Active components, derived from Kai-xin-san, a herbal formula, increase the expressions of neurotrophic factor NGF and BDNF on mouse astrocyte primary cultures via cAMP-dependent signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Kai-Xin-San (KXS), an ancient formula composed of Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma and Poria, was frequently applied for Alzheimer's disease and major depression disorders for thousands of years. However, its active components and molecular mechanism have not clearly been investigated. AIM OF THE STUDY: We aimed to reveal the active components of KXS on regulating neurotrophic factor NGF and BDNF expressions and its mechanisms on mouse astrocyte primary cultures. MATERIALS AND METHODS: Extracts of KXS had been prepared by water reflux and chemical standardization was carried out by HPLC-MS/MS. Various ethanol elution components were prepared by eluting ethanol on macro pore resin column and compound identification was carried out by high-resolution mass spectrometry. KXS extract, elution components and identified chemicals were applied on mouse astrocytes and expressions of NGF and BDNF and related metabolic enzymes were analyzed by qPCR and western blotting analysis. RESULTS: One compatible ratio of KXS named D-652 exerted the best effect on stimulation of NGF and BDNF expressions on mouse astrocytes. 70% ethanol elution fraction of D-652 exerted the highest increase tendency on expressions of NGF and BDNF by activating cAMP-dependent signaling pathway as well as stimulating enzymes accounting for neurotrophic factor synthesis. Combined with compound identification by high-resolution mass spectrometry, ginsenoside Rg1 and Rb1 might be the active compounds of this fraction on increasing NGF and BDNF expressions. CONCLUSIONS: The active compounds of KXS on increasing NGF and BDNF expressions might be the ginsenosides via activating cAMP-dependent signaling pathway as well as stimulating enzymes accounting for neurotrophic factor synthesis, which partly reveal the target of this formulae supported the clinically usage of this decoction.

Virtual screening and biophysical studies lead to HSP90 inhibitors.

Heat shock protein 90 (HSP90) is a molecular chaperone that plays important functional roles in cells. The chaperone activity of HSP90 is regulated by the hydrolysis of ATP at the protein's N-terminal domain. HSP90, in particular the N-terminal domain, is a current inhibition target for therapeutic treatments of cancers. This paper describes an application of virtual screening, thermal shift assaying and protein NMR spectroscopy leading to the discovery of HSP90 inhibitors that contain the resorcinol structure. The resorcinol scaffold can be found in a class of HSP90 inhibitors that are currently undergoing clinical trials. The proved success of the resorcinol moiety in HSP90 inhibitors validates this combined virtual screen and biophysical technique approach, which may be applied for future inhibitor discovery work for HSP90 as well as other targets.

[Preparation and in vitro evaluation of ampelopsin-loaded nanomicelles].

To improve the solubility and antitumor activity of ampelopsin, ampelopsin-loaded nanomicelles from the mixture of pluronic F127 and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS1000) were prepared by film-thin hydration method, in order to optimize the process conditions and physicochemical properties. The antitumor activities against MCF-7 cells between ampelopsin and nanomicelles were compared by MTT method, respectively. The results showed that the optimal nanomicelles were round with the nanometric size of (22.6±0.5) nm, encapsulation efficiency rate of (80.42±1.13)%, and drug-loading rate of (4.41±0.26)%. The solubility of ampelopsin in mixed nanomicelles significantly increased by 16 times. In different release media, the mixed nanomicelles could release more than 90% of drug in 8 h, and showed stronger cytotoxicity and inhibition against MCF-7 cells (P<0.01). The mixed nanomicelles can be used as new drug delivery system of ampelopsin.

Two adenovirus serotype 3 outbreaks associated with febrile respiratory disease and pharyngoconjunctival fever in children under 15 years of age in Hangzhou, China, during 2011.

Adenovirus serotype 3 and 7 outbreaks have occurred periodically in northern, eastern, and southern China since 1955, but there has been no report since the adenovirus serotype 7 outbreak first occurred in Hangzhou, China, in 1991. Here we explored the epidemiology and etiology of two adenovirus serotype 3 outbreaks in Hangzhou in 2011. One acute respiratory outbreak was found in Chun'an County, where a total of 371 cases were confirmed in 5 of 23 towns from 4 to 31 May 2011. The outbreak affected 18.57% (13/70) of schools and 14.49% (90/621) of classes. The incidence was 5.18% (371/7,163). The population was distributed among individuals ages 7 to 15 years. No parents or teachers were infected. Another pharyngoconjunctival fever outbreak was discovered in the Chenjinglun Swimming Center located in the Xihu District between 1 and 15 July 2011. A total of 134 cases were confirmed in 900 amateur swimmers, with an incidence of 14.89% (134/900). The ages ranged from 4 to 9 years. The two outbreaks had no severe complications or death. The viruses in 66.67% (10/15) of throat swabs from children with acute respiratory infections and 100% (10/10) of the swabs from children with pharyngoconjunctival fever were confirmed to be adenovirus serotype 3 with 100% homology by PCR. Of these samples, 60.0% (12/20) had a classical characteristic cytopathic effect, presented as grape-like clusters at 72 h after infection in HEp-2 cells. In conclusion, the acute respiratory infection and pharyngoconjunctival fever outbreak in Hangzhou were caused by the completely homologous type 3 adenovirus in subgenus B. Moreover, these outbreaks demonstrated rapid transmission rates, possibly due to close contact and droplet transmission.

All-trans retinoic acid stealth liposomes prevent the relapse of breast cancer arising from the cancer stem cells.

The relapse of cancer is mostly due to the proliferation of cancer stem cells which could not be eliminated by a standard chemotherapy. A new kind of all-trans retinoic acid stealth liposomes was developed for preventing the relapse of breast cancer and for treating the cancer in combination with a cytotoxic agent, vinorelbine stealth liposomes. In vitro studies were performed on the human breast cancer MCF-7 and MDA-MB-231 cells. In vivo evaluations were performed on the newly established relapse model with breast cancer stem cells. Results showed that the particle size of all-trans retinoic acid stealth liposomes was approximately 80nm, and the encapsulation efficiency was >90%. Breast cancer stem cells were identified with the CD44(+)/CD24(-) phenotype and characterized with properties: resistant to cytotoxic agent, stronger capability of proliferation, and stronger capability of differentiation. Inhibitory effect of all-trans retinoic acid stealth liposomes was more potent in cancer stem cells than in cancer cells. The mechanisms were defined to be two aspects: arresting breast cancer stem cells at the G(0)/G(1) phase in mitosis, and inducing the differentiation of breast cancer stem cells. The cancer relapse model was successfully established by xenografting breast cancer stem cells into NOD/SCID mice, and the formation and growth of the xenografted tumors were significantly inhibited by all-trans retinoic acid stealth liposomes. The combination therapy of all-trans retinoic acid stealth liposomes with vinorelbine stealth liposomes produced the strongest inhibitory effect to the relapse tumor model. It could be concluded that all-trans retinoic acid stealth liposomes could be used for preventing the relapse of breast cancer by differentiating cancer stem cells and arresting the cell-cycle, and for treating breast cancer as a co-therapy, thus providing a novel strategy for treating breast cancer and preventing relapse derived from breast cancer stem cells.