Conditioned medium from human dental pulp stem cells treats spinal cord injury by inhibiting microglial pyroptosis

Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains unclear.In the present study,we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem cells.We found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury,decreased expression of the microglial pyroptosis markers NLRP3,GSDMD,caspase-1,and interleukin-1β,promoted axonal and myelin regeneration,and inhibited the formation of glial scars.In addition,in a lipopolysaccharide-induced BV2 microglia model,conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway.These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,thereby promoting the recovery of neurological function after spinal cord injury.Therefore,conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.

Upregulation of circ0000381 atienuates microglial/macrophage pyroptosis after spinal cord injury

Neuroinflammation exacerbates secondary damage after spinal cord injury,while microglia/macrophage pyroptosis is important to neuroinflammation.Circular RNAs(circRNAs)play a role in the central nervous system.However,the functional role and mechanism of circRNAs in regulating microglia/macrophage pyroptosis after spinal cord injury are still poorly studied.In the present study,we detected microglia/macrophage pyroptosis in a female rat model of spinal cord injury,along with upregulated levels of circ0000381 in the spinal cord.Our further experimental results suggest that circ0000381 may function as a sponge to sequester endogenous microRNA423-3p(miR-423-3p),which can increase the expression of NOD-like receptor 3(NLRP3),a pyroptosis marker.Therefore,upregulation of circ0000381 may be a compensatory change after spinal cord injury to attenuate microglia/macrophage pyroptosis.Indeed,knockdown of circ0000381 expression exacerbated microglia/macrophage pyroptosis.Collectively,our findings provide novel evidence for the upregulation of circ0000381,which may serve as a neuroprotective mechanism to attenuate microglia/macrophage pyroptosis after spinal cord injury.Accordingly,circ0000381 may be a novel therapeutic target for the treatment of spinal cord injury.

Assessing the Impacts of High Speed Rail Development in China’s Yangtze River Delta Megaregion

This paper assesses the impacts of high speed rail (HSR) development in the Yangtze River Delta (YRD) Megaregion, China. After giving an introduction and conducting a literature review, the paper proposes a pole-axis-network system (PANS) model guiding the entire study. On the one hand, the HSR projects in the YRD Megaregion are expected to generate significant efficiency-related transportation and non-transportation benefits. As a result, the spillover effects from Shanghai and other major cities (poles) will greatly promote the urban and regional developments along the major HSR corridors (axes), and the entire megaregion will become more integrated economically, socially, and culturally. But, on the other hand, the HSR projects will also create serious social and geographic inequity issues, which need to be addressed as soon as possible in a proper way. This empirical study confirms the PANS model proposed.

Mechanisms of bone pain:Progress in research from bench to bedside

The field of research on pain originating from various bone diseases is expanding rapidly, with new mechanisms and targets asserting both peripheral and central sites of action. The scope of research is broadening from bone biology to neuroscience,neuroendocrinology, and immunology. In particular, the roles of primary sensory neurons and non-neuronal cells in the peripheral tissues as important targets for bone pain treatment are under extensive investigation in both pre-clinical and clinical settings. An understanding of the peripheral mechanisms underlying pain conditions associated with various bone diseases will aid in the appropriate application and development of optimal strategies for not only managing bone pain symptoms but also improving bone repairing and remodeling, which potentially cures the underlying etiology for long-term functional recovery. In this review, we focus on advances in important preclinical studies of significant bone pain conditions in the past 5 years that indicated new peripheral neuronal and non-neuronal mechanisms, novel targets for potential clinical interventions, and future directions of research.

Peracetic acid(PAA)-based pretreatment effectively improves medium-chain fatty acids(MCFAs)production from sewage sludge

Peracetic acid(PAA),known for its environmentally friendly properties as a oxidant and bactericide,is gaining prominence in decontamination and disinfection applications.The primary product of PAA oxidation is acetate that can serve as an electron acceptor(EA)for the biosynthesis of medium-chain fatty acids(MCFAs)via chain elongation(CE)reactions.Hence,PAA-based pretreatment is supposed to be beneficial for MCFAs production from anaerobic sludge fermentation,as it could enhance organic matter availability,suppress competing microorganisms and furnish EA by providing acetate.However,such a hypothesis has rarely been proved.Here we reveal that PAA-based pretreatment leads to significant exfoliation of extracellular polymeric substances(EPS)from sludge flocs and disruption of proteinic secondary structures,through inducing highly active free radicals and singlet oxygen.The production of MCFAs increases substantially to 11,265.6 mg COD L^(-1),while the undesired byproducts,specifically long-chain alcohols(LCAs),decrease to 723.5 mg COD L^(-1).Microbial activity tests further demonstrate that PAA pretreatment stimulates the CE process,attributed to the up-regulation of functional genes involved in fatty acid biosynthesis pathway.These comprehensive findings provide insights into the effectiveness and mechanisms behind enhanced MCFAs production through PAA-based technology,advancing our understanding of sustainable resource recovery from sewage sludge.

Spinal Cord Stimulation for Pain Treatment After Spinal Cord Injury

In addition to restoration of bladder, bowel, and motor functions, alleviating the accompanying debilitating pain is equally important for improving the quality of life of patients with spinal cord injury(SCI). Currently,however, the treatment of chronic pain after SCI remains a largely unmet need. Electrical spinal cord stimulation(SCS) has been used to manage a variety of chronic pain conditions that are refractory to pharmacotherapy. Yet, its efficacy, benefit profiles, and mechanisms of action in SCI pain remain elusive, due to limited research, methodological weaknesses in previous clinical studies, and a lack of mechanistic exploration of SCS for SCI pain control. We aim to review recent studies and outline the therapeutic potential of different SCS paradigms for traumatic SCI pain. We begin with an overview of its manifestations,classification, potential underlying etiology, and currentchallenges for its treatment. The clinical evidence for using SCS in SCI pain is then reviewed. Finally, future perspectives of pre-clinical research and clinical study of SCS for SCI pain treatment are discussed.

Shen-Qi-Wan Protects the Renal Peritubular Capillary Injury from Adenine-mediated Damage by Upregulating Aquaporin 1

Background:Shen-Qi-Wan(SQW),a commonly used prescription against chronic kidney disease(CKD)in Tradi-tional Chinese Medicine(TCM),has a nephroprotective action in adenine-induced kidney injury.However,the mechanism of SQW in renal injury remains unclear.Objective:This study was undertaken to measure the effect of SQW on peritubular capillary injury both in vivo and in vitro assays.Methods:The effect of SQW on the peritubular capillary injury was evaluated according to measuring hypothalamic-pituitary-adrenal(HPA)function,inflammatory cytokines,VEGF(vascular endothelial growth fac-tor),CD34(Cluster of differentiation 34),and AQP1(Aquaporin 1)levels in the kidney,cell migration,and lumen forming capacity.Results:SQW supplementation could ameliorate dysfunction of the HPA and renal function loss induced by adenine.SQW also significantly inhibited the inflammatory cytokines including MCP-1(monocyte chemotactic protein-1)and VCAM-1(vascular cell adhesion molecule-1)level.Alternatively,SQW administration showed an ameliorating effect from the toxicity and alleviated the injury of capillaries around renal tubules instigated by adenine through increasing AQP1 mRNA and protein level.SQW medicated the serum enhanced the migration and lumen formation ability of HMEC-1 cells,and significantly increased AQP1 protein level.Moreover,AQP1 knockdown efficiently inhibited the migration and lumen formation ability in HMEC-1 cells,and weakened the effect of SQW medicated serum.Conclusion:These results suggested that SQW attenuated peritubular capillary injury in adenine-induced CKD model rats through boosting angiogenesis in endothelial cell,and AQP1 may be a potential target of SQW for treating the renal injury.