Article
Chemistry, Multidisciplinary
Shaoqin Zheng, Jiahui Lin, Zhongqiu Pang, Hui Zhang, Yinuo Wang, Lanjing Ma, Haijiao Zhang, Xi Zhang, Maorong Chen, Xinjun Zhang, Chao Zhao, Jun Qi, Liu Cao, Min Wang, Xi He, Ren Sheng
Summary: In this study, researchers discovered that cholesterol binds specifically to the Fzd5 receptor, enabling its maturation and trafficking to the plasma membrane. Cholesterol stimulates tumor growth in Wnt-addicted pancreatic ductal adenocarcinoma through Fzd5-mediated signaling, while a natural compound can inhibit this process. These findings reveal a novel mechanism by which Fzd5 acts as a cholesterol sensor and suggest potential therapeutic opportunities for Wnt-dependent cancers.
Article
Plant Sciences
Yuhui Mi, Lei Zhong, Saijian Lu, Po Hu, Yang Pan, Xuelin Ma, Binghui Yan, Zhenhuan Wei, Guangming Yang
Summary: The study aimed to evaluate the healing effect of quercetin on cutaneous wound models in vivo and in vitro, and to reveal the mechanisms involved, including the Wnt/beta-catenin pathway and TERT.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Oncology
Quanxin Wu, Cheng Xu, Xianghua Zeng, Zhimin Zhang, Bo Yang, Zhiguo Rao
Summary: The study found that sFRP-4 expression was significantly downregulated in HCC tissues and cells compared to adjacent healthy tissues and MIHA cells. Overexpression of sFRP-4 inhibited HCC cell viability and proliferation, and accelerated HCC cell apoptosis. Furthermore, sFRP-4 inhibited the Wnt/beta-catenin signaling pathway by regulating GSK-3 beta and beta-catenin expression, restraining the malignant behavior of HCC cells.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Yuri Lee, Hai-long Piao, Jongchan Kim
Summary: The Wnt signaling pathway is crucial for regulating various cellular processes, and dysregulation of this pathway has been linked to human diseases, including cancer. In this study, researchers aimed to identify the deubiquitinases (DUBs) that regulate the pathway through the essential component LEF1. They discovered that OTUD7B interacts with LEF1 and activates Wnt signaling. Furthermore, OTUD7B promotes the nuclear localization of LEF1, leading to increased interaction with beta-catenin. This study suggests that OTUD7B may serve as a potential therapeutic target in diseases where Wnt signaling is dysregulated, such as cancer.
Article
Oncology
Jing Zhang, Pengfei Li, Ting Li, Zhiqin Zhou, Huiling Wu, Lei Zhang
Summary: The study reveals that CORO6 is highly expressed in HCC samples with higher grades and correlates with poor patient outcomes. Depletion of CORO6 significantly impairs the cell survival, migratory, and invasive abilities of HCC cells, and enhances Wnt signaling in these cells.
Article
Medicine, Research & Experimental
Zheng Qin, Yupei Li, Jiameng Li, Luojia Jiang, Zhuyun Zhang, Kaixi Chang, Qinbo Yang, Shanshan Chen, Ruoxi Liao, Baihai Su
Summary: This study found that exosomal STAT1 derived from HP-treated HUVECs can promote VSMC calcification. Activation of the Wnt/beta-catenin pathway may be a potential mechanism of exosome-promoted VSMC calcification.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2022)
Article
Oncology
Yang Zhou, Jiang Xu, Haichang Luo, Xiangjing Meng, Ming Chen, Di Zhu
Summary: Abnormal activation of the Wnt/beta-catenin signaling pathway is closely related to tumorigenesis and immune surveillance, leading to increased resistance to immunotherapy.
Article
Plant Sciences
Fujiang Wang, Pengfei Tu, Kewu Zeng, Yong Jiang
Summary: The study found that the total glycosides and polysaccharides extracts of Cistanche deserticola can promote osteoblastogenic bone formation and improve bone microstructure damage in SAMP6 mice, and their therapeutic effect on osteoporosis is via activating the Wnt/beta-catenin signaling pathway.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Mingliang He, Xiaoyang Lv, Xiukai Cao, Zehu Yuan, Tesfaye Getachew, Yutao Li, Shanhe Wang, Wei Sun
Summary: SRY-box transcription factor 18 (SOX18) is expressed in dermal papilla cells (DPCs) of sheep hair follicles and plays a crucial role in promoting DPC proliferation through activating the Wnt/β-Catenin signaling pathway. Inhibition of the Wnt/β-Catenin signaling pathway can be rescued by SOX18, suggesting the essential role of SOX18 in governing DPC proliferation and hair growth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Shanshan Jia, Pin Guo, Junhua Lu, Xujun Huang, Laming Deng, Yan Jin, Lanyan Zhao, Xiaofang Fan
Summary: The study revealed that curcumol could ameliorate lung inflammation and airway remodeling in chronic asthmatic mice by inhibiting the abnormal activation of the Wnt/beta-catenin pathway.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Review
Oncology
Sheikh A. A. Umar, Bo Dong, Minakshi Nihal, Hao Chang
Summary: This review summarizes the role of FZD receptors in melanoma, including their involvement in embryonic development, tissue homeostasis, and cancer. Misregulated FZD signaling promotes tumor cell proliferation and invasion in melanoma, and both the canonical and non-canonical pathways are implicated.
FRONTIERS IN ONCOLOGY
(2022)
Article
Immunology
Mengjiao Zhang, Dongmei Yang, Honggang Yu, Qing Li
Summary: miR-497 is downregulated in inflammatory diseases but not in IBD. The study found that miR-497 can inhibit gut inflammation by suppressing the NF-kappa B pathway and cytokine release.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Agriculture, Dairy & Animal Science
Mingliang He, Xiaoyang Lv, Xiukai Cao, Zehu Yuan, Kai Quan, Tesfaye Getachew, Joram M. M. Mwacharo, Aynalem Haile, Yutao Li, Shanhe Wang, Wei Sun
Summary: In our study, we found that CRABP2 was highly expressed in Hu sheep hair follicles, indicating its potential influence on dermal papilla cells (DPCs). Our experiments demonstrated that overexpression of CRABP2 promoted DPC proliferation and activated the Wnt/beta-catenin pathway. These findings highlight the crucial role of CRABP2 in Hu sheep DPC proliferation and shed light on its function in hair follicles.
Article
Geriatrics & Gerontology
Y. Li, W. Cui, B. Song, X. Ye, Z. Li, C. Lu
Summary: This study found that SIRT1 activator has a negative regulatory effect on weight, blood lipid levels, and lesion conditions in AS mice, and reduces the CD34+/VEGFR2+ density in aortic tissues. In in vitro experiments, the SIRT1 activator promotes the proliferation and migration of EPCs and acts through the wnt/beta-catenin/GSK3 beta signaling pathway.
JOURNAL OF NUTRITION HEALTH & AGING
(2022)
Article
Environmental Sciences
Xuran Li, Tongtong Zhang, Wenting Lv, Hui Wang, Haoran Chen, Qinghua Xu, Hourong Cai, Jinghong Dai
Summary: Polystyrene microplastics (PS-MPs) are absorbed by organisms and affect cellular functions due to their small volume and biological permeability. Inhalation of PS-MPs has been found to induce pulmonary fibrosis in mice, accompanied by oxidative stress and activation of the Wnt/β-catenin signaling pathway.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2022)
Review
Pediatrics
Claire A. Murphy, Elaine Neary, Daniel P. O'Reilly, Sarah Cullivan, Afif El-Khuffash, Fionnuala NiAinle, Patricia B. Maguire, Naomi McCallion, Barry Kevane
Summary: The evaluation of haemostasis is particularly challenging in neonates due to their limited blood volume. The Calibrated Automated Thrombogram (CAT) has successfully elucidated several differences between haemostatic mechanisms in premature and term neonates compared with adults. However, the lack of evidence of CAT as an accurate predictor of neonatal bleeding, blood volume required, and the absence of an evidence-based treatment algorithm for abnormal CAT results limit its current application as a bedside clinical tool for the evaluation of sick neonates.
EUROPEAN JOURNAL OF PEDIATRICS
(2022)
Article
Cardiac & Cardiovascular Systems
Laura J. Corbin, Stephen J. White, Amy E. Taylor, Christopher M. Williams, Kurt Taylor, Marion T. van den Bosch, Jack E. Teasdale, Matthew Jones, Mark Bond, Matthew T. Harper, Louise Falk, Alix Groom, Georgina G. J. Hazell, Lavinia Paternoster, Marcus R. Munafo, Borge G. Nordestgaard, Anne Tybjaerg-Hansen, Stig E. Bojesen, Caroline Relton, Josine L. Min, George Davey Smith, Andrew D. Mumford, Alastair W. Poole, Nicholas J. Timpson
Summary: Epigenetic DNA hypomethylation at the F2RL3 gene induced by smoking may increase PAR4 expression, leading to downstream effects on platelet reactivity. F2RL3 DNA methylation may be a possible contributory pathway from smoking to cardiovascular disease risk.
CIRCULATION RESEARCH
(2022)
Article
Hematology
Sarah L. Millington-Burgess, Matthew T. Harper
Summary: The study revealed that R5421 can reduce platelet PS exposure and inhibit thrombin generation by maintaining flippase activity in procoagulant platelets, without directly inhibiting scramblase activity.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Sarah Kelliher, Luisa Weiss, Sarah Cullivan, Ellen O'Rourke, Claire A. Murphy, Shane Toolan, Aine Lennon, Paulina B. Szklanna, Shane P. Comer, Hayley Macleod, Ana Le Chevillier, Sean Gaine, Kate M. A. O'Reilly, Brian McCullagh, John Stack, Patricia B. Maguire, Fionnuala Ni Ainle, Barry Kevane
Summary: A study found that patients with moderate COVID-19 exhibited increased hypercoagulability and endothelial damage despite receiving thromboprophylaxis, which may have clinical implications.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Cell Biology
Luc R. A. Francis, Sarah L. Millington-Burgess, Taufiq Rahman, Matthew T. Harper
Summary: Thrombin activates platelets through PAR1 and PAR4, with PAR1 being the more rapidly activated receptor. Q94, an allosteric modulator of PAR1, has been reported to inhibit PAR1-G alpha q coupling in various cell lines, but its effects on human platelet activation have not been studied. Our data suggest that Q94 may have off-target effects in platelets independent of PAR1, precluding its use as a selective PAR1 allosteric modulator.
Article
Multidisciplinary Sciences
Rebecca B. Riddle, Karin Jennbacken, Kenny M. Hansson, Matthew T. Harper
Summary: Inflammatory diseases are characterized by excessive neutrophil infiltration, but lack of accurate in vitro and in vivo models hinders drug development. This study developed a 3D in vitro inflammation-on-a-chip model to mimic neutrophil migration across endothelium and extracellular matrix. The composition of the extracellular matrix was found to significantly affect neutrophil transmigration and response to inhibitors, providing potential for disease-specific drug development.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Annalisa Contursi, Rosa Fullone, Paulina Szklanna-Koszalinska, Simone Marcone, Paola Lanuti, Francesco Taus, Alessandra Meneguzzi, Giulia Turri, Melania Dovizio, Annalisa Bruno, Corrado Pedrazzani, Stefania Tacconelli, Marco Marchisio, Patrizia Ballerini, Pietro Minuz, Patricia Maguire, Paola Patrignani
Summary: This study aimed to investigate the release of EVs from activated platelets in CRC patients and healthy controls and their effect on gene expression and lipid mediator synthesis. The protein content of thrombin-stimulated mEVs was found to be modulated in CRC and could potentially serve as a noninvasive tool to discriminate patients from healthy subjects. Furthermore, the interaction between platelet mEVs and cancer cells may provide valuable prognostic information and aid in the development of targeted anticancer strategies.
Letter
Hematology
Ejaife O. Agbani, Ingeborg Hers, Alastair W. Poole
Letter
Hematology
Justin S. Trory, Attila Munkacsi, Kamila M. Sledz, Jordan Vautrinot, Lucy J. Goudswaard, Molly L. Jackson, Kate J. Heesom, Samantha F. Moore, Alastair W. Poole, Behnam Nabet, Varinder K. Aggarwal, Ingeborg Hers
Article
Multidisciplinary Sciences
Venkat M. K. Vadlamani, Kavinda K. J. Gunasinghe, Xavier W. Chee, Taufiq Rahman, Matthew T. Harper
Summary: CD39 is a key regulator that metabolizes extracellular ATP and ADP to AMP. This study demonstrates that soluble, recombinant CD39 exhibits substrate inhibition with ADP or ATP as the substrate. High concentrations of ATP or ADP significantly reduce CD39 activity. In contrast, inhibition is not observed with UDP or UTP as substrates. Understanding the substrate inhibition of CD39 is important for interpreting CD39 activity studies and investigations into drugs modulating CD39 activity.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Xiaojuan Zhao, Dominic Alibhai, Tony G. Walsh, Nathalie Tarassova, Maximilian Englert, Semra Z. Birol, Yong Li, Christopher M. Williams, Chris R. Neal, Philipp Burkard, Stephen J. Cross, Elizabeth W. Aitken, Amie K. Waller, Jose Ballester Beltran, Peter W. Gunning, Edna C. Hardeman, Ejaife O. Agbani, Bernhard Nieswandt, Ingeborg Hers, Cedric Ghevaert, Alastair W. Poole
Summary: Perfusion of megakaryocytes through the mouse lung vasculature generates a large number of functional platelets. This study reveals the mechanisms of thrombopoiesis in lung vasculature and provides insights for large-scale platelet generation.
NATURE COMMUNICATIONS
(2023)
Article
Hematology
Emma C. Josefsson, Sofia Ramstrom, Johannes Thaler, Marie Lordkipanidze, COAGAPO Study Grp
Summary: The study aimed to identify a set of markers and/or methods to detect and distinguish procoagulant platelets from apoptotic platelets. Using flow cytometry, a combination of three surface markers, including P-selectin (CD62P), phosphatidylserine (recognized by annexin V), and platelet-specific receptor GPIX (CD42a) or αIIb integrin (CD41, GPIIb), was recommended for differentiation. Procoagulant platelets are positive for all three markers, while apoptotic platelets are positive for annexin V and platelet-specific surface receptor(s) but negative for P-selectin.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Lucy J. Goudswaard, Christopher M. Williams, Jawad Khalil, Kate L. Burley, Fergus Hamilton, David Arnold, Alice Milne, Phil A. Lewis, Kate J. Heesom, Stuart J. Mundell, Andrew D. Davidson, Alastair W. Poole, Ingeborg Hers
Summary: Patients with COVID-19 have altered platelet function, which is associated with increased risk of thrombosis. Platelet protein expression is different in COVID-19 patients, and platelet functional responses are reduced. Platelets in COVID-19 patients also show increased association with neutrophils. These findings suggest that platelet-driven thromboinflammation may contribute to the increased risk of thrombosis in COVID-19 patients.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Jess Berry, Matthew T. Harper
Summary: This study investigated the potential of protease-activated receptor (PAR) antagonists to prevent occlusive thrombosis under conditions where dual antiplatelet therapy (DAPT) is insufficient. The results showed that DAPT had limited efficacy when tissue factor (TF) was present, but combining DAPT with PAR antagonism was effective in preventing occlusive thrombosis.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2022)