SREBF1 (Sterol Regulatory Element Binding Transcription Factor 1)

Moreover, troxerutin significantly (p < 0.05) upregulated the expression of PPARα and PPARγ, while the expression of FAS, SREBP-1c, TNF-α, and IL-6 genes were significantly (p < 0.05) downregulated simultaneously in the adipose tissue, skeletal muscles, and liver in a dose-dependent manner, compared to diabetic ct control rats. Troxerutin has considerable antidiabetic and antihypercholesterolemic potential and thus could be safely used as an alternative therapeutic compound to the standard antidiabetic drug metformin.

Furthermore, PS reduced hepatic pro-inflammatory cytokine mRNA levels: tumor necrosis factor α(tnf-α), cyclooxygenase 2 (cox-2), and interleukins (il-6, il-1β). In conclusion, dietary inclusion of 0.006%-0.018% PS effectively enhanced growth and antioxidant capacity, altered lipid handling, and affected transcriptional inflammatory responses.

Genetic silencing of SOAT1, while preserving SREBP-1 activity, resulted in the accumulation of free cholesterol and induced mitochondrial oxidative stress, impairing the growth of patient-derived organoids and xenografts from lung cancer and glioblastoma, the most lethal brain tumor, and significantly prolonging survival in preclinical mouse models. These findings reveal a dual role of SREBP-1 in controlling both cholesterol acquisition and storage to maintain cholesterol homeostasis, prevent lipotoxicity, and sustain tumor growth.

These findings offer preliminary clues for future risankizumab-based combination strategies in psoriasis.

Functional studies demonstrated that SREBP1 downregulation conferred resistance to cisplatin and reduced cell death in both organoid and xenograft models in human hypopharyngeal carcinoma (HPSCC)...Our findings establish SREBP1-mediated lipid rewiring as a critical determinant of HNSCC pathogenesis and treatment outcomes. Consequently, our model offers a promising solution for the swift and accurate evaluation of chemotherapy efficacy and identifies SREBP1 as a potential therapeutic target in HPSCC.

Conversely, both drugs promoted adipose triglyceride lipase (ATGL)-mediated lipolysis in obese rats and the effect of Res was superior to that of Caf. These findings suggest that Caf and Res have certain regulatory effects regarding obesity-related metabolic disorders, more likely through modulating lipogenesis and lipolysis-related proteins.

This disruption ultimately suppressed CYP24A1 transcription. Our findings revealed that pharmacological blockade of the LSH/CYP24A1/SCD axis triggers calcium-driven ferroptosis, positioning ATT as a potent, mechanism-based therapeutic for CRC.

Instead, it promoted the upregulation of fatty acid oxidation-related genes such as Peroxisome proliferator-activated receptor alpha (PPARα) and Acyl-CoA oxidase 1 (Acox1), helped maintain intestinal microbial balance, and enhanced the production of beneficial short-chain fatty acids (SCFAs), particularly butyrate and propionate. In conclusion, solvent fractionation effectively modulates the fatty acid composition of sheep fat, thereby influencing lipid metabolism and inflammatory responses through the regulation of key gene expression and modulation of the gut microenvironment.

In vivo expression analysis in thyroid and breast cancer patients confirmed that lipid metabolism and SREBF1 expression are associated with increased metastatic potential and clinical aggressiveness. These findings emphasize the RUNX2 role in cancer plasticity and indicate metabolic adaptation as an integral part of the trans-differentiation program induced by this TF during cancer progression.

Network pharmacology analysis combined with molecular docking suggested that the ferulic acid and adenosine in CX potentially modulate EGFR-the E2F1-hsa-miR-10a-5p axis. These findings elucidate CX's multi-target anti-GBM mechanisms and propose a novel therapeutic strategy combining metabolic intervention with miRNA-targeted therapy, providing novel insights into feed-forward loop regulation in miRNA networks.

The results of this study indicate that the reduction in cholesterol levels observed in breast cancer cells following IGFBP6 knockdown is primarily due to decreased exogenous uptake. These findings highlight the role of IGFBP6 in regulating cholesterol metabolism and further explain its clinical significance in predicting breast cancer recurrence and progression.

Our findings highlight shared and opposing genetic loci between CAD and cancer and provide insight into molecular intermediates mediating joint disease risk. Importantly, they indicate potential drug repurposing opportunities for dual CAD and cancer prevention while highlighting possible adverse and divergent effects of existing medications across both conditions.