O,O′-Diethyl {(Z)-[(2-chloro­phen­yl)(cyano)methyl­ene]amino­oxy}thio­phospho­nate

The title mol­ecule, C12H14ClN2O3PS, has a cis configuration with respect to the C=N bond. Inter­molecular C—H⋯O inter­actions inter­connect the mol­ecules into chains along the c axis. The chains are further connected into a two-dimensional network parallel to the bc plane by weak π–π inter­actions between adjacent aromatic rings (centroid–centroid distance = 3.772Å)

mGluR5 antagonism inhibits cocaine reinforcement and relapse by elevation of extracellular glutamate in the nucleus accumbens via a CB1 receptor mechanism.

Metabotropic glutamate receptor 5 (mGluR5) antagonism inhibits cocaine self-administration and reinstatement of drug-seeking behavior. However, the cellular and molecular mechanisms underlying this action are poorly understood. Here we report a presynaptic glutamate/cannabinoid mechanism that may underlie this action. Systemic or intra-nucleus accumbens (NAc) administration of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) dose-dependently reduced cocaine (and sucrose) self-administration and cocaine-induced reinstatement of drug-seeking behavior. The reduction in cocaine-taking and cocaine-seeking was associated with a reduction in cocaine-enhanced extracellular glutamate, but not cocaine-enhanced extracellular dopamine (DA) in the NAc. MPEP alone, when administered systemically or locally into the NAc, elevated extracellular glutamate, but not DA. Similarly, the cannabinoid CB1 receptor antagonist, rimonabant, elevated NAc glutamate, not DA. mGluR5s were found mainly in striatal medium-spiny neurons, not in astrocytes, and MPEP-enhanced extracellular glutamate was blocked by a NAc CB1 receptor antagonist or N-type Ca++ channel blocker, suggesting that a retrograde endocannabinoid-signaling mechanism underlies MPEP-induced glutamate release. This interpretation was further supported by our findings that genetic deletion of CB1 receptors in CB1-knockout mice blocked both MPEP-enhanced extracellular glutamate and MPEP-induced reductions in cocaine self-administration. Together, these results indicate that the therapeutic anti-cocaine effects of mGluR5 antagonists are mediated by elevation of extracellular glutamate in the NAc via an endocannabinoid-CB1 receptor disinhibition mechanism

Heterodichogamy in Kingdonia (Circaeasteraceae, Ranunculales)

Background and Aims Preliminary field observations in 2001 and 2002 suggested that Kingdonia uniflora (Circaeasteraceae, Ranunculales) exhibits heterodichogamy, an unusual kind of reproductive heteromorphy, hitherto unreported in Ranunculales and known from only one other genus in basal eudicots. Methods During several subsequent years flowers were observed in the field. Flowers were fixed in FAA and studied with microtome sections series and with the scanning electron microscope. Key Results The flowers proved to be heterodichogamous, with protandrous and protogynous morphs, which have a 1 : 1 ratio. Both morphs equally set fruit. Each year a single flower is formed at the tip of a rhizome or more rarely two flowers. The flowers are already open when they appear at the soil surface, before they are receptive and before pollen is dispersed. In both floral morphs the styles elongate early and the stigmas are positioned above the anthers before anthesis begins. In protogynous flowers the stigmas become receptive in this position; later the styles become reflexed and then the anthers dehisce. In contrast, in protandrous flowers the stamen filaments elongate during early anthesis such that the dehiscing anthers come to lie above the (still unreceptive) stigmas; after dehiscence of all anthers in a flower the styles begin to elongate and become receptive. Conclusions This is the first record of heterodichogamy in a representative of Ranunculales, in an herbaceous eudicot, and in a plant with uniflorous ramets. The occurrence of heterodichogamy in Kingdonia in which clonal reproduction appears to be dominant might be an adaptation to avoid mating between the ramets from a common mother individual (genet

Essential oils for the treatment of demodex

The Demodex infestation is widely spread among older people. The conventional treatment of demodex involves chemicals and antibiotics. However, these treatments have a number of side effects, such as environmental risks, acaricide resistance, toxicity to humans and animals. Benefit from abundant sources of plants and plant extractions have been a new choice for treating demodex infections. This review summarizes the anti-demodex and side effects of certain botanical essential oils. The high efficacy and low side effects of essential oils, such as TTO and its active ingredient terpinen-4-oil, camphor oil, sage oil, peppermint oil, neem oil, clove oil make them good candidates for the treatment of mites. Further studies on the biological mechanisms of the acaricide effects of these active essential oils and the structure-activity relations are necessary to clarify the functions of these drugs

Parthenolide induces proliferation inhibition and apoptosis of pancreatic cancer cells in vitro

<p>Abstract</p> <p>Background</p> <p>To explore the anti-tumor effects of parthenolide in human pancreatic cancer.</p> <p>Methods</p> <p>BxPC-3 cell, a human pancreatic cancer, was treated with parthenolide at different concentrations. The MTT assay was used to analyze cell viability. Flow cytometry and DNA fragmentation analysis were applied to evaluate apoptosis after parthenolide treatment. The wound closure and cell invasion assay were also employed in the study. Western blotting was used to demonstrate Bad, Bcl-2, Bax, caspase-9 and pro-caspase-3 expression.</p> <p>Results</p> <p>The MTT assay indicated that the pancreatic cancer growth could be dose-dependently inhibited by parthenoolide. This phenomenon was confirmed by flow cytometry and DNA fragmentation analysis. The wound closure assay and cell invasion assay showed that BxPC-3 cell was significantly suppressed by parthenolide at 7.5 μM and 15 μM. Western Blotting demonstrated the Bcl-2 and pro-caspase-3 were down-regulated while the Bax and caspase-9 were up-regulated. No alteration in Bad expression was found after treatment.</p> <p>Conclusions</p> <p>The parthenolide can inhibit the cell growth, migration, and induce the apoptosis in human pancreatic cancer. These findings may provide a novel approach for pancreatic cancer treatment.</p