Article
Oncology
Julia M. DeRogatis, Karla M. Viramontes, Emily N. Neubert, Monique L. Henriquez, Christian F. Guerrero-Juarez, Roberto Tinoco
Summary: Therapeutically targeting PSGL-1 can reinvigorate antitumor immunity by enhancing effector T-cell responses and reducing regulatory T cells, thus delaying tumor growth in a melanoma mouse model.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Medicine, Research & Experimental
Massimo Granai, Verena Warm, Antonio Vogelsberg, Jakob Milla, Karen Greif, Ulrich Vogel, Tamam Bakchoul, Peter Rosenberger, Leticia Quintanilla-Martinez, Christian M. Schurch, Karin Klingel, Falko Fend, Hans Bosmuller
Summary: This study aimed to explore the interplay between leukocyte activation and pulmonary endothelium in different disease stages of fatal COVID-19. The results showed that early leukocyte recruitment and secretion of proinflammatory cytokines and hypercoagulability were observed in critically ill patients infected with SARS-CoV-2. In addition, compared with control groups, COVID-19 patients exhibited increased expression of leukocyte trafficking molecules and endothelial activation.
LABORATORY INVESTIGATION
(2023)
Article
Chemistry, Medicinal
Vladimir Sladek, Pavel Smak, Igor Tvarosska
Summary: This study explores essential interactions of selectin-ligand binding using a multiscale approach, successfully reproducing most of the experimental findings. The results enable us to quantify the importance of specific residues and functional groups at the protein-ligand interface and identify differences in molecular recognition by the three selectins. Mutations in the E-, L-, and P-selectins, particularly at residues 46, 85, 97, and 107, play a crucial role in ligand engagement. The sulfation of tyrosine residues in PSGL-1, specifically the interaction between TyrSO3- at position 51 and Arg85 in P-selectin, is a significant factor in the increased affinity of P-selectin to PSGL-1 compared to E- and L-selectins. Based on the analysis of selectin-PSGL-1 interactions, a pharmacophore targeting five essential PSGL-binding sites is proposed.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Review
Virology
Silvere D. Zaongo, Yaokai Chen
Summary: P-selectin glycoprotein ligand-1 (PSGL-1) plays a crucial role in HIV infection. It inhibits HIV reverse transcription and reduces the infectivity of HIV virions produced by infected cells. However, PSGL-1 expression negatively affects immune cell functions, potentially predicting HIV disease progression.
Review
Immunology
Silvere D. Zaongo, Yanqiu Liu, Vijay Harypursat, Fangzhou Song, Huan Xia, Ping Ma, Yaokai Chen
Summary: Antiretroviral therapy (ART) is the only currently effective method to treat HIV-1 infection, but may be toxic to vital organs. Therefore, considering HIV-1 restriction factors from the innate immune system to explore novel therapeutic approaches is seen as a promising strategy by researchers.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Plant Sciences
Siya Wu, Jian Liu, Ya Zhang, Jianxi Song, Zhongshan Zhang, Yue Yang, Mingjiang Wu, Haibin Tong
Summary: This study determined the structural characteristics of SFF-32, a fucoidan fraction from S. fusiforme, and its antagonistic effect against P-selectin mediated function. It was found that SFF-32 inhibited P-selectin-mediated function by blocking the interaction between P-selectin and its physiological ligand PSGL-1, suggesting its potential as an anti-inflammatory lead compound.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Cell Biology
Lalitha Nayak, David R. Sweet, Asha Thomas, Stephanie D. Lapping, Kenneth Kalikasingh, Annmarie Madera, Vinesh Vinayachandran, Roshan Padmanabhan, Neelakantan T. Vasudevan, Jay T. Myers, Alex Y. Huang, Alvin Schmaier, Nigel Mackman, Xudong Liao, Andrei Maiseyeu, Mukesh K. Jain
Summary: Arterial and venous thrombosis are major global diseases with common mechanisms involving neutrophils. This study identified neutrophils as key effectors in thrombosis and demonstrated the feasibility of targeting them using immunoregulatory nanoparticles. Moreover, key molecular events and regulators of neutrophil activation were identified, providing potential targets for therapeutics against immunothrombosis.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Hematology
Patrick C. Hines, Michael U. Callaghan, Ahmar U. Zaidi, Xiufeng Gao, Ke Liu, Jennell White, Michael Tarasev
Summary: The study found that adhesion of blood cells to P-selectin and VCAM1 is significantly increased on VOC days in patients with SCD. By establishing optimal cutoff values and a multimarker risk score, a better ability to identify VOC risk was demonstrated.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Pharmacology & Pharmacy
Sherwin K. B. Sy, Chiaki Tanaka, Kai Grosch
Summary: The study developed a population pharmacokinetic (PK) and pharmacodynamic (PD) model for crizanlizumab, a monoclonal antibody for sickle cell disease. The results showed that crizanlizumab exhibited nonlinear PK and factors such as renal and hepatic impairments, concomitant hydroxyurea usage, and anti-drug antibody did not impact its exposure. The model can be used to extrapolate PK to pediatric population and evaluate alternative regimens and routes of administration.
CLINICAL PHARMACOKINETICS
(2023)
Review
Biochemistry & Molecular Biology
Angelo Zinellu, Arduino A. Mangoni
Summary: Statins can effectively decrease circulating levels of cell adhesion molecules, including P-selectin, L-selectin, and E-selectin, which are involved in the pathogenesis of atherosclerosis. Research indicates that statins have a significant impact on reducing these selectins independently of baseline lipid profiles and other patient characteristics, potentially contributing to cardiovascular risk reduction.
Article
Cell Biology
Fangyuan Zhou, Fang Zhang, Veronika Zarnitsyna, Larissa Doudy, Zhou Yuan, Kaitao Li, Rodger P. McEver, Hang Lu, Cheng Zhu
Summary: Selectins and integrins play crucial roles in recruiting leukocytes to inflamed tissues. Studies have found that E- and P-selectins have different effects on the activation of α(L)β(2), with varying responses observed at different temperatures.
JOURNAL OF CELL SCIENCE
(2021)
Article
Microbiology
Chao Jiang, Miao Mei, Ying Liu, Min Hou, Jun Jiao, Ya Tan, Xu Tan
Summary: The arms race between viruses and their hosts has influenced their evolutionary history and genetic composition. Restriction factors encoded by host genomes serve as the first line of defense against viral infections and are conserved throughout evolution to protect hosts from diseases, death, and even extinction. Recently characterized human restriction factor PSGL-1 demonstrates antiviral function in mice, as shown in vitro and in a knockout mouse model. The interaction between PSGL-1 and glycogag/glycoMA proteins from murine leukemia virus (MLV) demonstrates evidence of positive selection, reflecting the evolutionary pressure between PSGL-1 and its antagonists.
Article
Immunology
Qi Xu, Ming Shi, Lu Ding, Yu Xia, Liang Luo, Xiaofang Lu, Xiaoying Zhang, David Y. B. Deng
Summary: This study found that P-selectin induces the formation of NETs through the PSGL-1 and downstream Syk/Ca2+/PAD4 signaling pathway, playing an important role in acute pancreatitis. Inhibiting the P-selectin pathway may be a promising strategy for the treatment of AP.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Virology
Jonathan Burnie, Arvin Tejnarine Persaud, Laxshaginee Thaya, Qingbo Liu, Huiyi Miao, Stephen Grabinsky, Vanessa Norouzi, Paolo Lusso, Vera A. Tang, Christina Guzzo
Summary: PSGL-1 plays diverse roles in HIV-1 infection due to its functional activity on virion surfaces and broad incorporation among a wide range of viral isolates.
Review
Immunology
Julia M. DeRogatis, Karla M. Viramontes, Emily N. Neubert, Roberto Tinoco
Summary: PSGL-1, a molecule primarily involved in cellular migration, has been shown to function as a negative regulator of CD4(+) T cells in various diseases, including cancer. Blocking the PSGL-1 pathway on CD4(+) T cells may represent a new approach for cancer therapy to eradicate tumors.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Hematology
E. O. Artemenko, S. I. Obydennyi, K. S. Troyanova, G. A. Novichkova, D. Y. Nechipurenko, M. A. Panteleev
Summary: In this study, we investigated the adhesive properties of circulating plasma-derived and platelet-derived microvesicles (MVs) and their potential role in thrombus growth. The results showed that both types of MVs weakly bound fibrinogen but did not stably adhere to immobilized fibrinogen. Moreover, the presence of these MVs did not significantly affect thrombus formation. Therefore, MVs present in the plasma of healthy individuals are unlikely to directly contribute to thrombus formation under arterial flow conditions.
THROMBOSIS RESEARCH
(2024)
Letter
Hematology
Giuseppe Lippi, Camilla Mattiuzzi, Emmanuel J. Favaloro
THROMBOSIS RESEARCH
(2024)
Article
Hematology
Marium Malik, Maha Al-Ghafry, Abraham Haimed, Julia Su, Maribel Lema, Linda Shore-Lessersson, Suchitra S. Acharya
Summary: This study analyzed and evaluated leukemia-associated coagulopathy in newly diagnosed pediatric leukemia patients using CCTs and ROTEM. The results showed that fibrinogen and platelets played a significant role in causing coagulopathies in this population. This suggests the utility of using CCTs and ROTEM in the pediatric population to evaluate hemostatic function and guide blood product replacement.
THROMBOSIS RESEARCH
(2024)
Review
Hematology
Mohammad M. Elahi, Alexandra N. Witt, Edward L. G. Pryzdial, Paul B. McBeth
Summary: Thrombotic disease may be underdiagnosed in microgravity conditions, and the underlying factors are still poorly understood. A case of internal jugular vein thrombosis was recently diagnosed in a low-risk female astronaut, and six out of ten additional crew members showed risk factors for jugular venous flow. Observations in space and studies on Earth suggest that microgravity affects blood flow, coagulation, and vascular function.
THROMBOSIS RESEARCH
(2024)
Review
Hematology
Stian Ingemann-Molden, Christina Krogner Caspersen, Nanna Rolving, Anette Arbjerg Hojen, Frederikus A. Klok, Erik L. Grove, Barbara Cristina Brocki, Jane Andreasen
Summary: This study found that no single PROM covered all aspects considered important by PE patients. PROMs recommended in the ICHOM core set covered most aspects, but worrisome thoughts, hypervigilance around symptoms, and uncertainty of illness were not covered.
THROMBOSIS RESEARCH
(2024)
Article
Hematology
Haomin Yan, Tsutomu Sasaki, Yasufumi Gon, Kumiko Nishiyama, Hideaki Kanki, Hideki Mochizuki
Summary: The incidence of cancer-associated stroke has increased with the prolonged survival times of cancer patients. In this study, the researchers focused on the driver gene KRAS and found that KRAS mutations exacerbated neurological deficits after stroke and promoted tumor growth. They also identified the upregulation of pro-inflammatory responses and the promotion of STAT3 phosphorylation in mice with KRAS mutations. Additionally, the researchers found that colorectal cancer patients with stroke onset within 3 months after cancer diagnosis had a worse prognosis.
THROMBOSIS RESEARCH
(2024)
Letter
Hematology
Tomoki Togashi, Satomi Nagaya, Makiko Meguro-Horike, Haruto Matsumoto, Yuta Imai, Koichi Yamaguchi, Yoshinari Fujii, Haruka Moriya, Yuika Kikuchi, Ibuki Yasuda, Shin-ichi Horike, Eriko Morishita
THROMBOSIS RESEARCH
(2024)
Article
Hematology
Marta Najarro, Winnifer Briceno, Carmen Rodriguez, Alfonso Muriel, Sara Gonzalez, Ana Castillo, Ignacio Jara, Parth Rali, Catalin Toma, Behnood Bikdeli, David Jimenez
Summary: The CPES score is a useful tool in identifying the risk of hemodynamic deterioration in normotensive patients with acute PE, with acceptable C-statistic, excellent specificity, and low positive predictive value.
THROMBOSIS RESEARCH
(2024)
Article
Hematology
Lei Liu, Huifang Xu, Jian Wang, Haiyan Wang, Saisai Ren, Qian Huang, Mingyan Zhang, Hui Zhou, Chunyan Yang, Lu Jia, Yu Huang, Hao Zhang, Yanling Tao, Ying Li, Yanan Min
Summary: This study investigated the gut microbiota metabolites and cytokines, chemokines, and growth factors in patients with ITP and found their association with treatment responsiveness. The findings suggest that imbalanced secretion of cyto(chemo)kins/growth factors and inadequate levels of TMAO are characteristic of patients with ITP.
THROMBOSIS RESEARCH
(2024)
Article
Hematology
Roxanne Mcknight, Mohammad Salameh, Lee Ann Jones, Greta Anton, Lindsay Carter
Summary: This study evaluated the safety of fixed-dose heparin titration boluses in underweight patients with VTE. The results showed that although underweight patients required more frequent holding of heparin, there was no significant increase in bleeding risk.
THROMBOSIS RESEARCH
(2024)