Search

Acute lymphoblastic leukemia (ALL), a malignant transformation and proliferation of the lymphoid line of blood cells, is characterized by chromosomal abnormalities and genetic changes. The purpose of this research was the evaluation of expression level of miR-181a and -b in patients with ALL compared to the control group. Furthermore, we examined their expression level in hematopoietic stem-cell transplantation (HSCT) patients who developed acute graft-versus-host disease (aGVHD) in comparison with those without aGVHD and explore the relationship between their expression level and cytogenetic abnormalities. In this cross-sectional study, 76 newly diagnosed adult De novo ALL patients were enrolled who were admitted to our referral hospital. All patients received standard chemotherapy, consisting of daunorubicin. A total of 37 patients underwent HSCT from the related human leukocyte antigen-matched donors. ALL patients have been diagnosed with the coronavirus disease 2019 (COVID-19) and Torque teno viruses (TTVs). We assessed the expression levels of miR-181a and -b in the peripheral blood sample of ALL patients at the time of diagnosis prior to chemotherapy, and healthy matched individuals by RT–PCR. TTVs and COVID-19 load were also determined via RT–PCR. In conclusion, the expression level of miR-181a and -b were significantly higher in ALL patients than healthy controls and also increased in patients who developed aGVHD in comparison with those without aGVHD. MiR-181a and -b can be a useful biomarker in ALL and a useful indicator of aGVHD. The expression level of miR-181a in ALL patients with COVID-19 is significantly up-regulated, while it is reduced in these patients with TTV.

Brucellosis is considered as the most common bacterial zoonosis in the world. Although the laboratory findings are the most reliable diagnosis today, the current laboratory methods have many limitations. This research aimed to design and evaluate the performance of a novel technique based on the localized surface plasmon resonance (LSPR) to eliminate or reduce existing shortcomings. For this purpose, smooth lipopolysaccharides were extracted from Brucella melitensis and Brucella abortus and fixed on the surface of the gold nanoparticles through covalent interactions. After some optimizing processes, dynamic light scattering was used to characterize the probe. The detection of captured anti-Brucella antibody was performed by measuring the redshift on LSPR peak followed by the determination of cutoff value, which indicated a significant difference between controls and true positive patients (P value

Objectives An association between costimulatory molecule gene polymorphisms and viral infection after hematopoietic stem cell transplantation may be related to clinical outcomes, especially acute graft-versus-host disease. Cytotoxic T-lymphocyte antigen 4 has been suggested as a crucial negative regulator of the immune system. In this study, our objective was to investigate the association between cytotoxic T-lymphocyte antigen-4 gene polymorphisms (including -1722 T/C, -1661 A/G, -318 C/T, and +49 A/G) and torque teno virus infection after hematopoietic stem cell transplantation in patients with and without acute graft-versus-host disease. Materials and methods Our study included 71 recipients. We evaluated cytotoxic T-lymphocyte antigen 4 gene polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism method. Results Our results showed that the GG genotype of the cytotoxic T-lymphocyte antigen 4 +49 A/G was significantly more frequent in transplanted patients infected with torque teno virus, whereas the AG genotype was more common in transplanted patients who did not have this infection. In addition, the -1661 AA and GA genotypes and -318 TC genotypes were significantly more frequent in transplanted patients infected with the virus and who had low-grade (grades I and II) acute graft-versus-host disease. Among those with grade I graft-versus-host disease, the GG genotype of the cytotoxic T-lymphocyte antigen 4+49 A/G was more frequent in transplanted patients with torque teno virus infection, whereas the AG genotype was higher in transplanted patients who did not have this infection. Conclusions This is the first report indicating that cytotoxic T-lymphocyte antigen 4 gene polymorphism may be implicated in prevalence of torque teno virus infection after stem cell transplant. Further larger studies and evaluation of other costimulatory molecules are suggested.

Background: Programmed death-1 (PD-1) and inducible costimulator (ICOS) are immune checkpoint receptors participating in tumor immune evasion, which counters the activation signal provided through the T-cell receptor ligation. This study aimed to investigate the relationship between the expression of PD-1 and ICOS on mononuclear cells (MNCs) isolated from the peripheral blood of acute myeloid leukemia (AML) patients and their response to induction chemotherapy. Materials and Methods: Peripheral blood samples (5cc) were collected from 56 AML patients at first diagnosis before and after the induction therapy regimen for AML. PD-1 and ICOS expression were analyzed in all patients before and after the standard induction therapy regimen. Results: The expression of PD-1 and ICOS significantly decreased (66.7 and 16.3 fold, respectively) in AML patients following chemotherapy compared to its baseline value (P=0.01 and P=0.001, respectively). The expressions of PD-1 and ICOS were significantly different between favorable and poor risk groups. Conclusions: Lower PD-1 and ICOS expressions on the surface of MNCs before induction therapy were associated with a better response to treatments. In addition, PD-1 and ICOS expression on MNCs decreased after induction therapy.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly pathogenic with relatively high mortality and morbidity. In addition to pneumonia, acute respiratory distress syndrome, and microembolic disorder, a high proportion of patients with SARS-CoV-2 develop lymphopenia and cytokine storm disorder. This review explores the underlying mechanisms behind the pathogenesis of SARS-CoV-2, especially the immune mechanisms, which could be potentially used as therapeutic targets for the management of COVID-19.

Objective: Congestive Heart failure (CHF) is a complex multifactorial syndrome due to tissue hypo perfusion that is affected by some factors like inflammatory cytokines. In our study we investigated the exact gene expression of three inflammatory cytokines in ischemic and idiopathic cardiomyopathy patients.Materials and Methods: From 49 studied recipients in ischemic group, 23 (46.9%) were male and from 40 studied recipients in idiopathic dilated cardiomyopathy group, 19 (47.5%) were male. For the quantitative analysis of Interleukin (IL)1, IL-27 and TNF-α mRNAs expression level, the SYBR Green Real-Time PCR method was performed using SYBRPremix Ex TaqTM II (Tli RNaseH Plus) (Takara, Japan) and designed primers specific for each genes in an iQ5 thermocycler (BioRad Laboratories, USA) according to the manufacturer’s instructions.Results: Our results showed that the expression level of IL-1 and TNF-α were significantly higher in the ischemic patients compared to healthy controls (PConclusion: Although we would introduce IL1, IL-27 and TNF α as effective inflammatory cytokines on myocardial functions in ischemic and idiopathic cardiomyopathy patients; there is not any difference between these two groups in gene expression of three main inflammatory cytokines.

© 2021, The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG. Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly pathogenic with relatively high mortality and morbidity. In addition to pneumonia, acute respiratory distress syndrome, and microembolic disorder, a high proportion of patients with SARS-CoV-2 develop lymphopenia and cytokine storm disorder. This review explores the underlying mechanisms behind the pathogenesis of SARS-CoV-2, especially the immune mechanisms, which could be potentially used as therapeutic targets for the management of COVID-19.

Recently, dysregulated expression of various micro RNAs has been reported in hematologic malignancies, especially AML disease which affects normal hematopoiesis in these patients and thereby contribute to clinical outcome of AML patients, associated with either poor or favorable prognosis. Herein, we evaluated the expression of miR-181b and miR-222 in acute myeloid leukemia patients and correlation with response to therapy after hematopoietic stem cell transplantation. Eighty newly diagnosed AML patients and 80 healthy controls were recruited. The expression of miR-181b and miR-222 was evaluated by real-time SYBR Green PCR method. miR-181b gene expression was significantly increased (4.7 fold) whereas miR-222 was decreased (18.3 fold) in AML patients compared to controls (P = 0.03 and P 0.05). Also, miR-181b and miR-222 were not differentially expressed in AML patients with M3 compared to non-M3 FAB subtypes (P > 0.05). miR-181b and miR-222 are aberrantly expressed in AML patients and their baseline level is not associated with response to treatment.

Mutation of the genes encoding DNA methyltransferase 3A (DNMT3A) and isocitrate dehydrogenase 1/2 (IDH 1/2) is among the most commonly occurring mutation found in acute myeloid leukemia (AML) patients. This study was purposed to investigate the frequency of DNMT3A and IDH1/2 gene mutation and the clinical features of Iranian cytogenetically normal acute myeloid leukemia (CN-AML) patients harboring these mutations. Thirty-nine CN-AML patients were recruited at the time of diagnosis. PCR followed by direct sequencing was used to detect the mutations of DNMT3A (R882), IDH1 (R132), and IDH2 (R140 and R172). The results showed that of all CN-AML patients, DNMT3A, IDH1, and IDH2 mutations were observed in five (12.8%), five (12.8%), and five (13.2%) patients, respectively. In addition, the most frequent DNMT3A, IDH1, and IDH2 mutant types were R882C, R132C, and R140Q types, respectively. Our results also described that both DNMT3A and IDH1/2 mutations were not associated with significant change in hemoglobin (Hb) levels, white blood cell (WBC) and platelet count, and bone marrow blast percentage (P > 0.05). There was also no significant difference in the mutation status of DNMT3A and IDH1/2 genes regarding age and gender (P > 0.05). A positive relationship was observed between the co-occurrence of DNMT3A and IDH2 (P = 0.021) and FLT3-ITD and NPM1 (P = 0.044). Increasing sample size and longer follow-up of patients may provide additional data to understand the prognostic significance of the DNMT3A and IDH1/2 mutation in the management of CN-AML patients.

Background: Acute Myeloid Leukemia syndrome (AML) is a hematologic malignancy which is due to clonal extensive proliferation of leukemic precursor cells and is rapidly fatal unless treated or response to chemotherapy. Cytogenetic findings have important role in prognosis and categorization of AML. The aim of this study was to investigate the expression changes in CX3CL1 and Interlukin-6 (IL-6) genes before and after chemotherapy as remission induction therapy in AML patients. Materials and Methods: In this study 69 patients (36 males, 33 female) with AML was selected from tertiary medical heath center. A quantitative polymerase chain reaction (PCR) was done for mRNA expression of CX3CL1 and IL-6genes before and after induction chemotherapy. To obtain expression changes in CX3CL1 and IL-6genes, we used 2-ΔΔCT method. Results: The expression of CX3CL1 and IL-6 was significantly increased after induction chemotherapy. Also, the ΔCt mean of CX3CL1 and IL-6 mRNA was not significant between AML subtype groups. Conclusion: In conclusion, as we showed that chemotherapy significantly increase the expression of CX3CL1 and IL-6 which can be used as a prognostic factor of AML.

Introduction: By aging population, the heart failure and its life-threatening complications have become an enormous issue in public health. Regarding the inflammation as a major contributing pathological factor, the determination of most important inflammatory targets for immunomodulation is a problematic puzzle in the treatment of heart failure patients and the inflammatory pathways primarily involved in different underlying conditions contributing to heart failure can be an area which is worthy of focused research. Considering the dilated cardiomyopathy (DCM) as a relatively high-incident disease leading to heart failure, the aim of this study is to determine the difference in the expression level of interleukin (IL)-6 and IL-18 in patients with ischemic and idiopathic DCM. Methods: 39 non-diabetic patients with ischemic and 37 ones with idiopathic DCM were enrolled in the study. 48 healthy individuals were also considered as control group. For quantitative determination of the mRNA expression level of IL-6 and IL-18 genes, an in-house- SYBR Green real-time PCR was used and Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was considered as internal control gene. The left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) was calculated by 2D echocardiographic assessment. Data were finally analyzed via SPSS statistical software version 19.0 using independent t test and 2-∆∆Ct method and P

OBJECTIVES There are limited studies about the possible relationship between genetic variations of costimulatory genes and susceptibility to hematologic malignancies like leukemia and lymphoma. MATERIALS AND METHODS This cross-sectional study included 59 leukemia patients. The polymorphisms of costimulatory molecules, including the CTLA-4 gene (-318 C/T, -1722 T/C, -1661 A/G, +49 A/G), PD-1 gene (1.3 A/G, 1.9 C/T), ICOS gene (1720 C/T), and CD28 gene (17 C/T), were analyzed by polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS Our results showed that the TT genotype and T allele of the CTLA-4 -318 T/C polymorphism, the AA genotype of CTLA-4 +49 A/G polymorphism, and the CT genotype of PD-1 1.9 C/T polymorphism were significantly higher in healthy controls (P < .05). However, the AG genotype of the CTLA-4 +49 A/G, the CC genotype of the PD-1 1.9 C/T, and the CT genotype of the CD28 +17C/T polymorphism were significantly increased in patients with leukemia (P < .05). When the genotype frequency of costimulatory genes was compared between different leukemia groups, we observed that the A allele of the CTLA-4 +49 A/G and the CC genotype and C allele of the CD28 +17 C/T polymorphism were significantly higher in patients with acute leukemia than in those with chronic leukemia (P < .05). Among leukemia patients, the AA genotype of CTLA-4 +49A/G polymorphism was significantly increased in patients with acute myeloid leukemia, whereas the AG genotype was more prevalent in patients with acute lymphoblastic leukemia (P < .05). CONCLUSIONS We show for the first time that genetic variations of costimulatory molecules CTLA-4, CD28, and PD-1 may be associated with susceptibility of Iranian patients to leukemia.

Costimulatory molecules are important factors determining the outcome of bone marrow transplant. Because the host ability in costimulatory molecule function may be affected by gene polymorphisms, the aim of the present study was to investigate the effect of CTLA4, ICOS, PD.1 and CD28 gene polymorphisms in outcome of bone marrow transplant patients. A total of 72 recipients were included in this study. CTLA4 (-1722, -1661, -318, +49), ICOS (+1720), CD28 (+17) and PD.1 (PD.1.3, PD.1.9) gene polymorphisms were evaluated by PCR-RFLP. The results showed that no differences in the distribution of all mentioned costimulatory molecules genotypes and alleles were observed in the Graft Versus Host Disease (GVHD) group compared to the non-GVHD group. After gender classification, there is a significant association between GA genotype (CTLA4-1661) in male group with GVHD than without GVHD (p=0.03). Also, in this study we found significant associations between CC genotype and C allele of PD.1.9, and TT genotype and T allele of CD28 that had more frequency in grades 2-4 (p=0.04. p=0.02, p=0.01, p=0.003, respectively). Results indicate that the CC genotype and C allele of PD.1.9 and TT genotype and the T allele of CD28 are genetic risk factors for development of a severe grade of GVHD. This subject needs to be studied in different population.

Determinative associations may exist between costimulatory molecule gene polymorphisms with a variety of post hematopoietic stem cell transplantation (HSCT) viral related clinical outcomes especially acute graft versus host disease (aGVHD). Therefore in this study the associations between costimulatory molecule gene polymorphisms including: cytotoxic T-lymphocyte antigen-4 (CTLA4), programmed cell death-1 (PD-1), inducible T cell costimulator (ICOS), and cluster differentiation 28 (CD28) with active cytomegalovirus (CMV) infection were evaluated in HSCT patients. The 72 allogeneic HSCT patients with and without aGVHD were enrolled in this cross sectional study between years: 2004-2011. The single nucleotide polymorphisms in loci of the costimulatory molecules including: CTLA4 gene (-318 C/T, 1722 T/C, 1661 A/G, +49 A/G), PD-1 gene (PD-1.3 A/G, PD-1.9 C/T), ICOS gene (1720 C/T), and CD28 gene (+17 C/T) were analyzed in studied HSCT patients by PCR-RFLP methods. The active CMV infection was evaluated in fresh EDTA-treated blood samples of each allogeneic HSCT patients by CMV antigenemia kit according to manufacturer's instruction. Active CMV infection was found in 11 of 72 (15.27 %) of allogeneic HSCT patients. The T allele and TT genotype of the CD28 +17 C/T were significantly higher frequency in active CMV infected allogeneic HSCT patients experienced aGVHD. The G allele and GG genotype of the CTLA4 -1661 A/G were significantly higher frequent in active CMV infected allogeneic HSCT patients experienced low grade of aGVHD. Finally, finding of significant associations between CD28 +17 C/T and CTLA4 -1661 A/G genotypes with CMV active infection in allogeneic HSCT patients experienced aGVHD emphasize on the importance of the genetic pattern of costimulatory genes in outcomes of active CMV infection in HSCT patients needs completed studies.

Microvesicles are released by different cell types and shuttle mRNAs and microRNAs which have the possibility to transfer genetic information to a target cell and alter its function. Acute myeloid leukemia is a malignant disorder, and leukemic cells occupy all the bone marrow microenvironment. In this study, we investigate the effect of leukemia microvesicles on healthy umbilical cord blood hematopoietic stem cells to find evidence of cell information transferring. Leukemia microvesicles were isolated from acute myeloid leukemia patients and were co-incubated with healthy hematopoietic stem cells. After 7 days, cell count, hematopoietic stem cell–specific cluster of differentiation (CD) markers, colony-forming unit assay, and some microRNA gene expressions were assessed. Data showed a higher number of hematopoietic stem cells after being treated with leukemia microvesicles compared with control (treated with no microvesicles) and normal (treated with normal microvesicles) groups. Also, increased levels of microRNA-21 and microRNA-29a genes were observed in this group, while colony-forming ability was still maintained and high ranges of CD34+, CD34+CD38−, CD90+, and CD117+ phenotypes were observed as stemness signs. Our results suggest that leukemia microvesicles are able to induce some effects on healthy hematopoietic stem cells such as promoting cell survival and some microRNAs deregulation, while stemness is maintained.

Background: The pathogenic association of Transfusion Transmitted Virus or Torque teno Virus (TT Virus) single and mixed infections with leukemia was under evaluation in these years but confront with controversies. This hypothesis is based on the higher prevalence of TT Virus infection in patients with leukemia compared with controls. Objectives: The aim of this study was to determine the frequency of TT Virus, Cytomegalovirus (CMV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) infections in patients with leukemia and healthy controls. Patients and Methods: In this cross sectional study, 95 patients with leukemia and 100 healthy controls who were admitted to the Namazi Hospital affiliated to the Shiraz University of Medical Sciences, Shiraz, Iran, were enrolled between years 2012 and 2013. Blood samples treated with EDTA were collected from each patient with leukemia and controls. The existence of TT Virus infection was analyzed using the semi-nested PCR method. The immunological prevalence of HBV and HCV infections were evaluated using HBs-Ag and HCV-Ab ELISA based protocols, respectively. Active CMV infection was also evaluated using an immunofluorescence method. Also risk factors of leukemia and viral infections were statistically analyzed in patients with leukemia. Results: The TT Virus infection was significantly found in 40 of 95 (42.1%) and 12 of 100 (12%) patients with leukemia and controls, respectively. The HBs-Ag and HCV-Ab were detected in 27 of 95 (28.4%) and 18 of 69 (26.1%) patients with leukemia but were not found in the controls. Active CMV infection was also found in 11 of 69 (16%) patients and none of the controls. Significant co-infection of TT Virus was found with HBV (15 of 40; 37.5%), HCV (14 of 40; 35%) and CMV (7 of 40; 17.5%) in patients with leukemia. Conclusions: Confirmation of the significantly higher frequency of TT Virus, HBV, HCV and CMV single infection and their co-infection in patients with leukemia compared with healthy controls, emphasizes the determinative role of TT Virus pathogenesis in clinical outcomes observed in patients with leukemia, which requires extensive evaluation by further studies.

Background: Cirrhosis is one of the most severe liver complications, with multiple etiologies. The torque teno virus (TTV), also known as transfusion transmitted virus, which has a high incidence in the world population, is one of the possible increasing risk factors in patients with idiopathic fulminant hepatitis and cryptogenic cirrhosis. Objectives: The aim of this study was to evaluate solitary and co-infection with TTV, in patients with cryptogenic and determined cause of cirrhosis. Patients and Methods: In this cross-sectional study, 200 liver transplant patients were consecutively recruited between years 2007 and 2011. Patients were classified, based on recognition of the etiology of cirrhosis to determined (n = 81) and cryptogenic (n = 119) patient groups. The existence of TTV infection was analyzed, using a semi-nested polymerase chain reaction method. The presence of hepatitis B virus (HBV) infective markers, including HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B core antibody (HBcAb), and hepatitis B e antibody (HBeAb), was evaluated using qualitative polymerase chain reaction and enzyme linked immunosorbent assay protocols, respectively. Results: The TTV infection was found in 37 of 200 (18.5%) and 53 of 200 (26.5%) plasma and tissue samples of studied liver transplanted patients, respectively. The TTV genomic DNA was found in 32 (26.9%) and 28 (23.5%) of 119 liver tissue and plasma samples of transplanted patients with cryptogenic cirrhosis, respectively. The genomic DNA of TTV was also diagnosed in 21 (25.9%) and nine (11.1%) of the 81 liver tissue and plasma samples of patients with determined cirrhosis, respectively. Significant associations were found between TTV infection with HBV molecular and immunologic infective markers, in liver transplanted patients, with determined and cryptogenic cirrhosis. Conclusions: The diagnosis of the high frequency of solitary TTV and co-infection with HBV, in both liver transplanted patients with cryptogenic and determined cirrhosis, emphasized on the importance of TTV infection in the development of cirrhosis, especially in the cases of cryptogenic ones, prompting for further studies the confirm this agent in the etiology of determined cirrhosis.

Costimulatory gene polymorphisms have been proposed to affect the hepatitis B virus pathogenesis by affecting regulation of immune responses. The association between costimulatory molecule gene polymorphisms including CTLA4, PD.1, ICOS, and CD28 with hepatitis B virus infection has been evaluated in hematopoietic stem cell transplant patients.In a cross-sectional study, single-nucleotide polymorphisms in the loci of the costimulatory molecules were analyzed in 3 study groups. Hepatitis B virus infection was evaluated in plasma samples of each allogeneic and autologous hematopoietic stem cell transplant patients by a third generation HBsAg enzyme-linked immunosorbent assay kit according to the manufacturer 's instructions.Hepatitis B virus infection was found in 19 of 72 allogeneic (26.3%) and 26 of 59 autologous patients (44.1%). The T allele of CTLA4-318 and CC genotype of CD28+17 polymorphisms are significantly more frequent in hepatitis B virus-infected allogeneic hematopoietic stem cell transplant patients. The CC genotype of CD28 +17 was seen more frequently in hepatitis B virus-infected allogeneic hematopoietic transplant patients. The C allele of the PD.1.9 was seen more frequently in hepatitis B virus-infected allogeneic hematopoietic patients experiencing graft-versus-host disease. Also, the frequency of CT genotype and T allele of the PD.1.9 was significantly increased in hepatitis B virus-infected allogeneic hematopoietic stem cell transplant patients experiencing low-grade graft-versus-host disease.Associations of CTLA4 -318 and CD28 +17 with hepatitis B virus infection in allogeneic hematopoietic stem cell transplant patients was reported, also it was determined that PD.1.9 genotypes and hepatitis B virus infection in allogeneic hematopoietic stem cell transplant patients experiencing low-grade graft-versus-host disease was associated. However, better evaluations of the relations between costimulatory gene polymorphisms with hepatitis B virus infection in hematopoietic stem cell transplant patients requires further investigations.