lncRNA GAS5 suppresses rheumatoid arthritis by inhibiting miR-361-5p and increasing PDK4.

Rheumatoid arthritis (RA) is an inflammatory disease that causes hyperplasia of synovial tissue and cartilage destruction. This research was to investigate the effects of lncRNA GAS5/miR-361-5p/PDK4 on rheumatoid arthritis. By qRT-PCR, GAS5 and PDK4 were found to be overexpressed in synovial tissue, fibroblast-like synoviocytes of RA patients and LPS-induced chondrocytes, while the miR-361-5p expression was significantly reduced. GAS5 overexpression resulted in a decrease in the proliferation and Bcl-2 protein expression, and an increase in the Bax protein level. On the contrary, miR-361-5p sponged by GAS5 could accelerate chondrocyte proliferation, inhibit apoptosis. PDK4 targeted by miR-361-5p could inhibit RA, and partially eliminated the effect of miR-361-5p on RA. Our study suggested that GAS5 suppressed RA by competitively adsorbing miR-361-5p to modulate PDK4 expression.

Surfactant-Free Approach for Engineering an Ultrathin Ti-Doped Ni(OH)2 Nanosheet on Carbon Cloth: Experimental and Theoretical Insight into Boosted Alkaline Water Oxidation Activity.

Ti-based layered double hydroxides (LDHs) have enormous potential in photocatalysis, electrocatalysis, and photoelectrocatalysis. However, Ti-based LDHs are rarely reported because of the difficulties of the preparation process, in which the Ti precursors are more prone to hydrolysis into titanium hydroxide. In this work, toward robust, efficient, and earth-abundant electrocatalysts for water oxidation in alkaline environments, we have engineered Ti-doped Ni(OH)2 nanosheet arrays on carbon cloth [Ti-Ni(OH)2/CC] with a facile solvothermal and surfactant-free method. The experimental tests show that the activity of Ti-Ni(OH)2-1/CC (∼12.5 atom % Ti substitution) is optimal among these materials. In addition, the activity is correlated with the Ti substitution ratio and reversed with higher Ti doping level (≥25 atom % Ti substitution). Therein, η10 of Ti-Ni(OH)2-1/CC is as low as 196 mV, and it is still maintained at 210 mV after a long-term chronopotentiometry (CP) test at a constant current density of 10 mA cm-2 for 32 h, demonstrating superior activity and long-term durability. Density functional theory calculations further reveal that dilute Ti substitution produces extra active sites and promotes more optimal OH* adsorption to the surface of the electrocatalyst.

Anti-arthritic activity of ferulic acid in complete Freund's adjuvant (CFA)-induced arthritis in rats: JAK2 inhibition.

Ferulic acid (FA), a hydroxycinnamic acid, is an organic compound found in several plant species. Previous studies have shown that FA contains anti-inflammatory and anti-arthritic properties. This study aimed to investigate the anti-arthritic activity and possible mechanism(s) of action of FA in complete Freund's adjuvant (CFA)-induced arthritis. The progression of rheumatoid arthritis (RA) involves the activation of the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway by proinflammatory cytokines. Molecular docking of FA showed promising Janus kinase 2 (JAK2) inhibition with a docking score of - 6.7, which is comparable with that of ruxolitinib, a standard inhibitor. However, in vitro JAK2 inhibition assay showed a half maximal inhibitory concentration (IC50) of 6.67 ± 0.88 µg/ml. Both doses of FA (25 and 50 mg/kg) significantly attenuated primary (volume of paw edema) and secondary lesions. CFA-induced arthritic rats showed a significant decrease in body weight, A/G ratio, and Hb but showed a greater arthritic index, ESR levels, and percentage of lymphocytes. These alterations were significantly reduced in rats treated with FA and prednisolone. FA also reversed changes to biochemical parameters and inflammatory markers, such as C-reactive protein (CRP) and rhematoid factor (RF). Additionally, we found CFA-induced arthritis triggered the secretion of TNF- α, increased JAK2 levels, and reduced TGF-ß levels in tissue homogenates. However, in rats treated with FA, such alterations significantly improved. Thus, our results reveal that FA contains anti-arthritic activity, which is possibly mediated by the inhibition of the JAK/STAT pathway.

GSK-3ß and vitamin D receptor are involved in ß-catenin and snail signaling in high glucose-induced epithelial-mesenchymal transition of mouse podocytes.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is recognized to play an important role in diabetic nephropathy (DN). OBJECTIVE: To analyze the roles of glycogen synthase kinase 3ß (GSK-3ß), ß-catenin and Snail signaling in high glucose (HG)-induced mouse podocytes EMT. METHODS: Differentiated podocytes were divided into: the normal glucose group (NG: glucose 5.6mM), the HG groups (12.5HG: 12.5mM; 25HG: 25mM; and 50HG: 50mM of glucose), and the osmotic control group (NG+M: glucose 5.6mM and mannitol 44.4mM). GSK-3ß, ß-catenin and Snail were assessed using semi-quantitative RT-PCR, western blot and immunofluorescence. ß-catenin and Snail pathways were assessed after down-regulating GSK-3ß expression using an inhibitor (LiCl) or a small-interfering RNA (siRNA). RESULTS: HG increased GSK-3ß, ß-catenin and Snail expressions, and promoted EMT, as shown by decreased nephrin expression (epithelial marker), and increased α-SMA expression (mesenchymal marker). GSK-3ß inhibitor and GSK-3ß siRNA decreased ß-catenin and Snail expressions, and reversed HG-induced EMT. Immunofluorescence showed that GSK-3ß and ß-catenin did not completely overlap; ß-catenin was transferred to the nucleus in the 25HG group. VDR seems to be involved in HG-induced ß-catenin nuclear translocation. CONCLUSION: Down-regulating GSK-3ß expression decreased ß-catenin and Snail expression and reversed HG-induced podocytes EMT. Thus, modulating GSK-3ß might be a target to slow or prevent DN. © 2014 S. Karger AG, Basel.

In Situ Electrochemical Fabrication of Ultrasmall Ru-Based Nanoparticles for Robust N2H4 Oxidation.

Ultrasmall Ru nanoparticles is expected as a potential alternative to Pt for efficient hydrazine oxidation (HzOR). However, preparation of ultrasmall and well-distributed Ru nanoparticles usually suffered from the steps of modification of supports, coordination, reduction with strong reducing reagents (e.g., NaBH4) or pyrolysis, imposing the complexity. Based on the self-reducibility of C-OH group and physical adsorption ability of commercial Ketjen black (KB), we developed an efficient, stable and robust Ru-based electrocatalyst (A-Ru-KB) by coupling impregnation of KB in RuCl3 solution and simple in situ electrochemical activation strategy, which endowed the formation of ultrasmall and well-distributed Ru nanoparticles. Benefiting from an enhanced exposure of Ru sites and the faster mass transport, A-Ru-KB achieved 63.4 and 3.9-fold enhancements of mass activity compared with Pt/C and Ru/C, respectively, accompanied by a ∼144 mV lower onset potential and faster catalytic kinetics than Pt/C. In the hydrazine fuel cell, the open-circuit voltage and maximal mass power density of A-Ru-KB was 130 mV and ∼3.8-fold higher than those of Pt/C, respectively, together with the long-term stability. This work would provide a facile and sustainable approach for large-scale production of other robust metal (electro)catalysts with ultrasmall nanosize for various energy conversion and electrochemical organic synthesis.

A separable paper adhesive based on the starch-lignin composite.

One major defect in paper adhesives is that it is difficult to remove the adhesive in waste paper. These adhesives can easily adhere to paper-making equipment, which hampers recycling. Herein, the hyperbranched polyester H102 is used to act as dispersant, and grafting copolymerization of lignin onto the starch backbone was carried out by initiation of free radicals to prepare a bio-based paper adhesive in water. The results show that the adhesive can achieve the best adhesion properties under m(H2O)/m(St) = 15:1, m(SLS)/m(St) = 0.15:1, m(APS)/m(St) = 0.02:1, and pH = 4 at 80 °C for 6 h. The addition of H102 stabilizes the performance of the adhesive and extends the shelf life. The feasibility was verified by Fourier transform infrared spectroscopy (FT-IR), Ultraviolet-visible Spectrophotometry (UV-vis), Thermogravimetric analysis (TG), X-ray diffraction (XRD) and rheological property analysis. Moreover, the as-prepared adhesive can be dissolved in H2O by heating, which is beneficial to improve the recovery and recycling of waste paper compared with the traditional adhesives.

Boosting Oxygen Electroreduction over Strained Silver.

Manipulating the strain effect of Ag without any foreign metals to boost its intrinsic oxygen reduction reaction (ORR) activity is intriguing, but it remains a challenge. Herein, we developed a class of Ag-based electrocatalysts with tunable strain structures for efficient ORR via ligand-assisted competitive decomposition of Ag-organic complexes (AgOCs). Benefiting from the superior coordination capability, 4,4'-bipyridine as a ligand triggered a stronger competition with NaBH4 for Ag ions during reduction-induced decomposition of AgOCs in comparison with the counterparts of the pyrazine ligand and the NO3- anion, which moderately modulated the compressive strain structure to upshift the d-band center of the catalyst and increase the electron density of Ag. Accordingly, the O2 adsorption was obviously improved, and the stronger repulsion effect between the Ag sites and the 4e ORR product, i.e., the electron-rich OH-, was generated to promote the desorption of OH- via the Ag-OH bond cleavage, which enabled more Ag sites to be regenerated after ORR. Both of these led to an enhancement to the intrinsic ORR activity of the Ag-based catalyst. This competitive decomposition of metal-organic complex strategy would provide a facile method to design other catalysts with the well-tuned strain structures for energy conversion and heterocatalysis.

Good performance of p16/Ki-67 dual-stain cytology for detection and post-treatment surveillance of high-grade CIN/VAIN in a prospective, cross-sectional study.

BACKGROUND: The limited sensitivity of Papanicolaou (Pap) cytology and the low specificity of HPV testing in detecting cervical or vaginal lesions means that either precancers are missed or women without lesions are overtreated. To improve performance outcomes, p16/Ki-67 dual-stain cytology has been introduced as a useful biomarker. METHODS: A prospective, cross-sectional study was performed and included 599 patients. Clinical performance estimates of Pap cytology, HPV DNA assay, and p16/Ki-67 dual-stain cytology for the detection of CIN2+/VAIN2+ were determined and compared. RESULTS: The sensitivity and specificity of p16/Ki-67 dual-stain cytology in detecting histology proven CIN2+/VAIN2+ was 91.6% and 95.0%, respectively, while that of Pap cytology was 42.1% and 95.2%, respectively, and that of HPV DNA testing was 100% and 41.6%, respectively. Among the three tests, the AUC of p16/Ki-67 immunocytochemistry was the largest, both for detecting cervical lesions and vaginal lesions, at 0.932 and 0.966, respectively. Among women who were HPV 16/18 positive or 12-other hrHPV positive and Pap positive (≥ASCUS), dual staining reduced the number of unnecessary colposcopy referrals from 274 to 181. Among the women who were 12-other hrHPV positive and Pap negative, dual staining could prevent underdiagnosis in six patients with CIN2+/VAIN2+ when used as a triage marker. Dual staining also identified four women with high-grade lesions detected by diagnostic conization but with negative colposcopy-guided biopsy results. CONCLUSION: p16/Ki-67 dual staining may be a promising tool for predicting high-grade cervical and vaginal lesions.

Knockdown of enhancer of rudimentary homolog inhibits proliferation and metastasis in ovarian cancer by regulating epithelial-mesenchymal transition.

Ovarian cancer (OC) is the deadliest gynecological malignancy. The pathogenesis of molecular in epithelial ovarian cancer (EOC), main histological type of OC, has not been completely defined. Enhancer of rudimentary homolog (ERH) had been reported to participate in transcriptional regulation, mRNA splicing, DNA repair and DNA synthesis by binding a variety of proteins. In this study, immunohistochemical staining revealed that the protein expression of ERH was associated with histological type, lymph node metastasis and pathological grade in EOC patients. To verify the association of ERH with the prognosis of OC, a GSE microarray dataset was downloaded from the Gene Expression Omnibus (GEO) database. Survival analysis suggested that ERH may be associated with poor prognosis of OC. In addition, shRNA was used to knockdown the protein and mRNA expression levels of ERH in the OC cell line SKOV3. Inhibition of ERH expression slowed proliferation, promoted apoptosis and inhibited metastasis and invasion by regulating epithelial-mesenchymal transition (EMT) in SKOV3 cells. These results indicate that ERH protein promotes the development of OC and provides an experimental basis for ERH as the potential target for ovarian cancer treatment.

Removal of copper and cadmium ions from alkaline solutions using chitosan-tannin functional paper materials as adsorbent.

We successfully absorbed the copper ion (Cu2+) and cadmium ion (Cd2+) from alkaline aqueous solutions using the prepared chitosan-tannin (CTS/TA) functional paper as absorbent materials. The kinetics of the adsorption, the adsorption isotherms, and the influence of the solution flow rate and pH were investigated detailly. The adsorption data were described well by Langmuir isotherms, with maximum copper (Cu2+) and cadmium (Cd2+) adsorption capacities of 684.93 and 813.01 mg/m2, respectively. The experimental results also showed that the adsorption of these heavy metals was selective in the order of Cu2+ > Cd2+, as Cu2+ competed with Cd2+ for bonding sites at solution concentrations greater than or equal to 200 mg/L. The results of this study illustrated that the chitosan-tannin functional paper materials mainly followed a complexation-adsorption model, and the best adsorption capacity was achieved at pH = 9. The desorption of heavy ions from this adsorbent and its reusability of functional paper was also involved. Therefore, this novel, environment-friendly functional paper can surely act as an effective adsorbent for the removal and recovery of heavy metals in alkaline aqueous solutions.

Serum retinol-binding protein 4 is associated with insulin resistance in patients with early and untreated rheumatoid arthritis.

OBJECTIVE: Retinol-binding protein 4 (RBP4), systemic inflammation and insulin resistance (IR) are linked, yet the determinants of RBP4 and its impact on IR in rheumatoid arthritis (RA) are incompletely understood. The aim of this study was to explore the prevalence of IR in RA and investigate whether the serum levels of RBP4 were associated with IR in patients with RA. METHODS: In this study, 403 individuals with newly diagnosed and untreated RA were consecutively recruited. We calculated the Disease Activity Score assessed using 28-joint counts for swelling and tenderness (DAS28). Levels of serum RBP4, interleukin-6 (IL-6) and tumor necrosis factor (TNF) α were tested. IR was defined as Homeostasis model assessment for insulin resistance (HOMA-IR) index greater than or equal 2.40. RESULTS: In those 403 patients, 68 (16.9%) were male and the median age was 43 years (IQR: 36-52). There was an evidently positive correlation between increased serum levels of RBP4 and increasing severity of RA (DAS28) (r = 0.403, P < 0.001). Furthermore, a modest positive correlation between levels of serum RBP4 and HOMA-IR score (r = 0.251; P < 0.0001) was found. Eighty-five patients (21.1%) in patients with RA were defined as IR (HOMA-IR ≥ 2.40), which was significantly higher than in normal cases (4.7%). In the patients with IR, serum levels of RBP4 were higher when compared with those in patients free-IR P < 0.001. The IR distribution across the quartiles of RBP4 ranged between 5.0% (first quartile) to 39.0% (fourth quartile), P for trend < 0.001. For each 1unit increase of RBP4, the unadjusted and adjusted risk of IR increased by 8% (OR: 1.08; 95% CI: 1.05-1.11, P < 0.001) and 5% (1.05; 1.02-1.09, P = 0.001), respectively. When RBP4 was added to the model containing established significant risk factors, AUROC (standard error) was increased from 0.768 (0.025) to 0.807(0.021). A significant difference in the AUC between the established risk factors alone and the addition of RBP4 was observed (difference, 0.039[0.004]; P = 0.02). CONCLUSION: Elevated serum levels of RBP4 were associated with increased risk of IR and might be useful in identifying RA at risk for IR and/or impaired glucose tolerance for early prevention strategies, especially in obese and women patients.

Preparation and Application of Phosphorylated Xylan as a Flocculant for Cationic Ethyl Violet Dye.

In this study, phosphorylated birchwood xylan was produced under alkali conditions using trisodium trimetaphosphate. Three single-factor experiments were used to explore the influences of time, temperature, and the molar ratio of trisodium trimetaphosphate to xylan on the degree of substitution (DS) and charge density of xylan. The response surface methodology was used to explore the interaction of these three factors. Phosphorylated xylan with a maximum DS of 0.79 and a charge density of -3.40 mmol/g was produced under the optimal conditions of 80 °C, 4 h, and a molar ratio of xylan/sodium trimetaphosphate (STMP) of 1/3. Fourier transform infrared (FTIR), ascorbic acid method analyses, and inductively coupled plasma⁻atomic emission spectrometer (ICP-AES) analyses confirmed that the phosphate groups were successfully attached to xylan. Thermogravimetric analysis confirmed that phosphorylated xylan was less stable than birchwood xylan. Furthermore, the phosphorylated xylan was applied as a flocculant for removing ethyl violet dye from a simulated dye solution. The results indicated that more than 95% of the dye was removed from the solution. The theoretical and experimental values of charge neutralization for the dye removal were close to one another, confirming that charge neutralization was the main mechanism for the interaction of dye and phosphorylated xylan. The impacts of salts on the flocculation efficiency of phosphorylated xylan were also analyzed.