Activin A maintains cerebral cortex neuronal survival and increases voltage-gated Na^+ neuronal current

Activin A, which was first described in 1986, has been shown to maintain hippocampal neuronal survival. Activin A increases intracellular free Ca2＋ via L-type Ca2＋ channels. Our previous study showed that activin A promotes neurite growth of dorsal root ganglia in embryonic chickens and inhibits nitric oxide secretion. The present study demonstrated for the first time that activin A could maintain cerebral cortex neuronal survival in vitro for a long period, and that activin A was shown to increase voltage-gated Na＋ current （/Na） in Neuro-2a cells, which was recorded by patch clamp technique. The present study revealed a novel mechanism for activin A, as well as the influence of activin A on neurons by regulating expressions of vasoactive intestine peptide and inducible nitric oxide synthase.

Recent advances in construction of small molecule-based fluorophoredrug conjugates

As a powerful tool to advance drug discovery,molecular imaging may provide new insights into the process of drug effect and therapy at cellular and molecular levels.When compared with other detection methods,fluorescence-based strategies are highly attractive and can be used to illuminate pathways of drugs’transport,with multi-color capacity,high specificity and good sensitivity.The conjugates of fluorescent molecules and therapeutic agents create exciting avenues for real-time monitoring of drug delivery and distribution,both in vitro and in vivo.In this short review,we discuss recent developments of small molecule-based fluorophore-drug conjugates,including non-cleavable and cleavable ones,that are capable of visualizing drug delivery.

Direct Effects of Activin A on the Activation of Mouse Macrophage RAW264.7 Cells

Macrophages play critical roles in innate immune and acquired immune v/a secreting pro-inflammatory mediators, phagocytosing microorganisms and presenting antigens. Activin A, a member of transforming growth factor （TGF-β） superfamily, is produced by macrophages and microglia cells. In this study, we reported a direct effect of activin A as a pro-inflammatory factor on mouse macrophage cell line RAW264.7 cells. Our data revealed that activin A could not only increase IL-1β and IL-6 production from RAW264.7 cells, but also promote pinocytic and phagocytic activities of RAW264.7 cells. In addition, activin A obviously up-regulated MHC Ⅱ expression on the surface of RAW264.7 cells, whereas did not influence MHC I expression. Activin A also enhanced CD80 expression, which is a marker of activated macrophages, but did not influence RAW264.7 cell proliferation. These data suggest that activin A may regulate primary macrophage-mediated innate and acquired immune response via promoting the activation of rest macrophages.

A Critical Role of Activin A in Maturation of Mouse Peritoneal Macrophages in vitro and in vivo

Activin A, a multifunctional factor of the transforming growth factor-beta （TGF-β） superfamily, is mainly produced by microglia and macrophages, and its anti-inflammatory and pro-inflammatory activities are both related to macrophage functions. However the direct effect of activin A on the rest macrophages in vivo remains unclear. In the present study, the results showed that activin A not only increased NO and IL-1β release, but also promoted phagocytic abilities of mouse peritoneal macrophages in vitro and in vivo, whereas it did not influence MHC Ⅰ and MHC Ⅱ expression. Moreover, we found that activin A significantly upregulated the expressions of CD14 and CD68, markers of mature macrophages, on the surface of macrophages in vitro and in vivo. These data suggest that activin A can induce primary macrophage maturation in vitro and in vivo, but may not trigger the acquired immune response via regulating expression of MHC molecules involved in presentation of antigen.

Intracellular effects of prodrug-like wortmannin probes

Wortmannin, a known inhibitor of phosphoinositide 3-kinases(PI3 Ks), their low selectivity and high toxicity is still problematic and less is known about their effects on PI3 Ks in cellular systems. Hence, we have synthesized a series of multifunctional wortmannin probes with the ability to self-activate, by installing a clickable handle at C11 site, and secondary amine and cancer-targeting moiety at C20 site respectively. MTT assay first confirmed that self-activating probes have better inhibition potency and biotin enhanced their cancer cell uptake. Further experiments showed most of probes can target PI3 K/Akt/mTOR pathway with prolonged turn-over time. Protein profiling and pull-down results were observed that the derivatives not only labelled four PI3 Ks with selectivity, but also engaged in covalent interactions with numerous cellular proteins which could be the major reason of their high toxicity.