Dimethyl fumarate: Regulatory effects on the immune system in the treatment of multiple sclerosis

Dimethyl fumarate (DMF) is an important oral treatment option for various autoimmune diseases, such as multiple sclerosis (MS) and psoriasis. DMF and its dynamic metabolite, monomethyl fumarate (MMF) are the major compounds that exert therapeutic effects on several pathologic conditions in part, through downregulation of immune responses. The exact mechanism of DMF is yet to be fully understood even though its beneficial effects on the immune system are extensively studied. It has been shown that DMF/MMF can affect various immune cells, which can get involved in both the naive and adaptive immune systems, such as T cells, B cells, dendritic cells, macrophages, neutrophils, and natural killer cells. It is suggested that DMF/MMF may exert their effect on immune cells through inhibition of nuclear factor-κB translocation, upregulation of nuclear factor erythroid-derived 2(E2)-related factor antioxidant pathway, and activation of hydroxyl carboxylic acid receptor 2. In this review, the mechanisms underlying the modulatory functions of DMF or MMF on the main immune cell populations involved in the immunopathogenesis of MS are discussed.     

MiRNAs and inflammatory bowel disease: An interesting new story

Inflammatory bowel disease (IBD), as a chronic and recurrent inflammatory disorder, is caused by a dysregulated and aberrant immune response to exposed environmental factors in genetically susceptible individuals. Despite huge efforts in determining the molecular pathogenesis of IBD, an increasing worldwide incidence of IBD has been reported. MicroRNAs (miRNAs) are a set of noncoding RNA molecules that are about 22 nucleotides long, and these molecules are involved in the regulation of the gene expression. By clarifying the important role of miRNAs in a number of diseases, their role was also considered in IBD; numerous studies have been performed on this topic. In this review, we attempt to summarize a number of studies and discuss some of the recent developments in the roles of miRNAs in the pathophysiology, diagnosis, and treatment of IBD.     

A comparative study of feeding methods: Effect on the growth,behaviour and biochemical performance of juvenile Beluga sturgeon (Huso huso Linnaeus, 1758)

This study compared the influence of feeding methods on growth parameters of young‐of‐year Beluga sturgeon Huso huso in a 6‐week trial. Fish with an average weight 150.3 ± 0.8 g (±SE) were stocked into nine circular concrete tanks (30 fish per tank) in an open circular system with water temperature of 18.9°C. All fish were fed by three different feeding methods: (a) hand‐fed (HF), (b) continuously available (automated feeder; AF), (c) half of daily feed provided by hand, and another half by automated feeder (combined feeding). For the hand‐feeding method, fish were fed at 09:00, 14:00, 19:00, and 24:00. The entire automatic feeding groups were fed with the same amount of feed. The mean final body weight was the highest in fish fed by AF compared to fish fed by HF. Body weight increase, condition factor, specific growth rate, and feed conversion ratio did not differ among the feeding groups. Fish fed by AF revealed higher swimming activity than the HF group. No significant changes were found in hematocrit, glucose and total protein concentrations among treatments. The results showed less dependence of growth and physiology of Beluga sturgeon on feeding method, but automated‐feeding was shown to be suitable for sturgeon rearing because of further low labour costs in rearing systems.     

Intravenous immunoglobulin G treatment increases live birth rate in women with recurrent miscarriage and modulates regulatory and exhausted regulatory T cells frequency and function

Exhausted T cells and regulatory T (Treg) cells have been recently proposed to be new risk factors for recurrent miscarriage (RM). Intravenous immunoglobulin G (IVIG) treatment reported to modulate various immune cells. In this study, the effects of IVIG on the frequency and function of exhausted T cells, exhausted Tregs, and Treg cells, as well as pregnancy outcome in women with unexplained RM (URM), were investigated. Ninety-four pregnant women with RM were enrolled. At the time of positive pregnancy, blood samples were drawn. Forty-four patients with URM were included as IVIG receiving treated group and received 400 mg/kg of IVIG and the rest fifty patients were considered as a control group and received no IVIG administration. IVIG was given intravenously every 4 weeks during 32 weeks of gestation. Blood samples of patients were collected after the latest administration. Exhausted T cells, exhausted Tregs, and Treg cells were evaluated pre- and posttreatment in both groups. IVIG induced a significant decrease in the frequency of exhausted Tregs population and function as well as a significant increase in Treg cells population, however, IVIG failed to affect population and the function of exhausted T cells. Pregnancy outcome was successful in IVIG treated women (86.3%) and were significantly different (P = 0.0006) in compared with the untreated URM subjects (42%). Therefore, employing of IVIG increases Treg cells and diminishes exhausted Tregs responses in RM patients with cellular immune anomalies throughout the pregnancy. Immunemodulatory effects of IVIG are probably associated with successful pregnancy outcome.     

Dysregulated expression of STAT1, miR-150, and miR-223 in peripheral blood mononuclear cells of coronary artery disease patients with significant or insignificant stenosis

Coronary artery disease (CAD) is a multicellular disease characterized by chronic inflammation. Peripheral blood-mononuclear cells (PBMCs), as a critical component of immune system, actively cross-talk with pathophysiological conditions induced by endothelial cell injury, reflecting in perturbed PBMC expression. STAT1 is believed to be relevant to CAD pathogenesis through regulating key inflammatory processes and modulating STAT1 expression play key roles in fine-tuning CAD-related inflammatory processes. This study evaluated PBMC expressions of STAT1, and its regulators (miR-150 and miR-223) in a cohort including 72 patients with CAD with significant ( ≥ 50%) stenosis, 30 patients with insignificant ( < 50%) coronary stenosis (ICAD), and 74 healthy controls, and assessed potential of PBMC expressions to discriminate between patients and controls. We designed quantitative real-time polymerase chain reaction (RT-qPCR) assays and identified stable reference genes for normalizing PBMC quantities of miR-150, miR-223, and STAT1 applying geNorm algorithm to six small RNAs and five mRNAs. There was no significant difference between CAD and ICAD patients regarding STAT1 expression. However, both groups of patients had higher levels of STAT1 than healthy controls. miR-150 and miR-223 were differently expressed across three groups of subjects and were downregulated in patients compared with healthy controls, with the lowest expression levels being observed in patients with ICAD. ROC curves suggested that PBMC expressions may separate between different groups of study subjects. PBMC expressions also discriminated different clinical manifestations of CAD from ICADs or healthy controls. In conclusion, the present study reported PBMC dysregulations of STAT1, miR-150, and miR-223, in patients with significant or insignificant coronary stenosis and suggested that these changes may have diagnostic implications.     

mRNA translation during oocyte maturation plays a key role in development of primordial germ cells in<Emphasis Type="Italic">Xenopus</Emphasis> embryos

It is believed that cytoplasmic localization in the egg is necessary for development of primordial germ cells (PGCs) inXenopus embryos. In this study, we sought to determine if translation of maternal mRNA during oocyte maturation is involved in the development of PGCs. Donor oocytes were collected from both stimulated (those who receive gonadotropin) and unstimulated females, artificially matured and fertilized using a host transfer technique. Using chloramphenicol (50 μM and 500 μM RNA), RNA translation was inhibited during oocyte maturation. Our results showed that in unstimulated embryos treated with 50 μM chloramphenicol, there was a significant reduction in the number of PGCs reaching genital ridges. In stimulated embryos, however, the number of PGCs was unchanged unless a higher concentration (500 (μM) of chloramphenicol was used. From these results it is suggested that maternal mRNA translation during oocyte maturation plays a key role in development of PGCs.     

Lengthening the nose with a tongue-and-groove technique

Lengthening the short nose is often a major task. The ability to maintain proper alignment between the nasal base and dorsum may prove difficult without sacrificing the suppleness of the former. In this article, the authors introduce a technique of nose lengthening that ensures alignment of the tip with the rest of the nose yet avoids tip rigidity, unless a significant increase in tip projection is also planned. Two spreader grafts are placed, one on either side of the septum, and are extended beyond the caudal septal angle proportional to the planned nasal lengthening. A columella strut, with the cephalocaudal dimension equaling the combination of the width of the existing medial crura plus the amount of planned nasal lengthening, is placed between the medial crura in continuity with the caudal septum and is fixed to the medial crura using 5-0 clear nylon or polydioxanone suture. If additional projection beyond what is achievable by mere placement of a columella strut is required, the strut is fixed to the spreader grafts in a more projected position. Otherwise, the columella strut is simply positioned between the extensions of the spreader grafts. It is necessary to mobilize the lower lateral cartilages to prevent excessive columella show. This procedure has been performed on 23 patients over the past 12.5 years, with 20 patients enjoying good-to-excellent results. The advantages of this technique include its predictability and reproducibility, and the ability to elongate the nose with a mobile nasal base that is in line with the rest of the nose. If suture fixation is used to gain more projection, the technique proves dependable but the nose will become more rigid than is optimal. The requirement of three pieces of properly shaped septal cartilage, which might not be available when a secondary rhinoplasty is performed, is the major disadvantage of this operation. Furthermore, the procedure is, to some degree, labor-intensive.