Loss of Smad7 Promotes Inflammation in Rheumatoid Arthritis

Objective: Smad7 is an inhibitory Smad and plays a protective role in many inflammatory diseases. However, the roles of Smad7 in rheumatoid arthritis (RA) remain unexplored, which were investigated in this study.Methods: The activation of TGF-β/Smad signaling was examined in synovial tissues of patients with RA. The functional roles and mechanisms of Smad7 in RA were determined in a mouse model of collagen-induced arthritis (CIA) in Smad7 wild-type (WT) and knockout (KO) CD-1 mice, a strain resistant to autoimmune arthritis induction.Results: TGF-β/Smad3 signaling was markedly activated in synovial tissues of patients with RA, which was associated with the loss of Smad7, and enhanced Th17 and Th1 immune response. The potential roles of Smad7 in RA were further investigated in a mouse model of CIA in Smad7 WT/KO CD-1 mice. As expected, Smad7-WT CD-1 mice did not develop CIA. Surprisingly, CD-1 mice with Smad7 deficiency developed severe arthritis including severe joint swelling, synovial hyperplasia, cartilage damage, massive infiltration of CD3+ T cells and F4/80+ macrophages, and upregulation of proinflammatory cytokines IL-1β, TNFα, and MCP-1. Further studies revealed that enhanced arthritis in Smad7 KO CD-1 mice was associated with increased Th1, Th2 and, importantly, Th17 over the Treg immune response with overactive TGF-β/Smad3 and proinflammatory IL-6 signaling in the joint tissues.Conclusions: Smad7 deficiency increases the susceptibility to autoimmune arthritis in CD-1 mice. Enhanced TGF-β/Smad3-IL-6 signaling and Th17 immune response may be a mechanism through which disrupted Smad7 causes autoimmune arthritis in CD-1 mice

Study of ϒ(nS)→BcP decays with perturbative QCD approach

With the potential prospects of the ϒ(nS) at high-luminosity dedicated heavy-flavor factories, the color-favored ϒ(nS)→Bcπ, BcK weak decays are studied with the pQCD approach. It is found that branching ratios for the ϒ(nS)→Bcπ decay are as large as the order of O(10−11), which might be measured promisingly by the future experiments

The ϒ(nS)→BcDs, BcDd decays with perturbative QCD approach

The ϒ(nS)→BcDs, BcDd weak decays are studied with the pQCD approach firstly. It is found that branching ratios Br(ϒ(nS)→BcDs)∼O(10−10) and Br(ϒ(nS)→BcDd)∼O(10−11), which might be measurable in the future experiments

Study on the ϒ(1S)→BcDs decay

The branching ratio and direct CP asymmetry of the ϒ(1S)→BcDs weak decay are estimated with the perturbative QCD approach firstly. It is found that (1) the direct CP-violating asymmetry is close to zero, (2) the branching ratio Br(ϒ(1S)→BcDs)≳10−10 might be measurable at the future experiments

Oncogenic KSHV-encoded interferon regulatory factor upregulates HMGB2 and CMPK1 expression to promote cell invasion by disrupting a complex lncRNA-OIP5-AS1/miR-218-5p network.

Kaposi's sarcoma (KS), a highly disseminated tumor of hyperproliferative spindle endothelial cells, is the most common AIDS-associated malignancy caused by infection of Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV-encoded viral interferon regulatory factor 1 (vIRF1) is a viral oncogene but its role in KSHV-induced tumor invasiveness and motility remains unknown. Here, we report that vIRF1 promotes endothelial cell migration, invasion and proliferation by down-regulating miR-218-5p to relieve its suppression of downstream targets high mobility group box 2 (HMGB2) and cytidine/uridine monophosphate kinase 1 (CMPK1). Mechanistically, vIRF1 inhibits p53 function to increase the expression of DNA methyltransferase 1 (DNMT1) and DNA methylation of the promoter of pre-miR-218-1, a precursor of miR-218-5p, and increases the expression of a long non-coding RNA OIP5 antisense RNA 1 (lnc-OIP5-AS1), which acts as a competing endogenous RNA (ceRNA) of miR-218-5p to inhibit its function and reduce its stability. Moreover, lnc-OIP5-AS1 increases DNA methylation of the pre-miR-218-1 promoter. Finally, deletion of vIRF1 from the KSHV genome reduces the level of lnc-OIP5-AS1, increases the level of miR-218-5p, and inhibits KSHV-induced invasion. Together, these results define a novel complex lnc-OIP5-AS1/miR-218-5p network hijacked by vIRF1 to promote invasiveness and motility of KSHV-induced tumors

Enzyme-Assisted Extraction Optimization, Characterization and Antioxidant Activity of Polysaccharides from Sea Cucumber Phyllophorus proteus

Enzyme-assisted extraction optimization, characterization and in vitro antioxidant activity of polysaccharides from sea cucumber Phyllophorus proteus (PPP) were investigated in the present study. The optimal extraction conditions with a yield of 6.44 ± 0.06% for PPP were determined as follows: Extraction time of 2.89 h, ratio of extraction solvent to raw material of 16.26 mL/g, extraction pH of 6.83, exraction temperature of 50 °C and papain concentration of 0.15%. Three purified fractions, PPP-1a, PPP-1b and PPP-2 with molecular weights of 369.60, 41.73 and 57.76 kDa, respectively, were obtained from PPP by chromatography of FPA98Cl and Sepharose CL-6B columns. Analysis of monosaccharide compositions showed that PPP-1a consisted of N-acetyl-galactosamine (GalNAc), galactose (Gal) and fucose (Fuc), PPP-1b of Fuc as the only monosaccharide and PPP-2 of glucuronic acid, GalNAc and Fuc. Sulfate contents of PPP, PPP-1a, PPP-1b and PPP-2 were determined to be 21.9%, 20.6%, 25.2% and 28.0% (w/w), respectively. PPP and PPP-1a had higher molecular weight and intrinsic viscosity than those of the PPP-1b and PPP-2. PPP, PPP-1a, PPP-1b and PPP-2 exhibited obvious activities of scavenging 1,1-diphenyl-2-picrylhydrazyl radical, hydroxyl radical, superoxide radical and ABTS radical in different extent, which suggested that the polysaccharides from Phyllophorus proteus may be novel agents having potential value for antioxidation