Developing sustained dual-drug therapy for tendon sports injuries

Tendon plays an important role in regulating body locomotion and providing additional stability to the body. However, tendon is susceptible to injuries and the healing process could be devastating along with the several issues, namely adhesion formations, slow healing and failure at fixation sites, which have deferred the success of proper tendon healing via tendon tissue engineering. This dissertation thus aims to create a sustained dual-drug therapy to address these issues. For adhesion formation, naproxen sodium (NPS) has been shown to be able to avoid this symptom through inhibiting inflammation process. [Continues.

The influence of a changing bacterial community on trace metal scavenging in a deep-sea particle plume

An extensive set of particle samples was collected from the extended (nonbuoyant) hydrothermal plume, the distal remnant plume, and the adjacent waters in a transect across the Southern Juan de Fuca Ridge. Bacterial capsules comprised the primary species of particulate Mn. However, the data also showed significant shifts in the relative abundance of distinctive subpopulations of this bacterial community, as expressed by several consistently recurring capsule morphologies. The data are discussed with respect to distance from plume origins (relative plume age), total bacterial numbers, experimentally determined scavenging rate constants and total particulate and dissolved Mn. The relative distribution of one morph (Fibrous) corresponded (r = .825, p \u3c 0.001) to that of the scavenging rate constant, k1 (Cowen et al., 1990) for dissolved Mn onto particles. The greatest Mn deposits (by a factor of over 10×) were associated with this same morph, which was also the numerically dominant capsule morph at the off-axis stations where total particulate Mn plume values were highest. The disequilibrium in the particle population and the geochemical cycle of Mn in an evolving hydrothermal vent plume is reflected in the distribution coefficients for Mn (KD), which increase with distance from vent origins. The potential influence that changing subpopulations of bacteria may exert on the overall scavenging behavior of Mn in this evolving natural particle population is emphasized

Vacancy induced zero energy modes in graphene stacks: The case of ABC trilayer

The zero energy modes induced by vacancies in ABC stacked trilayer graphene are investigated. Depending on the position of the vacancy, a new zero energy solution is realised, different from those obtained in multilayer compounds with Bernal stacking. The electronic modification induced in the sample by the new vacancy states is characterised by computing the local density of states and their localisation properties are studied by the inverse participation ratio. We also analyse the situation in the presence of a gap in the spectrum due to a perpendicular electric field.Comment: 6 pages, 4 figures Published in special issue: Exploring Graphene, Recent Research Advance

Albiflorin attenuates inflammation and apoptosis by upregulating AMPK-mediated expression of CDX2 in a mouse model of ulcerative colitis

Purpose: To investigate the mechanism underlying the ameliorative effect of albiflorin (AF) on ulcerative colitis (UC) in dextran sulphate sodium (DSS)-induced mice model. Method: Female C57BL/6 mice were administered DSS to establish a mice model of UC. After one week, the mice received AF, and the body weight and length of colon were measured. The histopathological features of colon tissues treated with hematoxylin-eosin (H & E) stain were examinedby microscopy. Expression of inflammatory cytokines and apoptosis-related proteins were determined using enzyme-linked immunosorbent assay (ELISA) and western blotting. Results: The relative abundance of goblet cells and crypts of mice were significantly reduced in DSSinduced UC mice model; furthermore, focal ulcers and mucosal damage were apparent. Moreover, treatment with DSS decreased body weight and colon length, downregulated Bcl-2 and AMPK pathwayrelated proteins, increased inflammatory cytokines levels, and upregulated Bax and cleaved caspase-3. In contrast, treatment with AF completely ameliorated DSS-induced effects. Conclusion: AF treatment attenuated DSS-induced inflammation response and apoptosis via AMPK pathway and modulation of CDX2 expression in UC mice model. Keyword: Albiflorin, Ulcerative colitis, AMPK, CDX2, Apoptosi

Reduced RET expression in gut tissue of individuals carrying risk alleles of Hirschsprung's disease

Receptor tyrosine kinase (RET) single nucleotide polymorphisms (SNPs) are associated with the Hirschsprung's disease (HSCR). We investigated whether the amount of RET expressed in the ganglionic gut of human was dependent on the genotype of three regulatory SNPs (-5G>A rs10900296 and -1A>C rs10900297 in the promoter, and C>T rs2435357 in intron 1). We examined the effects of three regulatory SNPs on the RET gene expression in 67 human ganglionic gut tissues using quantitative real-time PCR. Also, 315 Chinese HSCR patients and 325 ethnically matched controls were genotyped for the three SNPs by polymerase chain reaction (PCR) and direct sequencing. The expression of RET mRNA in human gut tissue did indeed correlate with the genotypes of the individuals. The lowest RET expression was found for those individuals homozygous for the three risk alleles (A-C-T/A-C-T), and the highest for those homozygous for the 'wild-type' counterpart (G-A-C/G-A-C), with expression values ranging from 218.32±125.69 (mean ± SE) in tissues from individuals carrying G-A-C/G-A-C to 31.42±8.42 for individuals carrying A-C-T/A-C-T (P 5 0.018). As expected, alleles -5A, -1C and intron 1 T were associated with HSCR (P 5 5.94 × 10-31, 3.12 3 10-24 and 5.94 × 10-37, respectively) as was the haplotype encompassing the three associated alleles (A-C-T) when compared with the wild-type counterpart G-A-C (χ2 5 155.29, P « 0.0001). To our knowledge, this is the first RET expression genotype-phenotype correlation study conducted on human subjects to indicate common genetic variants in the regulatory region of RET may play a role in mediating susceptibility to HSCR, by conferring a significant reduction of the RET expression. © The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]

Receptor Quaternary Organization Explains G Protein-Coupled Receptor Family Structure.

The organization of Rhodopsin-family G protein-coupled receptors (GPCRs) at the cell surface is controversial. Support both for and against the existence of dimers has been obtained in studies of mostly individual receptors. Here, we use a large-scale comparative study to examine the stoichiometric signatures of 60 receptors expressed by a single human cell line. Using bioluminescence resonance energy transfer- and single-molecule microscopy-based assays, we found that a relatively small fraction of Rhodopsin-family GPCRs behaved as dimers and that these receptors otherwise appear to be monomeric. Overall, the analysis predicted that fewer than 20% of ∼700 Rhodopsin-family receptors form dimers. The clustered distribution of the dimers in our sample and a striking correlation between receptor organization and GPCR family size that we also uncover each suggest that receptor stoichiometry might have profoundly influenced GPCR expansion and diversification

Brain Structural Alterations in Left-Behind Children: A Magnetic Resonance Imaging Study

Parental migration has caused millions of children left behind, especially in China and India. Left-behind children (LBC) have a high risk of mental disorders and may present negative life outcomes in the future. However, little is known whether there are cerebral structural alterations in LBC in relative to those with parents. This study is to explore the effect of parental migration on brain maturation by comparing gray matter volume (GMV) and fractional anisotropy (FA) of LBC with well-matched non-LBC. Thirty-eight LBC (21 boys, age = 9.60 ± 1.8 years) and 30 non-LBC (19 boys, age = 10.00 ± 1.95 years) were recruited and underwent brain scans in 3.0 T MR. Intelligence quotient and other factors including family income, guardians’ educational level and separation time were also acquired. GMV and FA were measured for each participant and compared between groups using 2-sample t-tests with atlas-based analysis. Compared to non-LBC, LBC exhibited greater GMV in emotional and cortico-striato-thalamo-cortical circuits, and altered FA in bilateral superior occipitofrontal fasciculi and right medial lemniscus (p < 0.05, Cohen’s d > 0.89, corrected for false-discovery rate). Other factors including family income, guardians’ educational level and separation time were not associated with these brain changes. Our study provides empirical evidence of altered brain structure in LBC compared to non-LBC, responsible for emotion regulation and processing, which may account for mental disorders and negative life outcome of LBC. Our study suggests that absence of direct biological parental care may impact children’s brain development. Therefore, public health efforts may be needed to provide additional academic and social/emotional supports to LBC when their parents migrate to seeking better economic circumstances, which has become increasingly common in developing countries

Pre-treatment Resting-State Functional MR Imaging Predicts the Long-Term Clinical Outcome After Short-Term Paroxtine Treatment in Post-traumatic Stress Disorder

Background: The chronic phase of post-traumatic stress disorder (PTSD) and the limited effectiveness of existing treatments creates the need for the development of potential biomarkers to predict response to antidepressant medication at an early stage. However, findings at present focus on acute therapeutic effect without following-up the long-term clinical outcome of PTSD. So far, studies predicting the long-term clinical outcome of short-term treatment based on both pre-treatment and post-treatment functional MRI in PTSD remains limited.Methods: Twenty-two PTSD patients were scanned using resting-state functional MRI (rs-fMRI) before and after 12 weeks of treatment with paroxetine. Twenty patients were followed up using the same psychopathological assessments 2 years after they underwent the second MRI scan. Based on clinical outcome, the follow-up patients were divided into those with remitted PTSD or persistent PTSD. Amplitude of low-frequency fluctuations (ALFF) and degree centrality (DC) derived from pre-treatment and post-treatment rs-fMRI were used as classification features in a support vector machine (SVM) classifier.Results: Prediction of long-term clinical outcome by combined ALFF and DC features derived from pre-treatment rs-fMRI yielded an accuracy rate of 72.5% (p < 0.005). The most informative voxels for outcome prediction were mainly located in the precuneus, superior temporal area, insula, dorsal medial prefrontal cortex, frontal orbital cortex, supplementary motor area, lingual gyrus, and cerebellum. Long-term outcome could not be successfully classified by post-treatment imaging features with accuracy rates <50%.Conclusions: Combined information from ALFF and DC from rs-fMRI data before treatment could predict the long-term clinical outcome of PTSD, which is critical for defining potential biomarkers to customize PTSD treatment and improve the prognosis