The JAK (Janus kinase) family of protein tyrosine kinases and the STATs (signal transducers and activators of transcription) have been shown to be activated in response to a number of cytokines and growth factors. In this study, we evaluated the activation of JAK/STAT pathway upon human interleukin-5 (hIL-5) stimulation of two different hIL-5-responsive cell lines, hIL-5 receptor alpha-subunit (hIL-5R alpha) cDNA-transfected TF-1 (TF-h5R alpha) and butyric-acid-treated YY-1 (YY-Bu), and peripheral eosinophils. Immunoprecipitation and electrophoretic mobility shift analysis revealed that tyrosine phosphorylation of JAK2 and activation of STAT5 were induced upon stimulation with hIL-5 in all three cell types, while STAT1 activation was only observed in eosinophils. These results indicate that JAK2/STAT5 activation is a common JAK/STAT pathway for hIL-5-mediated signal in these cells.
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http://dx.doi.org/10.1159/000237712 | DOI Listing |
Introduction: The prognostic differences between neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) remain unclear.
Methods: This study aims to compare the prognostic outcomes of NEC and MiNEN by analyzing the clinicopathological features of these diseases and exploring factors affecting progression after radical surgery. Additionally, we employed whole-exome sequencing to investigate the molecular mechanisms influencing the prognosis of both conditions.
Biomedicine (Taipei)
December 2024
Million-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
Introduction: Although the HaCaT keratinocyte model has been used in previous research to study the effects of antipsoriatic agents, there is still a lack of comprehensive understanding of the mechanism of imiquimod (IMQ)-induced proliferation and signal transduction in psoriasis-like keratinocytes.
Objectives: This study aimed to investigate the molecular mechanisms and pathways associated with psoriasis-like inflammation caused by IMQ in human keratinocytes.
Materials And Methods: HaCaT cells were exposed to different concentrations of IMQ to induce inflammation similar to that observed in psoriasis.
CNS Neurosci Ther
January 2025
Computational Biology Center, Tianjin Anding Hospital, Nankai University Affiliated Tianjin Anding Hospital, Tianjin Mental Health Center of Tianjin Medical University, Tianjin, China.
Background: Clozapine exhibits significant therapeutic efficacy in schizophrenia, especially treatment-resistant schizophrenia. However, clozapine can cause agranulocytosis, a fatal adverse effect, and the aim of this study is to explore this mechanism based on network pharmacology and molecular docking.
Method: Six and two databases were used to identify targets associated with clozapine and agranulocytosis, respectively.
Curr Hematol Malig Rep
January 2025
Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Purpose Of Review: More than a decade following the discovery of Calreticulin (CALR) mutations as drivers of myeloproliferative neoplasms (MPN), advances in the understanding of CALR-mutant MPN continue to emerge. Here, we summarize recent advances in mehanistic understanding and in targeted therapies for CALR-mutant MPN.
Recent Findings: Structural insights revealed that the mutant CALR-MPL complex is a tetramer and the mutant CALR C-terminus is exposed on the cell surface.
Blood
January 2025
Children's Hospital of Philadelphia & University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States.
Philadelphia chromosome-like B-cell acute lymphoblastic leukemia (Ph-like ALL) is driven by genetic alterations that induce constitutive kinase signaling and is associated with chemoresistance and high relapse risk in children and adults. Preclinical studies in the most common CRLF2-rearranged/JAK pathway-activated Ph-like ALL subtype have shown variable responses to JAK inhibitor-based therapies, suggesting incomplete oncogene addiction and highlighting a need to elucidate alternative biologic dependencies and therapeutic vulnerabilities, while the ABL-class Ph-like ALL subtype appears preferentially sensitive to SRC/ABL- or PDGFRB-targeting inhibitors. Which patients may be responsive versus resistant to tyrosine kinase inhibitor (TKI)-based precision medicine approaches remains a critical knowledge gap.
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