A Systematic, Integrated Study on the Neuroprotective Effects of Hydroxysafflor Yellow A Revealed by<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mrow><mml:mtext>H</mml:mtext></mml:mrow><mml:mrow><mml:mtext>1</mml:mtext></mml:mrow></mml:mrow></mml:math>NMR-Based Metabonomics and the NF-<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mrow><mml:mi mathvariant="bold">κ</mml:mi></mml:mrow></mml:math>B Pathway

Hydroxysafflor yellow A (HSYA) is the main active component of the Chinese herbCarthamus tinctoriusL.. Purified HSYA is used as a neuroprotective agent to prevent cerebral ischemia. Injectable safflor yellow (50 mg, containing 35 mg HSYA) is widely used to treat patients with ischemic cardiocerebrovascular disease. However, it is unknown how HSYA exerts a protective effect on cerebral ischemia at the molecular level. A systematical integrated study, including histopathological examination, neurological evaluation, blood-brain barrier (BBB), metabonomics, and the nuclear factor-κB (NF-κB) pathway, was applied to elucidate the pathophysiological mechanisms of HSYA neuroprotection at the molecular level. HSYA could travel across the BBB, significantly reducing the infarct volume and improving the neurological functions of rats with ischemia. Treatment with HSYA could lead to relative corrections of the impaired metabolic pathways through energy metabolism disruption, excitatory amino acid toxicity, oxidative stress, and membrane disruption revealed by1H NMR-based metabonomics. Meanwhile, HSYA treatment inhibits the NF-κB pathway via suppressing proinflammatory cytokine expression and p65 translocation and binding activity while upregulating an anti-inflammatory cytokine.</jats:p

TNFAIP1 contributes to the neurotoxicity induced by Aβ25–35 in Neuro2a cells

Background: Amyloid-beta (Aβ) accumulation is a hallmark of Alzheimer’s disease (AD) that can lead to neuronal dysfunction and apoptosis. Tumor necrosis factor, alpha-induced protein 1 (TNFAIP1) is an apoptotic protein that was robustly induced in the transgenic C. elegans AD brains. However, the roles of TNFAIP1 in AD have not been investigated. Results: We found TNFAIP1 protein and mRNA levels were dramatically elevated in primary mouse cortical neurons and Neuro2a (N2a) cells exposed to Aβ25–35. Knockdown and overexpression of TNFAIP1 significantly attenuated and exacerbated Aβ25–35-induced neurotoxicity in N2a cells, respectively. Further studies showed that TNFAIP1 knockdown significantly blocked Aβ25–35-induced cleaved caspase 3, whereas TNFAIP1 overexpression enhanced Aβ25–35-induced cleaved caspase 3, suggesting that TNFAIP1 plays an important role in Aβ25–35-induced neuronal apoptosis. Moreover, we observed that TNFAIP1 was capable of inhibiting the levels of phosphorylated Akt and CREB, and also anti-apoptotic protein Bcl-2. TNFAIP1 overexpression enhanced the inhibitory effect of Aβ25–35 on the levels of p-CREB and Bcl-2, while TNFAIP1 knockdown reversed Aβ25–35-induced attenuation in the levels of p-CREB and Bcl-2. Conclusion: These results suggested that TNFAIP1 contributes to Aβ25–35-induced neurotoxicity by attenuating Akt/CREB signaling pathway, and Bcl-2 expression

Synthesis, Biological Evaluation and Mechanism Studies of Deoxytylophorinine and Its Derivatives as Potential Anticancer Agents

Previous studies indicated that (+)-13a-(S)-Deoxytylophorinine (1) showed profound anti-cancer activities both in vitro and in vivo and could penetrate the blood brain barrier to distribute well in brain tissues. CNS toxicity, one of the main factors to hinder the development of phenanthroindolizidines, was not obviously found in 1. Based on its fascinating activities, thirty-four derivatives were designed, synthesized; their cytotoxic activities in vitro were tested to discover more excellent anticancer agents. Considering the distinctive mechanism of 1 and interesting SAR of deoxytylophorinine and its derivatives, the specific impacts of these compounds on cellular progress as cell signaling transduction pathways and cell cycle were proceeded with seven representative compounds. 1 as well as three most potent compounds, 9, 32, 33, and three less active compounds, 12, 16, 35, were selected to proform this study to have a relatively deep view of cancer cell growth-inhibitory characteristics. It was found that the expressions of phospho-Akt, Akt, phospho-ERK, and ERK in A549 cells were greater down-regulated by the potent compounds than by the less active compounds in the Western blot analysis. To the best of our knowledge, this is the first report describing phenanthroindolizidines alkaloids display influence on the crucial cell signaling proteins, ERK. Moreover, the expressions of cyclin A, cyclin D1 and CDK2 proteins depressed more dramatically when the cells were treated with 1, 9, 32, and 33. Then, these four excellent compounds were subjected to flow cytometric analysis, and an increase in S-phase was observed in A549 cells. Since the molecular level assay results of Western blot for phospho-Akt, Akt, phospho-ERK, ERK, and cyclins were relevant to the potency of compounds in cellular level, we speculated that this series of compounds exhibit anticancer activities through blocking PI3K and MAPK signaling transduction pathways and interfering with the cell cycle progression

Assessment of ¹H NMR Spectroscopy for Specific Metabolite Fingerprinting of <i>Angelica sinensis</i>

The 1H NMR fingerprints of fractionated non-polar extracts (CSPD A) from the roots of Angelica sinensis of six different specimens were assigned by comparison with the 1H NMR spectra of the isolated pure compounds. The 1H NMR fingerprints showed exclusively characteristic resonance signals of the major constituents of the plant. The 1H NMR fingerprint established for an authentic sample of A. sinensis can be used for authenticating A. sinensis species. </jats:p

A facile route to dual-crosslinking polymeric hydrogels with enhanced mechanical property

Abstract Polymeric hydrogels with excellent biocompatibility, high hydrophilicity, and water-holding capacity have attracted considerable concerns in widely fields. However, most hydrogels exhibit poor mechanical property, which largely limited their applications. Herein, a novel dual-crosslinking polymeric hydrogel crosslinked by covalent bonds and metal coordination interactions between Fe3+ and –COO- was fabricated through accessible method. The metal coordination interactions within the hydrogel were established through dipping in the FeCl3 solution to reinforce the backbones of the hydrogel. The obtained polymeric hydrogel exhibits enhanced tensile strength (∼4.92 MPa), stiffness (∼6.168 MPa), and toughness (∼2.835 MJ m−3).</jats:p

Field-Control Performance of Direct Current Memory Flux Orthogonal Magnetizing Controllable Reactor

Aiming at the condition that the exciting power is bigger when the orthogonal magnetizing controllable reactor adjusts the flux in wide range and there is coupling between the alternate current(AC) magnetic circuit and the direct current (DC) circuit. This paper proposed a kind of orthogonal magnetizing controllable reactor based on DC memory flux. The aluminum nickel cobalt alloy (AlNiCo) magnet with low coercive force and high residual flux density was used so that the DC flux could be online tuned without additional copper loss. This paper designed the new type of orthogonality magnetic structure without coupling between the AC-DC circuit and magnetic circuit. The simulated analysis result shows that this electric reactor realizes the unidirectional control from the DC magnetic circuit to AC magnetic circuit, which makes the inductor of electric reactor controllable more easily. Keywords: DC memory flux; orthogonal magnetizing controllable reactor; AlNiCo;</jats:p