Mohammad Reza Mirzaei

Outcome of Capparis Spinosa Fruit Extracts Treatment on Liver, Kidney, Pancreas and Stomach Tissues in Normal and Diabetic Rats

Aim and objectives: Herbal drugs such as, Capparis Spinosa (CS) has been used to treat several diseases from heart and cardiovascular disorders to diabetes in traditional Iranian medicine. The present study was aimed to determine beneficiary effects of CS fruit extract on a number of tissues in healthy and type 1 diabetic rat. Materials and methods: In this experimental study, sixty male wistar rats were randomly divided into 6 groups (n=10) and subjected to gavage tube therapy for one months by following protocol: group I and IV: diabetic control and non-diabetic control rats which only received distilled water; groups II and III: non diabetic treatment rats which received 200 mg/kg and 800 mg/kg CS extract per day respectively; groups V and VI: diabetic treatment rats which received 200 mg/kg and 800 mg/kg CS extract per day respectively. Diabetes was induced by intra-peritoneal injection of 50 mg/kg of streptozotocin (STZ). After 4 weeks, their blood were collected and the serum levels of creatinine, bilirubin, urea, uric acid, AST, ALT and ALP were measured. The liver, kidney, pancreas and stomach tissues were immediately excised, and after slide preparation processes, the histological changes were studied. Results: Our results illustrated that the gastric tissue in the diabetic group showed a small degree of changes and was not affected significantly by administration of the CS fruit extract. Liver, pancreas and kidney of diabetic rats exhibited considerable changes, like cellular necrosis. These changes in diabetic treatment groups were at lowest amounts. The decrease levels of creatinine, liver enzymes, and other factors were supporting these changes. Conclusions: This study demonstrates that the CS fruit extract could be aid prevention of damage to the tissues due to the decreased levels of harmful oxidants in the body in diabetes. Moreover, according to our previous results altogether we showed beneficial impact of the plant on the treatment of diabetes.

An in vitro evaluation of anti-aging effect of guluronic acid (G2013) based on enzymatic oxidative stress gene expression using healthy individuals PBMCs

BACKGROUND Aging is usually associated with increased levels of oxidants, and may result in damages caused by oxidative stress. There is a direct relationship between aging and increased incidence of inflammatory diseases. The present research intended to study the anti-aging and anti-inflammatory effects of the drug G2013 (guluronic acid) at low and high doses on the genes expression of a number of enzymes involved in oxidative stress (including SOD2, GPX1, CAT, GST, iNOS, and MPO) in peripheral blood mononuclear cells (PBMCs) of healthy individuals under in vitro conditions. METHODS Venous blood samples were taken from 20 healthy individuals, the PBMCs were isolated and their RNAs extracted and their cDNAs were synthesized, and the genes expression levels were measured using the qRT-PCR technique. RESULTS Our results indicated that this drug could, at both low and high doses, significantly reduce the expression of the genes for SOD2, GPX1, CAT, and GST compared to the LPS group (p<0.0001). Moreover, it was noticed that the drug is able to significantly reduce gene expression levels at the high dose and at both doses (low and high), for iNOS and MPO compared to the LPS group (p<0.0001), respectively. CONCLUSIONS The present research showed that G2013, as a novel NSAID drug with immunomodulatory properties, could modulate the expression levels of the genes for SOD2, GPX1, CAT, GST, iNOS, and MPO, to the level of healthy gene expression, and possibly it might reduce the pathological process of aging and age-related inflammatory diseases.

Expression of Inhibitor of Apoptosis Gene Family Members in Bladder Cancer Tissues and the 5637 Tumor Cell Line

Background: Apoptosis is suppressed in cancer tissues and tumor cell lines because anti-apoptosis genes are over- expressed. The inhibitor of apoptosis proteins (IAP) gene family contributes to control of apoptosis. The expression profile of eight genes of the IAP family in biopsies from patients with a history of bladder cancer and normal bladder tissues, as well as a bladder tumor cell line (5637), was assessed in the present study. Methods: Cancer tissue samples were obtained at surgery and the 5637 tumor cell line was cultured in RPMI1640 medium. Beyond tumor margins were selected as normal tissue. Expressional profile of interested genes was obtained by using specific primers and the real-time PCR method. Results: The results showed that expression of seven of the studied genes was up-regulated in cancer tissues and the cell line whereas BIRC4 (XIAP) was down-regulated in both. Conclusions: The results showed that these genes were expressed to a greater extent in cancer tissue and cancer cells than in normal tissues. The data suggested that over-expression of anti-apoptotic genes such as IAP family members, can trigger cells to escape from apoptosis.

Effect of β-D-Mannuronic Acid (M2000) on Oxidative Stress Enzymes’ Gene Using Healthy Donor Peripheral Blood Mononuclear Cells for Evaluating the Anti-Aging Property

OBJECTIVE This research aimed to study the anti-aging and anti-inflammatory effects of low and high doses of the β-D-mannuronic (M2000) on gene expression of enzymes involved in oxidative stress (including SOD2, GST, GPX1, CAT, iNOS, and MPO) in peripheral blood mononuclear cells (PBMCs) of healthy donors under in vitro conditions. METHODS The PBMCs were separated and the RNAs were then extracted and the cDNAs synthesized, and expression levels of the mentioned genes were detected by qRT-PCR. RESULTS Our results indicated that the high dose of this drug could significantly reduce the expression level of the SOD2 gene compared to the lipopolysaccharide (LPS) group (p < 0.0001). Moreover, it was found that the high dose of this drug could significantly decrease the expression level of the GST gene compared to the LPS group (p < 0.0001). However, no significant reductions were observed in expression levels of the CAT and GPX1 genes compared to the LPS group. Furthermore, our data revealed that the level of iNOS and MPO gene expression was significantly reduced, in both doses of M2000, respectively, compared to the LPS group (p < 0.0001). CONCLUSION This research showed that M2000 as a novel NSAID with immunosuppressive properties could modify oxidative stress through lowering expression levels of the SOD2, GST, iNOS, and MPO genes compared to the healthy expression levels, with a probable reduction of the risk of developing inflammatory diseases related to age and aging.

Down-regulation of anti-apoptotic genes in tumor cell lines is facilitated by suppression of OCT4B1

PURPOSE The OCT4B1 as a variant of OCT4 is expressed in both cancer cells and tissues. The anti-apoptotic property of this variant aid cancer cells to escape from apoptosis. Therefore, the aim of the present study was to determine the effects of OCT4B1 suppression on regulation of 25 genes involved in anti-apoptotic pathway in tumor cell lines. MATERIAL AND METHODS AGS (gastric adenocarcinoma), 5637 (bladder tumor) and U-87MG (brain tumor) cells were transfected with specific OCT4B1 siRNA and a scramble siRNA by siRNA silencing gene technology, using Lipofectamine 2000 commercial kit. The real-time PCR technique was employed to examine and calculate fold changes of evaluated genes using the 2-ΔΔCT formula. RESULTS Present results demonstrated that 22 (88%) of interested genes were similarly down-regulated in all three examined cell lines. Our results also indicated that three genes (CASP2, IGF1R,TNF) were up-regulated. The CFLAR gene was down-regulated in AGS, while it was inversely up-regulated in 5637 and U87MG cells. CONCLUSIONS It may possibly be concluded that suppression of OCT4B1 can lead to apoptosis in tumor cell lines and this is at least facilitated via down-regulation of examined anti-apoptotic genes. Accordingly, suppression of OCT4B1 may probably be considered as useful tool in cancer therapy and research.