Inhibition of miR-665 alleviates lipopolysaccharide-induced inflammation via up-regulation of SOCS7 in chondrogenic ATDC5 cells

Purpose: To examine the effect and mechanism of action of miR-665 in osteoarthritis.Methods: An in vitro inflammatory injury model of osteoarthritis was established using chondrogenic ATDC5 cells with lipopolysaccharide (LPS) treatment. The expression levels of inflammatory cytokines were determined by enzyme-linked immunosorbent assays (ELISAs) and by quantitative real-time polymerase chain reaction (qRT-PCR). A binding target for miR-665 was predicted using TargetScan and then evaluated using a dual-luciferase reporter assay.Results: Treatment with LPS significantly up-regulated the inflammatory cytokine expressions of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α), in ATDC5 cells (p < 0.01), and the expression of miRNA-665 was significantly increased in LPS-treated ATDC5 cells (p < 0.01).Knockdown of miR-665 down-regulated the expression levels of these inflammatory cytokines. Suppressor of cytokine signaling 7 (SOCS7) was identified as a target of miR-665. Data from qRT-PCR and western-blot analyses indicated that SOCS7 expression was promoted by miR-665  inhibition and inhibited by miR-665 over-expression. LPS treatment significantly decreased the expression of SOCS7 protein in ATDC5 cells (p < 0.01), and over-expression of SOCS7 attenuated the LPS-stimulated inflammatory injury. In addition, over-expression of miR-655 enhanced the inflammatory injury and reversed the protective effect of SOCS7 against LPS-stimulated inflammation.Conclusion: Inhibition of miR-665 alleviated LPS-stimulated inflammatory injury in ATDC5 cells via the up-regulation of SOCS7, suggesting a potential therapeutic target for osteoarthritis. Keywords: MiR-665, Lipopolysaccharide, Inflammation, SOCS7, Chondrogenic, ATDC

3-O-Caffeoylquinic acid in Periploca forrestii Schltr extract ameliorates collagen-induced arthritis by inducing IL17/IL23 cells in rats

Purpose: To study the therapeutic effect of 3-O-caffeoylquinic acid (3-O-CQA) from Periploca forrestii extract (PFE) on collagen-mediated arthritis (CIA) in rats, as well as the potential underlying mechanism of action. Methods: PFE and 3-O-CQA were successively and intragastrically administered to CIA rats. Paw swelling, arthritic scores and H & E staining were used to evaluate the therapeutic effect of 3-O-CQA. Moreover, to determine the effects of PFE and 3-O-CQA on fibroblast-resembling synoviocytes obtained from arthritic subjects (RAFLS), the viability of RAFLS cultured in vitro was measured with MMT, while apoptotic lesions were analyzed by flow cytometry. The levels of IL-6 in CIA and RAFLS were determined by enzyme-linked immunosorbent assay (ELISA), while quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR) and immunoblotting were used to assess their mRNA and polypeptide levels, respectively. Results: PFE in 3-O-CQA ameliorated swelling and reduced arthritic scores in CIA rat model, and also decreased cytokine levels (p < 0.05). By decreasing mRNA and protein expressions, 3-O-CQA repressed the phosphorylation of STAT3 and JAK2 as well as the protein levels of IL-23 and RORγt (p < 0.05). Conclusion: The results of this study show that CIA and RAFLS are ameliorated in rats by 3-O-CQA in PFE through regulation of IL17/ IL23 and Th17 cells. Thus, 3-O-CQA affords a therapeutic strategy for the management of collagen-induced arthritis. Keywords: Arthriti; Periploca forrestii Schltr extract; 3-O-Caffeoylquinic acid; Interleukin (IL)-17; IL-23; Th17 cell

Striking Isotopologue-Dependent Photodissociation Dynamics of Water Molecules:The Signature of an Accidental Resonance

Investigations of the photofragmentation patterns of both light and heavy water at the state-to-state level are a prerequisite for any thorough understanding of chemical processing and isotope heterogeneity in the interstellar medium. Here we reveal dynamical features of the dissociation of water molecules following excitation to the (C) over tilde (010) state using a tunable vacuum ultraviolet source in combination with the high-resolution H(D)-atom Rydberg tagging time-of-flight technique. The action spectra for forming H(D) atoms and the OH(OD) product state distributions resulting from excitation to the (C) over tilde (010) states of H2O and D2O both show striking differences, which are attributable to the effects of an isotopologue-specific accidental resonance. Such accidental-resonance-induced state mixing may contribute to the D/H isotope heterogeneity in the solar system. The present study provides an excellent example of competitive state-to-state nonadiabatic decay pathways involving at least five electronic states

Effect of Miao medicine, Jinwujiangu decoction, on IL- 17/IL-23 inflammatory axis of fibroblast-like synoviocytes in rheumatoid arthritis

Purpose: To explore the influence of the Miao medicine, Jinwujiangu decoction, on the interleukin (IL)- 17/IL-23 inflammatory axis of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA).Methods: Synovial tissue samples were randomly divided into a blank control group, high-dose (0.06mg/mL), medium-dose (0.6mg/mL), and low-dose (6.0mg/mL) groups of Jinwujiangu decoction, a leflunomide group, and a tripterygium glycosides group. Proliferation of RA synovial cells was detected by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Enzyme-linked immunosorbent assay (ELISA) was used to determine the secretion of IL-6, transforming growth factor beta (TGF-β), and IL-17. Real-time polymerase chain reaction was used to evaluate the expression of IL-23R, IL-17R, RAR-related orphan receptor alpha (RORα), RORγt, and signal transducer and activator of transcription (STAT3) mRNA. The protein activities of IL-17R, STAT3 and pSTAT3 were assessed by Western blot assay.Results: Jinwujiangu decoction inhibited the proliferation of RA synovial cells. Treatment with different drug concentrations resulted in downregulation of IL-6, TGF-β, and IL-17 secretion. The expression levels of IL-23R, IL-17R, RORα, RORγt, and STAT3 mRNA in RA-FLS were significantly reduced after intervention with different drugs. Protein expression levels of STAT3, pSTAT3, and IL-17 in the different drug treatment groups were significantly decreased.Conclusion: Jinwujiangu decoction inhibits the secretion of IL-6 and TGF-β in RA-FLS, and intervenes to regulate gene expression of IL-23/IL-17 inflammation axis and suppress immune inflammation. The results of this study provide new evidence for the study of anti-inflammatory mechanism of TCM compound prescription.Keywords: Jinwujiangu decoction, IL-17/IL-23, Fibroblast-like synoviocytes, Rheumatoid arthritis, Ethnomedicin

Prediction and Verification of the Major Ingredients and Molecular Targets of Tripterygii Radix Against Rheumatoid Arthritis

Tripterygii Radix exhibits good clinical efficacy and safety in rheumatoid arthritis (RA) patients, but its effective components and mechanism of action are still unclear. The purpose of this study was to explore and verify the major ingredients and molecular targets of Tripterygii Radix in RA using drug-compounds-biotargets-diseases network and protein-protein interaction (PPI) network analyses. The processes and pathways were derived from Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The most important compounds and biotargets were determined based on the degree values. RA fibroblast-like synoviocytes (RA-FLS) were separated from RA patients and identified by hematoxylin and eosin (HE) staining and immunohistochemistry. The purity of RA-FLS was acquired by flow cytometry marked with CD90 or VCAM-1. RA-FLS were subjected to control, dimethyl sulfoxide (control), kaempferol, or lenalidomide treatment. Cell migration was evaluated by the transwell assay. The relative expression of biotarget proteins and cytokines was analyzed by western blotting and flow cytometry. In total, 144 chemical components were identified from Tripterygii Radix; kaempferol was the most active ingredient among 33 other components. Fourteen proteins were found to be affected in RA from 285 common biotargets. The tumor necrosis factor (TNF) signaling pathway was predicted to be one of the most latent treatment pathways. Migration of RA-FLS was inhibited and the expression of protein kinase B (AKT1), JUN, caspase 3 (CASP3), TNF receptor 1 and 2 (TNFR1 and TNFR2), interleukin-6 (IL-6), and TNF-α was significantly affected by kaempferol. Thus, this study confirmed kaempferol as the effective component of Tripterygii Radix against RA-FLS and TNF signaling pathway and its involvement in the regulation of AKT1, JUN, CASP3, TNFR1, TNFR2, IL-6, and TNF-α expression

Ultraviolet photochemistry of ethane:implications for the atmospheric chemistry of the gas giants

Chemical processing in the stratospheres of the gas giants is driven by incident vacuum ultraviolet (VUV) light. Ethane is an important constituent in the atmospheres of the gas giants in our solar system. The present work describes translational spectroscopy studies of the VUV photochemistry of ethane using tuneable radiation in the wavelength range 112 ≤ λ ≤ 126 nm from a free electron laser and event-triggered, fast-framing, multi-mass imaging detection methods. Contributions from at least five primary photofragmentation pathways yielding CH(2), CH(3) and/or H atom products are demonstrated and interpreted in terms of unimolecular decay following rapid non-adiabatic coupling to the ground state potential energy surface. These data serve to highlight parallels with methane photochemistry and limitations in contemporary models of the photoinduced stratospheric chemistry of the gas giants. The work identifies additional photochemical reactions that require incorporation into next generation extraterrestrial atmospheric chemistry models which should help rationalise hitherto unexplained aspects of the atmospheric ethane/acetylene ratios revealed by the Cassini–Huygens fly-by of Jupiter

Identification of Target Genes at Juvenile Idiopathic Arthritis GWAS Loci in Human Neutrophils

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease among children which could cause severe disability. Genomic studies have discovered substantial number of risk loci for JIA, however, the mechanism of how these loci affect JIA development is not fully understood. Neutrophil is an important cell type involved in autoimmune diseases. To better understand the biological function of genetic loci in neutrophils during JIA development, we took an integrated multi-omics approach to identify target genes at JIA risk loci in neutrophils and constructed a protein-protein interaction network via a machine learning approach. We identified genes likely to be JIA risk loci targeted genes in neutrophils which could contribute to JIA development

Hydroxyl super rotors from vacuum ultraviolet photodissociation of water

Free electron lasers provide a state-of-the-art tool to investigate the photochemistry of water. Here, the authors show that highly rotationally excited hydroxyl radicals, so-called “super rotors” existing above the bond dissociation energy, are observed from the photodissociation of water, which may have implications for understanding the interstellar medium