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Background and Aims: Sirtuin-1 (SIRT1) has antidiabetic effects through the regulation of insulin secretion and modulation of inflammation. The SIRT1 rs3758391 gene polymorphism affects the level of SIRT1. The current study aimed to investigate the possible influence of SIRT1 gene variants in relation to oxidative stress parameters on the susceptibility to type 2 diabetes mellitus (T2DM) and its microvascular complications., Methods: In this case-control study 398 individuals including 300 patients with T2DM (100 T2DM without complication, 100 diabetic neuropathy patients and 100 patients with diabetic retinopathy) and 98 healthy subjects were studied for SIRT1 rs3758391 T > C variants. Also, the glutathione peroxidase (GPx) activity and the levels of glutathione (GSH), malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidative status (TOS) were determined by colorimetric methods. SIRT1 genotypes were detected using the polymerase chain reaction-restriction fragment length polymorphism method., Results: The C allele of SIRT1 reduced the risk of T2DM, diabetic neuropathy and diabetic retinopathy. Significantly lower levels of GSH, GPx, and TAC were found in diabetic patients compared to control group. However, the level of MDA was significantly higher in patients compared to healthy individuals. Considering all individuals, the GPx activity increased in the presence of the SIRT1 CC, and TC genotypes compared to the TT genotype. Among all studied individuals the activity of GPx was significantly higher in normal body mass index (BMI) subjects than overweight, and obese individuals. However, among overweight and obese diabetic, diabetic retinopathy and diabetic neuropathy patients the mean level of TOS was significantly higher compared to patients with normal BMI., Conclusions: Our findings suggest a protective role for SIRT1 C allele against T2DM and diabetic neuropathy and diabetic retinopathy. We found in the presence of this allele the GPx activity increased. Also, we detected an enhanced oxidative stress level among overweight and obese patients with diabetes and its complications that could be involved in the pathogenesis of the disease., Competing Interests: Zohreh Rahimi is an Editorial Board member of Health Science Reports and a coauthor of this article. To minimize bias, they were excluded from all editorial decision‐making related to the acceptance of this article for publication. The remaining authors declare no conflict of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Spermatogonial stem cells (SSCs) maintain spermatogenesis through self-renewal and differentiation. The proliferation of SSCs in culture systems can provide a valuable source of germ cells. Several studies have investigated new reproductive technologies, including the production of transgenic animals and recombinant proteins secreted from milk in goats. While studies in other species exist, research on goat SSC culture remains limited. We investigated the impact of different testosterone concentrations on the survival and colonisation of cocultured goat SSCs with Sertoli cells. Cells were isolated from immature goats using two-step enzymatic digestion and enriched by differential exclusion method. DMEM/F12 culture medium containing 1% antibiotic and 5% FBS, supplemented with GDNF (20 ng/mL), EGF, bFGF and LIF (10 ng/mL), was used with different testosterone concentrations (0, 60, 120 and 240 μg/mL) and cultured for 10 days. SC subpopulations were confirmed using PGP9.5 immunocytochemistry, and the expression of germ cell markers (ID-4, UCHL-1, THY-1, β1-integrin, BCL6B, VASA, PLZF and OCT-4) was evaluated through RT-PCR. Alkaline phosphatase activity provided additional SSC presence. The survival rate of SSCs after isolation and the number and area of colonies on Days 4, 7 and 10 were measured using an inverted microscope. The presence of PGP 9.5 antigens and germ cell markers (ID-4, UCHL-1, THY-1, β1-integrin, BCL6B, VASA, PLZF and OCT-4) was confirmed by immunocytochemistry and RT-PCR, respectively. According to the results, the group with 60 μg/mL testosterone had the highest number and area of colonies. The number of colonies in the 60 μg/mL testosterone group was significantly higher than the control group (p < 0.05), but no significant difference was observed compared to other groups (p ≥ 0.05). This study suggests that a low testosterone concentration (60 μg/mL) is optimal for goat SSC colonisation and viability in coculture with Sertoli cells, potentially leading to advancements in goat reproductive technologies., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

The methylation pattern of non-imprinting genes was little studied, although it is widely known that the abnormal methylation levels of imprinting genes are associated with different forms of male infertility. The purpose of this research was to assess the CREM gene's methylation status and seminal characteristics in infertile individuals who were potential intracytoplasmic sperm injection (ICSI) candidates. A total of 45 semen samples (15 normospermia, 15 asthenospermia, and 15 oligoasthenoteratospermia) were examined. Using aniline blue (AB) staining, we carried out conventional semen analysis, chromatin quality, and sperm maturity testing. DNA was taken from semen samples, and all isolated DNA was assessed using Nanodrop and gel electrophoresis. A quantitative methylation-specific polymerase chain reaction (Q-MSP) approach was used to quantify the methylation at the DMRs of the CREM gene. According to our findings, sperm count (P=0.012), concentration (P= 0.019), motility (P=0.006), progression (P=0.006), and normal morphology (P=0.004) were all inversely correlated with abnormal sperm chromatin condensation. Additionally, we noted that the methylation level of the CREM gene was considerably more significant in the oligoasthenoteratospermia group compared to the asthenospermia and normospermia groups (P<0.05). Additionally, sperm count (P=0.043), progression (P=0.026), and normal morphology (P=0.024) were all inversely linked with CREM methylation. Overall, the abnormal CREM methylation patterns have a negative impact on sperm parameters. Additionally, the CREM gene's DNA methylation status may serve as an epigenetic indicator of male infertility., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Breast cancer (BC) is the most common malignancy in women in western countries. A significant part of malignant cases is caused by genetic mutation. Mutations in the gene phosphatase and tensin homologue deleted on chromosome (PTEN) have been proven in various malignancies. The present study was conducted with the aim of investigating the prevalence of BC due to PTEN gene mutation, as well as estimating the chance of developing BC due to the occurrence of PTEN gene mutation. The present study was conducted using a systematic review method based on PRISMA 2020 statements. The search was done in PubMed, Web of Science (WOS), Scopus, and direct scientific databases. The search was performed using the keywords breast cancer, breast malignancy, PTEN, polymorphism, mutation, variant, and their equivalents. Statistical analysis was performed using the second version of Comprehensive Meta-Analysis Software. A total of 2138 articles were collected. After removing duplicate articles, checking the title and abstract, and then checking the full text of the documents, finally 64 articles were approved and entered the systematic review process. Analysis of these studies with a sample size of 231,179 showed the prevalence of breast cancer patients with PTEN mutations. The combined results of 64 studies showed that the prevalence of PTEN mutations has a 3.3 (95% CI 2.2-5) in BC patients, and an analysis of 6 studies showed that the odds ratio of developing BC due to PTEN mutation is 3.7 (95% CI 1.1-11.9). The results of this study show that mutation in the PTEN gene increases the chance of developing BC. However, it was found that a small part of patients gets BC due to the occurrence of mutation in this gene., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Oral lichen planus (OLP) is an inflammatory mucocutaneous disorder with an immune-mediated pathogenesis. The tumor necrosis factor-α (TNF-α) level in the serum of OLP patients is significantly higher than in the control group. TNF-α-857 C/T polymorphism can be related to the increased TNF-α level in blood circulation. This study investigated the relationship between TNF-α (-857 C/T) polymorphism and OLP patients in an Iranian population., Methods: Saliva samples were taken from 200 people, including 100 patients with OLP and 100 healthy people who did not have significant differences in age and sex. Then, DNA was extracted from them and the TNF-α (-857 C/T) genotype was identified using the polymerase chain reaction with confronting two-pair primers method. Statistical Package for the Social Sciences version 16 software analyzed the results., Results: The frequency of C/C, C/T, and T/T genotypes of the TNF-α-857 C/T polymorphism in the patient group were 78%, 18%, and 4%, respectively, and in the control group were 72%, 23%, and 5%, respectively. The differences between the two groups regarding allele ( χ 2   =  0.97, p   = 0.32) and genotype ( χ 2   =  0.96, p   = 0.62) frequency among the studied population were insignificant., Conclusion: This study showed that the difference in the frequency of single nucleotide polymorphism TNF-α-857 C/T polymorphism in the patient and control group had no significant relationship with the increased OLP incidence. Also, no significant association was observed between allele and genotype frequency of TNF-α (-857 C/T) with OLP subtypes., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Background: The objective was to elucidate the potential epigenetic regulatory mechanism in  HMOX1 expression in preeclampsia. Materials & methods: HMOX1 promoter DNA methylation was evaluated in the placental tissue and blood of preeclamptic and normotensive pregnant women. HMOX1 and miR-153-3p gene expression were assessed in placental tissue and peripheral blood mononuclear cells (PBMCs). Related microarray datasets in the Gene Expression Omnibus database were also analyzed. Results: In placental tissue, despite HMOX1 expression downregulation, there was no significant change in HMOX1 methylation. In PBMCs, there was no significant alteration in HMOX1 expression, while hypomethylation was observed in blood. The miR-153-3p expression increased in the placental tissue and in the PBMCs of preeclampsia. Conclusion: DNA methylation does not affect HMOX1 expression, while miR-153-3p might be a biomarker for preeclampsia.

Background and Aims: Preeclampsia (PE) is a serious medical condition that usually causes high blood pressure and affects multiple organs. Considering the adverse effect of oxidative stress on the process of PE in pregnant women and regarding the role of the Nrf2 gene in placental oxidative pathways, this study was conducted to investigate the DNA methylation status of Nrf2 in PE and healthy pregnant women., Materials and Methods: The present case-control study consisted of 70 PE and 70 healthy pregnant women. Blood and placenta samples were taken from all subjects, and the percentage of the Nrf2 gene methylation in the samples was assessed by the Methyl Light PCR method. Also, the Nrf2 gene expression was evaluated by real-time PCR. The total antioxidant capacity (TAC) and total oxidative status (TOS) were measured by the colorimetric method., Results: In PE women, there was a significant increase in blood pressure, term of pregnancy, and BMI. In addition, there were enhanced Nrf2 DNA methylation percentage in placenta tissue and increased TOS levels in placenta tissue and blood compared to healthy pregnant women (P < 0.05). Also, in the PE group, there was a significant decrease in Nrf2 gene expression and TAC level in placenta tissue compared to the control group (P < 0.05)., Conclusion: The Nrf2 gene undergoes epigenetic modifications of DNA hypermethylation in the PE placenta. Decreased expression of this gene and the changes in the level of oxidative parameters (TAC, TOS) confirm it., (© 2024. The Author(s).)

Background: Oral lichen planus (OLP) is a T-cell-mediated autoimmune disease that affects the epithelial cells of the oral cavity. This study was performed to investigate any possible relationship between - 1031(T/C) polymorphism (rs1799964) of the tumor necrosis factor α (TNF-α) gene with the risk and severity of oral lichen planus (OLP) disease among an Iranian population., Method: Saliva samples were collected from 100 patients with OLP and a similar number of healthy controls (age and sex-matched). Then, DNA was extracted from the collected samples for genotyping TNF-α-1031 T/C polymorphism using the PCR-CTPP method. The results were assessed using SPSS software., Results: The findings revealed a significantly higher prevalence of the C allele in OLP patients (53%) compared to healthy controls (36%), suggesting an association between TNF-alpha gene polymorphism and OLP. A multivariate logistic regression analysis supported this finding, as the presence of the C allele was significantly associated with an increased risk of OLP [χ2 = 4.17, p = 0.04, 95% CI = 1.01-2.65, OR = 1.64]. However, our data indicated no significant association between TNF-alpha-1031 T/C gene polymorphism and OLP severity., Conclusions: These findings provide the first evidence supporting a possible role of TNF-α-1031 T/C gene polymorphism in OLP susceptibility in the Iranian population. The findings of this study demonstrate a positive association between TNF-α-1031 C/T allele distribution and the risk of OLP disease in the Iranian population. Therefore, carrying the C allele may increase the susceptibility to OLP disease., (© 2024. The Author(s).)

Male infertility accounts for nearly 40%-50% of all infertile cases. One of the most prevalent disorders detected in infertile men is errors in the MEST differentially methylated region (DMR), which has been correlated with poor sperm indexes. The aim of our study was to characterize the methylation pattern of the MEST gene, along with assessing seminal factors and chromatin condensation in sperm samples from both infertile patients and fertile cases, all of whom were candidates for intracytoplasmic sperm injection. We collected forty-five semen specimens from men undergoing routine spermiogram analysis at the Infertility Treatment Center. The specimens consisted of 15 samples of normospermia as the control group, 15 individuals of asthenospermia, and 15 individuals of oligoasthenoteratospermia as the cases group. Standard semen analysis and the chromatin quality and sperm maturity tests using aniline blue staining were performed. The DNA from spermatozoa was extracted and treated with a sodium bisulfite-based procedure. The methylation measure was done quantitatively at the DMRs of the MEST gene by quantitative methylation-specific polymerase chain reaction (qMSP). The mean percentages of total motility, progression, and morphology in normospermia were significantly higher than oligoasthenoteratospermia and asthenospermia, and they were substantially higher in asthenospermia compared to oligoasthenoteratospermia (P ≤ 0.05). The mean percentages of histone transition abnormality and MEST methylation in oligoasthenoteratospermia were significantly higher than asthenospermia and normospermia (P ≤ 0.05). A negative correlation existed between the histone transition abnormality and MEST methylation with sperm parameters. In conclusion, chromatin integrity, sperm maturity, and MEST methylation may be considered important predictors for addressing male factor infertility. Therefore, we suggest that male infertility may be linked to methylation of the imprinted genes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objective: Chimeric antigen receptor (CAR) T cell therapy has recently emerged as a promising approach for the treatment of different types of cancer. Improving CAR T cell manufacturing in terms of costs and product quality is an important concern for expanding the accessibility of this therapy. One proposed strategy for improving T cell expansion is to use genetically engineered artificial antigen presenting cells (aAPC) expressing a membrane-bound anti-CD3 for T cell activation. The aim of this study was to characterize CAR T cells generated using this aAPC-mediated approach in terms of expansion efficiency, immunophenotype, and cytotoxicity., Materials and Methods: In this experimental study, we generated an aAPC line by engineering K562 cells to express a membrane-bound anti-CD3 (mOKT3). T cell activation was performed by co-culturing PBMCs with either mitomycin C-treated aAPCs or surface-immobilized anti-CD3 and anti-CD28 antibodies. Untransduced and CD19-CARtransduced T cells were characterized in terms of expansion, activation markers, interferon gamma (IFN-γ) secretion, CD4/CD8 ratio, memory phenotype, and exhaustion markers. Cytotoxicity of CD19-CAR T cells generated by aAPCs and antibodies were also investigated using a bioluminescence-based co-culture assay., Results: Our findings showed that the engineered aAPC line has the potential to expand CAR T cells similar to that using the antibody-based method. Although activation with aAPCs leads to a higher ratio of CD8+ and effector memory T cells in the final product, we did not observe a significant difference in IFN-γ secretion, cytotoxic activity or exhaustion between CAR T cells generated with aAPC or antibodies., Conclusion: Our results show that despite the differences in the immunophenotypes of aAPC and antibody-based CAR T cells, both methods can be used to manufacture potent CAR T cells. These findings are instrumental for the improvement of the CAR T cell manufacturing process and future applications of aAPC-mediated expansion of CAR T cells.

MicroRNAs are a set of small non-coding RNAs that could change gene expression with post-transcriptional regulation. MiRNAs have a significant role in regulating molecular signaling pathways and innate and adaptive immune system activity. Moreover, miRNAs can be utilized as a powerful instrument for tissue engineers and regenerative medicine by altering the expression of genes and growth factors. MiR-1290, which was first discovered in human embryonic stem cells, is one of those miRNAs that play an essential role in developing the fetal nervous system. This review aims to discuss current findings on miR-1290 in different human pathologies and determine whether manipulation of miR-1290 could be considered a possible therapeutic strategy to treat different non-malignant diseases. The results of these studies suggest that the regulation of miR-1290 may be helpful in the treatment of some bacterial (leprosy) and viral infections (HIV, influenza A, and Borna disease virus). Also, adjusting the expression of miR-1290 in non-infectious diseases such as celiac disease, necrotizing enterocolitis, polycystic ovary syndrome, pulmonary fibrosis, ankylosing spondylitis, muscle atrophy, sarcopenia, and ischemic heart disease can help to treat these diseases better. In addition to acting as a biomarker for the diagnosis of non-malignant diseases (such as NAFLD, fetal growth, preeclampsia, down syndrome, chronic rhinosinusitis, and oral lichen planus), the miR-1290 can also be used as a valuable instrument in tissue engineering and reconstructive medicine. Consequently, it is suggested that the regulation of miR-1290 could be considered a possible therapeutic target in the treatment of non-malignant diseases in the future., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Oral Lichen Planus (OLP) is a chronic inflammatory mucosal disease. The pathogenesis of OLP is unknown. The Single Nucleotide Polymorphism (SNP) that occurs in the regulatory position + 781 could affect the expression of interleukin-8. This polymorphism is probably associated with increased serum levels of IL-8. The current study aimed to investigate the genotype and allele frequencies of IL-8( + 781 C/T) in OLP patients and whether it is associated with the severity of OLP disease in an Iranian population., Methods: Three milliliters of saliva were taken from 100 patients with OLP and 100 healthy individuals who were matched in age and gender. After DNA extraction from saliva samples of patients and healthy individuals, the genotype of IL-8 at position + 781 is detected using the PCR-RFLP method. The results were analyzed using SPSS software., Results: Frequency of C/C, T/C, and T/T genotypes at position IL-8 + 781 gene in the patient group were 47%, 41%, and 12%, respectively, and in the control group, were 37%, 42%, and 21%. The difference between the two groups regarding allele frequency distribution was statistically significant (χ 2  = 3.86, p = 0.049, 95% CI = 0.44-1, OR = 0.66). Our results indicated the significantly higher frequency of the TT genotype in the erosive OLP compared to the nonerosive group (p = 0.03, OR = 0.89, 95% CI = 0.49-1.6)., Conclusion: This study depicted the difference in the frequency of SNP IL-8 + 781 C/T allele in the patient and control groups had a significant association with the risk of OLP. In addition, our data revealed that IL-8 + 781 C/T polymorphisms might be associated with the severity of OLP in the Iranian population., (© 2023. The Author(s).)

In this study, salt leaching (SL) technique was used to prepare a chitosan/polyvinyl alcohol (CS/PVA) polymeric composite in order to load metformin nanoparticles (METNPs). Sodium chloride was added to the CS/PVA (0.5:0.1) composite to create a porous hydrogel using the SL technique. METNPs were then prepared by water/oil (w/o) method and loaded into the hydrogel structure. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis confirmed that >80 % of the METNPs were in the range of 10 nm. As a result, encapsulation increased due to the increase in surface-to-volume ratio. Scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) results confirmed that creating porosity in the polymer composition by the SL method led to increased CS/PVA polymer chain mobility. The drug encapsulation increased due to more porosity, and the release in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) was according to the controlled diffusion kinetics. Furthermore, the drug release from CS/PVA composite was anomalous carrier type that could be attributed to the addition of salt. However, due to the increase the amount of PVA and the creation of a monotonous composite structure, encapsulation of drug decreased, which is in accordance with the polymer relaxation mechanism., Competing Interests: Declaration of competing interest This manuscript is authored by Kasra Yari, Gelareh Gharati, and Iman Akbari, who declare no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Recurrent miscarriage (RM) is a major reproductive health issue. RM is a multi-factorial disease, and is affected by environmental, genetic, and epigenetic factors. Genetics has a common role in recurrent miscarriage occurrence. It seems that molecular genetics has a great role in RSA incidence. So, in these years, RM has become for a major subject of genetics research. There are many genes that are involved in each phase for successful reproduction. This research aimed to evaluate the effect of all studied polymorphisms in studies on RSA that have not been included in any meta-analysis. PubMed, Scopus, and Web of Science databases were recruited to investigate the related articles. The systematic review results identified 143 studies worldwide. Thirteen genes have been included in assessing the case-control studies. Sixty-four SNPs were recruited to assess the association between genetic factors and RSA susceptibility. Ninety-two studies containing twenty-two SNPs (from 10 genes) were included in the quantitative analysis. Bioinformatic analysis indicated that rs12722482 showed "Damaging Status" by double servers, and rs315952 and rs854560 had "Possibly damaging" status in the PolyPhen-2 server. MethPrimer server indicated that there is "CpG Island" in the rs10895068, rs1130355, and rs41557518 variants, and rs10895068-G allele makes a CpG dinucleotide which can change the gene methylation and result in altering the gene expression. So, further studies on rs12722482 and rs10895068 can demonstrate valuable results. To the best of our knowledge, this systematic review has covered the all studied polymorphisms of HLA-C, HLA-G, PON1, AGTR1, TAFI, FAS, FAS-L, ESR1, PGR, CTLA-4, MMP-2, MMP-3, MMP-9, and IL1RN for the first time. Also, we did a novel meta-analysis for AGTR1 rs5186, TAFI rs1926447, rs3742264, HLA-G rs1063320, rs1233334, rs1736936, rs2249863, PON1 rs662, rs854560, FAS rs2234767, rs1800682, FAS-L rs763110, ESR1, rs9340799, rs3798759, PGR rs1042838, CTLA4 rs4553808, rs5742909, rs231775, rs3087243, and MMP-2 rs243865 and updated statistical finding for rs2234693 and rs371194629. Rs2234693, rs9340799, rs231775, and rs371194629 demonstrated a significant association with RSA risk. Some variations showed significant association, while further studies are suggested to confirm the results. Finally, Rs4553808 and rs5742909 revealed no significant deviation in the results. It is suggested that these SNPs may be excluded from subsequent case-control studies or other analyses., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background & Objective: Breast cancer (BC) is known to be the most prevalent cancer among women. One-carbon metabolism disturbance might play an important role in the etiology of BC. The present study aimed to investigate the thymidylate synthase (TYMS), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and methionine synthase reductase (MTRR) variants as good candidates for studying the role of genetic variants of folate metabolizing enzymes in the risk of BC., Methods: The present case-control study includes 100 BC patients and 141 healthy females. The TYMS  2R/3R (rs34743033), MTR  c.2756A>G (rs1805087), and MTRR c.66A>G (rs1801394) variants were detected by polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (RFLP), and a designed amplification-refractory mutation system (ARMS) method, respectively., Results: The 3R allele of TYMS enhanced the risk of BC by 2.84-fold ( P <0.001). In the presence of TYMS 3R/3R, compared to TYMS 2R/3R, there was a trend toward enhancing the risk of metastasis by 4.15-fold (95% CI: 0.96-17.85, P =0.055). The frequencies of MTR c.2756A>G and MTRR c.66A>G variants were not significantly different among patients and controls., Conclusion: We observed that the TYMS 3R is a risk allele for susceptibility to BC and this allele may increase the risk of metastasis in BC patients. .

BACKGROUND The incidence of multiple primaries in cancer patients is 2-17%. However, the synchronous co-occurrence of adenocarcinoma of the breast and follicular lymphoma is rare. CASE REPORT We describe a case series of 3 post-menopausal women who presented to our institute with a breast lump. On further investigations, 2 of them had invasive ductal carcinoma and 1 had invasive lobular carcinoma of the breast. All 3 cancers were estrogen/progesterone receptor (ER/PR)-positive and human epidermal growth factor receptor 2 (HER-2)-negative. During the staging PET scans, all 3 patients had increased FDG uptake in axillary, mesenteric, and inguinal lymph nodes, respectively, raising concerns for metastatic disease. However, subsequent biopsies revealed them as follicular lymphomas occurring as a second concurrent primary malignancy. All patients underwent radical mastectomies with sentinel lymph node dissection followed by chemotherapy and hormonal therapy. Most of the lymphomas were low grade, which the oncologist closely followed. CONCLUSIONS Very few cases of breast cancer and follicular lymphoma co-occur; this is not limited to the axillary lymph nodes and can occur in any part of the lymphatic chain. Regional lymph node enlargement detected on examination or imaging does not always indicate metastasis. A high index of suspicion is needed followed by lymph node biopsy to rule out any second primary malignancy.

Background: The association of 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) and its receptor, vitamin D receptor (VDR), with cancer types have been studied. However, there are controversial findings regarding the association of specific VDR polymorphisms with different kinds of cancers. In the current study, we investigated the association of VDR polymorphisms (Fok1 (rs2228570), ApaI (rs7975232), BsmI (rs1544410), and TaqI (rs731236)) with the risk of gastric cancer in a Kurdish population of Kermanshah in Iran for the first time., Methods: In this case-control study, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used in 99 gastric cancer patients and 100 healthy subjects as controls., Results: The frequencies of f ( FokI ), b ( BsmI ), t ( TaqI ), and a ( ApaI ) alleles were: 55.6%, 27.3%, 62.1%, and 44.95% in the patient group, respectively and 42%, 29.5%, 54.5%, and 46.0% in the control group, respectively. Analysis of the results indicated that there was a positive association between the frequency of FokI genotypes with gastric cancer risk ( p = 0.021). However, no statistically significant association of BsmI , Taq1, and ApaI polymorphisms of VDR was detected in gastric patients when compared with healthy individuals., Conclusion: VDR- FokI polymorphism could increase the risk of GC development and predispose to the disease by mechanisms.

Objective: The current research was conducted to study the association between the SNP309 and del1518 polymorphisms with the breast cancer in the patients with the Kurdish ethnic background from western Iran. Also, a systematic review of the relevant case-control studies on the MDM2 polymorphisms in the patients with breast cancer was performed., Methodology: Two mL of peripheral blood was taken from 100 patients with breast cancer and 100 healthy individuals. The frequencies of MDM2 SNP309 and del1518 genotypes and alleles were determined using the PCR-RFLP and PCR methods, respectively., Results: The frequency of the TT, TG, and GG of MDM2-SNP309 genotypes in the patients was obtained as 23%, 52%, and 25%, and they were equal to 22%, 40%, and 38% in the control group, respectively. Also, considering the MDM2-del1518 polymorphism, the frequencies of ins/ins, ins/del, and del/del genotypes were equal to 52%, 41%, and 7% in the breast cancer group and they were equal to 62, 30, and 8% in the control group, respectively. Analysis of the results indicated that the GG genotype plays a protective role for the breast cancer in the recessive model (GG vs TT + TG) of SNP309 (χ 2  = 3.916, P = .048, and OR = 0.54)., Conclusion: Our findings revealed that the GG genotype of MDM2-SNP309 can play a protective role in the breast cancer disease. Also, our systematic review indicated that the SNP309, SNP285, and del1518 of MDM2 gene in different populations mostly did not have a significant association with the risk of breast cancer., (© 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Sodium alginate (SA) is a natural biopolymer that is used as biodegradable and non-toxic material in medical and pharmaceutical fields. Although crosslinked SA with calcium ions in the presence of monovalent salts are unstable. The aim of this work is to employe plant mucilage in combination of SA beads to improve the properties of SA beads. SA beads containing metformin drug (MET) were modified using basil seed mucilage (BSM) to achieve controlled release was investigated. The presence of BSM in the SA structure results in more stability, less swelling, and consequently lower release. The effect of pH 1.2 and pH 7.4 on its release and swelling of the beads was studied, and the results showed that the lowest swelling and release was from the acidic environment. Sodium Tripolyphosphate (TPP) as a cross-linker in the bead structure caused a lower release and swelling. The chemical structure of beads was confirmed by FTIR, SEM indicated the porous structure of SA bead and continuous structure of SA/BSM bead and DSC indicated that the presence of BSM in the bead structure decreased the chain motility. Also, cytotoxicity of BSM was investigated by MTT method, and the mucilage toxicity was not confirmed until 3 ml., (Copyright © 2020. Published by Elsevier B.V.)

The present study aimed to determine the effect of low-intensity training with blood flow restriction (BFR) on the response rate of anabolic hormones. Forty healthy and untrained young men, aged 18 to 25 years old, were randomly divided into five groups: one session of BFR training (BFR1), two sessions of BFR training (BFR2), one session of resistance training without BFR (WBFR1), two sessions of resistance training without BFR (WBFR2), and the control group (without training). BFR groups had three sets of 20 repetitions with 20-30% 1RM, and none-BFR groups had three sets of 10 repetitions with 70-80% 1RM for six weeks. Both BFR1 and WBFR1 groups trained 3day a week (1 session in a day and three sessions a week), BFR2 and WBFR2 groups trained three days a week (but two sessions a day and six sessions in a week) and Control group did not perform any training. The mean changes in growth hormone(GH), testosterone(TS), and vascular endothelial growth factor (VEGF) hormones were determined by ELISA technique before, after a first training session and after six weeks of the training program. To the analysis of data, two way repeated measures ANOVA at a significant level of P&lt;0.05  also were used. The results showed a significant increase in GH levels in each of the four training groups as compared with the pre-test and the control group after a first training session and after six weeks of the training program (P&lt;0.05). There was no significant increase in TS levels in each of the four training groups, as compared with the pre-test and the control group in both acute and chronic TS response (P&gt;0.05). Only the WBFR1 group did not significantly increase in VEGF levels after the first training session (P&gt;0.05). In chronic VEGF response, there were no significant changes observed in all training groups as compared with the control group(P&gt;0.05). Despite the effectiveness of low-intensity BFR training, such as high-intensity resistance training on hormonal responses, two sessions per day training with the same volume does not necessarily result in larger responses in all hormones than one session per day training.

Background: We aimed to determine the promoter methylation status of the retinoic acid receptor-beta 2 (RARβ2) gene among breast cancer patients and to review relevant studies in this field in various populations., Methods: We analyzed 400 samples which comprised blood specimens from 102 breast cancer patients, 102 first-degree female relatives of patients, 100 cancer-free females, 48 breast cancer tissues, and 48 adjacent normal breast tissues from the same patients. The RARβ2 methylation status was determined using methylation-specific polymerase chain reaction (MSP) and DNA sequencing methods., Results: The presence of combined partially methylated (MU) and fully methylated (MM) forms of the RARβ2 gene (MU+MM) in the blood of patients was associated with susceptibility to breast cancer (odds ratio = 4.7, p = 0.05). A significantly higher frequency of the MM genotype was observed in cancer tissue (10.4%) compared to matched adjacent normal breast tissue (0%) (p = 0.02)., Conclusion: We found a higher frequency of RARβ2 gene methylation in the blood and cancer tissues of patients compared to the blood of controls and adjacent normal breast tissues. The survey of studies on various populations demonstrated a higher RARβ2 methylation frequency in breast cancer patients compared to normal individuals, and many reports suggest a significant association between hypermethylation of the gene and susceptibility to breast cancer., Competing Interests: The authors declare no potential or actual conflicts of interest in relation to the current article., (Copyright © 2019 by S. Karger AG, Basel.)

Mutations in certain genes have been suggested to be associated with the pathogenesis of chronic lymphocytic leukemia (CLL), which is the most common leukemia in adults. In a case-control study, 100 patients with CLL and 105 healthy individuals were investigated for Notch homolog 1, translocation-associated ( Drosophila ) (NOTCH1) c.7544-7545delCT, recombinant splicing factor 3B subunit 1 (SF3B1) c.2098A>G, mouse double minute 2 homolog (MDM2) 40-bp insertion/deletion and myeloid differentiation primary response 88 (MYD88) L265P mutations by using allele specific-polymerase chain reaction (AS-PCR), a designed AS-PCR, PCR and PCR-restriction fragment length polymorphism methods, respectively. The presence of NOTCH1 and SF3B1 mutations were confirmed by genomic DNA sequencing. The NOTCH1 mutation was detected in 10% of patients and not detected in the control group. A higher frequency of NOTCH1 mutation was detected in patients with stage III CLL (62.5%) compared with stages 0-II CLL (37.5%) (odds ratio, 4.69-fold; 95% confidence interval, 1.0-21.9; P=0.049). The SF3B1 mutation was observed in 12% of the patients compared with 1.9% of the controls (P=0.012). The presence of MDM2 polymorphism was not associated with the risk or the stage of the disease. In addition, the MYD88 L265P mutation was not detected in the patients or the controls. The current study established the frequency of NOTCH1, SF3B1, MDM2 and MYD88 mutations in patients with CLL from the Kurdish population of Western Iran. In summary, a high frequency of NOTCH1 and SF3B1 mutations were identified in patients with CLL compared with healthy individuals, and the NOTCH1 mutation was associated with a high stage of the disease.

Background: Chloronicotinic insecticide are a class of pesticides that are commonly used as insecticides. Among the frequently used chloronicotinic pesticide, imidacloprid (IM) was developed in 1986. The residual of this insecticide or any pesticides may have serious public health threats., Methods: Both degradation and mineralization of the imidacloprid (IM) in aqueous solution was studied under various experimental conditions using different advanced oxidation processes namely, ultraviolet C (UVC), UVC + TiO 2 , and UVC + ZnO. All the experiments were performed using a lab-scale batch photoreactor with a working volume of 100 mL equipped with low-pressure mercury vapor lamp (9 W, 18 cm long, Philips Co.), emitting UV radiation with maximum intensity at 254 nm. The possible intermediates and a reaction pathway for photocatalytic degradation of the IM were also evaluated., Results: It was observed that under optimal condition for UVC/TiO 2 process (C 0  = 100 mg/L, pH = 7.5, t = 20 min, TiO 2 dose = 100 mg/L), IM was effectively degraded (88.15%) and followed the first order kinetics model. The degradation efficiency increased with increasing of illumination time and is more favorable in alkaline pH compared to acidic pH. Degradation of the IM in photocatalytic process was compared with photolysis showing a significant synergy effect in the case of the photocatalytic degradation process, leading at 20 min illumination time to a 36.7% increase of the IM removal efficiency in comparison to the single UVC. The GC/MS chromatograms before and after treatment confirmed the effectiveness of the UVC/TiO 2 process in simplifying the nature of IM and its conversion to more simple and degradable compounds., Conclusion: The heterogeneous UVC/TiO 2 process was found to be an efficient chemical-less method that is appropriate for degradation of IM from aqueous phase., Competing Interests: Conflicts of interestThe authors declare they have no conflicts of interest.

Periodontitis is a chronic inflammatory disease that influences the protective tissues of teeth. IL-8, a member of the chemokine super-family, plays vital roles in the pathogenesis of periodontitis with activation and migration of neutrophils in inflammatory regions. The purpose of present study was to evaluate the association of interleukin-8 - 845 T/C and + 781 C/T polymorphisms with periodontitis in an Iranian population. A total of 65 patients with periodontitis including 18 patients with chronic periodontitis and 47 patients with aggressive periodontitis and 55 controls were enrolled into our study. Interleukin-8 - 845 T/C and + 781 C/T polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. For + 781C/T locus, in the dominant genetic model there was a significant difference between TT vs. CC + CT genotypes that significantly had a protective role against periodontitis disease with a value of 0.38 (95% CI 0.16-0.90, p = 0.02). Also, the analysis of results showed a significant positive association between the distribution of IL-8 - 845 T/C alleles and the risk of periodontitis disease (χ 2  = 6.2, p = 0.01) that presence of C allele of IL-8 - 845 increased the risk of periodontitis disease by 9.08-fold [OR 9.08 (95% CI 1.14-72.12, p = 0.03)]. In conclusion, our results demonstrate a positive association between distribution of IL-8 - 845 T/C alleles and risk of periodontitis disease.

The efficient DNA extraction from insects has been suggested as a critical and main step affecting molecular entomology for taxonomic identification, the establishment of DNA barcoding library and analysis of genetic diversity relationship between insect populations. For successfully apply these molecular techniques, high-quantity and high-quality of the extracted DNA are required. Several protocols for efficient genomic DNA extraction from insects have been developed. In this research, we represent a rapid, reliable and cost-effective method that it is not reliant on poisonous and enzymatic reagents for DNA extraction from insect tissues. Results showed that high quantity and high-quality of the isolated DNA by this method is suitable and can be used directly for PCR, also is enough to do hundreds of molecular reactions. In conclusion, we described a fast, cost-effective, non-toxic and enzyme-free protocol for high yield genomic DNA extraction from green Lacewings (Chrysoperla carnea) tissues in basic equipment laboratories.

Background: The control of auto-reactive cells is defective in rheumatoid arthritis (RA). Regulatory T (Treg) cells which play a key role in the modulation of immune responses have an impaired function in RA. Foxp3 is a master regulator of Treg cells which its expression is under the tight control of epigenetic mechanisms. In the current study, we analyzed the epigenetic modulation of the Foxp3 Treg-specific demethylated region (TSDR) and Helios gene expression to determine Treg cells alteration in RA patients., Methods: We have recruited 20 newly diagnosed patients with RA and 41 healthy controls in our study. The measurement of Foxp3 and Helios gene expression was performed by the real-time PCR technique and the methylation level of TSDR was analyzed by bisulfite treatment and quantitative methylation-specific PCR (Q-MSP)., Results: We found that RA patients had significantly lower level of Foxp3 gene expression and TSDR demethylation compared to healthy subjects (P < 0.001 and P = 0.006, respectively). Inversely, the Helios gene expression was elevated significantly in RA patients group (P = 0.048). We also observed a significant correlation between Foxp3 and Helios gene expression (P = 0.016) as well as a significant correlation between FoxP3 expression and demethylation rate of TSDR (P = 0.010)., Conclusion: Our results suggested that both epigenetic modifications and Helios gene expression may have important roles in the pathogenesis of RA through their effects on Foxp3 gene expression.

The fenugreek is one of the most important medicinal plants belongs to Fabaceae, originated in West Asia, Iran and Mediterranean regions. This research included a qualitative study of fenugreek proteins using SDS-PAGE electrophoresis on polyacrylamide gel and the separation of protein bands of fenugreek leaves in different treatments of vermicompost fertilizer and cultivating dates. Results showed that a band (about 80 kDa) on the first planting date (May 31) is observed in all samples except for sample a1 (10 t/ha vermicompost on May 31). Another significant difference was the band contained in the third planting date (31 September) and in the molecular weight of about 15 kDa, which was not seen in other dates. This difference can be due to the synthesis of this protein with the mentioned weight under the conditions of reducing the temperature in the early fall. It also showed more differences in two-dimensional electrophoresis, for example, in 14 kDa and PI in the range of 4.5-4.7 in treatment without fertilizer, no protein expression was observed, which was consistent with the results of the SDS-PAGE test.

The interaction of FAS/FAS ligand (FASL) serves an important role in the upregulation of apoptotic processes through different mechanisms in cells. Previous studies have established that the polymorphisms FAS -670A/G and FASL -844C/T are associated with risk of generalized aggressive periodontitis (GAP) in different ethnic populations. Therefore, in the present study, it was investigated for the first time whether FAS -670A/G and FASL -844C/T polymorphisms were associated with risk of GAP in Iran. This case-control study performed the polymerase chain reaction-restriction fragment length polymorphism method in 25 patients with GAP and 110 normal subjects as controls. The results indicated that there was no significant difference in FAS -670A/G genotype frequency between the GAP and control groups. A higher frequency of the combined genotype (AG+GG) was observed in the GAP patients (96.0%) compared with the control subjects (90.9%), though this was not significant [χ 2 =0.705, degrees of freedom (df)=1, P=0.401]. Similarly, the prevalence of the G allele was non-significantly higher in the GAP group (62.0%) compared with that in the controls (60.0%; χ 2 =0.012, df=1, P=0.913). For FASL-844C/T polymorphism, the frequency of the combined genotype (CT+TT) was higher in the GAP group (96.0%) when compared with the control subjects (91.8%); however its association was not statistically significant (χ 2 =0.519, df=1, P=0.471). The frequency of the T allele only marginally differed between the groups, being 60.0% in the GAP group and 50.9% in the controls (χ 2 =3.627, df=1, P=0.057). These results indicated that there were no significant associations between the FAS -670A/G and FASL -844C/T polymorphisms and the risk of disease in GAP patients when compared with normal individuals.

Stevia rebaudiana Bertoni is one of two species that contains steviol glycosides. Among steviol glycosides that extracted from leaves, stevioside and rebaudioside A are the two major and the sweetest glycosides that are about 200-300 times sweeter than sucrose with zero calories. The best method for stevia propagation is tissue culture. So, for investigation of nutrients in medium, we studied the effect of different concentrations of MS media (MS, 0.5 MS, 0.25 MS, 0 MS) on morphological traits, UGT74G1 and UGT76G1 genes expression and accumulation of steviol glycosides in stevia leaves. The best growth rate (0.472 mm/d) has occurred in plants grown in MS media. Also, the highest gene expression of UGT74G1 gene (1.000 Total lab unit) was seen under MS treatment. However, the highest expression level of UGT76G1 gene (1.701 Total lab unit) was observed at plants grown in 0 MS. The highest amount of both Stevioside and Rebaudioside A (14.23 and 8.12, respectively) were accumulated in plants under MS treatment. Obviously, dilution of MS media associated with decreasing in both expression of the intended genes and accumulation of steviol glycosides.

Objective: The FAS/FASL interaction plays a central role in up-regulation of apoptosis in testis. Studies indicated that the FAS-670A/G and FASL-844C/T polymorphisms are associated with the risk of idiopathic azoospermia in different ethnic groups. Therefore, the current study aims to investigate the association between FAS-670A/G and FASL-844C/T polymorphisms with male idiopathic infertility in Western Iran., Study Design: The analysis of FAS-670A/G and FASL-844C/T polymorphisms were carried out using the PCR-RFLP approach, on 102 infertile men and 110 normal fertile men as control group., Results: The results suggested that there were no significant difference in genotypic frequencies of FAS-670A/G polymorphism between infertile and control groups. On the other hand, significant result was observed for the frequency of FASL-844C/T polymorphism in infertile men in comparison to control group (P=0.02). Indeed, men with FASL-844TT and CT genotypes had an increased risk of idiopathic azoospermia in comparison to those with CC genotype (OR=2.02, 95% CI [1.05-3.88, P=0.03] and OR=1.44, 95% CI [0.46-4.49, P=0.53]), respectively., Conclusion: Our findings speculate that the FASL-844C/T polymorphism is associated with the risk of male infertility and this variation can be considered as a genetic risk factor for idiopathic azoospermia among Western Iranian men population. Summing up, these data indicated that the genetic variations in FAS/FASL system have a critical role in spermatogenesis defects and subsequent male infertility., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Exercise-induced muscle damage (EIMD) is accompanied by inflammatory and immune responses. However, due to the repeated bout effect, there will probably be less EIMD. Hence, the purpose was to investigate inflammatory and immune responses over a three-day period of downhill running in active females. Eleven moderately trained healthy females performed three 60-minute bouts of downhill running in -13.5% grade, separated by 24 hours, at a speed eliciting 70-80% of their VO2peak on level grade. Delayed onset muscle soreness (DOMS), range of motion (ROM) and maximum knee isotonic strength (1RM) were measured pre- and two-hour post every bout. Blood variables, including CBC, serum lactate dehydrogenase (LDH), creatine kinase (CK), myoglobin (Mb), IL-10, IL-6 and Monocyte chemoattractant protein-1 (MCP-1) were measured at 1 hour before the first bout and two hours after every bout. Data was analysed by repeated measure ANOVA (P<0.05). Although CK, LDH, Mb, IL-10, IL-6, MCP-1, total leukocyte count, monocytes and neutrophils increased significantly following the first bout, CK, LDH, Mb, IL-10, monocytes and neutrophils were only significantly higher following the third bout compared to the baseline (all P<0.05). Moreover, IL-10 and IL-6 decreased following the second and third bouts compared to the first bout (P<0.05). In comparison with the baseline, lymphocytes decreased after the second bout, DOMS increased following the second and third bouts, 1RM decreased following the first and second bouts (all P<0.05). ROM showed no significant difference. The three-day period of downhill running did not exacerbate EIMD and inflammatory response was partly attenuated.

Leptin is a 16-kDa peptide hormone secreted by adipose tissue that participates in the regulation of energy homeostasis. The aim of this study was to determine the effect of leptin injection on mRNA expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) and comparison of PPAR-γ mRNA expression in rat's adipose and liver tissue. Twenty adult male rats were divided into the following groups: Group 1asa control (n=10) that did not receive any treatment. Group 2as a treatment (n=10) that received leptin (30 µg ⁄ kg BW) intraperitoneally (ip) for two successive days. Blood samples were taken before and one day after second leptin injection for triglyceride (TG), Free Fatty Acid (FFA), HLD-cholesterol, and LDL-cholesterol measurement. Total RNA was extractedfrom the adipose tissue and liver tissues of rats.  Adipose and liver tissue cells' cDNA was synthesized to characterize the expression of PPAR-γ. Gene expression of PPAR-γ mRNA was tested by RT- PCR technique. Results show leptin decreases expression of PPAR-γ on rat. Low levels of PPAR-γ mRNA were detected in adipose and liver tissues of treatment rats in comparison to control group. In treatment group, the level of PPAR-γ mRNA in liver tissue was very lower than the adipose tissue. The levels of HDL and FFA in treatment rats were increased whereas serum levels TG, VLDL and LDL were not changed. It is concluded that leptin signal with suppressing of PPAR-γ mRNA expression in rat's adipose and liver tissues can result in lipolysis instead of lipogenesis.

Human parvovirus B19 (B19) is a small, non-enveloped virus and belongs to Parvoviridae family. B19 persists in many tissues such as thyroid tissue and even thyroid cancer. The main aim of this study was to determine the presence of B19, its association with increased inflammation in thyroid tissue, and thus its possible role in thyroid cancer progression. Studies have shown that virus replication in non-permissive tissue leads to overexpression of non-structural protein and results in upregulation of proinflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha. A total of 36 paraffin-embedded thyroid specimens and serum were collected from patients and 12 samples were used as control. Various methods were employed, including polymerase chain reaction, real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. The results have shown the presence of B19 DNA in 31 of 36 samples (86.11%). Almost in all samples, the levels of non-structural protein 1, nuclear factor kappa B, tumor necrosis factor alpha, and interleukin 6 were simultaneously high. The presence of parvovirus B19 has a significant positive correlation with nuclear factor kappa B, tumor necrosis factor alpha, and interleukin 6 levels. This study suggests that B19 infection may play an important role in tumorigenesis and thyroid cancer development via the inflammatory mechanisms.

Diabetes is known to alter both oxidative and glycolytic pathways in a fiber type-dependent manner. The aim of present study was to investigate the effects of endurance training on muscle NHE1 and NBC1 genes and proteins expression in type 2 diabetic rats. Male wistar rats (n=30), 4 weeks old and 95.7±10.8g, were randomly selected and divided into control, diabetic without training and diabetic with training groups. Diabetes was induced by injection of low dose of streptotozin and feeding with high-fat diet. The Endurance training was performed for 7 weeks that started with relatively low speed and duration of 20 m min-1 for 20 min in the first week and gradually reached to 30 m min-1 for 35min in the last week. NHE1 and NBC1 genes and proteins expression were determined by Real time-PCR and western blotting techniques, respectively, in Soleus as an oxidative and EDL (Extensor digitorum longus) as a glycolytic muscle preparation. NHE1 mRNA and protein expression reduced significantly in EDL and Soleus in the diabetic without training group compared with the control group. However, reduction in the expression of NBC1 gene and protein in the diabetic without training group compared to controls did not significant. Endurance training increased NHE1 and NBC1 genes and proteins expression in both EDL and Soleus in the diabetic training group compared to control groups. In conclusion, endurance training may improve the capacity of pHi regulation in muscles by lactate-independent pathway.

Breast cancer, with a lifelong risk of one in nine, is the most common cancer among women. In Iran, breast cancer is one of the growing and important women's health problems. Several environmental, genetic and epigenetics factors have been suggested to have a role in breast cancer development. Epigenetics alterations are heritable changes in gene expression that occur without causing any change in DNA sequence. DNA methylation as a main epigenetics modification in human cancer is found as a promising biomarker in early detection of breast cancer. Association between epigenetics changes of many gene promoters with the risk of breast cancer has been investigated worldwide. This aberrant methylation may be occur in specific genes related to cell cycle, cell adhesion, apoptosis and DNA repairing mechanisms and results in silencing of these important genes. In this review study, we have gathered all the data until December 2015 about epigenetics modifications among Iranian population with breast cancer.  We searched international web databases such as: PubMed, Scopus, and Persian web databases; IranMedex and Magiran to investigate the association of epigenetics change and incidence of breast cancer among Iranian population. Using "methylation" or "epigenetics" key words and "Iran" as affiliation, all the published data were 31. After arbitrary limitation in search keywords the result have been 20 articles.  Data analysis show that "ER-α" and "E-Cadherin" are most common studied genes in epigenetics modifications. Also, maximum studies were done in Tehran and Tabriz. We thought that more studies will be helpful to reveal the relation of methylation status in candidate genes with the breast cancer risk in Iranian populations.

Periodontal disease is one of the most prevalent inflammatory illnesses and is a main cause of tooth loss in human population. Tumor necrosis factor-α (TNF-α) gene is one of pro-inflammatory cytokines which has important role in pathogenesis of periodontal disease. The main purpose of this study is to determine genotype abundance of TNF-α-1031 gene in both groups of patients and controls, and also investigation of relation of single nucleotide polymorphism (SNP) these genotypes with periodontal disease risk. DNA was extracted from blood tissue of 31 patients and 54 controls. The TNF-α-1031 polymorphism was evaluated by polymerase chain reaction- confronting two-pair primer (PCR-CTPP) method. In the GAP group, the frequencies of TT, TC and CC genotypes were 35.48%, 61.29 and 3.23%, respectively. In controls the frequencies of TT, TC and CC genotypes were 22.22%, 72.22%, and 5.56%, respectively. Results of this study showed that there was no significant association between TNF-α (-1031 T/C promoter) gene polymorphisms and the risk of generalized aggressive periodontitis disease.

Breast cancer is the most common cancer with high morbidity and mortality among women worldwide. Aberrant hypermethylation in promoter regions of the tumor suppressor genes such as PTEN gene is a key event in the progression and development of breast cancer. The aim of the present study was to evaluate an association between PTEN gene methylation status with the risk of breast cancer in an Iranian population. We studied 255 individuals, including 103 patients with breast cancer, 102 first-degree female relatives of patients (mother, sister, or daughter of patients), and 50 healthy individuals as a control group. Genomic DNA was extracted from peripheral blood leukocytes, and the PTEN promoter methylation status was detected using methylation-specific PCR (MSP) method with specific methylated and unmethylated primers. In some samples, direct DNA sequencing was used to confirm the results obtained by the MSP method. The frequency of PTEN-methylated (MM) genotype was 6 % in the healthy control group, 23.3 % in relatives of patients, and 41.7 % in patients (χ (2) = 24.62, p < 0.001). There were significant differences in the frequency of PTEN-methylated genotype between healthy control compared to that in patients (χ (2) = 15.1, p < 0.001) and also compared to that in relatives of patients (χ (2) = 6.9, p = 0.009). In the presence of PTEN MM genotype, there was a 3.1-fold susceptibility to breast cancer compared to the UU genotype (p < 0.001). Also, in the presence of PTEN M allele, the risk of breast cancer was 2.71-fold compared to the presence of U allele (p < 0.001). Our findings indicated increased frequency of hypermethylation of PTEN promoter in the studied patients and their relatives that could be considered as one of the epigenetic factors affecting the risk of breast cancer in Iranians.

All organisms have Deoxyribonucleic acid (DNA) within their cells. DNA is a complex molecule that contains all of the information necessary to build and maintain an organism. DNA extraction is one of the most basic and essential techniques in the study of DNA that allow huge advances in molecular biology, biotechnology and bioinformatics laboratories. Whole blood samples are one of the main sources used to obtain DNA and there are many different protocols available in this issue. In current research, compared four DNA extraction protocols from blood samples; include modified phenol-chloroform protocol, two salting-out and enzyme free method and from commercial kit. The extracted DNAs by these protocols were analyzed according to their time demands, quality and quantity, toxicity and functionality in PCR method. Also the quality and quantity of the extracted DNA were surveyed by gel electrophoresis and Nanodrop spectrophotometry methods. It was observed that there are not significantly differences between these methods about DNA Purity (A260/A280), but the DNA yield (ng DNA/μl) of phenol/chloroform method was higher than other methods. In addition, phenol/chloroform was the most toxic method and it takes more time than other methods. Roche diagnostics GmbH kit was the most expensive among the four methods but the least extraction time was required and it was the safest method.

The Helicobacter pylori is a Gram-negative, microaerophilic bacterium found usually in the stomach and use a number of mechanisms to survive in the stomach lumen. The presence of these bacteria in the stomach can lead to gastritis and reduction in stomach acid production. Acute inflammation can directly damage to the peripheral cells that are responsible for the secretion of acid. The risk of developing gastric carcinoma is associated to heterogeneity of Helicobacter pylori virulence factors. The HopQII is one of the outer membrane proteins involved in bacterial adherence to gastric mucosa and has been suggested to also play a role in the virulence of H. pylori. The purpose of the current study was to investigate the association between different H. pylori virulence hopQII allele and patients with gastroduodenal disorders. For this purpose 58 stomach biopsies of patients with gastric cancer and 100 saliva samples from healthy individuals were collected. Then genomic DNA was purified and PCR for was done for desired genes via specific primers. The H. pylori infections were diagnosed by PCR for GlmM gene. Then frequencies of hopQII+ and hopQII- genotypes was determined in H. pylori infected cases. Statistical analysis showed that there were not significant differences between healthy and diseased ones for genotype hopQII+.

Matrix metalloproteinases (MMPs) are involved in multiple physiological and pathological processes. Variable frequency of the MMPs gene variants might affect the susceptibility to certain diseases. The aim of present study was to investigate the frequency of MMP-7 A-181G and MMP-2 C-735T variants in healthy population of Western Iran with Kurdish ethnic background. Individuals were medical students and staff members of the Medical School of Kermanshah University and blood donors that consisted of 221 females and 94 males. Control subjects were free of general and genetic diseases. Two hundred and eighty available samples including 192 females and 88 males were studied for MMP-2 C-735T polymorphism. Genomic DNA was extracted from peripheral blood leukocytes. The MMP-7 A-181G and MMP-2 C-735T polymorphisms were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The prevalence of MMP-7 G allele was 40% in studied individuals. The overall frequency of MMP-2 -735T allele was 15%. There was a higher frequency of MMP-2 T allele in females (16.9%) compared to males (10.8%, p=0.059). There were 30 (13.6%) women and 8 men (8.5%) with concomitant presence of MMP-7 AG and MMP-2 CT genotypes. All nine (4.1%) individuals with combined presence of MMP-7 GG and MMP-2 CT genotypes were women. The present study reports the frequency of two MMPs gene polymorphisms in healthy population of Western Iran. Our findings might be useful in evaluating the risk of MMPs in certain diseases. Also, our study suggests genetic admixture and similarities between our population with some Asian and European populations.

Interactions between efavirenz (EFZ) with calf thymus DNA (CT-DNA) were investigated in vitro under stimulated physiological conditions using multispectroscopic techniques, cyclic voltammetry viscosity measurement, and gel electrophoresis. Methylene blue and acridine orange dyes were used as spectral probes by fluorescence spectroscopy. Hypochromicity was observed in ultra-violet (UV) absorption band of EFZ. Considerable fluorescence enhancement of EFZ was observed in the presence of increasing amounts of DNA solution and the binding constants (Kf ) and corresponding numbers of binding sites (n) were calculated at different temperatures. Thermodynamic parameters including enthalpy change (ΔH) and entropy change (ΔS) were calculated to be -304.78 kJ mol(-1) and -924.52 J mol(-1)  K(-1) according to the van 't Hoff equation, which indicated that reaction is predominantly enthalpically driven. In addition, UV/vis absorption titration of DNA bases confirmed that EFZ interacted with guanine and cytosine preferentially. Gel electrophoresis of DNA with EFZ demonstrated that EFZ also has the ability to cleave supercoiled plasmid DNA. Circular dichroism study showed stabilization of the right-handed B form of CT-DNA. All results suggest that EFZ interacts with CT-DNA via an intercalative mode of binding., (Copyright © 2015 John Wiley & Sons, Ltd.)

The Helicobacter pylori use a number of mechanisms to survive in the stomach lumen and can lead to gastritis and reduction in stomach acid secretion. It has been found that the risk of developing gastric carcinoma is associated to heterogeneity of H. pylori virulence factors such as HopQ. The HopQ is one of the outer membrane proteins involved in bacterial adherence to gastric mucosa and has been suggested to also main role in the virulence of H. pylori. The purpose of the current study was to investigate the association between different H. pylori virulence hopQI (types I) genotyping and patients with gastroduodenal disorders. For this purpose 58 stomach biopsies of the patients with gastric cancer and 100 saliva samples from healthy and H. pylori infected individuals were collected and studied. Then genomic DNA was purified and PCR was done for desired gene via specific primers. The H. pylori infections were diagnosed using PCR for GlmM gene. Then frequencies of hopQI+ and hopQI- genotypes were determined in H. pylori infected cases. Statistical analysis showed that there were not significant differences between healthy and diseased ones for genotypes hopQI+ and hopQI-. Then the hopQI+ cannot be as a risk factor genotype for gastric cancer.

Background: Gastric cancer (GC) is the second leading cause of cancer-related death worldwide. Several environmental, genetic and epigenetic factors have been suggested to have a role in GC development. Epigenetic mechanisms like histone changes and promoter hyper-methylation are now being increasingly studied. Associations between methylation of many gene promoters with the risk of gastric cancer have been investigated worldwide. Such aberrant methylation may result in silencing of specific genes related to cell cycling, cell adhesion, apoptosis and DNA repair. Thus this molecular mechanism might have a key role in proliferation and migration of cancerous cells., Materials and Methods: In this review article we included studies conducted on DNA methylation and gastric cancer in Iranian populations. Using Science direct, Pubmed/PMC, Springer, Wiley online library and SciELO databases, all published data until 31 January 2016 were gathered. We also searched Science direct data base for similar investigations around the world to make a comparison between Iran and other countries., Results: By searching these databases, we found that the association between methylation of seven gene promoters and gastric cancer had been studied in Iran until 31 January 2016. These genes were p16, hLMH1, E-cadherin, CTLA4, THRβ, mir9 and APC. Searching in science direct database also showed that 92 articles had been published around the world till January 2016. Our investigation revealed that despite the importance of GC and its high prevalence in Iran, the methylation status of only a few gene promoters has been studied so far. More studies with higher sample numbers are needed to reveal the relation of methylation status of gene promoters to gastric cancer in Iran., Conclusions: Further studies will be helpful in identifying associations of DNA methylation in candidate genes with gastric cancer risk in Iranian populations.

Generalized aggressive periodontitis (GAP) is a subtype of periodontal diseases that characterized by rapid destruction of periodontal supporting tissues. The MnSOD Val-9Ala mutation of manganese superoxide dismutase gene (MnSOD Val-9Ala) and its correlation with periodontal diseases has been studied in different populations. The purpose of this study was to investigate the possible association of MnSODVal-9Ala polymorphism with periodontitis disease in sample of GAP patients in Iran for the first time. Following a GAP examination, 50 GAP patients and 100 healthy individuals were recruited. Genomic DNA was extracted from peripheral blood leukocytes and the MnSODVal-9Ala polymorphismwas detected using PCR-RFLP method. The frequency of Ala/Ala, Ala/Val and Val/Val genotypes in healthy individuals were 25, 66 and 9%, respectively. In periodontitis patients, frequencies were as Ala/Ala (12%), Ala/Val (50%) and Val/Val (38%) genotypes. There was a significant positive association between distribution of MnSOD Val-9Ala genotypes and the risk of periodontitis disease (p<0.05). Our results indicated that MnSOD Val-9Ala gene polymorphism has a positive association with the risk of periodontitis disease.

Background: Matrix metalloproteinases (MMPs) are upregulated in tumors. The MMP-7 A-181G polymorphism is associated with increased expression of the MMP-7 gene. Aim of the present study was to investigate the association between the MMP-7 A-181G polymorphism and susceptibility to breast cancer., Patients and Methods: The MMP-7 A-181G variants were studied in a cohort of 251 subjects consisting of 100 breast cancer patients and 151 healthy controls; all were from Western Iran. The MMP-7 A-181G genotypes were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis., Results: The frequencies of the MMP-7 AA, AG, and GG genotypes in healthy individuals were 34.4, 50.4, and 15.2%, respectively. In breast cancer patients, the frequencies of AA (34%), AG (52%), and GG (14%) genotypes (p = 0.95) were similar to those in the controls. There was a trend toward an increased frequency of the combined genotype of MMP-7 AG+GG in patients with lymph node metastasis (70.4%) compared to those without metastasis (66.7%). Also, in patients with invasive lobular carcinoma, the frequency of the MMP-7 AG+GG genotype tended to be higher (71.4%) compared to that in patients with invasive ductal carcinoma (66.2%) (p = 0.78)., Conclusion: Our findings indicate that the MMP-7 A-181G polymorphism may not be correlated with susceptibility to breast cancer in our population.

Advances in cell-replacement strategies for diabetes have focused on renewable sources of glucose-responsive, insulin-producing cells (IPCs). One of the most proper alternatives is multipotent skin-derived precursors cells (SKPs), which can be differentiated into IPCs. In this study, we reported the isolation and expansion of human skin-derived precursors (hSKPs) followed by their differentiation into IPCs in vitro, through exposure to suitable differentiation factors. The gene expression of endocrine β cell markers was analyzed by reverse transcriptase-polymerase chain reaction. In addition, insulin production was examined immunocytochemically, and insulin and C-peptide secretion were examined using enzyme-linked immunosorbent assay. Dithizone-stained cellular clusters were observed after approximately 20 d. The clusters were found to be immunoreactive to insulin and expressed multiple genes related to pancreatic β cell development and function: insulin, Pdx-1, Islet-1, NeuroD, Glut-2, Pax-4, Ngn-3, and Nkx2.2, but not to other pancreas-specific hormones such as glucagon and somatostatin. Cellular clusters were also able to secrete detectable amounts of insulin and C-peptide in a glucose dose-dependent manner. These findings suggest that human SKPs can differentiate into functional IPCs. This may offer a safer cell source for future stem cell-based therapies.

Context: Among the essential amino acids, phenylalanine, tryptophan, and tyrosine are aromatic amino acids which are synthesized by the shikimate pathway in plants and bacteria. Herbicide glyphosate can inhibit the biosynthesis of these amino acids. So, identification of the gene tolerant to glyphosate is very important. It has been shown that the common reed or Phragmites australis Cav. (Poaceae) is relatively tolerant to glyphosate., Objective: The aim of the current research is identification, cloning, sequencing, and registering of partial aro A gene of the common reed P. australis., Materials and Methods: The partial aro A gene of common reed (P. australis) was cloned in Escherichia coli and the amino acid sequence was identified/determined for the first time., Results: This is the first report for isolation, cloning, and sequencing of a part of aro A gene from the common reed. A 670 bp fragment including two introns (86 bp and 289 bp) was obtained. The open reading frame (ORF) region in part of gene was encoded for 98 amino acids. Alignment showed high similarity among this region with Zea mays (L.) (Poaceae) (94.6%), Eleusine indica L. Gaertn (Poaceae) (94.2%), and Zoysia japonica Steud. (Poaceae) (94.2%). The alignment of amino acid sequence of the investigated part of the gene showed a homology with aro A from several other plants. This conserved region forms the enzyme active site., Conclusion: The alignment results of nucleotide and amino acid residues with related sequences showed that there are some differences among them. The relative glyphosate tolerance in the common reed may be related to these differences.