Cell death can occur in different modes, ferroptosis, pyroptosis, apoptosis, and necroptosis. Recent studies have shown that pyroptosis can be effectively regulated and that like necroptosis, pyroptosis has been regarded as a type of programmed cell death. The mechanism of its occurrence can be divided into canonical inflammasome-induced pyroptosis and noncanonical inflammasome-induced pyroptosis. In the past research, pyroptosis has been shown to be closely related to various diseases, such as tumors, neurodegenerative diseases, and central nervous system trauma, and studies have pointed out that in central nervous system trauma, pyroptosis is activated. Furthermore, these studies have shown that the inhibition of pyroptosis can play a role in protecting nerve function. In this review, we summarized the mechanisms of pyroptosis, introduce treatment strategies for targeted pyroptosis in central nervous system trauma, and proposed some issues of targeted pyroptosis in the treatment of central nervous system injury.

Hematopoietic stem cells (HSCs) from different sources show varied repopulating capacity, and HSCs lose their stemness after long-time ex vivo culture. However, the underlying mechanisms of the stemness differences because of the cell sources and the culture stimulation are not fully understood. Here, we applied single-cell RNA-seq (scRNA-seq) to analyze the naïve and stimulated human CD34+ cells from cord blood (CB) and (mPB). We collected over 16,000 single-cell data to construct a comprehensive trajectory inference map and characterized the HSC population on the hierarchy top, which is under quiescent state. Then we compared HSCs in CB to those in mPB and HSCs of naïve samples to those of cultured samples, and identified stemness-related genes (SRGs) associated with culture time (CT-SRGs) and cell source (CS-SRGs), respectively. Interestingly, CT-SRGs and CS-SRGs share genes enriched in the signaling pathways such as mRNA catabolic process, Translational initiation, Ribonucleoprotein complex biogenesis and Cotranslational protein targeting to membrane, suggesting dynamic protein translation and processing may be a common requirement for stemness maintenance. Meanwhile, CT-SRGs are enriched in pathways involved in glucocorticoid and corticosteroid response that affect HSCs homing and engraftment. In contrast, CS-SRGs specifically contain genes related purine and ATP metabolic process which is important to initiate hematopoiesis. Finally, we presented an application through a small-scale drug screening using Connectivity Map (CMap) against CT-SRGs and found a small molecule cucurbitacin I, targeting STAT3/JAK2, can efficiently expand HSCs ex vivo while maintaining its stemness. These results indicate SRGs revealed by scRNA-seq can provide helpful insights to understand the stemness differences under diverse circumstances, and CT-SRGs can be a valuable database to identify candidates enhancing functional HSC expansion during ex vivo culture.

Isocorydine (ICD) is a type of isoquinoline alkaloid originating from Corydalis edulis, which has been used to relieve spasm, dilate blood vessels, and treat malaria as well as hypoxia in clinic. However, its effect on inflammation and underlying mechanisms remains unclear. The aim of our study was to determine the potential effects and mechanisms of ICD on pro-inflammatory interleukin-6 (IL-6) expression in bone marrow-derived macrophages (BMDMs) and acute lung injury mouse model. A mouse model of acute lung injury was established by intraperitoneal injection of LPS and treated with different doses of ICD. The body weight and food intake of mice were monitored to determine the toxicity of ICD. The tissue samples of lung, spleen and blood were taken to assess the pathological symptoms of acute lung injury and the expression levels of IL-6. Further, BMDMs isolated from C57BL/6 mice were cultured in vitro and treated with granulocyte-macrophage colony-stimulating factor (GM-CSF), LPS and different doses of ICD. CCK-8 assay and flow cytometry were performed to assess the viability of BMDMs. The expression of IL-6 was detected by RT-PCR and ELISA. RNA-seq was carried out to detect the differential expression genes of ICD-treated BMDMs. Western blotting was used to detect the change in MAPK and NF-κB signaling pathways. Our findings show that ICD ameliorates IL-6 expression and attenuates phosphorylation of p65 and JNK in BMDMs, and can protect mice from acute lung injury.

Background Hematopoietic stem cells (HSCs) from different sources show varied repopulating capacity, and HSCs lose their stemness after long‐time ex vivo culture. A deep understanding of these phenomena may provide helpful insights for HSCs. Methods Here, we applied single‐cell RNA‐seq (scRNA‐seq) to analyse the naïve and stimulated human CD34 + cells from cord blood (CB) and mobilised peripheral blood (mPB). Results We collected over 16 000 high‐quality single‐cell data to construct a comprehensive inference map and characterised the HSCs under a quiescent state on the hierarchy top. Then, we compared HSCs in CB with those in mPB and HSCs of naïve samples to those of cultured samples, and identified stemness‐related genes (SRGs) associated with cell source (CS‐SRGs) and culture time (CT‐SRGs), respectively. Interestingly, CS‐SRGs and CT‐SRGs share genes enriched in the signalling pathways such as mRNA catabolic process, translational initiation, ribonucleoprotein complex biogenesis and cotranslational protein targeting to membrane, suggesting dynamic protein translation and processing may be a common requirement for stemness maintenance. Meanwhile, CT‐SRGs are enriched in pathways involved in glucocorticoid and corticosteroid response that affect HSCs homing and engraftment. In contrast, CS‐SRGs specifically contain genes related to purine and ATP metabolic process, which is crucial for HSC homeostasis in the stress settings. Particularly, when CT‐SRGs are used as reference genes for the construction of the development trajectory of CD34 + cells, lymphoid and myeloid lineages are clearly separated after HSCs/MPPs. Finally, we presented an application through a small‐scale drug screening using Connectivity Map (CMap) against CT‐SRGs. A small molecule, cucurbitacin I, was found to efficiently expand HSCs ex vivo while maintaining its stemness. Conclusions Our findings provide new perspectives for understanding HSCs, and the strategy to identify candidate molecules through SRGs may be applicable to study other stem cells.