Image_5_Cromolyn prevents cerebral vasospasm and dementia by targeting WDR43.TIF

BackgroundCerebral vasospasm (CV) can cause inflammation and damage to neuronal cells in the elderly, leading to dementia.PurposeThis study aimed to investigate the genetic mechanisms underlying dementia caused by CV in the elderly, identify preventive and therapeutic drugs, and evaluate their efficacy in treating neurodegenerative diseases.MethodsGenes associated with subarachnoid hemorrhage and CV were acquired and screened for differentially expressed miRNAs (DEmiRNAs) associated with aneurysm rupture. A regulatory network of DEmiRNAs and mRNAs was constructed, and virtual screening was performed to evaluate possible binding patterns between Food and Drug Administration (FDA)-approved drugs and core proteins. Molecular dynamics simulations were performed on the optimal docked complexes. Optimally docked drugs were evaluated for efficacy in the treatment of neurodegenerative diseases through cellular experiments.ResultsThe study found upregulated genes (including WDR43 and THBS1) and one downregulated gene associated with aneurysm rupture. Differences in the expression of these genes indicate greater disease risk. DEmiRNAs associated with ruptured aortic aneurysm were identified, of which two could bind to THBS1 and WDR43. Cromolyn and lanoxin formed the best docking complexes with WDR43 and THBS1, respectively. Cellular experiments showed that cromolyn improved BV2 cell viability and enhanced Aβ42 uptake, suggesting its potential as a therapeutic agent for inflammation-related disorders.ConclusionThe findings suggest that WDR43 and THBS1 are potential targets for preventing and treating CV-induced dementia in the elderly. Cromolyn may have therapeutic value in the treatment of Alzheimer’s disease and dementia.</p

Image_4_Cromolyn prevents cerebral vasospasm and dementia by targeting WDR43.JPEG

BackgroundCerebral vasospasm (CV) can cause inflammation and damage to neuronal cells in the elderly, leading to dementia.PurposeThis study aimed to investigate the genetic mechanisms underlying dementia caused by CV in the elderly, identify preventive and therapeutic drugs, and evaluate their efficacy in treating neurodegenerative diseases.MethodsGenes associated with subarachnoid hemorrhage and CV were acquired and screened for differentially expressed miRNAs (DEmiRNAs) associated with aneurysm rupture. A regulatory network of DEmiRNAs and mRNAs was constructed, and virtual screening was performed to evaluate possible binding patterns between Food and Drug Administration (FDA)-approved drugs and core proteins. Molecular dynamics simulations were performed on the optimal docked complexes. Optimally docked drugs were evaluated for efficacy in the treatment of neurodegenerative diseases through cellular experiments.ResultsThe study found upregulated genes (including WDR43 and THBS1) and one downregulated gene associated with aneurysm rupture. Differences in the expression of these genes indicate greater disease risk. DEmiRNAs associated with ruptured aortic aneurysm were identified, of which two could bind to THBS1 and WDR43. Cromolyn and lanoxin formed the best docking complexes with WDR43 and THBS1, respectively. Cellular experiments showed that cromolyn improved BV2 cell viability and enhanced Aβ42 uptake, suggesting its potential as a therapeutic agent for inflammation-related disorders.ConclusionThe findings suggest that WDR43 and THBS1 are potential targets for preventing and treating CV-induced dementia in the elderly. Cromolyn may have therapeutic value in the treatment of Alzheimer’s disease and dementia.</p

Image_1_Cromolyn prevents cerebral vasospasm and dementia by targeting WDR43.TIF

BackgroundCerebral vasospasm (CV) can cause inflammation and damage to neuronal cells in the elderly, leading to dementia.PurposeThis study aimed to investigate the genetic mechanisms underlying dementia caused by CV in the elderly, identify preventive and therapeutic drugs, and evaluate their efficacy in treating neurodegenerative diseases.MethodsGenes associated with subarachnoid hemorrhage and CV were acquired and screened for differentially expressed miRNAs (DEmiRNAs) associated with aneurysm rupture. A regulatory network of DEmiRNAs and mRNAs was constructed, and virtual screening was performed to evaluate possible binding patterns between Food and Drug Administration (FDA)-approved drugs and core proteins. Molecular dynamics simulations were performed on the optimal docked complexes. Optimally docked drugs were evaluated for efficacy in the treatment of neurodegenerative diseases through cellular experiments.ResultsThe study found upregulated genes (including WDR43 and THBS1) and one downregulated gene associated with aneurysm rupture. Differences in the expression of these genes indicate greater disease risk. DEmiRNAs associated with ruptured aortic aneurysm were identified, of which two could bind to THBS1 and WDR43. Cromolyn and lanoxin formed the best docking complexes with WDR43 and THBS1, respectively. Cellular experiments showed that cromolyn improved BV2 cell viability and enhanced Aβ42 uptake, suggesting its potential as a therapeutic agent for inflammation-related disorders.ConclusionThe findings suggest that WDR43 and THBS1 are potential targets for preventing and treating CV-induced dementia in the elderly. Cromolyn may have therapeutic value in the treatment of Alzheimer’s disease and dementia.</p

Image_6_Cromolyn prevents cerebral vasospasm and dementia by targeting WDR43.JPEG

BackgroundCerebral vasospasm (CV) can cause inflammation and damage to neuronal cells in the elderly, leading to dementia.PurposeThis study aimed to investigate the genetic mechanisms underlying dementia caused by CV in the elderly, identify preventive and therapeutic drugs, and evaluate their efficacy in treating neurodegenerative diseases.MethodsGenes associated with subarachnoid hemorrhage and CV were acquired and screened for differentially expressed miRNAs (DEmiRNAs) associated with aneurysm rupture. A regulatory network of DEmiRNAs and mRNAs was constructed, and virtual screening was performed to evaluate possible binding patterns between Food and Drug Administration (FDA)-approved drugs and core proteins. Molecular dynamics simulations were performed on the optimal docked complexes. Optimally docked drugs were evaluated for efficacy in the treatment of neurodegenerative diseases through cellular experiments.ResultsThe study found upregulated genes (including WDR43 and THBS1) and one downregulated gene associated with aneurysm rupture. Differences in the expression of these genes indicate greater disease risk. DEmiRNAs associated with ruptured aortic aneurysm were identified, of which two could bind to THBS1 and WDR43. Cromolyn and lanoxin formed the best docking complexes with WDR43 and THBS1, respectively. Cellular experiments showed that cromolyn improved BV2 cell viability and enhanced Aβ42 uptake, suggesting its potential as a therapeutic agent for inflammation-related disorders.ConclusionThe findings suggest that WDR43 and THBS1 are potential targets for preventing and treating CV-induced dementia in the elderly. Cromolyn may have therapeutic value in the treatment of Alzheimer’s disease and dementia.</p

Image_2_Cromolyn prevents cerebral vasospasm and dementia by targeting WDR43.TIF

BackgroundCerebral vasospasm (CV) can cause inflammation and damage to neuronal cells in the elderly, leading to dementia.PurposeThis study aimed to investigate the genetic mechanisms underlying dementia caused by CV in the elderly, identify preventive and therapeutic drugs, and evaluate their efficacy in treating neurodegenerative diseases.MethodsGenes associated with subarachnoid hemorrhage and CV were acquired and screened for differentially expressed miRNAs (DEmiRNAs) associated with aneurysm rupture. A regulatory network of DEmiRNAs and mRNAs was constructed, and virtual screening was performed to evaluate possible binding patterns between Food and Drug Administration (FDA)-approved drugs and core proteins. Molecular dynamics simulations were performed on the optimal docked complexes. Optimally docked drugs were evaluated for efficacy in the treatment of neurodegenerative diseases through cellular experiments.ResultsThe study found upregulated genes (including WDR43 and THBS1) and one downregulated gene associated with aneurysm rupture. Differences in the expression of these genes indicate greater disease risk. DEmiRNAs associated with ruptured aortic aneurysm were identified, of which two could bind to THBS1 and WDR43. Cromolyn and lanoxin formed the best docking complexes with WDR43 and THBS1, respectively. Cellular experiments showed that cromolyn improved BV2 cell viability and enhanced Aβ42 uptake, suggesting its potential as a therapeutic agent for inflammation-related disorders.ConclusionThe findings suggest that WDR43 and THBS1 are potential targets for preventing and treating CV-induced dementia in the elderly. Cromolyn may have therapeutic value in the treatment of Alzheimer’s disease and dementia.</p

Table_3_DeepCausality: A general AI-powered causal inference framework for free text: A case study of LiverTox.XLSX

Causality plays an essential role in multiple scientific disciplines, including the social, behavioral, and biological sciences and portions of statistics and artificial intelligence. Manual-based causality assessment from a large number of free text-based documents is very time-consuming, labor-intensive, and sometimes even impractical. Herein, we proposed a general causal inference framework named DeepCausality to empirically estimate the causal factors for suspected endpoints embedded in the free text. The proposed DeepCausality seamlessly incorporates AI-powered language models, named entity recognition and Judea Pearl's Do-calculus, into a general framework for causal inference to fulfill different domain-specific applications. We exemplified the utility of the proposed DeepCausality framework by employing the LiverTox database to estimate idiosyncratic drug-induced liver injury (DILI)-related causal terms and generate a knowledge-based causal tree for idiosyncratic DILI patient stratification. Consequently, the DeepCausality yielded a prediction performance with an accuracy of 0.92 and an F-score of 0.84 for the DILI prediction. Notably, 90% of causal terms enriched by the DeepCausality were consistent with the clinical causal terms defined by the American College of Gastroenterology (ACG) clinical guideline for evaluating suspected idiosyncratic DILI (iDILI). Furthermore, we observed a high concordance of 0.91 between the iDILI severity scores generated by DeepCausality and domain experts. Altogether, the proposed DeepCausality framework could be a promising solution for causality assessment from free text and is publicly available through https://github.com/XingqiaoWang/https-github.com-XingqiaoWang-DeepCausality-LiverTox.</p

Table_2_DeepCausality: A general AI-powered causal inference framework for free text: A case study of LiverTox.XLSX

Causality plays an essential role in multiple scientific disciplines, including the social, behavioral, and biological sciences and portions of statistics and artificial intelligence. Manual-based causality assessment from a large number of free text-based documents is very time-consuming, labor-intensive, and sometimes even impractical. Herein, we proposed a general causal inference framework named DeepCausality to empirically estimate the causal factors for suspected endpoints embedded in the free text. The proposed DeepCausality seamlessly incorporates AI-powered language models, named entity recognition and Judea Pearl's Do-calculus, into a general framework for causal inference to fulfill different domain-specific applications. We exemplified the utility of the proposed DeepCausality framework by employing the LiverTox database to estimate idiosyncratic drug-induced liver injury (DILI)-related causal terms and generate a knowledge-based causal tree for idiosyncratic DILI patient stratification. Consequently, the DeepCausality yielded a prediction performance with an accuracy of 0.92 and an F-score of 0.84 for the DILI prediction. Notably, 90% of causal terms enriched by the DeepCausality were consistent with the clinical causal terms defined by the American College of Gastroenterology (ACG) clinical guideline for evaluating suspected idiosyncratic DILI (iDILI). Furthermore, we observed a high concordance of 0.91 between the iDILI severity scores generated by DeepCausality and domain experts. Altogether, the proposed DeepCausality framework could be a promising solution for causality assessment from free text and is publicly available through https://github.com/XingqiaoWang/https-github.com-XingqiaoWang-DeepCausality-LiverTox.</p

Table_1_DeepCausality: A general AI-powered causal inference framework for free text: A case study of LiverTox.XLSX

Causality plays an essential role in multiple scientific disciplines, including the social, behavioral, and biological sciences and portions of statistics and artificial intelligence. Manual-based causality assessment from a large number of free text-based documents is very time-consuming, labor-intensive, and sometimes even impractical. Herein, we proposed a general causal inference framework named DeepCausality to empirically estimate the causal factors for suspected endpoints embedded in the free text. The proposed DeepCausality seamlessly incorporates AI-powered language models, named entity recognition and Judea Pearl's Do-calculus, into a general framework for causal inference to fulfill different domain-specific applications. We exemplified the utility of the proposed DeepCausality framework by employing the LiverTox database to estimate idiosyncratic drug-induced liver injury (DILI)-related causal terms and generate a knowledge-based causal tree for idiosyncratic DILI patient stratification. Consequently, the DeepCausality yielded a prediction performance with an accuracy of 0.92 and an F-score of 0.84 for the DILI prediction. Notably, 90% of causal terms enriched by the DeepCausality were consistent with the clinical causal terms defined by the American College of Gastroenterology (ACG) clinical guideline for evaluating suspected idiosyncratic DILI (iDILI). Furthermore, we observed a high concordance of 0.91 between the iDILI severity scores generated by DeepCausality and domain experts. Altogether, the proposed DeepCausality framework could be a promising solution for causality assessment from free text and is publicly available through https://github.com/XingqiaoWang/https-github.com-XingqiaoWang-DeepCausality-LiverTox.</p