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Introduction : Cutaneous leishmaniasis is a public health problem in Iran. Actually Antimony compounds commonly used in the treatment of this disease. Using these drugs associated with limitations and several side effects. Research for introducing a new and effective drug is considere. In the present study, the effect of 5 - fluorouracil on growth of Leishmania major promastigotes were evaluated in vitro conditions. In addition the effect of fluorouracil on induction of apoptosis in promastigotes of the leishmania major were investigated. Material and Methods: Different concentrations of 5–fluorouracil(12, 25, 50 and 100 µg/ml) were tested in three times and the IC50 was calculated by counting the number of parasites. Viability percent of promastigotes was determined after adding drug by MTT assay. Flow cytometry was used to investigate the induction of apoptosis in the parasites. Findings: The 5–fluorouracil has inhibitory effects on the growth of Leishmania promastigotes.IC50 was measured 26.17 µg/ml after 24h. Analysis of the results of flow cytometry showed that the 5 - fluorouracil induces apoptosis in Leishmania major promastigotes. Discussion and Conclusion: The 5-fluorouracil has antileishmanial effects on leishmania major. So it can be suggested to evaluate in vivo condition against cutaneous leishmaniasis.

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Introduction: Endometriosis is a gynecological disease characterized by the presence of endometrial cells outside the uterine cavity. Apoptosis plays an important role in the pathophysiology of endometriosis. Fas is a cell surface receptor that is expressed in endometrium and plays a crucial in the apoptosis. This study investigated the association between Fas rs1800682 gene polymorphism and susceptibility to endometriosis.

Material &methods: This case-control study was done on 100 endometriosis patients and 100 normal women. Genomic DNA was extracted from blood samples. The polymorphism was determined by using Tetra-ARMS PCR technique. The association between Fas rs1800628 polymorphism and the endometriosis risk was examined by using odds ratios (OR) and 95% of confidence intervals (CIs).

Findings: The frequency of the GG genotype in patients and controls was 22% and 10%, respectively. There was significant difference in the distribution of GG genotype between endometriosis patients and controls(OR=3.3, 95%CI= 1.4-7.9, P=0.007). Also, statistically significant association was observed between G allele and the risk of endometriosis development (OR= 1.8, 95%CI= 1.2-2.7, P= 0.004).

Discussion & Conclusion: This is the first study in regard to the association of Fas rs1800628 polymorophism with endometriosis risk in Iranian population. The results of this study showed that there were significant differences in the genotype distribution and allelic frequency between case and control groups. These finding suggest that the Fas rs1800628 gene polymorphism may contribute to endometriosis susceptibility in Iranian population.

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Introduction: Apoptosis or programmed cell death plays an important role in the pathogenesis of many diseases. Diabetes mellitus is a devastating effect on reproductive system of male sexual function in human and animal models and increased apoptosis. Kudzu root is an ISO Flavonin and saponins and often is used as a reducing agent is glucose. Kudzu is able to lower blood glucose in non-insulin dependent  and also, by eliminating free radicals that lead to the reduction of oxidative stress. This study was conducted on the effect of Kudzu roots on apoptosis in the testes of rats diabetic.

Materials & methods: In this study, 32 male Wistar rats were randomly selected and divided into four groups: control, diabetic rats, diabetic rats treated with Kudzu 100 mg/kg, diabetic rats treated with Kudzu 50 mg / kg. Diabetic by intraperitoneal injection of streptozotocin55 mg/kg  was induced. One week after injection, they were treated with a dose Kudzu 50 and 100 mg/kg for five weeks using gavage. Testicular damage by H & E staining and immunohistochemistry and hormonal and Blood biochemical factors were measured.

Findings: Diabetic rats showed a significant increase in apoptosis in the testis. Decrease in seminiferous tubule diameter of diabetic rats, Sertoli cells, sperm count,Insulin and testosterone levels were shown. In rats treated with Kudzu roots it resulted in significant reduction of apoptosis in diabetic rats and significantly increased body weight, plasma Insulin and testosterone levels. It was observed that the oral administration roots of  Kudzu increase sperm count, sperm cell of Sertoli cells.

Discussion & Conclusions: The results of this study confirmed the occurrence of apoptosis in diabetes and root Kudzu of the anti-apoptotic effect notes.

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Introduction: Diabetes is associated with different neurological disorders in the nervous system that will eventually lead to cell damage. The previous studies have shown the beneficial effects of exercise on brain damage caused by diabetic neuropathy in animal models. In the present study, the effect of aerobic exercise training on cell death in the hippocampal CA1 area neurons in diabetic male rats was investigated.

Materials & methods: 21 adult male Wistar rats (weighing 260-300 g) were purchased from Tehran Pasteur Institute and were randomly divided into three groups: sham group, diabetic group and diabetic + exercise training group (7 rats per group). Diabetes was induced intraperitoneally streptozotocin (STZ) administration at the dose of 60mg/kg. The diabetes criterion was the blood glucose level higher than 250 mg/dl. One week after induction of diabetes, the rats in exercise training group were trained to run on a treadmill 5 days a week for 4 weeks. Necrotic cell death was detected by Nissl staining and apoptosis was detected by TUNEL staining.

Findings: The results showed that aerobic exercise training significantly reduced the diabetes-induced necrotic cell death (p<0.01) and apoptosis (p<0.05) in the hippocampal CA1 area neurons.

Discussion & conclusions: This study showed that aerobic exercise training has neuroprotective effects against diabetic neuropathy. This neuroprotective mechanism of exercise can be an effective way to reduce cerebral complications of diabetes. 

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Introduction: Many scientific and medical studies in the recent years have shown that Eugenol could be an effective reagent in preventing and reducing cancer progression by antioxidant and anti-inflammatory activities and induction of apoptosis in cancer cells. In this regard the present study also examined the effect of Eugeonl on the viability and expression of CASP8 and CASP9 genes in human colorectal cancer cell line (HT-29).
 
Materials & Methods: In the present study, human colorectal cancer cell line (HT-29) was cultured in RPMI-1640 medium enriched with 10% bovine serum. The cells were treated in different concentration (250, 500, 750, 900, 1000 μM) of Eugenol and incubated for 24, 48 and 72 hours. After that cell viability was analyzed by MTT assay. The expression of CASP8 and CASP9 genes was also evaluated by Real-time PCR analysis in treated cells at 750 μM concentration of Eugeonl and during 24, 48 and 72 hours, incubation.
 
Findings: Along with increasing concentration and duration of Eugenol treatment, both cell lines encountered a decrease in the percentage of live cells. Although this reduction was found to be much higher in the cancer cells than in fibroblastic cells. Also, in the treated group with a concentration of 750 μm, expression of CASP8 and CASP9 genes significantly increased compared to control groups.
 
Discussion & Conclusions: Eugenol may have an inhibitory effect on the growth, proliferation and invasion of colon cancer cells by increasing the expression of CASP8 and CASP9 genes, and inducing apoptosis in HT-29 cancer cells and reducing the risk of cancerous cell proliferation it turns out.

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Introduction: The combined therapy of cancer is more effective than using a single medication for the treatment of cancer. This study aimed at investigating the anticancer effects of cisplatin and cisplatin in combination with Titanium dioxide (TiO₂) nanoparticles on the PC-3 prostate cancer cells.
 
Materials & Methods: The PC-3 cells were cultured in a RPMI1640 medium. Cell viability was assessed by MTT assay during 24, 48, and 72 h, and IC₅₀ was determined. The RNA was extracted, and then the cDNA was synthesized. The expression level of BCL2L12 gene was compared to that of the TBP reference gene using Real-Time Polymerase Chain Reaction method.
 
Findings: Cisplatin and cisplatin with TiO₂ nanoparticles exerted a dose and time dependent inhibitory effect on the viability of PC-3 cells. The expressions of the BCL2L12 gene in cisplatin-treated PC-3 cells at 24, 48, and 72 h were 3.58, 0.08, and 0.17, respectively. Moreover, the corresponding values in cisplatin-treated cells with TiO₂ nanoparticles (10μg/ml) were 0.09, 0.05, and 0.02 at 24, 48, and 72 h, respectively, and in cisplatin-treated cells with TiO₂ nanoparticles (25μg/ml) were 0.54, 0.04, and 0.07 at 24, 48, and 72 h, respectively (P<0.05).
 
Discussion & Conclusions: This study revealed that simultaneous treatment with cisplatin and TiO₂ nanoparticles (10μg/ml) at low concentration (6.2 and 12.5) can cause more cell death than cisplatin treatment alone. This may be due to the facilitation of cisplatin entry into the cell in the presence of TiO₂ nanoparticles.
 

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Introduction: Diabetes is the most prevalent endocrine disease. Apoptosis and necroptosis play a major role in the development of diabetes-related heart diseases; however, the effects of continuous and interval exercise on apoptosis and necroptosis of the heart cells in diabetics are unclear. This study aimed to investigate the effect of different intensities of aerobic exercise on apoptosis and necroptosis of the cardiac tissue of diabetic mice.
 
Materials & Methods: In total, 32 mature, male, and white Wistar rats (mean age of 12±2 weeks and weight of 175±15 g) were randomly divided into four groups of eight animals per group. The groups included a healthy control (C), diabetic control (D), diabetic with moderate-intensity continuous training (55 min with 26 m/min speed daily) (D+MICT), and diabetic with high-intensity interval training at the 85-90% of maximum speed (D+HIIT) (5 days/week for 8 weeks). Before the training protocol, the running speed was calculated to obtain the maximum oxygen consumption. Western blot analysis was utilized to evaluate the changes in the expression of the proteins associated with apoptosis and necroptotic death path in the diabetic heart muscle myocardium. Furthermore, the one-way analysis of variance was used to determine the differences among the study groups. A p-value less than 0.05 was considered statistically significant. Ethics code: IAU.SARI.REC.1397.8
 
Findings: The results indicated that type 2 Diabetes Mellitus significantly increased both apoptotic and necroptotic cell death (P=0.001). However, both continuous and interval training moderated the apoptotic cell death (P≤0.05). Nonetheless, the effect of interval training was higher than that of the continuous one. It is worth mentioning that only interval training had a significant effect on reducing the necroptosis (P≤0.05).
 
Discussions & Conclusions: It seems that continuous and interval exercise affects apoptotic death; however, intense interval exercise is more effective in necroptotic death.
 

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Introduction: There is growing evidence about the use of antioxidants to reduce the side effects of chemotherapy and cancer drug resistance. Therefore, this study aimed to use vitamin C as an antioxidant and determine its effect on drug resistance in HT29 cells.
 
Materials & Methods: During this case-control study, HT29 cells were first cultured and evaluated by MTT assay for cell death in the presence of vitamin C and 5FU. DAPI staining was also performed to visualize cell apoptosis. After RNA extraction and cDNA preparation, to determine the molecular mechanism of apoptosis by the drug and the inhibition effect or aggravation of vitamin C on cellular signaling of apoptosis, expression of growth-related genes and apoptosis of Caspase-3 and Bax were measured by real-time PCR.
 
Findings: The results of the MTT test showed that vitamin C had no significant effect on cell apoptosis induced by 5-FU. DAPI and DNA ladder assay results from HT29 cells showed qualitative changes in cell apoptosis. In addition, real-time PCR results revealed increased expression of Bax and Caspase-3 in HT29 colon cancer cells treated with chemotherapy.
 
Discussions & Conclusions: Our findings showed that vitamin C did not prevent the effect of chemo drug although it had no positive effect on the growth of cancer cells. Therefore, vitamin C intake by patients undergoing chemotherapy will not affect the drug's effect on the tumor and may protect the patient from side effects.
 

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Introduction: Ischemia followed by apoptosis and follicles mortality are problems that occur after cryopreservation and ovarian tissue transplantation. The present study used hyaluronic acid hydrogel as a capsule to reduce ischemia and apoptosis in vitrified ovarian tissue transplantation of rats.
Material & Methods: In total, 22 adult female rats (~ 8-week old) with normal estrous cycle were ovariectomized, and their right ovaries were then vitrified and divided into two groups after being warmed, including vitrified-transplanted (VT) (n=11) and vitrified-encapsulated in hyaluronic acid hydrogel-transplanted (VT+HA) (n=11) that were auto transplanted into the dorsal muscle. Following that, a daily vaginal smear was obtained from the 4th day after transplantation of the rats. The ovaries were removed at the end of the first estrous cycle (approximately 15 days after transplantation), and some apoptotic genes including P53, c-Myc, Bax, Bcl-2, and Caspase 3 were evaluated by the real-time PCR.
Findings: All transplants were completely successful (100%). The results also showed that the expression of the P53, c-Myc, Bax, and Caspase 3 genes were higher in the VT group, compared to the VT+HA group. However, this difference was statistically significant only in the c-Myc gene (P<0.05).
Discussion & Conclusion: Hyaluronic acid hydrogel was able to reduce the rate of apoptosis in the capsule group (VT+HA), compared to the non-capsule group (VT) after transplantation.

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Introduction: Long non-coding RNAs play an important role in regulating gene expression, RNA processing, histone modification, and rearrangement of chromatin genes. These molecules can also be involved in many biological processes, such as organogenesis, cell differentiation, development, genome imprinting, quantitative compensation, and tumorigenesis. High expression of MALAT1 (a type of lncRNA) in many cancers, including breast cancer, indicates that a disorder of MALAT1 regulation is an important factor in the development of many types of cancer. Breast cancer is the most common cancer among women worldwide, and the invasion, as well as metastasis of this disease, are considered among the main causes of death. The present study aimed to knock out the MALAT1 gene in the MDA-MB-361 breast cancer cell line and evaluate its function and effects on the expression of genes associated with apoptosis.
Material & Methods: In this study, two types of sgRNA were designed by CHOPCHOP software for exon 1 of the MALAT1 gene. These sgRNAs were cloned separately into two CRISPR vectors to generate the recombinant vectors PX459-sgRNA1 and PX459-sgRNA2. Co-transfection of these two recombinant vectors into the MDA-MB-361 cancer cell line was performed using lipofectamine 2000. MALAT1 gene editing was investigated in the cells receiving recombinant vectors. The expression of genes related to apoptosis was analyzed by Real-Time PCR. Cell proliferation and apoptosis were assessed by MTT and flow cytometry methods, respectively.
(Ethic code: IR.IAU.M.REC.1399.010)
Findings: The MALAT1 gene was edited by the CRISPR method in MDA-MB-361 cells. The rate of cell proliferation in the cells of the treatment group, compared to the control groups, showed a significant decrease (P<0.05). Apoptosis levels were significantly increased in cancer cells the MALAT1 gene of which had been deleted. Moreover, the expression of BCL2 and survivin anti-apoptotic genes in treated (edited) cells was significantly reduced, compared to control cells (P<0.05). Increased expression of proapoptotic genes P53, BAK, BAX, and FAS was also observed in the edited cells (P<0.05).
Discussion & Conclusion: The results of this study confirm that the deletion of the MALAT1 gene has a significant effect on increasing apoptosis and reducing cell proliferation. A reduction in the expression of the MALAT1 gene can prevent the growth and proliferation of breast cancer cell lines. Therefore, it seems that the control of MALAT1 oncogene expression is useful and effective for controlling tumors.
 

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Introduction: Cerebral ischemia-reperfusion causes complex pathological mechanisms that lead to tissue damage, such as neuronal apoptosis. Usnic acid is a secondary metabolite of lichen and has various biological properties including antioxidant and anti-inflammatory activities. This study aimed to investigate the neuroprotective effects of usnic acid on apoptotic cell death and apoptotic-related proteins (Bax and Bcl-2) in the CA1 area of the hippocampus following cerebral ischemia-reperfusion.
Material & Methods: A total of 42 male Wistar rats were randomly divided into three groups (sham, ischemia-reperfusion, and ischemia-reperfusion+usnic acid). Ischemia was induced by occlusion of both common carotid arteries for 20 min. Usnic acid (25 mg/kg, intraperitoneally) was injected at the beginning of reperfusion time. The expression levels of Bax and Bcl-2 proteins were measured using the immunofluorescence method, and the rate of apoptotic cell death was determined using the TUNEL staining method.
(Ethic code: IR.SHMU.REC.1397.186)
Findings: In this study, cerebral ischemia increased apoptotic cell death in the CA1 area of the hippocampus. It was demonstrated that usnic acid significantly decreased apoptotic cell death by decreasing the expression of Bax pro-apoptotic protein and increasing the expression of Bcl-2 (anti-apoptotic protein).
Discussion & Conclusion: It can be concluded that usnic acid has a neuroprotective effect against cerebral ischemia-reperfusion damages by reducing cell death.
 

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Introduction: Evidence shows that secondary metabolites of saffron can be used in the formulation of new drugs for the treatment of various human cancers. It is demonstrated that saffron crocin inhibits the proliferation of cancer cells while having no inhibition effect on the growth of normal cells. Consumption of this substance also reduces the side effects of cancer chemotherapy. Therefore, the present study was performed to investigate the effect of crocin on the proliferation and apoptosis of breast cancer cells and determine its molecular mechanism.
Material & Methods: Initially, MCF7 breast cancer cells were prepared from the Pasteur Institute of Iran Cell Bank and cultured in RPMI1640 medium with  FBS 10%. To determine the effect of crocin toxicity on cancer cells, treatment was conducted at different concentrations and different hours, and (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay was performed. The cell proliferation or cell apoptosis was evaluated as well. DAPI staining was performed to demonstrate cell apoptosis. After RNA extraction and cDNA preparation, the expression of an apoptosis-related gene (PTEN) and Akt pathway genes were measured by Real-time polymerase chain reaction (PCR) to determine the mechanism of the crocin effect.
Findings: Results of the MTT assay showed that crocin inhibited the proliferation of MCF7 cells and induced apoptosis in these cells. In addition, real-time PCR results showed that crocin increased PTEN gene expression (P=0.041) in MCF7 breast cancer cells and significantly decreased Akt1 gene expression (P=0.038).
Discussion & Conclusion: The results indicate that crocin stimulates the apoptotic cells in MCF7 breast cancer cells and can be used as a new therapeutic strategy for the treatment of breast cancer.
 

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Introduction: The increasing trend of cancer morbidity and mortality is a major human health concern, indicating the necessity for the design and introduction of novel anticancer compounds. The use of nanotechnology products is a new approach to cancer treatment. Therefore, the current study was performed to synthesize Titanium Dioxide nanoparticles (NPs) functionalized with glutamine and conjugated to Thiosemicarbazide (TiO₂@Gln-TSC) to inhibit the proliferation of liver cancer cells line (HepG2) and evaluate the effect of TiO₂@Gln-TSC NPs on the expression of apoptotic genes.
Material & Methods: TiO₂@Gln-TSC NPs were synthesized by a chemical method and characterized by Fourier-transform infrared spectroscopy (FT-IR), Energy-dispersive X-ray spectroscopy (EDS), Scanning electron microscopy (SEM), and Transmission electron microscopy (TEM). The cytotoxicity of the Titanium Dioxide nanoparticles was evaluated by the MTT assay, and relative gene expression was studied by Real Time PCR method.
Findings: The results showed that the synthesized Titanium Dioxide nanoparticles were spherical with a size range of 59 to 82 nm. The particles had a considerable anti-proliferative effect on liver cancer cells line with IC₅₀ of 80 µg/mL. The treatment of the cancer cell line with TiO₂@Gln-TSC NPs significantly increased the expression of the CASP3, BAX, and BCL2 by 2.8, 2.7, and 1.3 folds, respectively, which indicated the activation of apoptotic pathways in the treated cells.
Discussion & Conclusion: The results showed that the TiO₂@Gln-TSC NPs could inhibit the proliferation of liver cancer cells line and by triggering the apoptosis pathway.

 

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