The study of the neurophysiology of high strain rate nerve injury

The study of the mechanism of traumatic brain injury (TBI) processes at the cellular level is vital to obtain characterization of nerve cell damage after mechanical deformation. This understanding is needed to find feasible therapeutic targets for mechanically damaged neurons. To study the cellular level of TBI damage, development of a new in vitro cellular model of TBI might be done to simulate in vivo cellular TBI. In this research, two studies were performed: (1) the design and construction of an in vitro cell stretching device to mechanically injure cells and (2) the characterization of the molecular and cellular level of the TBI mechanism. The cell stretching device design allows for the precise control of cell strain and duration of stretching cells such that TBI can be mimicked. Analysis of the cellular and molecular level mechanisms of TBI in the proposed in vitro model might help in the design of therapeutic strategies for the treatment of TBI. Our proposed mechanism of injury due to TBI is as follows: after the cell is stretched, a cellular signaling molecule is released to activate the cellular signaling pathway. The activated cell signal may activate kinases which phosphorylate proteins and initiate new protein synthesis. Newly phosphorylated and synthesized proteins may activate the apoptotic process. Using a variety of pharmacological agents, one could block steps in the hypothesized mechanism and examine the effect of those agents on downstream cellular processes and cell apoptosis. For example, the inhibitions of calcium transport, protein synthesis, and caspases were performed to examine the initial activation of the signaling pathway and the role of both in the apoptosis process. Proteomics of TBI may help the understanding of the mechanism of TBI related protein expression. This work will contribute to the discovery of new therapeutic targets and better treatments for TBI

Effect of Osteoconductive Hyaluronate Hydrogels on Calvarial Bone Regeneration

11Yscopu

Four new Microbacterium species isolated from seaweeds and reclassification of five Microbacterium species with a proposal of Paramicrobacterium gen. nov. under a genome-based framework of the genus Microbacterium

The taxonomic relationships of 10 strains isolated from seaweeds collected from two beaches in Republic of Korea were studied by sequencing and analyses of 16S rRNA genes and whole genomes. For the construction of a more reliable and robust 16S rRNA gene phylogeny, the authentic and nearly complete 16S rRNA gene sequences of all the Microbacterium type strains were selected through pairwise comparison of the sequences contained in several public databases including the List of Prokaryotic names with Standing in Nomenclature (LPSN). The clustering of the ten study strains into five distinct groups was apparent in this single gene-based phylogenetic tree. In addition, the 16S rRNA gene sequences of a few type strains were shown to be incorrectly listed in LPSN. An overall phylogenomic clustering of the genus Microbacterium was performed with a total of 113 genomes by core genome analysis. As a result, nine major (≥ three type strains) and eight minor (two type strains) clusters were defined mostly at gene support index of 92 and mean intra-cluster OrthoANIu of >80.00%. All of the study strains were assigned to a Microbacterium liquefaciens clade and distributed further into four subclusters in the core genome-based phylogenetic tree. In vitro phenotypic assays for physiological, biochemical, and chemotaxonomic characteristics were also carried out with the ten study strains and seven closely related type strains. Comparison of the overall genomic relatedness indices (OGRI) including OrthoANIu and digital DNA–DNA hybridization supported that the study strains constituted four new species of the genus Microbacterium. In addition, some Microbacterium type strains were reclassified as members of preexisting species. Moreover, some of them were embedded in a new genus of the family Microbacteriaceae based on their distinct separation in the core genome-based phylogenetic tree and amino acid identity matrices. Based on the results here, four new species, namely, Microbacterium aurugineum sp. nov., Microbacterium croceum sp. nov., Microbacterium galbinum sp. nov., and Microbacterium sufflavum sp. nov., are described, along with the proposal of Paramicrobacterium gen. nov. containing five reclassified Microbacterium species from the “Microbacterium agarici clade”, with Paramicrobacterium agarici gen. nov., comb. nov. as the type species

Validation of Submaximal Step Tests and the 6-Min Walk Test for Predicting Maximal Oxygen Consumption in Young and Healthy Participants.

Background: This study aimed to test the validity of three different submaximal tests (i.e., 3-min step test with 20.3-cm step box height (3MST20), 3-min step test with 30-cm step box height (3MST30), and 6-min walk test (6MWT)) in estimating maximal oxygen consumption (VO2max) in young and healthy individuals. Methods: The 3MST20, 3MST30, 6MWT, as well as the cardiopulmonary exercise test (CPET) were performed in 73 participants (37 men and 36 women; mean age: 30.8 ± 9.3 years). All participants visited the clinic three times in a random order for anthropometric measurements, three submaximal tests, and the VO2max test. Multiple linear regression analyses were conducted to construct the VO2max prediction equations for each submaximal test. Results: The prediction equations developed based on multiple regression analyses for each submaximal tests were as follows: 3MST20: VO2max = 86.0 - 10.9 × sex (male = 1, female = 2) - 0.4 × age - 0.1 × weight - 0.1 × heart rate recovery at 30 s (HRR30s); 3MST30: VO2max = 84.5 - 10.2 × sex (male = 1, female = 2) - 0.4 × age - 0.1 × weight - 0.1 × HRR30s; and 6MWT: VO2max = 61.1 - 11.1 × sex (male = 1, female = 2) - 0.4 × age - 0.2 × weight - 0.2 × (distance walked·10-1). The estimated VO2max values based on formulated equations were 37.0 ± 7.9, 37.3 ± 7.6, and 36.9 ± 7.9 mL∙kg-1∙min-1 derived from the 3MST20, 3MST30, and 6MWT, respectively. These estimated VO2max values were not significantly different from the measured VO2max value, 37.3 mL∙kg-1∙min-1. The estimated VO2max based on the 3MST20, 3MST30, and 6MWT results explained 73.4%, 72.2%, and 74.4% of the variances in the measured VO2max (p < 0.001), respectively. Conclusions: The 3MST20, 3MST30, and 6MWT were valid in estimating VO2max in relatively young and healthy Asian individuals

Direct transfer of viral and cellular proteins from varicella-zoster virus-infected non-neuronal cells to human axons

10.1371/journal.pone.0126081PLoS ONE105e012608

Anti-inflammatory effects of Radix Gentianae Macrophyllae (Qinjiao), Rhizoma Coptidis (Huanglian) and Citri Unshiu Pericarpium (Wenzhou migan) in animal models

<p>Abstract</p> <p>Background</p> <p>KHU14, an ethanolic extract of <it>Radix Gentianae Macrophyllae </it>(<it>Qinjiao</it>), <it>Rhizoma Coptidis </it>(<it>Huanglian</it>) and <it>Citri Unshiu Pericarpium </it>(<it>Wenzhou migan</it>) was tested for its anti-inflammatory effects.</p> <p>Methods</p> <p>Three out of 20 herbs were found to have anti-inflammatory effects. The formulation of these herbs, i.e. KHU14 was tested for croton oil-induced ear edema, carrageenan-induced paw edema, acetic acid-induced capillary permeability, cotton pellet and delayed type hypersensitivity.</p> <p>Results</p> <p>KHU14 exhibited anti-inflammatory effects in animal models of acute and chronic inflammation. The anti-inflammatory activity of KHU14 observed was comparable to that of celecoxib. KHU14 inhibited the production of NO and PGE₂in LPS/IFN-gamma-stimulated peritoneal macrophages, and reduced edema and the amount of infiltrated cells in animal models.</p> <p>Conclusion</p> <p>KHU14 exhibited anti-inflammatory effects as demonstrated in typical immunological tests for anti-inflammation <it>in vitro </it>and <it>in vivo</it>.</p

CKD-712, (S)-1-(α-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, Inhibits the NF-κB Activation and Augments Akt Activation during TLR4 Signaling

Since CKD-712 has been developed as an anti-inflammatory agent, we examined the effect of CKD-712 during TLR4 signaling. Using HEK293 cells expressing TLR4, CKD-712 was pre-treated 1 hr before LPS stimulation. Activation of NF-κB was assessed by promoter assay. The activation of ERK, JNK, p38, IRF3 and Akt was measured by western blotting. CKD-712 inhibited the NF-κB signaling triggered by LPS. The activation of ERK, JNK, p38 or IRF3 was not inhibited by CKD-712. On the contrary the activation of these molecules was augmented slightly. The activation of Akt with stimulation of LPS was also enhanced with CKD-712 pre-treatment at lower concentration, but was inhibited at higher concentration. We suggest that during TLR4 signaling CKD-712 inhibits NF-κB activation. However, CKD-712 augmented the activation of Akt as well as Map kinases. Therefore, we suggest that CKD-712 might have a role as an immunomodulator