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Introduction: Breast cancer is a severe life-threatening condition in which many women are involved yearly. One factor that has recently been noticed and investigated as a diagnostic predictor of this type of cancer is the number of tumor buds and the relation of this factor with a patient's survival rate. Materials and methods: This study includes 150 female patients over 18 years old with a mean age of 53.99 ± 12.56 years old with breast cancer, which was diagnosed at various medical centers, including Rouhani Hospital itself, and referred to Rouhani Hospital Medical Center, Babol, Iran. The number of intratumoral and peritumoral buds in patients' microscopic slides were archived and evaluated along with tumor microenvironment on hematoxylin and eosin (H&E) slides and compared to other clinicopathological findings. This article precisely investigated the relationship between the number of intratumoral and peritumoral buds with patients' 5-year survival rate. Also, the relationship between age, tumor stage, grade, size, the number of lymph nodes involved, and the presence of metastasis with the number of intratumoral and peritumoral buds was studied. Results and discussion: The result showed a significant statistical association between the number of intratumoral and peritumoral buds with tumor size, tumor stage, presence of metastasis, the number of lymph nodes involved, and 5-year survival rate. On the other hand, there is not a significant statistical association between the number of intratumoral and peritumoral buds with age and tumor grade. Conclusion: Our investigation revealed a significant statistical relationship between the number of tumor buds and patients' survival rate. So, this factor should be considered significant to help those patients increase their survival ratio. [ABSTRACT FROM AUTHOR]

Teucrium persicum Boiss. an Iranian endemic plant is used in Iranian traditional medicine. E-cadherin transmembrane protein participates in adherens junctions and is the main partner for β-catenin protein. The GC-MS analysis was used to detect the chemical constituents of the methanolic extract. Its effects on the transcription of the E-cadherin encoding gene, cellular levels, and localization of E-cadherin protein in PC-3 cells were investigated. About 70 chemical constituents were identified. Indirect immunofluorescence microscopy and western blotting results revealed the restoration of E-cadherin protein at cell adhesion contact sites in cells treated with T. persicum extract. Gene expression studies revealed that the extract increased the transcription of the E-cadherin encoding gene in PC-3 cells. These results suggest that T. persicum extract may contain potent compounds that provide further support for the anticancer properties of T. persicum. Surely, detailed molecular investigations are needed to find the mechanism(s) behind these effects. [ABSTRACT FROM AUTHOR]

Background: Three main cell signaling pathways including the endoplasmic reticulum stress (ERS) response, autophagy, and apoptosis play critical roles in both cell survival and death. They were found to crosstalk with one another during tumorigenesis and cancer progression. This study aimed to investigate the expression of the spliced form of X-box binding protein 1 (XBP1s), p62, and caspase-3, as the essential biomarkers of ERS, autophagy, and apoptosis in patients with colorectal cancer (CRC), as well as the correlation between their expression and clinicopathological data. Methods: This retrospective study was conducted on formalinfixed paraffin-embedded (FFPE) blocks, which were collected from patients and their tumor margins, from the tumor bank of Imam Khomeini Hospital (Tehran, Iran) from 2017 to 2019. Tissue microarray (TMA) was used to measure the XBP1s, p62, and caspase-3 biomarkers. Data were analyzed using SPSS software version 20, and P≤0.05 was considered statistically significant. Results: Evaluating the total of 91 patients, a significant relationship was found between XBP1s expression and TNM stage (P=0.003), primary tumor (pT) (P=0.054), and the degree of differentiation (P=0.006); and between caspase-3 with pT (P=0.004), and lymphovascular invasion (P=0.02). However, no significant correlation was found between p62 and clinicopathological data. Furthermore, a positive relationship between XBP1s and p62 was confirmed (correlation coefficient: 22.2% and P=0.05). Conclusion: Our findings indicated that XBP1s could be considered as a target for therapy in personalized medicine. [ABSTRACT FROM AUTHOR]

Background and Aim: The present study investigates the probiotic, antibacterial, technological, and safety properties of lactic acid bacteria (LAB) isolated from traditional yogurt in Chaharmahal and Bakhtiari, Iran. Materials and Methods: After serial dilution, culture was carried out in MRS culture media with 19 distinct rod bacteria. The gram-positive and catalase-negative LAB isolates were identified using Gram Staining, catalase, H2S, Indole, Motility and Oxidase biochemical assays, carbohydrate fermentation patterns, and 16S rDNA analysis. Then their probiotic potential (resistance to stomach acid and bile salt, hydrophobicity, auto-aggregation and co-aggregation, adherence capacity, and safety analysis) was evaluated. Results: It was found that LAB strains belonged to Seven species belonging to five genera, including L. plantarum, L. brevis, L. rhamnosus, L. paracasei, L. casei, L. fermentum, and L. jensenii. After three hours of incubation at pH 2, strains lost 3–6 log units with L. rhamnosus strain IDC-D21 and L. paracasei strain DBR-D20, showing the most resilience to low pH and simulated GIT juices. The L. rhamnosus strain IDC-D21 and L. plantarum strain LRO-7 strains had the highest and lowest hydrophobicity (34.8 and 25.6%), respectively. Besides, the L. rhamnosus strain IDC-D21 had the highest degree of auto-aggregation (17.29%), followed by the L. paracasei strain DBR-D20 (14.28%). Also, the L. rhamnosus strain IDC-D21 showed the highest co-aggregation degree (19.07%). Conclusion: According to the research findings, L. rhamnosus strain IDC-D21 is recommended for application as a coculture in the dairy industry. Indeed, it has the best probiotic and technical features. [ABSTRACT FROM AUTHOR]

Simple Summary: Comprehensive studies on non-hematologic tumors in patients with inborn errors of immunity are scarce. Using a well-established registry of patients with long-term follow-up, molecular defects associated with these cancers were reported for the first time among these patients. Using the retrospective data available of this national registry of patients with primary immune defects, we clarified that almost all cancer hallmarks are involved in the development of non-hematologic cancers in patients presenting with non-hematologic cancers. Inborn errors of immunity (IEI) are a heterogeneous group of inherited disorders, and almost 500 genes associated with these disorders have been identified. Defects in IEI genes lead to diverse clinical manifestations including increased susceptibility to recurrent or prolonged infections, immune dysregulation phenotypes (such as severe atopy, allergy, autoimmunity, and uncontrolled inflammation, lymphoproliferation), as well as predisposition to malignancies. Although the majority of IEI patients present hematologic cancers, the characteristics of other types of cancers are not well described in these groups of patients. By investigating 5384 IEI patients registered in the Iranian national registry the clinical and immunologic phenotypes of patients with non-hematologic cancers were compared with other malignant and non-malignant patients. Solid tumors were reported <20% of malignant IEI patients (n = 27/144 patients) and appeared to be very heterogeneous by type and localization as well as molecular defects (mainly due to DNA repair defect resulted from ATM deficiency). The correlation between the type of malignancy and survival status was remarkable as patients with non-hematologic cancers survive higher than IEI patients with hematologic cancers. Our findings showed that different types of malignancy could be associated with specific entities of IEI. Therefore, the education of physicians about the risk of malignancies in IEI is required for personalized treatment and appropriate management of patients. [ABSTRACT FROM AUTHOR]

Early diagnosis of primary immunodeficiencies is crucial for timely treatment and preventing unwanted complications. Next-generation sequencing (NGS) and detailed clinical and immunological evaluation can help early detect such disorders. This study aimed to confirm the diagnosis of two cases of autosomal recessive hyper-immunoglobulin E (IgE) syndrome (AR-HIES), presenting with irreversible eye involvement. Two unrelated patients with suspected AR-HIES were referred to the Immunology, Asthma and Allergy Research Institute (IAARI), Tehran, Iran. Immunological screening tests were performed for AR-HIES, which showed elevated serum IgE levels, eosinophilia, and low T-lymphocyte responses. NGS was performed, and the results were confirmed by Sanger sequencing. Sequence analysis showed a mutation in intron 17 of the dedicator of cytokinesis 8 (DOCK8) gene in the first patient, and a homozygous three base-pair deletion in exon 45 of DOCK8 in the second patient. This is the first time such mutations are reported and these variants are predicted to be damaging. Both patients suffered from persistent viral infections along with cytomegalovirus (CMV) retinitis. Suspicion of these two novel DOCK8 mutations can benefit patients presenting with recalcitrant ophthalmic viral involvements and relevant immunological test results. This would lead to earlier referrals for immunologic and genetic confirmation and thus, a more timely intervention with hematopoietic stem cell transplantation (HSCT). [ABSTRACT FROM AUTHOR]

One of the most common and deadly brain tumors is Glioblastoma multiforme (GBM). Due to recent advances in angiogenesis and its related key factors, this process as a hallmark in glioblastoma has attracted more consideration from the research community. Temozolomide (TMZ) as the first-line treatment used to treat GBM but, resistance to TMZ limits its effectiveness and the need for better treatments is still felt. Therefore, we aimed to examine the Synergistic effects of Gefitinib (GFI) in combination with Temozolomide on VEGF and MMPs in glioma cell line (U87MG). Our results displayed that GFI could induce cytotoxic effects in U87MG with IC50 values of 11 μM. U87MG cells produced large amounts of VEGF without any stimuli, and the results showed that GFI in combination with TMZ caused a significant decrease in VEGF production in these cells. In this study, we demonstrated that after treating with TMZ and GFI, there was more decrease in the levels of MMP 2 and 9 secretions in cells than treatment with GFI and TMZ doses alone. This study indicates synergistic effects of GFI plus TMZ against glioma are mediated by the potentiated anti-angiogenesis. Therefore, it can be considered as a promising plan for future studies. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that myeloid cell leukemia-1 (Mcl-1) is the target gene for microRNA -101 (miRNA-101), and decreased levels of miRNA-101 are associated with elevated levels of Mcl-1 and lung cancer survival. The objective of the present study was to investigate the effect of miRNA-101 on the sensitivity of A549 lung cancer cells to etoposide. Methods: The study was conducted during 2018 and 2019 at Arak University of Medical Sciences, Arak, Iran. The effect of miRNA- 101 on Mcl-1 expression was assessed using reverse transcriptionquantitative polymerase chain reaction 3-(4, 5-Dimethylthiazol- 2-yl)-2, 5-diphenyltetrazolium bromide (MTT), and trypan blue exclusion assays were performed to determine the effect of treatments on cell survival and proliferation, respectively. The interaction between miRNA-101 and etoposide was evaluated using the combination index analysis of Chou-Talalay. Apoptosis was quantified using ELISA cell death assay. ANOVA and Bonferroni's tests were used to determine statistical differences between the groups (P<0.05). GraphPad Prism software (version 6.01) was used for data analysis. Results: The results showed that miRNA-101 clearly inhibited the expression of Mcl-1 and reduced the growth of A549 cells, relative to blank control and negative control miRNA (P<0.05). Transfection of miRNA-101 synergistically enhanced the sensitivity of the A549 cells to etoposide. Apoptosis assay data also showed that miRNA-101 triggered apoptosis and augmented the etoposide-mediated apoptosis. Conclusion: Up-regulation of miRNA-101 inhibited cell survival and proliferation, and sensitized A549 cells to etoposide by suppressing Mcl-1 expression. miRNA-101 replacement therapy can be considered as an effective therapeutic strategy in non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

Background: Targeted drug delivery is a novel method to specifically deliver anticancer therapeutics to tumor sites. Gonadotropin-releasing hormone (GnRH) is a decapeptide, and its target binding property has attracted attention as a means of targeted drug delivery. Human pancreatic ribonuclease 1 (hpRNase1) has been shown to exert anticancer properties, when fused to a targeting moiety. The goal of the present study was to add a GnRH targeting peptide to the N-terminus of hpRNase1 to specifically target GnRH receptor (GnRH-R) expressing cells. Methods: This in vitro study was conducted at Shiraz Institute for Cancer Research (Shiraz, Iran) in 2019. The coding sequence of GnRH and hpRNase1 were fused, and the chimeric protein together with non-fused hpRNase1 were produced in E. coli (BL21). The recombinant proteins were purified, and their biological activity was evaluated using MTT and apoptosis assays. Non-parametric Kruskal--Wallis tests with Dunn's post hoc tests were performed to determine the significant differences between the study groups. Results: GnRH-hpRNase1 chimeric protein specifically inhibited the proliferation of PC-3 (P=0.021), LNCaP (P=0.034), and AD-Gn (P=0.041) cells, while the growth of negative cells (AD-293) was not significantly affected (P=0.081). GnRH-hpRNase1 decreased the IC50 values more than non-fused hpRNase1, by approximately 26.5-fold (P=0.036) for PC-3 cells, and exerted its growth inhibitory effects through apoptosis induction. Conclusion: Fusion of GnRH to hpRNase1 structure produced an enzyme, which could specifically target tumor cells. This approach can be used to eliminate tumors that harbor GnRH-R. [ABSTRACT FROM AUTHOR]

Grapefruit mint (Mentha suaveolens × piperita) is a hybrid, perennial, and aromatic plant widely cultivated all over the world and used in the food, cosmetics, and pharmaceutical industries mostly for its valuable essential oil. Herein, we evaluated the anticancer activity of the grapefruit mint essential oil, cultivated in Iran. For the chemical composition analysis of essential oil, GC–MS was used. MTT assay was utilized for assessing the cytotoxic activity of the essential oil. The type of cell death was determined by annexin V/PI staining. Essential oil effect on the expression of maternally expressed gene 3 (MEG3), a regulatory lncRNA involved in cell growth, proliferation, and metastasis, was studied using qRT-PCR. Linalool (43.9%) and linalool acetate (40.1%) were identified as the dominant compounds of essential oil. Compared with MCF-7, the MDA-MB-231 cells were more sensitive to essential oil (IC 50 = 7.6 μg/ml in MCF-7 and 5.9 μg/ml in MDA-MB-231 after 48 h). Essential oil induced cell death by apoptosis. Wound healing scratch assay confirmed the anti-invasive effect of essential oil. In addition, essential oil upregulated the tumor suppressor MEG3 in breast cancer cells. These results provide new insights into grapefruit mint essential oil potential application as an anticancer adjuvant in combination treatments for breast cancer patients. [Display omitted] [ABSTRACT FROM AUTHOR]

Killer‐cell immunoglobulin‐like receptors (KIRs) are important because of their key roles in NK cell development and function. Some KIR genes have been associated with the incidence of haematological malignancies. This study was designed to determine whether the inheritance of specific KIR genes is associated with susceptibility to acute myelogenous leukaemia (AML) in Persians living in south‐western Iran. KIR genes and KIR2DS4 variants were typed by polymerase chain reaction–sequence‐specific primer (PCR‐SSP) in 167 patients with AML and 169 healthy controls. Our results showed 10% of patients—mostly females—were classified as M3. Flt3 mutations were detected in 26% of patients, most of whom had internal tandem duplication (ITD). The frequency of activating KIRs (aKIRs)—mainly KIR3DS1—was higher in patients, whereas inhibitory KIRs (iKIRs)—particularly KIR3DL1 and KIR2DL1—were more common among controls. The incidence of the KIR2DS4fl allele was higher among patients with non‐M3 AML than controls. We also found a higher frequency of 4 or more iKIR genes in the controls and a higher frequency of 4 or more aKIR genes in the patients. Individuals with more iKIR than aKIR belonged predominantly to the control group. Individuals with the telomeric AA genotype who had inherited the KIR2DS4fl allele were more frequent in the patient group. According to our results, increased frequency of aKIRs in patients with AML may lead to the hyperactivation of NK cells against malignant cells with reduced or lack of HLA class I molecules followed by NK cell exhaustion which allow malignant cells to progress. [ABSTRACT FROM AUTHOR]

Background: Testicular cell conditioned medium (TCCM) has been shown to induce female germ cell development in vitro from embryonic stem cells (ESCs). Testicular cells (TCs) secrete a variety of growth factors such as growth differentiation factor-9 (GDF-9), bone morphogenetic protein 4 (BMP-4), stem cell factor (SCF), leukemia inhibitory factor (LIF), and other, that could improve oocyte maturation. Here we have investigated the effect of human TCCM (hTCCM) on in vitro maturation (IVM) and morphology of mouse oocytes. Materials and Methods: In this experimental study, 360 germinal vesicle (GV) oocytes were obtained from NMRI mice, aged 4-6 weeks that had received 5 IU pregnant mare's serum gonadotropin (PMSG) 48 hours before. GV oocytes were subjected to IVM. 120 GV oocytes were cultured in each medium; hTCCM as the test group, DMEM + 20%FBS as the control group and Ham's F10 + HFF medium as the sham group. The rates of the IVM and perivitelline space (PVS) changes were recorded at 8, 16 and 24 hours after culture. The metaphase II (MII) oocytes were subjected for in vitro fertilization (IVF) and the fertilization rate was evaluated after 1, 2, and 3 days. Results: There was a significant difference between the maturation rates in hTCCM (31.67% MII) and the control [0% MII, P<0.05, (7.5% MI, 52.5% deg. and 40%GV)] groups but there was not a significant difference between the maturation rates in hTCCM and the sham group (53.33% MII, P>0.05). IVF success rate for MII oocytes obtained from IVM in the hTCCM group was 28.94% (n=11). Our data showed that hTCCM is an effective medium for GV oocyte growth and maturation compared to the control medium. Conclusion: Our findings show that TCCM supports oocyte IVM in mice and affect oocyte morphology. [ABSTRACT FROM AUTHOR]

Background: Blood malignancies are among the leading causes of cancer related deaths in the world. Different environmental and genetic risk factors are involved in progression of blood malignancies. It has been shown that the lifestyle changes have affected the epidemiological patterns of these malignancies. Hematologic cancers are the 5th common cancer among Iranian population. It has been observed that there is a rising trend of blood malignancies incidences during the recent decades. Therefore, it is required to design novel diagnostic methods for the early detection of such malignancies in this population. Main body: In present review we have summarized all of the significant genes which have been reported among Iranian patients with blood malignancies. The reported genes were categorized based on their cell and molecular functions to clarify the molecular biology and genetics of blood malignancies among Iranian patients. Conclusion: It was observed that the epigenetic and immune response factors were the most frequent molecular processes associated with progression of blood malignancies among Iranian population. This review paves the way of introducing a population based panel of genetic markers for the early detection of blood malignancies in this population. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are innate lymphocytes that eliminate infected and transformed cells. They discriminate healthy from diseased tissue through killer cell Ig-like receptor (KIR) recognition of HLA class I ligands. Directly impacting NK cell function, KIR polymorphism associates with infection control and multiple autoimmune and pregnancy syndromes. Here we analyze KIR diversity of 241 individuals from five groups of Iranians. These five populations represent Baloch, Kurd, and Lur, together comprising 15% of the ethnically diverse Iranian population. We identified 159 KIR alleles, including 11 not previously characterized. We also identified 170 centromeric and 94 telomeric haplotypes, and 15 different KIR haplotypes carrying either a deletion or duplication encompassing one or more complete KIR genes. As expected, comparing our data with those representing major worldwide populations revealed the greatest similarity between Iranians and Europeans. Despite this similarity we observed higher frequencies of KIR3DL1 * 001 in Iran than any other population, and the highest frequency of HLA-B*51, a Bw4-containing allotype that acts as a strong educator of KIR3DL1 * 001 + NK cells. Compared to Europeans, the Iranians we studied also have a reduced frequency of 3DL1 * 004 , which encodes an allotype that is not expressed at the NK cell surface. Concurrent with the resulting high frequency of strong viable interactions between inhibitory KIR and polymorphic HLA class I, the majority of KIR-A haplotypes characterized do not express a functional activating receptor. By contrast, the most frequent KIR-B haplotype in Iran expresses only one functional inhibitory KIR and the maximum number of activating KIR. This first complete, high-resolution, characterization of the KIR locus of Iranians will form a valuable reference for future clinical and population studies. [ABSTRACT FROM AUTHOR]

Background: Sulfur mustard (SM), also known as mustard gas, was first widely used in the Iraq–Iran. After SM exposure, the most prominent clinical signs are the development of extensive non-healing skin wounds and pulmonary signs, persisting over long time. Since the most frequent complications in SM-intoxicated patients are respiratory and dermatologic lesions, and with respect to the important role of endothelial progenitor cells (EPCs) in the pathophysiology of these lesion, we conducted this study to recognize the potential effects of SM on biological features of EPCs in patients exposed with this gas. Methods: In this study, 30 patients with the history of SM exposure during the Iran–Iraq war (1984–1988), 27 patients with pulmonary signs with no history of SM exposure and 20 healthy participants were included. Cell population and function of EPCs were assessed 4 years post-exposure. For this purpose, circulating EPCs (cEPCs) were harvested and cultivated, then the biological features of these cells, including migratory, proliferative, and tubulogenic activities were analyzed. We also measured serum antioxidants levels and mRNA levels of some proangiogenic factors in EPCs from SM-intoxicated patients. Results: Our results showed lesser number of cEPCs in patients exposed with SM, which was associated with decreased proliferative, migratory, and tubulogenic activity of these cells. Also, we found the lesser serum activity of SOD, GPX and MDA in the SM group than in the healthy control group. Conclusions: SM exposure resulted in decreased proliferation and migration of EPCs, which was associated with decreased tubule formation and angiogenic factors. [ABSTRACT FROM AUTHOR]

Background and Aim: A variety of bacteria like Staphylococcus aureus utilize quorum sensing to perform their important activities such as biofilm formation and production of virulence factors. Interfering with the bacterial QS will disable the bacteria to perform above-mentioned vital activities. The principal aim of the study was to evaluate the effects of five plant extracts against bacterial Quorum sensing of Staphylococcus aureus. Materials and Methods: Thirteen strains of Staphylococcus aureus were isolated from patients with dental implant infection and identified. The plant species were collected from vicinity gardens of Fars Province and extracted using 96% ethanol. The anti-QS and antimicrobial susceptibility methods were then carried out to evaluate their bactericidal and QS properties with the use of Agrobacterium tumefaciens NTL/PZLR4. Furthermore, the biofilm production of the isolates was evaluated by microtiter plate (MTP) assay. Ethical Considerations: This study with research ethics codes 01-16-1-1959 and 73/118248 has been approved by research ethics committee at Islamic Azad University, Jahrom and research sciences branch, respectively. Findings: The results of the study disclosed that the extract of raspberry blossom possesses significantly (p<0.05) anti-QS property (>21 mm). The anti-QS activity was proved by creating clear halo sides of the wells formed by Agrobacterium tumefaciens NTL/PZLR4. Moreover, the extracts of tarragon, wheat flower, flixweed and basil showed antimicrobial properties. Conclusion: According to the anti-biofilm and anti-QS properties of raspberry blossom extract against the isolates of Staphylococcus aureus, it could be considered as a mouthwash against dental bacterial infection with the identification of active compounds in the raspberry. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma multiform (GBM) is the most common and most malignant of the glial tumors that begins primarily in brain tissue. Genetic background could be considered as an important predisposing factor in GBM. Autocrine motility factor receptor (AMFR) is a cytokine receptor that participates in a lot of physiologic and pathologic processes like: Cellular motility and metastasis. So, it seems that this protein has an essential role in pathophysiology of several cancers and could be a potential diagnostic and or therapeutic target in GBM. The aim of this study is to investigate the association of AMFR (rs2440472, rs373191257) gene polymorphism and GBM in a representative Iranian population. Materials and Methods: This study includes 81 cases of GBM and 117 control subjects. After DNA extraction, polymerase chain reaction - high resolution melting reaction was performed. For each single nucleotide polymorphisms, 12 samples were selected for sequencing. Data was analyzed using Chi-square test and Logistic regression. Results: For rs2440472, frequency of GG genotype in the case group was increased compared to the control group (51.9% vs. 34.2% respectively, P = 0.013). After adjusting for sex and age by logistic regression our results were the same (P = 0.017, odds ratio = 2.056). Allelic frequencies for rs2440472 among cases and controls were not significantly different (P = 0.058). For rs373191257, genotypic and allelic frequencies were not significantly different between two groups. Conclusion: Our results showed the possible association between the AMFR rs2440472 gene polymorphism with susceptibility to GBM. [ABSTRACT FROM AUTHOR]

Background and Aims: Lactobacillus salivarius is a well-known probiotic bacterium, which is commonly isolated from gastro-intestinal tract of human and animals. The objectives of the present study were isolation, molecular detection and antimicrobial characterization of L. salivarius from buffalo’s raw milk. Materials and Methods: A total number of 20 buffalo milk samples were collected aseptically from traditional buffalo farms in Urmia city, Iran. Milk samples were cultured and incubated on MRS agar, then suspected colonies were primarily determined according to their appearance and biochemical characteristics. Bacteria species were confirmed by polymerase chain reaction accompanied by restriction fragment length polymorphism (PCR-RFLP) and nucleotide sequencing of 16s rRNA gene. Antimicrobial activity of L. salivarius against pathogenic bacteria including Listeria monocytogenesis, Escherichia coli, Salmonella typhimurium, and Staphylococcus aureus was examined using agar-spot and agar-disk diffusion methods. Cell surface hydrophobicity of L. salivarius was also investigated according to microbial adhesion to xylene and toluene hydrocarbons. Results: From 60 suspected colonies which were selected according to phenotypic characteristics, 23 colonies were confirmed as lactic acid bacteria based on the molecular identification. Only one isolate belonged to L. salivarius. The antimicrobial activity results showed a significant growth inhibitory effect of L. salivarius on pathogenic bacteria comparing to standard bacteria. L. salivarius had the most inhibitory effect on S. aureus while it had the least inhibitory against S. typhimurium. The hydrophobicity of L. salivarius to xylene and toluene were 55.3% and 55.6% respectively. Conclusions: Based on the results, the frequency of the Lactobacillus genus s was very low in buffalo milk. In addition, isolated L. salivarius had strong antimicrobial activity against pathogenic bacteria. [ABSTRACT FROM AUTHOR]

Although free-living ciliated protists (Ciliophora) commonly inhabit aquatic and terrestrial biotopes of mild to moderate salinity (PSS-practical salinity scale S = 10–150), very few have adapted to life at more extreme salinities (>150 to saturation). Such extreme halophiles or halotrophs are of interest from the standpoints of evolution, cell physiology, ecology, and even astrobiology. In this work, we present the morphology, 18S rRNA gene sequence, and phylogenetic analysis of a novel spathidiid ciliate (Ciliophora, Litosatomatea) that thrives in saturated brines of Maharloo Lake, Iran. Based on its unique combination of morphologic features, its molecular characterization, and its unusual ecology, it is assigned to a newly erected monotypic genus incertae sedis in order Spathidiida. The new species differs from other spathidiids by: a cell with a very short acutely pointed tail, the absence of a circumoral kinety with, instead, inclined, interrupted circumoral kinetofragments at the anterior end of somatic kineties and brush rows abutting the oral bulge, the absence of a contractile vacuole, a heteromorphic dorsal brush comprising five or six rows, and an extreme (at or near saturation) hypersaline habitat. We briefly discuss the persistent uncertainties regarding the phylogenetic relationships within the order Spathidiida. [ABSTRACT FROM AUTHOR]

Background: Examinations on blood samples and gingival crevicular fluid of subjects with chronic periodontitis showed that smoking increased production of cytokines. Objective: To evaluate the expression of immune markers on mononuclear inflammatory cell infiltrate at periodontitis and healthy tissue among smoking and non-smoking subjects. Methods: This case-control study was performed on 41 patients who referred to a clinic of periodontology at a Mashhad dental school in Iran in 2016. The participants were all of Iranian Khorasanian ethnicity with age range of 35-65 years. Gingival biopsies were obtained during routine periodontal flap procedure. Immunohistochemistry using markers of CD20, CD3, CD68, and CD45RO was carried out. Data was analyzed by SPSS version 15, using one-way ANOVA and Tukey HSD test. Results: Nonsmoker subjects showed significantly greater numbers of CD20+, CD68+, CD3+ cells compared to smoker subjects, both at healthy and periodontitis tissue biopsies (p<0.00), whereas there was no significant difference in terms of CD45RO (p=0.120). Conclusion: Cigarette smoking, results in infiltrative mononuclear chronic inflammatory cells reduction in connective periodontium. [ABSTRACT FROM AUTHOR]

Mindfulness-based Stress Reduction (MBSR) is a treatment program for relieving stress and coping with chronic illnesses. In recent three decades, studies have shown that MBSR has a positive effect on physical and psychological dimensions of chronic illnesses. Chemically pulmonary injured veterans have chronic pulmonary and psychological problems due to mustard gas exposure and complications of Iran-Iraq war. These stresses have negative effects on their general health and immune system. To the best of our knowledge, this is the first study conducted on psychoneuroimmunology and MBSR in these patients. Forty male pulmonary injured veterans were randomly divided in two groups with 20 participants (MBSR and wait-list control). Then MBSR group received 8 weekly sessions of intervention. We tested mental health based on general health questionnaire (GHQ)-28 questionnaire, health-related quality of life (based on St. George respiratory questionnaire (SGRQ) ) and immunity in MBSR groups; before and after intervention "mixed factorial analyses of variance" test was used for analyzing data fpr each dependent variable and appropriate t-tests were done in The necessary condition. Results showed that mental health and health- related quality of life, in MBSR group compared to wait-list control improved [F (1,38)=26.46, p<0.001; F (1,38)=49.52, p<0.001 respectively] significantly.  Moreover, a significant increase was reported in the lymphocyte proliferation with phytohemagglutinin (PHA) [F (1,38)=16.24, p<0.001], and peripheral blood IL-17 [F (1,38)=56.71, p<0.001] However, lymphocyte (CD4+, CD8+, and NK-cell) percentages were not affected significantly [F (1,38)=2.21, p=0.14] ,[F (1,38)=0.90, p=0.78] and [F (1,38)=1.79, p=0.18], respectively. This study suggests that MBSR may be a new treatment approach for improving immunity and overall health in chemically pulmonary injured veterans. [ABSTRACT FROM AUTHOR]

Increase in cases of various cancers has encouraged the researchers to discover novel, more effective drugs from plant sources. This study is a review of medicinal plants in Iran with already investigated anticancer effects on various cell lines. Thirty-six medicinal plants alongside their products with anticancer effects as well as the most important plant compounds responsible for the plants’ anticancer effect were introduced. Phenolic and alkaloid compounds were demonstrated to have anticancer effects on various cancers in most studies. The plants and their active compounds exerted anticancer effects by removing free radicals and antioxidant effects, cell cycle arrest, induction of apoptosis, and inhibition of angiogenesis. The investigated plants in Iran contain the compounds that are able to contribute effectively to fighting cancer cells. Therefore, the extract and active compounds of the medicinal plants introduced in this review article could open a way to conduct clinical trials on cancer and greatly help researchers and pharmacists develop new anticancer drugs. [ABSTRACT FROM AUTHOR]

Aim: The present study aimed to study the immunological changes seen in the intestinal epithelium of the celiac patients could also be detected in the peripheral blood lymphocyte populations. Background: Celiac disease (CD) is a small bowel enteropathy caused by permanent wheat gluten intolerance. One of the earliest signs of CD is an increase in the numbers of the intestinal intraepithelial lymphocytes (iIEL). Patients and methods: In this case-control study, totally 13 untreated subjects with acceptable criteria for CD without any complication and 16 healthy subjects without any positive criteria for CD were selected. Peripheral blood T cells were analyzed by two-color flow cytometry in both groups. Results: The mean age of patients was 33.6 ± 3.4 years and two patients had Marsh IIIB, five patients had Marsh IIIA and six patients had Marsh II histology class. The mean percentages of the γδSTCR+ T cells in the patients were significantly higher than the controls (p=0.015). However, the mean percentages of the αβTCR+ T cells were significantly lower in the untreated patients than the controls (p=0.025). There were no significant difference between the mean percentages of lymphocytes expressing the CD3, CD4 and CD8 molecules in the patients and the controls. Conclusion: The change in the percentages of the peripheral blood T cells expressing the γδSTCR and αβTCR in the celiac patients could be used in conjunction with the other serological markers to identify new CD cases. [ABSTRACT FROM AUTHOR]

Background: Cytotoxic effects of some of the members of papaveraceae family have been reported in Iranian folk medicine. Recent reports has indicated that alkaloids fraction of opium may be responsible for its cytotoxic effect; however, the mechanism of this effect is not fully understood. This study has been designed to investigate the selective cytotoxic, genotoxic and also apoptosis induction effects of noscapine, papaverine and narceine, three non-addictable opium alkaloids, on HT29, T47D and HT1080 cancer cell lines. Mouse NIH3T3 cell line was chosen to present non-cancerous cells and Doxorubicin was selected as the positive control. Methods: Cells were treated by different concentrations of Noscapine, Papaverine, Narceine and doxorubicin; viability was assessed by MTT assay. The genotoxicity and apoptosis induction were tested with comet assay and Annexin-V affinity when the concentration of each these drugs is less than its IC50. In addition, the DNA damage and caspase activity of the T47D cells were examined and the results were compared. Results: This study noted the cytotoxicity and genotoxicity of noscapine and papaverine, specifically on cancerous cell lines. Furthermore, papaverine induces apoptosis in all studied cancer cell lines and noscapine showed this effect in T47D and HT29 cells but not in NIH-3 T3 cells as noncancerous cell line. narceine also showed genototoxicity in the studied cell lines at its IC50 concentration. Conclusions: This experiment suggests that noscapine and papaverine may be of use in cancer treatment due to their specific cytotoxicity and genotoxicity. However, further in vivo studies are needed to confirm its usefulness in cancer treatment. [ABSTRACT FROM AUTHOR]

Aims To examine the association of fasting insulin, insulin resistance and reduced β-cell function with incident Type 2 diabetes and pre-diabetes (isolated impaired fasting glucose/isolated impaired glucose tolerance and combined impaired fasting glucose/impaired glucose tolerance). Methods An Iranian population comprising 1532 men and 2221 women, aged ≥ 20 years, with normal fasting glucose and normal glucose tolerance at baseline, were enrolled in the study. Multivariable Cox proportional hazard models were used to calculate the hazard ratios and 95% CIs of fasting insulin, updated homeostasis model assessments of insulin resistance and β-cell function for incident Type 2 diabetes, isolated impaired fasting glucose, isolated impaired glucose tolerance and combined impaired fasting glucose/impaired glucose tolerance. Results During a median follow-up of 9.2 years, the annual incidence rates (95% CI) of diabetes were 3.73 (2.74-4.94) and 4.06 (3.21-5.06) per 1000 person-years in men and women, respectively. In both men and women, fasting insulin and homeostasis model assessment of insulin resistance (≥ 75th percentile) were significantly associated with incident diabetes and combined impaired fasting glucose/impaired glucose tolerance; however, reduced β-cell function as measured by homeostasis model assessment of β-cell function (< 25th percentile) was associated with incident isolated impaired fasting glucose solely in men [hazard ratio 1.35 (95% CI 1.02-1.78)] in multivariable analysis including waist-hip ratio). Hyperinsulinaemia, insulin resistance and β-cell dysfunction were not related to the incidence of isolated impaired glucose tolerance in either gender. Conclusions Fasting hyperinsulinaemia and insulin resistance were strong risk factors for progression to diabetes and combined impaired fasting glucose/impaired glucose tolerance in a population with normal fasting glucose/normal glucose tolerance. In addition, impaired β-cell function at baseline was related to the development of isolated impaired fasting glucose only in men and, in both men and women, neither insulin resistance nor β-cell dysfunction were associated with incident isolated impaired glucose tolerance. [ABSTRACT FROM AUTHOR]

Background: Human β-defensin 126 (12kDa) is a small cationic glycoprotein that is highly rich of cysteine. DEFB126 gene is located on the subtelomeric end of 20p1.3 in human. High expression of this protein is reported in epididymis. This polypeptide coats the plasma membrane of sperm during epididymal transit. It is likely that β -defensin 126 might have role in unexplained male infertility since it involves in sperm maturation and capacitation. The current research designed to investigate if there is relation between β-defensin 126 gene mutation and unexplained male infertility. Materials and Methods: In this case- control study we followed a two cytosine nucleotides deletion of β-defensin 126 gene in 35 Iranian men with unexplained infertility and 40 fertile men with normal spermogeram as control group. Standard PCR, SSCP(Single strand conformational polymorphism), and sequencing were used to detect genetic alteration of β-defensin 126. ELISA was performed for the assessment of the protein expression on sperm cells. Results: Analysis of genetic data revealed 28.6% homozygote deletion in unexplained infertile men while this deletion was detected in 7.5% of controls. The deletion frequency was statistically higher in infertile patients than normal control group (p<0.05). The protein expression was less in men with del/del genotype compare to the other genotypes (p<0.005). Conclusion: Our study shows that this common sequence variation of β-defensin 126 takes part in impairment of male reproductive function. Consequently, men with the del/del genotype are significantly less fertile than men who carry the wild type allele. [ABSTRACT FROM AUTHOR]

Background: Opioid drugs are used in the treatment of acute post-surgical pain and chronic pain, such as those associated with cancer. Opioid used is associated with complications such as analgesic tolerance, dependence and opioid abuse. The molecular mechanisms of unwanted opioid responses are varied but recent advances have highlighted elevations in pro-inflammatory cytokines and pro-inflammatory glial following chronic administration of morphine. In this study we investigated the neurodegenerative effects of morphine through its effects on Toll-Like Receptor 4 (TLR4) in the male rat hippocampus and evaluated the level of Interleukin-1 beta (IL-1β). Then we compared the difference between inhibitory effects on mu opioid receptors (by β-Funaltrexamine, β-FNA) and TLR4 (by Ibudilast). Subsequently, we assessed the amount of IL-1β and the number of granular cells in male rat hippocampus. Methods: Adult male rats (n=24) were treated with sucrose, morphine, Ibudilast (7.5 mg/kg) and β-FNA (20 mg/kg) for 30 days. Their brains were isolated and hemisected with one hippocampus for granular cell and the other used for IL-1 β immunoblotting. Results: Data showed that Ibudilast suppresses IL-1 β expression significantly more than β-FNA. The granular cell count displayed significant differences. Conclusions: Our results suggested that Ibudilast can be used for controlling and treatment of morphine-induced CNS inflammations or traumatic conditions. [ABSTRACT FROM AUTHOR]

Nowadays, scientific findings in the field of regeneration of nervous system have revealed the possibility of stem cell based therapies for damaged brain tissue related disorders like stroke. Furthermore, to achieve desirable outcomes from cellular therapies, one needs to monitor the migration, engraftment, viability, and also functional fate of transplanted stem cells. Magnetic resonance imaging is an extremely versatile technique for this purpose, which has been broadly used to study stroke and assessment of therapeutic role of stem cells. In this review we searched in PubMed search engine by using following keywords; "Stem Cells", "Cell Tracking", "Stroke", "Stem Cell Transplantation", "Nanoparticles", and "Magnetic Resonance Imaging" as entry terms and based on the mentioned key words, the search period was set from 1976 to 2012. The main purpose of this article is describing various advantages of molecular and magnetic resonance imaging of stem cells, with focus on translation of stem cell research to clinical research. [ABSTRACT FROM AUTHOR]

Hydatidosis, caused by Echinococcus granulosus is one of the most important zoonotic diseases, throughout most parts of the world. Hydatidosis is endemic in Iran and responsible for approximately 1% of admission to surgical wards. There are extensive genetic variations within E. granulosus and 10 different genotypes (G1-G10) within this parasite have been reported. Identification of strains is important for improvement of control and prevention of the disease. No new review article presented the situation of Echinococcus granulosus genotypes in Iran in the recent years; therefore in this paper we reviewed the different studies regarding Echinococcus granulosus genotypes in Iran. [ABSTRACT FROM AUTHOR]

Specific alleles at the HLA-DRB1, -DQA1, and -DQB1 loci seem to be associated with variable risks of developing type 1 diabetes (T1D). This study assessed the distribution of HLA-DR and -DQ alleles among Iranian T1D patients and healthy controls. In this study, HLA-DRB1, -DQA1, and -DQB1 alleles were determined in 100 children with T1D and 100 unrelated healthy controls. The following alleles were found to have a strong positive association with T1D: DRB1*0301, DRB1*0401, DRB1*0402, DQA1*0301, DQA1*0501, DQB1*0201, and DQB1*0302. Meanwhile, protective associations were found for DRB1*1001, DRB1*1101, DRB1*15, DRB1*16, DQA1*0102, DQA1*0103, DQB1*0301, DQB1*0501, and DQB1*0602 alleles. The haplotypes found most frequently among patients with T1D were DRB1*0301-DQA1*0501-DQB1*0201, DRB1*0401-DQA1*0301- DQB1*0302, and DRB1*0402-DQA1*0301-DQB1*0302, whereas DRB1*1101-DQA1*0501-DQB1*0301 and DRB1*16-DQA1*0102- DQB1*0501 haplotypes were negatively associated with the disease. These results confirm the previously reported association of specific HLA-DR and HLA-DQ alleles and haplotypes with T1D in Iranian population. The notable difference was the identification of DRB1*16-DQA1*0102-DQB1*0501 as a protective haplotype and the absence of a negative association of DRB1*1301-DQA1*0103-DRB1*0603 with T1D. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (SCC) is the most common cancer of oral region. The characteristic feature of SCC is invasion of dysplastic epithelium into the connective tissue. Oral SCC is more common in old patients. It is believed that etiology and pathogenesis of SCC in young patients differ from old patients and it is related to different molecular mechanism. In this study, histopathologic differentiation and proliferation activity (by Ki67) in oral SCC lesions of young patient (<40 years) and old patients (>50 years) have been compared. Materials and Methods: In a cohort study, Formalin Fixed and paraffin-embedded tissue sections of 20 oral SCC of young patients and 20 oral SCC of old patients were stained by H and E and immunohistochemically by biotin-streptavidin method. They were observed by two pathologists. Histological grade and Ki67 labeling index (LI) were determined. Data were analyzed by t-test and Mann-Whitney. Results: In cases of oral SCC in young patients, 80% were grade I and 20% were grade II and Ki67 LI was 21/5% in this age group. In cases of oral SCC in old patients, 75% were grade I and 25% were grade II and Ki67 LI was 21/6% in this age group. Conclusion: Histological and immunohistochemical evidence of this study show that oral SCC of young patients and oral SCC lesions of old patients didn't show any differences in histopathological differention and proliferative activity. [ABSTRACT FROM AUTHOR]

The effects of macerated extracts of Crocus sativus (Family Iridaceae) (saffron) on cell viability and cytokine release of stimulated peripheral blood mononuclear cells by phytohemagglutinin (PHA) and nonstimulated cells were examined. The effects of three concentrations of macerated extract, dexamethasone, and saline on cell viability and production of cytokines, including interleukin (IL)-4, IL-10, and interferon-γ (IFN-γ) were evaluated. In cells stimulated with PHA, different concentrations of the extract significantly inhibited cell viability of lymphocytes ( P<.001 for all concentrations). High concentrations of the extract (500 μg/mL) also inhibited secretion of IFN-γ in stimulated cells and IL-10 secretion in both stimulated and nonstimulated cells ( P<.05 for all cases). The effects of high and low concentrations of the extract (500 and 50 μg/mL, respectively) on IL-4 secretion were lower than that of dexamethasone ( P<.05 to P<.001). The extract showed a stimulatory effect on IFN-γ and IL-4 secretion in nonstimulated cells. The ratios of IFN-γ to IL-4 in the presence of all concentrations of saffron on stimulated cells were significantly higher than for the control group ( P<.05 to P<.01). These results indicated that the extract of saffron leads to increased ratio of IFN-γ to IL-4. [ABSTRACT FROM AUTHOR]