Zhengbin Chai

Prohibitin 2 (PHB2) has been linked to mitochondrial inner-membrane organization, mitophagic recognition, receptor-associated signaling and nuclear transcription. Treating these observations as functions of a single uniform protein entity obscures important differences in localization, PHB1 dependence, membrane exposure and partner composition. Here, we use an evidence-based framework to distinguish context-defined PHB2 molecular states according to compartment or membrane topology, native-complex status and accessibility of defined molecular interfaces. Receptor-associated studies involving IGFBP6, grancalcin, SLAMF/B-cell receptor complexes, GALNT14-dependent IGF1R signaling and DDR2-TGFBR2 regulation support stimulus- and cell-restricted PHB2-containing systems, but do not establish a universal PHB2 surface receptor or a common trafficking route. Within mitochondria, crista architecture, respiratory competence and proteostasis are predominantly properties of the PHB1-PHB2 assembly, whereas damage-induced exposure of the PHB2 LC3-interacting region provides a subunit-specific mechanism for mitophagic recognition. PHB2 also contributes at distinct stages of PINK1-Parkin mitophagy, although the upstream PARL-PGAM5-PINK1 effect is less clearly separable from prohibitin-complex function than the mapped LIR-LC3 interaction. Divergent immune outcomes further vary with the mitochondrial cargo being removed and the experimental context: clearance of mitochondria that provide cytosolic mtDNA or other NLRP3-activating signals can limit inflammatory signaling, whereas turnover of MAVS-containing membranes can suppress type I interferon. Post-translational modifications regulate local PHB2 interactions or complex stability, but current evidence does not support a universal modification-driven trafficking program. Mechanistic and pharmacological studies should therefore define the relevant PHB2 state or molecular interface, verify native PHB1-PHB2 complex integrity and measure direct target engagement.

Angiogenesis is a crucial step in the growth and metastasis of invasive tumors. Tumor-induced angiogenesis is not due to a single factor; it involves activation of oncogenic signaling pathways and abnormal expression of angiogenesis-related genes within the complex tumor microenvironment (TME). Traditional research has primarily focused on the regulation of angiogenesis by protein-coding genes. In recent years, growing evidence has shown that long non-coding RNAs (lncRNAs) play important roles in angiogenesis. In this study, we systematically elucidate the molecular mechanisms by which lncRNAs regulate tumor-associated angiogenesis, including epigenetic, transcriptional, and post-transcriptional regulation. Furthermore, lncRNAs indirectly influence angiogenesis by regulating the functions of endothelial cells, cancer-associated fibroblasts, and tumor-associated macrophages within the TME. In addition, lncRNA-targeted therapeutic strategies have been summarized with specific emphasis on their potential integration with anti-angiogenic tumor therapy, including oligonucleotide-based silencing, restoration of tumor-suppressive lncRNAs, anti-vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) combination strategies, and nanomaterial-mediated delivery systems. This review aims to provide a theoretical foundation for innovative research on vascular targeted therapy for tumors.

The peptidyl arginine deiminase (PADI) family is a calcium ion-dependent group of isozymes with sequence similarity that catalyze the citrullination of proteins. Histones can serve as the target substrate of PADI family isozymes, and therefore, the PADI family is involved in NETosis and the secretion of inflammatory cytokines. Thus, the PADI family is associated with the development of inflammatory autoimmune diseases and cancer, reproductive development, and other related diseases. In this review, we systematically discuss the role of the PADI family in the pathogenesis of various diseases based on studies from the past decade to provide a reference for future research.

Background: The increasing incidence of gastrointestinal stromal tumors (GISTs) has led to the discovery of more novel prognostic markers. We aim to establish an unsupervised prognostic model for the early prediction of the prognosis of future patients with GISTs and to guide clinical treatment.Methods: We downloaded the GISTs dataset through the cBioPortal website. We extracted clinical information and pathological information, including the microsatellite instability (MSI) score, fraction genome altered (FGA) score, tumor mutational burden (TMB), and copy number alteration burden (CNAB), of patients with GISTs. For survival analysis, we used univariate Cox regression to analyze the contribution of each factor to prognosis and calculated a hazard ratio (HR) and 95% confidence interval (95% CI). For clustering groupings, we used the t-distributed stochastic neighbor embedding (t-SNE) method for data dimensionality reduction. Subsequently, the k-means method was used for clustering analysis.Results: A total of 395 individuals were included in the study. After dimensionality reduction with t-SNE, all patients were divided into two subgroups. Cluster 1 had worse OS than cluster 2 (HR=3.45, 95% CI, 2.22-5.56, PPPP values were less than 0.001.Conclusion: Based on the CNA of GISTs, patients can be divided into high-risk and low-risk groups. The high-risk group had a higher MSI score, FGA score, TMB and CNAB than the low-risk group. In addition, we established a prognostic nomogram based on the CNA and clinicopathological characteristics of patients with GISTs.

Sirtuin 2 (SIRT2), as a member of the sirtuin family, has representative features of evolutionarily highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase activity. In addition, SIRT2, as the only sirtuin protein colocalized with tubulin in the cytoplasm, has its own functions and characteristics. In recent years, studies have increasingly shown that SIRT2 can participate in the regulation of gene expression and regulate signal transduction in the metabolic pathway mainly through its post-translational modification of target genes; thus, SIRT2 has become a key centre in the metabolic pathway and participates in the pathological process of metabolic disorder-related diseases. In this paper, it is discussed that SIRT2 can regulate all aspects of gene expression, including epigenetic modification, replication, transcription and translation, and post-translational modification, which enables SIRT2 to participate in energy metabolism in life activities, and it is clarified that SIRT2 is involved in metabolic process-specific signal transduction mechanisms. Therefore, SIRT2 can be involved in metabolic disorder-related inflammation and oxidative stress, thereby triggering the occurrence of metabolic disorder-related diseases, such as neurodegenerative diseases, tumours, diabetes, and cardiovascular diseases. Currently, although the role of SIRT2 in some diseases is still controversial, given the multiple roles of SIRT2 in regulating physiological and pathological signal transduction, SIRT2 has become a key target for disease treatment. It is believed that with increasing research, the clinical application of SIRT2 will be promoted.