An insight to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis; evidence from high-throughput data integration and meta-analysis

Background Human T-lymphotropic virus 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive disease of the central nervous system that significantly affected spinal cord, nevertheless, the pathogenesis pathway and reliable biomarkers have not been well determined. This study aimed to employ high throughput meta-analysis to find major genes that are possibly involved in the pathogenesis of HAM/TSP. Results High-throughput statistical analyses identified 832, 49, and 22 differentially expressed genes for normal vs. ACs, normal vs. HAM/TSP, and ACs vs. HAM/TSP groups, respectively. The protein-protein interactions between DEGs were identified in STRING and further network analyses highlighted 24 and 6 hub genes for normal vs. HAM/TSP and ACs vs. HAM/TSP groups, respectively. Moreover, four biologically meaningful modules including 251 genes were identified for normal vs. ACs. Biological network analyses indicated the involvement of hub genes in many vital pathways like JAK-STAT signaling pathway, interferon, Interleukins, and immune pathways in the normal vs. HAM/TSP group and Metabolism of RNA, Viral mRNA Translation, Human T cell leukemia virus 1 infection, and Cell cycle in the normal vs. ACs group. Moreover, three major genes including STAT1, TAP1, and PSMB8 were identified by network analysis. Real-time PCR revealed the meaningful down-regulation of STAT1 in HAM/TSP samples than AC and normal samples (P = 0.01 and P = 0.02, respectively), up-regulation of PSMB8 in HAM/TSP samples than AC and normal samples (P = 0.04 and P = 0.01, respectively), and down-regulation of TAP1 in HAM/TSP samples than those in AC and normal samples (P = 0.008 and P = 0.02, respectively). No significant difference was found among three groups in terms of the percentage of T helper and cytotoxic T lymphocytes (P = 0.55 and P = 0.12). Conclusions High-throughput data integration disclosed novel hub genes involved in important pathways in virus infection and immune systems. The comprehensive studies are needed to improve our knowledge about the pathogenesis pathways and also biomarkers of complex diseases.Peer reviewe

CUTANEOUS LEISHMANIASIS: EVALUATION OF 248 CASES IN SHUSHTAR COUNTY, SOUTH-WEST OF IRAN

Objectives: leishmaniasis is one of six major tropical diseases that the World Health Organization has supported study and research about various aspects of the recommendations. Cutaneous leishmaniasis (CL) is considered a common parasitic disease. This study was performed to determine the frequency of patients with CL and the epidemiological situation in the county of Shushtar during 2009- 2013. Methods: In this descriptive study, information about subjects such as age, gender , number and location of wounds , city or village , month and season collected and have been interpreted with SPSS software and descriptive statistics. Results: Totally, 248 cases have detected during this study. About 82.7 percent percent of patients had more than 10 years of age and most cases (66.1 percent) were found in males. Nearly 48.4 percent of patients had one ulcer and 37.1 percentage of the wounds were observed on the hands and then in feet, face and in other parts of the body. Approximately 83.9 percent were in rural areas and most cases were in March month (16.9 percent). Conclusions: According to the environmental conditions for sand fly activity in some months in this area prevention and treatment of patients in urban and rural areas of Shushtar is a key priority. Key words: Epidemiology, Cutaneous Leishmaniasis, Iran

Historical Cohort of Severe Congenital Neutropenia in Iran:Clinical Course, Laboratory Evaluation, Treatment, and Survival

Introduction: Severe congenital neutropenia (SCN) is one of the primary immunodeficiency diseases developed by genetic alterations. Mutations in several genes including HAX-1, G6PC3, jagunal, and VPS45 account for autosomal recessive SCN. Patients and Methods:Patients with SCN registered in the Iranian Primary Immunodeficiency Registry and referred to our clinic at the Children's Medical Center were reviewed.Results: Thirty-seven eligible patients with a mean age of 28.51 ± 24.38 months at the time of diagnosis were included. Nineteen cases had consanguineous parents and 10 cases had confirmed or unconfirmed positive family history. The most prevalent infectious symptoms were oral infections followed by respiratory infections. We identified HAX-1 mutation in 4, ELANE mutation in 4 cases, G6PC3 mutation in 1, and WHIM syndrome in 1 case. Other patients remained genetically unclassified. After the median follow-up of 36 months from the time of diagnosis, the overall survival was 88.88%. The mean event-free survival was 185.84 months (95% CI: 161.02, 210.66). Discussion: Autosomal recessive SCN is more common in countries with high rates of consanguinity like Iran. The genetic classification was possible only for a few patients in our study. This might suggest that there are other autosomal recessive genes causative of neutropenia that have yet to be described.</p

Induced pluripotent stem cells modulate the Wnt pathway in the bleomycin-induced model of idiopathic pulmonary fibrosis

Abstract Background The Wnt signaling pathway has been implicated in the pathogenesis of fibrotic disorders and malignancies. Hence, we aimed to assess the potential of the induced pluripotent stem cells (IPS) in modulating the expression of the cardinal genes of the Wnt pathway in a mouse model of idiopathic pulmonary fibrosis (IPF). Methods C57Bl/6 mice were randomly divided into three groups of Control, Bleomycin (BLM), and BLM + IPS; the BLM mice received intratracheal instillation of bleomycin, BLM + IPS mice received tail vein injection of IPS cells 48 h post instillation of the BLM; The Control group received Phosphate-buffered saline instead. After 3 weeks, the mice were sacrificed and Histologic assessments including hydroxy proline assay, Hematoxylin and Eosin, and Masson-trichrome staining were performed. The expression of the genes for Wnt, β-Catenin, Lef, Dkk1, and Bmp4 was assessed utilizing specific primers and SYBR green master mix. Results Histologic assessments revealed that the fibrotic lesions and inflammation were significantly alleviated in the BLM + IPS group. Besides, the gene expression analyses demonstrated the upregulation of Wnt, β-Catenin, and LEF along with the significant downregulation of the Bmp4 and DKK1 in response to bleomycin treatment; subsequently, it was found that the treatment of the IPF mice with IPS cells results in the downregulation of the Wnt, β-Catenin, and Lef, as well as upregulation of the Dkk1, but not the Bmp4 gene (P values < 0.05). Conclusion The current study highlights the therapeutic potential of the IPS cells on the IPF mouse model in terms of regulating the aberrant expression of the factors contributing to the Wnt signaling pathway

Laboratory diagnosis, clinical manifestations, epidemiological situation and public health importance of cutaneous leishmaniasis in Shushtar County, Southwestern Iran

AbstractObjectiveTo investigate as a descriptive and cross sectional study on epidemiology, the laboratory diagnosis and clinical manifestation of Cutaneous Leishmaniasis (CL) in Shushtar County.MethodsThe investigation was carried out on referrals from different districts of Shushtar County and was diagnosed based on their ulcer clinical manifestations with CL using laboratory method. This study was actively developed over the period of 2008 to 2010. Surface of a clean slide was pressed on to the scraped part of the lesions and moved along to produce a smear on the slide. The slides were fixed with methanol, stained with standard Giemsa, and examined carefully under high magnification for an hour or more to look for amastigotes by a trained person. Two smears were prepared and examined from each patient and data were collected using different correlative patients characteristics to analyze information. The essential records including residential area, type and location of lesion, age, sex, the number of ulcers, season, and the history of traveling to endemic areas for this disease were carefully gathered.ResultsParasites presumed to be Leishmania major (L. major) based on the existence of a large vacuole in the cytoplasm. Totally 206 patients were referred to the central laboratory and their manifestation lesions were clinically examined. Of these, 64 cases (31.1%) were female and 142 cases (68.9%) were male. The findings documented that the rate of incidence of CL was in fall 61 cases (29/6%) and winter 80 cases (38/8%), which is one of the most important characteristics of zoonotic CL. Sixty-eight cases (33%) had ulcers on hands, 63 cases (30.6%) on feet and 30 cases (14.6%) on hands and feet. A total of 120 patients (58.3%) had only one ulcer. But 70 cases (34%) had 2 ulcers. The highest incidence was found among patients with two age groups of 20-29 years old (43.2%) and 10-19 years old (18%). The most cases resided in rural areas with 164 cases (79.6%).ConclusionsAnalyzing of the composed results revealed that this area could be considered as one of the endemic foci of zoonotic cutaneous leishmaniasis caused by L. major. In view of the high prevalence rate and distribution of leishmaniasis in Iran, it is in necessity of data gathering about vectors and reservoirs of each district for prevention. Designing control programs play prominent role in this case. With respect to the increased prevalence of CL in Shushtar districts, health care observers should pay further attention on preventing