Synergistic effects of Rapamycin and Fluorouracil to treat a gastric tumor in a PTEN conditional deletion mouse model.

The tumor suppressor gene phosphatase and tensin homolog (PTEN) in PI3K/Akt/mTOR pathway is essential in inhibiting tumor growth and metastasis. However, whether the mutation of PTEN gene could induce tumorigenesis and impact the treatment of gastric cancer is still unclear. The purpose of the study was to investigate the combined treatment of gastric tumorigenesis using Rapamycin and Fluorouracil (5-Fu) through interfering with the Akt/mTOR pathway in a mouse model with PTEN conditional deletion.

A highly-sensitive "turn on" probe based on coumarin β-diketone for hydrazine detection in PBS and living cells.

Herein, a new "turn on" fluorescent probe C-1 is developed to specifically detect hydrazine using coumarin nucleus as the fluorophore and β-diketone as the recognition group. The probe shows high selectivity towards hydrazine over other common ions and amine-containing species, as well as good water solubility and quantitative detectability of hydrazine in concentration range of 1-200 μM. The detection limit is as low as 1.

Atorvastatin induces mitochondrial dysfunction and cell apoptosis in HepG2 cells via inhibition of the Nrf2 pathway.

Atorvastatin (ATO) is a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor widely used to treat hypercholesterolemia. However, clinical application is limited by potential hepatotoxicity. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a master regulator of cellular antioxidants, and oxidative stress is implicated in statin-induced liver injury.

PM obtained from urban areas in Beijing induces apoptosis by activating nuclear factor-kappa B.

Background: Particulate matter (PM), which has adverse effects on citizen health, is a major air pollutant in Beijing city. PM is an indicator of PM in urban areas and can cause serious damage to human health. Many epidemiological studies have shown that nuclear factor-kappa B (NF-κB) is involved in PM-induced cell injury, but the exact mechanisms are not well understood.

Complexation of triptycene-derived macrotricyclic polyether with paraquat derivatives, diquat, and a 2,7-diazapyrenium salt: guest-induced conformational changes of the host.

Complexation between a triptycene-derived macrotricyclic polyether containing two dibenzo-[30]-crown-10 cavities and different functionalized paraquat derivatives, diquat, and a 2,7-diazapyrenium salt in both solution and solid state was investigated in detail. It was found that depending on the guests with different terminal functional groups and structures, the macrotricyclic polyether could form 1:1 or 1:2 complexes with the guests in different complexation modes in solution and also in the solid state. Especially, the conformation of the macrotricyclic polyether was efficiently adjusted by the encapsulated guests, which was to some extent similar to substrate-induced fit of enzymes.

Synthesis of triptycene-derived macrotricyclic host containing two dibenzo-[18]-crown-6 moieties and its complexation with paraquat derivatives: Li(+)-ion-controlled binding and release of the guests in the complexes.

A new triptycene-derived macrotricyclic host containing two dibenzo-[18]-crown-6 moieties was synthesized and shown to form 1:1 complexes with paraquat derivatives in solution, in which the guests all thread the central cavity of the host. However, it was interestingly found that, depending on the paraquat derivatives with different functional groups, the host can form stable 1:1 or 1:2 complexes in different complexation modes in the solid state, which is significantly different from those of the macrotricyclic host containing two dibenzo-[24]-crown-8 moieties. The formation of the complexes was also proved by the ESI MS and electrochemical experiments.

Formation of 1:2 host-guest complexes based on triptycene-derived macrotricycle and paraquat derivatives: anion-π interactions between PF6(-) and bipyridinium rings in the solid state.

A triptycene-derived macrotricyclic host containing two dibenzo-[30]-crown-10 moieties forms stable 1:2 host-guest complexes with paraquat derivatives in both solution and the solid state, in which anion-π interactions between PF(6)(-) and the bipyridinium rings play an important role. Moreover, it was found that binding and release of the guest molecules in the complexes could be easily controlled by the addition and removal of potassium ions.

[Mechanism of estrogen-mediated neuroprotection: regulation of mitochondrial function].

Numerous studies show the neuroprotective effects of estrogen, but the underlying mechanism still remains unclear. Recent studies indicate that mitochondria are critically involved in estrogen-mediated neuroprotection. Mitochondria are the main sources of cellular energy and reactive oxygen species (ROS), they play an important role in signaling transduction and cellular life-death decisions.

Complexation between pentiptycene derived bis(crown ether)s and CBPQT4+ salt: ion-controlled switchable processes and changeable role of the CBPQT4+ in host-guest systems.

The pentiptycene derived bis(crown ether)s with two 24-crown-8 moieties in the cis position could include the CBPQT(4+) ring inside their cavities to form 1:1 complexes, and the naphthalene groups connected in the crown ether moieties showed less effective complexation ability toward the CBPQT(4+) ring than the host containing two terminal benzene rings. This result was probably due to the stereohindrance effect of the naphthalene groups, and it was obviously different from that of the pentiptycene derived mono(crown ether)s. For the pentiptycene derived bis(crown ether) with two 24-crown-8 moieties in the trans position, it formed a 1:2 stable complex with the CBPQT(4+) salt in solution and in the solid state, in which the pentiptycene moiety played an important role in stabilizing the complex.

Self-assembled interwoven cages from triptycene-derived bis-macrotricyclic polyether and multiple branched paraquat-derived subunits.

On the basis of formation of a 1:2 complex between the triptycene-derived bis-macrotricyclic polyether and the paraquat derivative, two novel well-defined interwoven supramolecular cages were constructed by the [3 + 2] and [4 + 2] self-assembly of the polyether and trifurcated and cross paraquat-derived subunits under millimolar concentrations, respectively.

A new [3]rotaxane molecular machine based on a dibenzylammonium ion and a triazolium station.

A novel two-station [3]rotaxane molecular machine based on triptycene-derived macrotricyclic host was conveniently synthesized by the click reaction and methylation of the subsequent 1,2,3-tiazole group. The shuttle process of the [3]rotaxane molecular machine can be reversibly achieved by acid-base control.

A bifunctionalized [3]rotaxane and its incorporation into a mechanically interlocked polymer.

A novel bifunctionalized [3]rotaxane based on a triptycene-derived macrotricyclic host was conveniently synthesized. On the basis of the [3]rotaxane, a linear main-chain poly[3]rotaxane was further obtained by the highly efficient Huisgen 1,3-dipolar cycloaddition.

The antidepressant effects of curcumin in the forced swimming test involve 5-HT1 and 5-HT2 receptors.

Curcuma longa is a main constituent of many traditional Chinese medicines, such as Xiaoyao-san, used to manage mental disorders effectively. Curcumin is a major active component of C. longa and its antidepressant-like effect has been previously demonstrated in the forced swimming test.

[Impacts of modern biology on drug discovery].

Drug discovery has been improved greatly by series of new ideas and new technologies as well as new approaches emerging in the postgenomic era. On the one hand, the theoretics of drug discovery become more comprehensive and more profound as the development of numerous new disciplines such as genomics, proteomics, transcriptomics, metabonomics, bioinformatics and system biology; on the other hand, the pathways for new drug discovery are broadened by the continuous improvement of technological platforms including computer-aided drug design, high throughput screening, high content screening, biochip, transgenic and RNAi technology. Based on the recent advances on the modern biology, in this article, we specially reviewed the impacts of modern biology on the process of drug discovery.

Metallothionein protects against doxorubicin-induced cardiomyopathy through inhibition of superoxide generation and related nitrosative impairment.

Metallothionein (MT) has been shown to be an effective protector against DOX-induced cardiomyopathy, however the involved precise mechanisms are still unknown. The present study was undertaken to clarify whether the inhibition of superoxide generation and related nitrosative damage were involved in the metallothionein attenuation of DOX-induced cardiac injury. MT-I/II null (MT-/-) mice and corresponding wild-type mice (MT+/+) were pretreated with either saline or zinc (300 micromol/kg, s.