Neural stem cell-derived extracellular vesicles (NSC-derived EVs) alleviated ischemic stroke (IS) by suppressing the activation of nucleotide-binding domain leucine-rich repeats family protein 3 (NLRP3) inflammasome and neuronal pyroptosis. However, the specific mechanism needs further investigation. qRT-qPCR, Western blotting, and immunofluorescence detected related gene expression. Immunofluorescent analyzed the expression of Ki-67, βIII-Tubulin (Tuj1), and GFAP. Lactate dehydrogenase (LDH) release and IL-1β and IL-18 levels were analyzed by LDH and ELISA kits. TTC staining evaluated the infarction of brain tissues. Flow cytometric analysis measured caspase-1 activity. M6A methylated RNA immunoprecipitation PCR (MeRIP-PCR) measured methylation levels of G protein-coupled receptor 30 (GPR30). RIP and Co-IP analyzed the interactions of Y box binding protein (YBX1)/GPR30, YBX1/IGF2BP1 and NLRP3/speckle-type POZ protein (SPOP), as well as the ubiquitination levels of NLRP3. NSC-derived EVs inhibited the ischemia-reperfusion (I/R) injury of rats and the neuronal pyroptosis induced by oxygen-glucose deprivation/reoxygenation (OGD/R). Knockdown of EVs carrying YBX1 or GPR30 silencing abolished these inhibiting effects. GPR30 mRNA and IGF2BP1 protein were enriched by YBX1 antibody. YBX1 enhanced the stability of m6A-modified GPR30 by interacting with IGF2BP1 and thus promoting GPR30 expression. Knockdown of IGF2BP1 suppressed the binding between YBX1 and GPR30 mRNA. GPR30 promoted NLRP3 ubiquitination by interacting with SPOP. EVs carrying YBX1 could reduce the infarction of brain tissues and inhibit neuronal pyroptosis in rats with I/R injury. NSC-derived EVs carrying YBX1 increased the stability of m6A-modified GPR30 by interacting with IGF2BP1; the upregulation of GPR30 inhibited the activation of NLRP3 inflammasome through promoting NLRP3 ubiquitination by SPOP, ultimately suppressing the neuronal pyroptosis in IS.

Based on bioinformatics and machine learning methods, we conducted a study to screen the core genes of minimal change disease (MCD) and further explore its pathogenesis. First, we obtained the chip data sets GSE108113 and GSE200828 from the Gene Expression Comprehensive Database (GEO), which contained MCD information. We then used R software to analyze the gene chip data and performed functional enrichment analysis. Subsequently, we employed Cytoscape to screen the core genes and utilized machine learning algorithms (random forest and LASSO regression) to accurately identify them. To validate and analyze the core genes, we conducted immunohistochemistry (IHC) and gene set enrichment analysis (GSEA). Our results revealed a total of 394 highly expressed differential genes. Enrichment analysis indicated that these genes are primarily involved in T cell differentiation and p13k-akt signaling pathway of immune response. We identified NOTCH1, TP53, GATA3, and TGF-β1 as the core genes. IHC staining demonstrated significant differences in the expression of these four core genes between the normal group and the MCD group. Furthermore, GSEA suggested that their up-regulation may be closely associated with the pathological changes in MCD kidneys, particularly in the glycosaminoglycans signaling pathway. In conclusion, our study highlights NOTCH1, TP53, GATA3, and TGF-β1 as the core genes in MCD and emphasizes the close relationship between glycosaminoglycans and pathogenesis of MCD.

Diabetes has a substantial impact on public health, highlighting the need for novel treatments. Ubiquitination, an intracellular protein modification process, is emerging as a promising strategy for regulating pathological mechanisms. We hypothesize that ubiquitination plays a critical role in the development and progression of diabetes and its complications, and that understanding these mechanisms can lead to new therapeutic approaches.

To uncover the research trends and advances in diabetes ubiquitination and its complications, we conducted a bibliometric analysis.

Studies on ubiquitination in diabetes mellitus and its complications were retrieved from the Web of Science Core Collection. Visual mapping analysis was conducted using the CiteSpace software.

We gathered 791 articles published over the past 23 years, focusing on ubiquitination in diabetes and its associated complications. These articles originated from 54 countries and 386 institutions, with China as the leading contributor. Shanghai Jiao Tong University has the highest number of publications in this field. The most prominent authors contributing to this research area include Wei-Hua Zhang, with Zhang Y being the most frequently cited author. Additionally, The Journal of Biological Chemistry is noted as the most cited in this field. The predominant keywords included expression, activation, oxidative stress, phosphorylation, ubiquitination, degradation, and insulin resistance.

The role of ubiquitination in diabetes and its complications, such as diabetic nephropathy and cardiomyopathy, is a key research focus. However, these areas require further investigations.

Understanding the pathogenesis of diabetic cardiomyopathy (DCM), a common microvascular complication affecting the heart, is crucial for identifying new therapeutic targets and intervention strategies for DCM. Our study revealed a significant downregulation in Speckle-type POZ protein (SPOP) expression in DCM, while the overexpression of SPOP improved DCM-induced myocardial dysfunction, injury, fibrosis, hypertrophy, and ferroptosis. Mechanistically, SPOP facilitated the degradation of voltage-dependent anion channel 3 (VDAC3) by enhancing its ubiquitination. M6A demethylase AlkB homolog 5 (ALKBH5) reduced the mRNA stability of SPOP by decreasing m6A modification in its 3'UTR. The m6A reader insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) enhanced the stability of SPOP mRNA through recognition of m6A-modified SPOP 3'UTR. Furthermore, ALKBH5 promoted ferroptosis by inhibiting SPOP-induced VDAC3 degradation, while IGF2BP2 inhibited ferroptosis via activation of SPOP-induced VDAC3 degradation in high glucose-treated neonatal mouse ventricular cardiomyocytes (NMVCs). Overall, our study has unveiled a novel role of SPOP in the pathogenesis of ferroptosis and DCM, thereby significantly advancing our understanding of the involvement of ferroptosis during the progression of DCM. Moreover, this discovery offers promising potential therapeutic interventions targeting DCM.

The speckle-type POZ protein (SPOP) is demonstrated to be a specific adaptor of the cullin-RING-based E3 ubiquitin ligase complex that participates in multiple cellular processes. Up to now, SPOP involved in inflammatory response has attracted more attention, but the association of SPOP with animal virus infection is scarcely reported. In this study, chicken MyD88 (chMyD88), an innate immunity-associated protein, was screened to be an interacting partner of chSPOP using co-immunoprecipitation (Co-IP) combined with liquid chromatography-tandem mass spectrometry methods. This interaction was further confirmed by fluorescence co-localization, Co-IP, and pull-down assays. It was interesting that exogenous recombinant protein HA-chSPOP or endogenous chSPOP alone was mainly located in the nucleus but was translocated to the cytoplasm upon co-expression with chMyD88 or lipopolysaccharide stimulation. In addition, chSPOP reduced chMyD88 expression by ubiquitination in a dose-dependent manner, and the regulation of NF-κB activity by chSPOP was dependent solely on chMyD88. Importantly, chSPOP played a negative regulatory role in the MyD88/NF-κB signaling pathway and the production of proinflammatory cytokines. Moreover, we found that velogenic Newcastle disease virus (NDV) infection changed the subcellular localization of chSPOP and the expression patterns of chSPOP and chMyD88, and overexpression of chSPOP decreased the production of proinflammatory cytokines to enhance velogenic and lentogenic NDV replication, while siRNA-mediated chSPOP knockdown obtained the opposite results, thereby indicating that chSPOP negatively regulated MyD88/NF-κB signaling pathway mediated proinflammatory cytokine production to promote NDV replication. These findings highlight the important role of the SPOP/MyD88/NF-κB signaling pathway in NDV replication and may provide insightful information about NDV pathogenesis.

Kidney diseases, particularly Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD), are identified as global public health issues affecting millions of individuals. In addition, the frequency of renal diseases in the population has increased dramatically and rapidly in recent years. Renal disorders have become a significant public health burden. The pathophysiology of renal diseases is significantly connected with renal cell death, including apoptosis, necrosis, necroptosis, ferroptosis, pyroptosis, and autophagy, as is now recognized. Unlike other forms of cell death, pyroptosis is a unique planned cell death (PCD). Scientists have proven that pyroptosis is crucial in developing various disorders, and this phenomenon is gaining increasing attention. It is considered a novel method of inflammatory cell death. Intriguingly, inflammation is among the most significant pathological characteristics of renal disease. This study investigates the effects of pyroptosis on Acute Kidney Injury (AKI), Chronic Kidney Disease (CKD), Diabetic Nephropathy (DN), Immunoglobulin A (IgA) Nephropathy, and Lupus Nephritis (LN) to identify novel therapeutic targets for kidney diseases.

Diabetic kidney disease (DKD) is a prevalent and severe complications of diabetes and serves as the primary cause of end-stage kidney disease (ESKD) globally. Increasing evidence indicates that renal inflammation is critical in the pathogenesis of DKD. The nucleotide - binding oligomerization domain (NOD) - like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most extensively researched inflammasome complex and is considered a crucial regulator in the pathogenesis of DKD. The activation of NLRP3 inflammasome is regulated by various signaling pathways, including NF- κB, thioredoxin-interacting protein (TXNIP), and non-coding RNAs (ncRNA), among others. Natural products are chemicals extracted from living organisms in nature, and they typically possess pharmacological and biological activities. They are invaluable sources for drug design and development. Research has demonstrated that many natural products can alleviate DKD by targeting the NLRP3 inflammasome. In this review, we highlight the role of the NLRP3 inflammasome in DKD, and the pathways by which natural products fight against DKD via inhibiting the NLRP3 inflammasome activation, so as to provide novel insights for the treatment of DKD.