Spinal cord injury (SCI) results in a wide range of disabilities. Its complex pathophysiological process limits the effectiveness of many clinical treatments. Betulinic acid (BA) has been shown to be an effective treatment for some neurological diseases, but it has not been studied in SCI. In this study, we assessed the role of BA in SCI and investigated its underlying mechanism. We used a mouse model of SCI, and functional outcomes following injury were assessed. Western blotting, ELISA, and immunofluorescence techniques were employed to analyze levels of autophagy, mitophagy, pyroptosis, and AMPK-related signaling pathways were also examined. Our results showed that BA significantly improved functional recovery following SCI. Furthermore, autophagy, mitophagy, ROS level and pyroptosis were implicated in the mechanism of BA in the treatment of SCI. Specifically, our results suggest that BA restored autophagy flux following injury, which induced mitophagy to eliminate the accumulation of ROS and inhibits pyroptosis. Further mechanistic studies revealed that BA likely regulates autophagy and mitophagy via the AMPK-mTOR-TFEB signaling pathway. Those results showed that BA can significantly promote the recovery following SCI and that it may be a promising therapy for SCI.

Central nervous system (CNS) trauma, including traumatic brain injury (TBI) and spinal cord injury (SCI), remains a leading cause for morbidity and mortality worldwide. Past research has shown that cell death plays a critical role in the pathophysiology of CNS injuries. More recently, pyroptosis has been identified as a form of programmed inflammatory cell death, and it is a unique form of cell death in various aspects. Mechanistically, pyroptosis can be categorized into canonical (mediated by caspase-1) and non-canonical (mediated by caspase-4/5/11). In canonical pyroptosis, Nod-like receptors (NLRs) inflammasomes play a critical role, and their activation promotes the maturation and secretion of the inflammatory cytokines interleukin-1β/18 (IL-1β/18), cleavage of gasdermin D (GSDMD), and ultimately pyroptotic cell death. Despite a plethora of new knowledge regarding pyroptosis, detailed understanding of how pyroptosis is involved in CNS injuries and possible ways to improve clinical outcomes following CNS injuries remain elusive. This review discusses the current knowledge on how pyroptosis is involved in CNS injuries, focusing on new discoveries regarding how pyroptosis activation occurs, differences between CNS cell types following injury, time-course of inflammatory responses, and key regulatory steps of pyroptosis. In addition, we highlight various investigational agents that are capable of regulating key steps in pyroptotic cell death, and we discuss how these agents may be used as therapies to improve outcomes following CNS trauma.

Psoriasis is a chronic inflammatory skin disorder with a pathogenesis involving the interleukin-23/interleukin-17 axis. Salvianolic acid B exerts several pharmacological effects, such as antioxidation, anti-inflammation, and antitumor effects. The anti-psoriatic effects of salvianolic acid B have not been reported. In this study, we aimed to determine the optimum vehicle for salvianolic acid B, investigate its therapeutic effect on psoriatic-like skin conditions, and explore its underlying mechanisms of action. BALB/c mice were administered topical imiquimod to induce psoriasis-like skin and were then randomly assigned to control, vehicle control, salvianolic acid B in vehicles, and 0.25% desoximetasone ointment treatment groups. Barrier function, cytokine expression, histology assessment, and disease severity were evaluated. The results showed that salvianolic acid B-containing microemulsion alleviated disease severity, reduced acanthosis, and inhibited interleukin-23/interleukin-17 (IL-23/IL-17) cytokines, epidermal proliferation, and increased skin hydration. Our study suggests that salvianolic acid B represents a possible new therapeutic drug for the treatment of psoriasis. In addition, such formulation could obtain high therapeutic efficacy in addition to providing sufficient hydration for dry skin.

While children's orientations to achievement are strong predictors of attainments, little is known about how parental economic hardship during recessionary times influences children's orientations to their futures. The Youth Development Study has followed a community sample of young people in St Paul, Minnesota from mid-adolescence through their mid-thirties with nearannual surveys, and has recently begun surveying the children of this cohort. Using linked parent and child data, the present study examines the relationship between parental economic hardship and children's achievement orientations in the aftermath of the recent "Great Recession." Initial OLS analyses draw on 345 parent-child pairs, with data collected from parents during their adolescence, during the decade prior to the recession, and in 2011, and from their children (age 11 and older) in 2011. Then, first difference models are estimated, based on a smaller sample (N=186) of parents and children who completed surveys in both 2009 and 2011. Our findings indicate that when families are more vulnerable, as a result of low parental education and prior parental unemployment experience, children's achievement orientations are more strongly threatened by the family's economic circumstances. For example, as parental financial problems increased, economic expectations declined only among children of the least well-educated parents. Low household incomes diminished educational aspirations only when parents experienced unemployment during the ten years prior to the recent recession. Parental achievement orientations, as adolescents, were also found to moderate the impacts of shifts in the family's economic circumstances. Finally, boys reacted more strongly to their parents' hardship than girls.

Osteoarthritis (OA) is a degenerative joint disease characterized by destruction of articular cartilage. The inflammatory response is the most important factor affecting the disease process. As interleukin-1β (IL-1β) stimulates several key mediators in the inflammatory response, it plays a major role in the pathogenesis of OA. Maslinic acid (MA) is a natural compound distributed in olive fruit. Previous studies have found that maslinic acid has an inhibitory effect on inflammation, but its specific role in the progression of OA disease has not been studied so far. In this study, we aim to assess the protective effect of MA on OA progression by in vitro and in vivo experiments. Our results indicate that, in IL-1β-induced inflammatory response, MA is effective in attenuating some major inflammatory mediators such as nitric oxide (NO) and prostaglandin E2, and inhibits the expression of IL-6, inducible nitric oxide synthase, cyclooxygenase-2, and tumor necrosis factor-α (TNF-α) in a concentration-dependent manner. Also, MA downregulated the expression levels of thrombospondin motif 5 (ADAMTS5) and matrix metalloproteinase 13 in chondrocytes, resulting in reduced degradation of its extracellular matrix. Mechanistically, MA exhibits an antiinflammatory effect by inactivating the PI3K/AKT/NF-κB pathway. In vivo, the protective effect of MA on OA development can be detected in a surgically induced mouse OA model. In summary, these findings suggest that MA can be used as a safe and effective potential OA therapeutic strategy.