Article
Gastroenterology & Hepatology
Christian David Schmid, Victor Olsavszky, Manuel Reinhart, Vanessa Weyer, Felix A. Trogisch, Carsten Sticht, Manuel Winkler, Sina W. Kurschner, Johannes Hoffmann, Roxana Ola, Theresa Staniczek, Joerg Heineke, Beate K. Straub, Jens Mittler, Kai Schledzewski, Peter ten Dijke, Karsten Richter, Steven Dooley, Cyrill Geraud, Sergij Goerdt, Philipp-Sebastian Koch
Summary: This study established an HHT mouse model with liver vascular malformations and investigated the role of ALK1 signaling in liver vessel formation and metabolic function. The results showed that hepatic endothelial ALK1 signaling protects from development of vascular malformations and preserves organ-specific endothelial differentiation and angiocrine signaling.
Article
Biochemistry & Molecular Biology
Tobias Friedrich, Francesca Ferrante, Leo Pioger, Andrea Nist, Thorsten Stiewe, Jean-Christophe Andrau, Marek Bartkuhn, Benedetto Daniele Giaimo, Tilman Borggrefe
Summary: The study investigates the role of transcription factor RBPJ in the Notch signaling pathway. It is found that RBPJ not only participates in the Notch co-activator complex, but also functions as a repressor, playing a crucial role in regulating Notch target genes.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Kangping Liu, Hongfan Ge, Chengyin Liu, Yixin Jiang, Yaling Yu, Zhenlei Zhou
Summary: This study aimed to investigate the role of the differentiation of bone marrow mesenchymal stem cells (BMSCs) in the development of femoral head necrosis (FHN). The results showed that BMSCs isolated from FHN-affected broilers demonstrated enhanced lipogenic differentiation, activated Notch-RBPJ signaling pathway, and diminished osteogenic and chondrogenic differentiation. Treatment with methylprednisolone (MP) decreased the expressions of Runx2, BMP2, Col2a1, and Aggrecan, while increased the expressions of p-Notch1/Notch1, Notch2, and RBPJ. Jagged-1 (JAG-1)/DAPT could promote/inhibit the osteogenic or chondrogenic ability of MP-treated BMSCs, respectively, and the differentiation ability of BMSCs was restored after transfection with si-RBPJ.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yanzhu Shi, Deyu Zhang, Jingyi Chen, Qiwei Jiang, Songze Song, Yue Mi, Tao Wang, Qinong Ye
Summary: This study identified six key genes related to breast cancer metastasis, with BEND5 being the most significant one. Low expression of BEND5 is associated with advanced stage and shorter overall survival in breast cancer patients. Functional experiments showed that BEND5 can suppress the growth and metastasis of breast cancer. Mechanistically, BEND5 inhibits the Notch signaling pathway through interacting with the transcription factor RBPJ/CSL.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Ophthalmology
Rami Halabi, Charlene Watterston, Carrie Lynn Hehr, Risa Mori-Kreiner, Sarah J. Childs, Sarah McFarlane
Summary: Pathological blood vessel growth in the eye is associated with several diseases leading to vision loss. Sema3fa is identified as an endogenous antiangiogenic in the eye. The study provides a new model for studying choroid neovascularization resulting from primary changes in the retinal environment.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Cell Biology
Louise M. C. Webb, Sigrid Fra-Bido, Silvia Innocentin, Louise S. Matheson, Noudjoud Attaf, Alexandre Bignon, Julien Novarino, Nicolas Fazilleau, Michelle A. Linterman
Summary: Ageing profoundly impacts immune system by affecting Tfh cell formation, promoting early Tfh cell differentiation but not increasing GC-Tfh cells. Ageing alters TCR signalling, leading to increased expression of RBPJ, and modulation of RBPJ or Notch rescues age-associated early Tfh cell differentiation.
Article
Immunology
Corinne M. M. Nielsen, Xuetao Zhang, Kunal Raygor, Shaoxun Wang, Andrew W. W. Bollen, Rong A. A. Wang
Summary: Nielsen and Zhang et al. have shown that brain arteriovenous malformations induced by Notch4 can be normalized by deleting the Notch signaling mediator, Rbpj. Even when the causal factor is reintroduced, there are virtually no relapses in adults after complete regression. This study provides proof of concept for targeting a downstream mediator to treat AVM pathologies despite a sustained causal molecular lesion.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Cell Biology
Junchen Chen, Xiaoxue Dong, Xuejun Cheng, Qiang Zhu, Jinyu Zhang, Qian Li, Xiaoli Huang, Min Wang, Liping Li, Weixiang Guo, Binggui Sun, Qiang Shu, Wen Yi, Xuekun Li
Summary: Ogt deficiency in adult neural stem/progenitor cells leads to a decrease in the aNSPC pool, abnormal neurogenesis, and impaired cognitive function in adult mice. Mechanistic studies reveal that Ogt catalyzes the O-GlcNAc modification of the Notch TM/ICD fragment, which in turn affects neurogenic defects induced by Ogt deficiency.
Article
Neurosciences
Samantha Selhorst, Sera Nakisli, Shruthi Kandalai, Subhodip Adhicary, Corinne M. Nielsen
Summary: Pericytes, a type of perivascular cell, play important roles in vascular development and homeostasis. In the brain, they are involved in regulating blood flow and establishing the blood-brain barrier. Their role in neurovascular disease is not well understood. This study investigated the effects of pericytes in a mouse model of brain arteriovenous malformation (AVM). The results suggest that pericyte expansion and altered molecular expression may contribute to the development of brain AVM.
FRONTIERS IN HUMAN NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Wen Luo, Irene Garcia-Gonzalez, Macarena Fernandez-Chacon, Veronica Casquero-Garcia, Maria S. Sanchez-Munoz, Severin Muhleder, Lourdes Garcia-Ortega, Jorge Andrade, Michael Potente, Rui Benedito
Summary: The formation of arteries is not directly induced by a Notch-dependent arterial differentiation program, but depends on the timely suppression of endothelial cell-cycle progression and metabolism.
Article
Biochemistry & Molecular Biology
Zihan Mao, Dapeng Lin, Jian Xu
Summary: This study found that circ_0001535 plays an important role in the proliferation, migration, invasion, angiogenesis, and apoptosis of colorectal cancer (CRC) cells by regulating the expression of miR-433-3p and recombination signal-binding protein J kappa (RBPJ). In addition, in vivo experiments confirmed that knocking down circ_0001535 can inhibit tumor growth. These findings provide new insights into the molecular mechanism of CRC.
BIOCHEMICAL GENETICS
(2023)
Article
Cell Biology
Ram Lakhan, Chozha V. Rathinam
Summary: Deletion of canonical notch pathways in hematopoietic stem cells leads to compromised HSC maintenance and functions in response to stressors, while upregulating key notch target genes and increasing notch activity, which establish a functional link between Hif and Notch pathways in hematopoiesis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Medicinal
Mengjie Rui, Min Cai, Yu Zhou, Wen Zhang, Lianglai Gao, Ke Mi, Wei Ji, Dan Wang, Chunlai Feng
Summary: Notch signaling plays a critical role in breast cancer development and the currently available Notch inhibitors have limitations. In this study, we identified fidaxomicin as a potential RBPJ inhibitor and demonstrated its ability to suppress breast cancer growth by blocking RBPJ-dependent transcription.
Article
Biochemistry & Molecular Biology
Kaiji Fan, Ivelina Spassova, Jan Gravemeyer, Cathrin Ritter, Kai Horny, Anja Lange, Thilo Gambichler, Niels Odum, David Schrama, Dirk Schadendorf, Selma Ugurel, Juergen C. Becker
Summary: Merkel cell carcinoma is highly invasive and metastatic, with high expression of miR-375 which does not directly contribute to malignant phenotype. Transferred miR-375 causes fibroblast polarization towards cancer-associated fibroblasts by downregulating RBPJ and p53.
Article
Developmental Biology
Christian Sigloch, Dominik Spitz, Wolfgang Driever
Summary: Neural proliferation zones employ Delta/Notch signaling and HES/Her transcription factors to balance NSC maintenance and progenitor/neuron generation. In the thalamic proliferation zone of zebrafish larvae, nine Notch-dependent her genes and two Notch-independent her genes are differentially expressed, regulating NSC and progenitor populations. Among them, her6 plays a prominent role in maintaining NSCs and inhibiting NSC-to-progenitor lineage transitions. The redundancy and cross-regulation in the her gene network contribute to the robustness of NSC maintenance.
Meeting Abstract
Hematology
Kobina Dufu, Donna Oksenberg, Brian E. Cathers, Carlos J. Munoz, Cynthia R. Muller, Pedro Pedro Cabrales
Meeting Abstract
Hematology
Kobina Dufu, Donna Oksenberg, Brian E. Cathers, Carlos J. Munoz, Cynthia R. Muller, Pedro Pedro Cabrales
Article
Multidisciplinary Sciences
Cynthia R. Muller, Alexander T. Williams, Cynthia Walser, Allyn M. Eaker, Jose Luis Sandoval, Clayton T. Cuddington, Savannah R. Wolfe, Andre F. Palmer, Pedro Cabrales
Summary: This study evaluated the efficacy and safety of high molecular weight polymerized human hemoglobin (PolyhHb) as a resuscitation alternative to blood. The results showed that PolyhHb had reduced toxicities and minimal effects on vital organs and inflammation compared to fresh and stored blood, indicating a favorable safety profile.
SCIENTIFIC REPORTS
(2022)
Article
Engineering, Biomedical
Martin T. Spang, Ryan Middleton, Miranda Diaz, Jervaughn Hunter, Joshua Mesfin, Alison Banka, Holly Sullivan, Raymond Wang, Tori S. Lazerson, Saumya Bhatia, James Corbitt, Gavin D'Elia, Gerardo Sandoval-Gomez, Rebecca Kandell, Maria A. Vratsanos, Karthikeyan Gnanasekaran, Takayuki Kato, Sachiyo Igata, Colin Luo, Kent G. Osborn, Nathan C. Gianneschi, Omolola Eniola-Adefeso, Pedro Cabrales, Ester J. Kwon, Francisco Contijoch, Ryan R. Reeves, Anthony N. DeMaria, Karen L. Christman
Summary: This study demonstrates the safety and feasibility of using intravascularly infused extracellular matrix as a biomaterial for tissue repair in animal models of acute myocardial infarction, traumatic brain injury, and pulmonary arterial hypertension. The biomaterial, consisting of decellularized myocardial tissue, localizes to injured tissues and is degraded in 3 days. In animal models of myocardial infarction, the intracoronary infusion of the biomaterial led to reduced left ventricular volumes, improved wall-motion scores, and differential gene expression associated with tissue repair and inflammation. This intravascular delivery of pro-healing extracellular matrix may provide translational advantages for healing inflamed tissues 'from the inside out'.
NATURE BIOMEDICAL ENGINEERING
(2023)
Article
Hematology
Kobina Dufu, Carsten Alt, Steven Strutt, James Partridge, Tzechiang Tang, Vincent Siu, Hilary Liao-Zou, Peter Rademacher, Alexander T. Williams, Cynthia R. Muller, Xin Geng, Mira Patel Pochron, Annie Nguyen Dang, Pedro Cabrales, Zhe Li, Donna Oksenberg, Brian E. Cathers
Summary: The pathophysiologic mechanism of sickle cell disease (SCD) involves polymerization of deoxygenated haemoglobin S (HbS), leading to red blood cell (RBC) sickling, decreased RBC deformability, microvascular obstruction, haemolysis, anaemia, and downstream clinical complications. Pharmacological increase in the concentration of oxygenated HbS in RBCs has been shown to be a novel approach to inhibit HbS polymerization and reduce RBC sickling and haemolysis. GBT021601, a small molecule that increases HbS-oxygen affinity, inhibits HbS polymerization and prevents RBC sickling in blood from patients with SCD. It also has positive effects on RBC health and haemoglobin levels in a murine model of SCD.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Review
Pharmacology & Pharmacy
Nanthini Jayabalan, Bryan Oronsky, Pedro Cabrales, Tony Reid, Scott Caroen, Aishwarya M. Johnson, Natalia A. Birch, John D. O'Sullivan, Richard Gordon
Summary: Chronic unresolving inflammation is a key feature of many diseases, and dysregulated immune and inflammasome activation contributes to its progression. The NLRP3 inflammasome, a large cytosolic protein complex, is well-studied and a potential target for therapeutic intervention. RRx-001, a direct NLRP3 inflammasome inhibitor, is currently being investigated in clinical trials and has shown promise in treating small cell lung cancer and other diseases driven by immune and inflammasome activation.
Review
Biochemistry & Molecular Biology
Robert J. J. Asaro, Elisabetta Profumo, Brigitta Buttari, Pedro Cabrales
Summary: The presence of red blood cells (RBCs) in the vasculature and their reactivity have sparked discussions about their role(s) in health and disease. These roles are linked to the development of adhesiveness and eventual clearance by macrophages in the spleen. This review explores the mechanisms involved and provides novel perspectives for identifying RBC adhesiveness.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Engineering, Biomedical
Vinay P. Jani, Alexander T. Williams, Vivek P. Jani, Amy G. Tsai, Marcos Intaglietta, Pedro Cabrales
Summary: This study presents a new method for analyzing left ventricular pressure-volume signals using the Prony algorithm, which fits and quantifies the transfer function. The analysis of pressure and volume signals during severe hemorrhagic shock and after resuscitation showed significant differences in the number of poles and the composite transfer function. The implementation of the Prony analysis in this study demonstrates its potential for future applications in various physiological and pathophysiological conditions.
MEDICAL ENGINEERING & PHYSICS
(2023)
Article
Immunology
Tony Reid, Bryan Oronsky, Scott Caroen, Mary Quinn, Jeannie Williams, Pedro Cabrales, Nacer Abrouk
Summary: This study aimed to evaluate the safety and feasibility of RRx-001 and nivolumab in patients with advanced cancer. The results showed that the combination of RRx-001 and nivolumab was safe and well-tolerated, with preliminary evidence of anti-cancer activity. Therefore, further clinical trials are warranted.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Parasitology
Vinay P. Jani, Alexander T. Williams, Leonardo Carvalho, Pedro Cabrales
Summary: This article investigates changes in oxygen delivery, flux, and utilization in animal models of cerebral malaria. The results show impaired convective and diffusive oxygen flux along with impaired pial hemodynamics in both susceptible and resistant models of cerebral malaria. Furthermore, late-stage cerebral malaria shows impaired oxygen transport and affinity, while early-stage cerebral malaria and resistant strains only show impaired oxygen transport.
EXPERIMENTAL PARASITOLOGY
(2023)
Article
Medicine, Research & Experimental
Derek R. Lamb, Alisyn Greenfield, Kiruphagaran Thangaraju, Saini Setua, Gena Eiker, Qihong Wang, Amid Vahedi, Mohd. Asim Khan, Ahmad Yahya, Pedro Cabrales, Andre F. Palmer, Paul W. Buehler
Summary: This study compares the impact of different sizes of polymerized hemoglobin on tissue oxygenation in hemorrhagic shock. The results suggest that intermediate-sized polymerized hemoglobin is more effective for resuscitation in hypercholesterolemic guinea pigs.
MOLECULAR PHARMACEUTICS
(2023)
Meeting Abstract
Cardiac & Cardiovascular Systems
Pedro Cabrales, Tony Reid, Scott Caroen, Bryan Oronsky
Meeting Abstract
Cardiac & Cardiovascular Systems
Pedro Cabrales, Tony Reid, Scott Caroen, Bryan Oronsky
CIRCULATION RESEARCH
(2022)
Review
Medicine, General & Internal
Vinay P. Jani, Carlos J. Munoz, Krianthan Govender, Alexander T. Williams, Pedro Cabrales
Summary: Severe COVID-19 infection is essentially a microvascular disease that can have systemic implications. Research has shown that microvascular dysfunction is an important prognosticator for morbidity and mortality. In addition to pulmonary effects, patients with COVID-19 can also experience acute cardiac, renal, and thrombolytic complications.
AMERICAN JOURNAL OF THE MEDICAL SCIENCES
(2022)
Meeting Abstract
Oncology
Marcelo Raul Bonomi, Dukagjin Blakaj, David Sher, Rafi Kabarriti, Kyle Colvett, Seth Reiner, Vinita Takiar, Matthew Biagioli, Voichita C. Bar-Ad, Sharad Goyal, Brian C. Muzyka, Kenneth J. Niermann, Tony R. Reid, Bryan Oronsky, Nacer Abrouk, Scott Caroen, Pedro Cabrales, Stephen T. Sonis
JOURNAL OF CLINICAL ONCOLOGY
(2022)