Cuproptosis is a novel copper ion-dependent cell death type being regulated in cells, and this is quite different from the common cell death patterns such as apoptosis, pyroptosis, necroptosis, and ferroptosis. Interestingly, like with death patterns, cuproptosis-related genes have recently been reported to regulate the occurrence and progression of various tumors. However, in bladder cancer, the link between cuproptosis and clinical outcome, tumor microenvironment (TME) modification, and immunotherapy is unknown. To determine the role of cuprotosis in the tumor microenvironment, we systematically examined the characteristic patterns of 10 cuproptosis-related genes in bladder cancer (BLCA). By analyzing principal component data, we established a cuproptosis score to determine the degree of cuproptosis among patients. Finally, we evaluated the potential of these values in predicting BLCA prognosis and treatment responses. A comprehensive study of the mutations of cuproptosis-related genes in BLCA specimens was conducted at the genetic level, and their expression and survival patterns were evaluated using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Two cuproptosis patterns were constructed based on the transcription level of 10 cuproptosis-related genes, featuring differences in the prognosis and the infiltrating landscape of immune cells (especially T and dendritic cells) with interactions between cuproptosis and the TME. Our study further demonstrated that cuproptosis score may predict prognosis, immunophenotype sensitivity to chemotherapy, and immunotherapy response among bladder cancer patients. The development and progression of bladder cancer are likely to be influenced by cuproptosis, which may involve a diverse and complex TME. The cuproptosis pattern evaluated in our study may enhance understanding of immune infiltrations and guide more potent immunotherapy interventions.

DOX-doped MOF nanoparticles were prepared via a one-pot reaction and successively anchored with Fe3+ and HA for simultaneous targeted drug delivery and MR imaging.

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Periodontitis, a common chronic inflammatory disease of the periodontium, is caused by dental plaque formation induced by microorganisms. Recent studies have demonstrated that lncRNAs play a critical role in the regulation of gene expression and in the pathogenesis of diseases. To demonstrate that periodontitis is associated with lncRNAs, microarray analysis was used to detect differently expressed lncRNAs in chronic periodontitis and adjacent normal tissues. The results of some differently expressed lncRNAs were further confirmed using real-time PCR. A total of 8925 differentially expressed lncRNAs were detected, including 4313 upregulated lncRNAs and 4612 downregulated lncRNAs. Further lncRNA subgroup analysis showed there were 589 enhancer-like lncRNAs, 238 homeobox (HOX) cluster lncRNAs, and 1218 Rinn's lincRNAs, of which 656 lincRNAs were upregulated and 562 lincRNAs were downregulated. Therefore, we confirmed that lncRNAs were differently expressed in chronic periodontitis tissues compared with adjacent normal tissues, indicating that lncRNAs may exert partial or key roles in periodontitis pathogenesis and development. Taken together, this study may provide potential targets for future treatment of periodontitis and novel diagnostic biomarkers for periodontitis.

Background and Aim : We have previously shown that high-mobility group box 1 ( HMGB1 ) is an independent biomarker for shortened survival of prostate cancer (PCa) patients. However, the specific role of HMGB1 in tumor development and progression remains largely unknown. In this study, we investigated the molecular mechanisms of HMGB1 in PCa tumorigenesis. Methods : Gain-of-function and loss-of-function experiments were used to determine the biological functions of HMGB1 both in vitro and in vivo . Bioinformatic analysis, immunoprecipitation, and immunofluorescence assays were applied to discern and examine the relationship between HMGB1 and its potential targets. Specimens from 64 patients with PCa were analyzed for the expression of HMGB1 and its relationship with Brahma-related gene 1 ( BRG1 ) was examined by immunohistochemistry. Results : The results demonstrated that ectopic expression of HMGB1 facilitated growth and metastasis of PCa by enhancing Akt signaling pathway and promoting epithelial-mesenchymal transition (EMT), while silencing of HMGB1 showed the opposite effects. Mechanistically, HMGB1 exerted these functions through its interaction with BRG1 which may augment BRG1 function and activate the Akt signaling pathway thereby promoting EMT. Importantly, both HMGB1 and BRG1 expression was markedly increased in human PCa tissues. Conclusions : Taken together, these findings indicate that upregulation of HMGB1 promotes PCa development via activation of Akt and accelerates metastasis through regulating BRG1 -mediated EMT. HMGB1 could be used as a novel potential target for the treatment of PCa.

Heterogeneous nuclear ribonucleoprotein L (hnRNP-L) is a promoter of various kinds of cancers, but its actions in bladder cancer (BC) are unclear. In this study, we investigated the function and the underlying mechanism of hnRNP-L in bladder carcinogenesis. Our results demonstrated that enhanced hnRNP-L expression in BC tissues was associated with poor overall survival of BC patients. Depletion of hnRNP-L significantly suppressed cell proliferation in vitro and inhibited xenograft tumor growth in vivo. Furthermore, downregulation of hnRNP-L resulted in G1-phase cell cycle arrest and enhanced apoptosis accompanied by inhibition of EMT and cell migration. All these cellular changes were reversed by ectopic expression of hnRNP-L. Deletion of hnRNP-L resulted in decreased expression of Bcl-2, enhanced expression of caspases-3, -6 and -9 and inhibition of the MAPK signaling pathway. These findings demonstrate that hnRNP-L contributes to poor prognosis and tumor progression of BC by inhibiting the intrinsic apoptotic signaling and enhancing MAPK signaling pathways.

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Expression of the RNA-binding protein HnRNP-L was previously shown to associate with tumorigenesis in liver and lung cancer. In this study, we examined the role of HnRNP-L in prostate cancer (Pca). We found that HnRNP-L is overexpressed in prostate tissue samples from 160 PC patients compared with tissue samples from 32 donors with cancers other than Pca. Moreover, HnRNP-L positively correlated with aggressive tumor characteristics. HnRNP-L knockdown inhibited cell proliferation and promoted cell apoptosis of Pca cell lines in vitro, and suppressed tumor growth when the cells were subcutaneously implanted in an athymic mouse model. Conversely, overexpression of HnRNP-L promoted cell proliferation and tumor growth while prohibiting cell apoptosis. HnRNP-L promoted cell proliferation and tumor growth in Pca in part by interacting with endogenous p53 mRNA, which was closely associated with cyclin p21. In addition, HnRNP-L affected cell apoptosis by directly binding the classical apoptosis protein BCL-2. These observations suggest HnRNP-L is an important regulatory factor that exerts pro-proliferation and anti-apoptosis effects in Pca through actions affecting the cell cycle and intrinsic apoptotic signaling. Thus HnRNP-L could potentially serve as a valuable molecular biomarker or therapeutic target in the treatment of Pca.