Ahmad Movahedian

The striatal dopamine (DA) deficiency is known as the main cause of the clinical picture of Parkinson’s disease (PD). The disease is a progressive degeneration of dopaminergic neurons in the striatum. The treatment of PD is based on compensation for the brain’s supply of DA lost by drug therapy, deep brain stimulation, surgery, gene and cell therapies. Clinical studies have focused on the utility of stem cell-based therapies in PD. Embryonic and mesenchymal stem cells (MSCs) are widely used. Recently, human adipose derived stem cells (hADSCs) have been considered as a suitable source of tissue for this purpose. In this project, hADSCs differentiated into dopaminergic neurons and the specificity of the cell preparations was examined. Human adipose tissues were collected from healthy volunteers undergoing liposuction and hADSCs were isolated by collagenase-based enzymatic method. Flow cytometry was performed using the surface cluster of differentiation (CD) markers to confirm the cell typical properties. Then hADSCs were differentiated to dopaminergic neurons in neurobasal medium in the presence of differentiation factors and confirmed by immunocytochemistry via neuronal and dopaminergic markers. The isolated hADSCs were cultured and identified by the expression of MSCs surface markers including CD90, and CD44. These cells did not express hematopoietic surface markers such as CD45 and CD14. Differentiated cells express neuronal marker NeuN and dopaminergic marker tyrosine hydroxylase (TH). It is concluded that hADSCs can be easily taken from the patient’s own body and differentiated into dopaminergic cells having a lower risk of transplant rejection.

BACKGROUND: Atherosclerosis is one of the predominant causes of cardiovascular disease (CVD). Several studies indicated the significant pathophysiological role of salusin-beta in atherosclerosis. Cytokines are involved in all stages of atherosclerosis. Therefore, we aimed to assess the effect of salusin-beta on interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 18 (IL-18) (as inflammatory cytokines) and interleukin 1Ra (IL-1Ra) (as anti-inflammatory cytokines) levels in human umbilical vein endothelial cells (HUVECs). METHODS: The HUVECs were cultured in HUVEC completed medium and treated with different doses of salusin-beta for 6 and 12 hours. For the investigation of nuclear factor kappa beta (NF-kappa beta) signaling pathway involvement, cells were treated in the presence or absence of Bay 11-7082 (as NF-kappa beta inhibitor). The mRNA expression and protein level of cytokines were measured by a real-time polymerase chain reaction (PCR) system and enzyme-linked immunosorbent assay (ELISA) method, respectively. RESULTS: Salusin-beta increased mRNA expression and protein level of IL-6, IL-8 and IL-18. This protein decreased mRNA and protein level of IL-1Ra in HUVECs. NF-kappa beta signaling pathway was involved in the up-regulatory effect of salusin-beta on mRNA expression of pro-inflammatory cytokines. The down-regulatory effect of salusin-beta on IL-1Ra expression could not be influenced by Bay 11-7082 pre-treatment. CONCLUSION: It seems that salusin-beta may participate in a cascade pathway in vascular inflammation. Our findings suggested that salusin-beta has potential use as a therapeutic target for atherosclerosis.

Atherosclerosis accounts for numerous cardiovascular diseases, and cytokines have a critical role in acceleration or suppression of disease. Salusin-α presents a new class of bioactive peptides that can have anti-atherogenic properties. Therefore, the effects of salusin-α on the expression of some pro- and anti-inflammatory cytokines and on TNF-α-induced inflammatory responses in human umbilical vein endothelial cells (HUVECs) were examined. The involvement of the NF-κB pathway in effects of salusin-α in HUVECs was checked using Bay 11-7082 as an NF-κB inhibitor. The mRNA expression of pro-inflammatory cytokines including IL-6, IL-8, and IL-18 and anti-inflammatory cytokine IL-1Ra was assessed by real-time PCR. The protein levels of cytokines were measured by the ELISA method. Salusin-α suppressed both mRNA and protein expression of pro-inflammatory cytokines and induced mRNA and protein expression of IL-1Ra in HUVECs. Salusin-α suppressed TNF-α-induced inflammatory responses in HUVECs. The down-regulatory or up-regulatory effects of salusin-α on expression of cytokines could not be influenced by Bay 11-7082 pretreatment. Our findings indicate anti-inflammatory effects of salusin-α and suggest a novel peptide-based therapeutic strategy for atherosclerosis.

Background: The influence of the supplementation of pomegranate peel extract containing anthocyanins on atherosclerotic plaque formation induced by hypercholesterolemia was investigated in renal arteries in rabbits. Materials and Methods: After the determination of polyphenol and anthocyanin's content of P. granatum peel hydroalcoholic extract, 30 male rabbits were randomly divided into three groups. They were fed basic diet, hypercholesterolemic diet and hypercholesterolemic diet along with P. granatum peel extract (polyphenolic content for each rabbit 1 g/kg diet) for 2 month. Blood samples were collected at the begging, middle and end of the study in order to measure lipid concentration and oxidative and antioxidative status variables, and renal arteries were taken for the assessment of atherosclerotic plaques at the end of the study. Results: The results reveal that P. granatum peel extract significantly increases serum antioxidant capacity in the extract recipient group in comparison with hypercholesterolemic control (P < 0.05). No significant differences are observed in total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein and in mean size of accumulated fatty streaks in renal arteries in the extract treatment group in comparison with hypercholesterolemic control (P > 0.05). Conclusion: The results of this study indicate that consumption of pomegranate peel extract containing anthocyanins (polyphenol content 1 g/kg diet) despite of a significant increase in serum antioxidant capacity cannot protect the kidneys from hypercholesterolemia-induced damages during the treatment period.

Background: Studies show that polyunsaturated fatty acids (PUFAs) may have an inhibitory role in carcinogenesis. It was previously shown that PLA2 group 2A (PLA2G2A) messenger RNA (mRNA) expression is associated with less frequent metastasis and longer survival in gastric adenocarcinoma. This study intends to investigate the effect of PUFAs on the expression of PLA2G2A in patients with gastric cancer. Materials and Methods: Thirty-four patients with gastric cancer (GC) were randomly divided into two groups. The first group received cisplatin medication. The second group received cisplatin medication and supplements of ω-fatty acids for three courses. The total RNA was extracted from the tissues and cDNA was synthesized. The gene expression of PLA2G2A was evaluated by the real-time polymerase chain reaction (PCR) method. To confirm the changes in gene expression, frozen section was utilized. The frozen tissue samples were sectioned and stained using the immunohistochemistry technique. Results: After chemotherapy and chemotherapy plus supplement, the relative mean of PLA2G2A gene expression increased 1.5 ± 0.5-fold and 7.4 ± 2.6-fold, respectively (P = 0.006). The relative mean of gene expression in patients who received cisplatin and ω-fatty acids supplement increased more significantly (7.5 ± 3.3-fold) than in patients who received only cisplatin (P = 0.016). Conclusion: It was found that PUFAs increased the gene and protein expression of PLA2G2A in gastric cancer. Concerning the fact that studies reveal protective function of PLA2G2A in gastric cancer, it is suggested that increased expression of PLA2G2A is helpful. Furthermore, PUFAs can be considered as a useful therapeutic supplement for patients with gastric cancer.

Lallemantia royleana (Benth. in Wall.) Benth. (Lamiaceae) is a medicinal plant used in Iranian traditional and folklore medicine in the treatment of various nervous, hepatic, and renal diseases. In the present study, whole seeds of the herb were prepared and evaluated for hypolipidemic activities using an animal model. Animals were fed normal diets or diets supplemented with cholesterol (0.5%) for 12 weeks to evoke hypercholesterolemia. Moreover, hypercholesterolemic animals were treated with different doses of whole seeds of Balangu (0, 5, 10, and 20%) for 12 weeks. Results showed that the serum total cholesterol and triglyceride decreased in all groups treated with Balangu seeds p<0.05. Changes in the distribution of cholesterol in low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were found. LDL-C and HDL-C decreased significantly in all of the groups treated with whole seeds of the herb with respect to hypercholesterolemic group p<0.05. Our results showed that L. royleana seeds decreased the serum cholesterol and triglyceride levels in hypercholesterolemic animals but led to the increase of atherogenic index in all treated groups.

Background: Long-term memory is based on synaptic plasticity, a series of biochemical mechanisms include changes in structure and proteins of brain's neurons. In this article, we systematically reviewed the studies that indicate calcium/calmodulin kinase II (CaMKII) is a ubiquitous molecule among different enzymes involved in human long-term memory and the main downstream signaling pathway of long-term memory. Methods: All of the observational, case-control and review studies were considered and evaluated by the search engines PubMed, Cochrane Central Register of Controlled Trials and ScienceDirect Scopus between 1990 and February 2015. We did not carry out meta-analysis. Results: At the first search, it was fined 1015 articles which included "synaptic plasticity" OR "neuronal plasticity" OR "synaptic density" AND memory AND "molecular mechanism" AND "calcium/calmodulin-dependent protein kinase II" OR CaMKII as the keywords. A total of 335 articles were duplicates in the databases and eliminated. A total of 680 title articles were evaluated. Finally, 40 articles were selected as reference. Conclusions: The studies have shown the most important intracellular signal of long-term memory is calcium-dependent signals. Calcium linked calmodulin can activate CaMKII. After receiving information for learning and memory, CaMKII is activated by Glutamate, the most important neurotransmitter for memory-related plasticity. Glutamate activates CaMKII and it plays some important roles in synaptic plasticity modification and long-term memory.

Oxidative stress has been implicated as a prominent determinant in the development of several diseases such as atherosclerosis. Anti atherosclerotic effects of L-serine have been shown previously but its responsible mechanisms remained unidentified. This study aimed to investigate the antioxidant and cytoprotecrtive effects of L-serine and its possible mechanisms. For this purpose, cell viability analysis and nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) activity, heme oxygenase-1 (HO-1) concentration, total Nitric Oxide (NOx) production were evaluated in oxidative stress-induced Human Umbilical Vein Endothelial Cells (HUVECs) pretreated by L-serine. Cytoprotective effects of L-serine was measured through 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Nrf2 activity and HO-1 concentration were determined in the cell lysate by commercial immunoassay methods. NOx was assayed in the supernatant of culture medium through colorimetric Griess method. Pretreatment with L-serine (0.1-3.2 mM) protected endothelial cells from hydrogen peroxide-mediated cell cytotoxicity (H2O2, 0.5 mM) and lead to significant induction of Nrf2 activity, HO-1 expresssion and NOx production. These findings demonstrated that L-serine has antioxidant and cytoprotective effects through the elevation of some crucial antioxidant factors such as Nrf2, HO-1 and NO.