SOCS3 (Suppressor Of Cytokine Signaling 3)

Our findings indicate that circulating EV miRNAs in glioblastoma patients are associated with specific gene expression patterns in peripheral immune cells, suggesting a complex regulatory balance between pro-inflammatory and anti-inflammatory cues, potentially preceding full tumor-associated macrophage polarization. These molecular interactions may offer opportunities for developing early biomarkers or new therapeutic approaches.

Myeloid cells exhibited expression of immunomodulatory genes (RUNX3, DDIT4, IL4I1), and malignant T-cells expressed exhaustion-associated markers (CXCL13, SOCS3, F2R, ETV1), as opposed to AD and healthy control samples. Thus, our results provide a novel insight into the immune-stroma crosstalk in the tissue microenvironment of early-stage MF vs. AD skin lesions.

SOCS3 exerts dual tumor-suppressive effects in GBM by inhibiting JAK-STAT signaling and activating mitochondrial stress pathways. These findings provide mechanistic insights into the function of SOCS3 and support its potential as a therapeutic target in GBM by promoting UPRmt-driven apoptosis.

In vivo, STAT3 knockdown suppressed tumor formation and hepatosplenomegaly in mice inoculated with Ba/F3 cells expressing NPM-ALK, and these phenotypes were rescued by wild-type STAT3, but not by the T714A mutant. These findings indicate that STAT3 phosphorylation at T714 is required for subsequent Y705 phosphorylation, nuclear translocation, and transcriptional activation specifically within the context of NPM-ALK-mediated signaling.

Resistance to HIF-2α inhibitors such as Belzutifan underscores the need to better understand how HIF-2α is transcriptionally regulated in clear cell renal cell carcinoma (ccRCC)...Unlike prior studies focusing on VHL/HIF occupancy-driven enhancer activation, this work defines a trans-acting cytokine-JAK1-STAT3 pathway that transcriptionally controls EPAS1. Together, these findings reveal a targetable enhancer mechanism that sustains HIF-2α expression and suggest that combined inhibition of JAK1/STAT3 and HIF-2α may overcome therapeutic resistance in kidney cancer.

Conversely, compared with those of the model group, the expression of NPY, SOCS3, NLRP3, ASC, cleaved caspase-1, GSDMD-N, and IL-1β was significantly downregulated, and the expression of POMC and LEPR was significantly upregulated in the medium-and high-dose HLWDD groups and the metformin group. These results collectively indicate that HLWDD ameliorates olanzapine-induced feeding dysregulation by mitigating leptin resistance through suppression of NLRP3-driven neuroinflammatory pathways in the arcuate nucleus.

ICAM1, MST1, CXCL8, SOCS3, and IGFBP1 were identified as biomarkers of renal deficiency and blood stasis syndrome in AS. This study provides a biological basis for the differential diagnosis of TCM syndromes in AS, offering new insights into Chinese medicine evidence and more precise Chinese medicine treatments for AS.

FWHJ inhibits non-small cell lung cancer (NSCLC) by activating NR1D1 to stimulate the cGAS-STING pathway and suppress the JAK-STAT3 signaling axis, thereby enhancing anti-tumor immunity. This study provides a foundation for further investigation into the anti-tumor mechanisms of FWHJ and establishes a scientific basis for its potential application in lung cancer therapy.

For perturbation, the EZH2 inhibitor tazemetostat was evaluated in the CRPC-relevant C42 cell line with H3K27me3 readouts and transcriptomic profiling, with key changes validated by RT-qPCR...This multi-layer integrative analysis suggests that EZH2 is associated with proliferative malignant states and immunosuppressive microenvironment features in advanced PCa, including Treg-linked crosstalk. Transcriptomic profiling following EZH2 inhibition supports modulation of these programs by EZH2-targeted perturbation, while functional and causal mechanisms warrant further investigation.

Notably, the inhibitory effect of CL-E on STAT3 Tyr705 phosphorylation was reversed by MEK1/2 (U0126) or PKC inhibitors (bisindolylmaleimide II), indicating that CL-E modulates STAT3 signaling through an ERK-mediated mechanism. Collectively, these in vitro findings identify C. longa leaves as an underutilized botanical resource with the potential to regulate IL-6/STAT3 signaling, warranting in vivo evaluation to establish its efficacy, safety and pharmacokinetics, and to define potential therapeutic utility in IL-6/STAT3-driven conditions.

We propose that lidocaine can be repurposed as an immunomodulator for treating immune-mediated inflammatory diseases. However, future research should define optimal dosing strategies, validate its mechanisms of action in clinical trials, and explore its novel clinical applications as a complementary immunotherapy.

Functional assays demonstrated that DHA-treated cells exhibited increased secretion of TNF, IL1β, ROS, and PD-L1, accompanied by enhanced cytotoxic activity against hepatocellular carcinoma cells in a co-culture system. These findings reveal the molecular mechanisms underlying TAN polarization, and establish DHA as a potent immunomodulatory agent capable of reshaping TANs toward an anti-tumor phenotype.