showed a significant increment in the Bcl-2 expression, and a decrease in Caspas-3 gene in the epileptic group treated with CIN. Also, amount of total antioxidant capacity was higher in CIN treated group. Histological study of the brain regions revealed a significant decrease in the apoptotic and necrotic hippocampal cells in the treatment groups.

 Collectively, the present study showed CIN significantly induced neuroprotection effects for brain damage. It seems CIN can be a promising method for improving the effectiveness of therapy.

In animal models of inflammatory diseases, Mammalian sterile 20-like kinase 1 (Mst1) facilitates the programmed cell death as a novel pro-apoptotic kinase. This research aimed to determine the expression level of Mst1 gene in a rat model of SCI treated with valproic acid (VPA).

Severe rat model contusion was used for evaluation of the neuroprotective effect of valproic acid. The Basso-Beattie-Bresnahan test, was performed to determine locomotor functions. Hematoxylin/eosin staining and TUNEL assay were performed to detect cavity formation and apoptosis, respectively. The mRNA levels of the genes Mst1, nuclear factor (erythroid-derived 2)-like 2, and B-cell lymphoma 2 were evaluated, using quantitative real-time PCR acute spinal cord injury (RT-PCR).

The results revealed that Mst1 gene expression and TUNEL-positive cells in the VPA-treated group were significantly reduced as compared to the untreated group (p ≤ 0.05).

Our findings indicate that VPA has therapeutic potential and can be a candidate for the treatment of neurodegenerative disorders and traumatic injury as a promising drug.

Neural stem cells are undifferentiated cells that are located in limited areas of central nervous system. These cells have proliferation and self-renew ability and can be differentiated into neurons and glial cells. Mature nerve cells do not have proliferative ability; and due to the limited number of nerve stem cells, injuries to the nervous system are not recoverable. The purpose of this review is to identify characteristics and factors that may influence proliferation and differentiation of neural stem cells. These cells provide useful tools for in vitro study of neural cells developmental stages. Besides, they have extensive therapeutic applications providing an unlimited source of cells for tissue transplantation and repair. Overall, the identification of factors contributing to neural stem cell's proliferation and differentiation can be effective for body's natural capacity to repair nerve damages. For cell therapy purposes, application of induced medium or an appropriate stimulants may have an effective role in increasing the rate of growth and proliferation of these cells in vitro.

The antiapoptotic effect of ghrelin in various cell lines including bone marrow stromal cells (BMSCs) has been proved. However, the real mechanism of this effect is not clear. Caspase3 and Bcl2 are well-known pro- and antiapoptotic regulatory genes in eukaryotes. The aim of the study was to find out the effect of ghrelin on Caspase 3 and Bcl2 change in BMSCs. Rat BMSCs were cultivated in DMEM. Passage 3 BMSCs were treated with ghrelin 100 μM for 48 h. Real-time PCR for Caspase 3 and Bcl2 was carried out from B (untreated BMSCs), BH (BMSCs treated with 125 µM H2O2), BGH (BMSCs treated with 100 µM ghrelin then 125 µM H2O2) and BG (BMSCs treated with 100 µM ghrelin) groups. For immunofluorescence, cells were incubated with anti Caspase 3 and Bcl2monoclonal antibodies. Primary antibodies were visualized using the FITC method. All data are presented as means ± SEM. Values of P<0.05 were considered statistically significant. Ghrelin decreased mRNA expressions of Caspase-3 significantly as compared to the BH group (P<0.05). Also, Bcl-2 gene expression showed an increment in BG group as compare with BH and BGH groups (P<0.05). A high present of Bcl-2 positive cells were observed in the BGH group while Caspase-3 positive cells were significantly decreased in the BGH group compared with the BH group (P<0.05). Ghrelin probably enhances BMSCs viability through regulation of pro- and antiapoptotic genes Caspase 3 and Bcl2. However the signaling pathway of this effect should be elucidated in the future.

Non-obstructive azoospermia is mostly irreversible. Efforts to cure this type of infertility have led to the application of stem cells in the reproduction field. In the present study, testicular cell-mediated differentiation of male germ-like cells from bone marrow-derived mesenchymal stem cells (BM-MSCs) in an in vitro indirect co-culture system is investigated.
In this experimental study, mouse BM-MSCs were isolated and cultured up to passage three. Identification of the cells was evaluated using specific surface markers by flow-cytometry technique. Four experimental groups were investigated: control, treatment with retinoic acid (RA), indirect co-culture with testicular cells, and combination of RA and indirect co-culture with testicular cells. Finally, following differentiation, the quantitative expression of germ cell-specific markers including Dazl, Piwil2 and Stra8 were evaluated by real-time polymerase chain reaction (PCR).
Molecular analysis revealed a significant increase in Dazl expression in the indirect co-culture with testicular cells group in comparison to the control group. Quantitative expression level of Piwil2 was not significantly changed in comparison to the control group. Stra8 expression was significantly higher in RA group in comparison to other groups.
Indirect co-culture of BM-MSCs in the presence of testicular cells leads to expression of male germ cell-specific gene, Dazl, in the induced cells. Combination of co-culture with testicular cells and RA did not show any positive effect on the specific gene expressions.

Ghrelin is a peptide which has a proliferative and antiapoptotic effect in many cells including bone marrow stromal cells (BMSCs). Homeobox protein B4 (HOXB4) is a transcription factor involved in stem cell regeneration and survival. The aim of the study was to find out the efect of ghrelin on Hoxb4 expression in BMSCs.
In this experimental study, rat BMSCs were cultivated in Dulbecco’s Modified Eagle Medium (DMEM). Passage three BMSCs were treated with ghrelin 100 μM for 48 hours. Real-time polymerase chain reaction (PCR) was carried out from the untreated BMSCs (B), BMSCs treated with 125 μM H2O2 (BH), BMSCs treated with 100 μM ghrelin then 125 μM H2O2 (BGH) and BMSCs treated with 100 μM ghrelin (BG) groups. For immunofluorescence, cells were incubated with an anti-HOXB4 monoclonal antibody. Primary antibodies were visualized using the Fluorescein isothiocyanate (FITC) method. All data are presented as mean ± SEM and P Hoxb4 expression significantly increased in the BG compared with BH and BGH groups. Furthermore, 100 μM ghrelin, increased the mean of HOXB4 positive immunoreactive cells compared to the BH group.
Ghrelin probably enhances proliferation and viability of BMSCs through Hoxb4 upregulation. However, the signaling pathway and other biological outcomes of this effect should be elucidated in different stem cells.

Background and The use of an appropriate stimulus for increasing the rate of neural stem cell proliferation is one of the most important issues in cell therapy. This study aimed to investigate the effect of hydroethanolic extract of Stachys byzantina on hippocampus-derived neural stem cell proliferation and apoptosis.
In this experimental study, the neural stem cells were isolated from the hippocampus region of brain using enzymatic digestion. The neurospheres were dissociated to single cells and cultured on adherent plates. For these cells, immunocytochemical evaluation was performed for marker nestin. The isolated neural stem cells were pretreated with different doses of hydroethanolic extract of Stachys byzantina for 48 h, and then exposed to 125 μM of H2O2 for 30 min. The effects of this extract on cell survival and apoptosis were evaluated using MTT and TUNEL, respectively. To analyze the data, ANOVA and Tukey’s tests were run in SPSS, version 15.
In the current study, 800 µg/ml of Stachys byzantina extract significantly increased the proliferation rate of the neural stem cells. Furthermore, the results of the TUNEL staining demonstrated that Stachys byzantina extract did not have any protective effect on hydrogen peroxide-induced apoptosis.
Stachys byzantina extract increases the rate of neural stem cell proliferation. However, further studies are required to determine the effect of this extract on the treatment of neurodegenerative diseases.

The brain and spinal cord have a limited capacity for self-repair under damaged conditions. One of the best options to overcome these limitations involves the use of phytochemicals as potential therapeutic agents. In this study, we have aimed to investigate the effects of di-(2-ethylhexyl) phthalate (DEHP) on hippocampus-derived neural stem cells (NSCs) proliferation to search phytochemical candidates for possible treatment of neurological diseases using endogenous capacity. In this experimental study, neonatal rat hippocampus-derived NSCs were cultured and treated with various concentrations of DEHP (0, 100, 200, 400 and 600 µM) and Cirsium vulgare (C. vulgare) hydroethanolic extract (0, 200, 400, 600, 800 and 1000 µg/ml) for 48 hours under in vitro conditions. Cell proliferation rates and quantitative Sox2 gene expression were evaluated using MTT assay and real-time reverse transcription polymerase chain reaction (RT-PCR). We observed the highest average growth rate in the 400 µM DEHP and 800 µg/ml C. vulgare extract treated groups. Sox2 expression in the DEHP-treated NSCs significantly increased compared to the control group. Gas chromatography/mass spectrometry (GC/ MS) results demonstrated that the active ingredients that naturally occurred in the C. vulgare hydroethanolic extract were 2-ethyl-1-hexanamine, n-heptacosane, 1-cyclopentanecarboxylic acid, 1-heptadecanamine, 2,6-octadien-1-ol,2,6,10,14,18,22-tetracosahexaene, and DEHP. DEHP profoundly stimulated NSCs proliferation through Sox2 gene overexpression. These results provide and opportunity for further use of the C. vulgure phytochemicals for prevention and/or treatment of neurological diseases via phytochemical mediated-proliferation of endogenous adult NSCs.

Cerebrospinal fluid (CSF) has a broad range of molecules and neurotrophic factors which are essential for neurogenesis. Bone marrow mesenchymal stem cells (BMSCs) are multipotent stem cells that can differentiate into the cells with neural-like phenotype under the induction of appropriate growth factors. According to the significant role of Retinoic acid (RA) in neurogenesis, The aim of this study is differentiation of BMSCs into neuron-like cells using CSF, RA and combinative form of CSF and RA.
Material and Rat BMSCs were isolated and characterized. The CSF was prepared from cisterna magna of 19 days Wistar rat embryos. Then BMSCs were induced by 5% CSF (CSF group), 10-6 µM Retinoic acid (RA group) and CSF plus RA (CSR group) for 12 days. Morphology of differentiated cells was examined by inverted microscope and axonal outgrowth was measured using the image J software. In addition, the expression of neural-specific markers (Nestin and MAP-2) was examined by Immunocytochemistry.
The specific - neuronal morphology was observed in differentiated cells. The maximum axon length was seen in CSR group on 12th day of induction. The results of immunocytochemistry showed that the neuroprogenitor marker (Nestin) was expressed in all treated groups. However, MAP-2, as a mature neural marker, was expressed in CSR group.
The findings suggest that CSF accompanied RA lead to differentiation of cells with neuronal and glial phenotypes from BMSCs in vitro.

The present study was designed to evaluate the secondary microglial activation processes after spinal cord injury (SCI). A quantitative histological study was performed to determine ED-1 positive cells, glial cell density, and cavitation size in untreated SCI rats at days 1, 2, and 4, and weeks 1, 2, 3, and 4. The results of glial cell quantification along the 4900-µm long injured spinal cord showed a significant increase in glial cell density percentage at day 2 as compared to other days. Whereas the highest increase in ED-1 immunoreactive cells (monocyte/phagocyte marker in rats) was observed at day 2 (23.15%) post-injury. Evaluation of cavity percentage showed a significant difference between weeks 3 and 4 post-injury groups. This study provides a new insight into the multiphase immune response to SCI, including cellular inflammation, macrophages/microglia activation, glial cell density, and cavitation. Better understanding of the inflammatory processes associated with acute SCI would permit the development of better therapeutic strategies.

The primary phase of traumatic spinal cord injury (SCI) starts by a complex local inflammatory reaction such as secretion of pro-inflammatory cytokines from microglia and injured cells that substantially contribute to exacerbating pathogenic events in secondary phase. Valproic acid (VPA) is a histone deacetylase inhibitor. Acetylation of histones is critical to cellular inflammatory and repair processes. In this study, rats were randomly assigned to five experimental groups (laminectomy, untreated, and three VPA-treated groups). For SCI, severe contusion was used. In treated groups, VPA was administered intraperitoneally at doses of 100, 200 and 400 mg/kg daily three hours after injury for 7 days. To compare locomotor improvement among experimental groups, behavioral assessments were performed by the Basso, Beattie and Bresnahan (BBB) rating scale. The expression of neurotrophins was evaluated by RT-PCR and real-time PCR. VPA administration increased regional brain-derived neurotrophic factor and glial cell-derived neurotrophic factor mRNA levels. Local inflammation and the expression of the lysosomal marker ED1 by activated macrophages/microglial cells were reduced by VPA and immunoreactivity of acetylated histone and microtubule-associated protein were increased. The results showed a reduction in the development of secondary damage in rat spinal cord trauma with an improvement in the open field test (BBB scale) with rapid recovery.

Adult stem cells (ASC) are undifferentiated cells found throughout the body. These cells are promising tools for cell replacement therapy in neurodegenerative disease. Adipose tissue is the most abundant and accessible source of ASC. This study was conducted to evaluate effect of selegiline on differentiation of adipose-derived stem cells (ADSC) into functional neuron-like cells (NLC), and also level of the neurotrophin expression in differentiated cells. ADSC were transdifferentiated into NLC using selegiline where CD90, CD49d, CD31, CD106 and CD45 were used as markers for ADSC identification. Lipogenic and osteogenic differentiation of ADSC were used to characterize the ADSC. ADSC were treated with selegiline at different concentrations (from 10-6 to 10-11 mM) and time points (3, 6, 12, 24 and 48 h). Percentage of viable cells, nestin and neurofilament 68 (NF-68) immunoreactive cells were used as markers for differentiation. The optimal dose for neurotrophin expressions in differentiating cells was evaluated using reverse transcriptase-PCR. NLC function was evaluated by loading and unloading with FM1-43 dye. ADSC were immunoreactive to CD90 (95.67 ± 2.26), CD49d (71.52 ± 6.64) and CD31 (0.6 ± 0.86), but no immunoreactivity was detected for CD106 and CD45. The results of neural differentiation rative diseases using selegiline to induce ADSC differentiation to neuronal lineage.showed the highest percentage of nestin and NF-68 positive cells at 10-9 mM concentration of selegiline (exposed for 24 h). The differentiated cells expressed synapsin and neurotrophin genes except brain-derived neurotrophic factor. ADSC can be an alternative source in cell-based therapy for neurodegene.