Review
Oncology
Nagendra Awasthi, Clifford Liongue, Alister C. Ward
Summary: STAT proteins, an important family of evolutionarily conserved transcription factors, play key roles in blood and immune cell development and function. In addition to their classical role in transcriptional activation, STAT proteins also have non-canonical functions such as transcriptional repression and roles outside the nucleus. This review presents a revised framework for understanding the diverse functional modalities of STAT proteins.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Review
Cell Biology
Mohamad Mahjoor, Golnaz Mahmoudvand, Simin Farokhi, Alireza Shadab, Mojtaba Kashfi, Hamed Afkhami
Summary: The JAK/STAT signaling cascade plays a crucial role in regulating cell growth and differentiation, as well as immune responses and viral pathogenesis.
CELL COMMUNICATION AND SIGNALING
(2023)
Review
Biochemistry & Molecular Biology
Hyunjung Park, Sangjik Lee, Jaehun Lee, Hyuk Moon, Simon Weonsang Ro
Summary: This review highlights the importance of the JAK/STAT pathway in hepatocellular carcinoma (HCC) and its association with factors such as chronic inflammation and cirrhosis. It also summarizes recent advancements in targeting the JAK/STAT pathway for HCC treatment, emphasizing the potential of this pathway as a promising avenue for therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Feixue Wang, Xiang Zhang, Weixin Liu, Yunfei Zhou, Wenchao Wei, Dabin Liu, Chi Chun Wong, Joseph J. Y. Sung, Jun Yu
Summary: Activated NK cells in the liver promote NASH development by releasing pro-inflammatory cytokines and enhancing NASH progression through the cytokine-JAK-STAT1/3 axis. Modulation of NK cells may serve as a potential therapeutic strategy for NASH.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Review
Immunology
Alejandro V. Villarino
Summary: T cells adapt their metabolism to meet the energetic and biosynthetic demands, which is controlled by cytokines such as PI3K-AKT, mTOR, ERK-MAPK pathways, and JAK-STAT signaling. This review discusses how JAK-STAT influences T cell metabolism, focusing on adaptations required for naive, effector, regulatory, memory, and resident-memory states. JAK-STAT has both direct and indirect effects, regulating metabolism-related genes and instructing genes encoding upstream or regulatory factors. Cytokines impact various metabolic processes, including lipid, amino acid, and nucleotide synthesis, glycolysis, glutaminolysis, oxidative phosphorylation, and fatty acid oxidation.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Review
Oncology
Dipanjan Karati, Kakasaheb Ramoo Mahadik, Piyush Trivedi, Dileep Kumar
Summary: Cancer is a leading cause of death worldwide, and abnormal activation of the JAK-STAT signaling pathway plays an important role in carcinogenesis. JAK inhibitors have shown promising anticancer effects, but clinical trials are still ongoing.
CURRENT CANCER DRUG TARGETS
(2022)
Article
Environmental Sciences
Xin Yu, Linfeng Li, Matthew T. V. Chan, William Ka Kei Wu
Summary: Research suggests that there may be a correlation between herpes zoster and COVID-19 through similar subset of genes involved in cytokine-cytokine receptor interaction. Both diseases show augmented Th17 cell differentiation and IL-17 signaling.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2021)
Article
Chemistry, Medicinal
Sara La Manna, Sara Fortuna, Marilisa Leone, Flavia A. Mercurio, Ilaria Di Donato, Rosa Bellavita, Paolo Grieco, Francesco Merlino, Daniela Marasco
Summary: This study aimed to optimize the peptide structure and improve the biological activity of KIR-SOCS1. By utilizing different techniques, the researchers found that the size of the cyclic structure was crucial for its interaction with JAK2, and substituting native residues with un-natural building blocks enhanced the stability and affinity. These findings contribute to increasing the structural knowledge required for the recognition of SOCS1/JAK2 and advancing towards the development of more drug-like compounds.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Khaled Mukaddam, Sabrina Ruggiero, Steffen M. Berger, Dietmar Cholewa, Sebastian Kuhl, Daniel Vegh, Michael Payer, Michael M. Bornstein, Farah Alhawasli, Elizaveta Fasler-Kan
Summary: Zirconia implants have become widely used in dentistry due to their superior biological compatibility compared to traditional titanium implants, as they reduce bacterial adhesion, inflammation, and cellular interaction. This study investigated the activation of the JAK-STAT signaling pathway in osteoblast-like cells (MG-63) on zirconia and titanium surfaces using different cytokines. The results showed that various cytokines activated different STAT proteins on both surfaces, indicating the activation of the JAK-STAT pathway. The upregulation of MHC class I and class II proteins was observed when MG-63 cells were incubated on zirconia and titanium discs.
Review
Pharmacology & Pharmacy
Hong-Tai Tzeng, I-Tsu Chyuan, Jenn-Haung Lai
Summary: The JAK/STAT signaling pathway plays a crucial role in immune regulation, affecting cell proliferation, survival, inflammation, and immune tolerance. Aberrant activation of this pathway can lead to autoimmune diseases and cancer progression, while targeting JAK/STAT has shown efficacy in suppressing inflammation. The success of small-molecule JAK inhibitors in treating rheumatologic diseases highlights their therapeutic potential in other conditions.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Sara La Manna, Marilisa Leone, Flavia Anna Mercurio, Daniele Florio, Daniela Marasco
Summary: Researchers have designed several peptidomimetics to mimic the function of SOCS3 protein, with one chimeric peptide showing anti-inflammatory and antioxidant properties. The length and position of the cyclic analogues were found to play a crucial role in their structure and function.
Article
Medicine, General & Internal
Ali Razaghi, Attila Szakos, Marwa Alouda, Bela Bozoky, Mikael Bjornstedt, Laszlo Szekely
Summary: Critically ill COVID-19 patients with pleural effusion have a higher risk of longer hospitalization, multisystem inflammatory syndrome, and mortality. The study evaluated the pleural effusions of deceased COVID-19 patients and identified elevated levels of various protein markers, indicating overstimulation of the immune system and cytokine storm. The study also found damage to arterial and cardiovascular organs. Certain markers, such as CA12, CD40, IL-6, IL-8, PD-L1, and VEGFA, showed potential as biomarkers for disease severity and prognosis or as therapy targets. Additionally, the involvement of JAK/STAT pathways in hyperinflammation suggests the potential use of JAK inhibitors as an effective treatment.
Article
Chemistry, Medicinal
Magnus Nilsson, Magdalena Rhedin, Ramon Hendrickx, Susanne Berglund, Antonio Piras, Parmis Blomgran, Anders Cavallin, Mia Collins, Goran Dahl, Bilel Dekkak, Therese Ericsson, Niklas Hagberg, Ann Aurell Holmberg, Agnes Leffler, Anders J. Lundqvist, Thomais Markou, James Pinkerton, Lars Ronnblom, Stacey Siu, Vanessa Taylor, Tiiu Wennberg, Dimitrios Zervas, Arian D. J. Laurence, Suman Mitra, Maria G. Belvisi, Mark Birrell, Annika Borde
Summary: AZD0449 and AZD4604 show potential as inhibitors of signaling pathways involved in asthmatic immune responses, with target engagement demonstrated locally in the lung. These findings support the clinical development of AZD0449 and AZD4604 for the treatment of patients with asthma.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2022)
Review
Chemistry, Medicinal
Maddalena Napolitano, Gabriella Fabbrocini, Angelo Ruggiero, Vincenzo Marino, Mariateresa Nocerino, Cataldo Patruno
Summary: Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects children and adults, with dysfunction of the epidermal barrier and immune dysregulation playing key roles in its pathogenesis. Recent studies have highlighted the importance of Janus kinase (JAK) enzymes in AD, leading to the emergence of oral and topical JAK inhibitors as new treatment options. Abrocitinib, an oral JAK1 inhibitor, has shown promising results in reducing the severity of moderate-to-severe AD with minimal adverse events, comparable to established treatments like dupilumab.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Cell Biology
Nathanael A. Caveney, Robert A. Saxton, Deepa Waghray, Caleb R. Glassman, Naotaka Tsutsumi, Stevan R. Hubbard, Christopher Garcia
Summary: Janus kinases (JAKs) play a key role in cytokine signaling by mediating the transduction of signals downstream of cytokine receptors. The cryoelectron microscopy structure of a mouse JAK1 complex provides insights into the trans-activation step of JAK signaling and the allosteric mechanisms of JAK inhibition.