MLN51 and GM-CSF involvement in the proliferation of fibroblast-like synoviocytes in the pathogenesis of rheumatoid arthritis

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease of unclear etiology. This study was conducted to identify critical factors involved in the synovial hyperplasia in RA pathology. We applied cDNA microarray analysis to profile the gene expressions of RA fibroblast-like synoviocytes (FLSs) from patients with RA. We found that the MLN51 (metastatic lymph node 51) gene, identified in breast cancer, is remarkably upregulated in the hyperactive RA FLSs. However, growth-retarded RA FLSs passaged in vitro expressed small quantities of MLN51. MLN51 expression was significantly enhanced in the FLSs when the growth-retarded FLSs were treated with granulocyte – macrophage colony-stimulating factor (GM-CSF) or synovial fluid (SF). Anti-GM-CSF neutralizing antibody blocked the MLN51 expression even though the FLSs were cultured in the presence of SF. In contrast, GM-CSF in SFs existed at a significant level in the patients with RA (n = 6), in comparison with the other inflammatory cytokines, IL-1β and TNF-α. Most RA FLSs at passage 10 or more recovered from their growth retardation when cultured in the presence of SF. The SF-mediated growth recovery was markedly impaired by anti-GM-CSF antibody. Growth-retarded RA FLSs recovered their proliferative capacity after treatment with GM-CSF in a dose-dependent manner. However, MLN51 knock-down by siRNA completely blocked the GM-CSF/SF-mediated proliferation of RA FLSs. Taken together, our results imply that MLN51, induced by GM-CSF, is important in the proliferation of RA FLSs in the pathogenesis of RA

Isotropic three-dimensional gap in the iron-arsenide superconductor LiFeAs from directional heat transport measurements

The thermal conductivity k of the iron-arsenide superconductor LiFeAs (Tc ~ 18K) was measured in single crystals at temperatures down to T~50mK and in magnetic fields up to H=17T, very close to the upper critical field Hc2~18T. For both directions of the heat current, parallel and perpendicular to the tetragonal c-axis, a negligible residual linear term k/T is found as T ->0, revealing that there are no zero-energy quasiparticles in the superconducting state. The increase in k with magnetic field is the same for both current directions and it follows closely the dependence expected for an isotropic superconducting gap. There is no evidence of multi-band character, whereby the gap would be different on different Fermi-surface sheets. These findings show that the superconducting gap in LiFeAs is isotropic in 3D, without nodes or deep minima anywhere on the Fermi surface. Comparison with other iron-pnictide superconductors suggests that a nodeless isotropic gap is a common feature at optimal doping (maximal Tc).Comment: 4 pages, 3 figure

Anisotropy of the coherence length from critical currents in the stoichiometric superconductor LiFeAs

Miniature Hall-probe arrays were used to measure the critical current densities for the three main directions of vortex motion in the stoichiometric LiFeAs superconductor. These correspond to vortices oriented along the c-axis moving parallel to the ab-plane, and to vortices in the ab-plane moving perpendicular to, and within the plane, respectively. The measurements were carried out in the low-field regime of strong vortex pinning, in which the critical current anisotropy is solely determined by the coherence length anisotropy parameter, {\epsilon}_{\xi}. This allows extraction of {\epsilon}_{\xi} at magnetic fields far below the upper critical field B_c2. We find that increasing magnetic field decreases the anisotropy of the coherence length

Personalized probiotic strategy considering bowel habits: impacts on gut microbiota composition and alleviation of gastrointestinal symptoms via Consti-Biome and Sensi-Biome

Personalized probiotic regimens, taking into account individual characteristics such as stool patterns, have the potential to alleviate gastrointestinal disorders and improve gut health while avoiding the variability exhibited among individuals by conventional probiotics. This study aimed to explore the efficacy of personalized probiotic interventions in managing distinct stool patterns (constipation and diarrhea) by investigating their impact on the gut microbiome and gastrointestinal symptoms using a prospective, randomized, double-blind, placebo-controlled clinical trial design. This research leverages the multi-strain probiotic formulas, Consti-Biome and Sensi-Biome, which have previously demonstrated efficacy in alleviating constipation and diarrhea symptoms, respectively. Improvement in clinical symptoms improvement and compositional changes in the gut microbiome were analyzed in participants with predominant constipation or diarrhea symptoms. Results indicate that tailored probiotics could improve constipation and diarrhea by promoting Erysipelotrichaceae and Lactobacillaceae, producers of short-chain fatty acids, and regulating inflammation and pain-associated taxa. These findings suggest the potential of tailored probiotic prescriptions and emphasize the need for personalized therapeutic approaches for digestive disorders.Clinical trial registration: https://cris.nih.go.kr/cris/index/index.do, identifier KCT0009111