Iranian

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The proliferation of smooth muscle cells in the arterial wall (VSMC) is considered to play a key role in the development of atherosclerosis. To investigate the possible contribution of "stress" (experimentally-induced) to this process, blood from healthy volunteers, ages 21 to 65, screened to exclude major risk factors for coronary heart disease, was assayed for mitogenic activity after the subjects were exposed to one of 2 "stress" conditions. These consisted of a cognitive task with superimposed verbal harassment (group 1), and the cognitive task without harassment (group 2). Mitogenic activity was determined by studying the growth stimulatory effects of PDGF-depleted plasma derived serum (PDS) from "stressed" subjects added to cultured VSMC, as measured by incorporation of radioactive thymidine into DNA or increase in cell number. In addition, changes in the steady state of the mRNA for the c-myc protooncogene were also assayed in VSMC by Northern blot analysis, using sera showing the greatest differential "pre/post stress" mitogenic activity. Blood pressure (BP), heart rate (HR), cortisol, and serum total and HDL cholesterol were also evaluated. All measurements were made immediately before (baseline) and after a 30 min interval. Analysis of the data revealed that there were 33% of subjects in group 1 with an increase of thymidine incorporation 15% or greater than baseline, versus 21% in group 2. The average increases were 45% and 30%. A higher percentage (35-42%) of subjects in group 1 responded with increases in systolic and diastolic blood pressure, compared to subjects in group 2 (15‌20%) the average in blood pressure was 10-15%. Similarly, more subjects (52%) in group 1 had an elevated (average 10-15%) serum cortisol, compared to the 42% in group 2 subjects. HR, total HDL cholesterol showed slight changes only. These results suggest that psychoactive factors may affect cardiovascular systems via rapid elicited rises in serum mitogenic activity for VSMC.

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Gamma irradiation is routinely used for suppression of lymphocyte function in transfusion and transplantation procedures. In recent years, some investigators focused on the effects of ionizing radiation on special aspects of lymphocyte function and considered the possibility of its clinical application for treatment of some immunological disorders. In this study, we evaluated the effects of five different doses of &gamma-ray on proliferation and IL-5 production of peripheral blood lymphocytes. Lymphocytes were separated from blood and were treated with 5, 10, 20, 30 and 40 Gy irradiation (using a 137 Cs source) and then were cultured for 72 h in the presence of phytohemagglutinin (PHA). The proliferative response of samples was evaluated by MTT assay, and the supernatant of the cells was collected for IL-5 detection. The results showed that the ionizing radiation had a suppressive effect on lymphocyte proliferation. IL-5 production was affected in a dose-response manner, augmented in response to 5 and 10 Gy and reached to its peak value at 20 Gy. At 30 Gy, IL-5 production was diminished lower than peak value, but still remained higher than control baseline, and 40 Gy led to IL-5 values lower than baseline

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Background: Norepinephrine plays a trophic role in the control of cell replication and differentiation in target cells that express adrenergic receptors. Methods: In this study, we have tested the influence of infraphysiological, physiological and supraphysiological concentrations (0.0001 nM, 1 nM, 10000 nM) of human norepinephrine on the proliferation of breast cancer cells (human breast adenocarcinoma [MCF-7]) in co-culture with human adipocytes in three-dimensional collagen gel matrix culture. Cell proliferation and lipolysis rate were measured by 3-(4, 5-dimethylthiazolyl)-2, 5-diphenyl-tetrazolium bromide (MTT) and Oil red O colorimetric assay in second, 7th days of culture experiments. Results: Our results showed a direct correlation between lipolysis rate of adipocytes and proliferation rate of MCF-7 cells. Both physiological and supraphysiological concentrations of human norepinephrine significantly (P<0.05) increased the proliferation of MCF-7 cells synchronously with progress of adipocyte lipolysis. The proliferations of MCF-7 cells were significantly decreased after conversion of adipocytes to fibroblast-like cells by supraphysiological concentration of norepinephrine. There was no statistical difference in lipolysis of adipocytes and proliferation of MCF-7 cells in response to infraphysiological concentration of norepinephrine. Conclusion: These findings indicated that norepinephrine stimulated the proliferation of MCF-7 cells in coculture with human adipocytes as a lipolytic factor and that norepinephrine effect was suppressed by conversion of adipocytes to fibroblast-like cells, suggesting adipocytes as another target for prevention and therapy of breast cancer.

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Background: While articular chondrocytes are among those appropriate candidates for cartilage regeneration, the cell dedifferentiation during monolayer culture has limited their application. Several investigations have indicated the usefulness of alginate, but the topic of proliferation and differentiation of chondrocytes in alginate culture has still remained controversial. Methods: Rat articular chondrocytes were released by enzymatic digestion, plated at 5 × 104 cells/cm2 and culture-expanded. Passaged-5 cells were then cultivated in alginate as 2-mm beads for a period of two months during which the expansion rate and the level of cell differentiation were determined by [3-(A, 5- dimethylthiazolyl- 2-yl)-1, 5-diphenyl tetrazolium bromide] assay and real-time PCR analysis respectively and compared with those of chondrocytes in monolayer culture. Results: Average population doubling time in alginate cultures (10.04 ± 0.9 days) tended to be significantly (P<0.05) higher than that in monolayer cultures (2.94 ± 0.3 days). The period of alginate culture could be subdivided into expansion phase (Days 0-40) during which proliferation appeared to be high and differentiation phase (Days 40-60) during which the expression of cartilage-specific genes including collagen II and aggrecan tended to be upregulated. During both the proliferation and differentiation phases, the expression of collagen I was low. At chondrocytes monolayer cultures, the proliferating cells appeared to have a very low expression level of cartilage-specific genes and a high expression level of collagen I gene during the entire culture period (P<0.05). Conclusion: It seems that alginate provides conditions in which rat articular chondrocytes are able to undergo proliferation and differentiation in certain time point of cultivation period.

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Background: A growing body of preclinical data indicates that statins may possess antineoplastic properties however, some studies have raised the possibility that statins may also have carcinogenic potential. Methods: An air pouch model was used for angiogenesis. Single or multiple applications of croton oil on the back of Swiss albino mice with or without initiation by dimethylbenz(a)antheracene (DMBA) were used to evaluate the skin tumorgenesis, ultrastructural and histological alterations. Results: Atorvastatin (orally, 10 mg/kg/day) produced a significant (P<0.05) reduction in angiogenesis. Concurrent administration of mevalonate reversed the anti-angiogenic effect of atorvastatin. However, local injection of atorvastatin (200 µg) into the pouches induced a significant (P<0.5) increase in angiogenesis that was not reversed by co-administration of mevalonate. The disturbance of cell polarity, inflammatory response, thickness of epidermal layer, and mitotic index induced by croton oil were inhibited markedly and dose-dependently (P<0.001) by pre-treatment with atorvastatin. In spite of the strong anti-inflammatory and anti-proliferative effects of atorvastatin on epidermal cell proliferation, it was identified that the same doses of atorvastatin in DMBA-initiated and croton oil-promoted skin tumorgenesis in mice increased the incidence of tumors and their conversion into malignant carcinoma. Conclusion: The reasons for these discrepancies remain unclear, and could be related to ambivalent effects of atorvastatin on angiogenesis or to specific differences in the experimental conditions. It is suggested that the pro-angiogenic effect of the drug, which could be responsible for promotion of skin tumors, is independent of the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibition that can be mediated directly by atorvastatin.

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Background: The health risks of crack cocaine smoking on the oral mucosa has not been widely researched and documented. Objective: The purpose of this study was to analyze the proliferative activity of oral epithelial cells exposed to crack cocaine smoke using silver nucleolar organizer region (AgNOR) staining. Methods: Oral smears were collected from clinically normal-appearing buccal mucosa by liquid-based exfoliative cytology of 60 individuals (30 crack cocaine users and 30 healthy controls matched for age and gender) and analyzed for cytomorphologic and cytomorphometric techniques. Results: Crack cocaine users consumed about 13.3 heat-stable rocks per day and the time consumption of the drug was of 5.2 (± 3.3) years. Mean values of AgNOR counting for case and control groups were 5.18 ± 1.83 and 3.38 ± 1.02 (P<0.05), respectively. AgNOR area and percentage of AgNOR-occupied nuclear area were increased in comparison with the control (P<0.05). There was no statistically significant difference in the mean values of the nuclear area between the groups (P>0.05). Conclusion: This study revealed that crack cocaine smoke increases the rate of cellular proliferation in cells of normal buccal mucosa.

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Background: The cultured mesenchymal stem cells (MSC) have been used in many clinical trials however, there are still some concerns about the cultural conditions. One concern is related to the use of FBS as a widely used xenogeneic supplement in the culture system. Human platelet-rich plasma (hPRP) is a candidate replacement for FBS. In this study, the effect of hPRP on MSC proliferation and osteogenic differentiation has been evaluated. Methods: Human adipose-derived stem cells (hADSC) were expanded. Cells from the third passage were characterized by flow cytometric analysis and used for in vitro experiments. Resazurin and alizarin red stains were used for cell proliferation and osteogenic differentiation assays, respectively. Results: Treatment with hPRP resulted in a statistically significant increase in cell proliferation compare to the negative control group (P<0.001). Cell proliferation in the 15% hPRP group was also significantly higher than that in the 10% hPRP group (P<0.05). Additionally, it caused less osteogenic differentiation of the hADSC compared to the FBS (P<0.001), but in comparison to negative control, it caused acceptable mineralization (P<0.001). Conclusion: These findings indicate that hPRP not only improves the proliferation but also it can be a suitable substitution in osteogenic differentiation for clinical purposes. However, the clinical application value of hPRP still needs more investigation.

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Background: Hyperlipidemia and oxidized-low-density lipoproteins (Ox-LDL) are important independent cardiovascular risk factors that have been shown to stimulate vascular smooth muscle cell (VSMC) proliferation. The purpose of the present study was to investigate the effect of vitamin E on Ox-LDL, lipid profile, C-reactive protein (CRP), and VSMC proliferation of rat aorta. Methods: Male Wistar rats (n = 32) were divided into four groups namely: sham (SH), control (C), non-treated diabetic, and vitamin E-treated diabetic (VETD) groups. Ox-LDL, lipid profile, CRP and VSMC proliferation of aorta were measured after 42 days. Results: The results revealed that along with a significant increase in VSMC proliferation, the amount of CRP, Ox-LDL, and lipid profiles in diabetic rats. VSMC proliferation was significantly ameliorated, and elevated CRP, Ox-LDL, and lipid profiles were also restored to those of shams in VETD. Conclusions: These findings strongly support the idea that diabetes induces Ox-LDL-mediated oxidative stress and VSMC proliferation in aorta of rat and imply that vitamin E has a strong protective effect as an antioxidant.