Assessment of Bcl-xL, TAX, and HBZ Gene Expression in Adult T cell Leukemia/Lymphoma Patients.

Adult T cell leukemia/lymphoma is a malignancy with a poor prognosis caused by human T lymphocyte virus type 1 (HTLV-1) infection. Tax and HBZ are two major viral proteins that may be involved in oncogenesis by disrupting apoptosis. Because Bcl-xL plays an integral role in the anti-apoptotic pathway, this study examines the interaction between host apoptosis and oncoproteins. We investigated 37 HTLV-1-infected individuals, including 18 asymptomatic and 19 adult T cell leukemia/lymphoma (ATLL) subjects. mRNA was extracted and converted to cDNA from peripheral blood mononuclear cells, and then gene expression was determined using TaqMan q-PCR. Moreover, the HTLV-1 proviral load (PVL) was also measured using a commercial absolute quantification kit (Novin Gene, Iran). Data analysis revealed that the mean of TAX, HBZ, and PVL was significantly higher among the study groups (ATLL and carrier groups p = .003, p = .000, and p = .002 respectively). There was no statistical difference in Bcl-xL gene expression between the study groups (p = .323). It is proposed that this anti-apoptotic pathway may not be directly involved in the development of ATLL lymphoma. Bcl-xL, TAX, HBZ gene expression, and PVL can be utilized as prognostic markers.

Association of the matrix metalloproteinases (MMPs) family gene polymorphisms and the risk of coronavirus disease 2019 (COVID-19); implications of contribution for development of neurological symptoms in the COVID-19 patients.

BACKGROUND: Seemingly, the Matrix metalloproteinases (MMPs) play a role in the etiopathogenesis of coronavirus disease 2019 (COVID-19). Here in this study, we determined the association of MMP9 rs3918242, MMP3 rs3025058, and MMP2 rs243865 polymorphisms with the risk of COVID-19, especially in those with neurological syndrome (NS). METHODS: We enrolled 500 patients with COVID-19 and 500 healthy individuals. To genotype the target SNPs, the Real-time allelic discrimination technique was used. To determine serum levels of MMPs, Enzyme-linked immunosorbent assay (ELISA) was exerted. RESULTS: The MMP9 gene rs3918242 and MMP3 gene rs3025058 SNP were significantly associated with increased COVID-19 risk and susceptibility to COVID-19 with NS. The serum level of MMP-9 and MMP-3 was significantly higher in COVID-19 cases compared with the healthy controls. Serum MMP-9 and MMP-3 levels were also higher in COVID-19 subjects with NS in comparison to the healthy controls. The polymorphisms in MMP genes were not associated with serum level of MMPs. CONCLUSION: MMP9 and MMP3 gene polymorphisms increases the susceptibility to COVID-19 as well as COVID-19 with neurologic syndrome, but they probably have no role in the regulation of serum MMP-9 and MMP-3 levels.

HTLV, a multi organ oncovirus.

Human T lymphotropic virus (HTLV-I) is a retrovirus that has been recognized as a causative agent of two crucidal diseases, HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) and Adult T cell Leukemia-Lymphoma (ATLL). The virus not only induces those diseases in a small proportion of HTLV-I carriers (3-5%) but also it is associated with other diseases such as HTLV-I-Associated Arthropathy (HAAP), Cutaneous T Cell Lymphoma (CTCL), Graves' disease, uveitis, polymyositis, chronic respiratory diseases, lymphadenitis and dermatitis. Furthermore, HTLV related and accelerated disorders were more investigated, and the factors that might implicate in the development or progression of diseases have been discussed. We founded 13 categories of non-associated disease in studies such as Reproductive Disorders, Coronary Artery Disease (CAD), non -ATLL lymphoma, Co-infection, non-HAM/TSP neurological associated disease, non ATLL cutaneous associated disease, Autoimmune-Inflammatory related disease, Kidney disease, Liver disease, Respiratory disease, TB disease and Thyroid disease. With regard to the reviewed studies suggested HTLV-I disorders can divide into three manifests; related, accelerated and associated disease. However, interaction between HTLV-I infection and host immune response was complicated and vague. Some infectious patients indicated the involvement of inflammatory response of immune system, but in other individuals function of anti-inflammatory elements was observed. For a better understanding of this classification, more systematic studies should be designed and need to provide a global network to control and prevent HTLV affiliated diseases.

HTLV-1-host interactions on the development of adult T cell leukemia/lymphoma: virus and host gene expressions.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a lymphoproliferative disorder of HTLV-1-host interactions in infected TCD4+ cells. In this study, the HTLV-1 proviral load (PVL) and HBZ as viral elements and AKT1, BAD, FOXP3, RORγt and IFNλ3 as the host factors were investigated. METHODS: The study was conducted in ATLLs, HTLV-1-associated myelopathy/tropical spastic paraparesis patients (HAM/TSPs) and HTLV-1-asympthomatic carriers (ACs). The DNA and mRNA from peripheral blood mononuclear cells were extracted for gene expression assessments via qRT-PCR, TaqMan assay, and then confirmed by western blotting. RESULTS: As it was expected, the HTLV-1-PVL were higher in ATLLs than ACs (P = 0.002) and HAM/TSP (P = 0.041). The HBZ expression in ATLL (101.76 ± 61.3) was radically higher than in ACs (0.12 ± 0.05) and HAM/TSP (0.01 ± 0.1) (P = 0.001). Furthermore, the AKT1 expression in ATLLs (13.52 ± 4.78) was higher than ACs (1.17 ± 0.27) (P = 0.05) and HAM/TSPs (0.72 ± 0.49) (P = 0.008). However, BAD expression in ATLL was slightly higher than ACs and HAM/TSPs and not significant. The FOXP3 in ATLLs (41.02 ± 24.2) was more than ACs (1.44 ± 1) (P = 0.007) and HAM/TSP (0.45 ± 0.15) (P = 0.01). However, RORγt in ATLLs (27.43 ± 14.8) was higher than ACs (1.05 ± 0.32) (P = 0.02) but not HAM/TSPs. Finally, the IFNλ3 expression between ATLLs (31.92 ± 26.02) and ACs (1.46 ± 0.63) (P = 0.01) and ACs and HAM/TSPs (680.62 ± 674.6) (P = 0.02) were statistically different, but not between ATLLs and HAM/TSPs. CONCLUSIONS: The present and our previous study demonstrated that HTLV-1-PVL and HBZ and host AKT1 and Rad 51 are novel candidates for molecular targeting therapy of ATLL. However, high level of RORγt may inhibit Th1 response and complicated in ATLL progressions.

Assessment of HTLV-1 proviral load, LAT, BIM, c-FOS and RAD51 gene expression in adult T cell leukemia/lymphoma.

Adult T cell leukemia/lymphoma (ATLL) is a life-threatening malignancy of HTLV-1 infected Th lymphocytes. In the present study host-virus interactions were investigated by assessment of HTLV-1 proviral load (PVL) and host gene expression. A cross-sectional study was carried out on 18 ATLL, 10 HAM/TSP patients and 18 HTLV-1 asymptomatic carriers (ACs). DNA and mRNA of the peripheral blood mononuclear cells were extracted for PVL and LAT, BIM, c-FOS and RAD51 gene expression measurement using qRT-PCR. The mean PVL in ATLL patients was 11,430 ± 3770 copies/104 which was statistically higher than ACs, 530 ± 119 copies/104, (p < 0.001). The expression of BIM, and c-FOS in ATLL patients were higher than HTLV-1 ACs; however, there were no statistically significant differences. The expression of RAD51 as an essential player on DNA repair showed around 160 times increase in ATLL group (166 ± 95) compared to ACs (1.04 ± 0.34) which is statistically significant (p < 0.001). Interestingly, there was a positive correlation between RAD51 expression and HTLV-PVL. The expression of LAT as a central adaptor in TCR signaling interestingly was around 36 times higher in ATLL group than ACs (ATLL; 41.33 ± 19.91 vs. ACs; 1.15 ± 0.22, p < 0.001). This finding showed that TCR signaling pathway mainly provides the growth factors for transformed cells. Furthermore, the overexpression of RAD51 which has been induced in HTLV-1 infected cells as a consequence of virus replication is not able to overcome the DNA damage toward cell transformation.

A facile route to diastereomeric phosphorus ylides. Chemoselective synthesis of dialkyl (E)-2-[1-(2-oxocyclopentylidene)ethyl]-2-butenedioates.

2-Acetylcyclopentanone undergoes a smooth reaction with triphenylphosphine and dialkyl acetylenedicarboxylates to produce dialkyl 2-(1-acetyl-2-oxocyclopentyl)-3-(1,1,1-triphenyl-lambda(5)-phosphanylidene)succinates. These compounds undergo intramolecular Wittig reactions in boiling benzene to produce highly strained spirocyclobutene derivatives, which spontaneously undergo ring-opening reactions to produce dialkyl (E)-2-[1-(2-oxocyclopentyliden)ethyl]-2-butenedioates.