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Dual-specific phosphatase-8 (DUSP8), identified as the first gene in a genome-wide association study (GWAS), is implicated in cellular oxidative stress, proliferation, apoptosis, and drug resistance through its negative regulation of the dephosphorylation activities of JNK, ERK, and p38 within the MAPK pathway. Recent studies have shown that DUSP8 plays a pivotal role in the progression of several human diseases, notably colorectal cancer, diabetic kidney disease, and breast cancer. This suggests that DUSP8 may represent a novel target for clinical intervention in these diseases. This review first introduces the biological structure and function of DUSP8, with a focus on its relationship with a series of diseases and the regulatory mechanisms involved. Furthermore, we concentrate on unresolved scientific questions in the current research, aiming to establish a new theoretical foundation for the diagnosis and treatment of related diseases.
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http://dx.doi.org/10.1186/s12967-025-06499-y | DOI Listing |
Crit Rev Immunol
January 2025
Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Dist. Medchal,500078, Telangana State, India.
IL-2 agonists significantly modulate T cell regulation, impacting activation, proliferation, differentiation, and immune homeostasis. Interleukin-2 (IL-2) is crucial for T cell growth and function, binding to the IL-2 receptor to trigger signaling pathways that balance immune responses. IL-2 promotes the expansion of effector T cells and enhances regulatory T cells (Tregs), preventing autoimmune responses.
View Article and Find Full Text PDFJ Environ Pathol Toxicol Oncol
January 2025
Department of Clinical Laboratory Medicine, Fujian Medical University, Fuzhou, China.
Invasive ductal carcinoma (IDC) is a major type of breast cancer. The utilization of inhibitors targeting histone methyltransferases introduces novel therapeutic avenues for the treatment of cancer. Immunohistochemistry, Western blot, and reverse transcription quantitative polymerase chain reaction experiments were applied to assess the levels of EHMT2 in IDC and adjacent tissues.
View Article and Find Full Text PDFJ Environ Pathol Toxicol Oncol
January 2025
Department of Pharmacy, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
Despite advancements in systemic therapy, the mortality rate for patients with metastatic melanoma remains around 70%, underscoring the imperative for alternative treatment strategies. Through the establishment of a chemoresistant melanoma model and a subsequent drug investigation, we have identified pacritinib, a medication designed for treating myelofibrosis and severe thrombocytopenia, as a potential candidate to overcome resistance to melanoma therapy. Our research reveals that pacritinib, administered at clinically achievable concentrations, effectively targets dacarbazine-resistant melanoma cells by suppressing IRAK1 rather than JAK2.
View Article and Find Full Text PDFAtherosclerosis
September 2025
Department of Cardiothoracic and Macrovascular Surgery, Jingzhou Hospital Affiliated to Yangtze University, No.26 Chuyuan Avenue, Jingzhou District, Jingzhou City, Hubei Province, 434020, China. Electronic address:
Background And Aims: Aortic dissection (AD) is one of the most dangerous and tricky diseases in the field of cardiovascular surgery, severely affecting public health. Recent studies have found that SUMOylation is linked to the pathogenesis of cardiovascular diseases. However, we know very little about the molecular mechanisms of SUMOylation in AD.
View Article and Find Full Text PDFJ Med Chem
September 2025
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery o
Aberrant activation of fibroblast growth factor receptors (FGFRs) plays a critical role in tumorigenesis across multiple cancer types, driving the development of various FGFR inhibitors. Despite clinical advances, therapeutic efficacy remains limited by the emergence of drug resistance, primarily mediated by gatekeeper mutations in FGFRs. To overcome this challenge, we designed and synthesized a novel series of 7-(1-methyl-1-indole-3-yl)-5-pyrrolo[2,3-]pyrazine derivatives as covalent pan-FGFR inhibitors targeting both wild-type and gatekeeper mutants.
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