Elevated serum level of IL-4 in neuromyelitis optica and multiple sclerosis patients.

Mediators have important roles in the pathogenesis of autoimmune diseases. Interleukin 4 (IL-4) is one of the most important cytokines that has a regulatory effect on immune cells. In the current study, the serum level of IL-4 was assessed in the newly diagnosed neuromyelitis optica (NMO) and multiple sclerosis (MS) patients compared to healthy subjects. ELISA technique was used for assessment of the serum level of IL-4, and data analysis was performed by SPSS software. Serum level of IL-4 was elevated in both NMO and MS patients compared with healthy individuals (P < .001), but no statistically significant difference was identified between MS and NMO patients (P = .071). Furthermore, gender (female) and AQP4-Ab had significant impacts on the level of IL-4 in NMO patients (P < .001). These data show the crucial role of IL-4 in the pathogenesis of NMO and MS diseases. However, we suggest future studies to investigate the serum level of IL-4 in NMO and MS patients to clarify more roles of this cytokine in the pathogenesis of both diseases.

Association Study between Functional Polymorphisms of MMP9 Gene Promoter and Multiple Sclerosis Susceptibility in an Iranian Population.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) polymorphisms, C-1562 T and -90 (CA) n repeats, which influence transcriptional activity of this gene, are proposed to play a role in MS susceptibility and its development. In the present study, the possible association of MMP-9 polymorphisms in Iranian MS patients is studied. METHODS: Association of MMP-9 mentioned gene polymorphisms with MS susceptibility was evaluated in unrelated Iranian subjects referred to Al-Zahra Hospital, Isfahan, Iran during 2014 to 2017. RESULTS: -1562 T allele of MMP-9 was associated with increased MS risk. However, we found no overall significant effect of -90 (CA)n repeat on MS susceptibility. CONCLUSION: For as much as MMP-9 molecule is a potential target for MS therapy, to determine whether any of MMP-9 polymorphisms influence MS susceptibility in Iranian MS patients or not, concerning the significant influence of T allele on MS susceptibility and the non-significant association regarding CA repeats, further research is needed before proposing any definite conclusion.

Bone Repair with Differentiated Osteoblasts from Adipose-derived Stem Cells in Hydroxyapatite/Tricalcium Phosphate In vivo.

BACKGROUND: Recently, tissue engineering has developed approaches for repair and restoration of damaged skeletal system based on different scaffolds and cells. This study evaluated the ability of differentiated osteoblasts from adipose-derived stem cells (ADSCs) seeded into hydroxyapatite/tricalcium phosphate (HA-TCP) to repair bone. METHODS: In this study, ADSCs of 6 canines were seeded in HA-TCP and differentiated into osteoblasts in osteogenic medium in vitro and bone markers evaluated by reverse transcription polymerase chain reaction (RT-PCR). Scanning electron microscopy (SEM) was applied for detection of cells in the pores of scaffold. HA-TCP with differentiated cells as the test group and without cells as the cell-free group were implanted in separate defected sites of canine's tibia. After 8 weeks, specimens were evaluated by histological, immunohistochemical methods, and densitometry test. The data were analyzed using the SPSS 18 version software. RESULTS: The expression of Type I collagen and osteocalcin genes in differentiated cells were indicated by RT-PCR. SEM results revealed the adhesion of cells in scaffold pores. Formation of trabecular bone confirmed by histological sections that revealed the thickness of bone trabecular was more in the test group. Production of osteopontin in extracellular matrix was indicated in both groups. Densitometry method indicated that strength in the test group was similar to cell-free group and natural bone (P > 0.05). CONCLUSIONS: This research suggests that ADSCs-derived osteoblasts in HA-TCP could be used for bone tissue engineering and repairing.

Correlation of midkine serum level with pro- and anti-inflamatory cytokines in multiple sclerosis.

BACKGROUND: Midkine (MK) is a heparin-binding growth factor with promoting effects in inflammatory responses through enhancing leukocytes migration. OBJECTIVE: To study the correlation between MK serum levels and concentration of inflammatory cytokines in Multiple Sclerosis (MS) patients. METHODS: We evaluated the MK level and its relationship with inflammatory cytokines (IL-17 and IL-23) and anti-inflammatory ones (IL-10 and TGF-ß) in multiple sclerosis (MS) patients. The serum concentrations of MK and cytokines were assessed by ELISA in 32 MS patients in comparison with 32 healthy subjects. RESULTS: Our data showed that the MK concentration in MS patients is lower than healthy controls (341.15 ± 40.71 Pg/ml vs. 620.15 ± 98.61 Pg/ml, respectively, p=0.015). We also observed a significant decrease in IL-10, IL-23, and TGF-ß cytokine levels in MS patients. There was a significant correlation between MK and IL-23 concentrations in our study (r = +0.829, p≤ 0.001). CONCLUSION: These results confirm a role for MK in inflammatory reactions in MS.

Can vitamin d suppress endothelial cells apoptosis in multiple sclerosis patients?

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease of central nerves system, in which neurological disabilities occur in young adults. Despite increasing number of studies on MS, some aspects of this disorder are still unclear. In the previous studies, it has been proven that there is direct relation between MS incidence and vitamin D deficiency. Thereby, strong evidence in MS pathogenesis suggests that endothelial cells (EC) could be harmed in MS. In addition, functional changes in EC and macrovascular injuries lead blood-brain barrier disruption in MS. Current study is the first investigation to elucidate positive influences of vitamin D against EC apoptosis in MS. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured and then treated with sera from patients with active MS (in relapse) and sera from healthy volunteer participants as control group (each group n=15). 3-(4,5-dimethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay for cell surveillance and cell-death detection kit for evaluating apoptosis were used in this study. RESULTS: There was a significant decrease in apoptosis rate by the serum of patients, just when 1,25(OH)2D3 applied before treating HUVECs with sera from active MS (in relapse). Furthermore, the cells surveillance increased markedly with the presence of 1,25(OH)(2)D(3) in culture, too. CONCLUSION: Withregard to increment in EC apoptosis rate, which treated by the sera from MS patients and decrement in apoptosis rate by the presence of vitamin D in culture media, it could be proposed that vitamin D pre-treatment can be used for MS patients, due to its beneficial effects on protecting EC apoptosis.

Neurological manifestations in patients with antiphospholipid syndrome.

BACKGROUND: Anti-phospholipids syndrome (APS) is considered a non inflammatory auto-immune disease with a significant thrombophilic risk with varied clinical manifestations. The purpose of the current study was to investigate the frequency of thrombotic and non-thrombotic events in patients with APS. METHODS: In this retrospective study, 102 definite APS subjects were recruited (2007-2011) at Alzahra Hospital, Isfahan, Iran. The patients were referred to Multiple Sclerosis Clinic with the diagnosis of definite APS according to 2006 Sydney's criteria. Disorders associated with APS such as pregnancy complication, vascular thrombosis and livedo reticularis (LR) were assessed. Neurological signs and symptoms such as cognitive dysfunction were recorded. Data analyses were performed using SPSS software and P < 0.05 were considered to be statistically significant. RESULTS: Our findings showed that majority of female gender, higher rate of ischemic thrombotic stroke and high miscarriage lied in a large number of APS patients. CONCLUSION: Overall recurrent miscarriage is a common complication among (antiphospholidpid antibody) aPL patients. Furthermore, ischemic stroke is the second common neurological manifestations of APS patients.