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Biomedical subjects

Jie Peng

Publications and source records attributed to Jie Peng.

4 recordsLinked to original sources

Decoding SUMOylation as a metabolic stress sensor in aging and age-related disorders: Mechanisms, tissue specificity and therapeutic potential.

SUMOylation is a reversible post-translational modification increasingly recognized for its role in coordinating cellular responses to metabolic stress during aging. Emerging evidence indicates that it functions beyond a conventional modification, representing an adaptive stress‑responsive regulatory network that integrates metabolic, oxidative, inflammatory, and proteotoxic signals. Rather than acting on isolated pathways, this network finely tunes mitochondrial function, proteostasis, genome maintenance, immune balance, and epigenetic regulation. Accumulating evidence indicates that SUMO-dependent regulation exhibits remarkable tissue specificity, supporting mitochondrial adaptation and contractile integrity in skeletal muscle, shaping lipid and glucose metabolism in the liver, modulating proteotoxic stress and neuronal resilience in the brain, and contributing to immune cell differentiation and chronic low-grade inflammation during aging. In this review, we summarize current mechanistic insights into SUMO signaling across aging-relevant tissues, with particular emphasis on its functional interplay with other post-translational modifications, including ubiquitination and acetylation. We discuss how SUMOylation operates as a shared regulatory layer while enabling context-dependent outcomes that underlie diverse aging phenotypes and age-related disorders. Finally, we evaluate emerging translational approaches-ranging from pharmacological modulation of SUMO enzymes to lifestyle interventions such as caloric restriction and exercise-that highlight both the opportunities and challenges of targeting SUMO-regulated stress responses in aging. Together, this synthesis provides a framework for understanding how SUMOylation links metabolic stress to tissue-specific aging trajectories and therapeutic potential.

Aging

Hepatic metabolic adaptation to endurance exercise: temporal and sex differences by multiomics integration and validation.

BACKGROUND: Although endurance exercise benefits liver health, sex-specific adaptive trajectories remain unclear. This study mapped dynamic liver adaptation in males and females during prolonged training and identified underlying molecular programs. METHODS: Using publicly available time-resolved liver multi-omics data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we established a computational pipeline for differential analysis of transcriptomic, proteomic, phosphoproteomic, and metabolomic data with FDR correction, followed by FGSEA pathway enrichment. Kinase activities were inferred through ortholog mapping and PhosphoSitePlus. Cross-omics co-expression networks were constructed using WGCNA and topological overlap to link omics features with physiological phenotypes. For experimental validation, liver tissues were collected from endurance-trained Sprague-Dawley rats, and key nodes were confirmed by Western blotting, qRT-PCR, and immunofluorescence/immunohistochemical staining. Public scRNA-seq data were further integrated to map multi-omics signals to single-cell resolution and assess functional changes in specific cell types. RESULTS: The hepatic response to exercise stress was stage-specific, shifting from early transcriptional activation to later proteomic and metabolic remodeling. Multi-omics integration revealed distinct sex-associated adaptive trajectories: males were more strongly associated with energy metabolism, redox-related programs, and amino acid/organic acid catabolism, whereas females showed prominent membrane lipid remodeling, proteostasis -related programs, and mitochondrial/ribosomal translational features. Single-cell analysis showed that tissue remodeling occurred without major lineage turnover, instead involving altered communication among pre-existing cell communities. Validation of PPP1R3G identified a protein-dominant exercise-responsive marker, supporting the contribution of post-transcriptional or protein-level regulation. CONCLUSIONS: Hepatic adaptation to endurance stress follows a cross-omics evolutionary pattern with sex-specific reprogramming of energy supply and homeostatic maintenance. This time-resolved framework clarifies how exercise improves liver function and supports sex-oriented metabolic interventions and therapeutic target discovery.

Animals

Decreased intestinal abundance of Akkermansia muciniphila is associated with metabolic disorders among people living with HIV.

BACKGROUND: Previous studies have shown changes in gut microbiota after human immunodeficiency virus (HIV) infection, but there is limited research linking the gut microbiota of people living with HIV (PLWHIV) to metabolic diseases. METHODS: A total of 103 PLWHIV were followed for 48 weeks of anti-retroviral therapy (ART), with demographic and clinical data collected. Gut microbiome analysis was conducted using metagenomic sequencing of fecal samples from 12 individuals. Nonalcoholic fatty liver disease (NAFLD) was diagnosed based on controlled attenuation parameter (CAP) values of 238 dB/m from liver fibro-scans. Participants were divided based on the presence of metabolic disorders, including NAFLD, overweight, and hyperlipidemia. Akkermansia abundance in stool samples was measured using RT-qPCR, and Pearson correlation and logistic regression were applied for analysis. RESULTS: Metagenomic sequencing revealed a significant decline in gut Akkermansia abundance in PLWHIV with NAFLD. STAMP analysis of public datasets confirmed this decline after HIV infection, while KEGG pathway analysis identified enrichment of metabolism-related genes. A prospective cohort study with 103 PLWHIV followed for 48 weeks validated these findings. Akkermansia abundance was significantly lower in participants with NAFLD, overweight, and hyperlipidemia at baseline, and it emerged as an independent predictor of NAFLD and overweight. Negative correlations were observed between Akkermansia abundance and both CAP values and body mass index (BMI) at baseline and at week 48. At the 48-week follow-up, Akkermansia remained a predictive marker for NAFLD. CONCLUSIONS: Akkermansia abundance was reduced in PLWHIV with metabolic disorders and served as a predictive biomarker for NAFLD progression over 48 weeks of ART.

Humans

Learning directed acyclic graphs for ligands and receptors based on spatially resolved transcriptomic data of ovarian cancer.

To unravel the mechanism of immune activation and suppression within tumors, a critical step is to identify transcriptional signals governing cell-cell communication between tumor and immune/stromal cells in the tumor microenvironment. Central to this communication are interactions between secreted ligands and cell-surface receptors, creating a highly connected signaling network among cells. Recent advancements in in situ-omics profiling, particularly spatial transcriptomic (ST) technology, provide unique opportunities to directly characterize ligand-receptor signaling networks that power cell-cell communication. In this paper, we propose a novel statistical method, LRnetST, to characterize the ligand-receptor interaction networks between adjacent tumor and immune/stroma cells based on ST data. LRnetST utilizes a directed acyclic graph model with a novel approach to handle the zero-inflated distributions of ST data. It also leverages existing ligand-receptor regulation databases as prior information, and employs a bootstrap aggregation strategy to achieve robust network estimation. Application of LRnetST to ST data of high-grade serous ovarian tumor samples revealed both common and distinct ligand-receptor regulations across different tumors. Some of these interactions were validated through both a MERFISH dataset and a CosMx SMI dataset of independent ovarian tumor samples. These results cast light on biological processes relating to the communication between tumor and immune/stromal cells in ovarian tumors. An open-source R package of LRnetST is available on GitHub at https://github.com/jie108/LRnetST.

Humans