Contribution of P2X4 receptor in pain associated with rheumatoid arthritis: a review

Purinergic Signalling - Pain is the most common symptom reported by patients with rheumatoid arthritis (RA) even after the resolution of chronic joint inflammation. It is believed that...     

Enzymatic deinking of various types of waste paper: Efficiency and characteristics

The aim of the present study was to characterize the enzymatic deinking of various types of waste paper. Studies on the optimization of enzymatic deinking have been performed previously using commercially available enzyme preparations containing cellulase and hemicellulase. The enzymatic deinking of different types of waste paper demonstrated a high efficiency of 86.6% on laser-printed paper, but a low deinking efficiency of 12.9% was obtained with newspaper. All enzymatic treatments significantly improved the drainage rate of the deinked waste paper. Enzymatic deinking increased the tensile index of magazine paper but reduced the tensile index of bubble jet-printed paper, photocopy paper and newspaper. Enzymatic hydrolysis caused a 21.1% reduction in the tear index for bubble jet-printed paper, but a 3.1% increase in the tear index was obtained for laser-printed paper relative to respective blank. In addition, enzymatic hydrolysis increased the burst index by 4.7% relative to blank for laser-printed paper. However, photocopy paper showed the highest reduction (8.3%) in the burst index relative to blank. Taken together, these results suggest that enzymatic hydrolysis is both advantageous and detrimental to the mechanical properties of deinked paper. Thus, the proper regulation of enzymatic hydrolysis is crucial to improve the quality of recycled paper.     

One‐Step Fabrication of Ultrathin Porous Nickel Hydroxide‐Manganese Dioxide Hybrid Nanosheets for Supercapacitor Electrodes with Excellent Capacitive Performance

A facile one‐step hydrothermal co‐deposition method for growth of ultrathin Ni(OH)₂‐MnO₂ hybrid nanosheet arrays on three dimensional (3D) macroporous nickel foam is presented. Due to the highly hydrophilic and ultrathin nature of hybrid nanosheets, as well as the synergetic effects of Ni(OH)₂ and MnO₂, the as‐fabricated Ni(OH)₂‐MnO₂ hybrid electrode exhibits an ultrahigh specific capacitance of 2628 F g^?1. Moreover, the asymmetric supercapacitor with the as‐obtained Ni(OH)₂‐MnO₂ hybrid film as the positive electrode and the reduced graphene oxide as the negative electrode has a high energy density (186 Wh kg^?1 at 778 W kg^?1), based on the total mass of active materials.     

Cyanine 5.5 Conjugated Nanobubbles as a Tumor Selective Contrast Agent for Dual Ultrasound-Fluorescence Imaging in a Mouse Model

Nanobubbles and microbubbles are non-invasive ultrasound imaging contrast agents that may potentially enhance diagnosis of tumors. However, to date, both nanobubbles and microbubbles display poor in vivo tumor-selectivity over non-targeted organs such as liver. We report here cyanine 5.5 conjugated nanobubbles (cy5.5-nanobubbles) of a biocompatible chitosan–vitamin C lipid system as a dual ultrasound-fluorescence contrast agent that achieved tumor-selective imaging in a mouse tumor model. Cy5.5-nanobubble suspension contained single bubble spheres and clusters of bubble spheres with the size ranging between 400–800 nm. In the in vivo mouse study, enhancement of ultrasound signals at tumor site was found to persist over 2 h while tumor-selective fluorescence emission was persistently observed over 24 h with intravenous injection of cy5.5-nanobubbles. In vitro cell study indicated that cy5.5-flurescence dye was able to accumulate in cancer cells due to the unique conjugated nanobubble structure. Further in vivo fluorescence study suggested that cy5.5-nanobubbles were mainly located at tumor site and in the bladder of mice. Subsequent analysis confirmed that accumulation of high fluorescence was present at the intact subcutaneous tumor site and in isolated tumor tissue but not in liver tissue post intravenous injection of cy5.5-nanobubbles. All these results led to the conclusion that cy5.5-nanobubbles with unique crosslinked chitosan–vitamin C lipid system have achieved tumor-selective imaging in vivo.     

A Novel Anti-Tumor Inhibitor Identified by Virtual Screen with PLK1 Structure and Zebrafish Assay

Polo-like kinase 1 (PLK1), one of the key regulators of mitosis, is a target for cancer therapy due to its abnormally high activity in several tumors. Plk1 is highly conserved and shares a nearly identical 3-D structure between zebrafish and humans. The initial 10 mitoses of zebrafish embryonic cleavages occur every∼30 minutes, and therefore provide a rapid assay to evaluate mitosis inhibitors including those targeting Plk1. To increase efficiency and specificity, we first performed a computational virtual screen of∼60000 compounds against the human Plk1 3-D structure docked to both its kinase and Polo box domain. 370 candidates with the top free-energy scores were subjected to zebrafish assay and 3 were shown to inhibit cell division. Compared to general screen for compounds inhibiting zebrafish embryonic cleavage, computation increased the efficiency by 11 folds. One of the 3 compounds, named I2, was further demonstrated to effectively inhibit multiple tumor cell proliferation in vitro and PC3 prostate cancer growth in Xenograft mouse model in vivo. Furthermore, I2 inhibited Plk1 enzyme activity in a dose dependent manner. The IC₅₀ values of I2 in these assays are compatible to those of ON-01910, a Plk1 inhibitor currently in Phase III clinic trials. Our studies demonstrate that zebrafish assays coupled with computational screening significantly improves the efficiency of identifying specific regulators of biological targets. The PLK1 inhibitor I2, and its analogs, may have potential in cancer therapeutics.     

Retracted: Upregulated microRNA-31 inhibits oxidative stress-induced neuronal injury through the JAK/STAT3 pathway by binding to PKD1 in mice with ischemic stroke

Ischemic stroke (IS), which is characterized by high morbidity, disability, and mortality, is recognized as a major cerebrovascular disease. MicroRNA-31 (miR-31) was reported to participate in the progression of brain disease. The present study was conducted in order to investigate the effect of miR-31 on oxidative stress-induced neuronal injury in IS mice with the involvement of protein kinase D1 (PKD1) and the JAK/STAT3 pathway. C57BL/6J mice were used to establish the middle cerebral artery occlusion (MCAO) model. Astrocytes were transfected with miR-31 mimic, miR-31 inhibitor, si-PKD1, or JAK-STAT3 pathway inhibitor. Following the establishment of an oxygen–glucose deprivation (OGD) model, the astrocytes were cocultured with neuronal OGD. Lower miR-31, higher PKD1 expressions, and activated JAK/STAT3 pathway were found in both the MCAO and OGD models. miR-31 could negatively target PKD1. In an MCAO model, overexpressing miR-31 and silencing PKD1 reduced neuronal injury, cerebral infarct volume, neuron loss, and oxidative stress injury, inhibited the activation of JAK/STAT3 pathway and the expressions of PKD1, interleukin (IL)-1β, IL-6, tumor necrosis factor-α, malondialdehyde, 4-HNE, 8-HOdG, caspase-3, and Bax, but increased the superoxide dismutase content. In the OGD model, overexpression of miR-31 and silencing of PKD1 attenuated oxidative stress-induced neuronal injury, and diminished the lactate dehydrogenase leakage and reactive oxygen species level, accompanied by elevated neuronal viability. These results indicate that miR-31 alleviates inflammatory response as well as an oxidative stress-induced neuronal injury in IS mice by downregulating PKD1 and JAK/STAT3 pathway.     

Ubc9 acetylation modulates distinct SUMO target modification and hypoxia response

While numerous small ubiquitin‐like modifier (SUMO) conjugated substrates have been identified, very little is known about the cellular signalling mechanisms that differentially regulate substrate sumoylation. Here, we show that acetylation of SUMO E2 conjugase Ubc9 selectively downregulates the sumoylation of substrates with negatively charged amino acid‐dependent sumoylation motif (NDSM) consisting of clustered acidic residues located downstream from the core ψ‐K‐X‐E/D consensus motif, such as CBP and Elk‐1, but not substrates with core ψ‐K‐X‐E/D motif alone or SUMO‐interacting motif. Ubc9 is acetylated at residue K65 and K65 acetylation attenuates Ubc9 binding to NDSM substrates, causing a reduction in NDSM substrate sumoylation. Furthermore, Ubc9 K65 acetylation can be downregulated by hypoxia via SIRT1, and is correlated with hypoxia‐elicited modulation of sumoylation and target gene expression of CBP and Elk‐1 and cell survival. Our data suggest that Ubc9 acetylation/deacetylation serves as a dynamic switch for NDSM substrate sumoylation and we report a previously undescribed SIRT1/Ubc9 regulatory axis in the modulation of protein sumoylation and the hypoxia response.     

Myeloperoxidase G-463A polymorphism and susceptibility to coronary artery disease: A meta-analysis

Published data on the association between the myeloperoxidase (MPO) G-463A polymorphism and coronary artery disease (CAD) are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis on this topic was performed. PubMed, EMBASE and Chinese national knowledge infrastructure were searched for studies regarding the association between the MPO G-463A polymorphism and CAD. A logistic regression analysis was used to estimate the genetic effect and the possible genetic model of action. Summary odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were calculated. There was strong evidence for an association between the MPO G-463A polymorphism and CAD. The genetic model of action was most likely to be co-dominant. Overall, the data showed that AA and GA genotypes were significantly associated with reduced risk of CAD (AA vs. GG: OR = 0.37, 95% CI = 0.17–0.78; GA vs. GG: OR = 0.73, 95% CI = 0.57–0.92). In subgroup analyses by study population and sources of controls, statistically significant results were observed in the Chinese population (AA vs. GG: OR = 0.21, 95% CI = 0.10–0.43; GA vs. GG: OR = 0.57, 95% CI =0.44–0.74) and in hospital-based control studies (AA vs. GG: OR = 0.20, 95% CI = 0.10–0.39; GA vs. GG: OR = 0.61, 95% CI = 0.48–0.77). This meta-analysis suggests that the MPO G-463A variant genotypes may be associated with decreased risk of CAD. However, given the limited number of studies and the potential biases, the influence of this polymorphism on CAD risk needs further investigation.