Ventral subiculum promotes wakefulness through several pathways in male mice.

The ventral subiculum (vSUB), the major output structure of the hippocampal formation, regulates motivation, stress integration, and anxiety-like behaviors that rely on heightened arousal. However, the roles and underlying neural circuits of the vSUB in wakefulness are poorly known. Using in vivo fiber photometry and multichannel electrophysiological recordings in mice, we found that the vSUB glutamatergic neurons exhibited high activities during wakefulness. Moreover, activation of vSUB glutamatergic neurons caused an increase in wakefulness and anxiety-like behaviors and induced a rapid transition from sleep to wakefulness. In addition, optogenetic stimulation of vSUB glutamatergic terminals and retrograde-targeted chemogenetic activation of vSUB glutamatergic neurons revealed that vSUB promoted arousal by innervating the lateral hypothalamus (LH), nucleus accumbens (NAc) shell, and prefrontal cortex (PFC). Nevertheless, local microinjection of dopamine D1 or D2/D3 receptor antagonist blocked the wake-promoting effect induced by chemogenetic activation of vSUB pathways. Finally, chemogenetic inhibition of vSUB glutamatergic neurons decreased arousal. Altogether, our findings reveal a prominent contribution of vSUB glutamatergic neurons to the control of wakefulness through several pathways.

Two previously undescribed cholestanol saponins from the rhizomes of Paris fargesii var. petiolata.

Two previously undescribed cholestanol saponins, parpetiosides F - G (1-2), and six known analogs (3-8) were isolated from the rhizomes of Paris fargesii var. petiolata. Their structures were elucidated by extensive spectroscopic data analysis and chemical methods. Compound 1 was a rare 6/6/6/5/5 fused-rings cholestanol saponin with disaccharide moiety linked at C-26 of aglycone which was hardly seen in genus Paris. All of these compounds were discovered in this plant for the first time. In addition, the cytotoxicities of saponins (1-8) against three human cancer cell lines (U87, HepG2 and SGC-7901) were evaluated by CCK-8 method, and saponins 5-8 displayed certain cytotoxicities. The strong interactions between saponins 5-8 and SCUBE3, an oncogene for glioma cells, were displayed by molecular docking.

Activin receptor-like kinase 1 and its roles in angiogenesis / 中国病理生理杂志

Activin receptor-like kinase (ALK) 1 is a transforming growth factor-β/bone morphogenetic pro-teins superfamily type Ⅰ receptor, predominantly expressed in active endothelial cells. ALK1 has been shown to play a piv-otal role in regulating angiogenesis, which is involved in vascular formation during embryonic and early postnatal develop-ment and angiogenesis-related diseases, such as cardiovascular disorders and tumor. Understanding the exact function of ALK1 in angiogenesis will provide theoretical basis for anti-angiogenic strategy of ALK1 inhibition. In the present study, we briefly recapitulate ALK1 signaling pathway and its role in blood vessel formation and pathological neovascularization.

Improved anti-tumor efficacy and pharmacokinetics of bufalin via PEGylated liposomes / 中国药理学与毒理学杂志

OBJECTIVE To determine the characterization, anti-tumor efficacy and pharmacokinetics of bufalin- loaded PEGylated liposomes compared with bufalin entity. METHODS Bufalin- loaded PEGylated liposomes and bufalin- loaded liposomes were prepared reproducibly with homogeneous particle size by the combination of thin film evaporation method and high pressure homogenization method. The particle size and zeta potential of the liposomes were determined by dynamic light scattering technique. The direct imaging of morphology of liposomes was charactered by transmission electron microscope. The content of bufalin in liposomes was analysed by HPLC method. The entrapment efficiency and the particle size was applied to assess the stability profile, after storage at 4℃ on day 0, 7, 15, 30 and 90. The in-vitro release behaviours of bufalin from liposomes were conducted using dialysis bag technique at 37℃. In-vitro cytotoxicity studies were carried out using MTT〔3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide〕assay on several kinds of tumor cell lines including SW620, PC-3, MDA-MB-231, A549, U251, U87 and HepG2. In-vivo pharmacokinetic study of bufalin liposomes was evaluated by HPLC method. RESULTS Their mean particle sizes were 127.6 nm and 155.0 nm, mean zeta potentials were 2.24 mV and - 18.5 mV, entrapment efficiencies were 76.31% and 78.40% , respectively. In- vitro release profile revealed that the release of bufalin in bufalin- loaded PEGylated liposomes was slower than that of bufalin-loaded liposomes. The cytotoxicity of blank liposomes has been found within acceptable range, whereas bufalin-loaded PEGylated liposomes showed enhanced cytotoxicity to U251 cells compared with bufalin entity. In-vivo pharmacokinetics indicated that bufalin-loaded PEGylated liposomes could extend eliminate half-life time of bufalin in plasma in rats. CONCLUSION The results suggested that bufalin-loaded PEGylated liposomes improved the solubility and increased the drug concentration in plasma.