فهرست مطالب mohammad taher tahoori

Fibroblast-like synoviocytes (FLS), also known as synovial fibroblasts or type B synoviocytes, are the primary cells responsible for the structure of the synovial lining. They are crucial for the formation of a healthy, organized synovial lining. In rheumatic synovium affected by inflammation, the typical three-layered synovial lining transforms into a pannus-like structure. Various pro-inflammatory conditions in the joints of rheumatoid arthritis (RA) patients, characterized by elevated levels of cytokines, growth factors, and infiltration of inflammatory cells, strongly activate FLS cells. Moreover, environmental conditions in the joints of RA patients, such as high pressure and hypoxia, induce changes that further contribute to FLS activation and the development of aggressive characteristics. These changes include increased proliferation, reduced apoptosis, and enhanced cell migration, collectively referred to as a tumor-like phenotype. Additionally, FLS cells release inflammatory cytokines, amplifying inflammation and attracting immune cells to the joint. They also play a role in degrading the extracellular matrix and causing cartilage and bone damage through the production of enzymes like matrix metalloproteinases (MMPs), collagenase, aggrecans, and cathepsins. Recent therapeutic approaches have been directed at targeting the signaling pathways that activate FLS cells and inhibiting factors and cytokines produced by these cells to alleviate inflammatory symptoms and reduce joint damage. It is anticipated that these treatment strategies will complement existing therapies in the near future.

FLS cells are the main components of maintaining the health and nutrition of joints. These cells produce various cytokines, chemokines, angiogenic factors, as well as factors that contribute to the breakdown of matrix and cartilage. The main drivers of significant changes in inflamed joints are proliferation and resistance to apoptosis. Treatment strategies have been developed to target the signaling pathways that activate these cells, with a focus on improving inflammatory symptoms. It is expected that these treatment strategies will be incorporated into existing therapies in the near future.

Premature ovarian failure (POF), is menopause occurring before the age of 40, affecting 1-3% of women worldwide. The risk of POF increases with altered immunological parameters such as FAS and FASL genes, which play a fundamental role in embryogenesis and cellular homeostasis.

The study aimed to investigate the potential role of FAS and FASL genes in POF pathogenesis.

In this case-control study, the polymorphisms of FAS-670A/G and FASLIVS2nt_124A/G apoptotic genes were analyzed in 51 Iranian women suffering from POF, and 61 healthy controls. Isolation of DNA was done using the salting-out method, and genotypic analysis was performed for all the subjects using the polymerase chain reaction-restriction fragment length polymorphism method.

Our results revealed that homozygous FAS-670A/A and G/G, and heterozygous FAS-670A/G are not significantly different between cases and controls (p = 0.99). Also, in different genotyping models of FASIVS2nt_124, polymorphisms were not related to POF risk (p = 0.23).

There is no statistical association between these polymorphisms and POF risk in women referred to genetic counseling clinics.

Eptifibatide (Integrilin®) is a hepta-peptide drug which specifically prevents the aggregation of activated platelets. The peptide drugs are encapsulated into nanolipisomes in order to decreasing their side effects and improving their half-life and bioavailability. In this study, the in vitro cytotoxicity and hemocompatibility of RGD-modified nano-liposomes (RGD-MNL) encapsulated a highly potent antiplatelet drug (eptifibatide) was investigated. RGD-MNL encapsulated eptifibatide was prepared using lipid film hydration and freeze/thawing method. The morphology and size distribution (about 90 nm) of RGD-MNL were characterized using transmission electron microscopy (TEM). The in-vitro cytotoxicity of nano-liposomes was examined using the MTT, LDH release and reactive oxygen species (ROS) generation assays. The effect of RGD-MNL on red blood cells (RBC) was investigated using hemolysis and LDH release assays. The results revealed that RGD-MNL had no significant cytotoxic effect on HeLa and HUVEC cell lines, and also no ROS generation increase in the cells. In addition, the adverse effect of RGD-MNL on LDH release and membrane integrity of RBC was not observed. In conclusion, the recommended RGD-MNL formulations have not any significant cytotoxicity on normal cells or RBC and have potential for protecting and enhancing the activity of antiplatelet drugs.

MicroRNAs (miRNAs) are small preserved non-coding RNA molecules that regulate gene expression post-transcriptionally by targeting the 3' UTR of mRNAs for translational repression or degradation. The rising evidence has established the significant role of miRNAs within the regulation of immune system and the prevention of autoimmunity. MiR-146a has obtained an importance as a modulator of differentiation and the function of cells of the adaptive, as well as innate immunity rapidly. In this paper, we summarize the recent understanding of the role of miR-146a in adaptive and innate immune responses, as well as in autoimmunity.

Human Wharton’s Jelly-derived Mesenchymal Stem Cells (hWJ-MSCs) are easily available cells without transplant rejection problems or ethical concerns compared to bone-marrow-derived MSCs for prospective clinical applications. These cells display immunosuppressive properties and may be able to play an important role in autoimmune disorders. Regulatory T-cells (Treg) are important to prevent autoimmune disease development. Interleukin 35 (IL-35) induces the proliferation of Treg cell populations and reduces the activity of T helper 17 (Th17) and T helper 1 (Th1) cells, which play a central role in initiation of inflammation and autoimmune disease.Recent studies identified IL-35 as a new inhibitory cytokine required for the suppressive function of Treg cells. We created IL-35-producing hWJ-MSCs as a good vehicle for reduction of inflammation and autoimmune diseases. We isolated hWJ-MSCs based on explant culture. HWJ-MSCs were transduced at MOI=50 (Multiplicity of Infection) with lentiviral particles harboring murine Interleukin 35 (mIL-35). Expression of IL-35 in hWJ-MSCs was quantified by an IL-35 ELISA kit.IL-35 bioactivity was analyzed by inhibiting the proliferation of mouse splenocytes using CFSE cell proliferation kit. Frequency of CD4+CD25+CD127low/neg Foxp3+ Treg cells was measured by flow cytometry. There was an up to 85% GFP positive transduction rate, and the cells successfully released a high level of mIL-35 protein (750 ng/ml). IL-35 managed to inhibit CD4+ T cell proliferation with PHA, and improved the frequency of Treg cells.Our data suggest that transduced hWJ-MSCs overexpressing IL-35 may provide a useful approach for basic research on gene therapy for autoimmune disorders.

Programmed death 1 (PDCD1), a negative T-cell regulator which induces peripheral tolerance, belongs to Ig super and CD28/CTLA-4 families. PD-1 gene induces negative signals in T-cells during interaction with its ligands. Thus the aim of this study was to investigate the relationship between PD-1 polymorphism and the risk of rheumatoid arthritis (RA) in Iranian patients and healthy controls.

In this case-control study, genomic DNA was extracted from the whole blood samples using DNA purification kit (DNG-plus, Cinnagen, Iran). PD1.1G/A as a SNP located on promoter with position -536 were genotyped for 120 RA patients and 188 healthy controls through PCR-RFLP method. Association of genotypes and alleles frequency in the patients was compared with controls and analyzed using Chi-square test and 2×2 contingency table in SPSS software version 15.0. The diagnosis of RA patients and provision of their clinical information was done in Rheumatology Research Center of Tehran University of Medical Sciences, Tehran, Iran.

The A allele of the PD1.1 polymorphism located on the promoter of PD-1 gene was significantly more frequent in Iranian RA patients than the controls (p=0.04). There were no significant differences in PD1.1G/G genotype (p=0.08), PD1.1A/A genotype (p=0.39), and PD1.1G/A genotype (p=0.16) between RA cases and controls.

The findings of this study showed the presence of a significant relationship between the A allele of the PD1.1 (-536) of the promoter and susceptibility to RA in Iranian patients.