At present,treatments for Alzheimer's disease can temporarily relieve symptoms but cannot prevent the decline of cognitive ability and other neurodegenerative changes.Dendrobium nobile Lindl alkaloid is the main a...At present,treatments for Alzheimer's disease can temporarily relieve symptoms but cannot prevent the decline of cognitive ability and other neurodegenerative changes.Dendrobium nobile Lindl alkaloid is the main active component of Dendrobium nobile Lindl.Dendrobium nobile Lindl alkaloid has been shown to resist aging,prolong life span,and exhibit immunomodulatory effects in animals.This review summarizes the mechanisms behind the neuroprotective effects reported in Alzheimer's disease animal models.The neuroprotective effects of Dendrobium nobile Lindl alkaloid have not been studied in patients.The mechanisms by which Dendrobium nobile Lindl alkaloid has been reported to improve cognitive dysfunction in Alzheimer's disease animal models may be associated with extracellular amyloid plaque production,regulation of tau protein hyperphosphorylation,inhibition of neuroinflammation and neuronal apoptosis,activation of autophagy,and enhanced synaptic connections.展开更多
BACKGROUND Inflammatory bowel disease(IBD)is a global health burden that affects millions of individuals worldwide,necessitating extensive patient education.Large language models(LLMs)hold promise for addressing patie...BACKGROUND Inflammatory bowel disease(IBD)is a global health burden that affects millions of individuals worldwide,necessitating extensive patient education.Large language models(LLMs)hold promise for addressing patient information needs.However,LLM use to deliver accurate and comprehensible IBD-related medical information has yet to be thoroughly investigated.AIM To assess the utility of three LLMs(ChatGPT-4.0,Claude-3-Opus,and Gemini-1.5-Pro)as a reference point for patients with IBD.METHODS In this comparative study,two gastroenterology experts generated 15 IBD-related questions that reflected common patient concerns.These questions were used to evaluate the performance of the three LLMs.The answers provided by each model were independently assessed by three IBD-related medical experts using a Likert scale focusing on accuracy,comprehensibility,and correlation.Simultaneously,three patients were invited to evaluate the comprehensibility of their answers.Finally,a readability assessment was performed.RESULTS Overall,each of the LLMs achieved satisfactory levels of accuracy,comprehensibility,and completeness when answering IBD-related questions,although their performance varies.All of the investigated models demonstrated strengths in providing basic disease information such as IBD definition as well as its common symptoms and diagnostic methods.Nevertheless,when dealing with more complex medical advice,such as medication side effects,dietary adjustments,and complication risks,the quality of answers was inconsistent between the LLMs.Notably,Claude-3-Opus generated answers with better readability than the other two models.CONCLUSION LLMs have the potential as educational tools for patients with IBD;however,there are discrepancies between the models.Further optimization and the development of specialized models are necessary to ensure the accuracy and safety of the information provided.展开更多
Ischemic heart disease(IHD)remains a leading contributor to cardiovascular disease(CVD)worldwide.Despite advances in diagnostic and therapeutic approaches,translational research demands robust large animal models to b...Ischemic heart disease(IHD)remains a leading contributor to cardiovascular disease(CVD)worldwide.Despite advances in diagnostic and therapeutic approaches,translational research demands robust large animal models to bridge the gap between experimental interventions and clinical application.Among these,porcine models have gained prominence due to their anatomical,physiological,immunological,and genomic similarities to humans.This review provides a comprehensive overview of current methodologies for establishing porcine IHD models,critically assesses emerging rehabilitative strategies,and outlines innovative therapeutic technologies,with the goal of guiding model selection and fostering the development of novel treatment strategies.展开更多
The development of rodent models that accurately reflect the pathogenesis of alcoholic liver disease(ALD)in humans is crucial for evaluating the nutritional intervention of food bioactive ingredients in ALD.Although v...The development of rodent models that accurately reflect the pathogenesis of alcoholic liver disease(ALD)in humans is crucial for evaluating the nutritional intervention of food bioactive ingredients in ALD.Although various models have been employed to establish ALD models over the past few decades,most successful cases are associated with high mortality rates,operational difficulties,and incompatibility formation mechanism compared to human ALD.However,the ALD models established by oral administration that simulate human drinking behavior often fail to induce significant liver damage.Therefore,it is imperative to explore simple and effective modes of oral administration for establishing ALD models consistent with the pathophysiological process of human ALD.Herein,we summarized the pathogenesis of ALD and discussed several issues related to construct ALD models with rodents(mainly mice and rats)by oral administration,including animal selection,animal feeding,alcohol intervention,and evaluation criteria.The purpose of this review is to provide a standardized and efficient formula for ALD modeling,so as to facilitate efficacy evaluation and mechanism analysis of food bioactive ingredients in ALD.展开更多
AIM:To assess the performance of five distinct large language models(LLMs;ChatGPT-3.5,ChatGPT-4,PaLM2,Claude 2,and SenseNova)in comparison to two human cohorts(a group of funduscopic disease experts and a group of oph...AIM:To assess the performance of five distinct large language models(LLMs;ChatGPT-3.5,ChatGPT-4,PaLM2,Claude 2,and SenseNova)in comparison to two human cohorts(a group of funduscopic disease experts and a group of ophthalmologists)on the specialized subject of funduscopic disease.METHODS:Five distinct LLMs and two distinct human groups independently completed a 100-item funduscopic disease test.The performance of these entities was assessed by comparing their average scores,response stability,and answer confidence,thereby establishing a basis for evaluation.RESULTS:Among all the LLMs,ChatGPT-4 and PaLM2 exhibited the most substantial average correlation.Additionally,ChatGPT-4 achieved the highest average score and demonstrated the utmost confidence during the exam.In comparison to human cohorts,ChatGPT-4 exhibited comparable performance to ophthalmologists,albeit falling short of the expertise demonstrated by funduscopic disease specialists.CONCLUSION:The study provides evidence of the exceptional performance of ChatGPT-4 in the domain of funduscopic disease.With continued enhancements,validated LLMs have the potential to yield unforeseen advantages in enhancing healthcare for both patients and physicians.展开更多
The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cereb...The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.展开更多
AIM:To assess the possibility of using different large language models(LLMs)in ocular surface diseases by selecting five different LLMS to test their accuracy in answering specialized questions related to ocular surfa...AIM:To assess the possibility of using different large language models(LLMs)in ocular surface diseases by selecting five different LLMS to test their accuracy in answering specialized questions related to ocular surface diseases:ChatGPT-4,ChatGPT-3.5,Claude 2,PaLM2,and SenseNova.METHODS:A group of experienced ophthalmology professors were asked to develop a 100-question singlechoice question on ocular surface diseases designed to assess the performance of LLMs and human participants in answering ophthalmology specialty exam questions.The exam includes questions on the following topics:keratitis disease(20 questions),keratoconus,keratomalaciac,corneal dystrophy,corneal degeneration,erosive corneal ulcers,and corneal lesions associated with systemic diseases(20 questions),conjunctivitis disease(20 questions),trachoma,pterygoid and conjunctival tumor diseases(20 questions),and dry eye disease(20 questions).Then the total score of each LLMs and compared their mean score,mean correlation,variance,and confidence were calculated.RESULTS:GPT-4 exhibited the highest performance in terms of LLMs.Comparing the average scores of the LLMs group with the four human groups,chief physician,attending physician,regular trainee,and graduate student,it was found that except for ChatGPT-4,the total score of the rest of the LLMs is lower than that of the graduate student group,which had the lowest score in the human group.Both ChatGPT-4 and PaLM2 were more likely to give exact and correct answers,giving very little chance of an incorrect answer.ChatGPT-4 showed higher credibility when answering questions,with a success rate of 59%,but gave the wrong answer to the question 28% of the time.CONCLUSION:GPT-4 model exhibits excellent performance in both answer relevance and confidence.PaLM2 shows a positive correlation(up to 0.8)in terms of answer accuracy during the exam.In terms of answer confidence,PaLM2 is second only to GPT4 and surpasses Claude 2,SenseNova,and GPT-3.5.Despite the fact that ocular surface disease is a highly specialized discipline,GPT-4 still exhibits superior performance,suggesting that its potential and ability to be applied in this field is enormous,perhaps with the potential to be a valuable resource for medical students and clinicians in the future.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a prevalent chronic liver disorder driven by obesity and metabolic dysfunction.MASLD progresses to metabolic dysfunction-associated steatohe...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a prevalent chronic liver disorder driven by obesity and metabolic dysfunction.MASLD progresses to metabolic dysfunction-associated steatohepatitis,which is characterized by inflammation,hepatocyte injury,and fibrosis,increasing the risk of cirrhosis and liver failure.Recent studies suggest that neutrophil extracellular traps(NETs)and extracellular DNA(ecDNA)contribute to liver inflammation and fibrogenesis.However,their role in MASLD pathogenesis remains incompletely understood.AIM To investigate the dynamics of circulating NETs and ecDNA as potential biomarkers of liver injury in MASLD.METHODS Using three complementary mouse models,thioacetamide(TAA)-induced fibrosis,choline-deficient L-amino acid-defined(CDAA)diet-induced metabolic dysfunction-associated steatohepatitis,and cafeteria(CAF)diet-induced MASLD,we assessed the association between NET-related markers and liver damage.Blood samples were collected biweekly to analyze ecDNA and NET markers,including myeloperoxidase(MPO)and MPO-DNA complexes,using ELISA and real-time PCR.Liver histopathology was assessed for inflammation,fibrosis,and neutrophil infiltration.RESULTS The TAA and CDAA models exhibited significant liver injury,characterized by increased plasma alanine aminotransferase and aspartate aminotransferase levels,hepatocellular damage,and fibrosis.Elevated circulating NET markers(MPO and ecDNA)were observed in these models,with a strong correlation between NET formation and liver pathology.The CAF diet model induced steatosis but failed to elicit significant liver fibrosis or an increase in NET markers,suggesting that NETosis is associated with more severe liver damage.Notably,ecDNA and MPO levels correlated with neutrophil infiltration and fibrosis scores,indicating their potential as biomarkers of MASLD progression.CONCLUSION NETosis and ecDNA levels reflect liver injury severity in MASLD.NET markers and liver fibrosis were strongly associated in TAA and CDAA models,whereas CAF model showed minimal NET involvement.展开更多
This article evaluates the transformative potential of large language models(LLMs)as patient education tools for managing inflammatory bowel disease.The discussion highlights their ability to deliver nuanced and perso...This article evaluates the transformative potential of large language models(LLMs)as patient education tools for managing inflammatory bowel disease.The discussion highlights their ability to deliver nuanced and personalized infor-mation,addressing limitations in traditional educational materials.Key consider-ations include the necessity for domain-specific fine-tuning to enhance accuracy,the adoption of robust evaluation metrics beyond readability,and the integration of LLMs with clinical decision support systems to improve real-time patient education.Ethical and accessibility challenges,such as algorithmic bias,data privacy,and digital literacy,are also examined.Recommendations emphasize the importance of interdisciplinary collaboration to optimize LLM integration,en-suring equitable access and improved patient outcomes.By advancing LLM technology,healthcare can empower patients with accurate and personalized information,enhancing engagement and disease management.展开更多
Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse ...Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.展开更多
Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly inve...Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.展开更多
This letter evaluates the article by Gravina et al on ChatGPT’s potential in providing medical information for inflammatory bowel disease patients.While promising,it highlights the need for advanced techniques like r...This letter evaluates the article by Gravina et al on ChatGPT’s potential in providing medical information for inflammatory bowel disease patients.While promising,it highlights the need for advanced techniques like reasoning+action and retrieval-augmented generation to improve accuracy and reliability.Emphasizing that simple question and answer testing is insufficient,it calls for more nuanced evaluation methods to truly gauge large language models’capabilities in clinical applications.展开更多
BACKGROUND Congenital heart disease is most commonly seen in neonates and it is a major cause of pediatric illness and childhood morbidity and mortality.AIM To identify and build the best predictive model for predicti...BACKGROUND Congenital heart disease is most commonly seen in neonates and it is a major cause of pediatric illness and childhood morbidity and mortality.AIM To identify and build the best predictive model for predicting cyanotic and acyanotic congenital heart disease in children during pregnancy and identify their potential risk factors.METHODS The data were collected from the Pediatric Cardiology Department at Chaudhry Pervaiz Elahi Institute of Cardiology Multan,Pakistan from December 2017 to October 2019.A sample of 3900 mothers whose children were diagnosed with identify the potential outliers.Different machine learning models were compared,and the best-fitted model was selected using the area under the curve,sensitivity,and specificity of the models.RESULTS Out of 3900 patients included,about 69.5%had acyanotic and 30.5%had cyanotic congenital heart disease.Males had more cases of acyanotic(53.6%)and cyanotic(54.5%)congenital heart disease as compared to females.The odds of having cyanotic was 1.28 times higher for children whose mothers used more fast food frequently during pregnancy.The artificial neural network model was selected as the best predictive model with an area under the curve of 0.9012,sensitivity of 65.76%,and specificity of 97.23%.CONCLUSION Children having a positive family history are at very high risk of having cyanotic and acyanotic congenital heart disease.Males are more at risk and their mothers need more care,good food,and physical activity during pregnancy.The best-fitted model for predicting cyanotic and acyanotic congenital heart disease is the artificial neural network.The results obtained and the best model identified will be useful for medical practitioners and public health scientists for an informed decision-making process about the earlier diagnosis and improve the health condition of children in Pakistan.展开更多
Animal models constructed using pathogenic factors have significantly advanced drug development for Alzheimer's disease(AD).These predominantly transgenic models,mainly in mice,replicate pathological phenotypes th...Animal models constructed using pathogenic factors have significantly advanced drug development for Alzheimer's disease(AD).These predominantly transgenic models,mainly in mice,replicate pathological phenotypes through gene mutations associated with familial AD cases,thus serving as vital tools for assessing drug efficacy and for performing mechanistic studies.However,the speciesspecific differences and complex,heterogeneous nature of AD etiology pose considerable challenges for the translatability of these animal models,limiting their utility in drug development.This review offers a comprehensive analysis of widely employed rodent(mice and rats)and non-rodent models(Danio rerio(zebrafish),Drosophila melanogaster,and Caenorhabditis elegans),detailing their phenotypic features and specific research applications.This review also examines the limitations inherent in these models and introduces various strategies for expanding AD modeling across diverse species,emphasizing recent advancement in non-human primates(NHPs)as valuable models.Furthermore,potential insights from the integration of innovative technologies in AD research are discussed,while providing valuable perspectives on the future development of AD animal models.展开更多
Acute kidney injury(AKI)and chronic kidney disease(CKD)are significant public health issues associated with a long-term increase in mortality risk,resulting from various etiologies including renal ischemia,sepsis,drug...Acute kidney injury(AKI)and chronic kidney disease(CKD)are significant public health issues associated with a long-term increase in mortality risk,resulting from various etiologies including renal ischemia,sepsis,drug toxicity,and diabetes mellitus.Numerous preclinical models have been developed to deepen our understanding of the pathophysiological mechanisms and therapeutic approaches for kidney diseases.Among these,rodent models have proven to be powerful tools in the discovery of novel therapeutics,while the development of kidney organoids has emerged as a promising advancement in the field.This review provides a comprehensive analysis of the construction methodologies,underlying biological mechanisms,and recent therapeutic developments across different AKI and CKD models.Additionally,this review summarizes the advantages,limitations,and challenges inherent in these preclinical models,thereby contributing robust evidence to support the development of effective therapeutic strategies.展开更多
Neurodegeneration is a catastrophic process that develops progressive damage leading to functional andstructural loss of the cells of the nervous system and is among the biggest unavoidable problems of our age.Animalm...Neurodegeneration is a catastrophic process that develops progressive damage leading to functional andstructural loss of the cells of the nervous system and is among the biggest unavoidable problems of our age.Animalmodels do not reflect the pathophysiology observed in humans due to distinct differences between the neuralpathways,gene expression patterns,neuronal plasticity,and other disease-related mechanisms in animals andhumans.Classical in vitro cell culture models are also not sufficient for pre-clinical drug testing in reflecting thecomplex pathophysiology of neurodegenerative diseases.Today,modern,engineered techniques are applied to developmulticellular,intricate in vitro models and to create the closest microenvironment simulating biological,biochemical,and mechanical characteristics of the in vivo degenerating tissue.In THIS review,the capabilities and shortcomings ofscaffold-based and scaffold-free techniques,organoids,and microfluidic models that best reflect neurodegeneration invitro in the biomimetic framework are discussed.展开更多
Cardiovascular Diseases (CVDs) pose a significant global health challenge, necessitating accurate risk prediction for effective preventive measures. This comprehensive comparative study explores the performance of tra...Cardiovascular Diseases (CVDs) pose a significant global health challenge, necessitating accurate risk prediction for effective preventive measures. This comprehensive comparative study explores the performance of traditional Machine Learning (ML) and Deep Learning (DL) models in predicting CVD risk, utilizing a meticulously curated dataset derived from health records. Rigorous preprocessing, including normalization and outlier removal, enhances model robustness. Diverse ML models (Logistic Regression, Random Forest, Support Vector Machine, K-Nearest Neighbor, Decision Tree, and Gradient Boosting) are compared with a Long Short-Term Memory (LSTM) neural network for DL. Evaluation metrics include accuracy, ROC AUC, computation time, and memory usage. Results identify the Gradient Boosting Classifier and LSTM as top performers, demonstrating high accuracy and ROC AUC scores. Comparative analyses highlight model strengths and limitations, contributing valuable insights for optimizing predictive strategies. This study advances predictive analytics for cardiovascular health, with implications for personalized medicine. The findings underscore the versatility of intelligent systems in addressing health challenges, emphasizing the broader applications of ML and DL in disease identification beyond cardiovascular health.展开更多
Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrog...Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis.Developing effective diagnostic,preventative,and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease.Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD.Additionally,these models are limited in their ability to elucidate the interplay among amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation.In this study,we introduce a novel AD mouse model(APP/PS1-TauP301L-Adeno mice)designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms.Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAVDJ-EF1a-hTauP301L-EGFP and Adeno-GFAP-GFP viruses into the hippocampi of 5-month-old APP/PS1 mice.Three months post-injection,these mice exhibited pronounced astrogliosis,substantial amyloid-βplaque accumulation,extensiveneurofibrillarytangles,accelerated neuronal loss,elevated astrocytic GABA levels,and significant spatial memory deficits.Notably,these pathological features were less severe in AAVTauP301L-expressing APP/PS1 mice without augmented reactive astrogliosis.These findings indicate an exacerbating role of severe reactive astrogliosis in amyloid-βplaque and neurofibrillary tangle-associated pathology.The APP/PS1-TauP301L-Adeno mouse model provides a valuable tool for advancing therapeutic research aimed at mitigating the progression of AD.展开更多
Acetyltransferases,required to transfer an acetyl group on protein are highly conserved proteins that play a crucial role in development and disease.Protein acetylation is a common post-translational modification pivo...Acetyltransferases,required to transfer an acetyl group on protein are highly conserved proteins that play a crucial role in development and disease.Protein acetylation is a common post-translational modification pivotal to basic cellular processes.Close to 80%-90%of proteins are acetylated during translation,which is an irreversible process that affects protein structure,function,life,and localization.In this review,we have discussed the various N-acetyltransferases present in humans,their function,and how they might play a role in diseases.Furthermore,we have focused on N-acetyltransferase 9 and its role in microtubule stability.We have shed light on how N-acetyltransferase 9 and acetylation of proteins can potentially play a role in neurodegenerative diseases.We have specifically discussed the N-acetyltransferase 9-acetylation independent function and regulation of c-Jun N-terminal kinase signaling and microtubule stability during development and neurodegeneration.展开更多
BACKGROUND Ischemic heart disease(IHD)impacts the quality of life and has the highest mortality rate of cardiovascular diseases globally.AIM To compare variations in the parameters of the single-lead electrocardiogram...BACKGROUND Ischemic heart disease(IHD)impacts the quality of life and has the highest mortality rate of cardiovascular diseases globally.AIM To compare variations in the parameters of the single-lead electrocardiogram(ECG)during resting conditions and physical exertion in individuals diagnosed with IHD and those without the condition using vasodilator-induced stress computed tomography(CT)myocardial perfusion imaging as the diagnostic reference standard.METHODS This single center observational study included 80 participants.The participants were aged≥40 years and given an informed written consent to participate in the study.Both groups,G1(n=31)with and G2(n=49)without post stress induced myocardial perfusion defect,passed cardiologist consultation,anthropometric measurements,blood pressure and pulse rate measurement,echocardiography,cardio-ankle vascular index,bicycle ergometry,recording 3-min single-lead ECG(Cardio-Qvark)before and just after bicycle ergometry followed by performing CT myocardial perfusion.The LASSO regression with nested cross-validation was used to find the association between Cardio-Qvark parameters and the existence of the perfusion defect.Statistical processing was performed with the R programming language v4.2,Python v.3.10[^R],and Statistica 12 program.RESULTS Bicycle ergometry yielded an area under the receiver operating characteristic curve of 50.7%[95%confidence interval(CI):0.388-0.625],specificity of 53.1%(95%CI:0.392-0.673),and sensitivity of 48.4%(95%CI:0.306-0.657).In contrast,the Cardio-Qvark test performed notably better with an area under the receiver operating characteristic curve of 67%(95%CI:0.530-0.801),specificity of 75.5%(95%CI:0.628-0.88),and sensitivity of 51.6%(95%CI:0.333-0.695).CONCLUSION The single-lead ECG has a relatively higher diagnostic accuracy compared with bicycle ergometry by using machine learning models,but the difference was not statistically significant.However,further investigations are required to uncover the hidden capabilities of single-lead ECG in IHD diagnosis.展开更多
基金supported by Shijingshan’s Tutor Studio of Pharmacology,No.GZS-2016-07(to JSS)the Construction of National First Class Pharmacy Disciplineb,No.GESR-2017-85(to JSS)+1 种基金the Master Start Foundation of Zunyi Medical University,No.F-839(to DDL)a grant from Guizhou Chinese Medicine Administration,No.QZYY-2018-025(to DDL)。
文摘At present,treatments for Alzheimer's disease can temporarily relieve symptoms but cannot prevent the decline of cognitive ability and other neurodegenerative changes.Dendrobium nobile Lindl alkaloid is the main active component of Dendrobium nobile Lindl.Dendrobium nobile Lindl alkaloid has been shown to resist aging,prolong life span,and exhibit immunomodulatory effects in animals.This review summarizes the mechanisms behind the neuroprotective effects reported in Alzheimer's disease animal models.The neuroprotective effects of Dendrobium nobile Lindl alkaloid have not been studied in patients.The mechanisms by which Dendrobium nobile Lindl alkaloid has been reported to improve cognitive dysfunction in Alzheimer's disease animal models may be associated with extracellular amyloid plaque production,regulation of tau protein hyperphosphorylation,inhibition of neuroinflammation and neuronal apoptosis,activation of autophagy,and enhanced synaptic connections.
基金Supported by the China Health Promotion Foundation Young Doctors'Research Foundation for Inflammatory Bowel Disease,the Taishan Scholars Program of Shandong Province,China,No.tsqn202306343National Natural Science Foundation of China,No.82270578.
文摘BACKGROUND Inflammatory bowel disease(IBD)is a global health burden that affects millions of individuals worldwide,necessitating extensive patient education.Large language models(LLMs)hold promise for addressing patient information needs.However,LLM use to deliver accurate and comprehensible IBD-related medical information has yet to be thoroughly investigated.AIM To assess the utility of three LLMs(ChatGPT-4.0,Claude-3-Opus,and Gemini-1.5-Pro)as a reference point for patients with IBD.METHODS In this comparative study,two gastroenterology experts generated 15 IBD-related questions that reflected common patient concerns.These questions were used to evaluate the performance of the three LLMs.The answers provided by each model were independently assessed by three IBD-related medical experts using a Likert scale focusing on accuracy,comprehensibility,and correlation.Simultaneously,three patients were invited to evaluate the comprehensibility of their answers.Finally,a readability assessment was performed.RESULTS Overall,each of the LLMs achieved satisfactory levels of accuracy,comprehensibility,and completeness when answering IBD-related questions,although their performance varies.All of the investigated models demonstrated strengths in providing basic disease information such as IBD definition as well as its common symptoms and diagnostic methods.Nevertheless,when dealing with more complex medical advice,such as medication side effects,dietary adjustments,and complication risks,the quality of answers was inconsistent between the LLMs.Notably,Claude-3-Opus generated answers with better readability than the other two models.CONCLUSION LLMs have the potential as educational tools for patients with IBD;however,there are discrepancies between the models.Further optimization and the development of specialized models are necessary to ensure the accuracy and safety of the information provided.
基金supported by the National Key R&D Program of China(2023YFC3603800,2023YFC3603801)National Natural Science Foundation of China(82202793,82172534,82372574)+3 种基金Natural Science Foundation of Sichuan Province(2023NSFSC1999,2023NSFSC1495)Young and Middle-Aged Leading Talent Cultivation Project of Sichuan University(JH20231160)Noncommunicable Chronic Diseases-National Science and Technology Major Project(2024ZD0526000)1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC21038)。
文摘Ischemic heart disease(IHD)remains a leading contributor to cardiovascular disease(CVD)worldwide.Despite advances in diagnostic and therapeutic approaches,translational research demands robust large animal models to bridge the gap between experimental interventions and clinical application.Among these,porcine models have gained prominence due to their anatomical,physiological,immunological,and genomic similarities to humans.This review provides a comprehensive overview of current methodologies for establishing porcine IHD models,critically assesses emerging rehabilitative strategies,and outlines innovative therapeutic technologies,with the goal of guiding model selection and fostering the development of novel treatment strategies.
基金supported by the National Natural Science Foundation of China(32430083).
文摘The development of rodent models that accurately reflect the pathogenesis of alcoholic liver disease(ALD)in humans is crucial for evaluating the nutritional intervention of food bioactive ingredients in ALD.Although various models have been employed to establish ALD models over the past few decades,most successful cases are associated with high mortality rates,operational difficulties,and incompatibility formation mechanism compared to human ALD.However,the ALD models established by oral administration that simulate human drinking behavior often fail to induce significant liver damage.Therefore,it is imperative to explore simple and effective modes of oral administration for establishing ALD models consistent with the pathophysiological process of human ALD.Herein,we summarized the pathogenesis of ALD and discussed several issues related to construct ALD models with rodents(mainly mice and rats)by oral administration,including animal selection,animal feeding,alcohol intervention,and evaluation criteria.The purpose of this review is to provide a standardized and efficient formula for ALD modeling,so as to facilitate efficacy evaluation and mechanism analysis of food bioactive ingredients in ALD.
基金Supported by National Natural Science Foundation of China(No.82160195)Science and Technology Project of Jiangxi Provincial Department of Education(No.GJJ200169)+1 种基金Science and Technology Project of Jiangxi Province Health Commission of Traditional Chinese Medicine(No.2020A0087)Science and Technology Project of Jiangxi Health Commission(No.202130210).
文摘AIM:To assess the performance of five distinct large language models(LLMs;ChatGPT-3.5,ChatGPT-4,PaLM2,Claude 2,and SenseNova)in comparison to two human cohorts(a group of funduscopic disease experts and a group of ophthalmologists)on the specialized subject of funduscopic disease.METHODS:Five distinct LLMs and two distinct human groups independently completed a 100-item funduscopic disease test.The performance of these entities was assessed by comparing their average scores,response stability,and answer confidence,thereby establishing a basis for evaluation.RESULTS:Among all the LLMs,ChatGPT-4 and PaLM2 exhibited the most substantial average correlation.Additionally,ChatGPT-4 achieved the highest average score and demonstrated the utmost confidence during the exam.In comparison to human cohorts,ChatGPT-4 exhibited comparable performance to ophthalmologists,albeit falling short of the expertise demonstrated by funduscopic disease specialists.CONCLUSION:The study provides evidence of the exceptional performance of ChatGPT-4 in the domain of funduscopic disease.With continued enhancements,validated LLMs have the potential to yield unforeseen advantages in enhancing healthcare for both patients and physicians.
基金supported by the Grant PID2021-126715OB-IOO financed by MCIN/AEI/10.13039/501100011033 and"ERDFA way of making Europe"by the Grant PI22CⅢ/00055 funded by Instituto de Salud CarlosⅢ(ISCⅢ)+6 种基金the UFIECPY 398/19(PEJ2018-004965) grant to RGS funded by AEI(Spain)the UFIECPY-396/19(PEJ2018-004961)grant financed by MCIN (Spain)FI23CⅢ/00003 grant funded by ISCⅢ-PFIS Spain) to PMMthe UFIECPY 328/22 (PEJ-2021-TL/BMD-21001) grant to LM financed by CAM (Spain)the grant by CAPES (Coordination for the Improvement of Higher Education Personnel)through the PDSE program (Programa de Doutorado Sanduiche no Exterior)to VSCG financed by MEC (Brazil)
文摘The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.
基金Supported by National Natural Science Foundation of China(No.82160195,No.82460203)Degree and Postgraduate Education Teaching Reform Project of Jiangxi Province(No.JXYJG-2020-026).
文摘AIM:To assess the possibility of using different large language models(LLMs)in ocular surface diseases by selecting five different LLMS to test their accuracy in answering specialized questions related to ocular surface diseases:ChatGPT-4,ChatGPT-3.5,Claude 2,PaLM2,and SenseNova.METHODS:A group of experienced ophthalmology professors were asked to develop a 100-question singlechoice question on ocular surface diseases designed to assess the performance of LLMs and human participants in answering ophthalmology specialty exam questions.The exam includes questions on the following topics:keratitis disease(20 questions),keratoconus,keratomalaciac,corneal dystrophy,corneal degeneration,erosive corneal ulcers,and corneal lesions associated with systemic diseases(20 questions),conjunctivitis disease(20 questions),trachoma,pterygoid and conjunctival tumor diseases(20 questions),and dry eye disease(20 questions).Then the total score of each LLMs and compared their mean score,mean correlation,variance,and confidence were calculated.RESULTS:GPT-4 exhibited the highest performance in terms of LLMs.Comparing the average scores of the LLMs group with the four human groups,chief physician,attending physician,regular trainee,and graduate student,it was found that except for ChatGPT-4,the total score of the rest of the LLMs is lower than that of the graduate student group,which had the lowest score in the human group.Both ChatGPT-4 and PaLM2 were more likely to give exact and correct answers,giving very little chance of an incorrect answer.ChatGPT-4 showed higher credibility when answering questions,with a success rate of 59%,but gave the wrong answer to the question 28% of the time.CONCLUSION:GPT-4 model exhibits excellent performance in both answer relevance and confidence.PaLM2 shows a positive correlation(up to 0.8)in terms of answer accuracy during the exam.In terms of answer confidence,PaLM2 is second only to GPT4 and surpasses Claude 2,SenseNova,and GPT-3.5.Despite the fact that ocular surface disease is a highly specialized discipline,GPT-4 still exhibits superior performance,suggesting that its potential and ability to be applied in this field is enormous,perhaps with the potential to be a valuable resource for medical students and clinicians in the future.
基金Supported by Slovak Research and Development Agency,No.APVV-21-0370Ministry of Education,Science,Research and Sport of the Slovak Republic,No.VEGA 1/0706/25 and No.VEGA 1/0341/23.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a prevalent chronic liver disorder driven by obesity and metabolic dysfunction.MASLD progresses to metabolic dysfunction-associated steatohepatitis,which is characterized by inflammation,hepatocyte injury,and fibrosis,increasing the risk of cirrhosis and liver failure.Recent studies suggest that neutrophil extracellular traps(NETs)and extracellular DNA(ecDNA)contribute to liver inflammation and fibrogenesis.However,their role in MASLD pathogenesis remains incompletely understood.AIM To investigate the dynamics of circulating NETs and ecDNA as potential biomarkers of liver injury in MASLD.METHODS Using three complementary mouse models,thioacetamide(TAA)-induced fibrosis,choline-deficient L-amino acid-defined(CDAA)diet-induced metabolic dysfunction-associated steatohepatitis,and cafeteria(CAF)diet-induced MASLD,we assessed the association between NET-related markers and liver damage.Blood samples were collected biweekly to analyze ecDNA and NET markers,including myeloperoxidase(MPO)and MPO-DNA complexes,using ELISA and real-time PCR.Liver histopathology was assessed for inflammation,fibrosis,and neutrophil infiltration.RESULTS The TAA and CDAA models exhibited significant liver injury,characterized by increased plasma alanine aminotransferase and aspartate aminotransferase levels,hepatocellular damage,and fibrosis.Elevated circulating NET markers(MPO and ecDNA)were observed in these models,with a strong correlation between NET formation and liver pathology.The CAF diet model induced steatosis but failed to elicit significant liver fibrosis or an increase in NET markers,suggesting that NETosis is associated with more severe liver damage.Notably,ecDNA and MPO levels correlated with neutrophil infiltration and fibrosis scores,indicating their potential as biomarkers of MASLD progression.CONCLUSION NETosis and ecDNA levels reflect liver injury severity in MASLD.NET markers and liver fibrosis were strongly associated in TAA and CDAA models,whereas CAF model showed minimal NET involvement.
文摘This article evaluates the transformative potential of large language models(LLMs)as patient education tools for managing inflammatory bowel disease.The discussion highlights their ability to deliver nuanced and personalized infor-mation,addressing limitations in traditional educational materials.Key consider-ations include the necessity for domain-specific fine-tuning to enhance accuracy,the adoption of robust evaluation metrics beyond readability,and the integration of LLMs with clinical decision support systems to improve real-time patient education.Ethical and accessibility challenges,such as algorithmic bias,data privacy,and digital literacy,are also examined.Recommendations emphasize the importance of interdisciplinary collaboration to optimize LLM integration,en-suring equitable access and improved patient outcomes.By advancing LLM technology,healthcare can empower patients with accurate and personalized information,enhancing engagement and disease management.
文摘Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.
基金supported by the National Key Research and Development Program of China (2021YFA0805300,2021YFA0805200)National Natural Science Foundation of China (32170981,82371874,82394422,82171244,82071421,82271902)+1 种基金Guangzhou Key Research Program on Brain Science (202007030008)Department of Science and Technology of Guangdong Province (2021ZT09Y007,2020B121201006,2018B030337001)。
文摘Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.
文摘This letter evaluates the article by Gravina et al on ChatGPT’s potential in providing medical information for inflammatory bowel disease patients.While promising,it highlights the need for advanced techniques like reasoning+action and retrieval-augmented generation to improve accuracy and reliability.Emphasizing that simple question and answer testing is insufficient,it calls for more nuanced evaluation methods to truly gauge large language models’capabilities in clinical applications.
文摘BACKGROUND Congenital heart disease is most commonly seen in neonates and it is a major cause of pediatric illness and childhood morbidity and mortality.AIM To identify and build the best predictive model for predicting cyanotic and acyanotic congenital heart disease in children during pregnancy and identify their potential risk factors.METHODS The data were collected from the Pediatric Cardiology Department at Chaudhry Pervaiz Elahi Institute of Cardiology Multan,Pakistan from December 2017 to October 2019.A sample of 3900 mothers whose children were diagnosed with identify the potential outliers.Different machine learning models were compared,and the best-fitted model was selected using the area under the curve,sensitivity,and specificity of the models.RESULTS Out of 3900 patients included,about 69.5%had acyanotic and 30.5%had cyanotic congenital heart disease.Males had more cases of acyanotic(53.6%)and cyanotic(54.5%)congenital heart disease as compared to females.The odds of having cyanotic was 1.28 times higher for children whose mothers used more fast food frequently during pregnancy.The artificial neural network model was selected as the best predictive model with an area under the curve of 0.9012,sensitivity of 65.76%,and specificity of 97.23%.CONCLUSION Children having a positive family history are at very high risk of having cyanotic and acyanotic congenital heart disease.Males are more at risk and their mothers need more care,good food,and physical activity during pregnancy.The best-fitted model for predicting cyanotic and acyanotic congenital heart disease is the artificial neural network.The results obtained and the best model identified will be useful for medical practitioners and public health scientists for an informed decision-making process about the earlier diagnosis and improve the health condition of children in Pakistan.
基金supported by the National Key Research and Development Program of China(2021YFC2500100)Major Science&Technology Program of Sichuan Province(2022ZDZX0021)+2 种基金National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University(Z2024JC007)Sichuan Science and Technology Program(2024YFHZ0010,2024NSFSC1643)West China Hospital 1.3.5 Project for Disciplines of Excellence(ZYYC23016)。
文摘Animal models constructed using pathogenic factors have significantly advanced drug development for Alzheimer's disease(AD).These predominantly transgenic models,mainly in mice,replicate pathological phenotypes through gene mutations associated with familial AD cases,thus serving as vital tools for assessing drug efficacy and for performing mechanistic studies.However,the speciesspecific differences and complex,heterogeneous nature of AD etiology pose considerable challenges for the translatability of these animal models,limiting their utility in drug development.This review offers a comprehensive analysis of widely employed rodent(mice and rats)and non-rodent models(Danio rerio(zebrafish),Drosophila melanogaster,and Caenorhabditis elegans),detailing their phenotypic features and specific research applications.This review also examines the limitations inherent in these models and introduces various strategies for expanding AD modeling across diverse species,emphasizing recent advancement in non-human primates(NHPs)as valuable models.Furthermore,potential insights from the integration of innovative technologies in AD research are discussed,while providing valuable perspectives on the future development of AD animal models.
基金supported by the Zhejiang Provincial Natural Science Foundation of China(LZ22H050001)National Natural Science Foundation of China(82270704,81970573)+1 种基金“Lingyan”R&D Research and Development Project(2024C03165)Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents。
文摘Acute kidney injury(AKI)and chronic kidney disease(CKD)are significant public health issues associated with a long-term increase in mortality risk,resulting from various etiologies including renal ischemia,sepsis,drug toxicity,and diabetes mellitus.Numerous preclinical models have been developed to deepen our understanding of the pathophysiological mechanisms and therapeutic approaches for kidney diseases.Among these,rodent models have proven to be powerful tools in the discovery of novel therapeutics,while the development of kidney organoids has emerged as a promising advancement in the field.This review provides a comprehensive analysis of the construction methodologies,underlying biological mechanisms,and recent therapeutic developments across different AKI and CKD models.Additionally,this review summarizes the advantages,limitations,and challenges inherent in these preclinical models,thereby contributing robust evidence to support the development of effective therapeutic strategies.
文摘Neurodegeneration is a catastrophic process that develops progressive damage leading to functional andstructural loss of the cells of the nervous system and is among the biggest unavoidable problems of our age.Animalmodels do not reflect the pathophysiology observed in humans due to distinct differences between the neuralpathways,gene expression patterns,neuronal plasticity,and other disease-related mechanisms in animals andhumans.Classical in vitro cell culture models are also not sufficient for pre-clinical drug testing in reflecting thecomplex pathophysiology of neurodegenerative diseases.Today,modern,engineered techniques are applied to developmulticellular,intricate in vitro models and to create the closest microenvironment simulating biological,biochemical,and mechanical characteristics of the in vivo degenerating tissue.In THIS review,the capabilities and shortcomings ofscaffold-based and scaffold-free techniques,organoids,and microfluidic models that best reflect neurodegeneration invitro in the biomimetic framework are discussed.
文摘Cardiovascular Diseases (CVDs) pose a significant global health challenge, necessitating accurate risk prediction for effective preventive measures. This comprehensive comparative study explores the performance of traditional Machine Learning (ML) and Deep Learning (DL) models in predicting CVD risk, utilizing a meticulously curated dataset derived from health records. Rigorous preprocessing, including normalization and outlier removal, enhances model robustness. Diverse ML models (Logistic Regression, Random Forest, Support Vector Machine, K-Nearest Neighbor, Decision Tree, and Gradient Boosting) are compared with a Long Short-Term Memory (LSTM) neural network for DL. Evaluation metrics include accuracy, ROC AUC, computation time, and memory usage. Results identify the Gradient Boosting Classifier and LSTM as top performers, demonstrating high accuracy and ROC AUC scores. Comparative analyses highlight model strengths and limitations, contributing valuable insights for optimizing predictive strategies. This study advances predictive analytics for cardiovascular health, with implications for personalized medicine. The findings underscore the versatility of intelligent systems in addressing health challenges, emphasizing the broader applications of ML and DL in disease identification beyond cardiovascular health.
基金supported by the National Research Foundation of Korea (NRF)funded by the Ministry of Science,ICT&Future Planning (2022R1A2C2006229,2022R1A6A3A01086868)Korea Dementia Research Project through the Korea Dementia Research Center (KDRC)funded by the Ministry of Health&Welfare and Ministry of Science and ICT,Republic of Korea (RS-2024-00345328)KIST Institutional Grant (2E32851)。
文摘Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis.Developing effective diagnostic,preventative,and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease.Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD.Additionally,these models are limited in their ability to elucidate the interplay among amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation.In this study,we introduce a novel AD mouse model(APP/PS1-TauP301L-Adeno mice)designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms.Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAVDJ-EF1a-hTauP301L-EGFP and Adeno-GFAP-GFP viruses into the hippocampi of 5-month-old APP/PS1 mice.Three months post-injection,these mice exhibited pronounced astrogliosis,substantial amyloid-βplaque accumulation,extensiveneurofibrillarytangles,accelerated neuronal loss,elevated astrocytic GABA levels,and significant spatial memory deficits.Notably,these pathological features were less severe in AAVTauP301L-expressing APP/PS1 mice without augmented reactive astrogliosis.These findings indicate an exacerbating role of severe reactive astrogliosis in amyloid-βplaque and neurofibrillary tangle-associated pathology.The APP/PS1-TauP301L-Adeno mouse model provides a valuable tool for advancing therapeutic research aimed at mitigating the progression of AD.
基金supported by 1RO1EY032959-01 and RO1 supplement from NIH,Schuellein Chair Endowment Fund and STEM Catalyst Grant from the University of Dayton(to AS).
文摘Acetyltransferases,required to transfer an acetyl group on protein are highly conserved proteins that play a crucial role in development and disease.Protein acetylation is a common post-translational modification pivotal to basic cellular processes.Close to 80%-90%of proteins are acetylated during translation,which is an irreversible process that affects protein structure,function,life,and localization.In this review,we have discussed the various N-acetyltransferases present in humans,their function,and how they might play a role in diseases.Furthermore,we have focused on N-acetyltransferase 9 and its role in microtubule stability.We have shed light on how N-acetyltransferase 9 and acetylation of proteins can potentially play a role in neurodegenerative diseases.We have specifically discussed the N-acetyltransferase 9-acetylation independent function and regulation of c-Jun N-terminal kinase signaling and microtubule stability during development and neurodegeneration.
基金Supported by Government Assignment,No.1023022600020-6RSF Grant,No.24-15-00549Ministry of Science and Higher Education of the Russian Federation within the Framework of State Support for the Creation and Development of World-Class Research Center,No.075-15-2022-304.
文摘BACKGROUND Ischemic heart disease(IHD)impacts the quality of life and has the highest mortality rate of cardiovascular diseases globally.AIM To compare variations in the parameters of the single-lead electrocardiogram(ECG)during resting conditions and physical exertion in individuals diagnosed with IHD and those without the condition using vasodilator-induced stress computed tomography(CT)myocardial perfusion imaging as the diagnostic reference standard.METHODS This single center observational study included 80 participants.The participants were aged≥40 years and given an informed written consent to participate in the study.Both groups,G1(n=31)with and G2(n=49)without post stress induced myocardial perfusion defect,passed cardiologist consultation,anthropometric measurements,blood pressure and pulse rate measurement,echocardiography,cardio-ankle vascular index,bicycle ergometry,recording 3-min single-lead ECG(Cardio-Qvark)before and just after bicycle ergometry followed by performing CT myocardial perfusion.The LASSO regression with nested cross-validation was used to find the association between Cardio-Qvark parameters and the existence of the perfusion defect.Statistical processing was performed with the R programming language v4.2,Python v.3.10[^R],and Statistica 12 program.RESULTS Bicycle ergometry yielded an area under the receiver operating characteristic curve of 50.7%[95%confidence interval(CI):0.388-0.625],specificity of 53.1%(95%CI:0.392-0.673),and sensitivity of 48.4%(95%CI:0.306-0.657).In contrast,the Cardio-Qvark test performed notably better with an area under the receiver operating characteristic curve of 67%(95%CI:0.530-0.801),specificity of 75.5%(95%CI:0.628-0.88),and sensitivity of 51.6%(95%CI:0.333-0.695).CONCLUSION The single-lead ECG has a relatively higher diagnostic accuracy compared with bicycle ergometry by using machine learning models,but the difference was not statistically significant.However,further investigations are required to uncover the hidden capabilities of single-lead ECG in IHD diagnosis.
