Intracerebral Hemorrhage Prognosis Classification via Joint-Attention Cross-Modal Network.

Intracerebral hemorrhage (ICH) is a critical condition characterized by a high prevalence, substantial mortality rates, and unpredictable clinical outcomes, which results in a serious threat to human health. Improving the timeliness and accuracy of prognosis assessment is crucial to minimizing mortality and long-term disability associated with ICH. Due to the complexity of ICH, the diagnosis of ICH in clinical practice heavily relies on the professional expertise and clinical experience of physicians. Traditional prognostic methods largely depend on the specialized knowledge and subjective judgment of healthcare professionals. Meanwhile, existing artificial intelligence (AI) methodologies, which predominantly utilize features derived from computed tomography (CT) scans, fall short of capturing the multifaceted nature of ICH. Although existing methods are capable of integrating clinical information and CT images for prognosis, the effectiveness of this fusion process still requires improvement. To surmount these limitations, the present study introduces a novel AI framework, termed the ICH Network (ICH-Net), which employs a joint-attention cross-modal network to synergize clinical textual data with CT imaging features. The architecture of ICH-Net consists of three integral components: the Feature Extraction Module, which processes and abstracts salient characteristics from the clinical and imaging data, the Feature Fusion Module, which amalgamates the diverse data streams, and the Classification Module, which interprets the fused features to deliver prognostic predictions. Our evaluation, conducted through a rigorous five-fold cross-validation process, demonstrates that ICH-Net achieves a commendable accuracy of up to 87.77%, outperforming other state-of-the-art methods detailed within our research. This evidence underscores the potential of ICH-Net as a formidable tool in prognosticating ICH, promising a significant advancement in clinical decision-making and patient care.

Coaxial 3D Bioprinting Process Research and Performance Tests on Vascular Scaffolds.

Three-dimensionally printed vascularized tissue, which is suitable for treating human cardiovascular diseases, should possess excellent biocompatibility, mechanical performance, and the structure of complex vascular networks. In this paper, we propose a method for fabricating vascularized tissue based on coaxial 3D bioprinting technology combined with the mold method. Sodium alginate (SA) solution was chosen as the bioink material, while the cross-linking agent was a calcium chloride (CaCl2) solution. To obtain the optimal parameters for the fabrication of vascular scaffolds, we first formulated theoretical models of a coaxial jet and a vascular network. Subsequently, we conducted a simulation analysis to obtain preliminary process parameters. Based on the aforementioned research, experiments of vascular scaffold fabrication based on the coaxial jet model and experiments of vascular network fabrication were carried out. Finally, we optimized various parameters, such as the flow rate of internal and external solutions, bioink concentration, and cross-linking agent concentration. The performance tests showed that the fabricated vascular scaffolds had levels of satisfactory degradability, water absorption, and mechanical properties that meet the requirements for practical applications. Cellular experiments with stained samples demonstrated satisfactory proliferation of human umbilical vein endothelial cells (HUVECs) within the vascular scaffold over a seven-day period, observed under a fluorescent inverted microscope. The cells showed good biocompatibility with the vascular scaffold. The above results indicate that the fabricated vascular structure initially meet the requirements of vascular scaffolds.

SET and MYND domain-containing protein 3 inhibits tumor cell sensitivity to cisplatin.

Cisplatin resistance has been a major factor limiting its clinical use as a chemotherapy drug. The present study aimed to investigate whether SET and MYND domain-containing protein 3 (SMYD3), a histone methyltransferase closely associated with tumors can affect the sensitivity of tumors to cisplatin chemotherapy. Real time-qPCR, western blotting, the luciferase reporter, MTT and clonogenic assays were performed to detect the effects of SMYD3 on the chemotherapy capacity of cisplatin. In the present study, SMYD3 exhibited different expression patterns in MCF-7 and T47D breast cancer cells. In addition, this differential expression was associated with tumor cell resistance to cisplatin. Furthermore, SMYD3 knockdown following small interfering RNA transfection increased cisplatin sensitivity, whereas SMYD3 overexpression decreased cisplatin sensitivity. In addition, SMYD3 knockdown synergistically enhanced cisplatin-induced cell apoptosis. SMYD3 expression was downregulated during cisplatin treatment. In addition, transcriptional regulatory activities of SMYD3 3'-untranslated region were also downregulated. These results suggested that SMYD3 may affect cell sensitivity to cisplatin and participate in the development of cisplatin resistance, which is a process that may involve microRNA-124-mediated regulation.

MicroRNA-588 regulates invasion, migration and epithelial-mesenchymal transition via targeting EIF5A2 pathway in gastric cancer.

BACKGROUND: miRNAs are potential regulators of genes in many cancers. Here, we confirmed that the expression of miR-588 decreased in gastric cancer (GC) tissues and cells. MATERIALS AND METHODS: Sixty-seven GC tissues along with noncancerous tissues adjacent to them were included in the study. Quantitative real-time reverse transcription-PCR study was done to quantify the expression levels of mature miRNA. The expression of proteins was determined by Western blot and transwell chamber assay for invasion and migration studies. Immunohistochemical analysis and luciferase assay were done for evaluating the expression of epithelial-mesenchymal transition (EMT) markers and activity of EIF5A2, respectively. In vivo metastatic assay was done by injecting MGC-803 cells into nude mice. RESULTS: In the 5-year predicted survival study of GC patients included in the study, we found that miR-588 acted as a specific prognostic marker. Overexpression of miR-588 resulted in suppression of cell invasion, migration and progression of EMT, whereas suppression of miR-588 inverted the effects in both in vivo and in vitro experiments. miR-588 retained EIF5A2 by directly binding to the 3'-UTR. EIF5A2 was overexpressed in GC tissue samples, and the expression of miR-588 was inversely correlated to the levels of EIF5A2. The impact of miR-588 on invasion, migration and progression of EMT may be partially due to miR-588-mediated alterations of EiF5A2. CONCLUSION: Overall, the findings of the study suggest that miR-588 acts as a tumor suppressor by regulating the invasion, migration and EMT via EIF5A2 pathway, hence presenting miR-588 as a prognostic marker as well as a therapeutic target for GC.

MiR-373 drives the epithelial-to-mesenchymal transition and metastasis via the miR-373-TXNIP-HIF1α-TWIST signaling axis in breast cancer.

Our previous proteomics study revealed that thioredoxin-interacting protein (TXNIP) was down-regulated by miR-373. However, little is known of the mechanism by which miR-373 decreases TXNIP to stimulate metastasis. In this study, we show that miR-373 promotes the epithelial-to-mesenchymal transition (EMT) in breast cancer. MiR-373 suppresses TXNIP by binding to the 3'UTR of TXNIP, which in turn, induces cancer cell EMT and metastasis. TXNIP co-expression, but not the TXNIP-3'UTR, reverses the enhancement of EMT, migration, invasion and metastasis induced by miR-373. MiR-373 stimulates EMT, migration and invasion through TXNIP-dependent reactive oxygen species (ROS) reduction. Mechanistically, miR-373 up-regulates and activates the HIF1α-TWIST signaling axis via the TXNIP pathway. Consequently, TWIST induces miR-373 expression by binding to the promoter of the miR-371-373 cluster. Clinically, miR-373 is negatively associated with TXNIP and positively associated with HIF1α and TWIST, and activation of the miR-373-TXNIP-HIF1α-TWIST signaling axis is correlated with a worse outcome in patients with breast cancer. This signaling axis may be an independent prognostic factor for patients with breast cancer.

ACK1 promotes gastric cancer epithelial-mesenchymal transition and metastasis through AKT-POU2F1-ECD signalling.

Amplification of the activated Cdc42-associated kinase 1 (ACK1) gene is frequent in gastric cancer (GC). However, little is known about the clinical roles and molecular mechanisms of ACK1 abnormalities in GC. Here, we found that the ACK1 protein level and ACK1 phosphorylation at Tyr 284 were frequently elevated in GC and associated with poor patient survival. Ectopic ACK1 expression in GC cells induced epithelial-mesenchymal transition (EMT) and promoted migration and invasion in vitro, and metastasis in vivo; the depletion of ACK1 induced the opposite effects. We utilized SILAC quantitative proteomics to discover that the level of the cell cycle-related protein ecdysoneless homologue (ECD) was markedly altered by ACK1. Overexpression of ECD promoted EMT, migration, and invasion in GC, similar to the effects of ACK1 overexpression. Silencing of ECD completely blocked the augmentation of ACK1 overexpression-induced EMT, migration, and invasion. Mechanistically, ACK1 phosphorylated AKT at Thr 308 and Ser 473 and activated the AKT pathway to up-regulate the transcription factor POU2F1, which directly bound to the promoter region of its novel target gene ECD and thus regulated ECD expression in GC cells. Furthermore, the phosphorylation levels of AKT at Thr 308 and Ser 473 and POU2F1 and ECD levels were positively associated with ACK1 levels in clinical GC specimens. Collectively, we have demonstrated that ACK1 promotes EMT, migration, and invasion by activating AKT-POU2F1-ECD signalling in GC cells. ACK1 may be employed as a new prognostic factor and therapeutic target for GC.

Quercetin differently regulates insulin-mediated glucose transporter 4 translocation under basal and inflammatory conditions in adipocytes.

SCOPE: Quercetin is the most abundant dietary flavonol with beneficial regulation of glucose homeostasis, but its regulation of insulin action remains uncertain. This study aims to investigate the effects of quercetin on insulin-mediated glucose transporter 4 (GLUT4) translocation under basal and inflammatory conditions as well as the molecular mechanisms in adipocytes. METHODS AND RESULTS: The effects of quercetin on insulin-mediated GLUT4 translocation in 3T3-L1 cells under basal and insulin resistant conditions were investigated. Meanwhile, we investigated the effect of quercetin on AMP-activated protein kinase (AMPK) activation implicated in regulation of insulin action. Quercetin inhibited insulin-mediated GLUT4 translocation by inhibiting AS160 phosphorylation. Differently, when inflammatory challenge impaired insulin action in 3T3-L1 cells, quercetin inhibited IκB kinase ß (IKKß) phosphorylation and facilitated insulin signaling, leading to the restoration of insulin-mediated AS160 phosphorylation and downstream GLUT4 translocation. AMPK inhibitor Compound C or knockdown of AMPKα by small interfering RNA (siRNA) abolished both actions of quercetin. Results from mice adipose tissue (AT) further confirmed its positive regulation of AMPK phosphorylation and opposite effects on AS160 phosphorylation in vivo. CONCLUSION: Quercetin demonstrated divergent effects on insulin-mediated GLUT4 translocation in adipocytes under basal and insulin resistant conditions, which were related to its regulation of AMPK activity.

Quantitative proteomics characterization on the antitumor effects of isodeoxyelephantopin against nasopharyngeal carcinoma.

Isolated from Elephantopus scaber L., a Chinese medicinal herb that is widely used to prevent and treat cancers in China, isodeoxyelephantopin (ESI) exerted antitumor effects on several cancer cells. However, its antitumor mechanism is still not clear. In this study, we found that ESI could induce G2/M arrest and subsequently stimulate cell apoptosis in dose- and time-dependent manners. We used SILAC quantitative proteomics to identify ESI-regulated proteins in cancer cells, and found that 124 proteins were significantly altered in expression. Gene ontology and Ingenuity Pathway Analysis revealed that these proteins were mainly involved in the regulation of oxidative stress and inflammation response. Functional studies demonstrated that ESI induced G2/M arrest and apoptosis by inducing ROS generation, and that antioxidant N-acetyl-l-cysteine could block the ESI-induced antitumor effects. Accumulated ROS resulted in DNA breakage, subsequent G2/M arrest and mitochondrial-mediated apoptosis. ESI upregulated the expression of anticancer inflammation factors IL-12a, IFN-α, and IFN-ß through ROS-dependent and independent pathways. The current work reveals that ESI exerts its antitumor effects through ROS-dependent DNA damage, mitochondrial-mediated apoptosis mechanism and antitumor inflammation factor pathway.