Journal of Investigative Medicine最新文献

{"title":"Multiomics genetic insights into potential molecular targets for intracranial aneurysm.","authors":"Yitong Jia, Fa Lin, Runting Li, Yi Yang, Xiaolin Chen, Shuo Wang","doi":"10.1136/svn-2025-004175","DOIUrl":"https://doi.org/10.1136/svn-2025-004175","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to identify multiomics therapeutic targets for aneurysmal subarachnoid haemorrhage (aSAH) and unruptured intracranial aneurysm (uIA) using Mendelian randomisation (MR), summary-data-based MR (SMR) and postanalysis methods.</p><p><strong>Methods: </strong>Significant genetic variables were extracted from multiple databases, including Expression Quantitative Trait Loci (eQTL) from eQTLGen and Genotype-Tissue Expression V.8, protein QTL from eight plasma studies and methylation QTL from the 2018 genome-wide methylation study<i>.</i> Key molecules linked to aSAH and uIA were identified through MR (SMR) and colocalisation analysis. Functional research and drug development relied on postanalysis approaches, including single-cell analysis, enrichment studies and molecular docking.</p><p><strong>Results: </strong>Nine genes and one protein associated with aSAH, along with two genes and one protein for uIA, were identified. DNA methylation variations significantly influenced outcomes. Colocalisation analysis showed most key molecules shared genetic variants with the diseases. The prioritised targets were PSMA4, PRCP, TNFSF12 and RELT. Enrichment and protein-protein interaction studies indicated these proteins acted mainly through the Phosphoinositide 3-kinase-Ak strain transformation (PI3K-Akt) pathway and cytokine interactions. Molecular docking confirmed stable binding of PRCP with benazepril. Single-cell analysis revealed high expression of prioritised targets in inflammatory cells. Phenome-Wide Association Study suggested potential pleiotropy of priority targets.</p><p><strong>Conclusions: </strong>The study identified key targets for aSAH and uIA, providing insights for developing preventive therapies and advancing research on intracranial aneurysm mechanisms.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vascular β-amyloid potentially colocalises with phosphorylated tau in cerebral amyloid angiopathy.","authors":"Hsin-Hsi Tsai, Bo-Ching Lee, Chia-Ju Liu, Pu-Tien Chiang, Ya-Chin Tsai, Li-Kai Tsai, Syu-Jyun Peng","doi":"10.1136/svn-2024-003774","DOIUrl":"10.1136/svn-2024-003774","url":null,"abstract":"<p><strong>Background: </strong>Tau pathology is observed in cerebral amyloid angiopathy (CAA) and is related to cognitive impairment and neurodegeneration. However, the relationship between tau pathology and amyloid accumulation in the vasculature is unknown. We aimed to assess if regional associations exist between vascular amyloid and tau protein in sporadic CAA.</p><p><strong>Method: </strong>We assessed cerebral amyloid and hyperphosphorylated tau in patients with probable CAA or Alzheimer's disease (AD) using ¹¹C-Pittsburgh compound B (PiB) and ¹⁸F-T807 positron emission tomography (PET). PET data for each region of interest were extracted using an automated anatomical labelling atlas. We generated correlation matrices to investigate the regional correlations between PiB and T807 uptake, which were further adjusted for multiple comparisons. We evaluated if the severity of regional cortical superficial siderosis (cSS) mediates these associations.</p><p><strong>Results: </strong>67 patients with CAA (38 with intracerebral haemorrhage and 29 with cognitive impairment) and 21 patients with AD were included. Significant correlations between amyloid and tau PET uptake were observed in regions of interest for the temporal, parietal and occipital lobes in CAA (adjusted p<0.05); these correlations were not observed in AD. In CAA, the severity of regional cSS correlated positively with T807 uptake in the temporal (β=0.108, 95% CI 0.030 to 0.186, p=0.007) and occipital lobes (β=0.088, 95% CI 0.008 to 0.168, p=0.032). Regional cSS showed no mediating effect on the association between PiB and T807 in the occipital and temporal lobes.</p><p><strong>Conclusions: </strong>In CAA, tau pathology exhibits significant regional in situ correlations with amyloid deposition in the posterior brain, which suggests a distinct pathophysiology to AD.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of futile recanalisation in patients with large infarct: a post-hoc analysis of the ANGEL-ASPECT trial.","authors":"Tingyu Yi, Xiaochuan Huo, Xiaohui Lin, Mengxing Wang, Yan-Min Wu, Zhinan Pan, Xiufen Zheng, Ding-Lai Lin, Yuesong Pan, Zhongrong Miao, Wenhuo Chen","doi":"10.1136/svn-2024-003382","DOIUrl":"https://doi.org/10.1136/svn-2024-003382","url":null,"abstract":"<p><strong>Background: </strong>Studies on futile recanalisation after endovascular therapy (EVT) for anterior circulation large vessel occlusion with large infarct were scarce. The present study aimed to explore the incidence and independent predictors of futile recanalisation in patients with large infarct.</p><p><strong>Methods: </strong>This is a post-hoc analysis of the ANGEL-Alberta Stroke Program Early CT (ASPECT) trial. A favourable outcome was defined as a 90-day modified Rankin Scale score of 0-3; successful reperfusion was defined as extended thrombolysis in cerebral infarction 2b, 2c and 3 on final angiogram; and futile recanalisation was defined as unfavourable outcome despite successful reperfusion. We performed multivariate analysis to identify the predictors of futile recanalisation after EVT in patients with large infarct.</p><p><strong>Results: </strong>A total of 183 patients were included: 91 (49.7%) patients had futile recanalisation and 92 (51.3%) had meaningful recanalisation. In multivariable logistic regression analysis, nonmodifiable factors included older age (age ≥68 years, OR=3.4, 95%CI 1.5 to 7.7, p= 0.003), female sex (OR=2.78, 95%CI 1.28 to 7.27, p=0.01), higher National Institutes of Health Stroke Scale score (NIHSS ≥16, OR=3.1, 95%CI 1.2 to 8.3, p=0.035), diabetes (OR=3.1, 95%CI 1.2 to 8.3, p=0.017) and symptomatic intracranial haemorrhage (sICH) (OR=9.1, 95%CI 1.0 to 80.7, p=0.049), and modifiable factors included larger final infarct volume (FIV ≥174.7, OR=6.2, 95%CI 2.5 to 15.7, p<0.001) and postoperative respiratory failure (OR=14.1, 95%CI 1.6 to 124.8, p=0.018), which were independent predictors of futile recanalisation.</p><p><strong>Conclusions: </strong>Futile recanalisation occurred in approximately half of patients who had an acute stroke with large infarct after EVT in the ANGEL-ASPECT trial. Nonmodifiable factors that included old age, high baseline NIHSS score, diabetes mellitus, sICH and large FIV, and modifiable factors that included respiratory failure were independent predictors of futile recanalisation after EVT for large ischaemic strokes. Stroke-related pneumonia control may improve prognosis.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of depression and cognitive impairment and their inter-relationship and association with quality of life among older stroke survivors: the findings of a national survey in China.","authors":"Mu-Rui Zheng, Pan Chen, Yuan Feng, Qinge Zhang, Zhaohui Su, Teris Cheung, Gabor S Ungvari, Chee H Ng, Yu-Tao Xiang","doi":"10.1136/svn-2024-003623","DOIUrl":"https://doi.org/10.1136/svn-2024-003623","url":null,"abstract":"<p><strong>Background: </strong>Post-stroke depression (PSD) and post-stroke cognitive impairment (PSCI) are prevalent neuropsychiatric problems that are associated with high disability burden and low quality of life (QoL). This study explored the PSD-PSCI network, along with the interaction and association with QoL among Chinese older stroke survivors.</p><p><strong>Methods: </strong>Data from the 2017-2018 wave of the Chinese Longitudinal Healthy Longevity Survey were obtained to investigate the inter-relationship between PSD and PSCI among older stroke survivors. Central and bridge symptoms within the PSD-PSCI network and their association with QoL were explored. Depressive symptoms, cognitive impairment and QoL were measured using the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10), Mini-Mental State Examination and the WHO QoL-brief version, respectively.</p><p><strong>Results: </strong>The prevalence of PSD and PSCI among older stroke survivors was 31.5% and 22.1%, respectively. In the PSD-PSCI network, 'feeling blue/depressed' (CESD3, strength: 1.117) and 'Attention and calculation' (At_C, strength: 0.972) were the most influential symptoms, while 'Naming' (Nam, bridge strength: 0.175) was the most significant bridge symptom. Notably, 'Sleep disturbances' (CESD10) had the strongest association with lower QoL.</p><p><strong>Conclusion: </strong>This study revealed that both PSD and PSCI were prevalent among older stroke survivors. The key central and bridge symptoms in the PSD-PSCI network, along with those symptoms that negatively impact on QoL, should be prioritised in targeted interventions to enhance treatment outcomes in this population.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Definitions of white matter hyperintensity change: impact on estimates of progression and regression.","authors":"Angela C C Jochems, Susana Muñoz Maniega, Una Clancy, Carmen Arteaga Reyes, Daniela Jaime Garcia, Maria Del C Valdés Hernández, Francesca M Chappell, Gayle Barclay, Charlotte Jardine, Donna McIntyre, Iona Gerrish, Stewart Wiseman, Michael S Stringer, Michael J Thrippleton, Fergus Doubal, Joanna M Wardlaw","doi":"10.1136/svn-2024-003300","DOIUrl":"10.1136/svn-2024-003300","url":null,"abstract":"<p><strong>Background: </strong>White matter hyperintensity (WMH) progression is well documented; WMH regression is more contentious, which might reflect differences in defining WMH change. We compared four existing WMH change definitions in one population to determine the effect of definition on WMH regression.</p><p><strong>Methods: </strong>We recruited patients with minor non-disabling ischaemic stroke who underwent MRI 1-3 months after stroke and 1 year later. We assessed WMH volume (in absolute mL and % intracranial volume) and applied four different definitions, including two thresholds (based on SD or mL), percentile and quintile approaches.</p><p><strong>Results: </strong>In 198 participants, mean age 65.5 (SD=11.13), baseline WMH volume was 15.46 mL (SD=19.2), the mean net WMH volume change was 0.98 mL (SD=2.84), range -7.98 to +12.84 mL. Proportion regressing/stable/progressing WMH were threshold 1 (SD), 29.8%/55.6%/14.6%; threshold 2(mL), 29.8%/16.7%/53.5%; percentile approach, 28.3%/21.2%/50.5%. The quintile approach includes five groups with quintile 3 reflecting no change (N=40), quintiles 1 and 2 any WMH decrease (N=80) and quintiles 4 and 5 any WMH increase (N=78).</p><p><strong>Conclusions: </strong>Different WMH change definitions cause big differences in how participants are categorised; additionally, non-normal WMH distribution precludes use of some definitions. Consistent use of an appropriate definition would facilitate data comparisons, particularly in clinical trials of potential WMH treatments.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"411-414"},"PeriodicalIF":2.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of malignant swelling in space-occupying cerebellar infarction.","authors":"Enayatullah Baki, Lea Baumgart, Victoria Kehl, Felix Hess, Andreas Wolfgang Wolff, Arthur Wagner, Moritz Roman Hernandez Petzsche, Tobias Boeckh-Behrens, Bernhard Hemmer, Bernhard Meyer, Jens Gempt, Silke Wunderlich","doi":"10.1136/svn-2024-003360","DOIUrl":"10.1136/svn-2024-003360","url":null,"abstract":"<p><strong>Background: </strong>Malignant swelling is a fatal complication that can occur abruptly in space-occupying cerebellar infarction. We aimed to establish markers that predict malignant swelling in cerebellar infarction.</p><p><strong>Methods: </strong>We retrospectively analysed data of stroke patients who were treated in our hospital between 2014 and 2020. Malignant swelling was defined as a mass effect in the posterior cranial fossa, accompanied by a decrease in consciousness due to compression of the brainstem and/or the development of obstructive hydrocephalus. Statistical analyses were performed on multiple variables to identify predictors of malignant swelling.</p><p><strong>Results: </strong>Among 7284 stroke patients, we identified 487 patients with an infarct in the cerebellum. 93 patients were suitable for analysis having space-occupying cerebellar infarction. 33 of 93 (35.5%) patients developed malignant swelling. Multivariable analysis revealed infarct volume as the main predictor being independently associated with the development of malignant swelling with a cut-off infarct volume of 38 cm³ being associated with a swelling rate of >50% (OR 32.0, p<0.001). Higher NIHSS (National Institutes of Health Stroke Scale) score on admission (median NIHSS 12 vs 4, OR 1.078; p=0.008) and the presence of additional brainstem infarction (51.5% vs 16.7%, OR 5.312; p=0.013) were associated with the development of malignant swelling in univariate analyses. 13 of 33 (39.4%) cases of malignant swellings occurred after more than 3 days.</p><p><strong>Conclusions: </strong>Infarct volume was the key significant predictor of malignant swelling in space-occupying cerebellar infarction. With many cases of malignant swelling occurring after more than 72 hours, we advocate prolonged neurological monitoring.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"323-329"},"PeriodicalIF":2.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angioplasty and/or stenting following successful mechanical thrombectomy for intracranial atherosclerosis-related emergent large vessel occlusive stroke (ASSET): protocol of a multicentre randomised trial.","authors":"Geng Liao, Hongyu Qiao, Chengbo Dai, Weiwen Yi, Liang Zhang, Zai Liang, Li Li, Yuemei He, Zhenyu Zhang, Zhong Ji, Li'an Huang","doi":"10.1136/svn-2024-003435","DOIUrl":"10.1136/svn-2024-003435","url":null,"abstract":"<p><strong>Rationale: </strong>The management of residual stenosis after mechanical thrombectomy in patients with intracranial atherosclerotic stenosis-related emerge large vessel occlusive (ICAS-LVO) stroke is still unclear question in clinical practice.</p><p><strong>Aim: </strong>To demonstrate the design of a clinical trial on emergency balloon angioplasty and/or stenting (BAS) combined with standard medical treatment (SMT) for residual stenosis of ICAS-LVO stroke patients with successful recanalisation.</p><p><strong>Design: </strong>ASSET is a multicentre, prospective, randomised, open-label, blinded end-point, controlled clinical trial designed (PROBE) by investigators. This trial evaluates the effectiveness and the safety of emergency BAS in combination with SMT compared with SMT alone in ICAS-LVO stroke patients with successful recanalisation (defined as expanded treatment in cerebral ischaemia grade of 2b50-3 and maintained for more than 20 min) and residual stenosis (defined as ≥50%) up to 24 hours after the onset of symptoms or the last known well.</p><p><strong>Outcome: </strong>The primary outcome assessed at 90 (±7) days after randomisation is the incidence of ischaemic stroke in the responsible vessel. Symptomatic intracranial haemorrhage within 24 (±3) hours is the primary safety outcome.</p><p><strong>Discussion: </strong>The ASSET trial is designed to provide strong evidence on the effectiveness and safety of emergency BAS to treat residual stenosis after successful recanalisation in patients with ICAS-LVO stroke.</p><p><strong>Trial registration number: </strong>ChiCTR2300079069.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"379-385"},"PeriodicalIF":2.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142356519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advance Consent for participation in Acute Stroke Trials (ACTION): protocol for a feasibility study.","authors":"Ubong Udoh, Rena Seeger, Brian Dewar, Emma Cummings, Sophia Gocan, Stuart Nicholls, Mark Fedyk, Victoria Shepherd, Jeff Perry, Robert Fahed, Tim Ramsay, Jamie Brehaut, Michael D Hill, Alexandre Y Poppe, Bijoy K Menon, Richard H Swartz, Dar Dowlatshahi, Michel Shamy","doi":"10.1136/svn-2023-003029","DOIUrl":"10.1136/svn-2023-003029","url":null,"abstract":"<p><strong>Introduction: </strong>Obtaining informed consent for research from patients in medical emergencies remains a challenge, particularly in acute stroke care as treatment must be administered quickly and patients often arrive in the hospital in a state of incapacitation. Adaptations to standard consenting approaches-such as the use of surrogate consent or deferral of consent-have significant limitations. This feasibility study aims to test a new consenting approach in acute stroke care that we call advance consent. Advance consent has the potential to render emergency trial enrolment faster, fairer and more transparent, leading to more generalisable results.</p><p><strong>Methods and design: </strong>We will conduct a five-part study at The Ottawa Hospital, a quaternary care stroke centre: (1) administering questionnaires in the Ottawa Hospital Stroke Prevention Clinic that will examine patients' perspectives on research participation and advance consent; (2) inviting participants to consent in advance to any or both currently enrolling acute stroke trials; (3) tracking patient enrolment into these trials over 1 year; (4) administering a follow up questionnaire to participants at 1 year and (5) administering a questionnaire to participating hospital staff in order to interrogate their experiences with advance consent. Outcomes include but are not limited to eligibility rate, recruitment rate, withdrawal rate and the proportion of patients whose advance consent results in trial enrolment.</p><p><strong>Conclusion: </strong>This study will test the feasibility of enrolling patients at risk of stroke into acute stroke trials using advance consent.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"386-390"},"PeriodicalIF":2.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes-mediated delivery of miR-486-3p alleviates neuroinflammation via SIRT2-mediated inhibition of mitophagy after subarachnoid hemorrhage.","authors":"Bin Sheng, Sen Gao, XiangXin Chen, Yang Liu, Niansheng Lai, Jin Dong, Jiaqing Sun, Yan Zhou, Lingyun Wu, Chun-Hua Hang, Wei Li","doi":"10.1136/svn-2024-003509","DOIUrl":"10.1136/svn-2024-003509","url":null,"abstract":"<p><strong>Background: </strong>Neuroinflammation participates in the pathogenesis of subarachnoid haemorrhage (SAH); however, no effective treatments exist. MicroRNAs regulate several aspects of neuronal dysfunction. In a previous study, we found that exosomal miR-486-3p is involved in the pathophysiology of SAH. Targeted delivery of miR-486-3p without blood-brain barrier (BBB) restriction to alleviate SAH is a promising neuroinflammation approach.</p><p><strong>Methods: </strong>In this study, we modified exosomes (Exo) to form an RVG-miR-486-3p-Exo (Exo/miR) to achieve targeted delivery of miR-486-3p to the brain. Neurological scores, brain water content, BBB damage, flow cytometry and FJC staining were used to determine the effect of miR-486-3p on SAH. Western blot analysis, ELISA and RT-qPCR were used to measure relevant protein and mRNA levels. Immunofluorescence staining and laser confocal detection were used to measure the expression of mitochondria, lysosomes and autophagosomes, and transmission electron microscopy was used to observe the level of mitophagy in the brain tissue of mice after SAH.</p><p><strong>Results: </strong>Tail vein injection of Exo/miR improved targeting of miR-486-3p to the brains of SAH mice. The injection reduced levels of neuroinflammation-related factors by changing the phenotype switching of microglia, inhibiting the expression of sirtuin 2 (SIRT2) and enhancing mitophagy. miR-486-3p treatment alleviated neurobehavioral disorders, brain oedema, BBB damage and neurodegeneration. Further research found that the mechanism was achieved by regulating the acetylation level of peroxisome proliferator-activated receptor γ coactivator l alpha (PGC-1α) after SIRT2 enters the nucleus.</p><p><strong>Conclusion: </strong>Exo/miR treatment attenuates neuroinflammation after SAH by inhibiting SIRT2 expression and stimulating mitophagy, suggesting potential clinical applications.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"335-346"},"PeriodicalIF":2.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone marrow-derived mesenchymal stem cell ameliorates post-stroke enterobacterial translocation through liver-gut axis.","authors":"Xiaotao Su, Tiemei Li, Yuge Wang, Lei Wei, Banghao Jian, Xinmei Kang, Mengyan Hu, Chunyi Li, Shisi Wang, Danli Lu, Shishi Shen, Huipeng Huang, Yuxin Liu, Xiaohui Deng, Bingjun Zhang, Wei Cai, Zhengqi Lu","doi":"10.1136/svn-2024-003494","DOIUrl":"10.1136/svn-2024-003494","url":null,"abstract":"<p><strong>Background: </strong>Enterobacterial translocation is a leading contributor to fatal infection among patients with acute ischaemic stroke (AIS). Accumulative evidence suggests that mesenchymal stem cell (MSC) effectively ameliorates stroke outcomes. Whether MSC could inhibit post-stroke enterobacterial translocation remains elusive.</p><p><strong>Methods: </strong>Patients with AIS and healthy individuals were enrolled in the study. Mice subjected to transient middle cerebral artery occlusion were treated with bone marrow-derived MSC (BM-MSC) right after reperfusion. Enterobacterial translocation was evaluated with Stroke Dysbiosis Index and circulating endotoxin. Thickness of mucus was assessed with Alcian blue staining. Hepatic glucocorticoid (GC) metabolism was analysed with expression of HSD11B2, HSD11B1 and SRD5A1.</p><p><strong>Results: </strong>We report that the gut mucus layer was attenuated after the stroke leading to pronounced enterobacterial translocation. The attenuation of the gut mucus was attributed to diminished mucin production by goblet cells in response to the elevated systemic GC after cerebral ischaemia. Transferred-BM-MSC restored the mucus thickness, thus preserving gut microbiota homeostasis and preventing enterobacterial invasion. Mechanistically, the transferred-BM-MSC stationed in the liver and enhanced peroxisome proliferator-activated receptor γ signalling in hepatocytes. Consequently, expression of HSD11B2 and SRD5A1 was increased while HSD11B1 expression was downregulated which promoted GC catabolism and subsequently restored mucin production.</p><p><strong>Conclusions: </strong>Our findings reveal that MSC transfer improves post-stroke gut barrier integrity and inhibits enterobacterial translocation by enhancing the hepatic GC metabolism thus representing a protective modulator of the liver-gut-brain axis in AIS.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"359-370"},"PeriodicalIF":2.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}