Journal of Translational Medicine最新文献

{"title":"Non-electrophilic TRPA1 modulator MNP-021 protects neuronal and glial function from diabetes-associated glucotoxicity and neuroinflammation.","authors":"Alessandro De Carli, Carolina Filipponi, Beatrice Polini, Veronica Sancho-Bornez, Emy Basso, Fabio Filippini, Angela Dardano, Francesca Sardelli, Simona Daniele, Martina Contestabile, Franco Folli, Giovanna Finzi, Sara De Martin, Giuseppina Emanuela Grieco, Francesco Dotta, Guido Sebastiani, Grazia Chiellini, Mauro Pineschi, Michele Lai, Giuseppe Daniele","doi":"10.1186/s12967-026-09028-7","DOIUrl":"https://doi.org/10.1186/s12967-026-09028-7","url":null,"abstract":"<p><strong>Background: </strong>Diabetes-associated neurodegeneration is amplified by methylglyoxal (MGO)-driven dicarbonyl stress linking hyperglycemia to neuronal insulin resistance and maladaptive neuroinflammation. We tested the neuroprotective activity of MNP-021, a non-electrophilic transient receptor potential ankyrin 1 (TRPA1) modulator, in neurons and glial cells in vitro.</p><p><strong>Methods: </strong>SH-SY5Y neurons were pretreated with MNP-021 and challenged with MGO, then profiled by high-content imaging, RNA-seq, Seahorse Oxygen Consumption Rate (OCR) and Extracellular Acidification Rate (ECAR), glycolytic stress assays, and immunoblotting for AKT, ERK, and cAMP response element-binding protein (CREB). In an additional sustained glucotoxicity paradigm, differentiated SH-SY5Y cells were exposed to high glucose for 7 days and viability was assessed by LIVE/DEAD™ high-content imaging. HMC3 glial cells were treated with MNP-021, exposed to Lipopolysaccharide (LPS), Tumor Necrosis Factor-α (TNF-α) or Aβ(25-35), and tested for viability and inflammatory markers by Enzyme-Linked Immunosorbent Assay (ELISA) and RT-qPCR.</p><p><strong>Results: </strong>MGO increased nucleus-to-cytoplasm area ratio by 49% and dysregulated glucose handling, increasing 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose (2-NBDG) uptake by ~ 25%, with GLUT1/GLUT4 membrane redistribution; MNP-021 normalized morphology, glucose uptake, and transporter localization without cytotoxicity up to 10 µM. RNA-seq identified 754 MGO-deregulated genes, including ISR/metabolic nodes such as glucokinase (GCK), Sestrin-2 (SESN2), phosphoglycerate dehydrogenase (PHGDH), Phosphoserine Aminotransferase 1 (PSAT1), phosphoenolpyruvate carboxykinase 2 (PCK2); MNP-021 buffered stress-induced transcription with limited baseline effects, modulated mitochondrial morphology and redox-associated fluorescence while preserving overall respiratory flux and blunting stress-evoked compensatory glycolysis. MNP-021 restored pro-survival signaling (pAKT/pERK and nuclear pCREB), including insulin responsiveness during MGO exposure. In a sustained high-glucose model, MNP-021 reduced the high-glucose-associated increase in cell death, extending its protective effects beyond the acute MGO paradigm. MNP-021 reduced Interleukine-6 (IL-6)/TNF-α release while increasing Interleukine-10 (IL-10) and Arginase 1 (ARG1) (~ 1.9-fold vs. LPS/TNF-α) in HMC3 glial cells, shifting them toward a pro-resolving IL-10/ARG1 program with reduced amyloid β-peptide <sub>25-35</sub> (Aβ<sub>(25-35)</sub>)-evoked cytokine release and Glucagon-Like Peptide-1 (GLP-1) remaining very low (≤ 10 pg/mL) and not significantly increased in this system.</p><p><strong>Conclusions: </strong>MNP-021 coordinates transcriptomic restraint, transporter-level glucose handling, mitochondrial resilience, and pro-survival/pro-resolving signaling in neuron-microglia cell models. These findings support further preclinical evaluation o","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"24 1","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149297888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-altitude environments elevate central and peripheral α-synuclein levels and accelerate PD-related pathology.","authors":"Hao-Lun Sun, Dong-Yu Fan, Jun-Hao Xie, Qing Du, Rui-Jie Zeng, Jian-Ni Hu, Jun Liang, Li Zhu, Xu Wang, Hao-Xiang Wang, Qing Zhao, Rong Zhang, Yan-Jiang Wang, Hong-Da Zhao, Wang-Sheng Jin","doi":"10.1186/s12967-026-09103-z","DOIUrl":"https://doi.org/10.1186/s12967-026-09103-z","url":null,"abstract":"<p><strong>Background: </strong>High-altitude exposure has been linked to an increased risk of Parkinson's disease (PD), potentially through hypoxic neuronal damage, yet the involvement of α-synuclein (α-syn) remains poorly understood. This study integrates population-based surveys, animal experiments, and clinical cross-sectional data to elucidate the role of high-altitude environments in PD pathogenesis.</p><p><strong>Methods: </strong>A cross-sectional study was conducted among middle-aged and elderly high-altitude residents. Additional cohorts (low-altitude PD patients, low-altitude controls, and high-altitude controls) were enrolled for plasma and erythrocytic α-syn measurement, and a subset of PD patients underwent transcranial sonography to assess correlations between erythrocyte indices and substantia nigra echogenicity. A53T transgenic mice were exposed to high altitude for six months and evaluated by behavioral tests, omics sequencing, α-syn assays, and immunohistochemistry. Erythrocyte-derived extracellular vesicles from PD patients were intravenously injected into wild-type mice to assess brain entry.</p><p><strong>Results: </strong>The crude prevalence of PD tended to be higher in high-altitude populations than the national average. A53T mice exposed to high altitude displayed more severe motor deficits, elevated brain α-syn levels, and pronounced dopaminergic neuron loss. Omics analyses revealed enrichment of pathways related to IL-17, sphingosine-1-phosphate signaling, and oxidative stress in brain tissue from high-altitude versus low-altitude A53T mice, suggesting blood-brain barrier disruption and impaired α-syn clearance. In peripheral blood, both high-altitude mice and humans exhibited elevated α-syn levels compared with their low-altitude counterparts, and erythrocyte indices correlated positively with α-syn levels. After normalization to erythrocyte count and hemoglobin, however, erythrocytic α-syn did not differ between high-altitude and low-altitude controls. In mice, intravenously injected human-derived erythrocytic vesicles entered the brain.</p><p><strong>Conclusions: </strong>Chronic high‑altitude exposure is associated with peripheral and central α‑syn accumulation, which may be driven by a hypoxia‑induced erythrocyte pool expansion and increased α-syn burden, potentially aggravating PD‑related neuropathology.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"24 1","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149298409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiotensinogen as a molecular hub in interorgan communication.","authors":"Jianan Zhou, Ximing Ye, Yuying Wang, Min Hong, Jiabing Rong, Jianan Wang, Yinchuan Xu","doi":"10.1186/s12967-026-09074-1","DOIUrl":"https://doi.org/10.1186/s12967-026-09074-1","url":null,"abstract":"<p><p>Angiotensinogen (AGT) is the sole precursor of angiotensin peptides, its physiological relevance is not determined solely by precursor abundance. Although the liver supplies the bulk of circulating AGT, the protein detected in peripheral tissues may arise from local synthesis, vascular retention, glomerular filtration, barrier crossing, or receptor-mediated uptake. Moreover, the molecular form in which AGT exists carries functional implications: intact AGT and des(Ang I)AGT produce effects that are distinct from-and under certain conditions, opposing to-those of angiotensin II (Ang II). This review repositions AGT as a context-sensitive mediator of interorgan crosstalk, with a clear demarcation between preclinical models and human data. Studies using source-specific knockout and lineage tracing in mice offer the strongest causal evidence for liver-to-kidney AGT trafficking; most other proposed axes lack such granular resolution. Human genetic loss-of-function studies have definitively established AGT's indispensability for renal morphogenesis and blood-pressure regulation, while observational cohorts and biomarker studies rarely determine its tissue origin or delivery route. Ultimately, the functional output of AGT across organ systems depends on its source, molecular state, local accessibility, enzymatic processing, and the receptor environment. Therapeutic agents that target hepatocytes, such as zilebesiran and tonlamarsen, produce durable AGT suppression and could potentially ease treatment burden relative to conventional daily angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Their slow offset of action, combined with a current lack of solid cardiovascular and renal outcome data, raises an unresolved but critical question: what is the safety margin for AGT reduction before renal self-regulation, fluid-electrolyte balance, or pressor responses to physiological stress become compromised? Overall, AGT does not function as a ubiquitous interorgan signaling molecule; instead, it functions as an upstream determinant whose impact is highly context-dependent, shaped by its site of production, route of dissemination, and mode of processing. This review systematically differentiates experimentally established source-to-target circuits from plausible but as-yet-unconfirmed pathways and outlines the mechanistic and clinical benchmarks that must be met for the safe, tissue-selective application of AGT-targeted therapy.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"24 1","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149298437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial dysfunction in diabetic neuropathy: a core pathogenic hub and therapeutic implications.","authors":"Xiaotong Wu, Xiaobo Li, Nengjun Lou, Xianghua Zhuang, Shihong Chen","doi":"10.1186/s12967-026-09015-y","DOIUrl":"https://doi.org/10.1186/s12967-026-09015-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Diabetic neuropathy is a heterogeneous complication of diabetes in which sensory loss, neuropathic pain, autonomic dysfunction and distal axonal degeneration cannot be fully explained by hyperglycaemia alone. Because peripheral axons, Schwann cells and autonomic neurons depend on sustained bioenergetic support, mitochondrial injury has emerged as a central link between metabolic overload, neuroinflammation and progressive nerve dysfunction.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main body: &lt;/strong&gt;This review synthesizes evidence that hyperglycaemia, lipotoxicity and microvascular stress impair electron transport, oxidative phosphorylation and mitochondrial DNA stability, leading to excessive reactive oxygen species generation, calcium dyshomeostasis, mitochondrial permeability transition pore opening and maladaptive metabolic reprogramming. Disrupted fission-fusion balance, defective axonal transport, impaired mitophagy and abnormal mitochondria-associated endoplasmic reticulum membranes further weaken mitochondrial quality control in long peripheral axons. These changes engage SARM1-related NAD+ depletion, inflammasome activation, cGAS-STING signalling, apoptosis and glial-neuronal metabolic failure, thereby connecting bioenergetic collapse with pain sensitisation, distal axonal degeneration and autonomic dysfunction. Across painful and painless diabetic peripheral neuropathy, corneal small-fibre neuropathy, autonomic neuropathy and diabetes-related central nervous system injury, mitochondrial mechanisms appear shared, but endpoints and dominant cell types differ. Translationally, exercise and dietary strategies, metabolic regulators, SARM1 and calcium-pathway targeting, mitophagy modulation, mitochondria-directed antioxidants, and traditional Chinese medicine or natural products are discussed as metabolism-oriented interventions. Current evidence supports target engagement in experimental systems, but human validation, tissue exposure data, structural nerve endpoints and high-quality disease-modifying trials remain insufficient.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Mitochondrial dysfunction functions as a core pathogenic hub-rather than the sole cause-linking substrate overload, redox imbalance, calcium stress, organelle quality-control failure, inflammatory signalling, and axonal degeneration in diabetic neuropathy. The most actionable translational path is not symptomatic antioxidant use alone but biomarker-guided, mechanism-stratified trials that connect mitochondrial target modulation with small-fibre structure, nerve function, safety, and patient-centred outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Search strategy and evidence selection: &lt;/strong&gt;For this narrative review, PubMed was searched from database inception to 1 August 2026, supplemented by backward reference screening of relevant original studies and recent reviews. Search terms included \"diabetic neuropathy\", \"diabetic peripheral neuropathy\", \"mitochondria\", \"oxidative phosphorylation\", \"oxid","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"24 1","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13711899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149287376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI-based intratumoral and peritumoral heterogeneity for predicting intracranial progression in EGFR-mutant lung adenocarcinoma patients with treatment-naive brain metastases receiving first-line third-generation EGFR-TKIs.","authors":"Guangchuan Deng, Houying Li, Zhengjun Dai, Jing Fan, Xiaopeng Song, Guodong Pang, Zhenxiang Li, Fang Zhao","doi":"10.1186/s12967-026-09109-7","DOIUrl":"https://doi.org/10.1186/s12967-026-09109-7","url":null,"abstract":"<p><strong>Purpose: </strong>To develop and externally test a multiparametric MRI habitat-based framework integrating intratumoral heterogeneity (ITH), peritumoral heterogeneity (PTH), and clinical characteristics for predicting intracranial progression in patients with EGFR-mutant lung adenocarcinoma and de novo brain metastases receiving first-line third-generation (3rd-gen) EGFR-TKI monotherapy.</p><p><strong>Materials and methods: </strong>This retrospective multicenter study included patients with EGFR-mutant lung adenocarcinoma and de novo brain metastases who received first-line 3rd-gen EGFR-TKI monotherapy. Patients were assigned to an internal training cohort (n = 90) and an external testing cohort (n = 51). The binary prediction outcome was intracranial progression within 20 months after treatment initiation. Pretreatment contrast-enhanced T1-weighted imaging, T2-weighted imaging, and diffusion-weighted imaging were analyzed. The index brain metastasis and a 6-mm peritumoral region were segmented, followed by voxel-wise habitat clustering. Habitat-specific radiomic features were extracted and selected to construct ITH, PTH, and combined intratumoral-peritumoral habitat (PITH) signatures. Clinical predictors were evaluated using univariable and multivariable logistic regression. Support vector machine models were evaluated using receiver operating characteristic, decision curve, calibration, and Kaplan-Meier analyses.</p><p><strong>Results: </strong>A total of 141 patients were analyzed, including 75 with progressive disease (PD) and 66 without PD (non-PD). Multivariable logistic regression identified EGFR mutation subtype (odds ratio [OR] = 2.390, 95% confidence interval [CI]: 1.187-4.811, P = 0.015) and the maximum diameter of the index brain metastasis as independent predictors (OR = 2.048, 95% CI: 1.204-3.483, P = 0.008). Models based on imaging heterogeneity features outperformed the clinical model overall. The clinical model achieved an AUC of 0.662, while the ITH, PTH, and PITH models achieved AUCs of 0.715, 0.724, and 0.758, respectively. The combined model showed favorable performance (AUC 0.795, accuracy 76.5%, sensitivity 70.4%, and specificity 83.3%). Patients classified by the combined model as high risk had significantly shorter intracranial progression-free survival (iPFS), than those classified as low risk (log-rank P = 0.019).</p><p><strong>Conclusion: </strong>The proposed framework integrating ITH, PTH, and clinical features may provide a noninvasive approach for predicting intracranial progression risk and stratifying prognosis in patients with EGFR-mutant lung adenocarcinoma with newly diagnosed BMs receiving first-line 3rd-gen EGFR-TKI monotherapy.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"24 1","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13718074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149297682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor regarding \"Genetic susceptibility to decompression sickness: molecular mechanisms, genomic advances, and precision prevention strategies\".","authors":"Emmanuel Dugrenot, Emmanuel Gouin, Clément Lévêque, Jérémy Orsat, Frauke Tillmans","doi":"10.1186/s12967-026-08937-x","DOIUrl":"10.1186/s12967-026-08937-x","url":null,"abstract":"","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"24 1","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: A brain-penetrant chimeric protein combines direct glioma targeting with myeloid cell-mediated immune reprogramming.","authors":"Elisabetta Mori, Elisa De Santis, Marta Scalera, Julia Meissel, Elena Ellmeier, Alessandra Flori, Luca Menichetti, Gudula Schmidt, Antonino Cattaneo, Stefano Angiari, Mario Costa, Eleonora Vannini","doi":"10.1186/s12967-026-09089-8","DOIUrl":"https://doi.org/10.1186/s12967-026-09089-8","url":null,"abstract":"","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"24 1","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic effect of gastric microbiome and host genetic factor predispose to gastric cancer.","authors":"Tsubasa Shimogama, Tomomitsu Tahara, Takuya Shijimaya, Jumpei Yamazaki, Narumi Yano, Takuya Ohtsu, Ryo Yasuoka, Sanshiro Kobayashi, Naohiro Nakamura, Yu Takahashi, Takashi Tomiyama, Yusuke Honzawa, Toshiro Fukui, Makoto Naganuma","doi":"10.1186/s12967-026-09009-w","DOIUrl":"10.1186/s12967-026-09009-w","url":null,"abstract":"<p><strong>Objective: </strong>Complex interaction between host genetic and environmental factors has a role in Helicobacter pylori (H. pylori)-related gastric tumorigenesis, while involvement of non-Helicobacter pylori gastric microbiome may be also relevant to this process. We aimed to evaluate whether combining the non-Helicobacter pylori gastric microbiome signatures and the gastric cancer (GC) predisposing genetic factors (PSCA rs2294008 and MUC1 rs4072037 polymorphisms) stratify a high GC risk subpopulation in a Japanese cohort.</p><p><strong>Methods: </strong>In 620 subjects including 219 GC patients and 410 non-cancers, microbiome-based GC risk was defined as the gastric microbiome signatures of 47 GC-predisposing bacteria. Genetic risk of GC was also defined as the presence of PSCA rs2294008 and MUC1 rs4072037 risk alleles. Adding effect of gastric microbiome and genetic factor was evaluated in relation to GC susceptibility, histological degree of gastritis and somatic changes in the gastric mucosa including DNA methylation and telomere shortening.</p><p><strong>Results: </strong>Individuals possessing the risk of both microbiome and genotype showed significant risk for developing GC with highest OR (odds ratio, e.g., OR = 23.55 in comparison with non-cancer) compared to individuals having risk microbiome or genotype alone (microbiome, OR = 11.16; genotype, OR = 2.76). The individuals having both risks also showed highest degrees of intestinal metaplasia and DNA methylation, and shortest telomere.</p><p><strong>Conclusions: </strong>Our findings suggested an existence of combined effect of host genetic factor and gastric microbiome predispose to gastric tumorigenesis, that can be used as the diagnostic tool to further stratify a high GC risk subpopulation.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"24 1","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of methylation and mutation modifications on melanoma progression through evaluation of paired primary and secondary lesions from same patients.","authors":"Antonella Manca, Maria Cristina Sini, Luca Nuvoli, Sara Simi, Silvia Costabile, Guido Bellezza, Vincenzo De Giorgi, Antonio Guadagno, Paola Ghiorzo, Mario Mandalà, Daniela Massi, Giuseppe Palmieri","doi":"10.1186/s12967-026-09082-1","DOIUrl":"https://doi.org/10.1186/s12967-026-09082-1","url":null,"abstract":"","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"24 1","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From equilibrium to dynamic metabolic imaging: the evolving role of magnetic resonance spectroscopic imaging in neurodegenerative disorders.","authors":"Marta M Pokotylo, Josh P Peters, Aaron Diercks, Farhad Haj Mohamad, Norbert Brüggemann, Andrey N Pravdivtsev, Jan-Bernd Hövener, Jannik Prasuhn","doi":"10.1186/s12967-026-09084-z","DOIUrl":"10.1186/s12967-026-09084-z","url":null,"abstract":"<p><strong>Background: </strong>Dysregulated brain metabolism is increasingly recognized to play a significant role in the development and progression of neurodegenerative diseases (NDDs). Conventional imaging methods, such as positron emission tomography (PET), are limited to assessing tracer uptake and offer no insight into its downstream metabolic fate. Additionally, PET provides no insight into dynamic metabolic fluxes and turnover, which reflect biochemical processes. In contrast, magnetic resonance spectroscopy and spectroscopic imaging MRS(I) allow non-invasive, spatially resolved in vivo investigation of specific metabolites, without the use of radioactive tracers.</p><p><strong>Main body: </strong>¹H-MRS(I) is one of the most widely utilized techniques due to its accessibility, while heteronuclear approaches, including ²H-, ¹³C-, ¹⁵N-, and ¹⁷O-MRS(I), broaden MRS(I)'s utility by expanding the scope of accessible metabolites. Technical and methodological advances in nuclear spin hyperpolarization-enhanced MRI further improve signal-to-noise ratio, enabling in vivo detection of low-abundance metabolites. Furthermore, revival of ²H-MRS(I) has opened new avenues for dynamic metabolic investigation without hyperpolarization. In this review, we provide a conceptual framework for transitioning from a static to a dynamic MRS(I) approach and discuss key considerations for tracer selection, nuclear spin hyperpolarization methods, acquisition hardware, reconstruction, preprocessing, and metabolic modeling. We outline major methodological and translational challenges, including low signal-to-noise ratio, field strength, and vendor hardware variability, as well as a lack of standardization across acquisition, reconstruction, preprocessing, and modeling strategies.</p><p><strong>Conclusion: </strong>Dynamic MRS(I) provides a promising foundation for in vivo brain metabolism investigation in NDDs, offering mechanistic insights into metabolic fluxes, reprogramming, and bottlenecks. Although dynamic MRS(I) is limited to a few research institutions, ongoing technical and methodological advances are improving its feasibility, biochemical specificity, and broader implementation. Standardized and harmonized acquisition, reconstruction, and preprocessing protocols are necessary to enable broad clinical implementation of these approaches. Nevertheless, the shift from static to dynamic MRS(I) has great potential to advance biomarker and diagnostic tool development, patient stratification, and longitudinal disease monitoring in NDDs, provided that current challenges and limitations are sufficiently addressed.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"24 1","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}