[Prokaryotic expression of chimeric trimer protein [3M[2]e-HA2-NP] derived from conserved domains of influenza virus A/H1N1 as a promising universal subunit vaccine]

Background and Aim: Influenza A virus is an important respiratory pathogen which can cause high rates of morbidity and mortality during seasonal epidemics and pandemics. Current vaccines are not capable of producing effective immunity against different influenza virus subtypes. Designing universal vaccines using conversed domains of influenza virus antigens can overcome this limitation. The ectodomain of influenza M[2] protein [M[2]e], the hemagglutinin stalk domain [HA2], and nucleoprotein [NP] are the most conserved sequences among subtypes of influenza A viruses. The aim of this study was to attach part of the NP gene into the binary structure of 3M[2]e-HA2 and assessment of expression of a chimer trimer protein in prokaryotic system. This recombinant protein is considered as a promising antigenic candidate for a universal vaccine production

Materials and Methods: First, part of the NP gene segment of human influenza A/H1N1[PR/8/34]was amplified by PCR using designed specific primers. This amplified gene was cloned into pGEM-TEasy cloning vector. Then, the confirmed segment of NP gene was subcloned into PET28a/3M[2]e-HA2 recombinant expression vector, downstream of the HA2 segment. After confirmation of cloning, the chimer protein was expressed in E.coli BL21[DE3]

Results: The results of colony PCR, restriction enzyme digestion and sequencing indicated that the NP gene segment was correctly cloned into PET28a/3M[2]e-HA2. Chimer protein expression was analyzed by SDS-PAGE and confirmed by Western blotting

Conclusion: Design and production of recombinant protein [3M[2]e-HA2-NP] could be an important step towards the development of a universal influenza vaccine

expression studies of Bcl-xl gene subsequent effect of cholestasis and treatment by curcumin in hippocampus of male rats

Background: Cholestasis is a hepatic disease, which discomposes the secretion of bile and gives rise for the aggregation of bile compounds such as bile salts, in case of non-treatment, cholestasis finds the capability to influence on different organs such as heart and brain. Besides, the disease is also quite effective on the expression rate of apoptosis and mitochondrial biogenesis genes. Thus, we went through researching about the effects of cholestasis over the changes of expressions for genes run through apoptosis [BCL-XL] in hippocampus region of male rats. We also tried for fact-finding about the impact of curcumin drug, which holds treatment impact for chronic disease such as neoplastic, inflammatory, and nervous disorders over these genes expression in rats' hippocampus

Materials and methods: The animals were divided in 4 groups of BDL, BDL- Curcumin, Sham- Curcumin, and Control. Rats of BDL group experienced BDL surgery [closing bile tubes]. Besides, of surgery, rats of BDL-Curcumin group, treated with curcumin. Animals of Sham-Curcumin just received surgery stress and treated with drug, while the animals of CONTROL just experienced surgery stress without any other interference. Then, we removed hippocampus from rats' brains and after the RNA extraction and cDNA synthesis, we investigated genes expression measurement through Real Time PCR technique

Results: Curcumin drug increased the rate of BCL-XL gene expression at the rats' hippocampus

Conclusion: The data indicated that curcumin can alter apoptosis-induced by cholestasis at the hippocampus region

Doxorubicin loaded DNA aptamer linked myristilated chitosan nanogel for targeted drug delivery to prostate cancer

Recently, specific attention has been paid to aptamers, short DNA or RNA, as a tool for cancer diagnosis and therapy. In the present study MCS nanogels were prepared by Myristate: Chitosan at 1:9 ratio and were characterized by several techniques. A selected ssDNA aptamer [Apt] capable of detecting LNCaP cells was linked to Myristilated Chitosan nanogels [Apt-MCS] by glutaraldehyde and loaded with Doxorubicin [DOX] to be used in targeted drug delivery against the Prostate cancer cells. LNCaP and PC-3 cells were treated with Apt-MCS-DOX complex and the binding efficiency was estimated by flow cytometry. The binding affinity of the selected aptamers was above 70% compared to the initial library. The loading capacity of the nanogel was as high as 97% and up to 40% of DOX were released from MCS within 15 days. Cytotoxicity of nanodrug on LNCaP cells was determined by MTT assay. Apt-MCS-DOX was specifically binded to LNCaP cells whereas it didn't show any specificity to PC-3 cells as a negative control. Both MCS-DOX and Apt-MCS-DOX showed a lethal effect on LNCaP cells. Our results can lead to an aptamer based simple and applicable technique for early diagnosis and treatment of cancerous cells

Evaluation of in vivo bioactivity of a mutated streptokinase

Background: Immunogenicity of Streptokinase, as a thrombolytic drug, has limited its clinical use. Elimination of the amino acid residues that are responsible for immunogenicity while don't affect the bioactivity of streptokinase is worthy. Recently, we modified the streptokinase through the elimination of 42 amino acids from its' C-terminal and assessed its bioactivity in vitro. In this study, bioactivity of the mutated-streptokinase determined and compared with those of commercially available streptokinase [Heberkinase] in rabbits with induced blood clot

Materials and Methods: Recombinant mutated streptokinase was purified and its lipopolysaccharide contained remove and evaluated by LAL test. Thrombolytic activity of drug was evaluated by rabbit jugular vein as in vivo thrombosis model. The thrombolytic property of the drug was evaluated with determining of D-dimer in plasma

Results: The results showed in vivo bioactivity of both truncated and commercial streptokinase [p<0.05]. This study showed an important influence of the 42 amino acids of C-terminal in bioactivity of the streptokinase

Conclusion: Clinical use of the r-streptokinase requires more modification to restore its' activity in vivo. This product may be a promising choice for clinical use after confirmation of its stability and non-immunogenicity

Spiritual Therapy in Coping with Cancer as a Complementary Medical Preventive Practice

There are many of methods of treating cancer. However, the concept of curing the cancer is beyond our current knowledge. Some patients who have the cancer may seek an alternative manner of curing their disease. Alternative medicines, such as spiritual and complementary therapy, are able to cure the cancer and, at the least, are safe. Research on the importance of spirituality in cancer care has mainly been performed in geographically heterogeneous populations. The results are limited to these specific religious-cultural contexts and enlightened by contributions from ethnicity and religion. This article focused on the religiousness and spiritual support of cancer patients from diverse and heterogeneous groups around the globe. An electronic search of peer-reviewed articles was systematically performed to obtain the relevant literature with the CINAHL, PsycINFO, and PubMed databases. The keywords included religion, cancer, illness, psychotherapy, and spiritual and alternative treatment/therapies. The inclusion criteria for the reviews were that the documents were original quantitative research and published in English. Articles that were not directly relevant to the present objective were excluded. The present outcome of these review resources suggest that it may be helpful for clinicians to address spirituality, particularly with regard to prevention, healing, and survival of cancer patients. This article indicates that it may be useful for clinical oncologists to be informed of the prevalence of the use of spiritual medicine in their specialized field. In addition, patients should routinely be asked about the use of spiritual medicine as part of every cancer patient' evaluation.

Analysis of the antiproliferative effects of curcumin and nanocurcumin in MDA-MB231 as a breast cancer cell line

Cancer is one of the main cause of mortality in the world which appears by the effect of enviromental physico-chemical mutagen and carcinogen agents. The identification of new cytotoxic drug with low side effects on immune system has developed as important area in new studies of immunopharmacology. Curcumin is a natural polyphenol with anti-oxidative, anti-inflammatory and anti-cancer properties. Its therapeutic potential is substantially hindered by the rather low water solubility and bioavailability, hence the need for suitable carriers. In this report we employed nanogel-based nanoparticle approach to improve upon its effectiveness. Myristic acid-chitosan [MA-chitosan] nanogels were prepared by the technique of self-assembly. Curcumin was loaded into the nanogels. The surface morphology of the prepared nanoparticles was determined using SEM and TEM. The other objective of this study was to examine the in vitro cytotoxic activity of cell death of curcumin and nanocurcumin on human breast adenocarcinoma cell line [MDA-MB231]. Cytotoxicity and viability of curcumin and nanocurcumin were assessed by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide [MTT] and dye exclusion assay. Transmission electron microscopy confirmed the particle diameter was between 150 to 200 nm. Proliferation of MDA-MB231 cells was significantly inhibited by curcumin and nanocurcumin in a concentration-dependent manner in defined times. There were significant differences in IC[50] curcumin and nanocurcumin. curcumin -loaded nanoparticles proved more effective compared to TQ solution. The high drug-targeting potential and efficiency demonstrates the significant role of the anticancer properties of curcumin -loaded nanoparticles

Chromosome structural alteration an unusual abnormality characterizing human neoplasia

Background and Aim: Ring chromosomes are rare cytogenetic abnormalities that occur in less than 10% of hematopoietic malignancies. They are rare in blood disorder. The present review has focused on the ring chromosome associated with oncology malignancies

Materials and Methods: By reviewing the web-based search for all English scientific peer review articles published, was initiated using Medline/PubMed, Mitelman database [http:/cgap.nci.nih.gov/Chromosomes/Mitelman], and other pertinent references on websites about ring chromosomes in Oncology. The software program as End Note was used to handle the proper references for instruction to author. Karyotype descriptions were cited according to ISCN

Conclusion: Ring chromosomes are rare chromosomal aberrations, almost many times are of de novo origin, presenting a different phenotype regarding the loss of genetic material. The karyotype represents the main analysis for detection of ring chromosomes, but other molecular technics are necessary for complete characterization. The information of this review article adds to the spectrum of both morphology and genetic rearrangements in the field of oncology malignancies

BIRC5 genomic copy number variation in early-onset breast cancer

Background: Baculoviral inhibitor of apoptosis repeat-containing 5 [BIRC5] gene is an inhibitor of apoptosis that expresses in human embryonic tissues but it is absent in most healthy adult tissues. The copy number of BIRC5 has been indicated to be highly increased in tumor tissues; however, its association with the age of onset in breast cancer is not well understood

Methods: Forty tumor tissues of breast cancer were obtained from Tumor Bank of Cancer Institute, Imam Khomeini Hospital, Tehran, Iran. BIRC5 gene copy number variation [CNV] was evaluated using Multiplex Ligation-dependent Probe Amplification [MLPA] and then compared with the age of onset for each patient

Results: BIRC5 amplification was seen in 17.5% of cases. Also, a significant association was observed between BIRC5 gene amplification and individuals under 40 years of age [P=0.04]

Conclusion: BIRC5 gene has the potential to be a marker for the detection and prognosis of cancer at an early age

effect of preimplantation genetic screening on implantation rate in women over 35 years of age

Objective: Advanced maternal age [AMA] is an important factor in decreasing success of assisted reproductive technology by having a negative effect on the success rate of intra-cytoplasmic sperm injection [ICSI] particularly by increasing the rate of embryo aneuploidy. It has been suggested that the transfer of euploid embryos increases the implantation and pregnancy rates, and decreases the abortion rate. Preimplantation genetic screening [PGS] is a method for selection of euploid embryos. Past studies, however, have reported different results on the success of pregnancy after PGS in AMA. Investigating the pregnancy rate of ICSI with and without PGS in female partners over 35 years of age referred to infertility centers in Tehran

Materials and Methods: In this randomized controlled trial, 150 couples with the female partner over age of 35 were included. Fifty couples underwent PGS and the remaining were used as the control group. PGS was carried out using fluorescent in situ hybridization [FISH] for chromosomes 13, 18, 21, X and Y. Results of embryo transfer following PGS were evaluated and compared with those in the control group

Results: Implantation rates obtained in the PGS and control groups were 30 and 32% respectively and not significantly different [P>0.05]

Conclusion: PGS for chromosomes 13, 18, 21, X and Y does not increase implantation rate in women over 35 years of age and therefore the regular use of PGS in AMA is not recommended

Development of a high-resolution melting analysis method for CYP2C19*17 genotyping in healthy volunteers

Background: Genetic polymorphisms of drug metabolisms by cytochrome P450 [P450s] could affect drug response, attracting particular interest in the pharmacogenetics. Due to the importance of CYP2C19* 17 allele and its capability of super- fast metabolism and also lack of information about distribution of the alleles in Iranian population, this research aimed to use High Resolution Melting [HRM] method compared to PCR-RFLP for genotyping healthy Iranian population

Methods: Blood samples were collected from 100 healthy Iranian volunteers. DNA was extracted by salting out method. Real-time PCR was used for amplification of the CYP2C19 gene and the alleles were identified by HRM. Sequencing was used to confirm the amplified DNA fragments and data were analyzed using SPSS software ver.18

Results: The frequency of alleles CYP2C19*1/*1, CYP2C19*1/*17 and CYP2C19*17/*17 were estimated as 58.33, 29.1 and 11.1%, respectively. Specificity and sensitivity of HRM method were 90% and 100%, with respect to PCR-RFLP. Also, HRM analysis has been evaluated as a faster and more effective approach

Conclusion: Comparison of our results based on HRM analysis with PCR-RFLP showed that our developed method is rapid, accurate, fast and economic to study the CYP2C19*17 allele and it is appropriate for other similar population genetic studies

Different physical delivery systems: an important approach for delivery of biological molecules in vivo

Delivery of exogenous materials such as nucleic acids, peptides, proteins, and drugs into cells is an important strategy in modern cellular and molecular biology

Recently, the development of gene carriers for efficient gene transfer into cells has attracted a great attention. Furthermore, lack of effective drug delivery is one of the major problems of cancer chemotherapy

Many physical methods have been studied to enhance the efficiency of gene and drug delivery

These strategies help to cross the materials from membranes including needle injection, photodynamic therapy, jet injection, gene gun, electroporation, hydrodynamic injection, laser, magnetofection, and tattooing

The physical systems improve the transfer of genes from extracellular to nucleus by creating transient membrane pores using physical forces including local or rapid systemic injection, particle impact, electric pulse, ultrasound, and laser irradiation. The recent optimization techniques of transdermal patches could improve the transdermal drug delivery through the skin. Among different physical carriers, electroporation and gene gun are the most potent methods for gene transfection and drug delivery in vivo. However, the researchers have focused on enhancing their potency with the structural modifications

Regarding to numerous barriers for biomolecules delivery in cells, this review is concentrated on description and optimization of different physical delivery systems for gene or drug transfer across membrane

Association of tRNAThr 15927G: a mutation with the incidence of coronary artery disease

One of the leading causes of death in the world are cardiovascular diseases, among which coronary artery disease [CAD] is the most common one. It occurs as a result of narrowing of the arteries which supply blood to the heart due to a theroma plaque formation. This kind of heart disease can be considered as a multifactorial one as genetic and environmental factors are involved in its incidence. The already conducted studies have investigated the relationship between some of polymorphisms in different loci and CAD with the aim of on-time diagnosis of this disease, which may lead to its prevention and appropriate treatment. The aim of this study was to examine the association of tRNA Thr 15927 G: A mutation with the risk of CAD incidence to offer programs for early diagnosis and treatment of this disease in Iran. Fifty patients with CAD were included in the patient group, and fifty healthy participants were selected for the control group. 5mL of peripheral blood samples drawn from subjects in patient and control groups were collected in the tubes containing Ethylenediaminetetraacetic acid [EDTA]. After DNA extraction from blood with the employment of DNA extraction kit, its quality and quantity were measured using electrophoresis and NanoDrop devices, respectively. Then, the isolated DNA with the implementation of amplification-refractory mutation system [ARMS] and restriction fragment length polymorphism [RFLP] techniques was examined to determine and evaluate the target polymorphism in the intended locus. Sequencing method was also used to confirm the findings. To this end, 4 samples were randomly selected and sequenced.In the control group, 6 screened patients had the mutation while the others did not. Similar result was observed in the patient group. The findings of the present study reveal that there was not any significant relationship between tRNAThr 15927G: A mutation and risk of CAD incidence

Association of TNF-related apoptosis inducing ligand receptor [TRAIL-R] gene polymorphisms in Iranian Azeri patients with multiple sclerosis

Introduction: Multiple sclerosis [MS] is a chronic inflammatory demyelinating disorder of the central nervous system with various degrees of axonal damage. The TNF-related apoptosis inducing ligand receptor [TRAIL-R] might be playing an important role in the pathogenesis of MS. The objective of our study was to evaluate the association of two common polymorphisms is located in the TRAIL-R1 and TRAIL-R2 gene, in the pathogenesis of MS

Methods: We genotyped two single nucleotide polymorphisms in particular regions with single strand conformation polymorphism [SSCP] and Results obtained from the sequence of some samples, were analyzed using DNAMAN software. DNA was extracted from whole blood using the salting-out procedure. The distribution of genotype frequencies was analyzed using Pearson's x2 test. Statistical significance was defined as p < 0.05

Results: No Significant differences in SNP rs4872077 were found between the PRMS and PPMS groups and No association was found between the genotype status of the rs1001793 and rs4872077 polymorphisms and the age at onset, disease duration, EDSS

Conclusion: Our study suggests no association between TRAILR polymorphisms and MS Disease. Nevertheless, this polymorphisms does not appear to be a severity marker of the disease, neither modifying the clinical progression of MS nor its therapeutic response

Association analysis of DISC1 gene polymorphisms with Attention-Deficit Hyperactivity Disorder in Iranian population

Attention deficit hyperactivity disorder [ADHD] is a common heritable psychiatric disorder with a worldwide prevalence of 5%. The etiology of ADHD is still incompletely understood, but several studies, consistently indicate the strong role of genetic factors on this disorder. The aim of this study was to determine the effect of three SNPs rs11122319, rs11122330 and rs6675281 in the etiology of ADHD in an Iranian children. In this research work, for the first time, we investigated the association of three SNPs [rs11122330, rs6675281 and rs11122319] in theD/5C7 gene with ADHD in Iranian population. Two hundred fourthy subjects composed of 120 patients and 120 healthy controls were included and tetra-primer ARMS PCR technique was used for genotyping all selected SNPs. We found differences in genotype and allele distributions of rs 6675281 polymorphism between our patients and controls. The A, T and A alleles were the more frequent alleles in rs11122319, rs6675281 and rs11122330 polymorphisms in both case and control groups respectively. The TT genotype was more frequent in control group compared to patients. [P value = 0.008, OR= 1.5837, 95% Cl= 1.1012 to 2.2776], Our findings strengthens the role of DISC1 gene as a susceptibility locus for ADHD and indicate that rs6675281 polymorphism is a susceptibility factor for ADHD for the first time in children reported in an Iranian population in this part of the world

Detection of anticancer and apoptotic effect of the produced IgYs against the three extracellular domain of human DR5 protein

TNF alpha cytokine family in the body plays divers' roles in the cellular events such as cell proliferation, differentiation, necrosis, septic shock and apoptosis. In response to TNF therapy, several cell signaling pathways activated in cells which in different manners can lead to apoptosis or necrosis. However induction of apoptosis is depended on one of its important members, TRAIL and its receptors that will be followed by apoptosis activity. Tumor necrosis factor-related apoptosis-inducing ligand [TRAIL] and especially the DR5, is generating considerable interests as a possible anticancer therapeutic agent because of its selective activation in apoptosis of this receptor as a superior affinity to ligands. The study was performed in invitro assay and the anticancer effects of the produced antibodies were assumed by MTT and flowcytometric methods. In the first step for immunization of the hens, three selective small peptides from extracellular domain of DR5 which were chemically synthesized, injected to hens and after the proper immunization of them, IgYs were extracted from the egg yolk. After assumption of specificity of the purified IgYs against the whole DR5 protein, they were performed in MTT assay and flowcytometric colorimeter. After confirmation of synthesized peptides they were injected to hens with Fround`s complete adjuvant. With completing the immunization procedure the specificity of purified IgYs were confirmed by ELISA. The antibodies were significantly killed the MCF7 breast cancer cells, but had divers affect [proliferative] on normal hepatocyte cells. Additionally, significantly they induced apoptosis on the cancerous cells in contrast to control cells. The results clearly demonstrated that the produced IgYs with reduced cost and time managing could remarkably use as an effective anticancer drug

Anticancer activity of curcumin on human breast adenocarcinoma: role of Mcl-1 gene

Breast cancer is the second leading cause of cancer-related death among females in the world. To date, chemotherapy has been the most frequently used treatment for breast cancer and other cancers. However, some natural products have been used, as alternative treatments for cancers including breast cancer, due to their wide range of biological activities and low toxicity in animal models. The present study examined the anti-proliferative activity of curcumin and its effect[s] on the apoptosis of breast cancer cells. This study was performed by an in vitro assay and the anticancer effects of curcumin were determined by MTT [3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide]. We used quantitative real time Polymerase Chain Reaction [PCR] for detection of Mcl-1 gene expression in treated groups and then compared them to control samples. In the treatment group, there were higher levels of cell death changes than the control group. The results also showed that the Mcl-1 gene expression declined in the tested group as compared to the control group. Our present findings indicated that curcumin significantly inhibited the growth of human breast cancer cell MCF-7 by inducing apoptosis in a dose- and time- dependent manner, accompanied by a decrease in MCF-7 cell viability. Furthermore, our results showed that quantitative real-time PCR could be used as a direct method for detection Mcl-1 gene expression in tested samples and normal samples

comparison of anticancer activity of thymoquinone and nanothymoquinone on human breast adenocarcinoma

Cancer is one of the main causes of mortality in the world which is created by the effect of enviromental physico-chemical mutagen and carcinogen agents. The identification of new cytotoxic drugs with low side effects on immune system has developed as important area in new studies of pharmacology. Thymoquinone [TQ], derived from the medicinal spice Nigella sativa [also calledt black cumin] exhibit anti-inflammatory and anti-cancer activities. In this study we employed nanogel-based nanoparticle approach to improve upon its effectiveness. Myristic acid-chitosan [MA-chitosan] nanogels were prepared by the technique of selfassembly. Thymoquinone was loaded into the nanogels. The surface morphology of the prepared nanoparticles was determined using SEM and TEM. The other objective of this study was to examine the in-vitro cytotoxic activity of cell death of Thymoquinone and nanothymoquinone on human breast adenocarcinoma cell line [MCF7]. Cytotoxicity and viability of Thymoquinone and nanothymoquinone were assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide [MTT] and dye exclusion assay. Transmission electron microscopy confirmed the particle diameter was between 150 to 200 nm. Proliferation of MCF7 cells was significantly inhibited by Thymoquinone and nanothymoquinone in a concentration-dependent manner in defined times. There were significant differences in IC50 Thymoquinone and nanothymoquinone. TQ-loaded nanoparticles proved more effective compared to TQ solution. The high drug-targeting potential and efficiency demonstrates the significant role of the anticancer properties of TQ-loaded nanoparticles

[Designing and comparison of two types of chitosan nanogels for doxorubicine delivery]

Objective: Drug delivery systems related to different cancer therapies is now expanding. Chitosan [CS] is currently receiving enormous interest for medical and pharmaceutical applications due to its biocompatibility in animal tissues. In this study, two nanogels were prepared from CS. Some of the critical factors such as controlling the release, adsorption and specially targeting drug delivery are considered while preparing the nanogels

Methods: Phosphorylated CS [PCS] and Myristilated CS [MCS] nanogels were prepared by reacting CS with tripolyphosphate [TPP] and Myristate as cross-linking agents respectively and then were loaded with Doxorubicin [DOX]. The nanogels were characterized by different techniques such as scanning electron microscopy, dynamic light scattering and Fourier-transform infrared. The cytotoxicity of free DOX, MCS nanogels and DOX loaded MCS was evaluated by the MTT assay

Results: The result of DOX loading and releasing of the nanogels showed high loading capacity and drug loading efficiency of about 97%. Results indicated slow release of about 16-28% of DOX from PCS within 5 days and 18-40% from MCS within 15 days. DOX and MCS-DOX showed the same toxic effect on the prostate cancer cells [LNCaP]

Conclusion: Both PCS and MCS nanogels were qualified on the basis of size, loading and releasing capacity

effect of pentoxifylline drug on bax/bcl2 gene dosage expression changes following ischemic reperfusion injury in kidney

Global cerebral ischemia [GCI] and reperfusion induced apoptosis that lead to cell injury and death. The bax and bcl-2 are pro-apoptotic and anti-apoptotic genes, respectively. These genes belong to The B-cell lymphoma-2 [bcl-2] family.In this study; we assessed the effect of pentoxifylline drug on bax/bcl2 gene dosage expression changes following ischemic reperfusion injury in kidney. In this experimental study, 20 male wistar rats were accidently divided them on two tenth group of control and treatment groups. In the control group, celiotomy was performed by ventral midline incision. The left kidney was isolated, and then both the renal artery and vein were obstructed. After 60 minutes of warm ischemia, vessel obstruction resolved and the right kidney was removed. 72 hours after reperfusion, tissue samples were taken from left kidney for histopathology. All these steps in treatment group were exactly repeated after administration of 45 mg/kg/PO pentoxifylline [3 hours before operation] and in this group treatment was continued every 12h until 3 days. In this research quantitative real-time PCR is used for the detection expression Bcl2 and Bax genes in ischemia group and PNT drug group and compared to normal sample. The results showed the gene dosage ratio of bax/bcl2 in PNT group decline than to ischemia group. Therefore, the pentoxyfylline might have a role in control of apoptosis result from Ischemia- reperfusion

effect of MDMA and pentoxifylline drug on bad/bcl-xl gene dosage expression changes on rat liver

MDMA generally known as ecstasy, have deleterious effects on the serotonergic neurotransmitter system. Recent findings suggest that the liver and brain are major target organs of MDMA-related toxicities. Although most research is being dynamically performed on brain, however, the molecular mechanisms by which MDMA elicits adverse effects in both organs are poorly undrestood.The present study was performed to obtain evidence for molecular mechanism of apoptosis involved in MDMA-induced hepatotoxicity in rat liver after MDMAadministration. Moreover, the antagonistic effect of pentoxifylline was assessed on hepatotoxicity after MDMA administration. In this experimental study, sample size and power in each group were calculated as 10 rats with 95% confidence level and 5% confidence interval. In the study, four experimental groups were selected including Control Normal, MDMA, MDMA+PTX and PTX+MDMA. MDMA was dissolved in PBS and intraperitoneally injected three doses of 7.5mg/kg with two hours gap between doses. Pentoxyfilline also was injected as 100mg/kg, simultaneously with third dose of MDMA. After treatment, total RNA was isolated from liver tissue [5mg]. Absorbance at 260nm, 280nm and 230nm were measured and immediately reverse transcription was performed. Included target genes were BAD and BCL-XL as pro-apoptotic and anti-apoptotic gene, respectively. After set up and validation, Real-Time PCR were performed and obtaining data were statistically analyzed to determine significantly differences between groups. Using Real-Time quantitative PCR results, BCL-XL gene expression ratio significantly increased in MDMA+PTX group. Moreover, BAD gene expression ratio increased and up-regulated in PTX+MDMA group [P-value <0.001].Our study focused on molecular mechanism of MDMA in programmed cell death using gene expression quantification of a pro-apoptotic and anti-apoptoic gene in MDMA-induced hepatotoxocity. The results shown MDMA prompted apoptosis in liver and pentoxifylline protects hepatotoxicity after and befor taking MDMA