SARS-CoV-2 is a single strand RNA virus that causes ongoing pneumonia-like and severe respiratory disease. This disease is very important in immunosuppressed patients. Since not many studies have been done in people with cancer as high risk group, in this study we examined the different behaviors of this virus in different types of cancer. In this study, patients with a variety of solid and hematologic cancers were screened for SARS-CoV-2. The rates of infection, the rate of mortality, in patients with various cancers, as well as in the families of these patients have been studied. In this study, it was found that the prevalence of SARS-CoV-2 in patients with solid cancers was significantly lower than hematological cancers. Also, the mortality rate in hematological cancers was higher than in solid cancers (P<0.05). Assessments the families of these patients, it was found that patients with solid cancers were also less infected than their family members (P<0.05). Researchers of this study attributed these results to the chronic inflammation and M1 macrophages in these patients. It is essential that additional studies are conducted, especially in terms of biological function.

Cell-based immunotherapies have been selected for the front-line cancer treatment approaches. Among them, CAR-T cells have shown extraordinary effects in hematologic diseases including chemotherapy-resistant acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL). In this approach, autologous T cells isolated from the patient's body genetically engineered to express a tumor specific synthetic receptor against a tumor antigen, then these cells expanded ex vivo and re-infusion back to the patient body. Recently, significant clinical response and high rates of complete remission of CAR T cell therapy in B-cell malignancies led to the approval of Kymriah and Yescarta (CD19-directed CAR-T cells) were by FDA for treatment of acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Despite promising therapeutic outcomes, CAR T cells also can elicit the immune-pathologic effects, such as Cytokine Release Syndrome (CRS), Tumor Lysis Syndrome (TLS), and on-target off-tumor toxicity, that hampered its application. Ineffective control of these highly potent synthetic cells causes discussed potentially life-threatening toxicities, so researchers have developed several mechanisms to remote control CAR T cells. In this paper, we briefly review the introduced toxicities of CAR-T cells, then describe currently existing control approaches and review their procedure, pros, and cons.

Hereditary ataxias (HA) are a group of inherited neurological disorders caused by changes in genes. At least 115 different mutations in the senataxin (SETX) gene causing ataxia have been identified. There arc no reports of any SETX gene mutation among the Iranian population. Here we report on two cases with homozygous and heterozygous mutations in which one patient was affected by HA with oculomotor apraxia type 2, and the other was a carrier of the disorder. In 2016, the affected patient was referred to the Biogene Medical and Genetic Laboratory (Tehran, Iran) suffering from imbalance and tremor of both head and body. The coding regions of 18 genes, including the SETX gene, were screened. The target regions were captured using the NimbleGen chip followed by next-generation sequencing (NGS) technology on the Illumina Hiseq2500 platform. NGS, a DNA sequencing technology, has greatly increased the ability to identify new causes of ataxia; a useful tool for the prevention of primary manifestations and treatment of affected patients. In the present study, a novel mutation in the SETX gene has been identified.

Article type: Original article Article history: Received August 11, 2018 Revised September 5, 2018 Accepted September 8, 2018 DOI: 10.29252/jhehp.4.3.8

a Department of Basic Sciences, School of Microbiology Islamic Azad University, Damghan, Iran. b Department of Virology, Pasture Institute of Iran,Tehran, Iran. c Department of Microbiology and Immunology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran. d Department of Microbiology, College of Basic Science and Biology,Islamic Azad University Varamin, Iran. e Department of Molecular Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. f Department of Medical Genetics, Iran University of Medical Sciences,Tehran, Iran.

Prevalence of Shigella and Other Pathogenic Gram-negative Bacteria in the Patients with Diarrhea in Kashan City, Iran During 2015-2017

Human cytomegalovirus (HCMV) can be transmitted through blood transfusion and organ transplantation and could be cause of some complication in solid-organ transplant recipients. Current study is aimed to compare the sensitivity and Specificity of ELISA, Antigenemia assay and nested PCR methods to detection of Cytomegalovirus infection in renal transplantation patients. In this study blood samples were collected from 200 renal transplant recipients’ patients. DNA was extracted by commercial kit and Nested PCR was done by 2 pairs of internal and external primers. Anti CMV antibodies (IgM and IgG) were detected by ELISA and CMV-pp65 antigenemia assay (Ag) was used to detect CMV antigens. The sensitivity and Specificity of each test and all the methods together were evaluated, and SPSS software was used to analysis of data. From 200 patients, 193 (96.5%) were positive for CMV antibodies with the Specificity of 100 and sensitivity of 97.76%. 120 (60%) and 25 (12.5) samples were positive by nested PCR and Ag assay with the Specificity of 94.49 and 78.12 and sensitivity of 94.49 and 78.12, respectively. In the case of early diagnosis of the disease, nested PCR diagnose the infection 14 years earlier than Ag assay and was consistently positive, whereas false negative results were frequently observed with the pp65 Ag assay. The sensitivity and specificity of the two methods combined detection for CMV infection were 96.76% and 99.89%. ELISA can be used as a screening reliable detection test for CMV infection in recipient especially when PCR is unavailable. Combination of ELISA and CMV-PCR methods, provide a more effective method to monitor CMV infection.

BACKGROUND AND OBJECTIVE: Hematopoietic stem cells are one of the new therapeutic options for treating skin ulcers. Recently, a new perspective has been developed to better utilize stem cells using nanofiber scaffolds. The present study was conducted to investigate the effect of polycaprolactone/gelatin (PCL/GT) nanofiber scaffold on the therapeutic function of hematopoietic stem cells. METHODS: In this experimental study, 15 male BALB / c mice were divided into three groups of five, including the control group, the group receiving stem cells in the wound site (cell group) and the group receiving cell + PCL nanofiber scaffold. PCL/GT nanofiber scaffold was prepared by electrotherapy. After hematoxylin and eosin staining, the parameters of epidermal repair and hair follicle formation in the wound site were evaluated by fluorescence microscope and Image J and SPSS programs. FINDINGS: On day 28 after transplantation, the highest and lowest epidermal thicknesses were observed in the cell + scaffold group and control group, which were 10.5±0.3 and 27.3±0.9 μm, respectively, which was significant (p<0.05). Moreover, the highest and lowest number of hair follicles were observed in the cell + scaffold group and control group, respectively; 5.2±0.2 and 4.2±0.3. The difference between the two groups was significant (p<0.01) CONCLUSION: Polycaprolactone / gelatin (PCL/GT) nanofiber scaffold significantly increases the therapeutic function of hematopoietic stem cells in the wound site.

BACKGROUND AND AIM:Leukocyte adhesion deficiency type 1 (LAD-I) is a rare, autosomal recessive disorder of neutrophil migration, characterized by severe, recurrent bacterial infections, inadequate pus formation and impaired wound healing. The ITGB2 gene encodes the β2 integrin subunit (CD18) of the leukocyte adhesion cell molecules, and mutations in this gene cause LAD-I. The aim of the current study was to investigate the mutations in patients diagnosed with LAD-I and functional studies of the impact of two previously reported and a novel mutation on the expression of the CD18/CD11a heterodimer.MATERIALS AND METHODS:Blood samples were taken from three patients who had signed the consent form. Genomic DNA was extracted and ITGB2 exons and flanking intronic regions were amplified by polymerase chain reaction. Mutation screening was performed after Sanger sequencing of PCR products. For functional studies, COS-7 cells were co-transfected with an expression vector containing cDNA encoding mutant CD18 proteins and normal CD11a. Flow cytometry analysis of CD18/CD11a expression was assessed by dimer-specific IB4 monoclonal antibody.RESULTS:Two previously reported mutations and one novel mutation,p. Cys562Tyr, were found. All mutations reduced CD18/CD11 heterodimer expression.CONCLUSION:Our strategy recognized the p.Cys562Tyr mutation as a pathogenic alteration that does not support CD18 heterodimer formation. Therefore, it can be put into a panel of carrier and prenatal diagnosis programs.

Background and purpose: Application of three-dimensional scaffolds with the ability to simulate a three-dimensional in vivo environment has opened new perspective on targeted differentiation and therapeutic use of stem cells. In this study we examined the compatibility of CD93 stem cells with biodegradable pclgelatin scaffold. Materials and methods: In this experimental study, three-dimensional scaffolds made of PCL gelatin using electrospining synthesis and its molecular structure was tested by SEM electron microscopy. The scaffold surface was disinfected by UV ray. The hematopoietic CD93stem cells of those isolated previously were divided into two groups including normal cultured (plate) and culture on scaffolds (scaffold + cell). The survival and growth of the cells were measured through MTT assay and electron microscopy at 7, 14, and 28 days after culturing. Results: Electron microscopic analysis on the seventh day showed appropriate adhesion of CD93 cells on scaffold fibers and secretion of extracellular matrix. Survival rate of the cells at 7, 14, and 28 days after culturing were not significantly different between the two groups. But at the same days significant differences were observed in the Scaffold + Cell group (P< 0.05). Conclusion: This study suggests that PCL nanofiber scaffolds has high compatibility with CD93 stem cells and proximity to this scaffold lead to increased survival and growth of the cells. Further studies on the treatment of tissue damage and scarring by CD93 stem cells using this scaffold can be effective in increasing treatment efficiency.

Abnormal cell differentiation, in particular suppression of terminal cell differentiation, exists in all tumors. Therapeutic interventions to restore terminal differentiation ("differentiation therapy") are a very attractive way to treat cancer, especially leukemia. A variety of chemicals stimulates differentiation of leukemic cells, such as dimethyl sulfoxide (DMSO) and all-trans retinoic acid (ATRA). Tumor suppressor genes have a vital role in the gateway to terminal cell differentiation. In this study, we inhibited PTEN tumor suppressor gene expression by siRNA to investigate the effect of potentiating cell survival and inhibiting apoptosis on HL-60 cell differentiation by DMSO and ATRA. Our results show that PTEN siRNA increases HL-60 cell differentiation in the presence of DMSO and ATRA. At the same time, the presence of siRNA hampers accumulation of apoptotic cells during incubation. Our study suggests that manipulation of PTEN could hold promise for enhancing efficacy of differentiation therapy of acute myelogenous leukemia.

NETosis has been associated with a particular mode of cell death although it is still controversial as to what extent autophagy is involved in NETosis. Class I/AKT/mTOR pathway is a key regulator of autophagy. PTEN tumor suppressor gene encodes a dual specificity phosphatase that antagonizes the phosphatidylinositol 3-kinase in class the I/AKT/mTOR pathway. In this study, we investigated the effects of PTEN down-regulation as well as overexpression on NETosis. Our results show that 35% of HL-60 differentiated neutrophil-like cells generated NETs by PMA. The portion of the population that produced NETs in PTEN knockdown HL-60 differentiated neutrophils was 9% and in PTEN overexpressed HL-60 differentiated neutrophils, it was 56%. Our results show that increasing PTEN expression increases NETs formation in neutrophils, and its suppression reduces NETs.