Review
Endocrinology & Metabolism
Gaber El-Saber Batiha, Hayder M. Al-kuraishy, Thabat J. Al-Maiahy, Ali K. Al-Buhadily, Hebatallah M. Saad, Ali Al-Gareeb, Jesus Simal-Gandara
Summary: GDM triggers the expression and release of PAI-1, which is associated with inflammation, abnormal fibrinolysis, and thrombosis.
DIABETOLOGY & METABOLIC SYNDROME
(2022)
Article
Biochemistry & Molecular Biology
Machteld Sillen, Toshio Miyata, Douglas E. Vaughan, Sergei V. Strelkov, Paul J. Declerck
Summary: PAI-1 is a key regulator of the fibrinolytic system, with potential therapeutic significance in various pathological conditions. Small molecule inhibitors like TM5484 may inhibit PAI-1 by binding to the flexible joint region and inducing a substrate to inert form conversion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Machteld Sillen, Paul J. Declerck
Summary: PAI-1 is the primary inhibitor of fibrinolysis, mainly through fast-acting inhibition of tPA and uPA, as well as interactions with biological ligands, affecting pericellular proteolysis and tissue remodeling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Endocrinology & Metabolism
Yongzhuo Yu, Wenxuan Li, Lili Xu, Yangang Wang
Summary: Cardiovascular complications are a common cause of death in type 2 diabetes patients, and Plasminogen-activator Inhibitor 1 (PAI-1) plays a crucial role in their development and progression. Insulin resistance increases PAI-1 production, leading to an environment conducive to thrombosis and severe vascular disease. PAI-1 also exhibits circadian rhythm characteristics, which may explain the higher incidence of cardiovascular events in the morning. PAI-1 is a potential drug target, but currently, no PAI-1 inhibitors have been approved for clinical use. Chronotherapy, based on rhythm, may offer improved treatment for cardiovascular complications in diabetic patients.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Hematology
Tae Ito, Yuko Suzuki, Hideto Sano, Naoki Honkura, Francis J. Castellino, Tetsumei Urano
Summary: The study demonstrates the existence of three distinct forms of high-molecular-weight complexes between tPA and PAI-1. Peptide sequence analysis revealed that these complexes consist of nonacylated-enzyme inhibitor complexes, with only a fraction of the population releasing free tPA under physiological conditions.
THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Biology
C. Banfi, R. Baetta, S. S. Barbieri, M. Brioschi, A. Guarino, S. Ghilardi, L. Sandrini, S. Eligini, G. Polvani, O. Bergman, P. Eriksson, E. Tremoli
Summary: The research by Banfi et al. explores the role of Prenylcysteine oxidase 1 (PCYOX1) in atherosclerosis, revealing that its deficiency is anti-atherogenic. The study highlights the potential therapeutic opportunities in targeting PCYOX1 and expands our understanding of atherosclerosis pathophysiology. Additionally, they found that PCYOX1 is locally synthesized and transported by proatherogenic lipoproteins in atherosclerotic lesions, demonstrating its impact on lesion vulnerability and inflammation.
COMMUNICATIONS BIOLOGY
(2021)
Article
Cell Biology
Yong-Han Su, Yi-Zhen Wu, David K. K. Ann, Jenny Ling-Yu Chen, Ching-Ying Kuo
Summary: Obesity is a risk factor for various cancers, including breast cancer. Adipose tissue disturbance in obesity is closely related to cancer progression and resistance to standard treatments. In this study, diet-induced obesity promoted tumor growth and reduced tumor response to radiotherapy in the mouse model of triple-negative breast cancer. Serpine1 was found to be elevated in the blood of obese mice and enriched in the tumor microenvironment.
CELL DEATH & DISEASE
(2023)
Article
Medicine, General & Internal
Shaowei Jiang, Yang Wang, Liang Chen, Honghua Mu, Connor Meaney, Yiwen Fan, Janesh Pillay, Hairong Wang, Jincheng Zhang, Shuming Pan, Chengjin Gao
Summary: This study investigates the associations among serum levels of PAI-1, PAI-1 gene polymorphisms, immunological indicators, and clinical outcomes in septic patients. The results suggest that genetic polymorphisms of PAI-1 can affect serum levels of PAI-1, which in turn may influence mortality by affecting neutrophil activity.
CHINESE MEDICAL JOURNAL
(2023)
Editorial Material
Biochemistry & Molecular Biology
Hau C. Kwaan
Summary: The fibrinolytic system is composed of plasmin, plasminogen, activators, and inhibitors. It plays essential roles in physiological processes and the pathogenesis of disorders. Recent advancements offer opportunities for drug development in treating these disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Health Care Sciences & Services
Hee Young Cho, Han Sung Park, Eun Hee Ahn, Eun Ju Ko, Hyeon Woo Park, Young Ran Kim, Ji Hyang Kim, Woo Sik Lee, Nam Keun Kim
Summary: The study revealed that PAI-1 rs1050955 and REN 10795 rs5707 alleles may decrease the risk of RPL, while the tPA rs4646972 genotype may increase the risk of RPL.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Oncology
Zhen Chen, Rainer Will, Su Na Kim, Maike Anna Busch, Nicole Duenker, Philipp Dammann, Ulrich Sure, Yuan Zhu
Summary: Hyper-angiogenesis is a characteristic of glioblastoma (GBM), and ALDH1A3 has been found to be highly expressed in proliferating vasculature in GBM patients. This study demonstrated that ALDH1A3 acts as an angiogenesis promoter in GBM through the paracrine upregulation of PAI-1 and IL-8. Inhibition of PAI-1 or IL-8 hindered the hyper-angiogenesis phenotype caused by ALDH1A3. These findings highlight ALDH1A3-PAI-1/IL-8 as a potential target for anti-angiogenesis therapy in GBM.
Article
Multidisciplinary Sciences
Bo Han Chen, Xiao Qing Lu, Xian Hui Liang, Pei Wang
Summary: Diabetic kidney disease induces tubular degeneration and premature cellular senescence, partially mediated by Serpin E1 signaling.
SCIENTIFIC REPORTS
(2023)
Review
Biochemistry & Molecular Biology
Asmaa Anwar Ismail, Baraah Tariq Shaker, Khalid Bajou
Summary: Angiogenesis is a process involving the migration and proliferation of endothelial cells to form new blood vessels. The plasminogen activator-plasmin system plays a major role in this process, but paradoxically, plasminogen activator inhibitor-1 and urokinase-type plasminogen activator receptor promote angiogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Ophthalmology
Nurbadriah Binti Jasmiad, Rohana Binti Abd Ghani, Renu Agarwal, Zaliha Binti Ismail, Azlindarita Aisyah Mohd Abdullah, Mohd Yusri Idorus
Summary: This study compared the activity of tPA and PAI-1 in tears and serum of patients with DR and those without DR. The results showed significantly higher serum PAI-1 levels in patients with DR compared to those without DR. However, there were no significant correlations between tears and serum levels of PAI-1 and tPA. Further investigations on tear biomarkers are still relevant.
Review
Biochemistry & Molecular Biology
Marie Mennesson, Jean-Michel Revest
Summary: Stressful events have a complex biological response that follows a bell-shaped pattern. Low-stress conditions have beneficial effects, while overly intense stress can lead to stress-related pathologies. Glucocorticoid hormones in the hippocampus play a key role in the tPA/PAI-1 imbalance observed in stress-related disorders. Modulating the activity of tPA/PAI-1 proteins could be a potential therapeutic approach for these conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Dentistry, Oral Surgery & Medicine
N. Pechlivani, D. A. Devine, P. D. Marsh, A. Mighell, S. J. Brookes
ARCHIVES OF ORAL BIOLOGY
(2018)
Article
Hematology
Katherine J. Kearney, Nikoletta Pechlivani, Rhodri King, Christian Tiede, Fladia Phoenix, Ramsah Cheah, Fraser L. Macrae, Katie J. Simmons, Iain W. Manfield, Kerrie A. Smith, Benjamin E. J. Spurgeon, Khalid M. Naseem, Robert A. S. Ariens, Michael J. McPherson, Darren C. Tomlinson, Ramzi A. Ajjan
Article
Endocrinology & Metabolism
Nikolaos Kyriakakis, Nikoletta Pechlivani, Julie Lynch, Natalie Oxley, Fladia Phoenix, Khyatisha Seejore, Steve M. Orme, Ramzi Khan, Robert D. Murray
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2020)
Review
Biochemistry & Molecular Biology
Nikoletta Pechlivani, Katherine J. Kearney, Ramzi A. Ajjan
Summary: Targeting proteins involved in hypofibrinolysis represents a specific approach for developing effective and safe therapeutic agents to reduce thrombosis risk and improve clot instability in bleeding disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Nikoletta Pechlivani, Katherine J. Kearney, Christian Tiede, Ramsah Cheah, Fladia Phoenix, Sreenivasan Ponnambalam, James R. Ault, Michael J. McPherson, Darren C. Tomlinson, Ramzi A. Ajjan
Summary: This study developed a novel method for purifying fibrinogen using Affimer protein isolated from phage display systems and SulfoLink resin column. The purified fibrinogen showed comparable purity to commercial preparations and retained its functionality. Further purification using the Affimer column eliminated key contaminant proteins from commercial fibrinogen.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2022)
Meeting Abstract
Endocrinology & Metabolism
M. Almutairi, C. Tiede, K. Kearney, N. Pechlivani, F. Hawkins, N. Oxley, D. Tomlinson, R. Ajjan
Review
Cardiac & Cardiovascular Systems
Nikoletta Pechlivani, Ramzi A. Ajjan
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2018)