Noncoding RNAs, including long non‐coding RNAs (lncRNAs) and microRNAs, are involved in the development of neuropathic pain. Currently, we investigated that lncRNA X inactive–specific transcript (XIST) and toll‐like receptor 5 (TLR5) were greatly upregulated in chronic constriction injury rat models, whereas miR‐154‐5p (microRNA‐154‐5p) was significantly downregulated. Bioinformatics analysis was used to predict miR‐154‐5p as a target gene of XIST, and dual‐luciferase reporter tests proved the correlation between them. We observed that miR‐154‐5p was negatively modulated by XIST in vitro. XIST overexpression markedly induced neuropathic pain development in rats with chronic constriction injury, whereas the upregulation of miR‐154‐5p could reverse this phenomenon. Furthermore, TLR5 was demonstrated to be a target gene of miR‐154‐5p by using bioinformatics predictions. miR‐154‐5p negatively regulated TLR5 expression in vitro, and TLR5 was able to promote neuropathic pain development. In addition, overexpressing miR‐154‐5p can reverse the role of TLR5 neuropathic pain in vivo. Taken these together, we indicated that XIST could increase TLR5 expression by acting as a sponge of miR‐154‐5p in neuropathic pain development. This study revealed that XIST can contribute to neuropathic pain progression in rats through decreasing miR‐154‐5p and increasing TLR5. The XIST/miR‐154‐5p/ TLR5 axis can be provided as a novel therapeutic target in treating neuropathic pain.
Feng Shui woodlands are naturally or artificially formed green areas in southern China. They are precious for maintaining ecosystem balance in modern semiurban environments. However, they are generally small and geographically isolated from each other, and the status of genetic diversity of the plant species within them has been almost neglected. Therefore, we studied the genetic diversity of the endangered Erythrophleum fordii in eight Feng Shui woodlands (a total of 1,061 individuals) in Guangzhou, a large city in southern China, using microsatellites. For comparison, one population with 33 individuals sampled in a nature reserve was also studied.Although our results indicate that significant demographic declines occurred historically in E. fordii, such declines have not resulted in consistent reductions in genetic variation over generations in Feng Shui populations in the recent past, and the levels of genetic variation in these populations were higher than or comparable to the genetic variation of the population in the nature reserve. In addition, our parentage and paternity analyses indicated widespread and potential long-distance pollen flow within one Feng Shui woodland, indicating the presence of an unbroken pollination network, which would at least partially alleviate the genetic erosion due to habitat fragmentation and the unequal gene contributions of E. fordii parents to their progenies when favorable recruitment habitats are absent under most of the parent trees.Overall, our results suggest that E. fordii in Feng Shui woodlands may not be driven to extinction in the near future. Nevertheless, uncontrolled fast urban development with a lack of awareness of Feng Shui woodlands will cause the local extinction of E. fordii, which has already happened in some Feng Shui woodlands. K E Y W O R D Sbottleneck, demographic history, genetic diversity, microsatellites, parentage analysis | 10951 WANG et Al.
Dimerization is a promising strategy to develop novel drug candidates that could extend the biological spectrum, enhance the activity, overcome drug resistance, as well as improve pharmacological, pharmacokinetic, and physicochemical profiles. Isatin dimers possess a broad spectrum of biological properties and the isatin dimer indirubin has already been used in the clinic, revealing the potential of isatin dimers as putative drugs. This review covers the recent advances of isatin dimers as pharmacologically significant scaffolds and the structure–activity relationship to set up the direction for the design and development of isatin dimers with higher efficiency and lower toxicity.
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