Journal of Translational Medicine最新文献

Background: Intracerebral hemorrhage (ICH) represents one of the most severe forms of cerebrovascular injury, characterized by high mortality and lasting neurological dysfunction. Neural stem cells (NSCs), which are indispensable for neurogenesis, are mainly distributed in the hippocampus, a brain region essential for learning and memory. However, alterations in hippocampal NSCs following ICH and the mechanisms that mediate these changes remain poorly defined. The present study investigates the effects of ICH on hippocampal NSCs, focusing on the regulatory role of MTHFD2 in maintaining mitochondrial redox homeostasis through NADPH metabolism.

Methods: Both in vivo and in vitro ICH models were used, including a collagenase-induced mouse model and a hemin-treated NSC model, to examine molecular and cellular responses of hippocampal NSCs to hemorrhagic injury. Western blotting, RNA sequencing, CUT&Tag profiling, and ChIP-qPCR were employed to analyze the related pathways.

Results: We found that NSCs exhibited a time-dependent response after ICH, showing initial activation followed by gradual functional exhaustion and increased apoptosis. ICH induced persistent endoplasmic reticulum stress and significantly upregulated MTHFD2, a mitochondrial enzyme essential for one-carbon metabolism. Mechanistically, MTHFD2 was required to maintain mitochondrial integrity and redox homeostasis by regulating NADPH levels. Knockdown of MTHFD2 reduced NSC proliferation, increased apoptosis, and worsened cognitive impairment in ICH mice. Exogenous NADPH supplementation partially restored these changes, emphasizing the importance of redox balance in NSC survival and function.

Conclusions: Our findings identify MTHFD2 as a key metabolic regulator supporting NSC adaptation to ICH through NADPH-dependent mitochondrial mechanisms. Targeting mitochondrial redox metabolism may provide a potential strategy for preserving NSC function and improving cognitive recovery after ICH.

Background: Myocardial fibrosis represents a terminal pathological outcome in numerous cardiovascular diseases and is mechanistically linked to glycolytic dysregulation. However, systematic reviews integrating multidimensional evidence remain scarce.

Objective: This study aims to conduct a visual analysis of myocardial fibrosis and glycolysis research using CiteSpace and VOSviewer, quantifying research trends and key contributors.

Methods: Literature on "myocardial fibrosis" and "glycolysis" published between January 1, 2000, and December 31, 2024, was retrieved from the Web of Science, PubMed, and Scopus databases. After deduplication, 408 articles were included for analysis. CiteSpace and VOSviewer were employed to analyze data regarding countries, institutions, authors, and keywords.

Results: A total of 408 studies were included. Annual publications on myocardial fibrosis and glycolysis exhibited a fluctuating upward trend, increasing from 1 (2000) to 51 (2024). These publications were divided into three phases: Initial Exploration (2000-2003, 1 article per year), Slow Fluctuation (2004-2009, 3-5 articles per year), and Rapid Development (2010-2024). During the Rapid Development phase, publications surged from 25 in 2019 to 44 in 2020, peaked in 2021-2022 (45 and 48 articles, respectively), and rebounded to 51 in 2024. Key contributors: The U.S. (177 studies, 32% of global output) and China (115 studies, 20%) were the leading contributors, collectively accounting for 52% of total publications; top institutions were Univ. of Alberta (15 Myocardial fibrosis representstudies) and Univ. of Utah (14 studies); core authors included Archer, S.L. (10 studies) and Chen, J.-X. (8 studies), with Lopaschuk, G.D. topping co-citations (117). High-frequency keywords: "heart failure" (107), "expression" (81), "metabolism" (60), "glycolysis" (44); high-centrality ones: "cardiac hypertrophy" (0.25), "fatty acid oxidation" (0.21). Emerging frontiers: "extracellular matrix" (burst intensity = 3.01, 2021-2024), "pulmonary hypertension" (3.61, 2022-2024). Clustering analysis identified 10 clusters (Silhouette Value = 0.7628, Modularity Q = 0.5292), including #0 pulmonary arterial hypertension (2014) and #10 mitochondrial dysfunction (2019).

Conclusion: Our bibliometric analysis reveals three pivotal trends: (1) The U.S. (32%) and China (20%) lead international collaborative networks; (2) Glycolytic reprogramming, oxidative stress, and metabolic interventions are prevalent research focuses; (3) Mitochondrial dysfunction and extracellular matrix remodeling are emerging frontiers. These findings clarify the glycolysis-fibrosis axis and provide a framework for targeted anti-fibrotic therapies.