555 research outputs found
FSD-C10, a Fasudil derivative, promotes neuroregeneration through indirect and direct mechanisms.
FSD-C10, a Fasudil derivative, was shown to reduce severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through the modulation of the immune response and induction of neuroprotective molecules in the central nervous system (CNS). However, whether FSD-C10 can promote neuroregeneration remains unknown. In this study, we further analyzed the effect of FSD-C10 on neuroprotection and remyelination. FSD-C10-treated mice showed a longer, thicker and more intense MAP2 and synaptophysin positive signal in the CNS, with significantly fewer CD4(+) T cells, macrophages and microglia. Importantly, the CNS of FSD-C10-treated mice showed a shift of activated macrophages/microglia from the type 1 to type 2 status, elevated numbers of oligodendrocyte precursor cells (OPCs) and oligodendrocytes, and increased levels of neurotrophic factors NT-3, GDNF and BDNF. FSD-C10-treated microglia significantly inhibited Th1/Th17 cell differentiation and increased the number of IL-10(+) CD4(+) T cells, and the conditioned medium from FSD-C10-treated microglia promoted OPC survival and oligodendrocyte maturation. Addition of FSD-C10 directly promoted remyelination in a chemical-induced demyelination model on organotypic slice culture, in a BDNF-dependent manner. Together, these findings demonstrate that FSD-C10 promotes neural repair through mechanisms that involved both immunomodulation and induction of neurotrophic factors
Expression and biological significance of c-FLIP in human hepatocellular carcinomas
<p>Abstract</p> <p>Background</p> <p>c-FLIP can be considered as a tumor-progression factor in regard to its anti-apoptotic functions. In the present study, we intended to investigate the expression of c-FLIP in human HCC tissues, and its relation with drug-induced cell apoptosis through the specific inhibition of c-FLIP expression by siRNA in 7721 cells.</p> <p>Methods</p> <p>c-FLIP expression was quantified immunohistochemically in HCC tissues(eighty-six cases), and corresponding noncancerous tissues (fifty-seven cases). Patients with HCC were followed up for cancer recurrence. Then, the c-FLIP gene was silenced with specific siRNA in 7721 HCC cells. c-FLIP expression was detected by RT-PCR, Western Blot and immunocytochemical staining. The cellular viability and cell apoptosis were assayed <it>in vitro </it>with cells treated with doxorubicin.</p> <p>Results</p> <p>Positive immunostaining was detected for c-FLIP in 83.72% (72/86) human HCC tissues, 14.81% (4/27) hepatic cirrhosis, 11.11% (2/18) hepatic hemangioma tissues, and absent in normal hepatic tissues. The overexpression(more than 50%) of c-FLIP in HCC adversely affected the recurrence-free survival. Through c-FLIP gene silencing with siRNA, the expressions of c-FLIP mRNA and protein were remarkably down-regulated in 7721 HCC cells. And doxorubicin showed apparent inhibition on cell proliferations, and induced more apoptosis.</p> <p>Conclusion</p> <p>These results indicate that c-FLIP is frequently expressed in human HCCs, and its overexpression implied a lesser probability of recurrence-free survival. The specific silencing of c-FLIP gene can apparently up-regulate drug-induced HCC cell apoptosis, and may have therapeutic potential for the treatment of human HCC.</p
Mechanisms of Stress Tolerance in Xerophyte \u3cem\u3eZygophyllum xanthoxylum\u3c/em\u3e and Their Application in Genetic Improvement of Legume Forages
Xerophytes, naturally growing in desert areas, have evolved multiple protective mechanisms to survive and grow well in harsh environments. Zygophyllum xanthoxylum, a succulent xerophyte with excellent adaptability to adverse arid environments and a fodder shrub with high palatability and nutrient value, colonizes arid areas in China and Mongolia. In this study, we found that Z. xanthoxylum grew better responding to salt condition with a typical feature for halophytes and became more tolerant to drought in the presence of moderate salinity (50 mM NaCl); 50 mM NaCl alleviated deleterious impacts of drought on the growth of Z. xanthoxylum by improving the relative water content, inducing a significant drop in leaf water potential and, concomitantly, increasing leaf turgor pressure and chlorophyll concentrations resulting in an enhancement of overall plant photosynthetic activity. Subsequently, co-expression of genes encoding the tonoplast Na+/H+ antiporter (ZxNHX) and H+-PPase (ZxVP1-1) which involve in leaf Na+ accumulation under stress condition by compartmentalizing Na+ into vacuoles in Z. xanthoxylum significantly improved both drought and salt tolerance in legume forages, Lotus corniculatus L. and Medicago sativa L
Resonant spin Hall conductance in quantum Hall systems lacking bulk and structural inversion symmetry
Following a previous work [Shen, Ma, Xie and Zhang, Phys. Rev. Lett. 92,
256603 (2004)] on the resonant spin Hall effect, we present detailed
calculations of the spin Hall conductance in two-dimensional quantum wells in a
strong perpendicular magnetic field. The Rashba coupling, generated by
spin-orbit interaction in wells lacking bulk inversion symmetry, introduces a
degeneracy of Zeeman-split Landau levels at certain magnetic fields. This
degeneracy, if occuring at the Fermi energy, will induce a resonance in the
spin Hall conductance below a characteristic temperature of order of the Zeeman
energy. At very low temperatures, the spin Hall current is highly non-ohmic.
The Dresselhaus coupling due to the lack of structure inversion symmetry
partially or completely suppresses the spin Hall resonance. The condition for
the resonant spin Hall conductance in the presence of both Rashba and
Dresselhaus couplings is derived using a perturbation method. In the presence
of disorder, we argue that the resonant spin Hall conductance occurs when the
two Zeeman split extended states near the Fermi level becomes degenerate due to
the Rashba coupling and that the the quantized charge Hall conductance changes
by 2e^2/h instead of e^2/h as the magnetic field changes through the resonant
field.Comment: 9 pages, 7 figures. This is a sequel to Physical Review Letters 90,
256603 (2004
On-Line Error Detection of Annotated Corpus Using Modular Neural Networks
Abstract. This paper proposes an on-line error detecting method for a manually annotated corpus using min-max modular (M3) neural net-works. The basic idea of the method is to use guaranteed convergence of the M3 network to detect errors in learning data. To confirm the ef-fectiveness of the method, a preliminary computer experiment was per-formed on a small Japanese corpus containing 217 sentences. The results show that the method can not only detect errors within a corpus, but may also discover some kinds of knowledge or rules useful for natural language processing.
Effect of long-term topical latanoprost medication on conjunctival thickness in patients with glaucoma
AIM: To investigate the effect of long-term use of topically administered latanoprost on conjunctival thickness (CT) and conjunctival epithelium thickness (CET) in the patients with glaucoma.
METHODS: A series of 106 glaucomatous patients were included. Of the 106 eyes, 55 eyes were treated with latanoprost eye drops once a day (latanoprost group), while 51 eyes were treated with carteolol hydrochloride eye drops (carteolol group). All the included patients completed a 2-year follow-up. CT and CET were measured with optical coherence tomography (OCT) in all patients at presentation and at 2-year visit, respectively. Statistical analysis was then performed to compare the change in CT and CET.
RESULTS: At presentation, there was no difference in CET (t=0.400, P=0.689) or CT (t=1.14, P=0.259) between the two groups. No significant difference was found in CET (61.65±5.35 μm at baseline, 60.36±6.36 μm at 2-year follow-up, respectively; t=1.977, P=0.0531), while there was a significant decrease in CT from 201.45±14.99 μm at baseline to 167.81±14.57 μm at 2-year visit (t=14.1407, P<0.001) in the latanoprost group. At 2-year follow-up, no statistically difference was found in CET (62.24±5.27 μm; t=1.086, P=0.282) or CT (201.23±12.45 μm; t=1.44, P=0.154) compared to it at baseline (CET: 61.23±5.42 μm; CT: 198.76±13.68 μm, respectively) in the carteolol group.
CONCLUSION: A significant decrease in conjunctival thickness is found in glaucoma patients treated with long-term topical latanoprost; its potential effect on the outcome of filtration surgery should be considered
Hydroxysafflor Yellow A protects spinal cords from ischemia/reperfusion injury in rabbits
<p>Abstract</p> <p>Background</p> <p>Hydroxysafflor Yellow A (HSYA), which is one of the most important active ingredients of the Chinese herb <it>Carthamus tinctorius L</it>, is widely used in the treatment of cerebrovascular and cardiovascular diseases. However, the potential protective effect of HSYA in spinal cord ischemia/reperfusion (I/R) injury is still unknown.</p> <p>Methods</p> <p>Thirty-nine rabbits were randomly divided into three groups: sham group, I/R group and HSYA group. All animals were sacrificed after neurological evaluation with modified Tarlov criteria at the 48th hour after reperfusion, and the spinal cord segments (L4-6) were harvested for histopathological examination, biochemical analysis and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining.</p> <p>Results</p> <p>Neurological outcomes in HSYA group were slightly improved compared with those in I/R group. Histopathological analysis revealed that HSYA treatment attenuated I/R induced necrosis in spinal cords. Similarly, alleviated oxidative stress was indicated by decreased malondialdehyde (MDA) level and increased superoxide dismutase (SOD) activity after HSYA treatment. Moreover, as seen from TUNEL results, HSYA also protected neurons from I/R-induced apoptosis in rabbits.</p> <p>Conclusions</p> <p>These findings suggest that HSYA may protect spinal cords from I/R injury by alleviating oxidative stress and reducing neuronal apoptosis in rabbits.</p
Critical Role of FoxO1 in Granulosa Cell Apoptosis Caused by Oxidative Stress and Protective Effects of Grape Seed Procyanidin B2
Reactive oxygen species (ROS) are closely related to the follicular granulosa cell apoptosis. Grape seed procyanidin B2 (GSPB2) has been reported to possess potent antioxidant activity. However, the GSPB2-mediated protective effects and the underlying molecular mechanisms in granulosa cell apoptosis process remain unknown. In this study, we showed for the first time that GSPB2 treatment decreased FoxO1 protein level, improved granulosa cell viability, upregulated LC3-II protein level, and reduced granulosa cell apoptosis rate. Under a condition of oxidative stress, GSPB2 reversed FoxO1 nuclear localization and increased its level in cytoplasm. In addition, FoxO1 knockdown inhibited the protective effects of GSPB2 induced. Our findings suggest that FoxO1 plays a pivotal role in regulating autophagy in granulosa cells, GSPB2 exerts a potent and beneficial role in reducing granulosa cell apoptosis and inducing autophagy process, and targeting FoxO1 could be significant in fighting against oxidative stress-reduced female reproductive system diseases
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