Search

[Objectives] To explore the role and molecular mechanisms of aerobic exercise in post-stroke depression. [Methods] Wistar rats were randomly divided into sham, sedentary' and aerobic exercise (Ex) groups. The rats in sedentary and Ex groups received middle cerebral artery occlusion (MCAO) surgery. Aerobic exercise was performed 24 h after MCAO for four weeks in Ex group. The sucrose preference test (SPT), open field test (OFT), tail suspension test (TST) was performed, respectively. The levels of IL-lß, IL-6, TNF-a were detected by ELISA. [Results] Aerobic exercise successfully prevented depression-like symptom induced by ischemic stroke w'ith sedentary behavior as indicated by significant increase in sucrose preference (P <0.01) during SPT and decrease in immobility time (P <0. 01) during FST and TST. Aerobic exercise significantly reduced the high levels of IL-lß, IL-6, TNF-a induced by ischemic stroke and sedentary' behavior in the ischemic hippocampus (P <0.05). [Conclusions] Aerobic exercise after ischemic stroke can reverse depression and improve the inflammatory microenvironment in the hippocampus. [ABSTRACT FROM AUTHOR]

Objectives: To explore the effects of high-intensity intermittent training ( HIT) on the degree of depression, neuronal morphology, and the expreesion of bran-derived neurotrophic factor ( BDNF) in the hippocampal dentate gyrus ( DG) of ischemic hemisphere in rats with post-stroke depreesion (PSD), and to investigate the potential mechanisms. #Methods: 40 male Wistar rats were randomly divided into control group, sham-operation group (Sham), PSD model group, moderate intensity aerobic training group (MIAT) and HIT group (n =8 for each group ). Except the control and Sham group, all other groups were given the middle cerebral arter occlusion ( MCAO ) using the intraluminal thread method, and chronic unpredictable mild strees (CUMS) was applied. After succusful modeling, training programs of diferent intensity were perormed in the MIAT and the HIT group. Rats in the five groups were subjected to behavioral tests ( open field test and tail suspension test)) before and 28 d after training. Nisl staining was used to obsere the morphological changes of neurons in the left hippocampal DG area. The expreesions of BDNF protein were detected by western blotting and immunohistochemistry. Results : After 28 d of training, compared with the other groups, the PSD group's pause time of the central lattice was prolonged ; the immobility time increased in tail suspension test; the expreesion of BDNF decreased in the left hippocampal DG area. The diference was statisticaUy significant ( 8<0.01). Neurons of hippocampal DG neurons were loosely afranged ; cells were miising. Nisl body was lightly stained and even disolved ; the etiological findings in MIAT and HIT rats were revered ; the exprusion of BDNF was elevated. Nisl staining showed that the cells were aaranged neatly ; the layers were dense, and the Nisl body was deeply stained. The changes in HIT group were more significant than that in MIAT group (8 <0.05). Conclusions: Compared with the traditional medium-intensity aerobic training, high-intensity interval training can improve the depression-like behavior in rats with post-stroke depreesion. The potential mechanism might be that HIT increase the neuroplasticity and ex- preesion of BDNF in hippocampal DG area. [ABSTRACT FROM AUTHOR]

A nonlinear wave equation is investigated via the Riemann-Hilbert approach. Based on the spectral analysis for the Lax pair, a Riemann-Hilbert problem of the nonlinear wave equation is established. For the reflectionless cases, we obtain N-soliton solutions of the nonlinear wave equation and discuss the dynamic behavior of its soliton solutions. [ABSTRACT FROM AUTHOR]

On the basis of the spectral analysis for the Lax pair, a Riemann--Hilbert problem of the combined nonlinear Schrödinger and Gerdjikov--Ivanov equation is established. Using the inverse scattering transformation and the Riemann-Hilbert approach, the combined nonlinear Schrodinger and Gerdjikov-Ivanov equation is studied. As an application, N-soliton solutions of the combined nonlinear Schrödinger and Gerdjikov-Ivanov equation are obtained. In addition, some figures are given to illustrate the soliton characteristics of the nonlinear integrable equation. [ABSTRACT FROM AUTHOR]

The mechanism of nasopharyngeal carcinoma (NPC) remains unclear. The present study investigated the abnormal expression of long non-coding (lnc)RNAs in NPC tissues and one NPC cell line to identify the involvement of lncRNAs in the tumorigenesis of NPC. Using a quantitative reverse transcription polymerase chain reaction (RT-qPCR), the expression of lncRNA C22orf32-1 in NPC tissues and an NPC cell line was verified. The effects of lncRNA C22orf32-1 on NPC cells were investigated with a cell proliferation assay, cell scratch assay, Transwell assay and a cell apoptosis assay. The expression levels of lncRNA C22orf32-1 in NPC tissues and an NPC cell line were upregulated. lncRNA C22orf32-1 promoted the proliferation, migration and invasion of NPC cells, and reduced the apoptosis of NPC cells. The data demonstrated that lncRNA C22orf32-1 may facilitate the tumorigenesis of NPC, and may be used for the early diagnosis and treatment of NPC. [ABSTRACT FROM AUTHOR]

Bidirectional interactions between neurons and glial cells are crucial to the genesis of pathological pain. The mechanisms regulating these interactions and the role of this process in relaying synaptic input in the spinal dorsal horn remain to be established. We studied the role of glutamate transporters in the regulation of such interactions. On pharmacological blockade of glutamate transporters, slow inward currents (SICs) appeared spontaneously and/or were evoked by peripheral synaptic input in the spinal superficial dorsal horn neurons, including the spinothalamic tract neurons. We showed that the SICs were induced by the release of glutamate from glial cells. On inhibition of glutamate uptake, the stimulation-induced, synaptically released glutamate activated glial cells and caused glial cells to release glutamate. Glial-derived glutamate acted on extrasynaptic N-methyl-D -aspartate (NMDA) receptors mainly composed of NR2B receptors and generated SICs, which led to depolarization and action potential generation in superficial spinal dorsal horn neurons. Thus glutamate transporters regulate glutamatergic neuron–glia interactions at spinal sensory synapses. When glutamate uptake is impaired, glial cells function like excitatory interneurons—they are activated by peripheral synaptic input and release glutamate to activate postsynaptic neurons in spinal pain pathways. [ABSTRACT FROM AUTHOR]

Glial cell dysfunction and excessive glutamate receptor activation in spinal dorsal horn neurons are hallmark mechanisms of pathological pain. The way in which glial cell dysfunction leads to excessive glutamate receptor activation in the spinal sensory synapses remains unknown. We and others recently reported the downregulation of glial glutamate transporter (GT) protein expression in the spinal dorsal horn of neuropathic rats. In this study, we showed that excitatory postsynaptic currents originating from N-methyl-D-aspartate receptor activation (NMDA EPSCs) elicited by peripheral synaptic input in the spinal sensory synapses were enhanced in neuropathic rats with mechanical allodynia induced by partial sciatic nerve ligation. The enhanced NMDA EPSCs were accompanied by an increased proportion of NR2B receptor activation. Physically blocking the extrasynaptic glutamate with dextran or chemically scavenging the glutamate with glutamic-pyruvic transaminase ameliorated the abnormal NMDA EPSCs in neuropathic rats. Pharmacological blockade of glial GTs with dihydrokainic acid enhanced NMDA receptor activation elicited by synaptic input or puffed glutamate in normal control rats, but this effect was precluded in neuropathic rats. Thus extrasynaptic glutamate spillover and extrasynaptic NMDA receptor activation induced by deficient glial glutamate uptake in the synapses resulted in the excessive activation of NMDA receptors in neuropathic rats. It is suggested that extrasynaptic glutamate spillover may be a key synaptic mechanism related to phenotypic alterations induced by nerve injury in the spinal dorsal horn and that glial GTs are potential new targets in the development of analgesics. [ABSTRACT FROM AUTHOR]

Activation of N-methyl-D-aspartate (NMDA) receptors in the spinal dorsal horn neurons is a key process related to sensory transmission, neural plasticity, and pathogenesis of pain. In this study, we investigated how activation of NMDA receptors in spinal substantia gelatinosa neurons is regulated by glutamate re-uptake through glutamate transporters located in the astrocytic and neuronal plasma membranes. Using visualized whole cell patch recording techniques, NMDA excitatory postsynaptic currents evoked by graded peripheral inputs in spinal substantia gelatinosa neurons of spinal slices from young adult rats were analyzed before and after combined inhibition of glial and neuronal glutamate transporters by D-threo-β-benzyloxyaspartate (TBOA). Blockade of glutamate transporters increased the number and duration of NMDA receptors activated by weak and by strong primary afferent inputs as well as by exogenous glutamate. The enhancement in activation of NMDA receptors induced by TBOA was greater in neurons that have weaker synaptic input at baseline. Impaired glutamate uptake increased the open probability of NMDA channels and caused glutamate spillover outside the active synapses, leading to activation of extrasynaptic NMDA receptors and/or receptors located in neighboring synapses. Finally, blockade of glutamate transporters resulted in an increased proportion of NR2B subunit activation induced by peripheral input, and this increase was further augmented by stronger afferent input. These data indicate that glutamate transporters regulate spatiotemporal and intensity coding for sensory input and prevent excessive activation of glutamate receptors in the spinal dorsal horn. It is suggested that remedying dysfunctional glutamate transporters may be a potential new avenue to prevent the pathogenesis of pain. [ABSTRACT FROM AUTHOR]

Controlled modulation of T-cell response during immunotherapy, especially the balance between T helper 1 (Th1) and Th2 responses, is critical for generating effective immune response. Here we report that dual delivery of interleukin 10 (IL-10)-targeted small interfering RNA (siRNA) and DNA vaccines to dendritic cells (DCs), using a single particle carrier, efficiently enhances immune response and modulates it toward a stronger Th1 phenotype. Surface-functionalized polymer microparticles (MPs) carrying both IL-10-targeted siRNA and DNA antigens exhibited effective gene silencing, DNA transfection, and synergistically enhanced upregulation of maturation markers in primary DCs leading to increased T-cell proliferation, in vitro. Mice immunized with these dual-delivery carriers demonstrated a significant “switch” toward Th1 response as evidenced by increase in interferon γ (IFN-γ) production and decrease in IL-4 production by CD4+ T cells. This further led to enhanced antiviral cytotoxic T-lymphocyte activity. Such dual siRNA–DNA delivery provides a novel strategy to precisely control the type and strength of T-cell response during immunotherapy.Molecular Therapy (2008) 16 12, 2011–2021 doi:10.1038/mt.2008.206 [ABSTRACT FROM AUTHOR]

At atmospheric pressure and room temperature, dielectric barrier discharge induced plasma oxidation for achieving supported TiO2 photocatalysts derived from TiCl4 adsorbed onto g-Al2O3 pellets was studied. The supported TiO2/g-Al2O3photocatalysts prepared by a cyclic 'adsorption-discharge' approach, without requirement of heat treatment, exhibit high activity in the photocatalytic degradation reaction of formaldehyde. The mass spectra and optical emission spectra during O2/Ar discharge for oxidizing the adsorbed-state TiCl4 were measured. The mechanism for the TiO2 formation from adsorbed-state TiCl4 by plasma oxidation was discussed. [ABSTRACT FROM AUTHOR]

• BPIV3 enters MDBK cells through Clathrin-Mediated Endocytosis and Macropinocytosis in a acid-Dependent Manner. • Entry of BPIV3 into MDBK cells requires cathepsin L. • Macropinocytosis but not clathrin-mediated endocytosis for BPIV3 entry is dependent on actin dynamics. Bovine parainfluenza virus 3 (BPIV3) is an important respiratory pathogen of both young and adult cattle. No specific therapies are available for BPIV3. Understanding the viral internalization pathway of BPIV3 will provide new strategies for the development of antiviral treatments. Here, the entry mechanism of BPIV3 into MDBK cells was analyzed using chemical inhibitors and RNA silencing. Our data demonstrated that treatment with an inhibitor targeting the clathrin-mediated pathway or clathrin heavy chain (CHC) knockdown suppressed the entry of BPIV3 into MDBK cells. In contrast, sequestration of cellular cholesterol by nystatin or silencing of caveolin-1 had no effect on viral entry. Moreover, inhibition of critical modulators of macropinocytosis significantly reduced BPIV3 uptake. In addition, fluid-phase uptake was significantly increased in cells infected with BPIV3, which is indicative of virus-induced facilitation of macropinocytosis. These results suggest that BPIV3 enters MDBK cells via macropinocytosis and clathrin- but not caveolar-dependent endocytosis. Furthermore, inhibition of endosomal acidification and activation of cathepsin blocked BPIV3 entry, demonstrating that BPIV3 entered MDBK cells in a acid-dependent manner and required cathepsin L. Finally, we demonstrated that macropinocytosis but not clathrin-mediated endocytosis is dependent on actin dynamics during BPIV3 infection. [ABSTRACT FROM AUTHOR]

Presents a design for resonant cavity separate absorption and multiplication avalanche photodiodes in optical communication systems using AlGaAS/GaAs/InGaAs. Characteristics of the photodiode design; Frequency response of the developed design; Unity-gain and high-gain bandwidth product achieved by the photodiode.

The synaptonemal complex (SC) is an ordered but highly dynamic structure assembled between homologous chromosomes to control interhomologous crossover formation, ensuring accurate meiotic chromosome segregation. However, the mechanisms regulating SC assembly and dynamics remain unclear. Here, we identified two new SC components, SYP-5 and SYP-6, in Caenorhabditis elegans that have distinct expression patterns and form distinct SC assembly units with other SYPs through stable interactions. SYP-5 and SYP-6 exhibit diverse in vivo SC regulatory functions and distinct phase separation properties in cells. Charge-interacting elements (CIEs) are enriched in SC intrinsically disordered regions (IDRs), and IDR deletion or CIE removal confirmed a requirement for these elements in SC regulation. Our data support the theory that multivalent weak interactions between the SC units drive SC formation and that CIEs confer multivalency to the assembly units. [ABSTRACT FROM AUTHOR]

Background: Misfolded α-synuclein (α-Syn) aggregates participate in the pathogenesis of synucleinopathies, such as Parkinson's disease. Whereas much is known about how the various domains within full-length α-Syn (FL-α-Syn) contribute to the formation of α-Syn aggregates and therefore to their neurotoxicity, little is known about whether the individual peptides that can be generated from α-syn, possibly as intermediate metabolites during degradation of misfolded α-Syn aggregates, are neurotoxic themselves.Methods: A series of synthesized α-Syn peptides, corresponding to the locus in FL-α-Syn containing alanine 30, substitution of which with a proline causes a familial form of Parkinson's disease, were examined for their capacity of inducing release of microglial superoxide. The neurotoxicity of these peptides was measured according to their influence on the ability of neuroglial cultures deficient in gp91 (phox) , the catalytic unit of NADPH oxidase (Nox2), or wild-type cultures to take up (3)H-labeled dopamine and on the number of tyrosine hydroxylase-staining-positive neurons. Western blots and confocal images were utilized to analyze membrane translocation of p47 (phox) and p67 (phox) , phosphorylation of p47 (phox) and Erk1/2 kinase, and binding of α-Syn peptides to gp91 (phox) . Activation of brain microglia in mice injected with α-Syn peptides was demonstrated by immunostaining for major histocompatibility complex (MHC)-II along with qPCR for Iba-1 and MHC-II.Results: We report α-Syn (29-40) as a specific peptide capable of activating microglial Nox2 to produce superoxide and cause dopaminergic neuronal damage. Administered to mice, this peptide also activated brain microglia to increase expression of MHC-II and Iba-1 and stimulated oxidation reaction. Exploring the underlying mechanisms showed that α-Syn (29-40) peptide triggered Nox2 to generate extracellular superoxide and its metabolite H2O2 by binding to the catalytic unit gp91 (phox) of Nox2; diffusing into cytosol, H2O2 activated Erk1/2 kinase to phosphorylate p47 (phox) and p67 (phox) and further activated Nox2, establishing a positive feedback loop to amplify the Nox2-mediated response.Conclusions: Collectively, our study suggests novel information regarding how α-Syn causes neuronal injury, possibly including mechanisms involving abnormal metabolites of α-Syn aggregates. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Extracts from Ginkgo biloba L. leaves confer their therapeutic effects through the synergistic actions of flavonoid and terpenoid components, but some non-flavonoid and non-terpenoid components also exist in this extract. In the study of this paper, an investigation was carried out to compare the pharmacokinetic parameters of fourteen compounds to clarify the influences of non-flavonoid and non-terpenoid fraction (WEF) on the pharmacokinetics profile of the flavonoid fraction (FF) and the terpene lactone fraction (TLF) from Ginkgo biloba extracts. Materials and methods A selective and sensitive UPLC-MS/MS method was established to determine the plasma concentrations of the fourteen compounds to compare the pharmacokinetic parameters after orally administration of FF, TLF, FF-WEF, FF-TLF, TLF-WEF and FF-TLF-WEF with approximately the same dose. At different time points, the concentration of rutin (1), isoquercitrin (2), quercetin 3-O-[4-O-(-β-D-glucosyl)-α-L-rhamnoside] (3), ginkgolide C (4), bilobalide (5), quercitrin (6), ginkgolide B (7), ginkgolide A (8), luteolin (9), quercetin (10), apigenin (11), kaempferol (12), isorhamnetin (13), genkwanin (14) in rat plasma were determined and main pharmacokinetic parameters including T1/2, Tmax, Cmax and AUC were calculated using the DAS 3.2 software package. The statistical analysis was performed using the Student's t-test with P<0.05 as the level of significance. Results FF and WEF had no effect on the pharmacokinetic behaviors and parameters of the four terpene lactones, but the pharmacokinetic profiles and parameters of flavonoids changed while co-administered with non-flavonoid components. It was found that Cmax and AUC of six flavonoid aglycones in group FF-WEF, FF-TLF and FF-TLF-WEF had varying degrees of reduction in comparison with group FF, especially in group FF-TLF-WEF. On the contrary, the values of Cmax, Tmax and AUC of four flavonoid glycosides in group FF-TLF-WEF were significantly increased compared with those in group FF. Conclusions These results indicate that non-flavonoid components in Ginkgo biloba extracts could increase the absorption and improve the bioavailability of flavonoid glycosides but decrease the absorption and reduce the bioavailability of flavonoid aglycones. [ABSTRACT FROM AUTHOR]

During viral infection, extracellular dsRNA is a potent signaling molecule that activates many innate immune cells, including macrophages. TLR3 is a well-known receptor for extracellular dsRNA, and internalization of extracellular dsRNA is required for endosomal TLR3 activation. Preserved inflammatory responses of TLR3-deficient macrophages to extracellular dsRNA strongly support a TLR3-independent mechanism in dsRNA-mediated immune responses. The present study demonstrated that CDllb/ CD18 (Mac-1 [macrophage-1 Ag]), a surface integrin receptor, recognized extracellular dsRNA and induced macrophage im-mune responses. CDllb deficiency reduced inflammatory cytokine induction elicited by polyinosinic:polycytidylic acid (poly I:C; a synthetic dsRNA) in mouse sera and livers, as well as in cultured peritoneal macrophages. dsRNA-binding assay and confocal immunofluorescence showed that Mac-1, especially the CDllb subunit, interacted and colocalized with poly I:C on the surface of macrophages. Further mechanistic studies revealed two distinct signaling events following dsRNA recognition by Mac-1. First, Mac-1 facilitated poly I:C internalization through the activation of PI3K signaling and enhanced TLR3-dependent activation of IRF3 in macrophages. Second, poly I:C induced activation of phagocyte NADPH oxidase in a TLR3-independent, but Mac-1-dependent, manner. Subsequently, phagocyte NADPH oxidase-derived intracellular reactive oxygen species activated MAPK and NF-KB pathways. Our results indicate that extracellular dsRNA activates Mac-1 to enhance TLR3-dependent signaling and to trigger TLR3-independent, but Mac-l-dependent, inflammatory oxidative signaling, identifying a novel mechanistic basis for macrophages to recognize extracellular dsRNA to regulate innate immune responses. This study identifies Mac-1 as a novel surface receptor for extracellular dsRNA and implicates it as a potential therapeutic target for virus-related inflammatory diseases. [ABSTRACT FROM AUTHOR]

Somatic hybridization via PEG (Polyethylene 6000)-mediated protoplast fusion was achieved between two different wheat culture lines (Triticum aestivum L., 'Jinan' 177, T1 and T2) and Setaria italica (L.) P. Beauv. The T1 recipient originated from non-regenerable long-term cell suspensions, while T2 was derived from embryogenic calli with a high regeneration capacity. Donor protoplasts were obtained from embryogenic calli of S. italica (S) (with low regeneration capacity) irradiated with different doses of ultraviolet light. Twenty-three putative hybrid cell lines were produced in fusion combinations with the donor protoplasts treated with UV light for 30 s (combination I) and 1 min (combination II), but only one (from combination II) differentiated into green plants. Three cell lines from combination I and five cell lines from combination II possessed the nuclear genomes of T1, T2, and S. italica as revealed by cytological, isozyme, RAPD, and 5S rDNA spacer sequence analyses. Genomic in situ hybridization (GISH) analysis showed that most hybrid cell lines had 22–36 wheat chromosomes, 0–2 S. italica chromosomes, and 1–6 wheat – S. italica recombinant chromosomes, whereas the regenerable cell line had 44–56 wheat chromosomes and 3–6 recombinant chromosomes, but no intact S. italica chromosomes. RFLP analysis of organellar DNA revealed that mitochondrial and chloroplast DNA of both parents coexisted in all hybrid cell lines and recombined in most hybrid cell lines. These results indicate that the regeneration of hybrid plants involves not only the integration of S. italica nuclear and organellar DNA, but also the genome complementation of T1 and T2. [ABSTRACT FROM AUTHOR]

Li(Ni0.6Co0.2Mn0.2)O2 has been surface-modified by the lithium-ion conductor Li1.4)Al0.4)Ti1.6)(PO4)3 via a facile mechanical fusion method. The annealing temperature during coating process shows a strong impact on the surface morphology and chemical composition of Li(Ni0.6Co0.2Mn0.2)O2. The 600-°C annealed material exhibits the best cyclic stability at high charging cut-off voltage of 4.5 V (versus Li /Li) with the capacity retention of 90.9% after 100 cycles, which is much higher than that of bare material (79%). Moreover, the rate capability and thermal stability are also improved by Li1.4)Al0.4)Ti1.6)(PO4)3 coating. The enhanced performance can be attributed to the improved stability of interface between Li(Ni0.6Co0.2Mn0.2)O2 and electrolyte by Li1.4)Al0.4)Ti1.6)(PO4)3 modification. The results of this work provide a possible method to design reliable cathode materials to achieve high energy density and long cycle life. [ABSTRACT FROM AUTHOR]