JAK2 (Janus kinase 2)

It significantly suppressed the release of proinflammatory cytokines and downregulated the expression of interleuin-6 and interleukin-6 receptor as well as the ratios of phosphorylated Janus Kinase 2/Janus Kinase 2 and phosphorylated signal transducer and activator of transcription 3/ signal transducer and activator of transcription 3. These protective effects were positively correlated with the dosage of β-escin.ConclusionThe findings suggested that β-escin exerted neuroprotective effects in ischemic stroke by modulating the interleukin-6/Janus kinase 2/signal transducer and activator of transcription 3 pathway, thereby reducing neuroinflammation and apoptosis.

NFE2 gene mutations in MPNs were predominantly frameshift mutations. NFE2 gene mutations were correlated with older age, elevated levels of several inflammatory factors (including TNF-α、IFN-γ、IL-10、IL-12P70、IL-17) , and they mostly occurred in late-stage of MPNs.

The CCDC6::JAK2 chimeric protein retains the CCDC6 coiled-coil domain and the JAK2 kinase domain. Dimerization of chimeric proteins through coiled-coil domains promotes JAK2 autophosphorylation leading to constitutive activation of the JAK/STAT signaling pathway.

These findings unveil therapeutic strategies to potentially prevent leukemic evolution in MPN patients by inhibiting specific cytokine signaling. Our data establish a new paradigm for clonal evolution of blood neoplasms by showing that disease progression in MPN can arise from parallel acute myeloid leukemia (pAML) clones independent of the primary disease.

Although the JAK1/2 inhibitor Ruxolitinib is clinically approved, its efficacy is limited by toxicity to normal cells and the development of drug resistance...Moreover, through a compound screen, followed by chemical proteomics and compound optimization, WWQ-03-012 is discovered, which selectively degrades mutant JAK2, induces primary leukemia cells death, and inhibits MPN progression through targeting DESI2 enzymatic activity in vitro and in vivo. These studies provide a novel therapeutic strategy against mutated JAK2 signaling in MPN and sAML.

In conclusion, PathHDNN provided an effective pathway hierarchical-informed framework for accurately predicting patient responses to immunotherapy and identified key pathways yielding valuable insights into the biological mechanisms underlying treatment responses, which is essential for advancing precision medicine.

Induction chemotherapy (cytarabine and idarubicin) initially achieved remission, but subsequent relapses led to the use of venetoclax and 5-azacytidine, which again resulted in remission. This is the first report that molecularly characterizes the HMBOX1::JAK2 fusion in a de novo AML patient. The identification of this novel alteration adds to the growing and heterogeneous molecular landscape of AML and suggests a potential new avenue for targeted therapy.

Following parathyroidectomy, the patient's hemoglobin and hematocrit levels normalized without further treatment, suggesting remission of PV. This case report and literature review highlight a possible relationship between the calcium-parathyroid hormone axis and hematopoiesis, providing insight into potential shared pathophysiological mechanisms.

DCA activates the TGR5/JAK2/STAT3 axis to upregulate ATP4A, thereby promoting VFL epithelial cell proliferation and migration. These findings provide novel mechanistic insight linking bile acid reflux to VFL progression and identify TGR5/ATP4A as potential therapeutic targets.

Telmisartan was used as the internal standard (IS). Stability studies confirmed the analyte's integrity across multiple freeze-thaw cycles. The developed LC-MS/MS method is selective, sensitive, fully validated, and was successfully applied to pharmacokinetic studies.

These findings highlight the potential of targeting MSC-mediated pathways as a therapeutic strategy in polycythemia vera.

This study confirmed well-known gene-disease associations in myeloid malignancies but found no significant link between parvovirus B19 infection and specific somatic mutations or disease subtypes. These findings suggest that B19 infection may be incidental, underscoring the need for larger-scale studies to clarify its clinical relevance in patients with myeloid malignancies.