Apoptosis/necrosis induction by ultraviolet, in ER positive and ER negative breast cancer cell lines

Background: Ultraviolet (UV) light exposure has been one of the major inducers of apoptosis. UV exposure has caused pyrimidine dimers and DNA fragmentation which might lead to cell cycle arrest and apoptosis signals activation. UV induced apoptosis has investigated in MDA-MB 468 as an ER negative breast adenocarcinoma and MCF-7 as an ER positive breast cancer cell line. Apoptosis induction rate by UV might be different in these two types of cells due to different biological characteristics of the cell. Objectives: In this paper we have evaluated serial dose of UV-B exposure on ER positive and ER negative breast cancer cell lines and its effect on apoptosis or necrosis induction in these cells. Materials and Methods: MDA-MB468 and MCF-7 cell lines have cultured for 24 hours and UV exposure has carried out at 290 nm at dose of 154 J/m2 to 18 KJ/m2 using UV lamp. UV exposed cells have incubated in cell culture condition for 24 or 48 hours following UV exposure and the cells have stained and analyzed by flow cytometry for apoptosis evaluation by Annexin V/PI method. Results: Apoptosis rate (PI and Annexin V double positive cells) after 24 hours incubation was higher in 24 hours in comparison with 48 hours incubation in both cell lines. The frequency of PI positive MDA-MB 468 cells was higher than PI and Annexin V double positive cells after 48 hours. PI positive MDA-MB 468 cells were significantly higher than MCF-7 cells in 24 hours incubation time. Conclusions: The results have shown that MDA-MB 468 cells were more sensitive to UV exposure and DNA fragmentation and necrosis pathway was dominant in these cells. © 2015, Iranian Journal of Cancer Prevention

Comparison of effects of age and sex on serum protein electrophoretic pattern in one-humped camels (Camelus dromedarius) in Semnan, Iran

Abstract The aim of this study was to evaluate the influence of age and sex on the concentration of total serum protein measured by the biuret method and protein fractions determined using cellulose acetate electrophoresis in apparently healthy camels (Camelus dromedarius). Blood samples were collected from 21 camels (12 males and 9 females). The camels were further divided into two groups: 12 young camels at the age of 3 months to 2 years and 9 adult camels at the age of 3-15 years. Cellulose acetate electrophoresis of serum proteins identified five protein fractions in adult camels as young camels, these five protein fractions include albumin, α1 and α2, β and γ-globulins. In adult camels, serum levels (g/l) of total protein, albumin, α1-globulins, α2-globulins, β-globulins and γ-globulins were 80.9±3.10, 42.9±3.10, 1.3±0.22, 2.2±0.30, 11.8±0.30 and 22.6±0.20, respectively. However, in young camels, these levels (g/l) were 66.8±2.90, 40.2±2.40, 1.0±0.14, 2.6±0.30, 10.6±0.80 and 12.3±1.20, respectively. The albumin/globulin (A/G) ratio was 2.08±0.28 in adult camels and 3.77±0.53 in young ones. The mean serum concentrations of total protein and γ-globulins were significantly (P<0.05) higher and the A/G ratio was significantly lower in adult camels compared to young camels. The mean concentrations of γ-globulins were significantly higher and the A/G ratio was significantly (P<0.05) lower in females compared to male camels. The results of the present study indicate a significant effect of age and sex on the concentrations of some of the serum protein fractions in dromedary camels

Predicting Outcomes of Prostate Cancer Immunotherapy by Personalized Mathematical Models

Therapeutic vaccination against disseminated prostate cancer (PCa) is partially effective in some PCa patients. We hypothesized that the efficacy of treatment will be enhanced by individualized vaccination regimens tailored by simple mathematical models.We developed a general mathematical model encompassing the basic interactions of a vaccine, immune system and PCa cells, and validated it by the results of a clinical trial testing an allogeneic PCa whole-cell vaccine. For model validation in the absence of any other pertinent marker, we used the clinically measured changes in prostate-specific antigen (PSA) levels as a correlate of tumor burden. Up to 26 PSA levels measured per patient were divided into each patient's training set and his validation set. The training set, used for model personalization, contained the patient's initial sequence of PSA levels; the validation set contained his subsequent PSA data points. Personalized models were simulated to predict changes in tumor burden and PSA levels and predictions were compared to the validation set. The model accurately predicted PSA levels over the entire measured period in 12 of the 15 vaccination-responsive patients (the coefficient of determination between the predicted and observed PSA values was R(2) = 0.972). The model could not account for the inconsistent changes in PSA levels in 3 of the 15 responsive patients at the end of treatment. Each validated personalized model was simulated under many hypothetical immunotherapy protocols to suggest alternative vaccination regimens. Personalized regimens predicted to enhance the effects of therapy differed among the patients.Using a few initial measurements, we constructed robust patient-specific models of PCa immunotherapy, which were retrospectively validated by clinical trial results. Our results emphasize the potential value and feasibility of individualized model-suggested immunotherapy protocols

BK virus (BKV) quantifcation in urine samples of bone marrow transplanted patients is helpful for diagnosis of hemorrhagiccystitis

Background: Hemorrhagic cystitis (HC) in allogeneic bone marrow transplanted (BMT) patients isassociated with BK virus (BKV) reactivation manifested as BK viruria. However, since 77–90% of alladult BMT patients excrete BKV, viral reactivation alone cannot be responsible for HC. Recently, asignificant overrepresentation of C→G mutations in the Sp1 binding site in the non-coding controlregion (NCCR) of BKV was shown to be present in HC patients and absent in non-HC patients. Weaimed to investigate if this mutation resulted in excessive BKV excretion in HC patients. Study design:A Real-Time PCR was developed and used to quantify BKV in urine samples from 21 patients withHC, with and without the mutations, as well as from patients without HC.Material and method: A Real-Time PCR was developed and used to quantify BKV in urinesamples from 21 patients with HC, with and without the mutations, as well as from patients withoutHC.Results: Quantification of BKV was successful in 18 of 21 urine patients (six with and six withoutC→G mutations) and six patients without HC. A mean of 3.0×106 BKV copies/μl was detected inurine samples of HC patients with C→G mutations, compared to a mean of 1.5×106 BKV copies/μl inHC patients without C→G mutations and a mean of 1.0×106 BKV copies/μl in patients without HC.The obtained differences were however not statistically significant, due to one individual non-HCpatient with an extremely high BKV copy number. Nevertheless, while 50% of the samples in the HCgroups expressed 1×106 copies/μl or more, only one of the samples in the non-HC group contained avirus quantity higher than 5×105 copies.Conclusions: Although we could not confirm that the C→G mutations in the Sp1 site of BKV wereresponsible for an increased viral load in patients with HC, our data suggest that levels of BKV above104 copies/μl may indicate a risk for HC

SstI polymorphism of the apolipoprotein CIII gene in Iranian hyperlipidemic patients: A study in Semnan province

Objective(s)The Sst-I polymorphic site on the 3' untranslated region of the apo CIII gene, has been previously reported to be associated with hypertriglyceridemia. The aim of the present study was to explore the association between Sst-I polymorphism with plasma lipid and lipoprotein levels in hyperlipidemic (HLP) patients from Semnan province, Iran. Materials and Methods Genomic DNA was prepared from 76 patients with HLP and 75 matched healthy subjects. DNA samples were amplified by polymerase chain reaction. The samples were analyzed by restriction fragment length polymorphism (RFLP) method using SstI enzyme. Results The genotype and allelic frequencies for this polymorphism were significantly different between HLP and normolipidemic groups (P< 0.002). Plasma triglyceride (TG) level was higher in both groups, in S2S2 genotype was more than in the S1S1and S1S2 genotypes, however, there was no significant difference in comparison with the control group. Subjects with S1S2 + S2S2 genotypes in compare to S1S1 genotype had odd ratio of 2.8 (95 CI: 1.41-5.56, P< 0.003) for developing hypertriglyceridemia. Conclusion The results showed that the presence of rare S2 allele was associated with change in TG level in the selected population

Comparison of effects of age and sex on serum protein electrophoretic pattern in one-humped camels (Camelus dromedarius) in Semnan, Iran

The aim of this study was to evaluate the influence of age and sex on the concentration of total serum protein measured by the biuret method and protein fractions determined using cellulose acetate electrophoresis in apparently healthy camels (Camelus dromedarius). Blood samples were collected from 21 camels (12 males and 9 females). The camels were further divided into two groups: 12 young camels at the age of 3 months to 2 years and 9 adult camels at the age of 3-15 years. Cellulose acetate electrophoresis of serum proteins identified five protein fractions in adult camels as young camels, these five protein fractions include albumin, α1 and α2, β and γ-globulins. In adult camels, serum levels (g/l) of total protein, albumin, α1-globulins, α2-globulins, β-globulins and γ-globulins were 80.9±3.10, 42.9±3.10, 1.3±0.22, 2.2±0.30, 11.8±0.30 and 22.6±0.20, respectively. However, in young camels, these levels (g/l) were 66.8±2.90, 40.2±2.40, 1.0±0.14, 2.6±0.30, 10.6±0.80 and 12.3±1.20, respectively. The albumin/globulin (A/G) ratio was 2.08±0.28 in adult camels and 3.77±0.53 in young ones. The mean serum concentrations of total protein and γ-globulins were significantly (P&lt;0.05) higher and the A/G ratio was significantly lower in adult camels compared to young camels. The mean concentrations of γ-globulins were significantly higher and the A/G ratio was significantly (P&lt;0.05) lower in females compared to male camels. The results of the present study indicate a significant effect of age and sex on the concentrations of some of the serum protein fractions in dromedary camels.Keywords: Age, Camelus dromedarius, Electrophoresis, Semnan, Se

Evaluation of interleukin 12 and CD56Â + lymphocyte cells in pediatric hematopoietic stem cell transplantation for early diagnosis of acute graft versus host disease

The present study tried to explain CD56 + lymphocyte cells activities and possible prognostic role of these cells in Graft-Versus-Host-Disease (GVHD). The role of IL-12 activation and function is of interest in this study. Peripheral blood samples of 51 Hematopoietic Stem Cell Transplantation (HSCT) recipients collected at before (day � 8) and after (days 7 and 14). PBMC were collected by Ficoll separation and analyzed by Flow Cytometry using triple antibody (CD45-PerCP, CD56-FITC, and CD69-PE staining and control antibody. Levels of the cytokine IL-12 in the patient's serum were evaluated by ELISA. Percentage of CD56 + lymphocytes (CD56 +bright) cells was significantly increased at day 14 in patients with acute GVHD and percentage of lymphocytes expressing CD69 was significantly increased at days 7 and 14 posts HSCT in patients with acute GVHD in comparison to those in non-GVHD patients. Baseline serum IL-12 levels (pre-HSCT, day � 8) were significantly higher in those HSCT recipients who did not develop GVHD. This study showed that post-transplant CD56 + lymphocytes and pre-transplant serum levels of IL-12 play significant roles in the induction of and protection against GVHD, respectively. The increase in the percentage of CD69 + cells indicates the activation of lymphocyte in acute GVHD group. © 2016 Elsevier B.V

Association of adiponectin gene polymorphisms and their haplotypes with type 2 diabetes and related metabolic traits in an Iranian population

Introduction: Adiponectin is an adipocyte-secreted protein that contributes to glucose homeostasis. Contradictory reports are available on single nucleotide polymorphisms (SNPs) in the adiponectin gene and the risk of type 2 diabetes (T2D). We investigate the association of adiponectin gene SNPs (+45T/G and +276G/T) with serum adiponectin, insulin resistance, lipid profile, and T2D risk in an Iranian population. Method: The +45T/G and +276G/T SNPs were genotyped in 211 non-familial T2D patients and 202 non-diabetic subjects by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and TaqMan probe, respectively. Results: T2D was associated with a decrease in serum adiponectin level. The G allele and the GG and TG genotypes of +45T/G SNP were more abundant than the T allele and the TT genotype in T2D patients compared with controls (p < 0.001). The risk of T2D in individuals with the GG and TG genotypes of +45T/G SNP was 4 and 2 times more than that with the TT genotype, respectively. There was no statistically significant difference in the frequencies of allele and genotype of +276G/T SNP between the control and T2D groups. The presence of +45G/+276G haplotype was associated with an increased risk of T2D (OR = 2.01, 95 CI = 1.34�3.03, p = 0.04). Conclusion: Therefore, our results showed that +45T/G SNP is associated with the risk of T2D higher than +276G/T SNP in the studied population. © 2020, Research Society for Study of Diabetes in India

Variable Abnormalities in T and B Cell Subsets in Ataxia Telangiectasia

Background: Ataxia-telangiectasia (AT) is a rare genetic condition, caused by biallelic deleterious variants in the ATM gene, and has variable immunological abnormalities. This study aimed to examine immunologic parameters reflecting cell development, activation, proliferation, and class switch recombination (CSR) and determine their relationship to the clinical phenotype in AT patients. Methods: In this study, 40 patients with a confirmed diagnosis of AT from the Iranian immunodeficiency registry center and 28 age-sex matched healthy controls were enrolled. We compared peripheral B and T cell subsets and T cell proliferation response to CD3/CD28 stimulation in AT patients with and without CSR defects using flow cytometry. Results: A significant decrease in naïve, transitional, switched memory, and IgM only memory B cells, along with a sharp increase in the marginal zone-like and CD21low B cells was observed in the patients. We also found CD4+ and CD8+ naïve, central memory, and terminally differentiated effector memory CD4+ (TEMRA) T cells were decreased. CD4+ and CD8+ effector memory, CD8+ TEMRA, and CD4+ regulatory T cells were significantly elevated in our patients. CD4+ T cell proliferation was markedly impaired compared to the healthy controls. Moreover, immunological investigations of 15 AT patients with CSR defect revealed a significant reduction in the marginal zone, switched memory, and more intense defects in IgM only memory B cells, CD4+ naïve and central memory T cells. Conclusion: The present study revealed that patients with AT have a broad spectrum of cellular and humoral deficiencies. Therefore, a detailed evaluation of T and B cell subsets increases understanding of the disease in patients and the risk of infection. © 2020, Springer Science+Business Media, LLC, part of Springer Nature

Simultaneous disruption of circulating miR-21 and cytotoxic T lymphocytes (CTLs): Prospective diagnostic and prognostic markers for esophageal squamous cell carcinoma (ESCC)

Background: Esophageal squamous cell carcinoma (ESCC) as the most prominent type of esophageal cancer (EC) in developing countries encompasses a substantial contribution of cancer-related mortalities and morbidities. Cytotoxic T lymphocytes (CTLs) are the major subset of effector T cells against cancer. However, the microRNAs involved in the development and regulation of CTLs could be disrupted in cancers such as EC. Methods: Here, we evaluated the population of IL-10, TGF-β, IFN-γ, and IL-17a-producing CD3+CD8+ T cells, their association with the circulating levels of miR-21 and miR-29b, and their diagnostic and/or prognostic (after 160 weeks of follow-up) utilities in 34 ESCC patients (12 newly diagnosed: ND, 24 under-treatment: UT) and 34 matched healthy donors. Results: The population of IL-10 and TGF-β-producing CTLs (CD8+ Tregs) were considerably expanded, in addition to the overexpression of miR-21 in both groups (ND and UT) of ESCC patients, while the frequency of Tc17 and CD8+ Treg cells increased only in UT patients. The expression means of TGF-β and IL-10 in CTLs were considered to be excellent biomarkers (1 � area under the curve: AUC �0.9) in distinguishing ESCC patients and associated subgroups from healthy subjects. Moreover, the lower expressions of TGF-β, IL-17a, IL-10, and IFN-γ in CTLs were associated with ESCC better prognosis. Conclusions: The association between the impaired function of CD3+ CD8+ T cell subsets and miR-21 expression could be introduced as novel therapeutic targets and powerful diagnostic and prognostic markers for ESCC. © 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC