Article
Biochemistry & Molecular Biology
Romain Versele, Emmanuel Sevin, Fabien Gosselet, Laurence Fenart, Pietra Candela
Summary: The blood-brain barrier is a crucial barrier for maintaining brain homeostasis, and cytokine-induced neuroinflammation may play a role in BBB dysfunction and contribute to the progression of Alzheimer's disease. Cytokines like TNF-alpha and IL-1 beta can modulate BBB permeability, leading to amyloid-beta peptide accumulation and potentially influencing the progression of AD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Sophie F. F. Ellermann, Rianne M. M. Jongman, Matthijs Luxen, Timara Kuiper, Josee Plantinga, Jill Moser, Thomas W. L. Scheeren, Gregor Theilmeier, Grietje Molema, Matijs Van Meurs
Summary: Major surgery induces systemic inflammation and pro-inflammatory activation of endothelial cells, leading to postoperative organ damage. This study identifies activated kinases as potential therapeutic targets to interfere with excessive endothelial inflammation. Pharmacological inhibition of Axl and Fyn, two selected kinases, reduces TNF-alpha-induced endothelial inflammation in vitro.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hannah A. B. Whitmore, Dhanesh Amarnani, Michael O'Hare, Santiago Delgado-Tirado, Lucia Gonzalez-Buendia, Miranda An, Julien Pedron, John H. Bushweller, Joseph F. Arboleda-Velasquez, Leo A. Kim
Summary: RUNX1 is implicated in retinal diseases and its expression is influenced by TNF-α and high D-glucose stimulation via JNK pathway activation.
Article
Engineering, Biomedical
Seunggyu Kim, Joonha Park, Jin-Nyoung Ho, Danhyo Kim, Sangchul Lee, Jessie S. Jeon
Summary: Despite the advantages of microfluidic system, vascular systems for drug transport have been overlooked in microfluidic-based chemotherapeutic screening. In this study, we investigated the chemotherapeutic response of bladder tumor cells using a vascularized tumor on a chip. The chip allowed the establishment of tumor-hydrogel-endothelium interfaces and evaluation of drug resistance and efficacy. Our findings suggest that the vascularized tumor chip enables investigations of chemotherapeutic screening.
Article
Chemistry, Multidisciplinary
Xi-yu Mei, Jing-nan Zhang, Wang-ya Jia, Bin Lu, Meng-na Wang, Tian-yu Zhang, Li-li Ji
Summary: In this study, researchers found that Scutellarin (SC), a natural flavonoid, can reduce the metastasis of triple-negative breast cancer (TNBC) by alleviating tumor-associated vascular endothelial barrier injury. SC regulates the TNF alpha-TNFR2-ERK1/2-EZH2 signaling pathway and restores the reduced expression of junctional proteins, thereby suppressing TNBC metastasis.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Biochemistry & Molecular Biology
Jing-Ting Chiou, Yi-Jun Shi, Yuan-Chin Lee, Liang-Jun Wang, Ying-Jung Chen, Long-Sen Chang
Summary: SEM-LA activates TNF-α-mediated apoptosis in U937 cells through the NOX4/p38 MAPK/PP2A axis and promotes this process via Ca2+-NOX4-ROS axis-mediated p38 MAPK activation. Restoration of TTP expression alleviates the effects of TNF-α upregulation and cell death induced by SEM-LA.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Physiology
Kerstin Ebefors, Emelie Lassen, Nanditha Anandakrishnan, Evren U. Azeloglu, Ilse S. Daehn
Summary: The glomerulus is a key component in the kidney responsible for urine production, with its unique structure and intricate cellular interactions crucial for blood filtration. Recent research breakthroughs have not only advanced our understanding of the structure and multifunctional roles of glomerular cells, but also introduced new technologies promising to enhance our knowledge of glomerular biology.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Cell Biology
Khadeja-Tul Kubra, Nektarios Barabutis
Summary: Endothelial hyperpermeability is a hallmark of ARDS, and carefully devised UPR manipulation may offer novel therapeutic avenues for diseases related to endothelial barrier dysfunction.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Review
Oncology
Enrique Rozengurt, Guido Eibl
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease, and recent literature on the complex crosstalk between KRAS, YAP, and Src tyrosine kinase family (SFK) in PDAC development and maintenance highlights new mechanistic and translational advances. Studies have shown the importance of RAS dimerization in signal transduction and how certain SFK members can phosphorylate and inhibit RAS function, suggesting a less crucial role for RAS in certain subtypes of PDAC. This points to the potential of targeting SFK to combat drug resistance and aggressive features in PDAC treatment.
Article
Medicine, Research & Experimental
Songling Hu, Lin Zhu, Yimeng Song, Xinrui Zhao, Qianping Chen, Yan Pan, Jianghong Zhang, Yang Bai, Haowen Zhang, Chunlin Shao
Summary: This study revealed that hypofractionated irradiation on the thorax can cause distant testicular damage and result in radiation-induced abscopal reproductive effects (RIARE) in male mice. Mechanistically, thoracic irradiation induced nuclear translocation of Rac1 and activation of the TNF-alpha/p38 MAPK pathway. The interaction between YWHAZ and Rac1 is critical for the detrimental reproductive effects induced by thoracic irradiation.
Article
Cell Biology
Yong Li, Qi Zhang, Na Li, Liting Ding, Jinping Yi, Yue Xiao, Shibiao Chen, Xuan Huang
Summary: Ataxin-10 protein is identified as a novel negative modulator of endothelial activation by suppressing IRF-1 transcription activity, which can inhibit endothelial inflammation by suppressing the expressions of cytokines and monocyte adhesion. Its mechanism of action does not affect the MAPK/NF-kappa B signaling pathway stimulated by TNF-alpha.
MEDIATORS OF INFLAMMATION
(2021)
Article
Hematology
Ehteramolsadat Hosseini, Amin Solouki, Masood Haghshenas, Mehran Ghasemzadeh, Simone M. Schoenwaelder
Summary: Comparative analysis of platelets stored under continuous agitation and manual mixing conditions revealed that manually-mixed platelets exhibited higher levels of GPVI expression and adhesion/spreading capacity, indicating a role for biomechanical forces in modulating GPVI-dependent function. Additionally, lower GPVI expression in continuously-agitated platelets may be attributed to shear forces induced by agitation, leading to attenuated platelet adhesion/spreading capabilities during storage.
THROMBOSIS JOURNAL
(2022)
Article
Immunology
Esra'a Keewan, Shazia Beg, Saleh A. Naser
Summary: This study found that anti-TNF-alpha agents decreased ACE2 expression and increased the risk of viral infection through the Notch-1/IL-6 signaling pathway. Overall, this study warns against anti-TNF-alpha therapy in some patients with inflammatory conditions during the COVID-19 pandemic.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Pharmacology & Pharmacy
Angelo Corti, Teresa Calimeri, Flavio Curnis, Andres J. M. Ferreri
Summary: The blood-brain tumor barrier is a major obstacle for the delivery of anticancer drugs to brain tumors. This review focuses on the development of a drug called NGR-TNF that can target and alter the blood-brain tumor barrier. Preclinical studies have shown that NGR-TNF is a promising strategy for delivering TNF to tumor vessels and breaking the biological barriers. Clinical studies have also demonstrated the efficacy of NGR-TNF in improving patient survival. In addition, the review discusses the challenges and potential solutions for the instability and molecular heterogeneity of NGR-TNF, as well as other peptide/antibody-TNF fusion products and nanoparticles for targeting the blood-brain tumor barrier.
Article
Pharmacology & Pharmacy
Zhifeng Jiang, Feiyu Yang, Jingbo Qie, Chaoyuan Jin, Feng Zhang, Jie Shen, Lin Zhang
Summary: Intestinal barrier dysfunction, characterized by increased intestinal permeability to endotoxins and predisposition to immune enteropathy and colorectal cancer, is associated with TNF-α. This study demonstrated that TNF-α upregulates miR-21-3p expression through the NF-κB pathway, and miR-21-3p targets MTDH mRNA to regulate the Wnt pathway, potentially impacting intestinal barrier dysfunction.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Physiology
Joseph Balnis, Tanner C. Korponay, Catherine E. Vincent, Diane Singer, Alejandro P. Adam, David Lacomis, Chun Geun Lee, Jack A. Elias, Harold A. Singer, Ariel Jaitovich
JOURNAL OF APPLIED PHYSIOLOGY
(2020)
Article
Ophthalmology
Erin E. Godbout, Kevin W. Lau, Alejandro P. Adam, Edward J. Wladis
OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
(2020)
Article
Ophthalmology
Edward J. Wladis, Brandon Weller, Alejandro P. Adam
OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
(2020)
Article
Biochemistry & Molecular Biology
Katherine A. Overmyer, Evgenia Shishkova, Ian J. Miller, Joseph Balnis, Matthew N. Bernstein, Trenton M. Peters-Clarke, Jesse G. Meyer, Qiuwen Quan, Laura K. Muehlbauer, Edna A. Trujillo, Yuchen He, Amit Chopra, Hau C. Chieng, Anupama Tiwari, Marc A. Judson, Brett Paulson, Dain R. Brademan, Yunyun Zhu, Lia R. Serrano, Vanessa Linke, Lisa A. Drake, Alejandro P. Adam, Bradford S. Schwartz, Harold A. Singer, Scott Swanson, Deane F. Mosher, Ron Stewart, Joshua J. Coon, Ariel Jaitovich
Summary: The study conducted RNA-seq and high-resolution mass spectrometry on blood samples from COVID-19-positive and COVID-19-negative patients, identifying molecular features associated with disease severity and outcomes, offering pathophysiological insights and therapeutic suggestions. The observed dysregulation of platelet function, blood coagulation, acute phase response, and endotheliopathy further illuminated the unique COVID-19 phenotype. The findings are presented through a web-based tool enabling interactive exploration and machine learning prediction of COVID-19 severity.
Article
Physiology
Joseph Balnis, Alejandro P. Adam, Amit Chopra, Hau C. Chieng, Lisa A. Drake, Nina Martino, Ramon Bossardi Ramos, Paul J. Feustel, Katherine A. Overmyer, Evgenia Shishkova, Joshua J. Coon, Harold A. Singer, Marc A. Judson, Ariel Jaitovich
Summary: The COVID19 pandemic has resulted in over a million deaths globally, with a unique inflammatory signature associated with mortality in patients with severe COVID19. Plasma IL1RA and IL8 were positively associated with mortality, while RANTES and EGF were negatively associated with the outcome, though their leukocyte gene expression did not show significant correlation with mortality.
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY, INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
(2021)
Article
Hematology
Yao Wei Lu, Nina Martino, Brennan D. Gerlach, John M. Lamar, Peter A. Vincent, Alejandro P. Adam, John J. Schwarz
Summary: MEF2 is a critical regulator of vascular homeostasis with downstream effects on gene expression programs involved in atherosclerosis development and the promotion of an anti-inflammatory and antithrombotic endothelium. Its deficiency leads to systemic inflammation, hemorrhage, thrombocytopenia, leukocytosis, and rapid lethality. MEF2 also plays a role in regulating multiple pathways, including the expression of Klf2 and Klf4 for anti-inflammatory and antithrombotic endothelium, as well as Notch family genes for atheroprotection.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Hematology
Zeinab Hosseini, Michael Marinello, Christa Decker, Brian E. Sansbury, Sudeshna Sadhu, Brennan D. Gerlach, Ramon Bossardi Ramos, Alejandro P. Adam, Matthew Spite, Gabrielle Fredman
Summary: The study found that necroptotic cells impact resolution programs in atherosclerotic plaques and impair macrophages' clearance abilities. RvD1 may serve as a potential therapeutic strategy to limit necroptotic cells.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Biochemical Research Methods
Graham Spicer, Sylvia Gutierrez-Erlandsson, Ruth Matesanz, Hugo Bernard, Alejandro P. Adam, Alejo Efeyan, Sebastian Thompson
Summary: Temperature measurement at the nanoscale using nanothermometers has provided new insights for research in chemistry, physics, and biology. Various nanothermometers have been developed, but using intact DNA for temperature measurement remains a challenge.
JOURNAL OF BIOPHOTONICS
(2021)
Article
Biochemistry & Molecular Biology
Brendan J. O'Brien, Harold A. Singer, Alejandro P. Adam, Roman G. Ginnan
Summary: Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a crucial role in endothelial function downstream of an interleukin-6 (IL-6)/JAK/STAT3 signaling axis, promoting cell migration and proliferation, as well as in vivo angiogenesis. This study demonstrates that transcriptional regulation of CaMKII delta by STAT3 influences endothelial motility, proliferation, and angiogenesis, providing new insights into vascular remodeling mechanisms.
Article
Medicine, Research & Experimental
Nina Martino, Ramon Bossardi Ramos, Shuhan Lu, Kara Leyden, Lindsay Tomaszek, Sudeshna Sadhu, Gabrielle Fredman, Ariel Jaitovich, Peter A. Vincent, Alejandro P. Adam
Summary: Studies have shown that lack of SOCS3 protein in mice leads to severe kidney failure and death after shock, with associated changes including increased expression of prothrombotic and proadhesive genes and formation of neutrophil extracellular traps. It has been demonstrated that regulating SOCS3 protein levels is critical for inhibiting IL-6-mediated endotheliopathy during shock and may provide a promising therapeutic avenue for preventing multiorgan dysfunction.
Article
Ophthalmology
Edward J. Wladis, Alejandro P. Adam
Summary: Rosacea is a common chronic skin disease that predominantly affects people aged 40 and above, with no current cure. When it affects the eyelids and periocular skin, it can lead to dry eye and potential corneal damage. Research in the past decade has shed light on potential mechanisms leading to skin hypersensitivity and has provided promising avenues for development of novel therapeutics aimed at reducing skin inflammation.
Article
Cell Biology
Nina Martino, Ramon Bossardi Ramos, Dareen Chuy, Lindsay Tomaszek, Alejandro P. Adam
Summary: Increased levels of sIL-6Ra during inflammatory responses activate IL-6 signaling in endothelial cells, leading to endothelial activation. These findings have implications for understanding acute endotheliopathy.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Materials Science, Multidisciplinary
Paloma Rodriguez-Sevilla, Graham Spicer, Ana Sagrera, Alejandro P. Adam, Alejo Efeyan, Daniel Jaque, Sebastian A. Thompson
Summary: Fast, accurate, reliable, and remote measurement of intracellular temperature is crucial for understanding cellular processes. Nanothermometers based on GFP provide temperature readouts from the analysis of its luminescence polarization, but their reliability is still debated. This study sheds light on the issue by identifying cell activity as a bias mechanism that affects the reliability of intranuclear thermal measurements using GFP and other widely used thermometers. It emphasizes the importance of judiciously assessing the performance and reliability of chosen intracellular thermometers to advance the field and ensure indisputable results.
ADVANCED OPTICAL MATERIALS
(2023)
Article
Cell Biology
Ramon Bossardi Ramos, Nina Martino, Dareen Chuy, Shuhan Lu, Mei Xing G. Zuo, Uma Balasubramanian, Iria Di John Portela, Peter A. Vincent, Alejandro P. Adam
Summary: Endothelial dysfunction plays a crucial role in promoting organ failure during septic shock, but the underlying mechanisms are still unknown. This study reveals that kidney injury following lipopolysaccharide (LPS) insult leads to enhanced transcriptional and epigenetic responses in endothelial cells. The loss of SOCS3 further aggravates these responses, indicating a causal role of the STAT3-SOCS3 signaling axis in the acute endothelial response to LPS. The study also suggests that IL-6 mediates this response, and bioinformatics analysis identifies potential involvement of STAT, AP1, and interferon regulatory family (IRF) transcription factors. Knockdown of STAT3 or AP1 member JunB partially prevents the changes in gene expression, highlighting the roles of these transcription factors. These findings demonstrate the critical role of IL-6 signaling in regulating shock-induced epigenetic changes and sustained endothelial activation, offering a new therapeutic target for limiting vascular dysfunction.
JOURNAL OF CELL SCIENCE
(2023)
Article
Ophthalmology
Edward J. Wladis, Thilaka Arunachalam, Juliann E. LaJoie, Kevin W. Lau, Alejandro P. Adam
Summary: The study found enrichment of MYD88 in eyelid specimens of rosacea patients, indicating a potential role of the innate immune system in the pathogenesis of the disease. Inhibition of MYD88 may be an effective treatment strategy for managing rosacea.
ORBIT-THE INTERNATIONAL JOURNAL ON ORBITAL DISORDERS-OCULOPLASTIC AND LACRIMAL SURGERY
(2022)