The fluctuations of expression profiles of critical genes in the miRNA maturation process and pro-and anti-inflammatory cytokines in the pathogenesis and progression of multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a central nervous system disease known for immune-mediated demyelination, inflammatory, and neurodegeneration symptoms. Discovering molecular biomarkers to classify RRMS and SPMS patients, monitor the disease activity, and response to particular treatments is one area that has received notable attraction. MicroRNA (miRNA), a single-stranded non-coding RNA molecule, is a significant regulator of gene expression recruited in pathogenic mechanisms in diverse diseases, especially cancer and MS. Also, the relapsing-remitting features of MS exhibit that both inflammatory and anti-inflammatory cytokines are effective in the progression of the disease over time. METHODS AND RESULTS: It was assessed the expression patterns of the genes (Drosha, Pasha (DGCR8), and Dicer ) encoding the critical enzymes in the processing steps of miRNA maturation and major pro-inflammatory and anti-inflammatory cytokines (IFN-α, IFN-ß, and IL-6) in blood cells of 40 MS patients (two groups of 10 men and women in both clinical courses of RR and SPMS patients) in comparison with 20 healthy control group (10 males and 10 females). The highest transcription activity of Drosha was observed for RRMS patients (4.2 and 3.6-fold, respectively), and the expression ratio was down regulated in male and female patients with SPMS (3.9- and 3.1-fold, respectively). Considering the studied cytokines, the increase in expression ratio of IL-6 in SPMS patients and the decrease in transcript abundance of INF-α, and INF-ß cytokines are consistent with the progression of the disease. CONCLUSIONS: Our findings showed that the high and low transcriptional levels of the considered genes seem to be effective in the pathogenesis and progression of MS.

Tunable plasmonic tweezers based on graphene nano-taper for nano-bio-particles manipulation: numerical study.

We take advantage of graphene nano-taper plasmons to design tunable plasmonic tweezers for neuroblastoma extracellular vesicles manipulation. It consists of Si/SiO2/Graphene stack topped by a microfluidic chamber. Using plasmons of isosceles-triangle-shaped graphene nano-taper with a resonance frequency of 6.25 THz, the proposed device can efficiently trap the nanoparticles. The plasmons of graphene nano-taper generate a large field intensity in the deep sub-wavelength area around the vertices of the triangle. We show that by engineering the dimensions of the graphene nano-taper and an appropriate choice of its Fermi energy, the desired near-field gradient force for trapping can be generated under relatively low-intensity illumination of the THz source when the nanoparticles are placed near the front vertex of the nano-taper. Our results show that the designed system with graphene nano-taper of L = 1200 nm length and W = 600 nm base size and THz source intensity of I = 2 mW/µm2, can trap polystyrene nanoparticles with diameters of D = 140, 73, and 54 nm, and with trap stiffnesses of ky = 9.9 fN/nm, ky = 23.77 fN/nm, and ky = 35.51 fN/nm at Fermi energies of Ef = 0.4, 0.5, and 0.6 eV, respectively. It is well known that the plasmonic tweezer as a high-precision and non-contact means of control has potential applications in biology. Our investigations demonstrate that the proposed tweezing device with L = 1200 nm, W = 600 nm, and Ef = 0.6 eV can be utilized to manipulate the nano-bio-specimens. So that, at the given source intensity, it can trap the neuroblastoma extracellular vesicles, which are released by neuroblastoma cells and play an important role in modulating the function of neuroblastoma cells and other cell populations, as small as 88 nm at the front tip of isosceles-triangle-shaped graphene nano-taper. The trap stiffness for the given neuroblastoma extracellular vesicle is obtained as ky = 17.92 fN/nm.

Tooth Morphogenesis and FGF4 Expression During Development of Molar Tooth in Three Muroid Rodents: Calomyscus elburzensis (Calomyscidae), Mesocricetus auratus (Cricetidae) and Mus musculus (Muridae).

To date, no studies have examined the tooth formation during developmental stages of brush-tailed mice (Calomyscidae) and true hamsters (Cricetidae). Herein, we compared the timing of tooth morphogenesis and FGF4 expression pattern during development of the first lower molar in Goodwin's brush-tailed mouse, Calomyscus elburzensis with two other muroid rodents; the house mouse, Mus musculus (Muridae), model organism for tooth morphogenesis, and the golden hamster, Mesocricetus auratus which shares great similarities in cusp pattern with brush-tailed mice. All three species were bred in captivity and developing embryos were isolated at different embryonic days (E). Histological evaluation of lower molars was performed and spatiotemporal pattern of FGF4 expression was determined by immunohistochemistry. Results indicated that morphogenesis of the tooth cusps starts at the beginning of the cap stage of the first lower molar (E14 in house mouse, about E11.5 in golden hamster and E22 in Goodwin's brush-tailed mouse). During the cap to bell stage (E15 in house mouse, E12 in golden hamster and at about E24 in Goodwin's brush-tailed mouse), a decrease in the expression of FGF4 was observed in the mesenchyme, except for the cusp tips. According to our observations, the developmental process of the first lower molar formation in Goodwin's brush-tailed mouse began much later as compared with the other two species. Despite the differences in the temporal pattern of molar development between these three members of the same superfamily (Muroidea), the correlation in the expression of FGF4 with specific stages of tooth morphogenesis supported its regulatory function. Anat Rec, 300:2138-2149, 2017. © 2017 Wiley Periodicals, Inc.