ABSTRACT
Neuropathic pain (NP) has become a serious global health issue and a huge clinical challenge without available effective treatment. P2 receptors family is involved in pain transmission and represents a promising target for pharmacological intervention. Traditional Chinese medicine (TCM) contains multiple components which are effective in targeting different pathological mechanisms involved in NP. Different from traditional analgesics, which target a single pathway, TCMs take the advantage of multiple components and multiple targets, and can significantly improve the efficacy of treatment and contribute to the prediction of the risks of NP. Compounds of TCM acting at nucleotide P2 receptors in neurons and glial cells could be considered as a potential research direction for moderating neuropathic pain. This review summarized the recently published data and highlighted several TCMs that relieved NP by acting at P2 receptors.
ABSTRACT
It is well established that different sites within a protein evolve at different rates according to their role within the protein; identification of these correlated mutations can aid in tasks such as ab initio protein structure,structure function analysis or sequence alignment.Mutual Information is a standard measure for coevolution between two sites but its application is limited by signal to noise ratio.In this work we report a preliminary study to investigate whether larger sequence sets could circumvent this problem by calculating mutual information arrays for two sets of drug naive sequences from the HIV gp120 protein for the B and C subtypes.Our results suggest that while the larger sequences sets can improve the signal to noise ratio,the gain is offset by the high mutation rate of the HIV virus which makes it more difficult to achieve consistent alignments.Nevertheless,we were able to predict a number of coevolving sites that were supported by previous experimental studies as well as a region close to the C terminal of the protein that was highly variable in the C subtype but highly conserved in the B subtype.
ABSTRACT
To investigate the neurotoxic effect of human immunodeficiency virus (HIV) gp120 on cultured dorsal root ganglion (DRG)neurons in vitro, dissociated and organotypic mouse embryo's DRG cell culture models were established. Both dissociated and organotypic DRG cultures were treated with HIV gp120 in different concentration (250 pmol/L and 1 nmol/L, respectively, 2 times/7 days). For dissociated DRG cultural cells, microtubule-associated protein 2 (MAP2) immunofluorescent labeling was processed for observing the changes of neuronal cell body and neurites. The change of the ultrastructure in the organotypic cultured DRG was observed by electron microscopy.The difference of the number and length of neurites between the control group and HIV gp120 treated groups were significant (P＜0.001),whereas there was no significant difference in the diameter of neurons between them (P＞0.05). The ultrastructural changes included the decrease or loss of cristae in mitochondria and accumulation of many high densed particles between the microtubules and the neurofilaments by using both the concentrations of HIV gp120 treatment. The present results indicate that HIV gp120 had a directly neurotoxic effect on the cultured DRG neurons, especially more sensitive to mitochondria.