محمد خلج کندری

Recurrent spontaneous abortion (RSA) is the most common complication of pregnancy that refers to two or more miscarriages before the 20th week of pregnancy. HLA-G immunoglobulin molecule plays an important role in protecting the fetus against mother's immune system. The aim of this study was to investigate the association between rs1632943 and rs1736932 polymorphisms with recurrent spontaneous abortion in Northwest of Iran.

This case-control study included 100 women with history of RSA as our case group and 80 healthy women with one or more than one children as the control group. Genomic DNA was purified from their peripheral blood samples and their genotypes were determined by PCR-sequencing method. Using SPSS 16, statistical analysis was performed by chi-square test.

In rs1632943 polymorphism the frequency of CC, CA and AA genotypes were 8%, 33% and 59% in the patient group and 16.25%, 43.75% and % 40 in the control group, respectively. Statistical analysis showed that AA genotype was associated with the recurrent spontaneous abortion (P = 0.005). In the rs1736932 polymorphism, the frequency of CC, CG and GG genotypes were 8%, 32% and 60% in the patient group and 17.5%, 41.25% and 41.25% in the control group, respectively. Statistical analysis showed that GG genotype was associated with the recurrent miscarriage (P = 0.005). Also, haplotype analysis showed that H1 haplotype (GA) is associated with the disorder.

Results of the study showed that rs1632943 and ra1736932 polymorphisms

Cytomegalovirus (CMV) infection is one of the most prevalent infections among kidney transplant recipients. Due to the use of immunosuppressive medications in kidney transplant recipients, their immune system is low and complications of CMV infection such as transplant rejection are observed in them. The MICA gene encodes a stress-related protein that is involved in responding to the virus in virus-infected cells and cancer. One of the single nucleotide polymorphisms of the MICA gene is rs1051792. This polymorphism leads to a non-synonymous mutation which classifies the MICA alleles into strong (MICA-129 Met) and weak (MICA-129 Val) binders of the NKG2D receptor. The purpose of this study was to evaluate the association between MICA rs1051792 polymorphism and susceptibility to cytomegalovirus infection in kidney transplant recipients in the northwest of Iran.

This study included 51 cytomegalovirus-infected kidney transplant recipients as cases and 50 kidney transplant recipients without cytomegalovirus infection as control subjects. Genotyping was performed by PCR-RFLP technique.

The percentage of frequencies of the genotypes AA, AG, GG was 17.64%, 45.09%, and 37.25% in the cases and 16%, 48%, and 36% in the control group, respectively. The statistical analysis did not indicate significant differences between the case and control groups (p>0.05).

 The results do not support the association between MICA rs1051792 and susceptibility to cytomegalovirus infection in kidney transplant recipients. Findings emphasize the need to evaluate other candidates of the genetic polymorphisms in the study population.

This study aimed to evaluate the expression levels of TINCR in tumor and adjacent non-tumor tissues of 50 women diagnosed with invasive ductal carcinoma. The association of TINCR expression and the clinical characteristics of patients have also been studied.

Total RNA was isolated from tumor and adjacent non- tumor tissues of breast cancer patients using RNX-Plus. Then, PrimeScriptTM RT reagent was used for converting total RNA to cDNA. TINCR lncRNA levels were quantified by qRT-PCR and results was analyzed with paired sample t test. Moreover, for evaluation the TINCR biomarker potential, ROC curve analysis was used in breast cancer tumor tissues.

Reduced levels of TINCR were obtained in tumor tissues of breast cancer patients compared with adjacent non-tumor tissues (P<0.0001). TINCR expression had negative association with tumor size and lymph node metastasis in breast cancer tumor tissues.

TINCR lncRNA downregulation in tumor tissues of breast cancer patients indicates that its expression level could discriminate the tumor from non-tumor tissues in breast cancer patients. Furthermore, TINCR lncRNA have low levels in breast cancer patients with large tumor size, positive lymph node metastasis and luminal A and B subtypes.

Breast cancer is the most important cause of cancer mortality among women, therefore the study of its causative or aggravating factors seems necessary. In this study, the mRNA levels of the PHB2 gene were evaluated in tumor and adjacent non-tumor tissues of 50 women diagnosed with invasive ductal carcinoma of the breast.

RNX-Plus solution was used to isolate total RNA from tumor and adjacent non-tumor tissues of breast cancer patients. Thereafter, total RNA was converted to cDNA using PrimeScriptTM RT reagent kit. The mRNA levels of PHB2 were quantified by qRT-PCR and data were analyzed with a paired-samples t test. Furthermore, ROC curve analysis was performed to evaluate the diagnostic capacity of PHB2 expression in breast cancer tumor tissues.

A significantly lower level of PHB2 mRNA was observed in tumor tissues of breast cancer patients compared with adjacent non-tumor tissues (P<0.0001). PHB2 mRNA levels showed an approximately 2.5-fold reduction in tumor tissues compared with normal tissues (P = 0.001). Roc cure analysis showed that PHB2 mRNA level can discriminate tumors from non-tumor tissues with 91.3% specificity and 64.3% sensitivity (AUC=0.712, P<0.001).

Downregulation of PHB2 in breast cancer patients shows that its mRNA levels can possibly discriminate tumors from non-tumor tissues.

Alzheimer's disease (AD) is a multifactorial disorder that its progress and development are related to various genetic and environmental factors. The disease onset is affected by both genetic and environmental factors such as oxidative stress, inflammation, and mitochondrial dysfunction, and is remarkably related to age progress. Aluminum, a neurotoxic environmental factor, impairs memory performance and can cause neurodegenerative diseases such as AD. On the other hand, the regulatory RNA-binding product of Fragile X mental retardation (FMR1) gene exerts a translational inhibitory effect on the expression of amyloid precursor protein (APP), the main culprit in AD development. In the present study, we treated AlCl3-induced Alzheimer’s disease model rats with Frankincense and investigated its protective and therapeutic effects on the AlCl3-induced memory disturbance by behavioral and molecular assays. Also, Rivastigmine was used as a standard control. Morris Water Maze (MWM) was used to assay special memory working of the rats and quantitative real-time PCR (qRT-PCR) was applied to investigate the expression profile of the FMR1 gene in the hippocampus of the treated rats. MWM behavioral tests indicated that both Frankincense and Rivastigmine not only may prevent AlCl3-induced memory impairment but also may alleviate the memory declines induced by AlCl3 in the rats. Expression analysis showed significant upregulation of the FMR1 gene in response to both Frankincense and Rivastigmin treatments. Further, qRT-PCR results revealed that the AlCl3-induced downregulation of the FMR1 gene expression could significantly be reversed by both Frankincense and Rivastigmine, though Rivastigmine was more effective than Frankincense. In conclusion, our results highlighted that Frankincense might be effective both in the prevention and treatment of memory impairments, to some extent, by affecting the FMR1 gene expression.

 Recurrent Pregnancy Loss (RPL) is a multifactorial disease that affects 1-3% of couples. Since Human Leukocyte Antigen-G (HLA-G) gene is involved in fetal maternal immune tolerance, mutations in the HLA-G gene can affect the success rate of pregnancy.

 The present study aims to investigate the haplotype effect of rs1736933 and rs2735022 polymorphisms found in the HLA-G gene on the RPL.Methods In this case-control study, participants were 100 women with RPL and 80 women with normal fertility in northwestern Iran. The HLA-G gene promoter was amplified by Polymerase Chain Reaction (PCR) method and sequenced. The genotype and allele frequencies of the two polymorphisms were compared between the two groups by using t-test in SPSS software version 22. Haplotype analysis was performed using PHASE 2.1 and Haploview 4.2 applications

 C allele and CC genotype in rs2735022 polymorphism and the G allele and GG genotype in rs1736933 polymorphism showed a significant association with the RPL (P<0.05). Frequency of haplotypes AA, AC, GA, GC were 0.72, 0.23, 0.01, 0.03 in patients and 0.39, 0.01, 0.02, 0.59 in the control group (P<0.05). The linkage disequilibrium score was 94.

 Analysis of GC haplotype in rs2735022 and rs1736933 polymorphisms of the HLA-G gene can be helpful in genetic studies of women with RPL.

Genetic polymorphisms are one of the possible causes of recurrent abortion with unknown cause. This study was performed with aim to investigate the association and frequency of rs2249863 and rs1233334 polymorphisms of the upstream region of HLA-G gene with the recurrent spontaneous abortion in women from Northwest of Iran.

This case-control study was performed on 160 women from Northwest of Iran referring to the Madar infertility clinic of Tabriz between 2018 and 2019. Among them, 80 women with a history of recurrent spontaneous abortion (at least 2 abortions) were considered as case group and 80 women with at least one child and without any history of miscarriage as control group. After collecting blood samples, genome DNA was extracted and the polymorphisms were evaluated by PCR and sequencing technique. Data were analyzed using SPSS software (version 22) and Fisher test. P <0.05 was considered statistically significant.    

The frequencies of allele G and genotype GG in the rs2249863 polymorphism were significantly different between the case and control groups (P<0.05). In the rs1233334 polymorphism, although the frequencies of allele C and genotype CC were different between the case and control groups, but the differences were not statistically significant (P>0.05). Moreover, haplotype analysis identified the CG as the commonest haplotype that its frequency was significantly different between the case and control groups (P<0.05).

The rs2249863 polymorphism and CG haplotype of the rs2249863 and rs1233334 polymorphisms are associated with the recurrent spontaneous abortion in the studied population and they could be considered as potential risk factors for the disease.

Studies have suggested that HLA-G is involved in protecting the fetus against the motherchr('39')s immune system, and upstream polymorphisms of this gene may influence pregnancy success by effecting its expression. The aim of this study was to evaluate the association of upstream HLA-G gene polymorphism, rs1736933, with recurrent spontaneous abortion in East Azerbaijan women population.

This case-control study was performed on 80 women with at least one child and without any history of abortion, and 100 women with at least two recurrent spontaneous abortions which were diagnosed by gynecologist. 2 ml of blood was obtained from the participants and after DNA extraction, a segment of the HLA-G gene promoter was amplified by PCR and analyzed by agarose gel electrophoresis. PCR products were sequenced and genotyped. Allelic and genotypic frequencies of patient and control groups were compared.

Frequency of AA, CA, CC genotypes in the patient group were 8(8%), 37(37%), 55(55%) and in the control group were 16(20%), 33(41.25%), 31(38.75%) respectively. Comparison of genotypic frequencies between the two groups showed that CC homozygous genotype was associated with recurrent abortion (p= 0.015). Statistical analysis also showed a significant difference between the allelic frequencies of the two groups (p= 0.019).

The results of this study showed that the upstream HLA-G gene polymorphism, rs1736933, is associated with the recurrent abortion in East Azerbaijan women population.

Alzheimer’s disease is the most common cause of dementia in old people. AD is a progressive and irreversible neurodegenerative brain disorder. Sortilin receptor 1 (SORL1) is involved in cellular trafficking of amyloid precursor protein and plays an essential role in amyloid-beta peptide generation in the AD. The purpose of the present study was to evaluate the association of SORL1 rs2282649 and rs12285364 polymorphism with AD in Azeri population in the northwest of Iran.

This case- control study included 100 Alzheimer’s disease patients as our case and 83 healthy subjects as our control group. Genotypes were determined by (PCR- RFLP) technique.

In rs2282649 SNP the frequency of homozygous CC genotype was 36% in the case and 38.55% % in the control groups (P= 0.70). The frequencies of TT genotype were 12% and 7.23% in the case and control groups respectively (P = 0.25). The frequency of heterozygote CT genotype was 52% in the cases and 54.22% in the control group (P = 0.75). Also, in rs12285364 polymorphism the frequencies of homozygous CC genotype in the cases and the control groups were 93% and 90.36 % respectively (P= 0.5). The frequency of TT genotype was 0% in both case and control groups (P = 0.00). The frequencies of heterozygote CT genotype were 7% in the case and 9.64% in the control groups (P = 0.49).            

No statistically significant difference was observed between the case and control groups in regard to the frequencies of the genotypes. Therefore we can conclude that these polymorphisms are not associated with Alzheimer’s disease among the people in the northwest of Iran.

Breast cancer is the second most common cause of cancer-related death among females, which requires an exploration for markers to propose a more specific categorization of this cancer. Long noncoding RNAs (lncRNAs), the main subset of noncoding transcripts, are involved in tumorigenic processes. In this study, we investigated the expression of the fer- 1– like family member 4 (FER1L4) lncRNA and its competitive endogenous RNA network target gene, RB transcriptional corepressor 1 (RB1), in ductal carcinoma (invasive and in situ) tissue and its adjacent noncancerous tissue (ANCT). Furthermore, associations of FER1L4 and RB1 with various clinical features of the patients were analyzed.

Quantitative real-time PCR was used to measure the expression of the mentioned genes in 61 samples of ductal carcinoma and their ANCTs, and the data were analyzed using ANOVA and t tests.

FER1L expression was not significantly different in breast tumor samples compared with their ANCT samples, while RB1 showed significant downregulation in tumor tissues (P = 0.008). In addition, increased expression of FER1L4 and decreased RB1 expression were significantly correlated with lymph node metastasis in breast cancer patients (P < 0.05).

FER1L4 is not upregulated in breast cancer tissue. However, RB1 expression is significantly downregulated.

The therapeutic properties of Olibanum have been considered in traditional medicine since ages past. Recent studies indicated the effect of Olibanum on memory enhancement and prevention/treatment of Alzheimer's disease. Fragile X mental retardation protein is the product of the FMR1 gene that mediates memory formation through the development of communications between nerve cells. MAP1B is the FMRP target mRNA and its translation is inhibited by the effect of FMRP. Disturbance in the expression of FMR1 causes fragile X syndrome. Therefore, the aim of this study was to investigate the effect of aqueous extract of Olibanum on the expression of FMR1 and MAP1B genes in hippocampal tissue samples of rats. This study was conducted on 18 rats which were divided into groups of control (n=6) and two treatment groups with 75 (n=6) and 150 mg/kg (n=6) concentrations of aqueous extract of Olibanum. The hippocampus of rats was isolated after eight weeks of treatment by Olibanum extract.  Total RNA was extracted and cDNA was synthesized in this study. Subsequently, the expression of FMR1 and MAP1B genes was evaluated by a real-time polymerase chain reaction. Ethics code:IR.TBZMED.REC.1396.1000 According to the results, the aqueous extract of Olibanum at a concentration of 75 mg/kg increased the expression of FMR1. In addition, MAP1B gene expression decreased in a dose-dependent manner following treatment with Olibanum extract. However, these changes are not statistically significant (P>0.05). The FMRP is a negative translation regulator that mediates synaptic neuronal transmission through inhibition translation of target mRNA, such as MAP1B. Olibanum probably leads to synaptic flexibility and memory improvement through increasing the expression of FMR1 in neuronal cells. This study could pave the way on the use of Olibanum in the treatment of patients with fragile X syndrome in the future.

In the past, olibanum was used as an incense and perfume and a remedy for treating various diseases. Now, it is confirmed that olibanum improves memory and has a role in treatment and prevention of Alzheimer disease. CaMKIIα gene is known as molecular memory because of its role in cellular processes associated with memory. The aim of this research was to study the effect of ethanolic extract of olibanum on the expression of CaMKIIα in B65 and PC12 cells. To determine the effect of olibanum on cell viability, MTT assay was done and cells were treated with the extract in different concentrations and times. To study the gene expression, the cells were treated by two concentrations of the extract at four time points. Then, RNA was extracted, cDNA was synthesized, and the expression of CaMKIIα was quantified by qPCR. The qPCR data revealed that olibanum alternately changed the expression of CaMKIIα in a reducing and increasing pattern over time in B65 cells. However, the extract could not induce the expression of this gene in PC12 cells. According to the role of CaMKIIα as molecular memory and the positive effect of olibanum in memory improvement, current results could be helpful in understanding the molecular mechanisms by which olibanum affects memory performance.

Long-term memory depends on protein synthesis. The product of Camkiv gene promotes memory via activating its proteins. The treatment of laboratory animals by Olibanum leads to memory improvement and the recovery of Alzheimer. Therefore, the aim of this study is the evaluation of Olibanum ethanolic extract on the Camkiv expression in PC12 cells. Olibanum toxicity on the cell viability was investigated by MTT test. Cells were treated with concentrations 10,25,40,55,70 and 85 μg/ml of extract in time intervals 12,24,48 and 72 hours and their absorption rate was measured. Then, cells were treated by concentrations 2 and 20 μg/ml of extract in mentioned times. Extracted RNA was converted into cDNA and real-time PCR performed. Cell death was raised by increasing time and concentration of extract treatment. IC50 values were obtained as 71.01, 52.95, 21.05 and 13.85 μg/ml in 12, 24, 48 and 72 hours of treatment, respectively. Besides, concentrations 2 and 20 μg/ml significantly increased Camkiv expression following 24 hour treatment. The maximum expression of Camkiv was observed in 48 hour treatment. The effect of Olibanum on gene upregulation was stable until 72 hours. The Olibanum ethanolic extract can remarkably upregulate Camkiv expression for a long time. These results are consistent with the previous studies indicating the effect of Olibanum on upregulation of Bdnf, Camkiv -downstream gene. However, regarding the existence of the two-direction pathway in the expression regulation of Bdnf and Camkiv , comprehensive studies are required to determine exact mechanism of Olibanum function in the brain.

Warfarin is a commonly-prescribed anticoagulant used to treat and prevent thromboembolic events. The requirement for varying doses of warfarin depends on genetic and environmental components. In this study, the frequency of two single-nucleotide polymorphic variants of the vitamin K epoxide reductase complex subunit 1 (VKORC1) gene (1173 C>T (rs9934438) and 3730 G>A (rs7294)) and its correlation with warfarin maintenance doses were investigated in patients with heart valve replacement from West Azarbayejan, Iran. Blood samples were obtained from 185 patients; their genomic DNA was extracted and samples were genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay. To assess if the blood warfarin level is different among genotypes, we used a one-way analysis of variance (ANOVA) followed by a Tukey’s post-hoc comparison. The minor allele frequency was determined to be 54% for 1173T and 53.7% for 3730A. Patients who carried the G allele at position 3730 and T allele at position 1173 required a significantly lower daily mean warfarin dosage (P <0.001). Consideration of the VKORC1 gene polymorphism, especially at the initial stages of the therapy, can be helpful in pre-treatment dosing of warfarin, which, in turn, reduces the adverse effects resulting from inappropriate drug prescription.

Diagnosis of Alzheimer's disease usually occurs when serious damages have occurred in the brain and common treatments are ineffective in preventing it. One of the RNAs involved in Alzheimer's disease is a long noncoding RNA, called BDNF antisense (BDNF-AS). The aim of this study is to determine the presence and compare the BDNF-AS levels in plasma of Alzheimer's patients and healthy subjects, and to evaluate its potential as a plasma marker for Alzheimer's disease.
In this case-control study, 30 patients with late-stage Alzheimer's disease and 30 healthy subjects without neurological disease who matched the patients in terms of age were selected by a specialist according to the criteria for clinical diagnosis of Alzheimer's disease and their intravenous blood samples were collected. The plasma of the blood samples was isolated and total plasma RNA was extracted. After cDNA synthesis, the presence of BDNF-AS in plasma was examined by PCR. Finally, the relative level of BDNF-AS transcripts in plasma samples of patients with Alzheimer's disease and healthy subjects was evaluated using Real Time PCR.
FINDINGS: The results of this study showed that long noncoding RNA BDNF-AS was present in the plasma of patients and controls. Comparison of Real Time PCR data showed that BDNF-AS levels in the plasma of patients (0.107±0.021) showed significant increase compared to healthy subjects (0.039 ± 0.006).
The results of this preliminary study indicate that the levels of long noncoding RNA BDNF-AS in plasma can be used as a blood/plasma marker for the diagnosis of Alzheimer's disease.

The most important effects of Frankincense on memory are included prevention and relative treatment of Alzheimer disease, as well as memory enhancement of off springs of the rats that had received Frankincense during their pregnancy and lactation period. Considerably, Camk4, one of the important memory genes, induces downstream memory genes expression through phosphorylation and activation of transcription factors. Here, we aimed to study the effects of aqueous extract of Frankincense on the Camk4 gene expression in PC12 and B65 cell lines.
The effect of extract on the cell viability was evaluated by cell treatment in two time intervals with six concentrations of extract and 50% inhibition concentration was obtained. In this way, for gene expression studies, cells were treated by two concentrations of extract in two time points. RNA was extracted and converted to cDNA and qPCR was performed to investigate the expression of Camk4 gene.
The aqueous extract of Frankincense decreased the cell viability in a time and concentration dependent pattern. However, the extract was more toxic for B65 cell line than PC12. Also, it significantly increased the expression of Camk4 gene in the cells. Nevertheless, the increase was dependent to the extract concentration and the cell type. The low concentration of the extract was more effective to the expression of Camk4 gene than the high concentration as well as to its expression in the PC12 cell line than B65.
This study showed that Frankincense could regulate the expression of Camk4 gene in a concentration dependent pattern. However, further studies are needed to identify the mechanisms of Frankincense action in different cells.

Aim & Frankincense is a herbal product that has diverse therapeutic effects. Beta-boswellic acid, the main ingredient of frankincense, is poorly soluble in water and its bioavailability is very low. The aim of present study was to evaluate the effect of loading of beta-boswellic acid in dendrosomal nanoparticles on its bioavailability and cell uptake by MTT assay.
For MTT assay, B65 cells were treated with different doses of nave beta-boswellic acid or dendrosomal beta-boswelic acid for 24, 48 and 72 hours. After adding MTT, colorimetery was done using ELISA reader and IC50 was then calculated. The data was analyzed with One Way Anova program using SPSS v.16 software.
The IC50 for nave beta-boswellic acid and dendrosomal beta-boswellic acid was 88/09 and 58/42 µM in 24h, 58/37 and 44/87 µM in 48h and 21/09 and 16/69 µM in 72h respectively.
The results showed that loading of beta-boswellic acid in dendrosomal nanoparticles increases the cell toxicity effect of beta-boswellic acid. This observation might be due to the increased cell uptake of beta-boswellic acid in the presence of dendrosomal nanoparticles.

Targeting transgene carriers and vectors to individual cells and tissues is one of the most important goals of gene therapy. Bacteriophages are of appropriate transgene carriers and there are different methods for their targeting to target cells. Present study reports preparation of targeted M13-based bacteriophage particles by a chemical coupling strategy.

First, the pCMV-Script-GFP construct was produced via in vivo excision protocol from GFP Phage particles using ExAssist helper phage and XLOLR as specific host. Then, M13 phage particles bearing GFP (M13-GFP) were obtained by single stranded rescue using R408 helper phage. The human holotransferrin molecules were then coupled to the surface of phage particles by reductive amination chemistry. Transferrin molecules bind to the surface of phage particles were studied by phage-ELISA.

Phage-ELISA tests showed that holotransferrin molecules were coupled to the surface of M13 phage particles in a correct way and the transferrin-targgeted M13 phage particles were prepared. Further analysis showed that about 485 transferrin molecules coupled per phage particle.

The results show that chemical coupling might be considered as a suitable strategy for targeting of M13 particles via coupling of targeting molecules in high density to the phage surface.

Laboratory Studies show that Olibanum boosts the process of learning and memory. Alzheimer’ disease is one of the important cognitive abnormalities which affect memory. Moreover, increased expression of amyloid precursor protein (App) results in Alzheimer’ disease. This study with the aim of comparing the effects of Olibanum aqueous extract and rivastigmin on the expression of App gene in rats that are treated by AlCl3. 24 adult male rats with a weight range of 220±30 gr. were randomly divided into 4 groups (n=6) and treated for 120 days. Treating group are as follow: Group no. 1 as control, group no. 2 as Alzheimer's model, group no. 3 as Olibanum treated, group 4 as rivastegmin teated were received 1 ml of distilled water, AlCl3 20mg/kg, AlCl3 (20 mg/kg) for 60 days and then AlCl3 with the same dose plus aqueous extract of Olibanum (200 mg/kg) for another 60 days and, AlCl3 (20 mg/kg) for 60 days and then AlCl3 with the same dose plus rivastigmin (0.3 mg/kg) for another 60 days, respectively. Then, learning and spatial memory performance of the rats were examined in 6 successive days with Morris-Water-Maze. After behavioral tests, hippocampus of the rats was separated and isolated in –80 degree centigrade. Total RNA was extracted by using RNX-plus solution. Finally, the expression of App gene was examined by semi-quantitative RT-PCR. Results obtained from Morris-Water-Maze showed that AlCl3 impairs memory performance in rats while treatments with rivastigmin or aqueous extract of Olibanum improves learning in rats model. The App gene expression analysis revealed that this gene unregulate significantly by utilizing AlCl3. Comparing the effects of rivastigmin and aqueous extract of Olibanum showed that Olibanum but not rivastigmin decreases the expression of App. AlCl3 treatment can impair learning and spatial memory in rats while Olibanum or rivastigmin might improve their performance. Moreover, Olibanum impedes AlCl3-induced App up-regulation.

Recurrent spontaneous abortion (RSA) is defined by two or more consecutive miscarriages before 20 weeks of gestation. Adenosine deaminase (ADA) is an enzyme of purine salvage pathway and has two important isoenzymes ADA1 and ADA2. The adenosine deaminase G22A polymorphism (ADA*2) increases the level of adenosine. Adenosine may play a protective role against recurrent spontaneous abortions, since it regulates blood flow into the uterus and placenta. In consideration of the effect of decreased enzymatic activity of adenosine deaminase G22A polymorphism on adenosine levels we evaluated the protective effect of ADA*2 allele against recurrent spontaneous abortions in north-west of Iran. A total of 100 women were recruited to form two groups. First one, with a history of recurrent spontaneous abortions (N=50), and the second one, without a history of abortions (N=50). Genomic DNA was extracted from peripheral blood with a commercial kit and PCR-RFLP analysis was used to identify the G22A genetic polymorphism. Fisher's exact test and odds ratio values were used to compare the proportions of adenosine deaminase genotypes and alleles between women with and without a history of recurrent spontaneous abortion (p<0.05). The frequency of homozygotes (AA) was 2% in control group, whereas no homozygote (AA) was found in the case group. The frequency of heterozygotes (AG) was 20% in control group and 8% in the case group (p<0.05). The frequency of homozygotes (GG) was 78% in control group and 92% in the case group (p<0. 05). A significant increase in the frequency of AG genotype in controls (p=0.014, OR=0.348) relative to women with the history of RSA demonstrates the protective effect of AG genotype in controls. The data suggest that women carrying the G22A polymorphism (ADA*2 allele) and AG genotype which is associated with the lower enzymatic activity are better protected against recurrent spontaneous abortions.

Despite the progresses achieved in the treatment, detection and development of effective drugs for curing of diseases e.g. cancer, using of such therapeutics by patients is associated with severe side-effects. Since, most of them are not specific for cancerous cells; they may affect normal cells as well. So, targeted delivery of therapeutics is very important. Bacteriophages are a subtype of viral nanoparticles (VNPs) which can potentially deliver therapeutics to target cells/tissues, and this aspect of bacteriophage application has recently been considered by researchers. Plenty of studies show that not only bacteriophages have capacity for targeted delivering of imaging agents, drugs and genes into the cells/tissues but have appropriate profile of distribution in tissues and clearance from blood stream as well. Moreover, images obtained from different radioactive and optic imaging approaches have high-resolution in methods using bacteriophage because of their depth penetration into the tissues. Furthermore, bacteriophage-based approaches have more advantages such as safety and low cost. Regarding the plenty of advantages, it is expected that bacteriophages might be used as a suitable tool in diverse clinical trials in the near future. In the present study, the potential applications of bacteriophages are considered in medical imaging, targeted drug and gene delivery.

Learning is the acquisition of information about the world and memory is a mechanism to encode, store and retrieve the learned information. Weak memory and learning disorders are the most common cognitive problems. In the present study, the pharmacological effects of aqueous extract of Boswellia on learning and spatial memory in male rats was investigated using the Morris water maze (MWM) test. In this experimental study, 21 male rats were divided into 3 groups including a control group (distilled water) and two groups treated with aqueous extract of Boswellia 50 and 100 mg/kg) that received the treatment for 4 weeks. To evaluate learning ability of animals, Morris Water Maze was used. In the first and the last day of training, all groups showed significant reduction in escape latency (P<0.0001) and traveled distance (P<0.0001). In the sixth day of training, both treatment groups showed significant reduction in escape latency (P<0.05) and traveled distance (P<0.05) in comparison with the control group. The results suggest that intake of Boswellia facilitates the learning and spatial memory formation in rats via Morris water maze test method.

Recently، phage display libraries have received enormous attention for identification and isolation of pharmaceutical molecules with diagnostic and therapeutic properties. Peptide libraries are known as one of the most important and widely used types of phage display libraries. In the current study، we aimed to screen the Ph. D. TM-7 phage display peptide library through biopanning for the identification of human colon adenocarcinoma-binding peptide ligands. Three rounds of biopanning were performed on SW480 as the target cell and fibroblast (HF-SF-PI3)، AGS، KYSE-30 and Huh-7 as control cells. The displayed peptide-encoding regions in the genome of SW480-binding phages obtained from the final round of panning were amplified by plaque-PCR and subsequently sequenced. Bioinformatic tools were used to determine the sequence of target cell-binding peptides and further characterization of these peptides. Biopanning of the phage library led to the enrichment of several peptides among which the peptide with “HAMRAQP” was the most dominant. Bioinformatic analysis of the isolated peptides indicated that they are not target unrelated peptides (TUP). The peptides، in particular those with the highest frequency، due to having the capability of specific binding to SW480 cells represent the potential for use in targeting of therapeutic genes and drugs to colon cancer cells.

Due to some drawbacks associated with gene delivery vehicles including viral and non-viral vectors, scientists have continued their efforts to find an ideal gene delivery vehicle. Bacteriophages have been proposed as an attractive alternative gene delivery vehicle in view of their advantages such as protection of transgene, lack of immunogenicity and stability in different conditions. This study has been conducted with the aim of obtaining a construct based on M13 phage and evaluating its capability for delivering transgene to eukaryotic cells. pCMV-Script EX phagemid was constructed by intracellular excision of Lambda Zap CMV XR vector bearing GFP gene. Packaging of the construct using helper phage resulted in M13-GFP phage particles which used for transfection of human AGS cell line. Finally internalization of the phage particles into the AGS cell line was evaluated by PCR and florescence microscopy. Examination of the treated cells with florescence microscopy indicated that M13-GFP phage particles were able to internalize and express the transgene in eukaryotic cells, but the efficiency of this trasfer was very low. PCR analysis showed that internalization of the M13 GFP gene vehicle to eukaryotic cells was dose dependent. The results indicated that M13 phage could be an appropriate gene delivery vehicle, because it had trivial tropism for eukaryotic cells. This means that after displaying or coupling of appropriate targeting molecules on the surface of phage particles, transgene can effectively be delivered to the target cells.

Bacteriophage lambda comprises critical advantages that have made it as an ideal gene delivery vehicle into the eukaryotic cells. These advantages reside in both the structure and biology of the lambda phage، for example، recent investigations have revealed common ancestry for the tailed phages and eukaryotic DNA viruses. Considering these features as well as the double-stranded nature of its genome، bacteriophage lambda might comprise a great advantage for phage-mediated gene delivery into eukaryotic cells. A phage lambda-derived gene nanocarrier bearing reporter gene GFP (λ-GFP) was constructed and utilized to transfect AGS cell line. λ-GFP particle-mediated gene delivery and expression as well as its internalization by AGS cell line was investigated.