Effects of sleep on brain perivascular space in a cognitively healthy population

The magnetic resonance imaging (MRI) visible perivascular space (PVS) reportedly clears amyloid-β and metabolic waste during sleep. Previous studies reported an association between sleep and the PVS in small vessel disease, traumatic brain injury, and Alzheimer's disease. However, this relationship in a healthy cohort is still unclear. Here, we used the Human Connectome Project Aging dataset to analyze the relationship between sleep and the PVS in cognitively healthy adults across the aging continuum. We measured sleep parameters using the self-reported Pittsburgh Sleep Quality Index questionnaire. We found that older adults who had better sleep quality and sleep efficiency presented with a larger PVS volume fraction in the basal ganglia (BG). However, sleep measures were not associated with PVS volume fraction in the centrum semiovale (CSO). In addition, we found that body mass index (BMI) influenced the BG-PVS across middle-aged and older participants. In the entire cognitively healthy cohort, the effect of sleep quality on PVS volume fraction was mediated by BMI. However, BMI did not influence this effect in the older cohort. Furthermore, there are significant differences in PVS volume fraction across racial/ethnic cohorts. In summary, the effect of sleep on the PVS volume alteration was different in the middle-aged adults and older adults

Co-infection of dengue and Zika viruses mutually enhances viral replication in the mosquito Aedes aegypti

Abstract Background The mosquito Aedes aegypti transmits two of the most serious mosquito-borne viruses, dengue virus (DENV) and Zika virus (ZIKV), which results in significant human morbidity and mortality worldwide. The quickly shifting landscapes of DENV and ZIKV endemicity worldwide raise concerns that their co-circulation through the Ae. aegypti mosquito vector could greatly exacerbate the disease burden in humans. Recent reports have indicated an increase in the number of co-infection cases in expanding co-endemic regions; however, the impact of co-infection on viral infection and the detailed molecular mechanisms remain to be defined. Methods C6/36 (Aedes albopictus) cells were cultured in Dulbecco's modified Eagle medium/Mitsuhashi and Maramorosch Insect Medium (DMEM/MM) (1:1) containing 2% heat-inactivated fetal bovine serum and 1× penicillin/streptomycin solution. For virus propagation, the cells were infected with either DENV serotype 2 (DENV2) strain 16681 or ZIKV isolate Thailand/1610acTw (MF692778.1). Mosquitoes (Ae. aegypti UGAL [University of Georgia Laboratory]/Rockefeller strain) were orally infected with DENV2 and ZIKV through infectious blood-feeding. Results We first examined viral replication activity in cells infected simultaneously, or sequentially, with DENV and ZIKV, and found interspecies binding of viral genomic transcripts to the non-structural protein 5 (NS5). When we challenged Ae. aegypti mosquitos with both DENV2 and ZIKV sequentially to probe similar interactions, virus production and vector susceptibility to infection were significantly enhanced. Conclusions Our results suggest that DENV2 and ZIKV simultaneously establishing infection in the Ae. aegypti mosquito vector may augment one another during replication. The data also implicate the homologous NS5 protein as a key intersection between the flaviviruses in co-infection, highlighting it as a potential target for vector control

Decreased MicroRNA-221 is Associated with High Levels of TNF-a in Human Adipose Tissue-Derived Mesenchymal Stem Cells From Obese Woman

Aim: The present study aimed to investigate the regulation and involvement of miR-221 in the differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs). The relationships between miR-221 and pro-inflammatory markers and adipokines were also explored. Methods: Eight adipose tissues were obtained from four obese (mean body mass index (BMI) =31.7 kg/m2) and four lean (mean BMI= 21.5 kg/m2) women. hASCs were induced to differentiate, and the related gene expression were measured in the hASC-differentiated adipocytes using real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR). Results: During adipogenesis, miR-221 was significantly down-regulated; furthermore, miR-221 levels were lower in hASC-differentiated adipocytes from obese subjects than in the corresponding adipocytes from lean subjects. Higher TNF-α mRNA levels were associated with lower levels of miR-221. In addition, the miR-221 levels in the adipocytes were inversely correlated with BMI. Conclusion: Our results support the link between miR-221 and obesity development as well as obesity related inflammatory status

In Vitro Characterization of Neutralizing Hen Antibodies to Coxsackievirus A16

Coxsackievirus A16 (CA16) is one of the major causative agents of hand, foot, and mouth disease (HFMD). Children aged <5 years are the most affected by CA16 HFMD globally. Although clinical symptoms of CA16 infections are usually mild, severe complications, such as aseptic meningitis or even death, have been recorded. Currently, no vaccine or antiviral therapy for CA16 infection exists. Single-chain variable fragment (scFv) antibodies significantly inhibit viral infection and could be a potential treatment for controlling the infection. In this study, scFv phage display libraries were constructed from splenocytes of a laying hen immunized with CA16-infected lysate. The pComb3X vector containing the scFv genes was introduced into ER2738 Escherichia coli and rescued by helper phages to express scFv molecules. After screening with five cycles of bio-panning, an effective scFv antibody showing favorable binding activity to proteins in CA16-infected lysate on ELISA plates was selected. Importantly, the selected scFv clone showed a neutralizing capability against the CA16 virus and cross-reacted with viral proteins in EV71-infected lysate. Intriguingly, polyclonal IgY antibody not only showed binding specificity against proteins in CA16-infected lysate but also showed significant neutralization activities. Nevertheless, IgY-binding protein did not cross-react with proteins in EV71-infected lysate. These results suggest that the IgY- and scFv-binding protein antibodies provide protection against CA16 viral infection in in vitro assays and may be potential candidates for treating CA16 infection in vulnerable young children

The Bottlenecks of Preparing Virus Particles by Size Exclusion for Antibody Generation

Enterovirus 71 (EV71) is the major etiological agent contributing to the development of hand-foot-mouth disease (HFMD). There are not any global available vaccines or antibody drugs against EV71 released yet. In this study, we perform the virus immunization in a cost-effective and convenient approach by preparing virus particles from size exclusion and immunization of chicken. Polyclonal yolk-immunoglobulin (IgY) was simply purified from egg yolk and monoclonal single-chain variable fragments (scFv) were selected via phage display technology with two scFv libraries containing 6.0 × 106 and 1.3 × 107 transformants. Specific clones were enriched after 5 rounds of bio-panning and four identical genes were classified after the sequence analysis. Moreover, the higher mutation rates were revealed in the CDR regions, especially in the CDR3. IgY showed specific binding activities to both EV71-infected and Coxsackievirus 16-infected cell lysates and high infectivity inhibitory activity of EV71. However, while IgY detected a 37 kDa protein, the selected scFv seemingly detected higher size proteins which could be cell protein instead of EV71 proteins. Despite the highly effective chicken antibody generation, the purity of virus particles prepared by size exclusion is the limitation of this study, and further characterization should be carried out rigorously

Visible-Light-Induced Bactericidal Activity of a Nitrogen-Doped Titanium Photocatalyst against Human Pathogens

The antibacterial activity of photocatalytic titanium dioxide (TiO(2)) substrates is induced primarily by UV light irradiation. Recently, nitrogen- and carbon-doped TiO(2) substrates were shown to exhibit photocatalytic activities under visible-light illumination. Their antibacterial activity, however, remains to be quantified. In this study, we demonstrated that nitrogen-doped TiO(2) substrates have superior visible-light-induced bactericidal activity against Escherichia coli compared to pure TiO(2) and carbon-doped TiO(2) substrates. We also found that protein- and light-absorbing contaminants partially reduce the bactericidal activity of nitrogen-doped TiO(2) substrates due to their light-shielding effects. In the pathogen-killing experiment, a significantly higher proportion of all tested pathogens, including Shigella flexneri, Listeria monocytogenes, Vibrio parahaemolyticus, Staphylococcus aureus, Streptococcus pyogenes, and Acinetobacter baumannii, were killed by visible-light-illuminated nitrogen-doped TiO(2) substrates than by pure TiO(2) substrates. These findings suggest that nitrogen-doped TiO(2) has potential application in the development of alternative disinfectants for environmental and medical usages

Effect of Peptide Sequences on Supramolecular Interactions of Naphthaleneimide/Tripeptide Conjugates

In this study, we reported a significant difference in the supramolecular hydrogelation of newly discovered <b>NI-GFF</b> (NI-Gly-l-Phe-l-Phe) and <b>NI-FFG</b> (NI-l-Phe-l-Phe-Gly) on the basis of their phase diagrams. With a small difference in the peptide chain between <b>NI-GFF</b> and <b>NI-FFG</b>, we observed a significant difference in their self-assembly properties; <b>NI-GFF</b> formed a stable gel at neutral pH, whereas <b>NI-FFG</b> did not, under the same conditions. From spectroscopic and computational studies, intermolecular π–π interactions and extended hydrogen bonding interactions might reinforce the intermolecular interactions of <b>NI-GFF</b>, which may facilitate the formation of the self-assembled nanostructures and the hydrogel. In addition, the aggregation-induced emission (AIE)-active <b>NI-GFF</b> reveals relatively good biocompatibility compared with that of <b>NI-FFG</b> for two commonly used cell lines, suggesting that it is a promising candidate for use as a supramolecular material in biomedical applications. Our results highlight the importance of tripeptide sequences in a self-assembling hydrogel system

miR-107 promotes tumor progression by targeting the let-7 microRNA in mice and humans

MicroRNAs (miRNAs) influence many biological processes, including cancer. They do so by posttranscriptionally repressing target mRNAs to which they have sequence complementarity. Although it has been postulated that miRNAs can regulate other miRNAs, this has never been shown experimentally to our knowledge. Here, we demonstrate that miR-107 negatively regulates the tumor suppressor miRNA let-7 via a direct interaction. miR-107 was found to be highly expressed in malignant tissue from patients with advanced breast cancer, and its expression was inversely correlated with let-7 expression in tumors and in cancer cell lines. Ectopic expression of miR-107 in human cancer cell lines led to destabilization of mature let-7, increased expression of let-7 targets, and increased malignant phenotypes. In contrast, depletion of endogenous miR-107 dramatically increased the stability of mature let-7 and led to downregulation of let-7 targets. Accordingly, miR-107 expression increased the tumorigenic and metastatic potential of a human breast cancer cell line in mice via inhibition of let-7 and upregulation of let-7 targets. By mutating individual sites within miR-107 and let-7, we found that miR-107 directly interacts with let-7 and that the internal loop of the let-7/miR-107 duplex is critical for repression of let-7 expression. Altogether, we have identified an oncogenic role for miR-107 and provide evidence of a transregulational interaction among miRNAs in human cancer development