Neutrophil peptide 1 accelerates the clearance of degenerative axons during Wallerian degeneration by activating macrophages after peripheral nerve crush injury

Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still unclear.Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration.However,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear.This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury.The functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent assay.Axonal debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian degeneration.Macrophage inflammatory factor expression in different polarization states was detected using a protein chip.The results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 polarization.The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention.Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in vitro.Thus,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

FK506 contributes to peripheral nerve regeneration by inhibiting neuroinflammatory responses and promoting neuron survival

FK506(Tacrolimus)is a systemic immunosuppressant approved by the U.S.Food and Drug Administration.FK506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways remain unclear.In this study,we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve,increased the numbers of motor and sensory neurons,reduced inflammatory responses,markedly improved the conduction function of the injured nerve,and promoted motor function recovery.These findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.

Dynamic evaluation on sealing capacity of caprocks of the Meso-Neoproterozoic reservoirs in Ordos Basin,China

The Meso-Neoproterozoic is a new play in the Ordos Basin.A deeper understanding about the dynamic relationship between the caprocks and the source rocks is needed.Based on the comprehensive analysis of hydrocarbon source development characteristics of the Meso-Neoproterozoic and its overlying strata,as well as the formation contact relationships,lithology characteristics and exploratory drilling data,it is recognized that the Meso-Neoproterozoic contains two types of petroleum accumulation assemblage,that is,the“self-sourced indigenous”and“upper source rock-lower reservoir”assemblages.The former is mainly controlled by the development and distribution of source rocks of the Changcheng System,with the Lower Cambrian shale sequence as its caprock.The later is controlled by the superposition between the Meso-Neoproterozoic and its overlying source rocks and this assemblage is mainly distributed in Hangjinqi and Pingliang areas with the Carboniferous-Permian shale sequence as its caprock.The dynamic evaluation on the displacement pressure serves to reconstruct the displacement pressure history of the caprock.The results show that the shale sequence of the Cambrian Maozhuang Formation in well XY 1 in the southern Ordos Basin has possibly acquired the ability of sealing natural gas since the early of Late Triassic.Its displacement pressure increased rapidly up to 20 MPa during the Late Triassic-Jurassic and keeps at 9.2 MPa at present,indicating fair sealing ability.The Carboniferous-Permian caprocks in Hangjinqi area could have acquired the ability to seal natural gas in the Late Jurassic-Early Cretaceous,and the present-day displacement pressure is 9e12 MPa,indicating good sealing ability.The upper Paleozoic caprock in Pingliang area has been able to seal natural gas since the Early Jurassic,with a maximum displacement pressure of 23 MPa during the Cretaceous period and a current value of 17 e20 MPa,indicative of strong ability to seal natural gas.The sealing ability of caprocks of both the“selfsourced indigenous”and“upper source rock-lower reservoir”assemblages has come into being earlier than or at least no later than the peak gas generation of the source rocks and therefore the caprocks are dynamically effective in geohistory.The Meso-Neoproterozoic reservoirs in the Ordos Basin are well preserved and probabally of better potential for exploration in terms of the caprock-source rock combination.