Image_3_Bioinformatics analysis of potential common pathogenic mechanism for carotid atherosclerosis and Parkinson’s disease.TIF

BackgroundCerebrovascular disease (CVD) related to atherosclerosis and Parkinson’s disease (PD) are two prevalent neurological disorders. They share common risk factors and frequently occur together. The aim of this study is to investigate the association between atherosclerosis and PD using genetic databases to gain a comprehensive understanding of underlying biological mechanisms.MethodsThe gene expression profiles of atherosclerosis (GSE28829 and GSE100927) and PD (GSE7621 and GSE49036) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the common differentially expressed genes (DEGs) for these two disorders, we constructed protein-protein interaction (PPI) networks and functional modules, and further identified hub genes using Least Absolute Shrinkage and Selection Operator (LASSO) regression. The diagnostic effectiveness of these hub genes was evaluated using Receiver Operator Characteristic Curve (ROC) analysis. Furthermore, we used single sample gene set enrichment analysis (ssGSEA) to analyze immune cell infiltration and explored the association of the identified hub genes with infiltrating immune cells through Spearman’s rank correlation analysis in R software.ResultsA total of 50 shared DEGs, with 36 up-regulated and 14 down-regulated genes, were identified through the intersection of DEGs of atherosclerosis and PD. Using LASSO regression, we identified six hub genes, namely C1QB, CD53, LY96, P2RX7, C3, and TNFSF13B, in the lambda.min model, and CD14, C1QB, CD53, P2RX7, C3, and TNFSF13B in the lambda.1se model. ROC analysis confirmed that both models had good diagnostic efficiency for atherosclerosis datasets GSE28829 (lambda.min AUC = 0.99, lambda.1se AUC = 0.986) and GSE100927 (lambda.min AUC = 0.922, lambda.1se AUC = 0.933), as well as for PD datasets GSE7621 (lambda.min AUC = 0.924, lambda.1se AUC = 0.944) and GSE49036 (lambda.min AUC = 0.894, lambda.1se AUC = 0.881). Furthermore, we found that activated B cells, effector memory CD8 + T cells, and macrophages were the shared correlated types of immune cells in both atherosclerosis and PD.ConclusionThis study provided new sights into shared molecular mechanisms between these two disorders. These common hub genes and infiltrating immune cells offer promising clues for further experimental studies to explore the common pathogenesis of these disorders.</p

Image_2_Bioinformatics analysis of potential common pathogenic mechanism for carotid atherosclerosis and Parkinson’s disease.TIF

BackgroundCerebrovascular disease (CVD) related to atherosclerosis and Parkinson’s disease (PD) are two prevalent neurological disorders. They share common risk factors and frequently occur together. The aim of this study is to investigate the association between atherosclerosis and PD using genetic databases to gain a comprehensive understanding of underlying biological mechanisms.MethodsThe gene expression profiles of atherosclerosis (GSE28829 and GSE100927) and PD (GSE7621 and GSE49036) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the common differentially expressed genes (DEGs) for these two disorders, we constructed protein-protein interaction (PPI) networks and functional modules, and further identified hub genes using Least Absolute Shrinkage and Selection Operator (LASSO) regression. The diagnostic effectiveness of these hub genes was evaluated using Receiver Operator Characteristic Curve (ROC) analysis. Furthermore, we used single sample gene set enrichment analysis (ssGSEA) to analyze immune cell infiltration and explored the association of the identified hub genes with infiltrating immune cells through Spearman’s rank correlation analysis in R software.ResultsA total of 50 shared DEGs, with 36 up-regulated and 14 down-regulated genes, were identified through the intersection of DEGs of atherosclerosis and PD. Using LASSO regression, we identified six hub genes, namely C1QB, CD53, LY96, P2RX7, C3, and TNFSF13B, in the lambda.min model, and CD14, C1QB, CD53, P2RX7, C3, and TNFSF13B in the lambda.1se model. ROC analysis confirmed that both models had good diagnostic efficiency for atherosclerosis datasets GSE28829 (lambda.min AUC = 0.99, lambda.1se AUC = 0.986) and GSE100927 (lambda.min AUC = 0.922, lambda.1se AUC = 0.933), as well as for PD datasets GSE7621 (lambda.min AUC = 0.924, lambda.1se AUC = 0.944) and GSE49036 (lambda.min AUC = 0.894, lambda.1se AUC = 0.881). Furthermore, we found that activated B cells, effector memory CD8 + T cells, and macrophages were the shared correlated types of immune cells in both atherosclerosis and PD.ConclusionThis study provided new sights into shared molecular mechanisms between these two disorders. These common hub genes and infiltrating immune cells offer promising clues for further experimental studies to explore the common pathogenesis of these disorders.</p

Image_1_Bioinformatics analysis of potential common pathogenic mechanism for carotid atherosclerosis and Parkinson’s disease.TIF

BackgroundCerebrovascular disease (CVD) related to atherosclerosis and Parkinson’s disease (PD) are two prevalent neurological disorders. They share common risk factors and frequently occur together. The aim of this study is to investigate the association between atherosclerosis and PD using genetic databases to gain a comprehensive understanding of underlying biological mechanisms.MethodsThe gene expression profiles of atherosclerosis (GSE28829 and GSE100927) and PD (GSE7621 and GSE49036) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the common differentially expressed genes (DEGs) for these two disorders, we constructed protein-protein interaction (PPI) networks and functional modules, and further identified hub genes using Least Absolute Shrinkage and Selection Operator (LASSO) regression. The diagnostic effectiveness of these hub genes was evaluated using Receiver Operator Characteristic Curve (ROC) analysis. Furthermore, we used single sample gene set enrichment analysis (ssGSEA) to analyze immune cell infiltration and explored the association of the identified hub genes with infiltrating immune cells through Spearman’s rank correlation analysis in R software.ResultsA total of 50 shared DEGs, with 36 up-regulated and 14 down-regulated genes, were identified through the intersection of DEGs of atherosclerosis and PD. Using LASSO regression, we identified six hub genes, namely C1QB, CD53, LY96, P2RX7, C3, and TNFSF13B, in the lambda.min model, and CD14, C1QB, CD53, P2RX7, C3, and TNFSF13B in the lambda.1se model. ROC analysis confirmed that both models had good diagnostic efficiency for atherosclerosis datasets GSE28829 (lambda.min AUC = 0.99, lambda.1se AUC = 0.986) and GSE100927 (lambda.min AUC = 0.922, lambda.1se AUC = 0.933), as well as for PD datasets GSE7621 (lambda.min AUC = 0.924, lambda.1se AUC = 0.944) and GSE49036 (lambda.min AUC = 0.894, lambda.1se AUC = 0.881). Furthermore, we found that activated B cells, effector memory CD8 + T cells, and macrophages were the shared correlated types of immune cells in both atherosclerosis and PD.ConclusionThis study provided new sights into shared molecular mechanisms between these two disorders. These common hub genes and infiltrating immune cells offer promising clues for further experimental studies to explore the common pathogenesis of these disorders.</p

Image_2_Association Between Myasthenia Gravis and Memory: A Systematic Review and Meta-Analysis.pdf

Objective: The studies have produced contradictory results regarding the association between myasthenia gravis (MG) and cognitive function, especially for the cognitive domains of memory. This meta-analysis was dedicated to exploring the association between MG and memory, which was represented by the immediate recall and delayed recall.Methods: Using the random effects models, this study analyzed memory in MG based on data from the studies retrieved from four electronic databases from inception to February 2021. Disease severity was graded according to the Myasthenia Gravis Foundation of America (MGFA) classification. We defined ocular myasthenia gravis (OMG) (MGFA Grade I) as Class I, mild, and moderate generalized myasthenia gravis (GMG) (MGFA Grade IIa, IIb, IIIa, and IIIb) as Class II.Results: In total, eight studies of 274 patients and 211 healthy controls were included. The significant associations were found between MG and memory. Compared with the healthy control group, the patients with MG performed significantly worse in the terms of immediate recall [standardized mean difference (SMD) = −0.65, 95% CI = −0.97 to −0.33, P 2 = 64.1%] and delayed recall (SMD = −0.49, 95% CI = −0.88 to −0.1, P 2 = 76.3%). Compared with the patients with Class I MG, those with Class II MG did not have significantly different scores in immediate recall (SMD = −0.07, 95% CI = −0.35 to 0.21, P = 0.614, I2 = 0%) and delayed recall (SMD = 0.63, 95% CI = −0.29 to 1.55, P = 0.178, I2 = 87.9%).Conclusion: The patients with MG showed lower memory performance, such as both immediate and delayed recall ability. There was no association between the severity of MG and memory. Future studies should address whether these associations are casual and modifiable.</p

Image_1_Association Between Myasthenia Gravis and Memory: A Systematic Review and Meta-Analysis.pdf

Objective: The studies have produced contradictory results regarding the association between myasthenia gravis (MG) and cognitive function, especially for the cognitive domains of memory. This meta-analysis was dedicated to exploring the association between MG and memory, which was represented by the immediate recall and delayed recall.Methods: Using the random effects models, this study analyzed memory in MG based on data from the studies retrieved from four electronic databases from inception to February 2021. Disease severity was graded according to the Myasthenia Gravis Foundation of America (MGFA) classification. We defined ocular myasthenia gravis (OMG) (MGFA Grade I) as Class I, mild, and moderate generalized myasthenia gravis (GMG) (MGFA Grade IIa, IIb, IIIa, and IIIb) as Class II.Results: In total, eight studies of 274 patients and 211 healthy controls were included. The significant associations were found between MG and memory. Compared with the healthy control group, the patients with MG performed significantly worse in the terms of immediate recall [standardized mean difference (SMD) = −0.65, 95% CI = −0.97 to −0.33, P 2 = 64.1%] and delayed recall (SMD = −0.49, 95% CI = −0.88 to −0.1, P 2 = 76.3%). Compared with the patients with Class I MG, those with Class II MG did not have significantly different scores in immediate recall (SMD = −0.07, 95% CI = −0.35 to 0.21, P = 0.614, I2 = 0%) and delayed recall (SMD = 0.63, 95% CI = −0.29 to 1.55, P = 0.178, I2 = 87.9%).Conclusion: The patients with MG showed lower memory performance, such as both immediate and delayed recall ability. There was no association between the severity of MG and memory. Future studies should address whether these associations are casual and modifiable.</p

Table1_Characterization of the Different Subtypes of Immune Cell Infiltration to Aid Immunotherapy.XLS

Background?PD-1 ablation or PD-L1 specific monoclonal antibody against PD-1 can recruit the accumulation of functional T cells, leading to tumor rejection in the microenvironment and significantly improving the prognosis of various cancers. Despite these unprecedented clinical successes, intervention remission rates remain low after treatment, rarely exceeding 40%. The observation of PD-1/L1 blocking in patients is undoubtedly multifactorial, but the infiltrating degree of CD8+T cell may be an important factor for immunotherapeutic resistance.Methods:We proposed two computational algorithms to reveal the immune cell infiltration (ICI) landscape of 1646 lung adenocarcinoma patients. Three immune cell infiltration patterns were defined and the relative ICI scoring depended on principal-component analysis.Results:A high ICI score was associated with the increased tumor mutation burden and cell proliferation-related signaling pathways. Different cellular signaling pathways were observed in low ICI score subtypes, indicating active cell proliferation, and may be associated with poor prognosis.Conclusion:Our research identified that the ICI scores worked as an effective immunotherapy index, which may provide promising therapeutic strategies on immune therapeutics for lung adenocarcinoma.</p

Data_Sheet_1_Association Between Myasthenia Gravis and Memory: A Systematic Review and Meta-Analysis.pdf

Objective: The studies have produced contradictory results regarding the association between myasthenia gravis (MG) and cognitive function, especially for the cognitive domains of memory. This meta-analysis was dedicated to exploring the association between MG and memory, which was represented by the immediate recall and delayed recall.Methods: Using the random effects models, this study analyzed memory in MG based on data from the studies retrieved from four electronic databases from inception to February 2021. Disease severity was graded according to the Myasthenia Gravis Foundation of America (MGFA) classification. We defined ocular myasthenia gravis (OMG) (MGFA Grade I) as Class I, mild, and moderate generalized myasthenia gravis (GMG) (MGFA Grade IIa, IIb, IIIa, and IIIb) as Class II.Results: In total, eight studies of 274 patients and 211 healthy controls were included. The significant associations were found between MG and memory. Compared with the healthy control group, the patients with MG performed significantly worse in the terms of immediate recall [standardized mean difference (SMD) = −0.65, 95% CI = −0.97 to −0.33, P 2 = 64.1%] and delayed recall (SMD = −0.49, 95% CI = −0.88 to −0.1, P 2 = 76.3%). Compared with the patients with Class I MG, those with Class II MG did not have significantly different scores in immediate recall (SMD = −0.07, 95% CI = −0.35 to 0.21, P = 0.614, I2 = 0%) and delayed recall (SMD = 0.63, 95% CI = −0.29 to 1.55, P = 0.178, I2 = 87.9%).Conclusion: The patients with MG showed lower memory performance, such as both immediate and delayed recall ability. There was no association between the severity of MG and memory. Future studies should address whether these associations are casual and modifiable.</p

Image_2_Cuproptosis predicts the risk and clinical outcomes of lung adenocarcinoma.tif

Copper is an essential microelement for the body and a necessary coregulator for enzymatic reactions, yet an unbalanced copper level promotes reactive oxidation and cytotoxicity, which ultimately induces cell death. Several small molecules targeting copper-induced cell death have been investigated, yet few showed promising therapeutic effects in clinical trials. In March 2022, Science first introduced the concept and mechanisms of cuproptosis, suggesting that copper-induced cell death targets the tricarboxylic acid (TCA) cycle via protein lipoylation. Does this novel form of cell death take part in tumorigenesis or tumor progression? Is cuproptosis related to clinical outcomes of diseases? Is there a cuproptosis-related panel for clinical practice in cancer treatment? Herein, based on 942 samples of lung adenocarcinoma (LUAD), we analyzed on gene set level the existence and predictive value of cuproptosis in disease diagnosis and treatment. We screened out and identified the “cupLA” panel which indicates the risk of LUAD occurrence, clinicopathological features of LUAD patients, and could guide clinicians to refine LUAD subtypes and make treatment choices.</p

Image_3_Cuproptosis predicts the risk and clinical outcomes of lung adenocarcinoma.tif

Copper is an essential microelement for the body and a necessary coregulator for enzymatic reactions, yet an unbalanced copper level promotes reactive oxidation and cytotoxicity, which ultimately induces cell death. Several small molecules targeting copper-induced cell death have been investigated, yet few showed promising therapeutic effects in clinical trials. In March 2022, Science first introduced the concept and mechanisms of cuproptosis, suggesting that copper-induced cell death targets the tricarboxylic acid (TCA) cycle via protein lipoylation. Does this novel form of cell death take part in tumorigenesis or tumor progression? Is cuproptosis related to clinical outcomes of diseases? Is there a cuproptosis-related panel for clinical practice in cancer treatment? Herein, based on 942 samples of lung adenocarcinoma (LUAD), we analyzed on gene set level the existence and predictive value of cuproptosis in disease diagnosis and treatment. We screened out and identified the “cupLA” panel which indicates the risk of LUAD occurrence, clinicopathological features of LUAD patients, and could guide clinicians to refine LUAD subtypes and make treatment choices.</p

Table2_Development and validation of a TRP-related gene signature for overall survival prediction in lung adenocarcinoma.xlsx

The transient receptor potential (TRP) channel is a type of channel protein widely distributed in peripheral and central nervous systems. Genes encoding TRP can be regulated by natural aromatic substances and serve as a therapeutic target for many diseases. However, the role of TRP-related genes in lung adenocarcinoma (LUAD) remains unclear. In this study, we used data from TCGA to screen and identify 17 TRP-related genes that are differentially expressed between LUAD and normal lung tissues. Based on these differentially expressed genes (DEGs), we classified all patients with LUAD into two subtypes. Significant differences in prognosis, clinical features, and immune cell infiltration characteristics were observed between the two subtypes. Subsequently, a prognostic signature with 12 genes was established by applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, and all patients with LUAD were classified into low- and high-risk groups. Patients with LUAD in the low-risk group had a significantly longer survival time than those in the high-risk group (p < 0.001), which was confirmed by LUAD data from the GSE72094 and GSE68571 validation datasets. Combined with clinical characteristics, the risk score was found to be an independent predictor of overall survival (OS) in patients with LUAD. Additionally, patients with high TRP scores exhibited poorer clinical characteristics and immune status while showing a sensitive response to chemotherapeutic agents. In conclusion, the TRP score is a promising biomarker for determining the prognosis, molecular subtype, tumor microenvironment, and guiding personalized treatment in patients with LUAD.</p