Reza Mahmoudi

Embryonic neural stem cells (eNSCs) are immature precursors of the central nervous system (CNS), with self-renewal and multipotential differentiation capacities. These are regulated by endogenous and exogenous factors such as alpha-linolenic acid (ALA), a plant-based essential omega-3 polyunsaturated fatty acid. In this study, we investigated the effects of various concentrations of Alyssum homolocarpum seed oil (AHSO), containing natural ALA, stearic acid (SA), myristic acid (MA), and β-sitosterol, on proliferation and differentiation of eNSCs, in comparison to controls and to synthetic pure ALA. Treatment with natural AHSO (25 to 75 μM), similar to synthetic ALA, caused a significant ~ 2-fold increase in eNCSs viability, in comparison to controls. To confirm this proliferative activity, treatment of NSCs with 50 or 75 μM AHSO resulted in a significant increase in mRNA levels of notch1, hes-1 and Ki-67and NICD protein expression, in comparison to controls. Moreover, AHSO administration significantly increased the differentiation of eNSCs toward astrocytes (GFAP+) and oligodendrocytes (MBP+) in a dose dependent manner and was more potent than ALA, at similar concentrations, in comparison to controls. Indeed, only high concentrations of 100 μM AHSO, but not ALA, caused a significant increase in the frequency of neurons (β-III Tubulin+). Our data demonstrated that AHSO, a rich source of ALA containing also other beneficial fatty acids, increased the proliferation and stimulated the differentiation of eNSCs. We suggest that AHSO’s effects are caused by β-sitosterol, SA and MA, present within this oil. AHSO could be used in diet to prevent neurodevelopmental syndromes, cognitive decline during aging, and various psychiatric disorders.

Introduction: Many drugs with high efficacy are used to treat stomach ulcers, but they have many side effects. Therefore, much effort has been made to find new effective compounds from plant extracts. The aqueous extract of the internal layer of oak fruit (jaft) contains antioxidants and tannins; it has many desirable properties such as inhibition of the growth of pathogens. In this study, the preventing effect of Jaft extract on stomach ulcers induced by stress was investigated. Matherials and Methods: The effect of the extract on the prevention of gastric ulcer was investigated using a variety of methods including pH measurement, nitric oxide (NO), malondialdehyde (MDA), and histological methods. Rats were randomly divided into six groups. Five groups were gavage fed with different concentrations of Jaft extract, ranitidine and normal saline. The sixth group was gavage fed with normal saline as the control group. Ranitidine and normal saline were used as positive and negative controls, respectively. Data were analyzed by one-way analysis of variance (ANOVA) followed by Tukey's post hoc test using SPSS version 18.0. Results: It was revealed that the average thickness of the mucous glands and mucosal folds in the groups receiving the extract (250, 500 and 750 mg/kg) did not significantly decrease when compared with the situation of the control group (p<0.05). However, the average nitric oxide (NO) and malondialdehyde (MDA) in the control group meaningfully decreased in comparison with groups receiving the extract (250, 500 and 750 mg/kg). The average pH in groups receiving the extract and ranitidine significantly increased compared to the control group (p<0.05). Conclusions: Jaft extract contains abundant polyphenolic compounds and tannins and has several biological properties such as pharmacological properties, antioxidant activity, and inhibition of lipid oxidation. Therefore, it has the potential to prevent and treat stomach ulcers.

Ali Reza Fallahzadeh, Zohreh Rezaei, Hamid Reza Rahimi, Mehrazd Jafari Barmak, Hossein Sadeghi, Sadrollah Mehrabi, Seyed Mohammadreza Rabani, Iraj Ragerdi Kashani, Vahid Barati and Reza Mahmoudi. ToxicolRes 2017;33:255-63. https://doi.org/10.5487/TR.2017.33.3.255

Background: Matricaria chamomilla is an aromatic plant with antioxidant, anticancer, and anti-inflammatory properties. However, the inhibitory role of M. chamomilla on migration and invasion of human breast cancer cells remains unclear. Objective: This study investigated the methods to evaluate these anticancer mechanisms of M. chamomilla on human breast cancer MCF-7 and MDA-MB-468 cell lines. Materials and Methods: The cells were treated with hydroalcoholic extract of M. chamomilla at different concentrations (50–1300 μg/mL) for 24, 48, and 72 h in a culture medium containing 10% fetal bovine serum. This study quantified the 50% growth inhibition concentrations (IC₅₀) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; apoptosis and necrosis through Hoechst 33342/propidium iodide staining; cell proliferation and clone formation by clonogenic assay as well as cellular migration, invasion, and attachment. After 24, 48, and 72 h of treatment, the IC₅₀levels were 992 ± 2.3 μg/mL, 893 ± 5.4 μg/mL, and 785 ± 4.8 μg/mL against MDA-MB-468, respectively, and 1288 ± 5.6 μg/mL, 926 ± 2.5 μg/mL, and 921 ± 3.5 μg/mL, against MCF-7, respectively. Furthermore, increasing the extract concentrations induced cellular apoptosis and necrosis and decreased cellular invasion or migration through 8 μm pores, colonization and attachment in a dose-dependent manner. Results: It indicated time- and dose-dependent anti-invasive and antimigrative or proliferative and antitoxic effects of hydroalcoholic extract of aerial parts of chamomile on breast cancer cells. Conclusion: This study demonstrated an effective plant in preventing or treating breast cancer.

Evaluation of viability and subsequent developmental ability of mouse germinal vesicle breakdown oocytes vitrified in conventional straws. Oocytes with compact cumulus cells were cultured for 3 h in TCM199 medium GVBD and vitrified by two methods: the step-wise and single-step. After vitrification, the oocytes were thawed, and subjected to in vitro maturation and in vitro fertilization. Oocyte survival (post-thaw) was assessed by morphological appearance and staining, using propidium iodide (PI)/Hoechst 33342. The oocyte maturation and fertilization rates were examined in vitro. In the single-step method the rates of post thaw survival, maturation to metaphase II and cleavage (2-cell embryos) were 58.68%, 56.41% and 38.63%, respectively. In the step-wise method, the corresponding rates were 81.75%, 68.59% and 51.80%, respectively. Vitrification of mouse germinal vesicle breakdown oocytes by the step-wise method had the advantage of maintaining the viability and subsequent production of 2-cell embryos. In comparison with that in unvitrified control oocytes, the development of MII oocytes to 2-cell embryos was impaired following vitrification.

Adipose-derived stem cells (ADSC) could be an appealing alternative to bone marrow stem cells (BMSC) for engineering cell-based osteoinductive grafts. Meanwhile, prior studies have demonstrated that melatonin can stimulate osteogenic differentiation. Therefore, we assayed and compared the melatonin effect on osteogenic differentiation of BMSC with that of ADSC. Mesenchymal stem cells (MSC) were isolated from the bone marrow and fat of adult rats. Both cell types were cultured in osteogenic medium in the absence and presence of melatonin at physiological concentrations (20-200 pg/ml). After 4 weeks, the expression of osteocalcin gene was analyzed by reverse transcription-PCR, alkaline phosphatase (ALP) activity was assayed and alizarin red S and von Kossa staining were done. Cell viability and apoptosis were also assayed by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a tetrazole (MTT) and flow cytometry, respectively. The osteoblastic differentiation of ADSC as demonstrated by ALP activity was less than that of BMSC. The amount of matrix mineralization has shown by alizarin red S and von Kossa staining also showed statistical differences between the two MSC. The incidence of apoptotic cells was higher among ADSC than BMSC. The flow cytometry proves that cell growth reduction is due to a decrease in the number of the cells entering the S phase of the cell cycle. MTT assay indicated that viable cells were fewer among ADSC than BMSC in control groups. The results of the study suggest that BMSC have greater osteogenic potential than ADSC and that melatonin promotes osteogenic differentiation to BMSC, but has a negative effect on ADSC osteogenic differentiation.