Effective inhibition of foot-and-mouth disease virus (FMDV) replication in vitro by vector-delivered microRNAs targeting the 3D gene

<p>Abstract</p> <p>Background</p> <p>Foot-and-mouth disease virus (FMDV) causes an economically important and highly contagious disease of cloven-hoofed animals. RNAi triggered by small RNA molecules, including siRNAs and miRNAs, offers a new approach for controlling viral infections. There is no report available for FMDV inhibition by vector-delivered miRNA, although miRNA is believed to have more potential than siRNA. In this study, the inhibitory effects of vector-delivered miRNAs targeting the 3D gene on FMDV replication were examined.</p> <p>Results</p> <p>Four pairs of oligonucleotides encoding 3D-specific miRNA of FMDV were designed and selected for construction of miRNA expression plasmids. In the reporter assays, two of four miRNA expression plasmids were able to significantly silence the expression of 3D-GFP fusion proteins from the reporter plasmid, p3D-GFP, which was cotransfected with each miRNA expression plasmid. After detecting the silencing effects of the reporter genes, the inhibitory effects of FMDV replication were determined in the miRNA expression plasmid-transfected and FMDV-infected cells. Virus titration and real-time RT-PCR assays showed that the p3D715-miR and p3D983-miR plasmids were able to potently inhibit the replication of FMDV when BHK-21 cells were infected with FMDV.</p> <p>Conclusion</p> <p>Our results indicated that vector-delivered miRNAs targeting the 3D gene efficiently inhibits FMDV replication <it>in vitro</it>. This finding provides evidence that miRNAs could be used as a potential tool against FMDV infection.</p

Lentviral-mediated RNAi to inhibit target gene expression of the porcine integrin αv subunit, the FMDV receptor, and against FMDV infection in PK-15 cells

<p>Abstract</p> <p>Background</p> <p>shRNA targeting the integrin αv subunit, which is the foot-and-mouth disease virus (FMDV) receptor, plays a key role in virus attachment to susceptible cells. We constructed a RNAi lentiviral vector, iαv pLenti6/BLOCK -iT™, which expressed siRNA targeting the FMDV receptor, the porcine integrin αv subunit, on PK-15 cells. We also produced a lentiviral stock, established an iαv-PK-15 cell line, evaluated the gene silencing efficiency of mRNA using real-time qRT-PCR, integrand αv expression by indirect immunofluorescence assay (IIF) and cell enzyme linked immunosorbent assays (cell ELISA), and investigated the in vivo inhibitory effect of shRNA on FMDV replication in PK-15 cells.</p> <p>Results</p> <p>Our results indicated successful establishment of the iαv U6 RNAi entry vector and the iαv pLenti6/BLOCK -iT expression vector. The functional titer of obtained virus was 1.0 × 10⁶TU/mL. To compare with the control and mock group, the iαv-PK-15 group αv mRNA expression rate in group was reduced by 89.5%, whilst IIF and cell ELISA clearly indicated suppression in the experimental group. Thus, iαv-PK-15 cells could reduce virus growth by more than three-fold and there was a > 99% reduction in virus titer when cells were challenged with 10²TCID₅₀of FMDV.</p> <p>Conclusions</p> <p>Iαv-PK-15 cells were demonstrated as a cell model for anti-FMDV potency testing, and this study suggests that shRNA could be a viable therapeutic approach for controlling the severity of FMD infection and spread.</p

Myeloid-related protein 8/14 and the risk of cardiovascular death or myocardial infarction after an acute coronary syndrome in the Pravastatin or Atorvastatin Evaluation and Infection Theraphy: Thrombolysis in Myocardial Infarction (PROVE IT-TIMI 22) trial

Background Using a transcriptional profiling approach, we recently identified myeloid-related protein 8/14 (MRP-8/14) to be expressed by platelets during acute myocardial infarction (MI). Elevated concentrations of MRP-8/14 are associated with a higher risk for future cardiovascular events in apparently healthy individuals but have not been assessed with respect to prognosis in patients with acute coronary syndrome. Methods We performed a nested case-control study (n = 237 case-control pairs) among patients enrolled in the Pravastatin or Atorvastatin Evaluation and Infection Theraphy: Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial (mean follow-up 24 months) to investigate the risk of cardiovascular death or MI associated with MRP-8/14 measured at 30 days after an acute coronary syndrome. Results Patients with cardiovascular death or MI after 30 days (cases) had higher median [25th, 75th percentile] MRP-8/14 levels than patients who remained free of recurrent events (5.6 [2.8, 13.5] mg/L vs 4.0 [1.9, 10.1] mg/L, P = .020). The risk of a recurrent cardiovascular event increased with each increasing quartile of MRP-8/14 ( P-trend = 0.007) such that patients with the highest levels had a 2.0-fold increased odds (95% CI 1.1-3.6, P = .029) of a recurrent event after adjusting for standard risk indicators, randomized treatment, and C-reactive protein. Patients with elevated levels of MRP-8/14 and high-sensitivity C-reactive protein showed significantly increased risk of cardiovascular death or MI compared with patients with the lowest levels of both markers (adjusted odds ratio 2.1, 95% CI 1.2-3.8). Conclusions Myeloid-related protein 8/14 may be a useful biomarker of platelet and inflammatory disease activity in atherothrombosis and may serve as a novel target for therapeutic intervention

Collaborative collection effort strategies based on “Internet + recycling” business model

"Internet + recycling", a new and emerging collecting mode, is booming in conjunction with widespread Internet use in China. For the recycling of waste electrical and electronic equipment (WEEE), this paper studies collaborative collection effort strategies in a collection system consisting of a third-party and an e-tailer based on the "Internet + recycling" business model. Considering the collaboration occurring during collecting and selling and mutual influences of partners on the recycling of old products, the paper applies collection effort cost sharing mechanisms to promote recycling. Four models, namely, the centralized model (C-Model), unit transfer price model (P-Model), unilateral cost sharing model (U-Model) and bilateral cost sharing model (B-Model), are established, and optimal decisions and members' profits in various collaborative models are derived and compared. The results show that there exists an interval of profit sharing proportions in which each of the two cost sharing models is a Pareto improvement of the P-Model, and the total collection volume and profit of the collecting system increase in the B-Model relative to those in the U-Model under the same proportion of profit sharing. However, the B-Model is not necessarily a Pareto improvement of the U-Model. The results also show that profit improvements of both parties can be achieved without the third-party sharing the e-tailer's collection effort cost in the B-Model when the collaborative marginal profit is large enough. The paper further explores the impact of the collaborative marginal profit and third-party's market influence on the total collection volume and the efficiency of the collecting system. This study provides insight into the promotion of WEEE recycling and into the selection of collaborative strategies for Internet recycling enterprises. The work will prove beneficial to the development of the WEEE "Internet + recycling" industry

The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease

Late Transition Metal Catalysts with Chelating Amines for Olefin Polymerization

Polyolefins are the most consumed polymeric materials extensively used in our daily life and are usually generated by coordination polymerization in the polyolefin industry. Olefin polymerization catalysts containing transition metal–organic compound combinations are undoubtedly crucial for the development of the polyolefin industry. The nitrogen donor atom has attracted considerable interest and is widely used in combination with the transition metal for the fine-tuning of the chemical environment around the metal center. In addition to widely reported olefin polymerization catalysts with imine and amide donors (sp2 hybrid N), late transition metal catalysts with chelating amine donors (sp3 hybrid N) for olefin polymerization have never been reviewed. In this review paper, we focus on late transition metal (Ni, Pd, Fe, and Co) catalysts with chelating amines for olefin polymerization. A variety of late transition metal catalysts bearing different neutral amine donors are surveyed for olefin polymerization, including amine–imine, amine–pyridine, α-diamine, and [N, N, N] tridentate ligands with amine donors. The relationship between catalyst structure and catalytic performance is also encompassed. This review aims to promote the design of late transition metal catalysts with unique chelating amine donors for the development of high-performance polyolefin materials

Late Transition Metal Catalysts with Chelating Amines for Olefin Polymerization

Polyolefins are the most consumed polymeric materials extensively used in our daily life and are usually generated by coordination polymerization in the polyolefin industry. Olefin polymerization catalysts containing transition metal&ndash;organic compound combinations are undoubtedly crucial for the development of the polyolefin industry. The nitrogen donor atom has attracted considerable interest and is widely used in combination with the transition metal for the fine-tuning of the chemical environment around the metal center. In addition to widely reported olefin polymerization catalysts with imine and amide donors (sp2 hybrid N), late transition metal catalysts with chelating amine donors (sp3 hybrid N) for olefin polymerization have never been reviewed. In this review paper, we focus on late transition metal (Ni, Pd, Fe, and Co) catalysts with chelating amines for olefin polymerization. A variety of late transition metal catalysts bearing different neutral amine donors are surveyed for olefin polymerization, including amine&ndash;imine, amine&ndash;pyridine, &alpha;-diamine, and [N, N, N] tridentate ligands with amine donors. The relationship between catalyst structure and catalytic performance is also encompassed. This review aims to promote the design of late transition metal catalysts with unique chelating amine donors for the development of high-performance polyolefin materials