Article
Chemistry, Medicinal
Oscar Mammoliti, Adeline Palisse, Caroline Joannesse, Sandy El Bkassiny, Brigitte Allart, Alex Jaunet, Christel Menet, Beatrice Coornaert, Kathleen Sonck, Inge Duys, Philippe Clement-Lacroix, Line Oste, Monica Borgonovi, Emanuelle Wakselman, Thierry Christophe, Nicolas Houvenaghel, Mia Jans, Bertrand Heckmann, Laurent Saniere, Reginald Brys
Summary: Studies suggest that blocking S1P2 receptor signaling could be effective for treating idiopathic pulmonary fibrosis, with only a few antagonists disclosed so far. A chemical enablement strategy led to the discovery of a pyridine series with good antagonist activity, and further optimization identified a compound with potent activity in a phenotypic IL8 release assay and bleomycin-induced model of pulmonary fibrosis.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Gerhild van Echten-Deckert
Summary: Lipids are essential components of the CNS, and sphingolipids, a type of lipid, are highly concentrated in the brain. Sphingosine 1-phosphate (S1P), derived from membrane sphingolipids, has complex effects on the brain, which can be both beneficial and detrimental. However, the role of S1P in brain development and various brain pathologies is still controversial.
PHARMACOLOGY & THERAPEUTICS
(2023)
Review
Biochemistry & Molecular Biology
Celine Tolksdorf, Eileen Moritz, Robert Wolf, Ulrike Meyer, Sascha Marx, Sandra Bien-Moeller, Ulrike Garscha, Gabriele Jedlitschky, Bernhard H. Rauch
Summary: Sphingosine-1-phosphate (S1P) is a versatile signaling lipid that regulates various cellular processes. Platelets are an important source of S1P and can rapidly generate and release it to regulate cellular responses. Furthermore, platelet-generated and released S1P may also impact disease processes such as inflammation-driven vascular diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Leiye Yu, Licong He, Bing Gan, Rujuan Ti, Qingjie Xiao, Hongli Hu, Lizhe Zhu, Sheng Wang, Ruobing Ren
Summary: This study reveals the activation and regulation mechanism of human S1PR1 receptor through cryo-electron microscopy analysis. The S1PR1 receptor plays an essential role in the immune and vascular systems, and understanding its function in depth contributes to the development of related therapeutic approaches.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Chiara D'Aprile, Simona Prioni, Laura Mauri, Alessandro Prinetti, Sara Grassi
Summary: Lipid rafts are specialized membrane domains enriched in gangliosides, sphingomyelin, cholesterol, and proteins involved in signal transduction, modulating cell homeostasis. Sphingosine 1-phosphate participates in various signal transduction processes, with enzymes and receptors often localized in lipid rafts.
CELLULAR SIGNALLING
(2021)
Article
Medicine, Research & Experimental
Colin Niaudet, Bongnam Jung, Andrew Kuo, Steven Swendeman, Edward Bull, Takahiro Seno, Reed Crocker, Zhongjie Fu, Lois E. H. Smith, Timothy Hla
Summary: This study reveals the significance of S1P in vascular development. Activation of endothelial S1PR1 by circulating HDL-S1P can suppress neovascularization in retinopathy. These findings suggest that circulating HDL-S1P activation of endothelial S1PR1 serves as a protective mechanism against neovascular retinopathy.
EMBO MOLECULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Shah Alam, Sumaiya Yasmeen Afsar, Gerhild Van Echten-Deckert
Summary: In this study, the neural-targeted ablation of SGPL1 in a mouse model revealed that the accumulation of S1P due to SGPL1 deficiency led to increased expression of glycolytic enzymes, preferential entry of pyruvate into the TCA cycle, and elevated cellular ATP content. The high energy load activated mTOR, thus regulating astrocytic autophagy and potentially affecting neuronal viability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Michela Terlizzi, Chiara Colarusso, Giusy Ferraro, Anna Falanga, Maria Chiara Monti, Pasquale Somma, Ilaria De Rosa, Luigi Panico, Aldo Pinto, Rosalinda Sorrentino
Summary: Sex is a biological variable that can affect the activity of the lipid mediator S1P in lung conditions. This study found sex differences in circulating S1P levels among lung cancer patients, with ADK patients having lower levels compared to SCC patients. Additionally, the expression of S1P receptors and metabolic enzymes differed between male and female patients with different lung cancer types. These findings highlight the importance of considering sex differences when studying S1P as a prognostic mediator in lung cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Zafrul Hasan, Toan Q. Nguyen, Brenda Wan Shing Lam, Jovi Hui Xin Wong, Caleb Cheng Yi Wong, Clarissa Kai Hui Tan, Jiabo Yu, Chung Hwee Thiam, Yongliang Zhang, Veronique Angeli, Long N. Nguyen
Summary: The protein Spns2 is involved in regulating lymphocyte movement and has been shown to have potential as a drug target in autoimmune diseases. This study examined mice with a genetic deletion of Spns2 and found that it affected lymphocyte levels, S1P secretion, and lymph node vasculature. Additionally, these mice were resistant to multiple sclerosis, suggesting that targeting Spns2 could be a promising therapeutic approach for neuroinflammation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Medicine, Research & Experimental
Xuefeng Xu, Yi Han, Tianxin Zhu, Faxin Fan, Xin Wang, Yuqing Liu, Duosheng Luo
Summary: Osteoporosis is a common disease worldwide with significant economic burden. Understanding the role of SphK/S1P/S1PR signaling in regulating osteoblasts and osteoclasts is crucial for the treatment of osteoporosis. This review summarizes the effects of S1P on proliferation, differentiation, apoptosis, and functions, and focuses on S1P-based therapeutic approaches in bone metabolism.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Cell Biology
Yuan Yuan, Guowen Jia, Chao Wu, Wei Wang, Lin Cheng, Qian Li, Ziyan Li, Kaidong Luo, Shengyong Yang, Wei Yan, Zhaoming Su, Zhenhua Shao
Summary: This study presents five cryo-electron microscopy structures of S1PRs bound to diverse drug agonists and the heterotrimeric Gi protein. The structural and functional assays demonstrate the different binding modes of chemically distinct agonists of S1PRs, reveal the mechanical switch that activates these receptors, and provide a framework for understanding ligand selectivity and G protein coupling.
Review
Oncology
Eileen M. McGowan, Yiguang Lin, Size Chen
Summary: Obesity is closely associated with inflammation and increased cancer risk in the digestive system. Saturated fat diets and being overweight can cause chronic inflammation. Bioactive sphingolipids, signaling molecules made from saturated fats, play essential roles in maintaining healthy gastrointestinal immunity. Excessive levels of these molecules can lead to chronic inflammation, but drugs that block their activity have the potential to reduce gastrointestinal cancer risk.
Article
Neurosciences
Huitong Song, Holly P. McEwen, Thomas Duncan, Jun Yup Lee, Jonathan D. Teo, Anthony S. Don
Summary: SphK2 deficiency leads to decreased remyelination and maintenance of myelin with aging, possibly due to elevated levels of cytotoxic sphingosine and ceramide.
Article
Cell Biology
Michela Terlizzi, Chiara Colarusso, Pasquale Somma, Ilaria De Rosa, Luigi Panico, Aldo Pinto, Rosalinda Sorrentino
Summary: This study revealed that S1P plays a role in promoting inflammation and cytokine release in non-small cell lung cancer patients, emphasizing its role as a pro-tumor driver.
Article
Oncology
Vikas Satyananda, Masanori Oshi, Yoshihisa Tokumaru, Aparna Maiti, Nitai Hait, Ryusei Matsuyama, Itaru Endo, Kazuaki Takabe
Summary: High S1P export, driven by the simultaneous high expression of SphK1 and ABCC1, is associated with enhanced HCC progression and immune response, leading to significantly worse disease-specific survival and overall survival outcomes.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Medicine, Research & Experimental
Yuwen Zhu, Yan Guo, Yujia Xue, Anqi Zhou, Ying Chen, Yifei Chen, Xiulian Miao, Fangqiao Lv
Summary: BRG1 plays an important role in HSC-myofibroblast transition and targeting it could be a reasonable strategy for liver fibrosis intervention.
Article
Medicine, Research & Experimental
Liu Ye, Beibei Liu, Jingling Huang, Xiaolin Zhao, Yuan Wang, Yungen Xu, Shuping Wang
Summary: Doublecortin-like kinase 1 (DCLK1) is a significant prooncogenic factor that is strongly associated with the malignant progression and clinical prognosis of various cancers. DCLK1 plays important roles in stem cell marker regulation, tumor cell reprogramming, and immune evasion. However, the exact biological functions of DCLK1, especially the disparities between its alpha- and beta-form transcripts in cancer progression, remain ambiguous.
Article
Medicine, Research & Experimental
Jiahui Yang, Xiaoyu Chen, Tianjing Liu, Yongyan Shi
Summary: This article reviews the role of bile acids in necrotizing enterocolitis (NEC) and their potential therapeutic value. The dysregulation of bile acids is associated with intestinal injury, and inflammatory factors in the liver also play a crucial role in regulating bile acid transport. The bile acid metabolic pathway is important for regulating intestinal microbiota, cell proliferation, and barrier protection.
Review
Medicine, Research & Experimental
Zhenzheng Zhu, Yuemiao Xu, Yuwei Xia, Xinru Jia, Yixin Chen, Yuyue Liu, Leyin Zhang, Hui Chai, Leitao Sun
Summary: Bile acid, as the final product of cholesterol breakdown, plays a complex regulatory and signaling role in human metabolism. Research suggests that it has the potential to enhance metabolism and regulate chronic metabolic diseases through various pathways. The interaction between bile acid and gut microbiota is also of great significance.
Article
Medicine, Research & Experimental
Xin He, Hong-Xu Zhou, Xian Fu, Kai-Di Ni, Ai-Zhi Lin, Ling-Tong Zhang, Hou-Hua Yin, Qing Jiang, Xue Zhou, Yi-Wen Meng, Jun-Yan Liu
Summary: DON exposure causes an increase in deoxycholic acid (DCA), which contributes to intestinal injury. DCA may be a potential therapeutic target for DON enterotoxicity.
Article
Medicine, Research & Experimental
Zhitao Wang, Heng Ma, Abdul Nasir, Sufang Liu, Zhisong Li, Feng Tao, Qian Bai
Summary: This study reveals the involvement of TET1-mediated epigenetic regulation in chronic TMJ pain through trigeminal TNF alpha signaling.
Article
Medicine, Research & Experimental
Lu Yu, Hao Ran, Yaru Lu, Qian Ma, Huan Huang, Weibin Liu
Summary: This study found that the HIF-1 alpha inhibitor BAY 87-2243 can alleviate the symptoms of the Experimental Autoimmune Myasthenia Gravis (EAMG) inflammation model. BAY 87-2243 can restore the balance of CD4(+)T cell subsets, reduce the production of pro-inflammatory cytokines, and act as both an immune imbalance regulator and anti-inflammatory.
Article
Medicine, Research & Experimental
Alex Peralvarez-Marin, Montse Sole, Judith Serrano, Alice Taddeucci, Belen Perez, Clara Penas, Gemma Manich, Marcel Jimenez, Pilar D'Ocon, Francesc Jimenez-Altayo
Summary: This study provides the first evidence that TRPV2 channels may modulate vascular tone by balancing opposing inputs from the endothelium and smooth muscle, leading to net vasodilation. The amplification of TRPV2 channel-induced activity by NO emphasizes the pathophysiological relevance of these findings.
Article
Medicine, Research & Experimental
Amin Ullah, Jing Zhao, Jiakun Li, Rajeev K. Singla, Bairong Shen
Summary: Gastric cancer is the fifth-most prevalent and second-most deadly cancer worldwide. Late onset of symptoms makes early detection important. CXC chemokines play an important role in the pathological process of gastric cancer, but their exact role in diagnosis and prognosis is not fully understood. Inhibiting CXC chemokines shows promise as a targeted therapy.
Article
Medicine, Research & Experimental
Menna S. Zeyada, Salma M. Eraky, Mamdouh M. El-Shishtawy
Summary: The current study demonstrates the prophylactic and antifibrotic effects of Trig against BLM-induced PF by targeting multiple signaling pathways. The combination of Trig and Pirf may be a promising approach to enhance Pirf's anti-fibrotic effect.