A fundamental feature of both early nervous system development and axon regeneration is the guidance of axonal projections to their targets in order to assemble neural circuits that control behavior. In the navigation process where the nerves grow toward their targets, the growth cones, which locate at the tips of axons, sense the environment surrounding them, including varies of attractive or repulsive molecular cues, then make directional decisions to adjust their navigation journey. The turning ability of a growth cone largely depends on its highly dynamic skeleton, where actin filaments and microtubules play a very important role in its motility. In this review, we summarize some possible mechanisms underlying growth cone motility, relevant molecular cues, and signaling pathways in axon guidance of previous studies and discuss some questions regarding directions for further studies.
AimTo investigate the effects of catalpol on muscular atrophy induced by sciatic nerve crush injury (SNCI).MethodsSeventy male Kunming mice were randomized into five groups (n=10): model, sham, catalpol (Cat), rapamycin (Rapa), and catalpol+rapamycin (Rapa+Cat). The ratio of gastrocnemius muscle wet weight (right/left, R/L) between the operated leg (right) and the normal leg (left) was calculated, and acetylcholinesterase (AChE) immunohistochemistry assays were performed to observe the change of motor end plate (MEP), along with the sizes of denervated and innervated muscle fibers. The expression levels of LC3II, TUNEL, BAX/BCL-2, LC3II/LC3I and P62, Beclin1, mTOR, and p-mTOR (ser2448) proteins in muscle were examined by fluorescence immunohistochemistry or Western blotting.ResultsResults show that catalpol improved the results of the grid walking tests by reducing the percentage of foot slips, which increased the gastrocnemius muscle wet weight (R/L), enhanced AChE expression at the MEP, and enlarged the section area of the muscle. The expression of LC3II and TUNEL was significantly inhibited by catalpol. The BAX/BCL-2 ratio was significantly increased in muscles of denervated and control groups. Lower LC3II/LC3I and BAX/BCL-2 ratios in denervated muscles were also detected after catalpol treatment.ConclusionThese results indicated that apoptosis and autophagy play a role in the regulation of denervation-induced muscle atrophy after SNCI, and catalpol alleviates muscle atrophy through the regulation of muscle apoptosis and autophagy via the mTOR signaling pathway.
In insects, neuropeptides and their receptors not only play a critical role in insect physiology and behavior but also are the potential targets for novel pesticide discoveries. Aphidius gifuensis is one of the most important and widespread aphid parasitoids, and has been successfully used to control aphid. In the present work, we systematically identified neuropeptides and their receptors from the genome and head transcriptome of A. gifuensis. A total of 35 neuropeptide precursors and 49 corresponding receptors were identified. The phylogenetic analyses demonstrated that 35 of these receptors belong to family-A, four belong to family-B, two belong to leucine-rich repeat-containing GPCRs, four belong to receptor guanylyl cyclases, and four belong to receptor tyrosine kinases. Oral ingestion of imidacloprid significantly up-regulated five neuropeptide precursors and four receptors whereas three neuropeptide precursors and eight receptors were significantly down-regulated, which indicated that these neuropeptides and their receptors are potential targets of some commercial insecticides. The RT-qPCR results showed that dopamine receptor 1, dopamine receptor 2, octopamine receptor, allatostatin-A receptor, neuropeptides capa receptor, SIFamide receptor, FMRFamide receptor, tyramine receptor and short neuropeptide F predominantly were expressed in the head whilst the expression of ion transport peptide showed widespread distribution in various tissues. The high expression levels of these genes suggest their important roles in the central nervous system. Taken together, our study provides fundamental information that may further our understanding of neuropeptidergic signaling systems in the regulation of the physiology and behavior of solitary wasps. Furthermore, this information could also aid in the design and discovery of specific and environment-friendly insecticides.
BCMA-targeting chimeric antigen receptor (CAR) T cell therapy demonstrates impressive clinical response in multiple myeloma (MM). However, some patients with BCMA-deficient tumours cannot benefit from this therapy, and others can experience BCMA antigen loss leading to relapse, thus necessitating the identification of additional CAR-T targets. Here, we show that FcRH5 is expressed on multiple myeloma cells and can be targeted with CAR-T cells. FcRH5 CAR-T cells elicited antigen-specific activation, cytokine secretion and cytotoxicity against MM cells. Moreover, FcRH5 CAR-T cells exhibited robust tumoricidal efficacy in murine xenograft models, including one deficient in BCMA expression. We also show that different forms of soluble FcRH5 can interfere with the efficacy of FcRH5 CAR-T cells. Lastly, FcRH5/BCMA-bispecific CAR-T cells efficiently recognized MM cells expressing FcRH5 and/or BCMA and displayed improved efficacy, compared with mono-specific CAR-T cells in vivo. These findings suggest that targeting FcRH5 with CAR-T cells may represent a promising therapeutic avenue for MM.
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