Process development of chromatography-based purification on pandemic influenza virus-like particle based vaccines

Since 2013, the H7N9 avian influenza virus is considered a threat to global public health. The development of the H7N9 avian influenza vaccine is one of the most effective strategies to prevent influenza pandemics. Virus-like particles (VLPs) influenza vaccines is non-infectious viral structural proteins. Not only to retain the ability to produce neutralizing antibodies against to viral surface protein, but also safer than the conventional inactivated vaccines. In our previous study, we successfully expressed three structural proteins, hemagglutinin (HA), neuraminidase (NA) and matrix (M1) from influenza A / Taiwan / 1/2013 (H7N9) of the VLP in insect cells. In this study, we present a downstream purification method for the VLP platform. The purification process involves microfiltration, chromatography (using ion exchange, affinity and gel filtration combinations), concentration, diafiltration and sterile filtration steps. In this study, 600 ml of the harvest from the baculovirus expression system was used. The characteristics of VLP volume were examined by HA assay, SDS-PAGE and negative staining transmission electron microscopy (TEM). The overall recovery of HA protein was approximately 38%. In the evaluation of immunized mouse, such virus particles have been shown the HI titer \u3e256. This study demonstrated the chromatographic-based purification process can provide an effective VLP vaccine production for the preparation of the H7N9 influenza pandemic

A protein interaction based model for schizophrenia study

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is a complex disease with multiple factors contributing to its pathogenesis. In addition to environmental factors, genetic factors may also increase susceptibility. In other words, schizophrenia is a highly heritable disease. Some candidate genes have been deduced on the basis of their known function with others found on the basis of chromosomal location. Individuals with multiple candidate genes may have increased risk. However it is not clear what kind of gene combinations may produce the disease phenotype. Their collective effect remains to be studied.</p> <p>Results</p> <p>Most pathways except metabolic pathways are rich in protein-protein interactions (PPIs). Thus, the PPI network contains pathway information, even though the upstream-downstream relation of PPI is yet to be explored. Here we have constructed a PPI sub-network by extracting the nearest neighbour of the 36 reported candidate genes described in the literature. Although these candidate genes were discovered by different approaches, most of the proteins formed a cluster. Two major protein interaction modules were identified on the basis of the pairwise distance among the proteins in this sub-network. The large and small clusters might play roles in synaptic transmission and signal transduction, respectively, based on gene ontology annotation. The protein interactions in the synaptic transmission cluster were used to explain the interaction between the NRG1 and CACNG2 genes, which was found by both linkage and association studies. This working hypothesis is supported by the co-expression analysis based on public microarray gene expression.</p> <p>Conclusion</p> <p>On the basis of the protein interaction network, it appears that the NRG1-triggered NMDAR protein internalization and the CACNG2 mediated AMPA receptor recruiting may act together in the glutamatergic signalling process. Since both the NMDA and AMPA receptors are calcium channels, this process may regulate the influx of Ca²⁺. Reducing the cation influx might be one of the disease mechanisms for schizophrenia. This PPI network analysis approach combined with the support from co-expression analysis may provide an efficient way to propose pathogenetic mechanisms for various highly heritable diseases.</p

Panax notoginseng Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice

Panax notoginseng (PN) is a traditional Chinese herb experimentally proven to have anti-inflammatory effects, and it is used clinically for the treatment of atherosclerosis, cerebral infarction, and cerebral ischemia. This study aimed to determine the anti-inflammatory effects of PN against bleomycin-induced pulmonary fibrosis in mice. First, in an in vitro study, culture media containing lipopolysaccharide (LPS) was used to stimulate macrophage cells (RAW 264.7 cell line). TNF-α and IL-6 levels were then determined before and after treatment with PN extract. In an animal model (C57BL/6 mice), a single dose of PN (0.5 mg/kg) was administered orally on Day 2 or Day 7 postbleomycin treatment. The results showed that TNF-α and IL-6 levels increased in the culture media of LPS-stimulated macrophage cells, and this effect was significantly inhibited in a concentration-dependent manner by PN extract. Histopathologic examination revealed that PN administered on Day 7 postbleomycin treatment significantly decreased inflammatory cell infiltrates, fibrosis scores, and TNF-α, TGF-β, IL-1β, and IL-6 levels in bronchoalveolar lavage fluid when compared with PN given on Day 2 postbleomycin treatment. These results suggest that PN administered in the early fibrotic stage can attenuate pulmonary fibrosis in an animal model of idiopathic pulmonary fibrosis

Clinical significance of erythropoietin receptor expression in oral squamous cell carcinoma

BACKGROUND: Hypoxic tumors are refractory to radiation and chemotherapy. High expression of biomarkers related to hypoxia in head and neck cancer is associated with a poorer prognosis. The present study aimed to evaluate the clinicopathological significance of erythropoietin receptor (EPOR) expression in oral squamous cell carcinoma (OSCC). METHODS: The study included 256 patients who underwent primary surgical resection between October 1996 and August 2005 for treatment of OSCC without previous radiotherapy and/or chemotherapy. Clinicopathological information including gender, age, T classification, N classification, and TNM stage was obtained from clinical records and pathology reports. The mRNA and protein expression levels of EPOR in OSCC specimens were evaluated by Q-RT-PCR, Western blotting and immunohistochemistry assays. RESULTS: We found that EPOR were overexpressed in OSCC tissues. The study included 17 women and 239 men with an average age of 50.9 years (range, 26–87 years). The mean follow-up period was 67 months (range, 2–171 months). High EPOR expression was significantly correlated with advanced T classification (p < 0.001), advanced TNM stage (p < 0.001), and positive N classification (p = 0.001). Furthermore, the univariate analysis revealed that patients with high tumor EPOR expression had a lower 5-year overall survival rate (p = 0.0011) and 5-year disease-specific survival rate (p = 0.0017) than patients who had low tumor levels of EPOR. However, the multivariate analysis using Cox’s regression model revealed that only the T and N classifications were independent prognostic factors for the 5-year overall survival and 5-year disease-specific survival rates. CONCLUSIONS: High EPOR expression in OSCC is associated with an aggressive tumor behavior and poorer prognosis in the univariate analysis among patients with OSCC. Thus, EPOR expression may serve as a treatment target for OSCC in the future

Location-Aware Visual Question Generation with Lightweight Models

This work introduces a novel task, location-aware visual question generation (LocaVQG), which aims to generate engaging questions from data relevant to a particular geographical location. Specifically, we represent such location-aware information with surrounding images and a GPS coordinate. To tackle this task, we present a dataset generation pipeline that leverages GPT-4 to produce diverse and sophisticated questions. Then, we aim to learn a lightweight model that can address the LocaVQG task and fit on an edge device, such as a mobile phone. To this end, we propose a method which can reliably generate engaging questions from location-aware information. Our proposed method outperforms baselines regarding human evaluation (e.g., engagement, grounding, coherence) and automatic evaluation metrics (e.g., BERTScore, ROUGE-2). Moreover, we conduct extensive ablation studies to justify our proposed techniques for both generating the dataset and solving the task.Comment: EMNLP 202

Rainfall Variation under Different Climate Change Scenarios Based on Cmip3 and Cmip5 Projections: a Case Study in Taiwan

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchive

Pediatric Traffic Injuries on Halloween in the United Kingdom: Prevalence and Injury Severity

The study results serve as a reminder for parents, children, and drivers to be alert to the danger of traffic crashes on Halloween. The aim of this study was to examine whether Halloween is associated with a higher incidence of traffic injuries and whether traffic injuries sustained on Halloween are more severe than those sustained on other days. The U.K. STATS19 database, including the data of all road traffic crashes occurring from 1990 to 2017, was employed. A total of 73,587 pediatric traffic casualties (involving pedestrians, cyclists, and moped riders) were included. Between 17:00 and 19:00 (17:00~18:59) on Halloween, the number of casualties was higher than that on other public holidays and usual days. The logistic regression model revealed that, between 17:00 and 18:00 (17:00~17:59), the risk of being killed or seriously injured on Halloween was 34.2% higher (odds ratio = 1.342; 95% CI = 1.065–1.692) than that on other days. Pediatric crashes occurring on Halloween are associated with a higher number of injuries and increased injury severity

Correlation of Interleukin-17-Producing Effector Memory T Cells and CD4 +

Background and Objectives. Hyperparathyroidism and hyperphosphatemia contribute to the inflammatory effects in chronic hemodialysis (HD) patients. Interleukin-17-producing CD4+ effector memory T (Th17) cells and CD4+CD25+Foxp3 regulatory T (Treg) cells both play critical roles in immune activation and inflammation. We investigated the relationship between the Treg and Th17 cells and the phosphate level in chronic HD patients. Methods. 105 patients aged ≥35 years on chronic HD over 3 months were enrolled. The peripheral blood mononuclear cells were collected, cultured, and stimulated by phytohemagglutinin-L, phorbol myristate acetate, and ionomycin at different time points for T cell differentiation. Results. The T cell differentiation was as follows: Th17 cells (mean ± standard deviation (SD): 25.61% ± 10.2%) and Treg cells (8.45% ± 4.3%). The Th17 cell differentiation was positively correlated with the phosphate and albumin levels and negatively correlated with age. The Treg cell differentiation was negatively correlated with albumin level and age. In the nondiabetes group (n=53), the Th17 cell differentiation was predominantly correlated with the phosphate and iPTH (intact parathyroid hormone) levels as well as the dialysis vintage. Conclusion. Higher phosphate and iPTH levels and longer dialysis duration may increase Th17 cell differentiation, especially in the nondiabetic chronic HD patients

Synergistic Apoptosis-Inducing Antileukemic Effects of Arsenic Trioxide and Mucuna macrocarpa

The objective of this study was to examine the potential of enhancing the antileukemic activity of arsenic trioxide (ATO) by combining it with a folk remedy, crude methanolic extract of Mucuna macrocarpa (CMEMM). Human leukemia cells HL-60, Jurkat, and Molt-3 were treated with various doses of ATO, CMEMM, and combinations thereof for 24 and 48 h. Results indicated that the combination of 2.5 μM ATO and 50 μg/mL CMEMM synergistically inhibited cell proliferation in HL-60 and Jurkat cell lines. Apoptosis triggered by ATO/CMEMM treatment was confirmed by accumulation of cells in the sub-G1 phase in cell cycle analyses, characteristic apoptotic nuclear fragmentation, and increased percentage of annexin V-positive apoptotic cells. Such combination treatments also led to elevation of reactive oxygen species (ROS). The antioxidants N-acetyl cysteine (NAC), butylated hydroxytoluene, and α-tocopherol prevented cells from ATO/CMEMM-induced apoptosis. The ATO/CMEMM-induced activation of caspase-3 and caspase-9 can be blocked by NAC. In summary, these results suggest that ATO/CMEMM combination treatment exerts synergistic apoptosis-inducing effects in human leukemic cells through a ROS-dependent mechanism and may provide a promising antileukemic approach in the future