Modulation of Experimental Herpes Encephalitis-Associated Neurotoxicity through Sulforaphane Treatment

Reactive oxygen species (ROS) produced by brain-infiltrating macrophages and neutrophils, as well as resident microglia, are pivotal to pathogen clearance during viral brain infection. However, unchecked free radical generation is also responsible for damage to and cytotoxicity of critical host tissue bystander to primary infection. These unwanted effects of excessive ROS are combated by local cellular production of antioxidant enzymes, including heme oxygenase-1 (HO-1) and glutathione peroxidase 1 (Gpx1). In this study, we showed that experimental murine herpes encephalitis triggered robust ROS production, as well as an opposing upregulation of the antioxidants HO-1 and Gpx1. This antioxidant response was insufficient to prevent tissue damage, neurotoxicity, and mortality associated with viral brain infection. Previous studies corroborate our data supporting astrocytes as the major antioxidant producer in brain cell cultures exposed to HSV-1 stimulated microglia. We hypothesized that stimulating opposing antioxidative responses in astrocytes, as well as neurons, would mitigate the effects of ROS-mediated neurotoxicity both in vitro and during viral brain infection in vivo. Here, we demonstrate that the addition of sulforaphane, a potent stimulator of antioxidant responses, enhanced HO-1 and Gpx1 expression in astrocytes through the activation of nuclear factor-E2-related factor 2 (Nrf2). Additionally, sulforaphane treatment was found to be effective in reducing neurotoxicity associated with HSV-stimulated microglial ROS production. Finally, intraperitoneal injections of sulforaphane into mice during active HSV infection reduced neuroinflammation via a decrease in brain-infiltrating leukocytes, macrophage- and neutrophil-produced ROS, and MHCII-positive, activated microglia. These data support a key role for astrocyte-produced antioxidants in modulating oxidative stress and neuronal damage in response to viral infection

Minicircle-oriP-IFNγ: A Novel Targeted Gene Therapeutic System for EBV Positive Human Nasopharyngeal Carcinoma

) in which the transgene expression was under the transcriptional regulation of oriP promoter.. Immunohistochemistry was used to detect the expression and the activity of the IFNγ in tumor sections. Our results demonstrated that mc-oriP vectors mediated comparable gene expression and anti-proliferative effect in the EBV-positive NPC cell line C666-1 compared to mc-CMV vectors. Furthermore, mc-oriP vectors exhibited much lower killing effects on EBV-negative cell lines compared to mc-CMV vectors. The targeted expression of mc-oriP vectors was inhibited by EBNA1-siRNA in C666-1. This selective expression was corroborated in EBV-positive and -negative tumor models. as a safe and highly effective targeted gene therapeutic system for the treatment of EBV positive NPC

Magnetic Iron Oxide Nanoparticles: Synthesis and Surface Functionalization Strategies

Surface functionalized magnetic iron oxide nanoparticles (NPs) are a kind of novel functional materials, which have been widely used in the biotechnology and catalysis. This review focuses on the recent development and various strategies in preparation, structure, and magnetic properties of naked and surface functionalized iron oxide NPs and their corresponding application briefly. In order to implement the practical application, the particles must have combined properties of high magnetic saturation, stability, biocompatibility, and interactive functions at the surface. Moreover, the surface of iron oxide NPs could be modified by organic materials or inorganic materials, such as polymers, biomolecules, silica, metals, etc. The problems and major challenges, along with the directions for the synthesis and surface functionalization of iron oxide NPs, are considered. Finally, some future trends and prospective in these research areas are also discussed

Use of taxane-containing induction chemotherapy in combination with concurrent chemoradiotherapy in Chinese patients with locally advanced nasopharyngeal carcinoma: a meta-analysis

Rui Tian,1,* Hong Xun Ye,2,* Bao Guo Zhang,3 Dong Ying Gu,3 Bing Wen Zhang,1 Zhi Pan Teng,1 Mao Yong Jin,4 Jin Fei Chen,3 Jian Wei Qi1 1Department of E.N.T., Nanjing First Hospital, Nanjing Medical University, Nanjing, 2Department of Oncology, The People’s Hospital of Taixing, Taixing, 3Department of Oncology, Nanjing First Hospital, Nanjing Medical University, 4Department of Technology, Nanjing Delta Biotechnology Co., Ltd., Nanjing, People’s Republic of China *These authors contributed equally to this work Purpose: Taxane-containing induction chemotherapy (IC) regimens in combination with concurrent chemoradiotherapy (CCRT) have been compared with non-taxane-containing IC combined with CCRT in randomized controlled trials (RCTs) in Chinese patients with advanced nasopharyngeal carcinoma (NPC). This meta-analysis aimed to systematically evaluate their clinical efficacy and safety profiling in this ethnic population.Methods: The electronic databases, PubMed, Embase, MEDLINE, and Chinese Biomedical Database, were searched for eligible studies. The outcomes included overall response rate (ORR), 1-year survival rate, and different types of adverse events. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations.Results: A total of 12 RCTs (representing 835 patients) were identified. The pooled analysis showed that taxane-containing regimens had a significant improvement in ORR for nasopharyngeal lesion (OR =4.57, 95% CI =1.14–18.30, P=0.032, z=2.15) but not in cervical lymph nodes (OR =1.23, 95% CI =0.65–2.36, P=0.532, z=0.64) and in 1-year survival rates (OR =1.19, 95% CI =0.10–14.82, P=0.893, z=0.13) compared with non-taxane-containing regimens. Regarding the adverse events and toxicities, grade 3–4 leukopenia and neutropenia were significantly different between the two groups (P<0.001) in favor of the non-taxane-containing regimens, but grade 3–4 vomiting was significantly different between the two groups (P<0.005) in favor of the taxane-containing regimens.Conclusion: When combined with CCRT, taxane-containing IC regimens may be more efficient for short-term local control in Chinese patients with locally advanced NPC than the non-taxane-containing IC regimens. Moreover, the major toxic effects, which were bone marrow suppression, could be tolerated by majority of patients. More long-term follow-up and high-quality trials of NPC are needed to validate our findings.Keywords: randomized controlled trials, clinical efficacy, safety, survival rate, adverse events, cervical lymph node

Prediction of FRP debonding using the global-energy-balance approach

A major research programme was carried out to analyse the mechanism of FRP debonding from concrete beams using global-energy-balance approach (GEBA). The analyses developed in the study provide an essential tool that will enable fracture mechanics to be used to determine the load at which FRP plates will debond from concrete beams. This obviates the need for finite element (FE) analyses in situations where reliable details of the interface properties and crack-tip stress fields are not attainable for an accurate analysis. This paper presents an overview of the GEBA analyses that is described in detail elsewhere, and explains the slightly unconventional assumptions made in the analyses