According to the World Health Organization (WHO), cancer is the second-highest cause of mortality worldwide, killing nearly 9.6 million people annually. Despite the advances in diagnosis and treatment during the last couple of decades, it remains a serious concern due to the limitations of currently available cancer management strategies. Therefore, alternative strategies are highly required to overcome these glitches. In addition, many etiological factors such as environmental and genetic factors initiate the activation of the Janus kinase (JAK)-signal transducer and activator of the transcription (STAT) pathway. This aberrant activation of the JAK-STAT pathway has been reported in various disease states, including inflammatory conditions, hematologic malignancies, and cancer. For instance, many patients with myeloproliferative neoplasms carry the acquired gain-of-function JAK2 V617F somatic mutation. This knowledge has dramatically improved our understanding of pathogenesis and has facilitated the development of therapeutics capable of suppressing the constitutive activation of the JAK-STAT pathway. Our aim is not to be expansive but to highlight emerging ideas towards preventive therapy in a modern view of JAK-STAT inhibitors. A series of agents with different specificities against different members of the JAK family of proteins is currently undergoing evaluation in clinical trials. Here we give a summary of how JAK-STAT inhibitors function and a detailed review of current clinical drugs for managing cancer as a new therapeutic approach.
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http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.2023045403 | DOI Listing |
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Dr. Babasaheb Ambedkar Technological University, Lonere, Raigad, 402103, India.
Acute lung injury i.e. ALI and its serious form acute respiratory distress syndrome (ARDS) are incurable medical conditions associated with significant global mortality and morbidity.
View Article and Find Full Text PDFJ Psychiatry Neurosci
January 2025
From the Computational Biology Centre and the Laboratory of Psychiatric-Neuroimaging-Genetic and Comorbidity, Tianjin Anding Hospital, Tianjin Mental Health Centre of Tianjin Medical University, Nankai University Affiliated Tianjin Anding Hospital, Tianjin, China.
Background: Clozapine is superior to all other antipsychotics in treating schizophrenia in terms of its curative efficacy; however, this drug is prescribed only as a last resort in the treatment of schizophrenia, given its potential to induce cardiac arrest. The mechanism of clozapine-induced cardiac arrest remains unclear, so we aimed to elucidate the potential mechanisms of clozapine-induced cardiac arrest using network pharmacology and molecular docking.
Methods: We identified and analyzed the overlap between potential cardiac arrest-related target genes and clozapine target genes.
Tissue Cell
December 2024
Department of Neurosurgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China. Electronic address:
Glioblastoma is considered the most malignant central nervous system tumor. This study aimed to investigate effects of latent transforming growth factor-β binding protein-2 (LTBP2) on glioblastoma growth and associated mechanisms. LTBP2 gene transcription in glioblastoma was determined using RT-PCR.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, TX 75080.
The TRAMP complex contains two enzymatic activities essential for RNA processing upstream of the nuclear exosome. Within TRAMP, RNA is 3' polyadenylated by a subcomplex of Trf4/5 and Air1/2 and unwound 3' to 5' by Mtr4, a DExH helicase. The molecular mechanisms of TRAMP assembly and RNA shuffling between the two TRAMP catalytic sites are poorly understood.
View Article and Find Full Text PDFElife
January 2025
Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Cigarette smoking is a well-known risk factor inducing the development and progression of various diseases. Nicotine (NIC) is the major constituent of cigarette smoke. However, knowledge of the mechanism underlying the NIC-regulated stem cell functions is limited.
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