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Machine learning applications in stroke medicine:advancements,challenges,and future prospectives

Neural Regeneration Research 2024年第4期19卷 769-773页

作者： Mario Daidone Sergio Ferrantelli Antonino Tuttolomondo Internal medicine and stroke Care Ward Department of Health PromotionMother and Child CareInternal Medicine and Medical SpecialtiesUniversity of Palermo Molecular and Clinical medicine PhD Program University of Palermo

stroke is a leading cause of disability and mortality worldwide,necessitating the development of advanced technologies to improve its diagnosis,treatment,and patient *** recent years,machine learning techniques have emerged as promising tools in stroke medicine,enabling efficient analysis of large-scale datasets and facilitating personalized and precision medicine *** abstract provides a comprehensive overview of machine learning’s applications,challenges,and future directions in stroke *** introduced machine learning algorithms have been extensively employed in all the fields of stroke *** learning models have demonstrated remarkable accuracy in imaging analysis,diagnosing stroke subtypes,risk stratifications,guiding medical treatment,and predicting patient *** the tremendous potential of machine learning in stroke medicine,several challenges must be *** include the need for standardized and interoperable data collection,robust model validation and generalization,and the ethical considerations surrounding privacy and *** addition,integrating machine learning models into clinical workflows and establishing regulatory frameworks are critical for ensuring their widespread adoption and impact in routine stroke *** learning promises to revolutionize stroke medicine by enabling precise diagnosis,tailored treatment selection,and improved *** research and collaboration among clinicians,researchers,and technologists are essential for overcoming challenges and realizing the full potential of machine learning in stroke care,ultimately leading to enhanced patient outcomes and quality of *** review aims to summarize all the current implications of machine learning in stroke diagnosis,treatment,and prognostic *** the same time,another purpose of this paper is to explore all the future perspectives these techniques can provide in combating this disabling dis

关键词： cerebrovascular disease deep learning machine learning reinforcement learning stroke stroke therapy supervised learning unsupervised learning

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ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3027-3048页

作者： Mengdie Dong Yunjia Zhang Minghong Chen Yongkang Tan Jiao Min Xian He Fuhao Liu Jiaming Gu Hong Jiang Longbin Zheng Jiajing Chen Quanwen Yin Xuesong Li Xiang Chen Yongfeng Shao Yong Ji Hongshan Chen Department of Cardiovascular Surgery the First Affiliated Hospital of Nanjing Medical Universityand Key Laboratory of Cardiovascular and Cerebrovascular MedicineSchool of PharmacyNational Vaccine Innovation PlatformNanjing Medical UniversityNanjing 211166China Key Laboratory of Cardiovascular and cerebrovascular medicine School of PharmacyNanjing Medical UniversityNanjing 211166China Department of Clinical medicine Nanjing Medical University TIANYUAN Honors SchoolNanjing Medical UniversityNanjing 211166China Department of Anesthesiology Sir Run Run HospitalNanjing Medical UniversityNanjing 211166China Department of Cardiovascular Surgery the First Affiliated Hospital of Nanjing Medical UniversityNanjing 211166China Key Laboratory of Cardiovascular and cerebrovascular medicine Key Laboratory of Targeted Intervention of Cardiovascular DiseaseCollaborative Innovation Center for Cardiovascular Disease Translational MedicineState Key Laboratory of Reproductive MedicineSchool of Pharmacythe Affiliated Suzhou Hospital of Nanjing Medical UniversityGusu SchoolNanjing Medical UniversityNanjing 211166China National Key Laboratory of Frigid Zone Cardiovascular Diseases(NKLFZCD) Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China)College of PharmacyKey Laboratory of Cardiovascular Medicine Research and Key Laboratory of Myocardial IschemiaChinese Ministry of EducationNHC Key Laboratory of Cell Transplantationthe Central Laboratory of the First Affiliated HospitalHarbin Medical UniversityHarbin 150081China Key Laboratory of Targeted Intervention of Cardiovascular Disease Collaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjing Medical UniversityNanjing 211166China Department of Cardiology Huai’an First People’s Hospital Affiliated with Nanjing Medical UniversityHuai’an 223399China

Endothelial-to-mesenchymal transition(EndMT)is a key driver of *** glycolysis is increased in the endothelium of atheroprone areas,accompanied by elevated lactate *** lactylation,mediated by lactate,can regulate gene expression and participate in disease ***,whether histone lactylation is involved in atherosclerosis remains ***,we report that lipid peroxidation could lead to EndMT-induced atherosclerosis by increasing lactatedependent histone H3 lysine 18 lactylation(H3K18la)in vitro and in vivo,as well as in atherosclerotic patients’***,the histone chaperone ASF1A was first identified as a cofactor of P300,which precisely regulated the enrichment of H3K18la at the promoter of SNAI1,thereby activating SNAI1 transcription and promoting *** found that deletion of ASF1A inhibited EndMT and improved endothelial *** analysis based on Apoe^(KO)Asf1a^(ECKO) mice in the atherosclerosis model confirmed the involvement of H3K18la in atherosclerosis and found that endotheliumspecific ASF1A deficiency inhibited EndMT and alleviated atherosclerosis *** of glycolysis by pharmacologic inhibition and advanced PROTAC attenuated H3K18la,SNAI1 transcription,and EndMT-induced *** study illustrates precise crosstalk between metabolism and epigenetics via H3K18la by the P300/ASF1A molecular complex during EndMT-induced atherogenesis,which provides emerging therapies for atherosclerosis.

关键词： Histone lactylation Atherosclerosis Endothelial-tomesenchymal transition ASF1A SNAI1 Endothelial dysfunction Lactate Epigenetic

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mA reader YTHDF2 governs the onset of atrial fibrillation by modulating Cacna1c translation

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Science China Life Sciences 2024年

作者： Chuansheng Chen Guanghua Wang Qicheng Zou Ke Xiong Zhiwen Chen Beihua Shao Yi Liu Duanyang Xie Yong Ji Key Laboratory of Cardiovascular and cerebrovascular medicine Nanjing Medical University State Key Laboratory of Cardiovascular Diseases Shanghai East Hospital School of Medicine Tongji University Department of Pathology and Pathophysiology School of Medicine Tongji University Department of Cardiology School of Medicine Tongji University Shanghai Arrhythmia Research Center Shanghai East Hospital School of Medicine Tongji University

Atrial fibrillation（AF） is the most common arrhythmia, which is tightly associated with the abnormal expression and function of ion channels in the atrial cardiomyocytes. N6-methyladenosine（m6A）, a widespread chemical modification in eukaryotic m RNA, is known to play a significant regulatory role in the pathogenesis of heart disease. However, the significance of m6A regulatory proteins in the onset of AF remains unclear. Here, we demonstrate that the m6A reader protein YTHDF2 regulates atrial electrical remodeling and AF onset by modulating the Cav1.2 expression. Firstly, YTHDF2 expression was selectively upregulated in rat atrial cardiomyocytes with AF. Secondly,YTHDF2 knockout reduced AF susceptibility in mice. Thirdly, the knockout of YTHDF2 increased Cav1.2 protein levels in an m6A-independent manner, ultimately prolonging the atrial myocardial refractory period, a critical electrophysiological substrate for the onset of AF. Fourthly, the N-terminal domain of YTHDF2 was identified as critical for Cacna1c m RNA translation regulation. Overall, our findings unveil that YTHDF2 can alter Cav1.2 protein expression in an m6A-independent manner, thereby facilitating the onset of AF. Our study suggests that YTHDF2 may be a potential intervention target for AF.

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The burgeoning importance of PIWI-interacting RNAs in cancer progression

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Science China(Life Sciences) 2024年第4期67卷 653-662页

作者： Xinpei Deng Tianle Liao Jindong Xie Da Kang Yiwei He Yuying Sun Zhangling Wang Yongluo Jiang Xuan Miao Yixuan Yan Hailin Tang Lewei Zhu Yutian Zou Peng Liu State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China School of medicine Sun Yat-sen UniversityShenzhen 518107China Key Laboratory of Cardiovascular and cerebrovascular medicine Nanjing Medical UniversityNanjing 211166China Guanghua School of Stomatology Sun Yat-sen UniversityGuangzhou 510062China The First People’s Hospital of Foshan Foshan 528000China

PIWI-interacting RNAs(pi RNAs)are a class of small noncoding RNA molecules that specifically bind to piwi protein family members to exert regulatory functions in germ *** studies have found that pi RNAs,as tissue-specific molecules,both play oncogenic and tumor suppressive roles in cancer progression,including cancer cell proliferation,metastasis,chemoresistance and ***,the atypical manifestation of pi RNAs and PIWI proteins in various malignancies presents a promising strategy for the identification of novel biomarkers and therapeutic targets in the diagnosis and management of ***,the precise functions of pi RNAs in cancer progression and their underlying mechanisms have yet to be fully *** review aims to examine current research on the biogenesis and functions of pi RNA and its burgeoning importance in cancer progression,thereby offering novel perspectives on the potential utilization of pi RNAs and piwi proteins in the management and treatment of advanced cancer.

关键词： PIWI-interacting RNAs/piRNAs cancer progression metastasis chemoresistance stemness

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Overview of epigenetic degraders based on PROTAC, molecular glue, and hydrophobic tagging technologies

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Acta Pharmaceutica Sinica B 2024年第2期14卷 533-578页

作者： Xiaopeng Peng Zhihao Hu Limei Zeng Meizhu Zhang Congcong Xu Benyan Lu Chengpeng Tao Weiming Chen Wen Hou Kui Cheng Huichang Bi Wanyi Pan Jianjun Chen College of Pharmacy Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of EducationGannan Medical UniversityGanzhou 314000China College of Basic medicine Gannan Medical UniversityGanzhou 314000China Guangdong Provincial Key Laboratory of New Drug Screening NMPA Key Laboratory for Research and Evaluation of Drug MetabolismSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators(e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges,including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result,the design of new epigenetic modulators(e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging(Hy T) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review,we aim to provide an in-depth illustration of new degrading strategies(2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

关键词： Epigenetic Degrader PROTAC Molecularglue Hydrophobic tagging

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3'-Deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome

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Neural Regeneration Research 2024年第10期19卷 2270-2280页

作者： Yize Qi Yao Zhou Jiyang Li Fangyuan Zhu Gengni Guo Can Wang Man Yu Yijie Wang Tengfei Ma Shanwu Feng Li Zhou Institute for Stem Cell and Neural Regeneration and Key Laboratory of Cardiovascular&cerebrovascular medicine School of PharmacyNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Anesthesiology The Second People’s Hospital of LianyungangLianyungangJiangsu ProvinceChina Department of Anesthesiology Women’s Hospital of Nanjing Medical UniversityNanjing Maternity and Child Health Care HospitalNanjingJiangsu ProvinceChina

Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.

关键词： 3′-deoxyadenosin hippocampus long-term potentiation methamphetamine NOD-like receptor family pyrin domain containing-3(NLRP3)inflammasome synaptic plasticity

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Sanhua Tang(三化汤) protects against ischemic stroke by preventing blood-brain barrier injury: a network pharmacology and in vivo experiments

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Journal of Traditional Chinese medicine 2024年第4期44卷 794-803页

作者： LUO Shan YANG Fan CHEN Yuanchun ZHAO Ruoxi LIU Haiye GAO Fei MA Wencan GAO Weijuan YU Wentao College of Basic medicine Hebei University of Chinese MedicineShijiazhuang 050200China Graduate School Hebei University of Chinese MedicineShijiazhuang 050091China College of Acupuncture and Massage Hebei University of Chinese MedicineShijiazhuang 050200China Hebei Key Laboratory of Chinese medicine Research on Cardio-cerebrovascular Diseases Shijiazhuang 050091China Hebei International Joint Research Centre for Acupuncture and Moxibustion of Traditional Chinese medicine Shijiazhuang 050091China

OBJECTIVE:To assess the effect and mechanism of Sanhua Tang(三化汤,SHT)in treating ischemic stroke(IS)through the"Kaitong Xuanfu"theory by using network pharmacology and animal ***:The active ingredients and targets of SHT and IS were screened by public databases such as Traditional Chinese medicine systems pharmacology,GeneCards,and online mendelian inheritance in *** network topographies were constructed using R,Cytoscape 3.6.0,AutoDockTools,a user-sponsored molecular visualization system on an open-source foundation,and other software to analyze the correlation between targets and active *** middle cerebral artery occlusion(MCAO)model was established by *** were divided into the Sham group,MCAO group(M group),aloe-emodin(AE)group(MCAO rats treated with aloe-emodin),SHT at low dosage(SL group)(MCAO rats treated with SL),SHT at medium dosage(SM group),and SHT at high dosage(SH group).2,3,5-triphenyl tetrazolium chloride staining was used to detect the volume of cerebral infarction;Nissl staining was used to observe the morphology of neuronal cells;transmission electron microscopy was used to observe the integrity of the blood-brain barrier(BBB);enzymelinked immunosorbent assay was used to detect the content of interleukin-6(IL-6),IL-10,tumor necrosis factorα(TNF-α)in *** blot was used to detect the expression of vascular endothelial growth factor A(VEGFA)protein in the cerebral ischemic ***:Using network pharmacology and molecular docking validation,four active ingredients(lignan,naringenin,aloe-rhodopsin,andβ-sitosterol),seven target proteins(protein kinase b 1,IL-6,TNF,VEGFA,TP53,jun proto-oncogene,and cysteinyl aspartate specific proteinase 3),and inflammatory signaling pathways were *** experiments showed that the SH and AE groups had fewer neurological deficits,reduced brain infarct volumes,decreased serum inflammatory factor levels,increased expression of VEGFA protein,and less

关键词：三化汤 damage barrier

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Reveal the pharmacodynamic substances and mechanism of an edible medicinal plant Rhodiola crenulate in DSS-induced colitis through plasma pharmacochemistry and metabolomics

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Food Science and Human Wellness 2024年第4期13卷 2116-2131页

作者： Yu Peng Xiaoao Xiao Tingting Ji Xinyuan Wang Yixuan Xu Jianbo Xiao Hui Cao Zhiyong Chen Huifan Liu Yuanqing Gao Hongxun Tao Key Laboratory of Cardiovascular and cerebrovascular medicine School of PharmacyNanjing Medical UniversityNanjing 211166China School of Food and Biological Engineering Jiangsu UniversityZhenjiang 212013China Department of Analytical Chemistry and Food Science Faculty of ScienceUniversity of VigoVigo 36310Spain CISPAC Fontan BuildingCity of CultureSantiago de Compostela 15707Spain Shaanxi Academy of Traditional Chinese medicine Xi'an 710003China Guangdong Key Laboratory of Science and Technology of Lingnan Specialty Food Zhongkai University of Agriculture and EngineeringGuangzhou 510550China State Key Laboratory of Southwestern Chinese medicine Resources Chengdu 610075China

Rhodiola crenulate is the edible medicinal herbal medicine widely used for altitude sickness in ***,our previous work has found that *** extract(RCE)could significantly improve the pathology associated with dextran sulfate sodium-induced ***,the current research aims to reveal the pharmacodynamic material basis of RCE,as well as its mechanism against *** chemical characterization of RCE was performed by UHPLC-HR-MS,through which a total of 88 constituents were ***,our results also found 29 constituents absorbed into blood and 8 metabolized absorbable *** decreased flavonoids prototype and the elevated sulfated products of phenols were observed under pathophysiological conditions of *** metabolomics study revealed that colitis caused the alternation of fatty acid metabolism,steroid hormone biosynthesis and bile acid ***,RCE could prevent colitis by improving fatty acid metabolism and secondary bile acid metabolism.

关键词： Rhodiola crenulate Colitis Chemical characterization Plasma pharmacochemistry Metabolomics

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Mesenchymal stem cell therapy for liver fibrosis need“partner”:Results based on a meta-analysis of preclinical studies

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World Journal of Gastroenterology 2024年第32期30卷 3766-3782页

作者： Yan Xu Xue-Song Wang Xiao-Lei Zhou Wen-Ming Lu Xing-Kun Tang Yu Jin Jun-Song Ye Subcenter for Stem Cell Clinical Translation First Affiliated Hospital of Gannan Medical UniversityGanzhou 341000Jiangxi ProvinceChina School of Rehabilitation medicine Gannan Medical UniversityGanzhou 341000Jiangxi ProvinceChina Ganzhou Key Laboratory of Stem Cell and Regenerative medicine Gannan Medical UniversityGanzhou 341000Jiangxi ProvinceChina Department of Medical Genetics School of MedicineTongji UniversityShanghai 200092China Key Laboratory of Prevention and Treatment of Cardiovascular and cerebrovascular Diseases Ministry of EducationGannan Medical UniversityGanzhou 341000Jiangxi ProvinceChina

BACKGROUND The efficacy of mesenchymal stem cells(MSCs)in treating liver fibrosis has been demonstrated in several clinical ***,their low survival and liver implantation rates remain *** recent years,a large number of studies in animal models of liver fibrosis have shown that MSCs combined with drugs can improve the efficacy of MSCs in the treatment of liver fibrosis alone and inhibit its progression to end-stage liver *** has inspired new ways of thinking about treating liver *** To investigate the effectiveness and mechanisms of MSCs combined with drugs in treating liver *** Data sources included four electronic databases and were constructed until January *** subjects,interventions,comparators,outcomes,and study design principle were used to screen the literature,and the quality of the literature was evaluated to assess the risk of *** randomised controlled trials were selected,and the final 13 studies were included in the final *** A total of 13 studies were included after *** analysis showed that MSCs combined with drug therapy significantly improved liver function,promoted the repair of damaged liver tissues,reduced the level of liver fibrosis-related indexes,and effectively ameliorated hepatic fibrosis by modulating the hepatic inflammatory microenvironment,promoting the homing of MSCs,and regulating the relevant signaling pathways,and the treatment efficacy was superior to MSCs ***,the combined treatment statistics showed no amelioration in serum albumin levels(standardized mean difference=0.77,95%confidence interval:-0.13 to 1.68,P=0.09).CONCLUSION In conclusion,MSCs combined with drugs for treating liver fibrosis effectively make up for the shortcomings of MSCs in their therapeutic ***,due to the different drugs,the treatment mechanism and effect also ***,more randomized controlled trials are needed to compare the therapeutic effic

关键词： drugs alone partner

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Rationale and design of Tenecteplase Reperfusion Therapy in Acute Ischaemic cerebrovascular Events III (TRACE III): a randomised, phase III, open- label, controlled trial

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stroke & Vascular Neurology 2024年第1期9卷 82-89页

作者： Yunyun Xiong Bruce C V Campbell Marc Fisher Lee H Schwamm Mark Parsons Hao Li Yuesong Pan Xia Meng Xingquan Zhao Yongjun Wang Neurology Beijing Tiantan HospitalBeijingChina China National Clinical Research Center for Neurological Diseases BeijingChina Department of medicine and Neurology The University of MelbourneMelbourneVictoriaAustralia Neurology Beth Israel Deaconess Medical CenterBostonMassachusettsUSA Department of Neurology and Comprehensive stroke Center Massachusetts General HospitalBostonMassachusettsUSA Department of Neurology University of New South Wales South Western Sydney Clinical SchoolLiverpoolNew South WalesAustralia

Background and purpose Recombinant human TNK tissue-type plasminogen activator(rhTNK-tPA)was not inferior to alteplase for ischaemic stroke within *** study aimed to investigate the efficacy and safety of rhTNK-tPA in patients who had an ischaemic stroke due to large vessel occlusion(LVO)of anterior circulation beyond *** and design Tenecteplase Reperfusion Therapy in Acute Ischaemic cerebrovascular Events-III(TRACE III)is a multicentre,prospective,randomised,open-label,blind endpoint,controlled clinical *** who had an ischaemic stroke due to anterior circulation LVO(internal carotid artery,middle cerebral artery M1 and M2 segments)within 4.5–24hours from last known well(including wake-up stroke and no witness stroke)and with salvageable tissue(ischaemic core volumestroke Scale(NIHSS)at 72 hours,mRS score≤2 at 90 days,the rate of improvement on Tmax>6s at 24 hours and NIHSS score change from baseline at *** outcomes are symptomatic intracerebral haemorrhage within 36 hours and mortality at 90 *** TRACE III will provide evidence for the efficacy and safety of rhTNK-tPA in patients who had an ischaemic strokes due to anterior circulation LVO beyond *** registration number NCT05141305.

关键词： Therapy random Rational

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