Tehran University Medical Journal

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Background: Squamous cell carcinoma (SCC) is the most frequent oral cancer. Protec-tive effects of the consumption of vegetables and fruits on various forms of cancer in-cluding oral cancer have been determined. Tomato (Solanum lycopersicum L.) because of its lycopene and bioflavonoids contents possesses anti-carcinogenic properties. The aim of this study was to evaluate the preventive effects of tomato pulp on pre-neoplastic changes induced by 4-Nitroquinoline-1-oxid (4-NQO) in epithelial cells of lingual mucosa in the rats. Methods: Forty-eight male Wistar rats were randomly allocated into four equal groups. Group 1 served as control. Groups 2 to 4 assigned to receive 30 ppm 4-NQO in drinking water for 12 consecutive weeks. When the feeding of 4-NQO was started to the rats of groups 3 and 4, they received tomato pulp (20 and 40 ml/kg bw) daily through the oral gavage. Finally, histological evaluations for carcinogenesis were performed for tongues epithelial tissue. Results: There were no pathological alterations in epithelial tissue of lingual mucosa in control rats. In the epithelial cells of lingual mucosa of 4-NQO treated rats, premalig-nant alterations appeared after 12 weeks of the last application of the drug. Administration of tomato pulp at both doses (20 and 40 ml/kg bw) during the experiment reduced the severity of the lesions, as well as caused a significant reduction in the frequency of pre-neoplastic lesions of tongue epithelial cells (P= 0.024 and P= 0.008). The incidence of severe epithelial cells dysplasia of lingual mucosa in the high dose treatment group was significantly smaller than of low dose treatment group (P= 0.037). Conclusion: The results obtained showed that tomato pulp is effective in inhibiting the development of neoplasms in epithelial cells of lingual mucosa induced by 4-NQO in the rat.

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Background: Mycoplasma contamination in cell cultures is considered as a major economic, research and production problem. In this study, mycoplasma-infected Vero cell lines were treated by various dilutions of ciprofloxacin and enrofloxacin in a timely manner. Removal of mycoplasma contamination from infected cell cultures was evaluated and demonstrated by polymerase chain reaction (PCR) method. Methods: This study was done from October 2013 to May 2014, in Human Rabies Vaccine Laboratory, Pasteur Institute Production and Research Complex, Tehran, Iran. Different dilutions of ciprofloxacin and enrofloxacin were used in sequential passages for treatment of infected Vero cell line. Based on lowest passages of the cell line, antibiotic treatment with ciprofloxacin and enrofloxacin was done. Amelioration of the infection and removal of mycoplasma contamination was confirmed in each step by PCR method. The technique for order of preference by similarity to ideal solution, TOPSIS method, was used to suggest the most efficient concentration of ciprofloxacin and enrofloxacin. Results: Proposed concentration of ciprofloxacin is 20 μg/ml, and in the second order is 200 μg/ml. For enrofloxacin the best proposed concentrations are 30, 300 and 3 μg/ml respectively. Ciprofloxacin and enrofloxacin and ability of them for removal of mycoplasma and also the time of treatment were verified by evaluation of the recurrence of infection through consecutive subcultures of the treated cell line. Conclusion: Our results showed that 20 μg/ml of ciprofloxacin was the dilution of choice for mycoplasma elimination followed by 200 μg/ml of ciprofloxacin. Concentrations of 3, 30 and 300 of enrofloxacin, respectively, are appropriate for mycoplasma removal. More detailed works would be needed to verify the authenticity of the proposed simple and affordable way of mycoplasma elimination.

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Background: Biosynthesis of nanoparticles has attracted the attention of the scientific community in nanotechnology and biotechnology due to their extensive application in the area of material sciences and medicine. Nowadays, despite a various application of nanomaterial’s, there is a little information about their impact on human health. In this study, we investigated the comparative study on cytotoxicity effect of biological and commercial synthesized nanosilver on human gastric carcinoma (AGS) and normal lung fibroblast (MRC-5) cell lines. Methods: The current experimental study was carried out in Islamic Azad University, East Tehran Branch, from April to November 2014. The biological synthesis of nanosilver was obtained from Eucalyptus plant extract as a reducing agent. Further to more analysis, morphological study on size and shape of developed biological nanosilver was characterized by performing scanning electron microscopy and dynamic light scattering. AGS and MCR-5 cell lines were treated with various concentration of nanosilver for 24, 48 and 72 hours. Finally, the cell viability was evaluated by using MTT assay. Results: The results show that the nanosilver exerts a dose-dependent inhibitory effect on viability of cells. At 100µg/mL of commercial and biological synthesized nanosilver, the viability of AGS was reduced to 7.47±0.002% (P=0.002) and 3.65±0.01% (P=0.003) after 72 hours, respectively. In addition, the viability of MRC-5 at the same condition was reduced to 10.27±0.19% (P=0.001) and 9.16±1.53% (P=0.002), respectively. Conclusion: Based on a thorough literature surveys, the present study is the first research about biosynthesis of nanosilver using Eucalyptus plant extract. This eco-friendly and cost effective method can be used for large scale production of silver nanoparticle. In addition, based on the current obtained data, commercial and biological synthesized nanosilver can more inhibitory effect on cancer cells compared to the normal cells. Hence, silver nanoparticles might be used as a new strategy for treating many human cancers. However, further studies are necessary to ascertain their potential as anticancer agents.

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Background: Tumoral calcinosis is a hereditary disorder of metabolic dysfunction of phosphate regulation. It is an idiopathic calcinosis that characterized by the deposition of calcium phosphate in periarticular tissues that causes typically lobulated, well demarcated calcification around large joints particularly the extensor surfaces. It is usually painless. It is common in puberty age and adolescents. The involvement of the hand phalanges is very rare that can make a mistake in diagnosis if it is infected. Tumoral calcinosis is seen the same in both sexes. The electrolyte levels of calcium and phosphorus is normal and sometimes is hyperphosphatemia. It is the first report of tumoral calcinosis in Iran. Case report: A 7-year-old girl presented with redness, yellowish discharge and painful swelling of the left hip and the third web space of left hand admitted to Vali-e-Asr Hospital, Tehran, Iran, in 2013. The onset of the disease was 3.5 years ago. She did not mention the family history of the disease. The pain was at the left hip first. Six months later the third and fourth phalanges of the left hand was swollen. Physical examination revealed an erythematous mass in the extensor surfaces of the third and fourth metacarpals of the left hand. It was tender in palpation. The smear and culture of discharge was staphylococcus aureus. X-rays revealed calcification of the third and fourth metacarpals of the left hand. The entire lesion was managed by surgical excision. Successful postoperative medical management in the form of low calcium and low phosphorus diet and oral cloxacillin was performed. Conclusion: Tumoral calcinosis involves rarely the interphalangeal joints of hand. Because of its compression over adjacent nerves, it is painful. Sometimes it has a sterile discharge and rarely superimposed infections may occur. Radiologists can play a major role in early diagnosis and probable complications.

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Background: In the last decade due to emerge and remerge of influenza viruses, quality improvement of vaccines to increase immune responses in target populations have been more necessary. The potential of biologic adjuvant to stimulate and induce immune system is the basis of modern researches in prevention and controlling program of infectious diseases. In this study, the effect of the coding sequence of cellular Myxovirus resistance (Mx) protein as a biological adjuvant for inducing humoral immune response against influenza virus was investigated. Methods: The experimental study was performed on Balb/c mice in Razi Vaccine and Serum Research Institute from June to November 2014. Three conserved motifs of Mx were selected following sequence alignment between human, mouse and bird species. Potential of the motifs for stimulation immune responses against influenza virus were evaluated using in silico analysis. Based on the immune informatics data Mx1 sequence was the best immune inducer and cloned into pcDNA3.1 vector. Then formulated with inactivated H9N2 influenza antigen as adjuvant and injected to mice groups. The sera of vaccinated mice were collected prior to priming and boosting injections and also at defined weeks and analyzed with serological assays. Histopathological examination was done for evaluation of the vaccine and adjuvant safety. Results: The mean weight of the Balb/c mice in all control and treatment groups was similar and ranged from 21 to 37 gr (P= 0.05). The difference in increasing antibody titers against influenza virus in immunized mice who received Mx1-adjuvanted vaccine especially in second boosting was significant (P= 0.01) compared to the vaccine alone group. More than 78% of the immunized mice receiving two-time boosting have the mean antibody titer of >6 (Log2) which was higher (P= 0.001) comparing to the mice with one booster injection. Conclusion: These data revealed that Mx1 as biological adjuvant was able to increase antibody titer and induction memory immune responses against influenza immunization without causing any side effects.

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Cancer/Testis antigens (CTAs) as a group of tumor antigens are the novel subjects for developing cancer vaccine and immunotherapy approaches. They aberrantly express in tumors with highest normal expression in testis, and limited or no expression in normal tissues. There are important similarities between the processes of germ-cell and cancer cell development Spermatogenesis begins at puberty when expression of novel cell-surface antigens occurs when the immune system has been refined the ability to distinguish self from non-self. Whereas macrophage and lymphocytes are commonly found within interstitial spaces of the testis, these antigen-presenting cells are rarely seen within the seminiferous tubules. These observations have led to the concept of the immune privileged site for testis. Localized normal expression of the CT genes in testis that makes them immunogenic for immune system, in one side, and their abnormal expression in different kinds of cancer cells, in the other side, has make them as promising target for developing cancer vaccines and new cancer therapeutics approaches. In malignancies, gene regulation is disrupted which results aberrant expression of CT antigen in a proportion of tumors of various types. For some CTAs, data support their fundamental role in tumorigenesis. Several authors believe it is not clear whether they have an essential role in tumorigenesis or they are by-products of chromatin variations in cancer. There is a growing list of CTAs within them advanced clinical trials are running by using some of them in cancers like lung cancer, malignant melanoma and neuroblastoma. In this review we discuss the gene TSGA10 as an example of CT genes. TSGA10 expresses in its highest levels in elongating spermatids and localized in the fibrous sheath of mature sperm. This gene is proposed as a serological biomarker in cutaneous lymphoma. Its abnormal expression has been reported in different cancers such as acute lymphoblastic leukemia, breast, brain, gastrointestinal and a range of other cancers either in mRNA or protein levels. It has an important role in angiogenesis in cancer tumors because of its effects in the gene hypoxia-inducible factor (HIF1). Absence or lack of TSGA10 expression has been reported in ascosporic infertile men.

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Background: Seladin-1 protein protects the neural cells against amyloid beta toxicity and its expression decreased in vulnerable regions of Alzheimer's disease (AD) brains. On the other hand, changes in serum levels of S100 have been considered as a marker of brain damage in neurodegenerative diseases. Furthermore, this study was carried out to determine the relation between the change profile of serum S100&beta protein levels and hippocampal Seladin-1 gene expression in a rat model of sporadic AD. Methods: In this experimental study that established in Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Science, from March 2011 to April 2013, 72 animals were randomly divided into control, 4, 7, 14, and 21days ICV-STZ/Saline administrated rats. Alzheimer's model was induced by intracerebroventricular (ICV) injections of streptozotocin (STZ) [3 mg/kg] on days 1 and 3. Serum levels of S100&beta and hippocampal Seladin-1 gene expression were evalu-ated in experimental groups. The initial and step-through latencies (STL) were deter-mined using passive avoidance test. Results: Serum levels of S100&beta were significantly different between the STZ-7 day and STZ-14 day groups in comparison with the control, saline and STZ-4 day groups. As well as, there was a significant difference between the STZ-7 day group in comparison with the STZ-14 day and STZ-21 day groups (P=0.0001). Hippocampal Seladin-1 gene expression in STZ-14 day and STZ-21 day groups significantly decreased as compared to the control, saline and STZ-4 day groups (P=0.0001). However, significant correla-tion was detected between serum S100&beta protein decrement and Seladin-1 down regula-tion (P=0.001). Also, the STL was significantly decreased in 21 days ICV-STZ adminis-trated rats as compared to the control or saline groups (P=0.001). Conclusion: Monitoring the changes of serum S100&beta protein levels by relationship with changes in hippocampal Seladin-1 gene expression can be a useful indicator of neu-ronal damage in patients with Alzheimer's disease.

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Background: Breast cancer is the most common cancer in women around the world. It has been known for over a century that androgens and androgen receptor (AR) play a role in normal and neoplastic breast cells. The aim of this study was to determined the AR expression on tumor cells and its correlation with other prognostic and predictive factors as well as contribution of AR in patients overall survival (OS) and disease- free survival (DFS). Methods: This retrospective cross-sectional study performed on 189 patients who referred to Medical Oncology Ward of Cancer Institute, Tehran University of Medical Sciences, from April 2007 to February 2010. We performed an immunohistochemistry study for AR (AR441 clone, Dako, Germany) (10% cut-off point) and Ki-67 MIB-1 clone, Dako, Germany) on paraffin embedded blocks. Other data were extracted from patients’ documents. Results: Overall, AR expression was 49.1%. Mean age of the patients with and without AR was 47.86 and 48.49 years, respectively. AR positive tumors presented more in stage I/II than III/IV (P=0.02) and AR were more positive for estrogen receptor positive, lower grade of tumor (grade I/II versus III) and lower Ki-67 (P=0.01). AR positivity had neither correlation with progesterone receptor, HER2/neu, P53 expression or menopausal status. OS and DFS were higher in AR positive patients but did not reach statistical significance. In triple-negative breast cancer (TNBC) group, 25% of tumors showed AR expression. AR had non-significant positive correlation with OS in TNBC cancer patients. OS and DFS had significant statistic positive correlation with ER, PR and stage regardless of AR status. Conclusion: Based on this study, although androgen receptor expression showed correlation with other prognostic factors for survival in patients, we didn’t find statistically significant independent relationship between AR and overall survival in patients. As far as there isn’t any targeted therapy for triple-negative breast cancer (TNBC), prospective basic and clinical studies regarding AR inhibitors in the treatment of TNBC seems to be logical and valuable.

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Background: Human papilloma virus is a DNA virus from the papillomavirus family that is most prevalent in human cervical cancers and many studies showed the E6 and E7 proteins are present in the majority of cervical cancer cases. Development of universal HPV peptide-based vaccine with more serotypes coverage has considerable value. The aim of the study was to design a multi-epitope universal vaccine for major HPV based on E6 and E7 proteins and optimization the expression of polytopic construct contains E6 and E7 genes from different genotypes of human papilloma virus as a candid vaccine.

Methods: In this experimental study that was carried out in Pasteur Institute of Iran, Virology Department from October 2013 to November 2014. In order to design the polytypic construct, we predicted the most probable immunogenic epitopes of E6 and E7 from common high risk HPV16, 18, 31, 45 along with high prevalent type 6 and 11 using bioinformatics methods. The synthetic pET28a expression vector harboring E6 and E7 protein was transformed into Escherichia coli hosts and its expression was analyzed by SDS-PAGE and western blotting. Finally, in order to expression optimization of recombinant protein, cell density, induction time, growth temperature, IPTG (Isopropyl &beta-D-1-thiogalactopyranoside) concentration and cultures media were studied.

Results: In the present study the recombinant fusion protein was expressed successfully and the highest expression of target protein was achieved in super broth medium containing 0.1% glucose and 0.2% L-arabinose. In Super broth medium, the optimum condition for recombinant protein expression was occurred at OD600 of 0.8, 0.1mM IPTG, one hour’s incubation time at 37 °C and BL21 (A1) host.

Conclusion: The results of this study show that the optimum expression of E6 and E7 proteins from different genotypes of human papilloma virus can be performed. Moreover, by purification of recombinant protein and evaluation of its immunogenicity in mice, it can be used as a vaccine candidate against the human papilloma virus.

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Background: Undercarboxylated Osteocalcin (ucOC) may contribute to the regulation of glucose homeostasis. Undercarboxylated osteocalcin is special protein secreted by bone as an endocrine regulation of energy metabolism and glucose. It plays an important role in insulin secretion and sensitivity. The aim of this study was to survey the effect of eight weeks resistance training on serum levels of ucOC, adiponectin and insulin sensitivity in obese women.

Methods: This quasi-experimental study performed on twenty obese women (BMI> 30) in Amol City Sport clubs, Iran, in May 2014. Samples randomly divided into two groups: a control group and an experimental group.  The experimental group consisted of eight weeks of resistance training, three times a week in six stations (including the movements of the leg press, bench press, triceps, biceps, abdominal motion, pull side and half scott) and with an intensity of 55% to 75% of one repetition maximum. Blood samples were collected after 12- 14 hours, fast and before it and also after eight weeks (48 hours after the last training session). Kolmogorov-Smirnov test was performed to confirm that data was normally distributed. The obtained data was analyzed using paired-sample t-test, independent t-tests and one-way ANOVA at the significance level of P< 0.05.

Results: The results showed that resistance training had no significant effect on serum ucOC (P= 0.094) levels and insulin sensitivity (P= 0.178) in obesity. However, the experimental group after resistance training showed significantly higher adiponectin level than the upper limit of normal range (P= 0.003). There was no relationship between adiponectin and ucOC.

Conclusion: Resistance exercise can increase levels of serum undercarboxylated osteocalcin (ucOC) and adiponectin in obese women. It can be said that this type of activity could possibly be effective in glucose hemeostasis.

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Stem cells are undifferentiated and multi pluripotent cells which can differentiate into a variety of mature cells and tissues such as nervous tissue, muscle tissue, epithelial tissue, skeletal tissue and etc. Stem cells from all different source have three unique features: 1) Proliferative capability: Stem cells are capable of self dividing and self renewing for long periods or more than six months at least that called immortalization. 2) Undifferentiated nature: It’s considered as one of the essential characteristics of stem cell, so it doesn't have any tissue-specific construction. 3) Differentiation to the different cells from all organs: This ability can Induced by tissue specific transcription factors. Because of that, they are so important in prevention and treatment of human disease. Depending on the sources from which they derive, they have different types which can be used to produce special cells and tissues. The most significant types of stem cells are; embryonic stem cells (ESCs) which are derived from embryos, adult stem cells (ASCs) which are derived from differentiated cells in a specific tissue, induced pluripotent stem cells (iPSs) which are produced from adult differentiated cells that have been genetically reprogrammed to act resemble to an embryonic stem cell and cord blood stem cells which contains haematopoietic stem cells and derived from the umbilical cord after gestation. By providing a medium containing of special growth factor, it is possible to orientated stem cell differentiation pathway and gained certain cells from them. The important uses of stem cells includes damaged heart tissue cells improvements and bone tissue repairing, cancer treatment, damaged neurological and spinal tissue repairing, improving burns and injuries and the treatment of diabetes, infertility and spermatogenesis dysfunction. Furthermore, the application of them in gene therapy is an important issue in the modern medicine science due to the role of them in transferring gene into different cells. Today, this method have had considerable progress in the treatment of many disease. In this review study, some aspect of stem cells like types and characteristic, origin, derivation techniques, storage conditions and differentiation to target tissues, current clinical usage and their therapeutic capabilities will be discussed.

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Background: Platelet adhesion typically occurs by the critical role of GPIb-V-IX in capturing free-flowing platelets to the injured vessel wall where its rapid binding kinetics enables platelet tethering even under conditions of high shear through the interaction of the major ligand-binding subunit of GPIb-V-IX, GPIbα with subendothelial-bound vWF. During storage, platelet undesired activation may lead to platelet storage lesion (PSL) which changes the expression levels of platelet functional receptors including GPIbα. This study investigates the levels of expression and ectodomain shedding of platelet adhesive receptor GPIbα during the storage of platelet rich plasma (PRP) concentrates (PRP- PCs).

Methods: Five PRP-platelet concentrates were obtained from Iranian Blood Transfusion Organization (IBTO). The GPIbα expressions of platelets were analyzed on day 1, 3 and 5 after storage using flowcytometry. To examine the ectodomain shedding of this receptor the microparticle free supernatants obtained from stored platelets were subjected to western blot analysis. For control study, blood specimens was drawn from healthy consenting individuals and resting platelets were isolated while resuspended in Tyrode buffer.

Results: Our results indicated a continuous decrease of GPIbα expression during storage where the expression from fist day (Mean fluorescence intensity=86±5.9) was significantly reduced compared to that of fifth day (mean fluorescence intensity=61±7.7) after storage (P=0.0094). Conversely, shed GPIbα (Glycocalicin) demonstrated continuous elevation during five-day storage (P=0.0098). According to the results the shedding levels for the first day were increased from 0.31± 0.3 to 1.5± 0.4 by the day 5 after storage.  

Conclusion: Our study has demonstrated significant loss of platelet GPIbα during storage mostly due to receptor ectodomain shedding that leads to significant increase of soluble GPIbα in stored platelets. Considering the high levels of shed GPIbα in long stored platelets whether the transfusion of such products might be associated with defective adhesive function of platelets or possible proinflammatory effects could be of interests for future investigation.

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Background: Diabetes is associated with many pathological changes and one of the most important consequences of the diabetes is hepatic injury. The present study was performed to investigate the effect of eight weeks endurance training with consumption of cinnamon supplementation on plasma concentrations of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in women with type II diabetes.

Methods: In this quasi-experimental study, 36 female volunteers with type II diabetes (age 52.72±2.64 years and body mass index 29.28±2.94 Kg/m2) were participated. The subjects were homogenized regarding their body mass index and then were divided randomly into four groups (each group=9 patients): Training, training-cinnamon, cinnamon, and Control. Endurance training was performed for eight weeks (three sessions per week) at the intensity of 60-75% of maximum heart rate for 40-60 minutes. The consumption of cinnamon supplementation was 1.5 gr per day. Plasma concentrations of ALT and AST were measured following 12 hours fasting, 48 hours before and after performing the experiment, by the enzymatic method. Data were analyzed by paired t-test and factorial ANOVA, using SPSS version 21 (Chicago, IL, USA) and at the significant level of P<0.05.

Results: The levels of ALT was reduced in three experimental groups, which only its reduction was significant after consumption of cinnamon P<0.05. Also, plasma concentrations of AST increased in training-cinnamon and decreased in training and cinnamon groups which none of them was not significant. All interventions had no effect on blood fasting glucose in all experimental groups P>0.05. There was no significant difference between groups in pre and posttests.

Conclusion: The results confirm that cinnamon supplementation may be effective in improving the plasma levels of ALT but the intensity and duration of an effective exercise training especially with consumption of cinnamon supplementation simultaneously need more study in diabetic patients.

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Background: Most problems related to quality of care and patient safety are related to human negligence. One of the causes of these problems is forgetting to do something. This problem can be avoided with information technology in many cases. Some forgotten are very important. Among these is failure to comply with vaccination schedule by parents that can result in inappropriate outcomes. In this study, we developed and evaluated a SMS reminder system for regular and timely vaccination of children.

Methods: In this developmental-applied research, firstly, a child vaccination reminder system was designed and implemented to help parents reduce the forgetfulness. This system based on the child's vaccination history and the date of birth, offer time and type of future vaccines. Then the parents of 27 children, that their vaccination was between 22 June and 21 August 2015, referred to Children's Medical Center, were sent text messages by using this system. We evaluated the accuracy of the system logic by using some scenarios. In addition, we evaluated parents' satisfaction with the system using a questionnaire.

Results: In all cases but one, the system proposed the type and date of future children vaccines correctly. All the parents who have received text messages had good perception and satisfaction on the majority of questions (total mean score of 4.15 out of 5). Most parents (4.92 out of 5) stated that using the system to remind their visit for child immunization was helpful and willing to offer the system to their friends and other families.

Conclusion: Using the short message system is beneficial for parents to remind their children’s vaccination time and increases their satisfaction. So, it can be considered as an important and essential tool in providing healthcare services. SMS is an easy, cheap and effective way to improve the quality of care services.

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Background: Problems of live and inactivated influenza vaccines such as, increasing emerge and re-emerge viruses with high human mortality, current epidemics of influenza and direct transmission of avian viruses to human, affect the vaccination program. DNA vaccines as third generation of vaccines is specially considered for control of influenza in human and poultry. The main advantage of these vaccines is humoral and cellular immune responses and broad spectrum of using these vaccines for control of circulating strains of influenza. In this study the conserved fragment of HA2 to form of DNA vaccine was designed to induce immunity against influenza viruses and its heterologous protective immunity against these viruses was evaluated.

Methods: The experimental study was performed in Razi Vaccine and Serum Research Institute from December 2014 to July 2015 in Iran. The HA2 was cloned into pcDNA3.1 to assess the HA2 DNA vaccine and mice were immunized with the generated constructs in a DNA prime-DNA boost regimen in 4 groups. The humoral immune responses were analyzed at defined intervals by VN tests. The safety of the vaccine was evaluated by daily inspection and histopathological examination. For evaluation of cellular immunity, proliferation assay was used. Results: The antibody titre and cellular immunity of immunized mice was significantly higher than control group for two serotypes and the highest responses was in the group with two-time boosting (P<0.01). There were no any local, general and histopathology reactions in immunized mice. Conclusion: The HA2 DNA vaccine significantly enhanced circulatory antibody responses and cellular immunity against influenza current serotypes. This study showed the highest immune responses were in the group that immunized with HA2 in prime and two boosts. Besides that, this construct did not have any local and general reaction and any side effects in treated mice. So, this construct was introduced as candidate for control of influenza virus serotypes.

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Breast cancer that is caused by the accumulation of genetic and epigenetic alterations, is one of the main causes of death resulted from cancer. Various therapeutic approaches have been introduced for this cancer and the traditional diagnosis and treatment is based on the prognosis estimation using cancer anatomic features (TNM system) and clinical results, but studies show different responses of these treatments and recurrence after those in some patients. This diversity is resulted by the differences in biological and molecular characteristics. So genomic and molecular studies became more important and the role of targeted treatment based on an individual's genome was highlighted. Today, the progression in personalized medicine using specific individual genome profile has been possible. The ultimate goal of such studies, in the setting of the personalized medicine, is providing markers which can be used to risk assessment of progressing disease. This new science cause great development in the treatment of breast cancer by recognition of specific markers and application of targeted therapy. Trastuzumab and tamoxifen are the most common monoclonal antibodies applied in these patients depends on their biological and molecular profile. The good response to tamoxifen is seen only in patients with estrogen receptor (ER+) which inhibits the binding of estrogen to its receptor. Defect in the metabolizer enzyme of tamoxifen (CYP2D6), which convert it to the active forms, results in the increased risk of recurrence after treatment. Fulvestrant is another monoclonal antibody which its effect is similar to tamoxifen. Trastuzumab suppresses the cell growth by binding inhibition of epidermal growth factor to HER2 receptors. In the metastatic form of disease, the patients may show resistance to trastuzumab, so lapatinib is suitable alternative in these cases. Pertuzumab combination with trastuzumab and chemotherapy with taxane blocks the dimerization of HER2 with another form of HER receptors. The application of personalized medicine in triple negative phenotype is limited due to the lack of appropriate targets and biomarkers, it makes necessary to do further studies. The aim of this review was to describing the different aspects of personalized medicine and introducing the most important biomarkers and targets in the treatment of breast cancer.

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Background: Members of the tumor necrosis factor (TNF) superfamily of ligands and their receptors (TNFR) are critical regulators of the adaptive immune system. A proliferation inducing ligand (APRIL) is a member of tumor necrosis factor superfamily. APRIL was identified via database mining in 1998 by Hahne, et al. APRIL allows tumor cells to proliferate at a reasonable rate even in low serum. APRIL is abundantly expressed in many tumor cells and tumor tissues. Increasing level of APRIL expression related to replacement of -Arg-Lys-Arg-Arg- motif by -Ala-Lys-Arg-Ala- between amino acids 101-104 and thus abrogated APRIL processing. Previous studies have shown a correlation between APRIL expression with some autoimmune disease, breast cancer, stomach cancer, esophagus cancer and colorectal cancer. Herein, we explore correlation between serum APRIL with pancreatic cancer. Methods: Our study is performed in digestive disease research institute (DDRI) of the Shariati Hospital in Tehran City and affiliated Hospital of Tehran University of Medical Sciences. In this study, concentrations of serum APRIL in sera (30 pancreatic cancer patients and 30 healthy controls) from November 2011 to November 2013 collected and level of a proliferation inducing ligand measured by ELISA technique. In this study used from SPSS software, version 22 (IBM SPSS, Armonk, NY, USA) to perform statistical data analysis. Results: The case group measurement results compared with control groups results according to some characteristics such as age, smoking and, diabetes. ELISA analysis of APRIL measurements show that mean serum APRIL level of pancreatic cancer patients (7 ng/ml) was significantly higher than control group (5 ng/ml). The p-value of this study was 0.003. Conclusion: Our results indicate that serum APRIL, as a potential biomarker, has a positive diagnosis and prognosis value for pancreatic cancer.

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Background: Despite advances in the vaccinology and chemotherapy in the past century, tuberculosis is still responsible for two million deaths every year. Emergence of multi-drug resistant strain and coinfection of TB-HIV make it a serious concern. Treatment and control of tuberculosis is a great health burden in every community. Active tuberculosis in children has very severe consequences especially those who are under 5-years-old, therefore vaccine indication should be taken. Bacille Calmette-Guérin (BCG) is a live attenuated strain of Mycobacterium bovis that has been used for providing immunity or protection against tuberculosis (TB). In addition, BCG provides relative protection against leprosy and Buruli ulcer, it also can be used for treatment of bladder cancer. BCG is the most widely administered vaccine around the world. It has been given to over three billion individuals over the past decades. At first it was developed in 1908 at the Pasteur Institute in Lille by Albert Calmette and Camille Guérin. In fact BCG is a strain of Mycobacterium bovis that bear deletion in its genome following too long subculture in special media. Deletion in region of deletion 1 (RD1), a specific region of Mycobacterium bovis genome, has decreased pathogenicity of BCG strain. Following culture of BCG on different media since 1921 make genetic variation in the BCG strains that have specific characteristics. BCG should begin given to only immune-competent individuals and should not be administered to immunocompromised people. This vaccine is not effective in people formerly infected or sensitized with environmental mycobacteria. Previous meta-analysis studies indicate that BCG has variable range of protection from 0 to 80 percent against pulmonary TB, but is very effective against severe disseminated forms such as meningitis and miliary form of TB. Despite many research and develop new generation vaccine against TB, BCG vaccine still remains as the only effective vaccine because many efforts to replace it with better ones were unsuccessful.

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Background: Autosomal recessive polycystic kidney disorder (ARPCKD) is one of the most prevalent hereditary disorders in neonates and children. Its frequency is between 1/6000 to 1/55000 births. In the most severe cases, it can be diagnosed prenatally by the presence of enlarged, echogenic kidneys and oligohydramnios. However, in the milder forms, clinical manifestations are usually detected in neonatal and childhood period. PKHD1 gene located on chromosome 6 is linked with this disorder. About half of detected mutations in this gene are missense ones. The largest protein product of this gene is called the FPC/polyductin complex (FPC). It is a single-membrane spanning protein whose absence leads to abnormal ciliogenesis in the kidneys.

Case presentation: Here we present a 5-year-old female patient affected with ARPCKD. She has been born to a non-consanguineous healthy Iranian parents. No similar disorder has been seen in the family. Prenatal history has been normal. In order to find the genetic background, DNA was extracted from patient's peripheral blood lymphocytes. PKHD1 gene exons and exon-intron boundaries were sequenced using next generation sequencing platform. Two novel variants have been detected in compound heterozygote state in the patient (c.6591C>A, c.8222C>A). Bioinformatics tools predicted these variants to be pathogenic.

Conclusion: In the present study, we detected two novel variants in PKHD1 gene in a patient with ARPCKD. The relatively mild phenotype of this patient is in accordance with the missense mutations found. Molecular genetic tools can help in accurate risk assessment as well as precise genotype-phenotype correlation establishment in families affected with such disorder to decrease the birth of affected individuals through preimplantation genetic diagnosis or better management of disorder.

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Background: Doxorubicin (DOX) is a commonly used chemotherapeutic agent that causes hepatotoxicity via depletion of anti-oxidants and activation of apoptosis. Present study was aimed to investigate the interactive effects of two forced treadmill running and voluntary wheel running exercise training method and Nanocurcumin supplement on hepatic damage, in aging model subjects. Methods: This experimental research was performed in animals and exercise physiology laboratory of Faculty of Physical Education and Sport Sciences, University of Mazandaran, Iran, in April, 2014. The statistical population was eighty Wistar male rats that, received a daily injection of D-galactose solution for nine weeks (100 mg/kg body weight per day, i.p.) and then, they randomly assigned to 10 groups. The forced treadmill running protocol was progressively between 25 to 54 min/day at the intensity of 15 to 20 m/min for 5 days per week for six weeks and voluntary wheel running exercise was six weeks. DOX was administrated for 15 days (1 mg/mL/kg body weight per day, i.p.). Nanocurcumin supplement was administrated for 14 days (100 mg/kg body weight per day. orally). Superoxide dismutase and apoptosis inducing factor levels were measured by enzyme-linked immunosorbent assay (ELISA) method. Results: Implementation of two forced treadmill running and voluntary wheel running exercise with Nanocurcumin supplement, respectively led to insignificant decrease and increase in superoxide dismutase levels in comparison with the implementation of this exercise methods alone (P= 0.955 and P= 1.000, respectively). Apoptosis Inducing Factor levels following these two training method with Nanocurcumin supplement, has insignificant decrease in comparison with the implementation of this exercise methods alone (P= 1.000 and P= 1.000, respectively). Conclusion: Our findings suggest that, however implementation of these training methods with Nanocurcumin supplement, partly mitigates the side effects of doxorubicin, but this level of intervention is not sufficient to protect against doxorubicin-induced hepatotoxicity in aging model rats.