Electrospun mupirocin loaded polyurethane fiber mats for anti-infection burn wound dressing application

<p>Wound care treatment is a serious issue faced by the medical staffs due to its variety and complexity. Wound dressings are typically used to manage the various types of wounds. In this study, polyurethane (PU) fibers containing mupirocin (Mu), a commonly used antibiotic in wound care, were fabricated via electrospinning technique. The aim of this study was to develop biomedical electrospun fiber scaffolds for preventing wound infections with good compatibility and to demonstrate their applications as anti-infective burn wound dressings. The surface morphology of fibers was obtained by scanning electron microscopy. FT-IR spectra, water vapor transmission rate, and drug release study <i>in vitro</i> were tested to demonstrate the fiber scaffold characteristic. The prepared PU/Mu composite scaffolds had satisfactory antibacterial activity especially against <i>Staphylococcus aureus</i>. The cell studies revealed that the scaffolds were biocompatible and safe for cell attachment. Histological and immunohistochemical examinations were performed in rats, and the results indicated the histological analysis of tissue stained with H&E showed no obvious inflammation reaction. The results indicated that the electrospun scaffolds were capable of loading and delivering drugs, and could be potentially used as novel antibacterial burn wound dressings.</p

Table2_A Wnt-related gene expression signature to improve the prediction of prognosis and tumor microenvironment in gastric cancer.DOCX

Background: Most gastric cancer (GC) patients were diagnosed in the advanced stages without obvious symptoms, which resulted in the increased risk of death. Although the combination therapies have showed survival benefit of patients, there is still urgent need to explore the underlying mechanisms of GC development and potential novel targets for clinical applications. Numerous studies have reported the upregulation of Wnt signaling pathway in human GC, which play important role during GC development and progression. However, the current understanding of Wnt signaling pathway is still limited due to its complexity and contradictory effect on different stages of GC tumor microenvironment.Method: We used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset to screen Wnt signaling pathway-associated genes by ssGSEA and correlation analysis. Three molecular subtypes were constructed based on a consistent clustering analysis. The key Wnt-related genes were screened through univariate cox analysis, lasso, and stepwise regression. In addition, the Gene Set Enrichment Analysis (GSEA) were performed to explore potential molecular pathways regulated by the Wnt-related gene signatures. ESTIMATE was utilized for evaluating the immune cell populations in GC tumor microenvironment.Results: Three molecular subtypes associated to Wnt were identified, and 7 key Wnt-related genes were screened to establish a predictive RiskScore model. These three molecular subtypes showed significant prognostic differences and distinct functional signaling pathways. We also found the downregulated immune checkpoint expression in the clust1 with good prognosis. The RiskScore model was successfully validated in GSE26942 dataset. Nomogram based on RiskScore and Gender had better prognostic predictive ability.Conclusion: In summary, our study showed that the Wnt-related genes could be used to predict prognosis of GC patients. The risk model we established showed high accuracy and survival prediction capability.</p

Image3_A Wnt-related gene expression signature to improve the prediction of prognosis and tumor microenvironment in gastric cancer.JPEG

Background: Most gastric cancer (GC) patients were diagnosed in the advanced stages without obvious symptoms, which resulted in the increased risk of death. Although the combination therapies have showed survival benefit of patients, there is still urgent need to explore the underlying mechanisms of GC development and potential novel targets for clinical applications. Numerous studies have reported the upregulation of Wnt signaling pathway in human GC, which play important role during GC development and progression. However, the current understanding of Wnt signaling pathway is still limited due to its complexity and contradictory effect on different stages of GC tumor microenvironment.Method: We used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset to screen Wnt signaling pathway-associated genes by ssGSEA and correlation analysis. Three molecular subtypes were constructed based on a consistent clustering analysis. The key Wnt-related genes were screened through univariate cox analysis, lasso, and stepwise regression. In addition, the Gene Set Enrichment Analysis (GSEA) were performed to explore potential molecular pathways regulated by the Wnt-related gene signatures. ESTIMATE was utilized for evaluating the immune cell populations in GC tumor microenvironment.Results: Three molecular subtypes associated to Wnt were identified, and 7 key Wnt-related genes were screened to establish a predictive RiskScore model. These three molecular subtypes showed significant prognostic differences and distinct functional signaling pathways. We also found the downregulated immune checkpoint expression in the clust1 with good prognosis. The RiskScore model was successfully validated in GSE26942 dataset. Nomogram based on RiskScore and Gender had better prognostic predictive ability.Conclusion: In summary, our study showed that the Wnt-related genes could be used to predict prognosis of GC patients. The risk model we established showed high accuracy and survival prediction capability.</p

Image1_A Wnt-related gene expression signature to improve the prediction of prognosis and tumor microenvironment in gastric cancer.JPEG

Background: Most gastric cancer (GC) patients were diagnosed in the advanced stages without obvious symptoms, which resulted in the increased risk of death. Although the combination therapies have showed survival benefit of patients, there is still urgent need to explore the underlying mechanisms of GC development and potential novel targets for clinical applications. Numerous studies have reported the upregulation of Wnt signaling pathway in human GC, which play important role during GC development and progression. However, the current understanding of Wnt signaling pathway is still limited due to its complexity and contradictory effect on different stages of GC tumor microenvironment.Method: We used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset to screen Wnt signaling pathway-associated genes by ssGSEA and correlation analysis. Three molecular subtypes were constructed based on a consistent clustering analysis. The key Wnt-related genes were screened through univariate cox analysis, lasso, and stepwise regression. In addition, the Gene Set Enrichment Analysis (GSEA) were performed to explore potential molecular pathways regulated by the Wnt-related gene signatures. ESTIMATE was utilized for evaluating the immune cell populations in GC tumor microenvironment.Results: Three molecular subtypes associated to Wnt were identified, and 7 key Wnt-related genes were screened to establish a predictive RiskScore model. These three molecular subtypes showed significant prognostic differences and distinct functional signaling pathways. We also found the downregulated immune checkpoint expression in the clust1 with good prognosis. The RiskScore model was successfully validated in GSE26942 dataset. Nomogram based on RiskScore and Gender had better prognostic predictive ability.Conclusion: In summary, our study showed that the Wnt-related genes could be used to predict prognosis of GC patients. The risk model we established showed high accuracy and survival prediction capability.</p

Image2_A Wnt-related gene expression signature to improve the prediction of prognosis and tumor microenvironment in gastric cancer.JPEG

Background: Most gastric cancer (GC) patients were diagnosed in the advanced stages without obvious symptoms, which resulted in the increased risk of death. Although the combination therapies have showed survival benefit of patients, there is still urgent need to explore the underlying mechanisms of GC development and potential novel targets for clinical applications. Numerous studies have reported the upregulation of Wnt signaling pathway in human GC, which play important role during GC development and progression. However, the current understanding of Wnt signaling pathway is still limited due to its complexity and contradictory effect on different stages of GC tumor microenvironment.Method: We used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset to screen Wnt signaling pathway-associated genes by ssGSEA and correlation analysis. Three molecular subtypes were constructed based on a consistent clustering analysis. The key Wnt-related genes were screened through univariate cox analysis, lasso, and stepwise regression. In addition, the Gene Set Enrichment Analysis (GSEA) were performed to explore potential molecular pathways regulated by the Wnt-related gene signatures. ESTIMATE was utilized for evaluating the immune cell populations in GC tumor microenvironment.Results: Three molecular subtypes associated to Wnt were identified, and 7 key Wnt-related genes were screened to establish a predictive RiskScore model. These three molecular subtypes showed significant prognostic differences and distinct functional signaling pathways. We also found the downregulated immune checkpoint expression in the clust1 with good prognosis. The RiskScore model was successfully validated in GSE26942 dataset. Nomogram based on RiskScore and Gender had better prognostic predictive ability.Conclusion: In summary, our study showed that the Wnt-related genes could be used to predict prognosis of GC patients. The risk model we established showed high accuracy and survival prediction capability.</p

Table1_A Wnt-related gene expression signature to improve the prediction of prognosis and tumor microenvironment in gastric cancer.DOCX

Background: Most gastric cancer (GC) patients were diagnosed in the advanced stages without obvious symptoms, which resulted in the increased risk of death. Although the combination therapies have showed survival benefit of patients, there is still urgent need to explore the underlying mechanisms of GC development and potential novel targets for clinical applications. Numerous studies have reported the upregulation of Wnt signaling pathway in human GC, which play important role during GC development and progression. However, the current understanding of Wnt signaling pathway is still limited due to its complexity and contradictory effect on different stages of GC tumor microenvironment.Method: We used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset to screen Wnt signaling pathway-associated genes by ssGSEA and correlation analysis. Three molecular subtypes were constructed based on a consistent clustering analysis. The key Wnt-related genes were screened through univariate cox analysis, lasso, and stepwise regression. In addition, the Gene Set Enrichment Analysis (GSEA) were performed to explore potential molecular pathways regulated by the Wnt-related gene signatures. ESTIMATE was utilized for evaluating the immune cell populations in GC tumor microenvironment.Results: Three molecular subtypes associated to Wnt were identified, and 7 key Wnt-related genes were screened to establish a predictive RiskScore model. These three molecular subtypes showed significant prognostic differences and distinct functional signaling pathways. We also found the downregulated immune checkpoint expression in the clust1 with good prognosis. The RiskScore model was successfully validated in GSE26942 dataset. Nomogram based on RiskScore and Gender had better prognostic predictive ability.Conclusion: In summary, our study showed that the Wnt-related genes could be used to predict prognosis of GC patients. The risk model we established showed high accuracy and survival prediction capability.</p

High Fat Diet and High Sucrose Intake Divergently Induce Dysregulation of Glucose Homeostasis through Distinct Gut Microbiota-Derived Bile Acid Metabolism in Mice

A high calorie diet such as excessive fat and sucrose intake is always accompanied by impaired glucose homeostasis such as T2DM (type 2 diabetes mellitus). However, it remains unclear how fat and sucrose individually affect host glucose metabolism. In this study, mice were fed with high fat diet (HFD) or 30% sucrose in drinking water (HSD) for 24 weeks, and glucose metabolism, gut microbiota composition, as well as bile acid (BA) profile were investigated. In addition, the functional changes of HFD or HSD-induced gut microbiota were further verified by fecal microbiota transplantation (FMT) and ex vivo culture of gut bacteria with BAs. Our results showed that both HFD and HSD caused dysregulated lipid metabolism, while HFD feeding had a more severe effect on impaired glucose homeostasis, accompanied by reduced hyocholic acid (HCA) levels in all studied tissues. Meanwhile, HFD had a more dramatic influence on composition and function of gut microbiota based on α diversity indices, β diversity analysis, as well as the abundance of secondary BA producers than HSD. In addition, the phenotypes of impaired glucose homeostasis and less formation of HCA caused by HFD can be transferred to recipient mice by FMT. Ex vivo culture with gut bacteria and BAs revealed HFD-altered gut bacteria produced less HCA than HSD, which might closely associate with reduced relative abundance of C7 epimerase-coding bacteria g_norank/unclassified_f_Eggerthellaceae and bile salt hydrolase-producing bacteria Lactobacillus and Bifidobacterium in HFD group. Our findings revealed that the divergent effects of different high-calorie diets on glucose metabolism may be due to the gut microbiota-mediated generation and metabolism of BAs, highlighting the importance of dietary management in T2DM