Creatine (Cr) is an essential metabolite in the creatine kinase reaction, which plays a critical role in maintaining normal cardiac function. Chemical exchange saturation transfer (CEST) MRI offers a novel way to map myocardium Cr. This study aims to investigate the dynamic alteration in myocardium Cr during acute infarction using CEST MRI, which may facilitate understanding of the heart remodeling mechanism at the molecular level. Seven adult Bama pigs underwent cardiac cine, Cr CEST, and late gadolinium-enhanced (LGE) T -weighted (T w) imaging three and 14 days after myocardial infarction induction on a 3 T scanner. Cardiac structural and functional indices, including myocardium mass (MM), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF), were measured from cines. Infarct angle was determined from LGE T w images, based on which myocardium was classified into infarct, adjacent, and remote regions. Cr-weighted CEST signal was quantified from a three-pool Lorentzian fitting model and measured within each region and the entire myocardium. Student's t-test was conducted to evaluate any significant differences in measurements between the two time points. Correlation was assessed with Pearson correlation. P values less than 0.05 were considered statistically significant. Over the studied period, MM, EDV, and ESV did not alter significantly (P > 0.05), whereas significant increases of SV and EF and decrease of infarct angle were observed (P < 0.05). Meanwhile, the Cr-weighted CEST signal elevated significantly on Day 14 compared with Day 3 in the infarct (10.00 ± 1.28% versus 6.91 ± 1.54%, P < 0.01), adjacent (11.17 ± 2.00% versus 8.01 ± 1.58%, P = 0.01), and entire myocardium (11.03 ± 1.36% versus 8.19 ± 1.28%, P < 0.01). Moderate negative correlations were shown between the infarct angle and Cr-weighted CEST signals in the infarct (r = -0.80, P < 0.001), adjacent (r = -0.58, P = 0.03), and entire myocardium (r = -0.76, P < 0.01). In conclusion, the dynamic increase of myocardium Cr during acute infarction may interact with cardiac structural and functional recovery. The study provides supplementary insights into the heart remodeling process from the metabolic viewpoint.
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http://dx.doi.org/10.1002/nbm.4704 | DOI Listing |
Geroscience
January 2025
Buck Institute for Research On Aging, Novato, CA, 94945, USA.
Cells are subjected to dynamic mechanical environments which impart forces and induce cellular responses. In age-related conditions like pulmonary fibrosis, there is both an increase in tissue stiffness and an accumulation of senescent cells. While senescent cells produce a senescence-associated secretory phenotype (SASP), the impact of physical stimuli on both cellular senescence and the SASP is not well understood.
View Article and Find Full Text PDFEnviron Microbiol
January 2025
Department of Biochemistry, Genetics and Microbiology, Centre for Microbial Ecology and Genomics, University of Pretoria, Pretoria, South Africa.
Plant detritus is abundant in grasslands but decomposes slowly and is relatively nutrient-poor, whereas animal carcasses are labile and nutrient-rich. Recent studies have demonstrated that labile nutrients from carcasses can significantly alter the long-term soil microbial function at an ecosystem scale. However, there is a paucity of knowledge on the functional and structural response and temporal scale of soil microbiomes beneath large herbivore carcasses.
View Article and Find Full Text PDFMol Ther
January 2025
Academic Unit of Ophthalmology, Translational Health Sciences, University of Bristol, Bristol, BS8 1TD, UK; NIHR Biomedical Research Centre of Ophthalmology, Moorfields Eye Hospital, London, EC1V 2PD, UK. Electronic address:
Progress for ocular AAV gene therapy has been hindered by AAV-induced inflammation, limiting dose escalation and long-term efficacy. Broadly, the extent of inflammatory responses alters with age and sex, yet these factors are poorly represented in pre-clinical development of ocular AAV gene therapies. Here, we combined clinical imaging, flow cytometry and bulk-sequencing of sorted microglia to interrogate the longitudinal inflammatory response following intravitreal delivery of AAV2 in young (3-month), middle aged (9-month) and old (18-month) Cx3cr1-creER:R26tdTomato+/- mice of both sexes.
View Article and Find Full Text PDFBiophys J
January 2025
Department of Pharmacology, University of California Davis, California 95616.
In every heartbeat, cardiac muscle cells perform excitation-Ca signaling-contraction (EC) coupling to pump blood against the vascular resistance. Cardiomyocytes can sense the mechanical load and activate mechano-chemo-transduction (MCT) mechanism, which provides feedback regulation of EC coupling. MCT feedback is important for the heart to upregulate contraction in response to increased load to maintain cardiac output.
View Article and Find Full Text PDFGenome Med
January 2025
Department of Systems Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.
Background: Despite extensive analysis, the dynamic changes in prostate epithelial cell states during tissue homeostasis as well as tumor initiation and progression have been poorly characterized. However, recent advances in single-cell RNA-sequencing (scRNA-seq) technology have greatly facilitated studies of cell states and plasticity in tissue maintenance and cancer, including in the prostate.
Methods: We have performed meta-analyses of new and previously published scRNA-seq datasets for mouse and human prostate tissues to identify and compare cell populations across datasets in a uniform manner.
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