Investigating the effect of MAP2K1 gene (MEK1) in MAPK pathway in the induction of adult T-cell leukemia/lymphoma (ATLL).

Background and Objectives: HTLV-1 is responsible for two important diseases, HAM/TSP and ATLL. Approximately 10 to 20 million people are infected with HTLV-1 worldwide. Identifying altered genes in different cancers is crucial for finding potential treatment strategies. One of the proteins of the RAS/MAPK signaling pathway is MEK1, which is made from the MAP2K1 gene. The effects of the MAP2K1 gene on the MAPK signaling pathway are not yet fully elucidated. The current study aims to determine the MAP2K1 gene mutations and the level of MAP2K1 gene expression in ATLL patients compared to healthy individuals. Materials and Methods: Ten ATLL and 10 healthy control individuals were investigated in this study. We used ELISA test to screen anti-HTLV-I antibodies and PCR for confirmation of infection. Then, we extracted total RNA from fresh whole blood, and cDNA was synthesized. The expression levels of the MAP2K1 gene were examined by qRT-PCR, and to check possible mutations in the MAP2K1 gene; all samples were sequenced and analyzed by BioEdite Software. Results: MAP2K1 gene expression in the ATLL group was significantly higher than in the healthy control (P=0.001). The mutational sequencing analysis showed nucleotide 212 (S→R) change and identification mutations at different nucleotides that were entirely different from the nucleotide mutations defined in the UniProt database. Conclusion: These results could be a perspective in the prevention, prognosis, and targeted treatment of diseases in which the MAP2K1 gene plays a vital role.

Molecular epidemiology and phylogenetic analysis of human T-lymphotropic virus type 1 in the tax gene and it association with adult t-cell leukemia/lymphoma disorders.

BACKGROUND AND OBJECTIVES: Human T-lymphotropic virus type-1 (HTLV-1) belongs to retrovirus family that causes the neurological disorder HTLV-1 adult T-cell leukemia/lymphoma (ATLL). Since 1980, seven subtypes of the virus have been recognized. HTLV-1 is prevalent and endemic in some regions, such as Africa, Japan, South America and Iran as the endemic regions of the HTLV-1 in the Middle East. To study HTLV-1 subtypes and routes of virus spread in Iran, phylogenetic and phylodynamic analyses were performed and for as much as no previous phylogenetic studies were conducted in Tehran, we do this survey. To this purpose, the Tax region of HTLV-1 was used. MATERIALS AND METHODS: In this study 100 samples were collected from blood donors in Tehran. All samples were screened for anti-HTLV-I antibodies by ELISA. Then, genomic DNA was extracted from all positive samples (10 people), and for confirmation of infection, ordinary PCR was performed for both the HBZ and LTR regions. Moreover, the Tax region was amplified and purified PCR products were sequenced and analyzed, and finally, a phylogenetic tree was constructed using Mega X software. RESULTS: Phylogenetic analysis confirmed that isolates from Iran, Japan, Brazil, and Africa are located within the extensive "transcontinental" subgroup A clade of HTLV-1 Cosmopolitan subtype a. The Japanese sequences are the closest to the Iranian sequences and have the most genetic similarity with them. CONCLUSION: Through phylogenetic and phylodynamic analyses HTLV-1 strain in Tehran were characterized in Iran. The appearance of HTLV-1 in Iran was probably happened by the ancient Silk Road which linked China to Antioch.

Inhibition of growth and gene expression in Staphylococcus aureus by anti-gyrA peptide nucleic acid.

Aim: Multidrug-resistant Staphylococcus aureus isolates have become a serious concern in clinical microbiology. Antisense strategy, which specifically targets essential genes, could be helpful. Materials & methods:S. aureus cultures were treated with peptide conjugate-peptide nucleic acid (PPNA) specific for the gyrA gene. In addition, antimicrobial synergy with ciprofloxacin was tested. Results: The results indicated anti-gyrA-PPNA dramatically inhibited the growth of S. aureus isolates in Mueller Hinton Broth with complete elimination of bacteria observed on cell cultures. Specifically, PPNA reduced the gyrA transcripts up to 50%. With antisense interference, growth inhibition was augmented through combination with ciprofloxacin. Conclusion: This study suggested that anti-gyrA-PPNAs could be introduced as a novel candidate for developing antisense antibiotic to treat all S. aureus infections.

Genetic diversity and antibiotic susceptibility of uropathogenic Escherichia coli isolates from kidney transplant recipients.

PURPOSE: Uropathogenic Escherichia coli (UPEC) strains are a common cause of transplant rejection, morbidity, and mortality among kidney transplant recipients. The virulence of UPEC strains differs based on their pathogenicity islands (PAIs) and susceptibility to antibiotics. The present study evaluates the clonal relationship and antibiotic susceptibility of UPEC PAI-genotypes among Escherichia coli (E. coli) isolates from kidney transplant patients. PATIENTS AND METHODS: A total of 115 Escherichia coli (E. coli) isolates were collected from kidney transplant recipients with acute urinary tract infections (UTIs). Isolates were typed based on the presence of PAI-markers, and random amplified polymorphic DNA (RAPD). The disk diffusion method was performed for the antibiotic susceptibility pattern of isolates. RESULTS: According to the PAI-specific virulence markers, 69 (60%), 21 (18.3%), and 25 (21.7%) isolates were identified as genotypes related to UPEC 536, UPEC J96, and UPEC CFT073 strains, respectively. PAI III536 genotypes were the most prevalent genotype in this study. The findings showed a high-sensitivity to imipenem (93.9%) and nitrofurantoin (91.3%) and a low-sensitivity to trimethoprim/sulfamethoxazole (36.5%). Clonal association and similar antibiotic susceptibility pattern were seen in the PAI-related genotypes. CONCLUSION: Due to a similar pattern of antibiotic susceptibility of these clonal groups and increased resistance to some important antibiotics such as trimethoprim/sulfamethoxazole in the treatment of urinary tract infections, especially in kidney transplant patients, the spread of these clones should be considered as a serious concern.