Exploration of a predictive model based on genes associated with fatty acid metabolism and clinical treatment for head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent malignant tumors of the head and neck and presents high risks of recurrence and poor prognosis postoperatively. The aim of this study was to establish a predictive model based on fatty acid metabolism (FAM) genes to forecast the prognosis of HNSCC patients and the subsequent treatment strategies. METHODS: We accessed the TCGA and GEO databases for HNSCC genes and clinical data. The FAM risk score model was created and validated using a combination of univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) regression analysis. Combining risk scores and clinical characteristics, a nomogram was established and assessed. Subsequently, the function, gene mutation, immune difference, and chemotherapeutic drug sensitivity of the groups with high- and low-risk scores were analyzed. Consequently, the mode's validity was evaluated comprehensively by combining single gene analysis. RESULTS: The FAM risk score model for predicting HNSCC prognosis had certain validity. Patients in the high- and low-risk groups had genetic mutations, and the prognosis was the poorest for the high-risk groups with high genetic mutations. The patients with low-risk scores were suitable for immunotherapy since they had increased infiltration of immune cells. In contrast, the patients in the other groups were more suitable for chemotherapy. CONCLUSION: The results of this study demonstrated that the FAM risk score model may predict the prognosis of HSNCC and has a certain therapeutic guidance value.

Identification of cuproptosis-related subtypes and characterization of the tumor microenvironment landscape in head and neck squamous cell carcinoma.

BACKGROUND: Cuproptosis is considered a novel copper-dependent cell death model. In this study, we established a novel scoring system based on 10 cuproptosis-related genes (CRGs) to predict the prognosis and immune landscape of head and neck squamous cell carcinoma (HNSCC). METHODS: The RNA-seq data of HNSCC patients were downloaded from the GEO and TCGA databases and were merged into a novel HNSCC cohort. Multiomics landscape analyses were conducted, including tumor mutation burden (TMB), copy number variations and the interaction network of CRGs. Patients were then divided into different cuproptosis subtypes based on the expression of 10 CRGs and subsequently regrouped into novel gene clusters referring to differentially expressed genes. A cuproptosis score (CS) system was established using principal component analysis. The CIBERSORT, ssGSEA and ESTIMATE algorithms were used to assess the tumor immune microenvironment. Moreover, the immunotherapeutic and chemotherapeutic responses were assessed. RESULTS: Patients were divided into three cuproptosis subtypes and subsequently regrouped into three gene clusters, reflecting different immune infiltration. Assessed by the CS system, those with higher CSs exhibited worse prognosis and higher TMB frequency. Nevertheless, the immune-related analysis revealed patients in the low-CS group appeared immunosuppressive and easily suffered from immune escape. High CSs possibly show high expression of immune checkpoint genes and enhance chemotherapy sensitivity to cisplatin, docetaxel, and gemcitabine. CONCLUSION: We established a novel scoring system to predict the prognosis and immune landscape of HNSCC patients. This signature exhibits satisfactory predictive effects and the potential to guide comprehensive treatment for patients.

Construction of a necroptosis-related lncRNA signature to predict the prognosis and immune microenvironment of head and neck squamous cell carcinoma.

BACKGROUND: Previous studies have determined that necroptosis-related genes are potential biomarkers in head and neck squamous cell carcinoma (HNSCC). Herein, we established a novel risk model based on necroptosis-related lncRNAs (nrlncRNAs) to predict the prognosis of HNSCC patients. METHODS: Transcriptome and related information were obtained from TCGA database, and an nrlncRNA signature was established based on univariate Cox analysis and least absolute shrinkage and selection operator Cox regression. Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) analysis were used to evaluate the model, and a nomogram for survival prediction was established. Gene set enrichment analysis, immune analysis, drug sensitivity analysis, correlation with N6-methylandenosin (m6A), and tumor stemness analysis were performed. Furthermore, the entire set was divided into two clusters for further discussion. RESULTS: A novel signature was established with six nrlncRNAs. The areas under the ROC curves (AUCs) for 1-, 3-, and 5-year overall survival (OS) were 0.699, 0.686, and 0.645, respectively. Patients in low-risk group and cluster 2 had a better prognosis, more immune cell infiltration, higher immune function activity, and higher immune scores; however, patients in high-risk group and cluster 1 were more sensitive to chemotherapy. Moreover, the risk score had negative correlation with m6A-related gene expression and tumor stemness. CONCLUSION: According to this study, we constructed a novel signature with nrlncRNA pairs to predict the survival of HNSCC patients and guide immunotherapy and chemotherapy. This may possibly promote the development of individualized and precise treatment for HNSCC patients.

The possible mechanism of Hippophae fructus oil applied in tympanic membrane repair identified based on network pharmacology and molecular docking.

OBJECTIVE: This study aimed to explore the mechanisms of Hippophae fructus oil (HFO) in the treatment of tympanic membrane (TM) perforation through network pharmacology-based identification. METHODS: The compounds and related targets of HFO were extracted from the TCMSP database, and disease information was obtained from the OMIM, GeneCards, PharmGkb, TTD, and DrugBank databases. A Venn diagram was generated to show the common targets of HFO and TM, and GO and KEGG analyses were performed to explore the potential biological processes and signaling pathways. The PPI network and core gene subnetwork were constructed using the STRING database and Cytoscape software. A molecular docking analysis was also conducted to simulate the combination of compounds and gene proteins. RESULTS: A total of 33 compounds and their related targets were obtained from the TCMSP database. After screening the 393 TM-related targets, 21 compounds and 22 gene proteins were selected to establish the network diagram. GO and KEGG enrichment analyses revealed that HFO may promote TM healing by influencing cellular oxidative stress and related signaling pathways. A critical subnetwork was obtained by analyzing the PPI network with nine core genes: CASP3, MMP2, IL1B, TP53, EGFR, CXCL8, ESR1, PTGS2, and IL6. In addition, a molecular docking analysis revealed that quercetin strongly binds the core proteins. CONCLUSION: According to the analysis, HFO can be utilized to repair perforations by influencing cellular oxidative stress. Quercetin is one of the active compounds that potentially plays an important role in TM regeneration by influencing 17 gene proteins.

Association of anaemia on heart failure and left ventricular function: A bidirectional Mendelian randomization study.

AIMS: Observational studies have suggested that anaemia is associated with an increased risk of heart failure (HF). But the potential causal association is not clear. We aimed to investigate the association between anaemia and HF risk. METHODS AND RESULTS: A Mendelian randomization (MR) analysis was performed to confirm the causal association of anaemia with the risk of HF and left ventricular structure and function. Furthermore, a reverse-direction MR analyses was conducted to assess the causal effect of HF on anaemia. The MR analysis indicated that genetically predicted anaemia is associated with the increased risk of HF (meta: odd ratio (OR) = 1.12; 95% confidence interval (CI) [1.04, 1.20]; P = 0.002), and left ventricular mass index (ß = 1.051; 95% CI [0.384, 1.718]; P = 0.002), left ventricular mass (ß = 2.063; 95% CI [0.578, 3.547]; P = 0.006), left atrial minimum volume (ß = 0.076; 95% CI [0.008, 0.143]; P = 0.028), and left atrial maximum volume (ß = 0.090; 95% CI [0.023, 0.157]; P = 0.009). In the reverse-direction MR analyses, we found that genetic susceptibility to HF was significantly associated with the increased risk of anaemia (meta: OR = 1.40; 95% CI [1.24, 1.59]; P = 1.79 × 10-7 ). CONCLUSIONS: This MR study supports the genetic evidence that there is bidirectional causality between anaemia and the risk of HF as well as anaemia may cause left ventricular hypertrophy and enlargement of the left atrium. Considering the adverse causal effects between the two diseases, more attention should be paid to the prevention and treatment of anaemia in patients with HF.

Fabrication and Evaluation of Hyaluronidase-Responsive Scaffolds by Electrospinning with Antibacterial Properties for Tympanic Membrane Repair.

Tympanic membrane perforation (TMP) is prevalent in clinical settings. Patients with TMPs often suffer from infections caused by Staphylococcus aureus and Pseudomonas aeruginosa, leading to middle ear and external ear canal infections, which hinder eardrum healing. The objective of this study is to fabricate an enzyme-responsive antibacterial electrospun scaffold using poly(lactic-co-glycolic acid) and hyaluronic acid for the treatment of infected TMPs. The properties of the scaffold were characterized, including morphology, wettability, mechanical properties, degradation properties, antimicrobial properties, and biocompatibility. The results indicated that the fabricated scaffold had a core-shell structure and exhibited excellent mechanical properties, hydrophobicity, degradability, and cytocompatibility. Furthermore, in vitro bacterial tests and ex vivo investigations on eardrum infections suggested that this scaffold possesses hyaluronidase-responsive antibacterial properties. It may rapidly release antibiotics when exposed to the enzyme released by S. aureus and P. aeruginosa. These findings suggest that the scaffold has great potential for repairing TMPs with infections.

Identification of a cuproptosis-related lncRNA signature to predict the prognosis and immune landscape of head and neck squamous cell carcinoma.

Background: Cuproptosis is considered a novel copper-induced cell death model regulated by targeting lipoylated TCA cycle proteins. In this study, we established a novel signature based on cuproptosis-related lncRNAs (crlncRNAs) to predict the prognosis and immune landscape of head and neck squamous cell carcinoma. Methods: RNA-seq matrix, somatic mutation files, and clinical data were obtained from The Cancer Genome Atlas database. After dividing patients into two sets, a crlncRNA signature was established based on survival related crlncRNAs, which were selected by the univariate Cox analysis and least absolute shrinkage and selection operator Cox regression. To evaluate the model, Kaplan-Meier survival analysis and time-dependent receiver operating characteristic (ROC) were utilized, and a nomogram was established for survival prediction. Immune landscape analysis, drug sensitivity, cluster analysis, tumor mutation burden (TMB) and ceRNA network analysis were conducted subsequently. Results: A crlncRNA related prognosis signature was finally constructed with 12 crlncRNAs. The areas under the ROC curves (AUCs) were 0.719, 0.705 and 0.693 respectively for 1, 3, and 5-year's overall survival (OS). Patients in the low-risk group behaved a better prognosis, lower TMB, higher immune function activity and scores. In addition, patients from cluster 2 were more sensitive to chemotherapy and immunotherapy. Conclusion: In this study, we constructed a novel crlncRNA risk model to predict the survival of HNSCC patients. This reliable and acceptable prognostic signature may guide and promote the progress of novel treatment strategies for HNSCC patients.

Supertough and highly stretchable silk protein-based films with controlled biodegradability.

Naturally derived protein-based biopolymers are considered potential biomaterials in biomedical applications and eco-friendly materials for replacing current petroleum-based polymers due to their good biocompatibility, low environmental impact, and tunable degradability. However, current strategies for fabricating protein-based materials with superior properties and tailored functionality in a scalable manner are still lacking. Here, we demonstrate an aqueous-based scalable approach for fabricating silk protein-based films through controlled molecular self-assembly (CMS) of silk proteins with plasticizers and salt ions. The films fabricated using this method can achieve a toughness of up to 64±5 MJ/m3 with a stretchability of up to 574±31%. We also demonstrate the tunable enzymatic degradability, low in vitro cytotoxicity, and good in vivo biocompatibility of the films. Furthermore, the films can be patterned with predesigned complex structures through laser cutting and functionalized with bioactive components. The functional silk protein-based films show great potential in various applications, including flexible electronics, bioelectronics, tissue engineering, and bioplastic packaging. STATEMENT OF SIGNIFICANCE: Inspired by the naturally optimized multi-scale self-assembly of silk proteins in natural silks, we develop an aqueous-based approach for scalable production of superior protein-based films through controlled molecular self-assembly (CMS) of silk proteins with glycerol and calcium ions. The prepared silk films present outstanding mechanical properties, controlled enzymatic biodegradability, low in vitro cytotoxicity, and good in vivo biocompatibility. Notably, the films fabricated using this method can achieve a high toughness of 64±5 MJ/m3 with a stretchability of 594±31%. The approach introduced in this work provides a facile route toward making silk-based materials with superior properties. It also paves new avenues for developing functional protein-based materials with precisely controlled structures and properties for various applications.

Pyocyanin induces NK92 cell apoptosis via mitochondrial damage and elevated intracellular Ca2.

Pseudomonas aeruginosa-derived pigment pyocyanin (PCN) has been proved to induce cell apoptosis mediated by the generation of reactive oxygen species (ROS), which has been studied mainly in epithelial cells and neutrophils. However, we previously found that the PCN-producing strain PA14 induces cell apoptosis in human NK cell line NK92 more effectively than in PCN-deficient strain PA14-phZ1/2 via a yet undetermined mechanism. In the current study, we found that PCN-induced NK92 cell apoptosis occurs through mitochondrial damage despite inhibiting intracellular ROS generation. Intracellular Ca2+ ([Ca2+]i) and Bcl-2 family proteins act as important "priming signals" for apoptosis. PCN treatment increased [Ca2+]i in NK92 cells more than twofold after 2 h stimulation, whereas the Ca2+-chelating agent ethylene glycol tetra-acetic acid (EGTA) inhibited apoptosis. PCN triggered the activation of Bim, Bid, Bik, Bak, and phospho-Bad in NK92 cells in a concentration-dependent manner, but these pro-apoptotic Bcl-2 family proteins were not inhibited by EGTA. In this study, we describe the function of PCN in NK92 cells and identify mitochondrial damage as the mechanism underlying the apoptosis. [Ca2+]i and pro-apoptotic Bcl-2 family proteins are novel targets for PCN-induced apoptosis. Clarification of the cytotoxic diversity of PCN provides a new therapeutic target for defense from P. aeruginosa-induced immune cell damage.