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Background and Aim: Breast cancer is one of the most common types of cancer among Iranian women. To date, the usual cancer treatments have not been entirely effective. Therefore, creating anticancer products is of great importance. The aim of this study was to evaluate the cytotoxic, anticancer, and induction effects of Bacillus coagulans probiotic bacterial supernatant on SKBR3 cells. Materials and Methods: The anticancer potential and cytotoxic effect of different concentrations of probiotic bacterial supernatants (1, 2, 3, 4, 5, 6 and 7 mg/mL) were evaluated on SKBR3 cells for 24, 48, and 72 h by MTT technique. QRT-RCR was used to assess the expression of bax, bcl2, casp3, and casp9 genes, and flow cytometry was used to evaluate apoptosis in cancer cells. Results: The inhibitory effect of dose- and time-dependent B. coagulans supernatant showed that the supernatant of this probiotic bacterium had a cytotoxic effect on SKBR3 cancer cells. On the other hand, analysis of flow cytometry results and increased expression of bax, casp3, and casp9 pro-apoptotic genes and decreased bcl2 expression in cancer cells showed induction of apoptosis. Conclusion: The anticancer and cytotoxic effect of B. coagulans probiotic bacterial supernatant on SKBR3 cancer cells shows that with further research, this probiotic bacterium can be used as a new strategy for the possible treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Abstract Background One of the most important factors in the initiation and progression of atherosclerosis is the default in macrophage cholesterol homeostasis. Many genes and transcription factors such as Peroxisome Proliferators Activated Receptors (PPARs) and Acyl Coenzyme A: Cholesterol Acyltransferase1 (ACAT1) are involved in cholesterol homeostasis. Fatty Acids are important ligands of PPARα and the concentration of them can effect expression of ACAT1. So this study designed to clarified on the role of these genes and fatty acids on the lipid metabolism in foam cells. Methods This study examined effects of c9, t11-Conjugated Linoleic Acid(c9, t11-CLA), Alpha Linolenic Acid (LA), Eicosapentaenoic Acid (EPA) on the PPARα and ACAT1 genes expression by using Real time PCR and cholesterol homeostasis in THP-1 macrophages derived foam cells. Results Incubation of c9, t11-CLA, LA cause a significant reduction in intracellular Total Cholesterol, Free Cholesterol, cellular and Estrified Cholesterol concentrations (P ≤ 0.05). CLA and LA had no significant effect on the mRNA levels of ACAT1, but EPA increased ACAT1 mRNA expression (P = 0.003). Treatment with EPA increased PPARα mRNA levels (P ≤ 0.001), although CLA, LA had no significant effect on PPARα mRNA expression. Conclusion In conclusion, it seems that different fatty acids have different effects on gene expression and lipid metabolism and for complete conception study of the genes involved in lipid metabolism in foam cell all at once maybe is benefit.

Cadmium (Cd) is a toxic metal that is involved in apoptosis. The present study was conducted to investigate the mechanism of Cd-induced apoptosis and the protective effects of vitamin E on rat testes. Thirty-two adult Wistar rats were divided into four groups. The control group was injected with saline and three other groups received Cd, Cd+vitamin E, and vitamin E. Intraperitoneal injection was performed for 28 days. On the 29th day, the rats were slaughtered, their peritoneum was opened, and their left testis removed and weighed. The mRNA expression of apoptosis and mitochondrial dynamics genes were assessed using real-time PCR, and caspase-3/7 activation using the caspase-3/7 Assay. The groups were not significantly different in terms of testicular weight. Compared with the control group, the mRNA expression levels of Bax and caspase-9 genes increased in the rats' testes receiving Cd, the mRNA expression levels of mitofusin 1 (Mfn1) and mitofusin2 (Mfn2) genes decreased, and those of Bcl-2 remained unchanged. Vitamin E was found to significantly decrease the mRNA expression of Bax and caspase-9 genes and increase the mRNA Mfn1, Mfn2, and Bcl-2 in the rats' testes receiving Cd. The ratio of Bax/Bcl-2 and caspase-3/7 activity increased in the Cd-exposed rats compared with the control. Vitamin E remarkably attenuated the Cd-induced effects. According to the obtained results, Cd exerts its apoptotic effects through the mitochondrial pathway by increasing the ratio of Bax/Bcl-2 and activating caspases in the rats' testes, and vitamin E plays a protective role against Cd-induced apoptosis. [ABSTRACT FROM AUTHOR]

Background: Thymidine phosphorylase (TP) catalyses the conversion of thymidine into thymine. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disease which is caused by mutations in the nuclear gene encoding TP, bringing about severe impairment of TP-enzyme specific activity and accumulation of thymidine in plasma. The clinical manifestations of MNGIE are recognizable and homogenous, but not in the early stages of the disease. In patients who are suspected of having MNGIE, determination of TP-specific activity in leukocytes and thymidine levels in plasma are diagnostic. The methods that are usually used for the measurement of TP activity and plasma thymidine are not rapid or accurate enough and lack sensitivity. Methods: The specific activity of TP was measured by RP-HPLC in leukocytes of both the controls and the patients exhibiting clinical features suggestive of MNGIE. Moreover, plasma thymidine was assessed by the same method. Results: The patients had detectable plasma thymidine (>3 >mol/L) but it was undetectable in the healthy controls. The patients' TP-specific activity decreased to less than 5% relative to the controls (14±4 nmol/h/mg vs. 525±165 nmol/h/mg, P<0.05). A diagnostic algorithm for the definitive diagnosis of MNGIE is suggestible based on the results of this study which relies on the measurement of plasma thymidine, TP-specific activity in leukocytes, or both. Conclusion: In this study, we set up a sensitive and rapid assay for the evaluation of TP-specific activity by using RP-HPLC in Iran. In addition, we established reference values for TP-specific activity and plasma thymidine in the Iranian patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling for management of refractory diffuse diabetic macular edema (DME). Methods: In this prospective interventional case series, eyes with refractory diffuse DME unresponsive to macular photocoagulation and/or intravitreal bevacizumab, and best corrected visual acuity (BCVA) =20/200 and =20/60 underwent triamcinoloneassisted PPV with ILM peeling. Pre- and postoperative evaluations included a complete ophthalmologic examination, fluorescein angiography and optical coherence tomography (OCT). Main outcome measures were BCVA and central macular thickness (CMT). Results: Twelve eyes of 12 patients with mean age of 59.6±3.9 (range, 55-68) years were operated and followed for a mean period of 4.9±1.0 (range, 4-6) months. Mean BCVA at final examination was 0.82 ± 0.18 logMAR which was not significantly better than its preoperative value of 1.00 ± 0.80 logMAR (P=0.959). Visual acuity improved by at least 2 lines in 3 eyes (25%), remained stable in 7 eyes (58%) and decreased by at least 2 lines in 2 eyes (17%). Mean CMT at final examination was 315±95 μm, which was significantly less than its preoperative value of 467±107 μm (P=0.004). Complications included vitreous hemorrhage in 2 and cataract progression in 5 eyes. Conclusion: PPV with ILM peeling for refractory diffuse DME seems to reduce macular thickness, but does not significantly improve visual acuity as observed after an intermediate-term follow up of about 6 months. [ABSTRACT FROM AUTHOR]

Purpose: To report the long-term results of intravitreal bevacizumab (Avastin) therapy for choroidal neovascularization (CNV) secondary to non-age-related macular degeneration (non-AMD). Methods: This prospective interventional case series was conducted on patients with non-AMD CNV. All patients received 1.25 mg intravitreal bevacizumab and were followed for at least 18 weeks. Indications for retreatment were decreased visual acuity or recurrence of subretinal fluid or hemorrhage associated with leakage on fluorescein angiography. Primary outcome measures were changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT). Secondary outcome measures consisted of any adverse event related to the therapy. Results: The study included 31 eyes of 28 patients with non-AMD CNV including idiopathic (n=11), due to myopia (n=7), angioid streaks (n=5), and other disorders (n=8). Mean initial BCVA was 20/100 which improved to 20/60 at 6 weeks; 20/40 at 12, 18, 24, and 36 weeks; and 20/30 at 54 weeks. Serial optical coherence tomography measurements showed mean CMT of 288 μm at baseline, which was decreased to 209 μm at last visit (P=0.95). There was no correlation between the underlying disease and changes in BCVA during the follow-up period. Conclusion: Intravitreal bevacizumab significantly improved visual acuity in eyes with non-AMD CNV due to various etiologies. [ABSTRACT FROM AUTHOR]

Background: One of the most important factors in the initiation and progression of atherosclerosis is the default in macrophage cholesterol homeostasis. Many genes and transcription factors such as peroxisome proliferators activated receptors (PPARs) and acyl coenzyme A: cholesterol acyltransferase1 (ACAT1) are involved in cholesterol homeostasis. Fatty acids are important ligands of PPARalpha and the concentration of them can effect expression of ACAT1. So this study designed to clarified on the role of these genes and fatty acids on the lipid metabolism in foam cells., Methods: This study examined effects of c9, t11-conjugated linoleic acid(c9, t11-CLA), alpha linolenic acid (LA), eicosapentaenoic acid (EPA) on the PPARalpha and ACAT1 genes expression by using Real time PCR and cholesterol homeostasis in THP-1 macrophages derived foam cells., Results: Incubation of c9, t11-CLA, LA cause a significant reduction in intracellular total cholesterol, free cholesterol, cellular and esterified cholesterol concentrations (P < or = 0.05). CLA and LA had no significant effect on the mRNA levels of ACAT1, but EPA increased ACAT1 mRNA expression (P = 0.003). Treatment with EPA increased PPARalpha mRNA levels (P < or = 0.001), although CLA, LA had no significant effect on PPARalpha mRNA expression., Conclusion: In conclusion, it seems that different fatty acids have different effects on gene expression and lipid metabolism and for complete conception study of the genes involved in lipid metabolism in foam cell all at once maybe is benefit.