Red cell enzyme polymorphisms in three Iranian population samples: Tabriz,Yazd, Mashhad

Three population samples from Iran (Tabriz, Yazd, Mashhad) have been typed for four enzyme group polymorphisms: ACP1, ESD, AK, and PGD. The phenotype and allele frequencies are presented and compared with other Iranian populations. The AK allele frequencies do not show significant intergroup heterogeneity, whereas ACP1, ESD and PGD allele frequencies disclose obvious heterogeneity. The possible reasons therefore are discussed.     

DCPIP (2,6-dichlorophenolindophenol) as a genotype-directed redox chemotherapeutic targeting NQO1*2 breast carcinoma

Accumulative experimental evidence suggests feasibility of chemotherapeutic intervention targeting human cancer cells by pharmacological modulation of cellular oxidative stress. Current efforts aim at personalization of redox chemotherapy through identification of predictive tumour genotypes and redox biomarkers. Based on earlier research demonstrating that anti-melanoma activity of the pro-oxidant 2,6-dichlorophenolindophenol (DCPIP) is antagonized by cellular NAD(P)H:quinone oxidoreductase (NQO1) expression, this study tested DCPIP as a genotype-directed redox chemotherapeutic targeting homozygous NQO1*2 breast carcinoma, a common missense genotype [rs1800566 polymorphism; NP_000894.1:p.Pro187Ser] encoding a functionally impaired NQO1 protein. In a panel of cultured breast carcinoma cell lines and NQO1-transfectants with differential NQO1 expression levels, homozygous NQO1*2 MDA-MB231 cells were hypersensitive to DCPIP-induced caspase-independent cell death that occurred after early onset of oxidative stress with glutathione depletion and loss of genomic integrity. Array analysis revealed upregulated expression of oxidative (GSTM3, HMOX1, EGR1), heat shock (HSPA6, HSPA1A, CRYAB) and genotoxic stress response (GADD45A, CDKN1A) genes confirmed by immunoblot detection of HO-1, Hsp70, Hsp70B', p21 and phospho-p53 (Ser15). In a murine xenograft model of human homozygous NQO1*2-breast carcinoma, systemic administration of DCPIP displayed significant anti-tumour activity, suggesting feasibility of redox chemotherapeutic intervention targeting the NQO1*2 genotype.     

Intra-articular knee implantation of autologous bone marrow–derived mesenchymal stromal cells in rheumatoid arthritis patients with knee involvement: Results of a randomized,triple-blind,placebo-controlled phase 1/2 clinical trial

Background

In this study, we intend to assess the safety and tolerability of intra-articular knee implantation of autologous bone marrow–derived mesenchymal stromal cells (MSCs) in patients with rheumatoid arthritis (RA) and to determine the preliminary clinical efficacy data in this population. The trial registration numbers are as follows: Royan Institute Ethics Committee: AC/91/1133; NCT01873625.

TRAILR1 (rs20576) and GRIA3 (rs12557782) are not associated with interferon-β response in multiple sclerosis patients

Molecular Biology Reports - Multiple sclerosis (MS) is an autoimmune-type inflammatory disorder in human central nervous system. Recombinant interferon beta (IFN-β) decreases the number of...