ABSTRACT: BACKGROUND: Cerebral ischemia has been shown to induce activation of matrix metalloproteinases (MMPs), particularly MMP-9, which is associated with impairment of the neurovasculature, resulting in blood-brain barrier breakdown, hemorrhage and neurodegeneration. We previously reported that the thiirane inhibitor SB-3CT, which is selective for gelatinases (MMP-2 and 9), could antagonize neuronal apoptosis after transient focal cerebral ischemia. RESULTS: Here, we used a fibrin-rich clot to occlude the middle cerebral artery (MCA) and assessed the effects of SB-3CT on the neurovasculature. Results show that neurobehavioral deficits and infarct volumes induced by embolic ischemia are comparable to those induced by the filament-occluded transient MCA model. Confocal microscopy indicated embolus-blocked brain microvasculature and neuronal cell death. Post-ischemic SB-3CT treatment attenuated infarct volume, ameliorated neurobehavioral outcomes, and antagonized the increases in levels of proform and activated MMP-9. Embolic ischemia caused degradation of the neurovascular matrix component laminin and tight-junction protein ZO-1, contraction of pericytes, and loss of lectin-positive brain microvessels. Despite the presence of the embolus, SB-3CT mitigated these outcomes and reduced hemorrhagic volumes. Interestingly, SB-3CT treatment for seven days protected against neuronal laminin degradation and protected neurons from ischemic cell death. CONCLUSION: These results demonstrate considerable promise for the thiirane class of selective gelatinase inhibitors as potential therapeutic agents in stroke therapy.

Elucidation of the mechanisms of chemo-resistance and implementation of strategies to overcome it will be pivotal to improve the survival for osteosarcoma (OS) patients. We here suggest that sphingosine kinase-1 (SphK1) might be the key factor contributing to chemo-resistance in OS. Our Western-blots and immunohistochemistry results showed that SphK1 is over-expressed in multiple clinical OS tissues. Over-expression of SphK1 in OS cell line U2OS promoted its growth and endorsed its resistance against doxorubicin, while knocking-down of SphK1 by shRNA inhibited U2OS cell growth and increased its sensitivity to doxorubicin. Co-administration phenoxodiol with doxorubicin synergistically inhibited SphK1 activity to trigger cellular ceramide accumulation, and achieved synergistic anti-OS growth effect, accompanied with a significant increased of apoptosis and cytotoxicity. Increased cellular level of ceramide by the co-administration induced the association between Akt and Protein Phosphatase 1 (PP1) to dephosphorylate Akt, and to introduce a constitutively active Akt (CA-Akt) restored Akt activation and diminished cell growth inhibition. Further, phenoxodiol and doxorubicin synergistically activated apoptosis signal-regulating kinase 1(ASK1)/c-jun-NH2-kinase (JNK) signaling, which also contributed to cell growth inhibition. Significantly, the role of SphK1 in OS cell growth and the synergistic anti-OS effect of phenoxodiol and doxorubicin were also seen in a mice OS xenograft model. In conclusion, our data suggest that SphK1 might be a critical oncogene of OS and co-administration phenoxodiol with doxorubicin synergistically inhibited the activity of SphK1 to suppress osteosarcoma cell growth both in vivo and in vitro.

In H.264/advanced video coding (AVC), lossless coding and lossy coding share the same entropy coding module. However, the entropy coders in the H.264/AVC standard were original designed for lossy video coding and do not yield adequate performance for lossless video coding. In this paper, we analyze the problem with the current lossless coding scheme and propose a mode dependent template (MD-Template) based method for intra lossless coding. By exploring the statistical redundancy of the prediction residual in the H.264/AVC intra prediction modes, more zero coefficients are generated. By designing a new scan order for each MD-Template, the scanned coefficients sequence fits the H.264/AVC entropy coders better. A fast implementation algorithm is also designed. With little computation increase, experimental results confirm that the proposed fast algorithm achieves about 7.2% bit saving compared with the current H.264/AVC fidelity range extensions high profile.

The pathophysiology of Alzheimer's disease (AD) is comprised of complex metabolic abnormalities in different cell types in the brain. To date, there are not yet effective drugs that can completely inhibit the pathophysiological event, and efforts have been devoted to prevent or minimize the progression of this disease. Much attention has focused on studies to understand aberrant functions of the ionotropic glutamate receptors, perturbation of calcium homeostasis, and toxic effects of oligomeric amyloid beta peptides (Aβ) which results in production of reactive oxygen and nitrogen species and signaling pathways, leading to mitochondrial dysfunction and synaptic impairments. Aberrant phospholipase A(2)(PLA(2)) activity has been implicated to play a role in the pathogenesis of many neurodegenerative diseases, including AD. However, mechanisms for their modes of action and their roles in the oxidative and nitrosative signaling pathways have not been firmly established. In this article, we review recent studies providing a metabolic link between cytosolic PLA(2)(cPLA(2)) and neuronal excitation due to stimulation of ionotropic glutamate receptors and toxic Aβ peptides. The requirements for Ca(2+) binding together with its posttranslational modifications by protein kinases and possible by the redox-based S-nitrosylation, provide strong support for a dynamic role of cPLA(2) in serving multiple functions to neurons and glial cells under abnormal physiological and pathological conditions. Therefore, understanding mechanisms for cPLA(2) in the oxidative and nitrosative pathways in neurons will allow the development of novel therapeutic targets to mitigate the detrimental effects of AD.

A multiwavelength erbium-doped fiber (EDF) laser based on a nonlinear amplifying loop mirror (NALM) is proposed and experimentally demonstrated. The NALM provides intensity-dependent transmissivity to equalize different-wavelength powers and the transmission can be uniquely optimized by controlling the cavity loss associated with a section of un-pumped EDF, which also enhances the output signal-to-noise ratio (SNR). Through adjusting the polarization controllers (PCs), under only 70mW pump power, up to 62-wavelength output with channel spacing of 0.45 nm has been achieved. Also, the lasing tunability and stability are verified.

Two identical long-period fiber gratings (LPFGs) are difficult to produce in practice, notably for CO₂-laser or arc-discharge induced LPFGs. So it is meaningful to study the spectrum evolution of cascaded LPFGs with some deviation, named "mismatching" LPFGs. Theory and experiment demonstrate that the upper envelope of the fringe pattern is intrinsically curved but less dramatically than the lower envelope. Bending the grating pair to introduce proper cladding-mode loss can improve the contrast of the fringe pattern at a desired wavelength, which indicates that cascaded mismatching LPFGs can be used as high-quality comb filters or fiber sensors.

Accurate determination of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2) status was very important in selecting breast cancer treatment. Discordance of ER, PR, and HER2 status between core needle biopsy (CNB) and open excision biopsy (OEB) varied among reported studies. We performed a meta-analysis to compare the accuracy of CNB with that of OEB for ER, PgR, and HER2 status detection in breast cancer. Medical subject heading (MeSH) terms (Breast Neoplasm) and key words (biopsy OR mammotome) AND (incision OR excision OR surgery) AND (estrogen OR progesterone OR HER2 OR hormone). Patients with HER2 immunohistochemical 3+ or fluorescence in situ hybridization positive were classified into HER2[b] group. A total of 27 studies were eligible in this study. Aggregate positive ER and PgR rate was 80.0 and 69.5% for CNB; and 77.7 and 66.2% for OEB, respectively. The HER2 positive rate difference between CNB and OEB was only 0.2%. The pooled sensitivity of evaluating ER, PgR, and HER2 status in CNB compared with OEB was 0.970, 0.911, and 0.799 (0.813 for HER2[b]), respectively. All of AUC values for these status determination were larger than 0.9. Heterogeneity between studies was introduced by various factors in PgR and HER2[b] analysis. Subgroup analysis showed that the specificity and OR of CNB in studies with ER positive rate >78% was lower than studies with ER positive rate ≤78%(P < 0.05). This meta-analysis indicated that CNB had high diagnostic accuracy in evaluating ER, PgR, and HER2 status compared with OBE in breast cancer patients. In terms of 2-3% positive rate difference, ER and PgR status should be detected both on CNB and OEB samples, especially to retest their expression on CNB in patients with hormonal receptor negative tumors in OEB.

Pure dark red emission (650-670 nm) of NaYF(4):Yb/Er upconversion nanoparticles (UCNPs) is achieved by manganese ions (Mn(2+)) doping. In addition, the Mn(2+)-doping can also control the crystalline phase and size of the resulting UCNPs simultaneously. Drug delivery studies suggest the promise of these UCNPs as drug carriers for intracellular drug delivery and eventually as a multifunctional nanoplatform for simultaneous diagnosis and therapy.

The recognition of health benefits of phytomedicines and herbal supplements lead to an increased interest to understand the cellular and molecular basis of their biological activities. Apocynin (4-hydroxy-3-methoxy-acetophenone) is a constituent of the Himalayan medicinal herb Picrorhiza kurroa which is regarded as an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, a superoxide-producing enzyme. NADPH oxidase appears to be especially important in the modulation of redox-sensitive signaling pathways and also has been implicated in neuronal dysfunction and degeneration, and neuroinflammmation in diseases ranging from stroke, Alzheimer's and Parkinson's diseases to psychiatric disorders. In this review, we aim to give an overview of current literature on the neuroprotective effects of apocynin in the prevention and treatment of neurodegenerative disorders. Particular attention is given to in vivo studies.