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Chimeric antigen receptor (CAR)-T cell therapy has been confirmed improving remission rates in refractory patients or relapsed B-cell acute lymphoblastic leukemia (R/R B-ALL). However, the added benefits of undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T therapy remain a subject of debate. In this research we investigated the efficiency and long-term outcomes of CD19 CAR-T bridging with allo-HSCT in R/R B-ALL patients. A total of 42 patients were brought into the cohort studies. Our findings revealed that patients who appected CAR-T followed by HSCT had a 1-year overall survival (OS) rate of 70 % and a 1-year leukemia-free survival (LFS) rate of 95 %. Moreover, patients who underwent this combined treatment had higher OS and LFS rates compared to those who received CAR-T therapy alone. In conclusion, the results of this clinical trial provide compelling evidence for the safety and efficacy of using CAR-T therapy as a bridging strategy to allo-HSCT in patients with R/R B-ALL.

Cuproptosis and ferroptosis represent copper- and iron-dependent forms of cell death, respectively, and both are known to play pivotal roles in head and neck squamous cell carcinoma (HNSCC). However, few studies have explored the prognostic signatures related to cuproptosis and ferroptosis in HNSCC. Our objective was to construct a prognostic model based on genes associated with cuproptosis and ferroptosis. We randomly assigned 502 HSNCC samples from The Cancer Genome Atlas (TCGA) into training and testing sets. Pearson correlation analysis was utilized to identify cuproptosis-associated ferroptosis genes in the training set. Cox proportional hazards (COX) regression and least absolute shrinkage operator (LASSO) were employed to construct the prognostic model. The performance of the prognostic model was internally validated using single-factor COX regression, multifactor COX regression, Kaplan–Meier analysis, principal component analysis (PCA), and receiver operating curve (ROC) analysis. Additionally, we obtained 97 samples from the Gene Expression Omnibus (GEO) database for external validation. The constructed model, based on 12 cuproptosis-associated ferroptosis genes, proved to be an independent predictor of HNSCC prognosis. Among these genes, the increased expression of aurora kinase A (AURKA) has been implicated in various cancers. To further investigate, we employed small interfering RNAs (siRNAs) to knock down AURKA expression and conducted functional experiments. The results demonstrated that AURKA knockdown significantly inhibited the proliferation and migration of HNSCC cells (Cal27 and CNE2). Therefore, AURKA may serve as a potential biomarker in HNSCC.

Disulfidptosis is a novel cell death mode in which the accumulation of disulfide bonds in tumor cells leads to cell disintegration and death. Long-stranded noncoding RNAs (LncRNAs) are aberrantly expressed in hepatocellular carcinoma (HCC) and have been reported to carry significant potential as a biomarker for HCC prognosis. However, lncRNA studies with disulfidptosis in hepatocellular carcinoma have rarely been reported. Therefore, this study aimed to construct a risk prognostic model based on the disulfidptosis-related lncRNA and investigate the mechanisms associated with disulfidptosis in hepatocellular carcinoma. The clinical and transcriptional information of 424 HCC patients was downloaded from The Cancer Genome Atlas (TCGA) and divided into test and validation sets. Furthermore, 1668 lncRNAs associated with disulfidptosis were identified using Pearson correlation. Six lncRNA constructs were finally identified for the risk prognostic model using one-way Cox proportional hazards (COX), multifactorial COX, and lasso regression. Kaplan–Meier (KM) analysis, principal component analysis, receiver operating characteristic curve (ROC), C-index, and column-line plot results confirmed that the constructed model was an independent prognostic factor. Based on the disulfidptosis risk score, risk groups were identified as potential predictors of immune cell infiltration, drug sensitivity, and immunotherapy responsiveness. Finally, we confirmed that phospholipase B domain containing 1 antisense RNA 1 (PLBD1-AS1) and muskelin 1 antisense RNA (MKLN1-AS) were highly expressed in hepatocellular carcinoma and might be potential biomarkers in HCC by KM analysis and quantitative real-time PCR (RT-qPCR). This study demonstrated that lncRNA related to disulfidptosis could serve as a biomarker to predict prognosis and treatment targets for HCC.

Cuproptosis is an unusual form of cell death caused by copper accumulation in mitochondria. Cuproptosis is associated with hepatocellular carcinoma (HCC). Long noncoding RNAs (LncRNAs) have been shown to be effective prognostic biomarkers, yet the link between lncRNAs and cuproptosis remains unclear. We aimed to build a prognostic model of lncRNA risk and explore potential biomarkers of cuproptosis in HCC. Pearson correlations were used to derive lncRNAs co-expressed in cuproptosis. The model was constructed using Cox, Lasso, and multivariate Cox regressions. Kaplan–Meier survival analysis, principal components analysis, receiver operating characteristic curve, and nomogram analyses were carried out for validation. Seven lncRNAs were identified as prognostic factors. A risk model was an independent prognostic predictor. Among these seven lncRNAs, prostate cancer associated transcript 6 (PCAT6) is highly expressed in different types of cancer, activating Wnt, PI3K/Akt/mTOR, and other pathways; therefore, we performed further functional validation of PCAT6 in HCC. Reverse transcription–polymerase chain reaction results showed that PCAT6 was aberrantly highly expressed in HCC cell lines (HepG2 and Hep3B) compared to LO2 (normal hepatocytes). When its expression was knocked down, cells proliferated and migrated less. PCAT6 might be a potential biomarker for predicting prognosis in HCC.

Non-coding RNA (ncRNA) plays important roles in many critical regulation processes. Many ncRNAs perform their regulatory functions by the form of RNA-protein complexes. Therefore, identifying the interaction between ncRNA and protein is fundamental to understand functions of ncRNA. Under pressures from expensive cost of experimental techniques, developing an accuracy computational predictive model has become an indispensable way to identify ncRNA-protein interaction. A powerful predicting model of ncRNA-protein interaction needs a good feature set of characterizing the interaction. In this paper, a novel method is put forward to generate complex features for characterizing ncRNA-protein interaction (named CFRP). To obtain a comprehensive description of ncRNA-protein interaction, complex features are generated by non-linear transformations from the traditional k-mer features of ncRNA and protein sequences. To further reduce the dimensions of complex features, a group of discriminative features are selected by random forest. To validate the performances of the proposed method, a series of experiments are carried on several widely-used public datasets. Compared with the traditional k-mer features, the CFRP complex features can boost the performances of ncRNA-protein interaction prediction model. Meanwhile, the CFRP-based prediction model is compared with several state-of-the-art methods, and the results show that the proposed method achieves better performances than the others in term of the evaluation metrics. In conclusion, the complex features generated by CFRP are beneficial for building a powerful predicting model of ncRNA-protein interaction.

Background/Aims: Pulmonary arterial endothelial plexiform lesions are a basic pathological change associated with pulmonary vascular remodeling and are characterized by the formation of tumorlets as a result of over-growth of endothelial cells. Accumulating evidence suggests that platelet-derived growth factor (PDGF) participates in regulating the progression of pulmonary arterial hypertension. However, whether PDGF promotes the survival of pulmonary arterial endothelial cells (PAECs), as well as the specific molecular mechanisms that underlie its actions, remains unknown. Methods: MTT assays, caspase-3 and caspase-9 activity assays and western blot analysis were performed. Results: We found that both the mRNA and protein expression of PDGF-B was induced by hypoxia and that the inhibitory effects exerted by hypoxia on apoptosis were attenuated by inhibitors of PDGF beta. Moreover, PDGF-B inhibited apoptosis in a dose-dependent manner by stimulating the phosphorylation of both Akt and Stat3, and the PI3K/AKT pathway serves as an up-stream participant in the Stat3 activation stimulated by PDGF-B. Additionally, the anti-apoptotic effects of PDGF-B were abolished when PAECs were treated with either an inhibitor or small interfering RNA targeting Stat3. Conclusions: These observations suggest that PDGF-B is induced by hypoxia and protects against apoptosis via the PI3K/Akt/Stat3 signaling pathway.

Previous studies have highlighted that the transforming growth factor-β1 (TGF-β1) pathway may be activated by hypoxic conditions. TGF-β1 also participates in the regulation of proliferation, differentiation, migration and apoptosis of various cell types. Furthermore, TGF-β1 has been reported to participate in the regulation of the progression of pulmonary arterial hypertension (PAH). However, the effect of TGF-β1 on pulmonary arterial smooth muscle cells (PASMCs) and the corresponding molecular mechanisms remain unclear. The present study aimed to determine whether TGF-β1 protects against cell apoptosis in PASMCs, and identify the underlying molecular mechanisms. Western blotting, MTT and lactate dehydrogenase activity assays were performed, and the activity of caspase-3 and caspase-9 was detected in order to investigate the hypothesis. It was determined that TGF-β1 may facilitate cell growth in a dose-dependent manner in serum-starved PASMCs. Furthermore, it was observed that apoptosis in serum-starved PASMCs was inhibited by TGF-β1 via regulation of the expression levels of mitochondrial membrane proteins. Additionally, the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway was found to be activated by TGF-β1 in PASMCs, while the inhibition of PI3K/Akt signaling also prevented the apoptosis-limiting effects of TGF-β1. These observations suggest that TGF-β1 protects PASMCs from apoptosis and contributes to pulmonary vascular medial thickening via the PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]