Review
Immunology
Sunghark Kwon
Summary: JAKs are important enzymes in the JAK-STAT signaling pathway, and dysfunctional JAKs can lead to severe immune system-related diseases. Various JAK inhibitors have been developed to block abnormal JAK-STAT signaling, but drug selectivity and resistance to these inhibitors remain challenges. This review discusses the role and structure of JAKs, as well as strategies for disrupting JAK dimerization to develop novel inhibitors.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Xiaoli Pan, Junping Pei, Aoxue Wang, Wen Shuai, Lu Feng, Faqian Bu, Yumeng Zhu, Lan Zhang, Guan Wang, Liang Ouyang
Summary: This review provides an overview of the roles of the ERKs signaling pathway in cancer and the structure-activity relationships of small molecule inhibitors targeting ERKs. It offers important insights for drug design and optimization as well as potential therapeutic strategies to overcome drug resistance.
ACTA PHARMACEUTICA SINICA B
(2022)
Review
Dermatology
Stephanie Chapman, Michael Kwa, Linda Stein Gold, Henry W. Lim
Summary: The JAK-STAT pathway is important in inflammatory dermatoses, and JAK inhibitors have shown efficacy in treating various dermatologic conditions.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2022)
Review
Dermatology
Stephanie Chapman, Linda Stein Gold, Henry W. Lim
Summary: The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is important in the development of inflammatory skin conditions, and JAK inhibitors have shown efficacy in treating various dermatologic diseases. This review focuses on JAK inhibitors being investigated for the treatment of alopecia areata, vitiligo, sarcoidosis, necrobiosis lipoidica, granuloma annulare, and systemic lupus erythematosus, with a discussion on safety and the implications of JAK inhibitors during the COVID-19 pandemic.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Wijdan Al-Ahmadi, Thomas S. Webberley, Alex Joseph, Ffion Harris, Yee-Hung Chan, Reem Alotibi, Jessica O. Williams, Alaa Alahmadi, Thomas Decker, Timothy R. Hughes, Dipak P. Ramji
Summary: The study revealed significant impacts of ERK1 deficiency and STAT1 S727A modification on gene expression in macrophages, as well as key processes like inflammation and cell migration. These findings suggest potential therapeutic implications for the regulation of atherosclerosis.
Article
Plant Sciences
Xing Zhang, Jie Su, Jiacheng Lin, Lujiong Liu, Jiamin Wu, Wenli Yuan, Yibao Zhang, Qi Chen, Zi jian Su, Guihua Xu, Meng Sun, Yile Zhang, Xuan Chen, Wei Zhang
Summary: The Chinese herbal prescription Fu-Zheng-Tong-Luo (FZTL) formula is used to treat idiopathic pulmonary fibrosis (IPF). This study found that FZTL can alleviate IPF injury and inhibit lung fibroblast activation by regulating the JAK2/STAT3 signaling pathway, making it a potential complementary therapy for IPF.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Yuhan Su, Tianyu Tao, Xiuxing Liu, Wenru Su
Summary: This review summarizes the diverse roles of the JAK-STAT signaling pathway in ocular homeostasis and non-infectious uveitis (NIU) pathology, and discusses the safety and efficacy of JAK inhibitors for treating NIU and potential approaches for treatment optimization.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Neurosciences
Jie Han, Zhen Hua, Wen-jie Yang, Shu Wang, Fang Yan, Jun-nan Wang, Tao Sun
Summary: In this study, the analgesic effect of Resveratrol (Res) and its underlying mechanism were investigated in a rat model of spinal cord injury (SCI). The results showed that intrathecal administration with Res effectively alleviated mechanical allodynia in rats with SCI. It was also found that Res suppressed the production of pro-inflammatory factors and inhibited the expressions of the JAK2/STAT3 signaling pathway. These findings suggest that Res has the potential to be an effective treatment for neuropathic pain following SCI.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Ana Gomez-Larrauri, Patricia Gangoiti, Laura Camacho, Natalia Presa, Cesar Martin, Antonio Gomez-Munoz
Summary: Phosphatidic acid (PA) is a bioactive glycerophospholipid involved in the regulation of cell functions and pathologic processes. This study demonstrates that PA stimulates migration of lung adenocarcinoma cells through the LPA1 receptor and activation of MAPKs ERK1-2, p38, and JNK, as well as the JAK2/STAT3 pathway.
Article
Oncology
Biyin Chen, Li Song, Xiuzhen Nie, Fangfeng Lin, Zongyang Yu, Wencui Kong, Xiaoyan Qi, Wenwu Wang
Summary: This study described the regulatory mechanism of CXCL1 in colorectal cancer (CRC) and found that miR-302e could regulate CXCL1 to inactivate the JAK-STAT signaling pathway, affecting cell proliferation, migration, invasion, and apoptosis of CRC. The results provide a potential therapeutic target for CRC treatment.
FRONTIERS IN ONCOLOGY
(2021)
Review
Dermatology
Qi Yin, Albert Wolkerstorfer, Oren Lapid, Frank B. Niessen, Paul P. M. Van Zuijlen, Susan Gibbs
Summary: Keloid tissues contain inflammatory cells and upregulated pro-inflammatory cytokines. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway mediate cellular responses to these cytokines. Preclinical studies indicate a role for the JAK-STAT pathway in keloid pathogenesis and a potential role for JAK-STAT inhibitors in keloid treatment. Further investigation on relevant biomarkers in a human keloid skin model and in clinical studies is needed.
EXPERIMENTAL DERMATOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Chaekyun Kim
Summary: Bone homeostasis is regulated by the balanced actions of osteoblasts and osteoclasts, which differentiate from different progenitor cells. Mitogen-activated protein kinases (MAPKs), including ERKs, play a crucial role in the differentiation and function of osteoclasts. However, the role of ERKs in osteoclast differentiation is still controversial.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Chuwei Lin, Aneirin Alan Lott, Wei Zhu, Craig P. Dufresne, Sixue Chen
Summary: This study used metabolomics and proteomics to investigate the metabolites and protein profiles of the mpk4 mutant and the wild type plants. It revealed the involvement of MPK4 in polyamine synthesis and photosynthesis, providing insights into the metabolic networks potentially regulated by MPK4.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Lin Shang, Jiali Cao, Siqi Zhao, Jingya Zhang, Yanling He
Summary: This article reviews the pro-inflammatory mechanisms of the JAK-STAT signaling pathway, the regulatory roles of TYK2 in the pathogenesis of psoriasis, and provides updates on ongoing and recently completed clinical trials of TYK2 inhibitors.
JOURNAL OF INFLAMMATION RESEARCH
(2022)
Article
Dermatology
James G. Krueger, Iain B. McInnes, Andrew Blauvelt
Summary: Plaque psoriasis is a common, chronic, systemic, immune-mediated inflammatory disease. The Janus kinase-signal transducer and activator of transcription pathway plays a major role in psoriasis, but safety concerns persist with current JAK inhibitors. TYK2, a member of the JAK family, may offer a potential target for safer and more effective therapies in psoriasis treatment.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Deblina Guha, Taniya Saha, Sayantan Bose, Sreeparna Chakraborty, Subhanki Dhar, Poulami Khan, Arghya Adhikary, Tanya Das, Gaurisankar Sa
Article
Immunology
Abir K. Panda, Arunakumar Gangaplara, Maja Buszko, Kannan Natarajan, Lisa F. Boyd, Suveena Sharma, David H. Margulies, Ethan M. Shevach
JOURNAL OF IMMUNOLOGY
(2020)
Article
Immunology
Bisheng Zhou, Lissette Magana, Zhigang Hong, Long Shuang Huang, Sreeparna Chakraborty, Yoshikazu Tsukasaki, Cary Huang, Li Wang, Anke Di, Balaji Ganesh, Xiaopei Gao, Jalees Rehman, Asrar B. Malik
Article
Oncology
Kirti Kajal, Sayantan Bose, Abir K. Panda, Dwaipayan Chakraborty, Sreeparna Chakraborty, Subhadip Pati, Tania Sarkar, Subhanki Dhar, Dia Roy, Shilpi Saha, Gaurisankar Sa
Summary: The initiation of new blood vessel formation is crucial for tumor growth, with Treg cells secreting high levels of VEGFA to induce angiogenesis. FOXP3 and STAT3 binding to the VEGFA promoter in Treg cells promotes neo-angiogenesis in breast cancer. Targeting Tregs in mice with breast tumor reduces both tumor growth and neo-angiogenesis levels.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Immunology
Abir K. Panda, Yong-Hee Kim, Ethan M. Shevach
Summary: The study finds that the costimulatory receptor CD28 and the coinhibitory receptors CTLA-4 and PD-1 play important roles in the homeostatic proliferation of memory phenotype (MP) T cells in mice. The blockade of CD28 pathway enhances the homeostatic proliferation of MP T cells and T regulatory cells (Tregs). These findings have important implications for the use of biologic agents in treating autoimmune diseases or improving T effector cell function in cancer.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Kurt Bachmaier, Andrew Stuart, Abhalaxmi Singh, Amitabha Mukhopadhyay, Sreeparna Chakraborty, Zhigang Hong, Li Wang, Yoshikazu Tsukasaki, Mark Maienschein-Cline, Balaji B. Ganesh, Prasad Kanteti, Jalees Rehman, Asrar B. Malik
Summary: This study identified two functionally distinct subsets of neutrophils, ANP(high) and ANP(low) neutrophils. They differed in cell surface marker expression, transcriptomic profiles, and capacities to kill bacteria and produce inflammatory mediators.
Article
Multidisciplinary Sciences
Abhalaxmi Singh, Sreeparna Chakraborty, Sing Wan Wong, Nicole A. Hefner, Andrew Stuart, Abdul S. Qadir, Amitabha Mukhopadhyay, Kurt Bachmaier, Jae-Won Shin, Jalees Rehman, Asrar B. Malik
Summary: This study explores the potential of mannose-targeted nanoparticles for treating lung fibrosis by delivering TGF beta-siRNA into profibrotic macrophages, inhibiting the development of fibrosis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Sreeparna Chakraborty, Abhalaxmi Singh, Li Wang, Xinge Wang, Mark A. Sanborn, Zijing Ye, Mark Maienschein-Cline, Amitabha Mukhopadhyay, Balaji B. Ganesh, Asrar B. Malik, Jalees Rehman
Summary: Recent studies have found that training of tissue-resident macrophages through repeated noxious stimuli can enhance host defense responses. This study focused on lung-resident alveolar macrophages (AMs) and found that trained AMs displayed greater resilience to pathogen-induced cell death and had increased capacity for efferocytosis and injury resolution. Transcriptomic analysis and functional assays revealed that training induced expansion of a specific subset of AMs with a proresolving phenotype. Adoptive transfer of these trained AMs restricted inflammatory lung injury in mice exposed to lethal pathogens, highlighting the importance of trained immunity in preventing hyperinflammation and maintaining tissue homeostasis.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Meeting Abstract
Immunology
Sreeparna Chakraborty, Abhalaxmi Singh, Mark Maienschein-Cline, Amitabha Mukhopadhyay, Jalees Rehman, Asrar B. Malik
JOURNAL OF IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Kirti Kajal, Abir K. Panda, Jyotsna Bhat, Dwaipayan Chakraborty, Sayantan Bose, Pushpak Bhattacharjee, Tania Sarkar, Subhrangsu Chatterjee, Santosh K. Kar, Gaurisankar Sa
SCIENTIFIC REPORTS
(2019)
Meeting Abstract
Immunology
Abir Kumar Panda, Ethan M. Shevach
JOURNAL OF IMMUNOLOGY
(2018)