IR (Insulin receptor)

Overall, our findings suggest that PDX1 plays a tumor-promoting role in human PCa cells by influencing expression of metabolites in insulin, inflammatory, and epithelial-mesenchymal transition (EMT) signaling pathways. Given its potential role in metabolic regulation, full insights into the function of PDX1 in PCa could contribute to improved treatment and prevention strategies, particularly for men with PCa and comorbidities such as obesity and diabetes.

This work provides the first evidence that alkaloids derived from V. viride, especially jervine, may act as multi-target inhibitors against BC. However, further experimental validation is required to confirm their therapeutic efficacy.

Tumor IR expression was associated with higher fasting insulin, and higher fasting insulin was more prevalent among Black women. Further studies are needed to determine the importance of hyperinsulinemia and tumor IR expression in the development of TNBC.

In 3T3-L1 adipocytes, all five compounds significantly enhanced insulin-stimulated glucose uptake at 10 μM, achieving efficacy comparable to that of metformin. In MIN6 cells, xanthohumol and cirsilineol increased glucose-stimulated insulin secretion to levels comparable to exendin-4, while curcumin, hesperetin, and (-)-epicatechin produced modest but significant increases. In conclusion, this integrated computational and experimental framework identified food-derived natural compounds with validated dual-pathway therapeutic activity against T2DM, providing a systematic and reproducible methodology for multi-target drug discovery in complex metabolic disorders.

Murine eyelids treated with an IIS agonist demonstrated a more mesenchymal phenotype and significantly induced MYC expression. Collectively, these results suggest that the IIS pathway may represent a novel approach for regulating high MYC expression in SebCA.

However, we also report some non-conserved residues in VILPs that establish significant and unique interactions with residues in Zeb receptors. Furthermore, we identified residues in each VILP which can be potentially mutated into conserved insulin/IGF1 residues to possibly enhance the binding affinity of these peptides.

Using our approach, the following phytochemicals, with predicted moderate bioavailability, high GI absorption, and probable binding with insulin resistance targets, are recommended for further in vivo or in vitro validation for insulin resistance activity: boldione (a steroid); aurantiamide acetate and aurantiamide (peptide derivatives); O-ethyl-[(3,4-dihydroxyphenyl)methyl] carbamothioate and O-methyl-N-[(4-hydroxyphenyl)methyl] carbamothioate (thiocarbamates); 4α,6α-dihydroxyeudesman-8β,12-olide (a sesquiterpenoid); sanleng acid and tianshic acid (fatty acid derivatives); 2',5,5',7-tetrahydroxyflavone; 2',3,5,7-tetrahydroxyflavone; and 6-hydroxykaempferol (flavonoids). By combining network centrality measures of targets, using ROC-derived thresholds for docking energies, and considering ubiquity of phytochemicals, our refined network pharmacology approach may aid in discovering key bioactive phytochemicals as potential chemical markers for standardization and differentiation of an herbal drug.

When the time interval from primary surgery to ISNR was included, the interval from the primary surgery to ISNR (>2 years) and NLND were identified as significant factors for long OS (HR 0.21, HR 0.39). ISNR is type of a loco-regional recurrence, and NLND needs to be considered in multimodal (radiation and systemic chemo-) therapy.

In conclusion, our combinational sequencing approach unraveled several small non-coding RNAs with a significant post-transcriptional impact on BrCa cell signaling. The online version contains supplementary material available at 10.1007/s10142-026-01856-6.

Although rare, autoimmune causes of hypoglycemia should be considered when other causes are excluded or when results are equivocal. Management with pharmacotherapy can be effective in inducing remission but long-term monitoring is necessary as patients may relapse.

These findings suggest that exosomal lipid composition is modulated by tumour-stromal interactions and may contribute to systemic glucose dysregulation in PDAC. Identifying specific bioactive lipids within exosomes offers potential for developing biomarkers for early detection of PCRD and understanding the metabolic crosstalk in pancreatic cancer.

In this study, we investigated the effects of simvastatin, atorvastatin and rosuvastatin in BC cells stimulated by insulin. Consistent with these findings, survival analyses of large cohorts of patients revealed that high levels of NUPR1 are associated with poor BC prognosis. Overall, our results provide novel mechanistic evidence supporting the repositioning of statins in BC, particularly in tumors characterized by elevated IR expression and activity.