Dalian Medical University

About: Dalian Medical University is a education organization based out in Dalian, China. It is known for research contribution in the topics: Cancer & Apoptosis. The organization has 15623 authors who have published 9993 publications receiving 164145 citations.

Micelles of d-α-Tocopheryl Polyethylene Glycol 2000 Succinate (TPGS 2K) for Doxorubicin Delivery with Reversal of Multidrug Resistance.

Abstract: The purpose of this study is to investigate the ability of doxorubicin (DOX)-loaded d-α-tocopheryl polyethylene glycol 2000 succinate (TPGS 2K) micelles to overcome MDR in breast cancer treatment. The DOX-loaded TPGS 2K micelles exhibited an average size of around 23 nm, a near neutral zeta potential of around 4 mv and high encapsulation efficiency (85.22 ± 1.89%). The TPGS 2K conjugate did not have significant influences on the reduction of mitochondrial membrane potential (MMP) and the depletion of intracellular ATP level of MCF-7/ADR cells but had an evident effect on the inhibition of Verapamil-induced P-gp ATPase activity. In vitro cell culture experiments demonstrated the DOX-loaded TPGS 2K micelles, resulting in higher cellular uptake and more significant cytotoxicity effect against MCF-7/MDR cells than the free DOX solution. Additionally, the in vivo imaging study revealed DiR-loaded TPGS 2K micelles distributed selectively in MCF-7/ADR tumor-bearing nude mice and had a sufficient residence time. ...

Facilitation of TRPV4 by TRPV1 is required for itch transmission in some sensory neuron populations

Abstract: The transient receptor potential channels (TRPs) respond to chemical irritants and temperature. TRPV1 responds to the itch-inducing endogenous signal histamine, and TRPA1 responds to the itch-inducing chemical chloroquine. We showed that, in sensory neurons, TRPV4 is important for both chloroquine- and histamine-induced itch and that TRPV1 has a role in chloroquine-induced itch. Chloroquine-induced scratching was reduced in mice in which TRPV1 was knocked down or pharmacologically inhibited. Both TRPV4 and TRPV1 were present in some sensory neurons. Pharmacological blockade of either TRPV4 or TRPV1 significantly attenuated the Ca(2+) response of sensory neurons exposed to histamine or chloroquine. Knockout of Trpv1 impaired Ca(2+) responses and reduced scratching behavior evoked by a TRPV4 agonist, whereas knockout of Trpv4 did not alter TRPV1-mediated capsaicin responses. Electrophysiological analysis of human embryonic kidney (HEK) 293 cells coexpressing TRPV4 and TRPV1 revealed that the presence of both channels enhanced the activation kinetics of TRPV4 but not of TRPV1. Biochemical and biophysical studies suggested a close proximity between TRPV4 and TRPV1 in dorsal root ganglion neurons and in cultured cells. Thus, our studies identified TRPV4 as a channel that contributes to both histamine- and chloroquine-induced itch and indicated that the function of TRPV4 in itch signaling involves TRPV1-mediated facilitation. TRP facilitation through the formation of heteromeric complexes could be a prevalent mechanism by which the vast array of somatosensory information is encoded in sensory neurons.

Microglial priming in Alzheimer's disease.

Abstract: Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease of central nervous system (CNS). Nowadays, increasing evidence suggests that immune system plays a significant role in the mechanisms of AD's onset and progression. Microglia, the main participator in the immune system of CNS, is always regarded as a protector of our brain in a healthy state and also has a beneficial role in maintaining the homeostasis of CNS microenvironment. However, chronic and sustained stimulation can push microglia into the state termed priming. Primed microglia can induce the production of amyloid β (Aβ), tau pathology, neuroinflammation and reduce the release of neurotrophic factors, resulting in loss of normal neurons in quantity and function that has immense relationship with AD. The therapeutic strategies mainly aimed at modulating the microenvironment and microglial activity in CNS to delay progression and alleviate pathogenesis of AD. Overall, in this review, we highlight the mechanism of microglial priming, and discuss the profound relationship between microglial priming and AD. Besides, we also pay attention to the therapeutic strategies targeting at microglial priming.