Myricetin ameliorates cognitive impairment in 3×Tg Alzheimer’s disease mice by regulating oxidative stress and tau hyperphosphorylation

Background: Alzheimer's disease is characterized by abnormal β-amyloid (Aβ) plaque accumulation, tau hyperphosphorylation, reactive oxidative stress, mitochondrial dysfunction and synaptic loss. Myricetin, a dietary flavonoid, has been shown to exert neuroprotective effects in vitro and in vivo. Here, we aimed to elucidate the mechanism and pathways involved in the protective effect of myricetin. Methods: The effect of myricetin was assessed on Aβ42 oligomer-treated neuronal SH-SY5Y cells and in 3×Tg mice. Behavioral tests were performed to assess the cognitive effects of myricetin (14 days, ip) in 3×Tg mice. The levels of beta-amyloid precursor protein (APP), synaptic and mitochondrial proteins, glycogen synthase kinase3β (GSK3β) and extracellular regulated kinase (ERK) 2 were assessed via Western blotting. Flow cytometry assays, immunofluorescence staining, and transmission electron microscopy were used to assess mitochondrial dysfunction and reactive oxidative stress. Results: We found that, compared with control treatment, myricetin treatment improved spatial cognition and learning and memory in 3×Tg mice. Myricetin ameliorated tau phosphorylation and the reduction in pre- and postsynaptic proteins in Aβ42 oligomer-treated neuronal SH-SY5Y cells and in 3×Tg mice. In addition, myricetin reduced reactive oxygen species generation, lipid peroxidation, and DNA oxidation, and rescued mitochondrial dysfunction via the associated GSK3β and ERK 2 signalling pathways. Conclusions: This study provides new insight into the neuroprotective mechanism of myricetin in vitro in cell culture and in vivo in a mouse model of Alzheimer’s disease

Engineering Properties of Sweet Potato Starch for Industrial Applications by Biotechnological Techniques Including Genome Editing

Sweet potato (Ipomoea batatas) is one of the largest food crops in the world. Due to its abundance of starch, sweet potato is a valuable ingredient in food derivatives, dietary supplements, and industrial raw materials. In addition, due to its ability to adapt to a wide range of harsh climate and soil conditions, sweet potato is a crop that copes well with the environmental stresses caused by climate change. However, due to the complexity of the sweet potato genome and the long breeding cycle, our ability to modify sweet potato starch is limited. In this review, we cover the recent development in sweet potato breeding, understanding of starch properties, and the progress in sweet potato genomics. We describe the applicational values of sweet potato starch in food, industrial products, and biofuel, in addition to the effects of starch properties in different industrial applications. We also explore the possibility of manipulating starch properties through biotechnological means, such as the CRISPR/Cas-based genome editing. The ability to target the genome with precision provides new opportunities for reducing breeding time, increasing yield, and optimizing the starch properties of sweet potatoes

Combined live oral priming and intramuscular boosting regimen with Rotarix® and a nanoparticle-based trivalent rotavirus vaccine evaluated in gnotobiotic pig models of G4P[6] and G1P[8] human rotavirus infection

Human rotavirus (HRV) is the causative agent of severe dehydrating diarrhea in children under the age of five, resulting in up to 215,000 deaths each year. These deaths almost exclusively occur in low- and middle-income countries where vaccine efficacy is the lowest due to chronic malnutrition, gut dysbiosis, and concurrent enteric viral infection. Parenteral vaccines for HRV are particularly attractive as they avoid many of the concerns associated with currently used live oral vaccines. In this study, a two-dose intramuscular (IM) regimen of the trivalent, nanoparticle-based, nonreplicating HRV vaccine (trivalent S60-VP8*), utilizing the shell (S) domain of the capsid of norovirus as an HRV VP8* antigen display platform, was evaluated for immunogenicity and protective efficacy against P[6] and P[8] HRV using gnotobiotic pig models. A prime–boost strategy using one dose of the oral Rotarix® vaccine, followed by one dose of the IM trivalent nanoparticle vaccine was also evaluated. Both regimens were highly immunogenic in inducing serum virus neutralizing, IgG, and IgA antibodies. The two vaccine regimens failed to confer significant protection against diarrhea; however, the prime–boost regimen significantly shortened the duration of virus shedding in pigs challenged orally with the virulent Wa (G1P[8]) HRV and significantly shortened the mean duration of virus shedding, mean peak titer, and area under the curve of virus shedding after challenge with Arg (G4P[6]) HRV. Prime–boost-vaccinated pigs challenged with P[8] HRV had significantly higher P[8]-specific IgG antibody-secreting cells (ASCs) in the spleen post-challenge. Prime–boost-vaccinated pigs challenged with P[6] HRV had significantly higher numbers of P[6]- and P[8]-specific IgG ASCs in the ileum, as well as significantly higher numbers of P[8]-specific IgA ASCs in the spleen post-challenge. These results suggest the promise of and warrant further investigation into the oral priming and parenteral boosting strategy for future HRV vaccines.Instituto de VirologíaFil: Hensley, Casey. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Nyblade, Charlotte. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Zhou, Peng. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Parreño, Gladys Viviana. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). INCUINTA. Instituto de Virologia e Innovaciones Tecnologicas (IVIT); ArgentinaFil: Parreño, Gladys Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ramesh, Ashwin. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Frazier, Annie. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Frazier, Maggie. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Garrison, Sarah. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Fantasia-Davis, Ariana. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Cai, Ruiqing. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados UnidosFil: Huang, Peng-Wei. Cincinnati Children’s Hospital Medical Center. Division of Infectious Diseases; Estados UnidosFil: Xia, Ming. Cincinnati Children’s Hospital Medical Center. Division of Infectious Diseases; Estados UnidosFil: Tan, Ming. Cincinnati Children’s Hospital Medical Center. Division of Infectious Diseases; Estados UnidosFil: Tan, Ming. University of Cincinnati College of Medicine. Department of Pediatrics; Estados UnidosFil: Yuan, Lijuan. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unido

Gastrodin ameliorates synaptic impairment, mitochondrial dysfunction and oxidative stress in N2a/APP cells

Alzheimer's disease is characterized by abnormal β-amyloid and tau accumulation, mitochondrial dysfunction, oxidative stress, and synaptic dysfunction. Here, we aimed to assess the mechanisms and signalling pathways in the neuroprotective effect of gastrodin, a phenolic glycoside, on murine neuroblastoma N2a cells expressing human Swedish mutant APP (N2a/APP). We found that gastrodin increased the levels of presynaptic-SNAP, synaptophysin, and postsynaptic-PSD95 and reduced phospho-tau Ser396, APP and Aβ1-42 levels in N2a/APP cells. Gastrodin treatment reduced reactive oxygen species generation, lipid peroxidation, mitochondrial fragmentation and DNA oxidation; restored mitochondrial membrane potential and intracellular ATP production. Upregulated phospho-GSK-3β and reduced phospho-ERK and phospho-JNK were involved in the protective effect of gastrodin. In conclusion, we demonstrated the neuroprotective effect of gastrodin in the N2a/APP cell line by ameliorating the impairment on synaptic and mitochondrial function, reducing tau phosphorylation, Aβ1-42 levels as well as reactive oxygen species generation. These results provide new mechanistic insights into the potential effect of gastrodin in the treatment of Alzheimer’s disease

Yap1 Hydroxylation Suppress Prostate Cancer Metastasis

View full abstracthttps://openworks.mdanderson.org/leading-edge/1031/thumbnail.jp

Integration of Information Theory, K-Means Cluster Analysis and the Logistic Regression Model for Landslide Susceptibility Mapping in the Three Gorges Area, China

In this work, an effective framework for landslide susceptibility mapping (LSM) is presented by integrating information theory, K-means cluster analysis and statistical models. In general, landslides are triggered by many causative factors at a local scale, and the impact of these factors is closely related to geographic locations and spatial neighborhoods. Based on these facts, the main idea of this research is to group a study area into several clusters to ensure that landslides in each cluster are affected by the same set of selected causative factors. Based on this idea, the proposed predictive method is constructed for accurate LSM at a regional scale by applying a statistical model to each cluster of the study area. Specifically, each causative factor is first classified by the natural breaks method with the optimal number of classes, which is determined by adopting Shannon’s entropy index. Then, a certainty factor (CF) for each class of factors is estimated. The selection of the causative factors for each cluster is determined based on the CF values of each factor. Furthermore, the logistic regression model is used as an example of statistical models in each cluster using the selected causative factors for landslide prediction. Finally, a global landslide susceptibility map is obtained by combining the regional maps. Experimental results based on both qualitative and quantitative analysis indicated that the proposed framework can achieve more accurate landslide susceptibility maps when compared to some existing methods, e.g., the proposed framework can achieve an overall prediction accuracy of 91.76%, which is 7.63–11.5% higher than those existing methods. Therefore, the local scale LSM technique is very promising for further improvement of landslide prediction

Magnetic Porous Molecularly Imprinted Polymers Based on Surface Precipitation Polymerization and Mesoporous SiO2 Layer as Sacrificial Support for Efficient and Selective Extraction and Determination of Chlorogenic Acid in Duzhong Brick Tea

Magnetic porous molecularly imprinted polymers (MPMIPs) for rapid and efficient selective recognition of chlorogenic acid (CGA) were effectively prepared based on surface precipitation polymerization using CGA as template, 4-vinylpyridine (4-VP) as functional monomer, and mesoporous SiO2 (mSiO2) layer as sacrificial support. A computational simulation by evaluation of electronic binding energy is used to optimize the stoichiometric ratio between CGA and 4-VP (1:5), which reduced the duration of laboratory trials. The porous MIP shell and the rid of solid MIPs by magnet gave MPMIPs high binding capacity (42.22 mg/g) and fast kinetic binding (35 min). Adsorption behavior between CGA and MPMIPs followed Langmuir equation and pseudo-first-order reaction kinetics. Furthermore, the obtained MPMIPs as solid phase adsorbents coupled with high performance liquid chromatography (HPLC) were employed for selective extraction and determination of CGA (2.93 ± 0.11 mg/g) in Duzhong brick tea. The recoveries from 91.8% to 104.2%, and the limit of detection (LOD) at 0.8 μg/mL were obtained. The linear range (2.0–150.0 μg/mL) was wide with R2 > 0.999. Overall, this study provided an efficient approach for fabrication of well-constructed MPMIPs for fast and selective recognition and determination of CGA from complex samples

The evolution of gadolinium based contrast agents: from single-modality to multi-modality

Gadolinium-based contrast agents are extensively used as magnetic resonance imaging (MRI) contrast agents due to their outstanding signal enhancement and ease of chemical modification. However, it is increasingly recognized that information obtained from single modal molecular imaging cannot satisfy the higher requirements on the efficiency and accuracy for clinical diagnosis and medical research, due to its limitation and default rooted in single molecular imaging technique itself. To compensate for the deficiencies of single function magnetic resonance imaging contrast agents, the combination of multi-modality imaging has turned to be the research hotpot in recent years. This review presents an overview on the recent developments of the functionalization of gadolinium-based contrast agents, and their application in biomedicine applications