Relation between microRNA-155 and inflammatory mediators in multiple sclerosis.

Multiple sclerosis (MS) is a complex autoimmune condition affecting the central nervous system characterized by axonal damage, demyelination, and chronic inflammation. Multiple molecular and cellular components mediate neuroinflammation in MS. In human macrophages and microglia, miRNA-155 is an essential proinflammatory noncoding RNA that regulates phenotypic and functional polarization properties. This study was conducted to detect the plasma level of miRNA-155 in RRMS and assess its relationship with inflammatory and anti-inflammatory mediators. The study included 60 MS patients and 30 healthy controls. Real-time quantitative polymerase chain reaction was utilized to detect miRNA-155, iNOS, and SMAD2, whereas ELISA was used to determine TNF-α, IFN-É£, TGF-ß, and IL-10 levels. There was no significant difference in miRNA-155, SMAD2, and iNOS expression in MS patients compared to control subjects. In addition, there was a statistically significant increase in TNF-α, INF-É£, and TGF-ß levels. IL-10 levels did not differ significantly between MS patients and healthy controls. There was a positive correlation between miRNA-155 and TNF-α (p < 0.000, r = 0.922), INF-É£ (p < 0.000, r = 0.81), and iNOS (p < 0.000, r = 0.916) and inverse correlation between miRNA-155 and IL-10 (p < 0.000, r = -0.928), TGF-ß (p < 0.000, r = -0.904) and SMAD2 (p < 0.000, r = -0.848). We conclude that expression of miRNA-155 in MS may modulate macrophage/microglia polarization by increasing the secretion of TNF-α, IFN-É£ & iNOS and decreasing anti-inflammatory mediators IL10 and TGF-ß.

Possible role of rice bran extract in microglial modulation through PPAR-gamma receptors in alzheimer's disease mice model.

Alzheimer's Disease (AD), the most prevalent neurodegenerative disorder among elderly people, is ordinarily associated with progressive cognitive decline. Peroxisome proliferator-activated receptors-gamma (PPAR-γ) agonists can be targeted as a beneficial therapeutic strategy against AD. In the present study, we aimed to investigate the preventive and therapeutic effects of rice bran extract (RBE) as a possible PPAR-γ agonist on the microglial phenotype modulation in AD in mice compared to the effects of pioglitazone. This study included 64 adult male Swiss Albino mice divided into 8 groups, each group comprised 8 mice; control group, RBE group, lipopolysaccharide-induced neurodegeneration (a) (LPSa) group, (LPSb) group, RBE-preventive group (RBE + LPSa), pioglitazone-preventive group (PG + LPSa), RBE-treated group (RBE + LPSb), and pioglitazone-treated group (PG + LPSb). Cognitive functions were assessed by Y-maze and Morris water maze tests. The expression of PPAR-γ, CD45, arginase1, CD36, and CD163 genes was assessed by real time qPCR and the estimation of NF-kß protein level was done by Western blot technique. Moreover, the assessment of Aß42 and P-tau levels was performed by ELISA. Histopathological examination of brain tissues was performed for all the studied groups. Our results showed that RBE and pioglitazone could modulate microglial phenotype from M1 to M2 where they significantly decreased the expression of NF-κß and the pro-inflammatory microglial marker (CD45) in parallel with increasing the expression of the anti-inflammatory microglial and phagocytic markers (arginase1, CD163, and CD36). In addition, RBE and pioglitazone significantly increased PPAR-γ expression and reduced Aß42 deposition as well as p-tau protein levels. In conclusion, our study identified the possible role of PPAR-γ agonistic activity of RBE as a preventive and therapeutic agent in the treatment of the neuro-inflammation associated with AD.

Association of Angiotensin-Converting Enzyme (ACE) Gene Polymorphism with Inflammation and Cellular Cytotoxicity in Vitiligo Patients.

BACKGROUND: Vitiligo is a disorder with profound heterogeneity in its aetio-pathophysiology. Angiotensin converting enzyme (ACE) plays an important role in the physiology of the vasculature, blood pressure and inflammation. An insertion/deletion (I/D) polymorphism of the ACE gene was reported be associated with the development of vitiligo. OBJECTIVE: Our aim was to evaluate the ACE I/D polymorphism in vitiligo patients and controls. Our second aim was to find a possible association between ACE gene polymorphism and inflammatory mediators (as interleukin (IL)-6) and/or cellular cytotoxicity induced by serum nitrite (as a breakdown product of the cytotoxic nitric oxide) in vitiligo patients. METHODS: This case-control study included 74 vitiligo patients and 75 apparently healthy controls. The distribution of ACE gene I/D genotype was investigated using PCR. Serum ACE, IL-6 and nitrite were measured by colorimetric method, ELISA and Griess assay respectively. RESULTS: The ACE allele frequency was significantly different between vitiligo patients and healthy controls (P = 0.026). However there was no significant difference between the ACE genotyping frequency in both groups (P = 0.115). There were statistically significant higher VIDA score (P = 0.007), and serum IL-6 (P < 0.001) in patients with the DD genotype when compared to other genotypes. Serum nitrite in patients with the DD genotype was significantly higher (P = 0.007) when compared to patients with II genotype. Serum levels of ACE, IL-6 and nitrite in vitiligo patients were statistically significantly higher than those in controls. CONCLUSION: As a conclusion, ACE gene polymorphism might grant susceptibility to develop vitiligo. Serum IL-6 and nitrite levels might have an important role in the pathogenesis of vitiligo. Targeting these two factors might have an implication in the treatment of some resistant cases.

Osteopontin gene polymorphisms as predictors for the efficacy of interferon therapy in chronic hepatitis C Egyptian patients with genotype 4.

This study aimed to determine the relationship between osteopontin gene polymorphisms and its protein level and the efficacy of interferon-based therapies in Hepatitis C virus (HCV) patients. Hundreds HCV patients genotype 4, treated with pegylated interferon alfa-2b plus ribavirin and 60 healthy subjects were enrolled. All individuals were subjected to clinical and laboratory parameters, including hepatitis markers and HCV quantitation by real-time polymerase chain reaction. Single nucleotide polymorphisms (SNPs) of osteopontin (OPN) gene (nucleotide -155, -443 and -1748) were analysed by direct sequencing in addition to estimation of serum level of OPN. SNP at -443 (C/C versus C/T, T/T) was found to represent predictors for treatment response by univariate logistic regression analysis. OPN serum level was independent predictors for treatment response by both univariate and multivariate logistic regression analysis. SNP at nucleotide -443 and serum OPN protein levels could be used as useful markers to predict the efficacy of treatment.