PDK4 (Pyruvate Dehydrogenase Kinase 4)

In vivo, perivascular delivery of PDK4-IN-1 in the mouse carotid artery injury model significantly ameliorated neointimal hyperplasia. Inhibition of PDK4 perturbs pathological VSMC phenotypic switching, suppresses proliferation, promotes apoptosis and autophagy, and mitigates neointimal formation, highlighting PDK4 as a promising therapeutic target for vascular proliferative diseases.

Moreover, we elucidated the molecular mechanism through which the pre-B-cell leukemia transcription factor 1-insulin receptor substrate 1 signaling axis sustains metabolic homeostasis. Furthermore, we demonstrated that the blood-brain barrier-permeable trans-activator of transcription-pre-B-cell leukemia transcription factor 1 fusion protein constitutes a mechanistically innovative and highly translatable therapeutic strategy for Alzheimer's disease.

Notably, we highlight the potential regulatory role of ANK2 in the progression of CRC. This research provides theoretical support and new directions for early screening, diagnostic biomarker identification, and targeted therapy strategies for CRC.

Further analysis shows that PDK4 enhances the acetylation of β-catenin, a protein involved in cell movement, and that this modification is crucial for mesothelial cell invasion. Our results suggest that PDK4 regulates mesothelial cell invasion through β-catenin acetylation following metabolic reprogramming, offering a potential target for therapies aimed at inhibiting CRC-PM.

This study reveals a novel molecular mechanism through which ginsenoside Rg3 antagonises endometriosis, providing a critical theoretical basis and experimental foundation for the development of new targeted therapeutic strategies against this disease.

ACADL functions as a mitochondria-associated tumor suppressor that impedes LUAD progression through activation of the FOXO3a/PUMA signaling pathway, underscoring its potential as a therapeutic target for LUAD.

Multivariate COX regression analysis demonstrated that DLGAP1 was an independent prognostic factor for PAAD. Six hub genes might exert an influence on the initial lymphatic metastasis of PAAD through immune cell infiltration and ferroptosis.

These 4 genes were selected as hub genes as they are closely related to gluconeogenesis, the tricarboxylic acid cycle, lipid metabolism, amino acid metabolism and other mitochondrial metabolic pathways in PCa. In conclusion, 4 novel mitochondrial-related gene signatures that influence mitochondrial metabolism within the immune microenvironment were identified in PCa.

By further evaluating anti-proliferative, anti-migratory property with apoptotic inducing potential of Evo, we found there is a significant effect on A549 and A549CR cells. Together, these findings demonstrate that ZEB-2 can be an effective target of Evo mediating cisplatin resistance pathways and sensitize resistant lung cancer cells to cisplatin, providing a promising combinatorial therapeutic strategy to enhance NSCLC treatment efficacy.

In cachectic mouse models, Muribaculaceae and Muribaculum intestinale are reduced and exhibit a significant positive correlation with SCFA butyrate. Inulin or MI supplementation increased these bacteria, ameliorating cachexia. NaB attenuates muscle wasting through coordinated modulation of autophagy suppression, anti-inflammatory effects and metabolic reprogramming (including PDK4 downregulation and ATP elevation), collectively indicating the existence of a gut-muscle axis in cachexia progression. These findings underscore the potential of microbiota-targeted interventions in managing cancer cachexia and highlight the intricate interplay between gut microbiota and skeletal muscle health.

High-risk patients exhibited poor survival, enhanced immune infiltration, and potential sensitivity to AKT inhibitors, with several drugs, including gefitinib and paclitaxel, identified as promising candidates. Additional prognostic genes (DFFB, PSMB6, GLP1R, HDAC9, BACH2) displayed expression patterns largely consistent across HPA, TCGA, and RT-qPCR, with minor discrepancies likely due to sample size. This study integrates multi-omics and deep learning with experimental validation, providing insights into programmed cell death regulation and offering robust biomarkers and therapeutic targets for GC.

PDK4 functions as a tumor suppressor in GC, bridging metabolic reprogramming, epigenetic regulation, and immune microenvironment remodeling. Its downregulation contributes to disease progression and immune evasion, underscoring its potential as a prognostic biomarker and therapeutic target. Restoring PDK4 activity may serve as a promising strategy to mitigate GC aggressiveness and therapeutic resistance.