Daviescovington0255

We found that methimazole could inhibit the GFAP protein expression in scratched astrocytes and prolong the latency of wound healing in cultures. We also measured the phosphorylation of extracellular signal-regulated kinase (ERK) in these cultures and found that methimazole could significantly inhibit the scratch-induced GFAP upregulation. For the first time, our study demonstrated that methimazole might be a possible compound that could inhibit the astrocytic activation following CNS injury by reducing the ERK phosphorylation in astrocytes. see more Copyright © 2020 Lina Zhao et al.Background Gut barrier dysfunction with alterant mucosal permeability during sepsis is a challenge problem in clinical practice. Intestinal epithelial cells (IECs) are strongly involved in mucosal oxidative stress and inflammatory response. The current study aimed at investigating the effect of MitoQ, a mitochondrial targeted antioxidant, in the treatment of intestinal injury and its potential mechanism during sepsis. Methods 30 minutes before sepsis induction by lipopolysaccharide (LPS) treatment, mice were treated with MitoQ. Intestinal histopathology, mucosal permeability, inflammatory cytokines, and mucosal barrier proteins were evaluated in the present study. Results MitoQ pretreatment significantly decreased the levels of plasma diamine oxidase, D-lactate, and intestinal histological damage and markedly restored the levels of tight junction proteins (ZO-1 and occludin) following LPS challenge. Furthermore, MitoQ inhibited the LPS-induced intestinal oxidative stress and inflammatory response, evidenced by increased levels of intestinal superoxide dismutase and glutathione, and decreased levels of intestinal IL-1, IL-6, TNF-α, and nitric oxide levels. Mechanically, we found that MitoQ inhibited the oxidative stress via activating nuclear factor E2-related factor 2 (Nrf2) signaling pathway and its downstream antioxidant genes, including HO-1, NQO-1, and GCLM. Conclusions MitoQ exerts antioxidative and anti-inflammatory effects against sepsis-associated gut barrier injury by promoting Nrf2 signaling pathway. Copyright © 2020 Shengfeng Zhang et al.Silicosis is a devastating disease caused by inhalation of silica dust that leads to inflammatory cascade and then scarring of the lung tissue. Increasing evidences indicate that soluble receptor for advanced glycation end products (sRAGE) is involved in inflammatory diseases. However, no data on the possible relationship between sRAGE and inflammation of silicosis are available. In this study, serum from subjects with silicosis (n = 59) or from healthy controls (HC, n = 14) was analyzed for the secretion of sRAGE, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1), and oxidized low-density lipoprotein (ox-LDL). The associations between sRAGE and cytokines and ox-LDL and lung function were assessed by Pearson's correlation analyses. Mean levels of serum sRAGE were lower in silicosis than those in controls (p less then 0.05). The subjects who had a longer term of occupational exposure had higher levels of sRAGE (p less then 0.05). The secretion of TNF-α, IL-1β, IL-6, TGF-β1, and ox-LDL was significantly higher in the silicosis group than that in the HC group (p less then 0.05). Furthermore, the levels of sRAGE were negatively correlated with TNF-α, IL-6, IL-1β, and ox-LDL. There is no correlation between sRAGE and TGF-β1 and lung function. The optimal point of sRAGE for differentiating silicosis from healthy controls was 14250.02 pg/ml by ROC curve analysis. A decrease in serum sRAGE and its association with inflammatory response might suggest a role for sRAGE in the pathogenesis of silicosis. Copyright © 2020 Heliang Liu et al.The ontogeny of macrophages in most organs has already been established. Owing to the limited number and inaccessibility of synovial macrophages (SMs), the origin of SMs has not been fully elucidated. Previous studies suggested that SMs have two major origins, namely, tissue-resident and monocyte-derived SMs. However, no systematic analysis to identify SM ontology in either physiological or pathological conditions has been available to date. In this review, we summarize relevant studies on the two main origins of SMs in rheumatoid arthritis (RA) and forecast the future research directions for this field. Furthermore, we discuss the current state of RA therapy that is based on targeting different SM subsets. Copyright © 2020 Jiajie Tu et al.A general and efficient synthesis of α-haloglycine esters from commercially available feedstock chemicals, in a single step, is reported. The reactivity of these α-haloglycine esters with various nucleophiles was studied as surrogates of α-iminoesters upon activation with hydrogen-bond donor catalysts. DFT calculations on the α-haloglycine structures (X = F, Cl, Br) accompanied by an X-ray characterization of the α-bromoglycine ester support the existence of a "generalized" anomeric effect created by hyperconjugation. This peculiar hyperconjugative effect is proposed to be responsible for the enhanced halogen nucleofugality leading to a facile halogen abstraction by hydrogen-bond donor catalysts. This reactivity was exploited with thiourea catalysts on several catalytic transformations (aza-Friedel-Crafts and Mannich reactions) for the synthesis of several types of non-proteinogenic α-amino esters.To better probe large biomolecular complexes, developments in mass spectrometry (MS) have focused on improving technologies used to generate, transmit, and measure high m/z ions. The additional tandem-MS (MSn) capabilities of ion trap mass spectrometers (ITMS) facilitate experiments that facilitate probing complex biomolecular ions. In particular, charge reduction using gas-phase ion/ion reactions increase separation of charge states generated via electrospray ionization (ESI), which increases confidence in charge state assignments and therefore masses determined from the observed charge states. Current ITMS technologies struggle to generate and measure low charge states of large (>50 kDa) proteins and complexes because of power limitations associated with conventional high-frequency sine wave operation. Other approaches, including frequency scanning techniques and use of digital waveforms, reduce or eliminate some of these limitations. The work presented here studies five different operational modes for a quadrupole ion trap (QIT) mass spectrometer used to generate and measure low charge states of bovine serum albumin (BSA), pyruvate kinase (PK), and GroEL. While digital operation of a QIT presents limitations during the ion/ion reaction period of the experiment, it generally provided the best spectra in terms of resolution and signal at m/z > 50,000.Buckwheat (Fagopyrum esculentum) is cultivated worldwide and its flour is used in a variety of food products. Although functional analyses of genes in buckwheat are highly desired, reliable methods to do it have yet to be developed. In this study we established a simple and efficient transient gene expression system using buckwheat protoplasts isolated from young hypocotyls using 96-well plates as a high-throughput platform. The transformation efficiency was comparable with that of similar systems, such as Arabidopsis mesophyll protoplasts. Stable results were obtained in a typical example of the experiment to examine transcription factor activity. This system shows potential for the large-scale analysis of gene function using protoplast isolated from fewer and younger plants than the conventional system and may provide novel information for efficient buckwheat breeding. Copyright © 2020 by JAPANESE SOCIETY OF BREEDING.The zero-repeat subunit of 13S globulin, which lacks tandem repeat inserts, is trypsin-resistant and suggested to show higher allergenicity than the other subunits in common buckwheat (Fagopyrum esculentum Moench). To evaluate allelic variations and find novel alleles, the diversity of the zero-repeat genes was examined for two Japanese elite cultivars and 15 Pakistani landraces. The results demonstrated that two new alleles GlbNA1 and GlbNC1, plus three additional new alleles GlbNA2, GlbNA3, and GlbND, were identified besides the already-known GlbNA, GlbNB, and GlbNC alleles. In the Pakistani landraces, GlbNA was the most dominant allele (0.60-0.88 of allele frequency) in all except one landrace, where GlbNB was the most dominant allele (0.50 of allele frequency). Similar to GlbNC, the alleles GlbNA2 and GlbNA3 had extra ~200 bp MITE-like sequences around the stop codon. Secondary structure predictions of a sense strand demonstrated that the extra ~200 bp sequences of GlbNC, GlbNA2, and GlbNA3 can form rigid hairpin structures with free energies of -78.95, -67.06, and -29.90 kcal/mol, respectively. These structures may affect proper transcription and/or translation. In the GlbNC homozygous line, no transcript of a zero-repeat gene was detected, suggesting the material would be useful for developing hypoallergenic buckwheat. Copyright © 2020 by JAPANESE SOCIETY OF BREEDING.Common buckwheat (Fagopyrum esculentum) is a heterostylous self-incompatible (SI) species with two different flower morphologies, pin and thrum. The SI trait is controlled by a single gene complex locus, S. Self-compatible (SC) lines were developed by crossing F. esculentum and F. homotropicum; these lines have an SC gene, Sh , which is dominant over the s allele and recessive to the S allele. S-ELF3 has been identified as a candidate gene in the S locus and is present in the S and Sh but not s alleles. A single-nucleotide deletion in the S-ELF3 gene of the Sh allele results in a frame shift. To develop co-dominant markers to distinguish between ShSh and Shs plants, we performed a next-generation sequencing analysis in combination with bulked-segregant analysis. We developed four co-dominant markers linked to the S locus. We investigated the polymorphism frequency between a self-compatible line and leading Japanese buckwheat cultivars. Linkage between a developed sequence-tagged-site marker and flower morphology was confirmed using more than 1000 segregating plants and showed no recombination. The developed markers would be useful for buckwheat breeding and also to produce lines for genetic analysis such as recombinant inbred lines. Copyright © 2020 by JAPANESE SOCIETY OF BREEDING.Ecotype breeding is a key technology in common buckwheat (Fagopyrum esculentum Moench) for the breeding of highly adaptive cultivars and their introduction to other cultivation areas. However, the details of the relationship between photoperiod sensitivity and ecotype remain unclear. Here, we evaluated photoperiod sensitivity in 15 landraces from different parts of Japan, and analyzed quantitative trait loci (QTLs) for photoperiod sensitivity using two F2 segregating populations derived from the crosses between self-compatible lines ('Kyukei SC2' or 'Buckwheat Norin PL1', early days-to-flowering) and allogamous plants (intermediate or late days-to-flowering). We clarified that (1) photoperiod sensitivity and differences in ecotype are closely related; (2) photoperiod sensitivity is controlled by several QTLs common among population of different ecotypes; and (3) orthologues of GIGANTEA and EARLY FLOWERING 3 will be useful markers in future detailed elucidation of the photoperiod sensitivity mechanism in common buckwheat.