Music Therapy Alleviates Motor Dysfunction in Rats With Focal Cerebral Ischemia-Reperfusion Injury by Regulating BDNF Expression.

Background/Aim: Music-based therapy plays a role in central nervous system diseases. We aimed to explore the effect of different doses and durations of music therapy on motor function recovery after stroke and the underlying molecular mechanisms. Methods: Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1 h, which was followed by reperfusion. In experiment 1, the rats that survived 1 week after MCAO surgery were randomly allocated into four groups (n = 10 per group): MCAO group, 1 h music group (Mozart K.448 music therapy 1 h per day for 2 weeks), 12 h music group (Mozart K.448 music therapy 12 h/day for 2 weeks), and accelerated music group (reversely accelerated music therapy 12 h for 2 weeks, AM group). In experiment 2, the survived rats were randomly divied into three groups: MCAO group, 12 h music group (music therapy 12 h/day for 3 weeks), and 12 h music-R group (music therapy 12 h/day for 2 weeks and rest for 1 week). Three neuroscores were evaluated daily, starting on the first day after surgery until the end of the experiment. The rats were killed 3 weeks after MCAO surgery in experiment 1 or 4 weeks after surgery in experiment 2. Nissl staining of infart core, peri-infarct zone, and motor cortex was performed to assess neuronal survival and regeneration. Western blot and immunofluorescence were used to detect the expression and distribution of brain-derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) in ipsilateral hemispheres. Results: In the experiment of different music therapy doses, the motor function in the 12-h music group but not in the 1-h music group and AM group was significantly improved compared with that of the MCAO group. The BDNF protein level of the ipsilateral hemisphere motor cortex in the 12-h music group and the 1-h music group was higher than that of the MCAO group. The neurons and Nissl bodies were more in the 12-h music group than in the MCAO group. Immunofluorescence assay showed that a 12 h music therapy induces BDNF and GFAP accumulation at the damage boundary. In the experiment of different music therapy durations, 3 weeks music therapy (12 h music group) induced more longer cell synapses and more clearer cell-to-cell connections than 2 weeks music intervention (12 h music-R group). Moreover, the GFAP morphology in the 12-h music group was more similar to mature activated astrocytes than that in the 12-h music-R group. Conclusions: Music therapy may improve poststroke motor function and promote neuronal repair in the long term. The mechanism may be through stimulating BDNF and GFAP secretion in the injured motor cortex.

Simple and Effective Approach to Prepare an Epoxy-Functionalized Polymer and Its Application for an Electrochemical Immunosensor.

An epoxy-functionalized polymer based on a new skeleton has been prepared via an efficient method and it combined with aminated carbon nanotubes to form a new composite material. This new composite material was applied for the fabrication of an electrochemical immunosensor with good performance. The inexpensive and easily available IgG was used to test the performance of the prepared composite material. The levels of IgG were quantitatively analyzed using a differential pulse voltammetry detection system and the lowest detection limit was calculated to be 0.05 ng/mL. The detection system can also respond to IgG in the concentration range from 0.1 to 25 ng/mL.

Gut Microbiota-Derived Metabolites in the Development of Diseases.

Gut microbiota is increasingly recognized as a metabolic organ essential for human health. Compelling evidences show a variety set of links between diets and gut microbial homeostasis. Changes in gut microbial flora would probably contribute to the development of certain diseases such as diabetes, heart disease, allergy, and psychiatric diseases. In addition to the composition of gut microbiota, the metabolites derived from gut microbiota have emerged as a pivotal regulator in diseases development. Since high-fat and high-protein diets substantially affect the gut microbial ecology and human health, the current review summarizes the gut microbiota-derived metabolites such as short-chain fatty acids (SCFAs), amino acids, and their derivatives and highlights the mechanisms underlying the host responses to these bioactive substances.

Post Stroke Outcome: Global Insight into Persisting Sequelae Using the Post Stroke Checklist.

BACKGROUND: Following stroke, individuals commonly experience persisting loss of function. Whilst long-term care should involve continued support for ongoing stroke sequelae, this is often not routinely practiced globally. The Post Stroke Checklist was designed to standardise the process of detecting persisting treatable problems following stroke. AIMS: This cross-sectional study aimed to identify the long-term problems reported in Australian and Chinese participants at six months post stroke using the Post Stroke Checklist. It also aimed to provide global insight into poststroke sequelae by comparing the study results to previously published studies which administered the Post Stroke Checklist in other countries. METHODS: Participants were recruited from two hospitals in Australia and one hospital in China. The Post Stroke Checklist consists of 11 problem areas commonly experienced after stroke. This study follows a sequence of studies which have applied the checklist to monitor long-term outcomes after stroke in Germany, Italy, Singapore, Sweden and the United Kingdom. RESULTS: Comparisons between Australia (n = 112) and China (n = 97) demonstrated statistically significant differences on the Post Stroke Checklist items. Across all seven countries, collectively the most common persisting difficulties post-stroke related to: cognition, life after stroke, mood, mobility and activities of daily living. An analysis of means procedure compared individual countries for each checklist item against the overall group mean (all countries combined). CONCLUSIONS: Globally, individuals report persisting functional difficulties following stroke. There appear to be differences in the proportions affected across the various countries, and healthcare systems may benefit from geographically tailoring post-stroke care.

Label-Free Electrochemical Immunosensor Based on ß-Cyclodextrin-Functionalized Helical Carbon Nanotube and Ionic Liquid Containing Ferrocene and Aldehyde Groups.

We fabricated an electrochemical immunosensor for the detection of cardiac troponin I using ß-cyclodextrin-functionalized helical carbon nanotube and ionic liquid functionalized with ferrocene and aldehyde groups. ß-Cyclodextrin-functionalized helical carbon nanotube was first modified on the electrode surface. Then, ferrocene- and aldehyde-functionalized ionic liquid was modified on the surface of the electrode through host-guest interaction, resulting in an interface with aldehyde groups. The aldehyde groups attached to the ionic liquid capture antibody directly, which simplifies the fabrication of immunosensor. Because of the use of ionic liquid and helical carbon nanotube, the conductivity of the sensing interface was improved. Thus, the sensitivity of the fabricated immunosensor was increased. The immunosensor for cardiac troponin I shows a linear range from 0.05 to 20 ng mL-1 with a detection limit of 0.04 ng mL-1 (S/N = 3).

Label-Free Electrochemical Immunosensor Based on Ionic Liquid Containing Dialdehyde As a Novel Linking Agent for the Antibody Immobilization.

Demand for label-free electrochemical immunosensor has resulted in extensive research in improving the conductivity of a sensing interface and antibody immobilization. In this paper, an electrochemical immunosensor for prostate specific antigen based on dialdehyde-functionalized ionic liquid used as a novel linking reagent to replace glutaraldehyde for the antibody immobilization is described. The novel linking reagent enhanced the conductivity of the sensing interface. Thus, the proposed immunosensor had a wider linear range of 0.05-30 ng mL-1, with a lower detection limit of 0.04 ng mL-1 compared with the immunosensor based on glutaraldehyde for the antibody immobilization.

Hyperbaric Oxygen Alleviates the Inflammatory Response Induced by LPS Through Inhibition of NF-κB/MAPKs-CCL2/CXCL1 Signaling Pathway in Cultured Astrocytes.

The purpose of this study was to investigate the inhibition neuroinflammation mechanisms of hyperbaric oxygen therapy (HBOT). Primary astrocytes were incubated with lipopolysaccharide (LPS) after which they underwent HBOT and separate administration of inflammatory cytokine inhibitors. The respective expression of inflammatory factors was then detected. Results showed that LPS significantly induced increases in the expression levels of chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine C-C motif ligand 2 (CCL2), phospho-nuclear factor-kappa B (p-NF-κB), phospho-c-Jun N-terminal kinase (p-JNK), phospho-extracellular signal-regulated kinase (p-ERK), and phospho-p38 (p-p38) in cultured astrocytes and peaked at 3 h. HBOT downregulated the expression of some inflammation mediators including CXCL1 and CCL2. Furthermore, HBOT inhibited the expression of some up-stream regulators of inflammation mediators including p-NF-κB, p-JNK, p-p38 (at 3 and 6 h), and p-ERK (3 h). Inhibitors of NF-κB, ERK, and JNK (BAY117082, PD98059, and SP600125) significantly suppressed the expression of CXCL1 and CCL2 that were induced by LPS for 3 h. However, the p38 inhibitor, SB203580, had no obvious effect on expression levels of CXCL1 and CCL2. In conclusion, we found that HBOT inhibits neuroinflammation via regulation of the LPS-induced NF-κB/mitogen-activated protein kinases (MAPKs, JNK, and ERK) -CCL2/CXCL1 signaling pathways.

Human menstrual blood-derived stem cells promote functional recovery in a rat spinal cord hemisection model.

Spinal cord injury (SCI) is associated with a dismal prognosis including severe voluntary motor and sensory deficits in the presence of the current therapies, thus new and efficient treatment strategies are desperately required. Along with several advantages, such as easy accessibility, high-yield, potential of enormous proliferation, menstrual blood-derived mesenchymal stem cells (MenSCs) have been proposed as a promising strategy in regeneration medicine. In this study, the MenSCs were transplanted into incomplete thoracic (T10) spinal cord injury (SCI) rats, all rats were sacrificed at 7, 14, and 28 days after surgery. Based on the results, we found that MenSCs transplantation improved the hind limb motor function. Besides, H&E staining showed that MenSCs treatment markedly reduced cavity formation in the lesion site. Furthermore, treatment by MenSCs showed more MAP2-positive mature neurons, as well as axonal regeneration manifested by NF-200 and less expression of chondroitin sulfate proteoglycans (CSPGs) than the non-treatment in the lesion site. Additionally, immunofluorescence, Western blot, and qRT-PCR methods showed that levels of brain-derived neurotrophic factor (BDNF) were significantly higher in the injured spinal cord after implantation of MenSCs. Results of qRT-PCR indicated that inflammatory factors, including TNF-α and IL-1ß were inhibited after MenSCs transplantation. The improved motor function of hind limb and the increased cell body area of motor neurons were suppressed by blocking of the BDNF-TrkB signaling. It was eventually revealed that MenSCs implantation had beneficial therapeutic effects on the rehabilitation of the rat spinal cord hemisection model, mainly by enhancing the expression of BDNF. MenSCs transplantation may provide a novel therapeutic strategy for patients with SCI in the future.

Voltammetric immunoassay for α-fetoprotein by using a gold nanoparticle/dendrimer conjugate and a ferrocene derived ionic liquid.

An immunosensor is described for the voltammetric determination of α-fetoprotein. It is making use of an AuNP-dendrimer conjugate and an ionic liquid. A gold electrode was first modified with chitosan. Then, the AuNP-dendrimer conjugate was covalently immobilized on the electrode. Following this, an ionic liquid was placed on the electrode via formation of a covalent bond between the amino groups of PAMAM and the aldehyde groups of an ionic liquid containing ferrocene. Thus, the redox probe ferrocene becomes immobilized on the electrode surface. PAMAM increases the amount of ferrocene immobilized on the electrode due to its globular shape and rich amino groups. The use of AuNPs improves the conductivity of the electrode. The modified electrode was applied to the determination of α-fetoprotein in human serum and has a linear response that covers the 0.05 to 30 ng mL-1 α-fetoprotein concentration range, with a detection limit of 0.02 ng mL-1. This assay is stable, selective and reproducible. It is perceived to provide a powerful tool for the early detection of cancer markers. Graphical abstract Schematic of a voltammetric immunoassay for α-fetoprotein based on a gold nanoparticle/dendrimer conjugate and ionic liquids anchored with both aldehyde and ferrocene. Chit: chitosan; GA: glutaraldehyde ; PAMAM: G4 polyamidoaminic dendrimers; AuNP: Au nanoparticle; Fc: ferrocene; IL: ionic liquid. PB: phosphate buffer solution.

A novel label-free electrochemical immunosensor based on aldehyde-terminated ionic liquid.

In this paper, aldehyde-terminated ionic liquid was synthesized and used to fabricate a novel label-free electrochemical immunosensor for the determination of hepatitis B surface antigen. This sensor was formed from a gold electrode which was modified with a composite film containing the aldehyde-functionalized ionic liquid incorporated into nafion and anti-hepatitis B surface antigen antibody probes. Aldehyde-functionalized ionic liquid was used not only as a substrate for antibody immobilization, but also as a good material with high electrical conductivity, which greatly simplified the process of sensor fabrication. The proposed sensor exhibited a good performance in a linear range from 0.05 to 15ngmL-1 with a detection limit of 20pgmL-1 (S/N=3) and provided a novel strategy for clinical detection due to satisfying stability, selectivity and reproducibility.

A label-free electrochemical immunosensor based on a new polymer containing aldehyde and ferrocene groups.

In this work, a novel and convenient strategy for synthesis of a well-defined polymer containing both aldehyde and ferrocene functional groups by grafting 4-hydroxybenzaldehyde and ferrocenecarboxylhydrazide onto linear poly (vinylbenzyl chloride) was developed. The designed polymer film (polymer CAF) could be used as a new support matrix for fabrication of a label-free electrochemical immunosensor with high sensitivity, good stability and repeatability. With human IgG as an analyte model, the proposed electrochemical immunosensor showed a linear concentration range from 0.1 to 20ngmL-1 with a detection limit of 0.07ngmL-1 (S/N=3). Moreover, interfering proteins including HSA, IgM, and IgE were added into the analyte, the developed immnnosensor can detect human IgG with high specificity.

A Class of Multiresponsive Colorimetric and Fluorescent pH Probes via Three Different Reaction Mechanisms of Salen Complexes: A Selective and Accurate pH Measurement.

We report a class of multiresponsive colorimetric and fluorescent pH probes based on three different reaction mechanisms including cation exchange, protonation, and hydrolysis reaction of K(I), Ca(II), Zn(II), Cu(II), Al(III), and Pd(II) Salen complexes. Compared with traditional pure organic pH probes, these complex-based pH probes exhibited a much better selectivity due to the shielding function of the filled-in metal ion in the complex. Their pH sensing performances were affected by the ligand structure and the central metal ion. This work is the first report of "off-on-on'-off" colorimetric and fluorescent pH probes that possess three different reaction mechanisms and should inspire the design of multiple-responsive probes for important analytes in biological systems.

The fabrication of a label-free electrochemical immunosensor using Nafion/carbon nanotubes/charged pyridinecarboxaldehyde composite film.

A label-free electrochemical immunosensor based on Nafion/carbon nanotubes (CNTs)/charged pyridinecarboxaldehyde composite film was developed for the detection of hepatitis B surface antigen. Nafion/CNTs/charged pyridinecarboxaldehyde nanocomposites were prepared by dispersing charged pyridinecarboxaldehyde and CNTs in Nafion solution. The nanocomposites were cast on the electrode surface to form aldehyde-terminated composite film that can covalently bind antibody on the film without using other reagent. The immunosensor response was linearly changed with hepatitis B surface antigen concentration in the range from 0.1 to 25 ng ml(-1) with a detection limit (signal/noise ratio = 3) of 0.04 ng ml(-1). Some important advantages such as simple preparation, good stability, reproducibility, and selectivity of the immunosensor were achieved.

Electrochemical immunosensor based on Pd-Au nanoparticles supported on functionalized PDDA-MWCNT nanocomposites for aflatoxin B1 detection.

This paper reports a label-free electrochemical immunosensor for the determination of aflatoxin B1 (AFB1), which is based on a gold electrode modified by a biocompatible film of carbon nanotubes/poly(diallyldimethylammoniumchloride)/Pd-Au nanoparticles (CNTs/PDDA/Pd-Au). The nanocomposite was characterized by transmission electron microscopy and the electrochemical behavior of modified electrodes was investigated by cyclic voltammetry. The CNTs/PDDA/Pd-Au nanocomposites film showed good electron transfer ability, which ensured high sensitivity to detect AFB1 in a range from 0.05 to 25 ng mL(-1) with a detection limit of 0.03 ng mL(-1) obtained at 3σ (where σ is the standard deviation of the blank solution, n = 10). The proposed immunosensor provides a simple tool for AFB1 detection. This strategy can be extended to any other antigen detection by using the corresponding antibodies.

Downregulation of HMGA2 inhibits cellular proliferation and invasion, improves cellular apoptosis in prostate cancer.

Prostate cancer is the most commonly diagnosed cancer among men and is the second leading cause of cancer-associated deaths among men in the world. Unfortunately, treatment failures are common due to the metastasis and chemoresistance, but the underlying molecular mechanism remains unclear. Accumulating evidence has indicated that the deregulation of DNA-binding protein High Mobility Group A2 (HMGA2) is associated with the development and progression of cancer. This study aimed to explore the expression of HMGA2 in prostate cancer tissues and its correlation to the clinical pathology of prostate cancer, and to discuss the role of HMGA2 in the development of prostate cancer. The results showed that the expression of HMGA2 messenger RNA (mRNA) in the prostate cancer tissues and cells was significantly higher than that in normal prostate tissues and cells (p < 0.05), and the positive expression rate of HMGA2 mRNA in the prostate cancer tissues from patients with positive lymph node metastasis or with high Gleason grade was significantly higher than that from patients with negative lymph node metastasis or with low Gleason grade (p < 0.05). In order to explore the role of HMGA2 in prostate cancer, the expression of HMGA2 in the human prostate cancer PC3 cell line was downregulated by RNA interference. Then, the changes in proliferation, apoptosis, invasion, and migration of PC3 cells were examined by MTT test, PI staining, Annexin V-FITC staining, and Transwell chamber assay. Results showed that the abilities of proliferation, invasion, and migration were suppressed in HMGA2 knockdown PC3 cells, and the abilities of apoptosis were enhanced in HMGA2 knockdown PC3 cells. The expression of cyclin A and vimentin was downregulated in HMGA2 knockdown PC3 cells, and the expression of caspase 3 and E-cadherin was upregulated in HMGA2 knockdown PC3 cells. Taken together, the overexpression of HMGA2 in prostate cancer might be related to the tumorigenesis, invasion, and metastasis of prostate cancer, the downregulation of HMGA2 could inhibit cellular proliferation, invasion, and metastasis, and improve cellular apoptosis in prostate cancer, which might be a potential target for the treatment of prostate cancer.

Visual Spatial Attention Training Improve Spatial Attention and Motor Control for Unilateral Neglect Patients.

OBJECTIVE: To compare the effect of visual spatial training on the spatial attention to that on motor control and to correlate the improvement of spatial attention to motor control progress after visual spatial training in subjects with unilateral spatial neglect (USN). METHOD: 9 cases with USN after right cerebral stroke were randomly divided into Conventional treatment group + visual spatial attention and Conventional treatment group. The Conventional treatment group + visual spatial attention received conventional rehabilitation therapy (physical and occupational therapy) and visual spatial attention training (optokinetic stimulation and right half-field eye patching). The Conventional treatment group was only treated with conventional rehabilitation training (physical and occupational therapy). All patients were assessed by behavioral inattention test (BIT), Fugl-Meyer Assessment of motor function (FMA), equilibrium coordination test (ECT) and non-equilibrium coordination test (NCT) before and after 4 weeks treatment. RESULT: Total scores in both groups (without visual spatial attention/with visual spatial attention) improved significantly (BIT: P=0.021/P=0.000, d=1.667/d=2.116, power=0.69/power=0.98, 95%CI[-0.8839,45.88]/95%CI=[16.96,92.64]; FMA: P=0.002/P=0.000, d=2.521/d=2.700, power=0.93/power=0.98, 95%CI[5.707,30.79]/95%CI=[16.06,53.94]; ECT: P=0.002/ P=0.000, d=2.031/d=1.354, power=0.90/power=0.17, 95%CI[3.380,42.61]/95%CI=[-1.478,39.08]; NCT: P=0.013/P=0.000, d=1.124/d=1.822, power=0.41/power=0.56, 95%CI[-7.980,37.48]/95%CI=[4.798,43.60],) after treatment. Among the 2 groups, the group with visual spatial attention significantly improved in BIT (P=0.003, d=3.103, power=1, 95%CI[15.68,48.92]), FMA of upper extremity (P=0.006, d=2.771, power=1, 95%CI[5.061,20.14]) and NCT (P=0.010, d=2.214, power=0.81-0.90, 95%CI[3.018,15.88]). Correlative analysis shows that the change of BIT scores is positively correlated to the change of FMA total score (r=0.77, P<;0.01), FMA of upper extremity (r=0.81, P<0.01), NCT (r=0.78, P<0.01). CONCLUSION: Four weeks visual spatial training could improve spatial attention as well as motor control functions in hemineglect patients. The improvement of motor function is positively correlated to the progresses of visual spatial functions after visual spatial attention training.

Beneficial effects of hyperbaric oxygen on edema in rat hippocampus following traumatic brain injury.

Hyperbaric oxygen (HBO) therapy helps alleviate secondary injury following brain trauma [traumatic brain injury (TBI)], although the mechanisms remain unclear. In this study, we assessed recovery of post-TBI spatial learning and memory in rats using the Morris water maze (MWM) and measured changes in apparent diffusion coefficient in the hippocampus by diffusion-weighted imaging (DWI) to evaluate possible therapeutic effects of HBO on TBI-associated brain edema. DWIs were obtained 8, 24, 48 h, 7 days, and 14 days post-TBI. Daily HBO therapy significantly improved post-TBI MWM performance and reduced edema in the ipsilateral hippocampus, suggesting that the therapeutic efficacy of HBO is mediated, at least in part, by a reduction in brain edema.

The development of an electrochemical immunosensor using a thiol aromatic aldehyde and PAMAM-functionalized Fe3O4@Au nanoparticles.

In this work, a novel thiol aromatic aldehyde was synthesized. It can be used as a substrate to directly immobilize antibodies on a gold electrode, for which no additional chemical cross-linker is required. It was also applied as a linker to prepare Fe3O4@Au/PAMAM/Ab2-horseradish peroxidase bioconjugates, which introduced multiple enzymes onto a sensing interface owing to the high surface-to-volume ratio of Fe3O4@Au nanoparticles and many functional groups of the poly(amidoamine) dendrimer (PAMAM). The introduced multiple enzymes greatly improved the detection signal. Under optimal conditions, the proposed electrochemical immunosensor exhibited desirable performance for detection of IgG in the range 0.005-50 ng ml(-1) with a detection limit of 3 pg ml(-1) based on a signal-to-noise ratio of 3. It has great potential application in the area of clinical analysis.

Direct immobilization of antibodies on a new polymer film for fabricating an electrochemical impedance immunosensor.

A new polymer bearing aldehyde groups was designed and synthesized by grafting 4-pyridinecarboxaldehyde onto poly(epichlorohydrin). Antibodies can be directly immobilized on the surface of the polymer film through the covalent bonding of aldehyde groups of the film with amino groups of antibodies. In this study, human immunoglobulin G (IgG) was used as a model analyte for the fabrication of an electrochemical impedance immunosensor. Using the proposed immunosensor, IgG in the range from 0.1 to 80 ng ml(-1) was detected with a detection limit of 0.07 ng ml(-1) (signal/noise [S/N]=3). In addition, the electrochemical impedance immunosensor displays good stability and reproducibility.