Article
Chemistry, Medicinal
Alix Troster, Nathalie Jores, Konstantin S. Mineev, Sridhar Sreeramulu, Michael DiPrima, Giovanna Tosato, Harald Schwalbe
Summary: This concept paper describes the general strategies for EPHA2 inhibition with small molecules and summarizes the potential of targeting EPHA2 in CRC. EPHA2 plays a crucial role in the development and resistance mechanisms of CRC.
Article
Chemistry, Medicinal
Lorenzo Guidetti, Alfonso Zappia, Laura Scalvini, Francesca Romana Ferrari, Carmine Giorgio, Riccardo Castelli, Francesca Galvani, Federica Vacondio, Silvia Rivara, Marco Mor, Chiara Urbinati, Marco Rusnati, Massimiliano Tognolini, Alessio Lodola
Summary: In this study, a combined experimental and computational approach was used to investigate the molecular basis of the recognition between a prototypical Eph-ephrin antagonist and two representative receptors of the EphA and EphB subfamilies. The findings led to the design and synthesis of a novel antagonist selective for the EphA2 receptor.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Yan Xu, Dorothea Robev, Nayanendu Saha, Bingcheng Wang, Matthew B. Dalva, Kai Xu, Juha P. Himanen, Dimitar B. Nikolov
Summary: Eph receptor tyrosine kinases and ephrin ligands play crucial roles in cell communication, with dysfunctional signaling leading to disease. The formation of extensive signaling assemblies regulates neuronal migration and axon pathfinding.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Shuang Cui, Qiong Wu, Ming Liu, Mu Su, ShiYou Liu, Lan Shao, Xiao Han, Hongjuan He
Summary: This study identified a new super-enhancer EphA2-SE in various tumor cells, which drives the expression of oncogene EphA2 by recruiting FOSL2 and TCF7L2 transcription factors. Deletion of EphA2-SE inhibited tumor growth and metastasis by blocking PI3K/AKT and Wnt/β-catenin pathway, and overexpression of EphA2 rescued the effect of deletion. Animal models further confirmed that EphA2-SE deletion suppressed tumor proliferation in vivo.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Priya Jarwar, Shakeel Ahmed Sheikh, Yar Muhammad Waryah, Ikram Uddin Ujjan, Saima Riazuddin, Ali Muhammad Waryah, Zubair M. Ahmed
Summary: Hereditary congenital cataract (HCC) is clinically and genetically heterogeneous, with cataracts segregating in a recessive manner in three families with variability related to age of onset. Exome sequencing identified a novel EPHA2 variant in LUCC03 and a known variant in the other families. Computational modeling predicted that the variants cause misfolding of EPHA2. This study provides insights into the molecular and phenotypic landscape of EPHA2-related HCC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Javier Garcia-Ceca, Sara Montero-Herradon, Ana Gonzalez, Rosa Plaza, Agustin G. Zapata
Summary: The lack of EphA4 alters T-cell differentiation and the histological organization of the thymus, impacting various T cell subsets as well as the proportions of thymocytes selected positively and negatively.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Oncology
Hoi-Wing Leung, Carmen Oi Ning Leung, Eunice Y. Lau, Katherine Po Sin Chung, Etienne H. Mok, Martina Mang Leng Lei, Rainbow Wing Hei Leung, Man Tong, Vincent W. Keng, Cong Ma, Qian Zhao, Irene Oi Lin Ng, Stephanie Ma, Terence K. Lee
Summary: This study identified a EPHB2/beta-catenin/TCF1 positive feedback loop that enhances cancer stemness and sorafenib resistance in HCC, providing a targetable axis to combat acquired drug resistance in HCC.
Article
Biochemistry & Molecular Biology
Yuho Tamura, Yuta Nakamizo, Yuzo Watanabe, Ikuo Kimura, Hironori Katoh
Summary: This study reveals that the actin-binding protein Filamin A promotes the phosphorylation of EphA2 and plays a crucial role in glioblastoma cell proliferation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Amita R. Sahoo, Matthias Buck
Summary: This review focuses on the interaction between Eph receptors and ephrin ligands in regulating various processes from embryonic development to tissue homeostasis. It also highlights the importance of the transmembrane domain of Eph receptors in signal transduction and introduces techniques such as NMR and molecular modeling used to study them. Additionally, the use of transmembrane peptides to manipulate Eph receptor signaling is discussed, along with future directions for research in this field.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Kalin Wilson, Eileen Shiuan, Dana M. Brantley-Sieders
Summary: Over 25 years of research have identified EphA2 receptor tyrosine kinase as a promising molecular target for cancer treatment. Various targeting strategies, including drugs like dasatinib, therapeutic antibodies, and approaches harnessing antitumor immunity against EphA2-expressing cancer cells, have shown potential in preclinical studies. Completed and ongoing clinical trials are highlighting the promise and challenges of targeting EphA2 in cancer therapy.
Article
Cell Biology
Jeeho Kim, In-Youb Chang, Ho Jin You
Summary: This study found that the signaling factors EGFR, EphA2, and Ephexin1 are expressed at higher levels in lung and colorectal cancer patient tissues, and binding of EGFR to EphA2 is associated with increased tumor grade and metastasis. The study also revealed that Ephexin1 promotes the binding of EGFR and EphA2, and AKT-mediated phosphorylation of EphA2 plays a role in this process.
CELL DEATH & DISEASE
(2022)
Article
Hematology
Derek S. Sim, Cornell R. Mallari, John M. Teare, Maxine Bauzon, Terry W. Hermiston
Summary: CT-001 has enhanced activity and reduced thrombogenicity compared to WT FVIIa, showing efficacy in reducing blood loss and lower thrombotic risk in mouse models.
THROMBOSIS RESEARCH
(2022)
Review
Hematology
Midori Shima
Summary: rFVIIa has been used for over two decades worldwide to treat bleeding and prevent bleeding in patients with congenital hemophilia A or B with inhibitors, acquired hemophilia, congenital factor VII deficiency, and Glanzmann thrombasthenia. The approved dosage, administration, and indication of rFVIIa vary in the US, Europe, and Japan. This review provides an overview of the current status and future prospects of using rFVIIa in approved indications, with a focus on the Japanese perspective. Efficacy and safety of rFVIIa have been demonstrated in various studies and data from registries. The overall incidence of thrombosis for all approved indications was 0.17%, with specific rates ranging from 0.11% to 1.77% depending on the indication. Although new non-factor therapies have emerged, rFVIIa will continue to play a significant role in the treatment of patients, especially during breakthrough bleeding or surgical procedures.
ANNALS OF HEMATOLOGY
(2023)
Article
Genetics & Heredity
Steven J. Grzegorski, Yakun Zhao, Catherine E. Richter, Chia-Jui Ku, Kari Lavik, Divyani Paul, James H. Morrissey, Jordan A. Shavit
Summary: By using genome editing to generate knockouts of both f3a and f3b in zebrafish, it was found that a single copy of either f3a or f3b is necessary and sufficient for normal lifespan. Complete loss of TF leads to lethal hemorrhage, and TFa and TFb play predominant roles in venous and arterial circulation, respectively. Loss of TF predisposes to stress-induced cardiac tamponade.
Article
Immunology
Huazhi Zhang, Zhihui Cui, Ting Pan, Huijun Hu, Ruirui He, Ming Yi, Wanwei Sun, Ru Gao, Heping Wang, Xiaojian Ma, Qianwen Peng, Xiong Feng, Shuyan Liang, Yanyun Du, Chenhui Wang
Summary: EPHB2 plays a crucial role in colorectal cancer, particularly in TNF-induced signaling activation and proinflammatory cytokine production. The EPHB2-RNF186-TAB2-TAK1 signaling cascade is essential in colorectal epithelial cells and involved in the carcinogenesis of colorectal cancer.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Limnology
Claudia Patriarca, Vicente T. Sedano-Nunez, Sarahi L. Garcia, Jonas Bergquist, Stefan Bertilsson, Per J. R. Sjoberg, Lars J. Tranvik, Jeffrey A. Hawkes
Summary: Autotrophic dissolved organic matter (DOM) plays a significant role in the carbon biogeochemistry of aquatic systems, yet its complexity has not been thoroughly studied. This study used high-resolution mass spectrometry to investigate the DOM produced by the cyanobacteria Microcystis aeruginosa, revealing that this autotroph-derived DOM is highly susceptible to removal by heterotrophic bacteria, resulting in low concentrations in natural settings.
LIMNOLOGY AND OCEANOGRAPHY
(2021)
Article
Obstetrics & Gynecology
Ragnheidur Valdimarsdottir, Anna-Karin Wikstrom, Theodora Kunovac Kallak, Evangelia Elenis, Ove Axelsson, Hubert Preissl, S. J. Kumari A. Ubhayasekera, Jonas Bergquist, Inger Sundstrom Poromaa
Summary: Women with PCOS have higher testosterone levels during pregnancy than women without PCOS. High maternal testosterone levels in early second trimester are associated with an increased risk of developing preeclampsia in women with PCOS.
REPRODUCTIVE BIOMEDICINE ONLINE
(2021)
Article
Public, Environmental & Occupational Health
Oskar Karlsson, Joacim Rocklov, Alizee P. Lehoux, Jonas Bergquist, Anna Rutgersson, Martin J. Blunt, Linda S. Birnbaum
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
(2021)
Article
Clinical Neurology
Valter Niemela, Anne-Marie Landtblom, Dag Nyholm, Maria Kneider, Radu Constantinescu, Martin Paucar, Per Svenningsson, Sandy Abujrais, Joachim Burman, Ganna Shevchenko, Jonas Bergquist, Jimmy Sundblom
Summary: Identifying molecular changes in Huntington's disease is crucial for therapy development. Mass-spectrometry analysis revealed differences in protein expression between HD patients and controls, with PENK levels potentially serving as a marker for the state of medium spiny neurons in HD.
MOVEMENT DISORDERS
(2021)
Article
Genetics & Heredity
Amir Fallahshahroudi, Martin Johnsson, Enrico Sorato, S. J. Kumari A. Ubhayasekera, Jonas Bergquist, Jordi Altimiras, Per Jensen
Summary: The genetic variation in TSHR between red junglefowl and domestic chicken is reflected in differences in abundance, gene expression levels, hormone levels, sexual maturity, and behavior.
Article
Medicine, General & Internal
Dominic Stanculescu, Lars Larsson, Jonas Bergquist
Summary: This study suggests that maladaptive mechanisms inhibiting recovery in some ICU patients may also be present in ME/CFS, involving the suppression of pituitary gland tropic hormone secretion and a vicious circle of inflammation, oxidative and nitrosative stress (O&NS), and low thyroid hormone function. Further investigation through collaborative research projects is recommended.
FRONTIERS IN MEDICINE
(2021)
Article
Multidisciplinary Sciences
Maria Victoria Ruiz-Perez, Lourdes Sainero-Alcolado, Ganna Oliynyk, Isabell Matuschek, Nicola Balboni, S. J. Kumari A. Ubhayasekera, Marteinn Thor Snaebjornsson, Kamil Makowski, Kristina Aaltonen, Daniel Bexell, Dolors Serra, Roland Nilsson, Jonas Bergquist, Almut Schulze, Marie Arsenian-Henriksson
Summary: Metabolic pathways, especially lipid metabolism, are rewired in tumors to support their growth and adaptation to stressful environments. In neuroblastoma, inhibition of fatty acid synthesis led to increased neural differentiation and reduced tumor burden independently of MYCN-status, showing promise as a pharmacological intervention strategy.
Article
Genetics & Heredity
Sergey Nikulin, Galina Zakharova, Andrey Poloznikov, Maria Raigorodskaya, Daniel Wicklein, Udo Schumacher, Stepan Nersisyan, Jonas Bergquist, Georgy Bakalkin, Lidiia Astakhova, Alexander Tonevitsky
Summary: Knocking down ELOVL5 and IGFBP6 genes in breast cancer cells leads to a significant increase in the expression of MMP1 and a decrease in the expression of genes involved in intercellular adhesion, ultimately affecting the invasive potential of tumor cells.
FRONTIERS IN GENETICS
(2021)
Article
Oncology
Ariadna Lara Gutierrez, Julia Hedlund Lindberg, Ganna Shevchenko, Inger Gustavsson, Jonas Bergquist, Ulf Gyllensten, Stefan Enroth
Summary: Cervical cancer is the fourth most common cancer among women worldwide, and screening programs increase its detection rate and survivability. Molecular screening for the presence of HPV as an alternative to physical examinations offers cost-efficient solutions, and our study found that protein biomarkers can aid in the detection of cervical cancer pre-stages.
Article
Biochemistry & Molecular Biology
Henrik Hill, Andris Elksnis, Per Lundkvist, Kumari Ubhayasekera, Jonas Bergquist, Bryndis Birnir, Per-Ola Carlsson, Daniel Espes
Summary: Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter found in the central nervous system and immune cells. Research has shown that GABA has immune-modulatory and beta-cell stimulatory effects and could potentially be used to treat type 1 diabetes. However, a study measuring the levels of GABA in T1D patients found that the levels were unchanged compared to healthy controls, suggesting that GABA secretion from beta-cells has minimal impact on systemic levels. The study also found correlations between GABA levels and certain cytokines and GAD-autoantibodies, indicating potential alterations in local GABA levels within pancreatic islets.
Article
Biochemistry & Molecular Biology
Wei Hu, Yaorui Hu, Yao Pei, Rongrong Li, Fuyi Xu, Xiaodong Chi, Jia Mi, Jonas Bergquist, Lu Lu, Luping Zhang, Chunhua Yang
Summary: A study found that there were 46 differentially expressed proteins between cervical carcinoma (CC) and normal tissues, with Integrin beta 6, PPP1CB, TMPO, PTGES3, and DTX3L significantly upregulated in CC, while Desmin was significantly downregulated. Silencing DTX3L could suppress CC cell proliferation, migration, invasion, and tumorigenesis, and enhance cell apoptosis. Furthermore, DTX3L silencing inhibited the activity of the PI3K/AKT/mTOR signaling pathway. These findings suggest that DTX3L may regulate CC progression through the PI3K/AKT/mTOR signaling pathway and could serve as a potential biomarker and therapeutic target for CC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Sofia Persson, Kumari A. Ubhayasekera, Jonas Bergquist, Sahruh Turkmen, Inger Sundstroem Poromaa, Evangelia Elenis
Summary: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women, and hyperandrogenism can cause psychological morbidity and impaired quality of life. This study aimed to investigate whether hyperandrogenism persists into midlife and its impact on quality of life.
Article
Food Science & Technology
Julio Cesar Espana Amortegui, Heidi Pekar, Mark Dennis Chico Retrato, Malin Persson, Bengt Karlson, Jonas Bergquist, Aida Zuberovic-Muratovic
Summary: A LC-MS/MS method was developed for the simultaneous identification and quantification of cyanotoxins in edible bivalves. The method successfully detected and resolved two previously detected cyanotoxin congeners separately. The method showed limitations for certain cyanotoxins but overall was specific and robust for the parameters investigated. The method was applied to analyze mussel and oyster samples collected along the Swedish coast, and the results can contribute to future regulatory monitoring for cyanotoxins to ensure seafood safety.
Article
Infectious Diseases
Anja Naas, Peng Li, Clas Ahlm, Elisabeth Aurelius, Josef D. Jarhult, Silvia Schliamser, Marie Studahl, Wenzhong Xiao, Jonas Bergquist, Gabriel Westman
Summary: This study investigated the temporal changes of the CSF proteome in patients with herpes simplex encephalitis (HSE) and its association with factors such as anti-NMDAR serostatus, corticosteroid treatment, brain MRI, and neurocognitive performance. The results showed that the composition and activation pathways of CSF proteins vary at different stages of the disease. Additionally, it was found that several proteins were less abundant in patients with anti-NMDAR seropositivity compared to seronegativity.
INFECTIOUS DISEASES
(2023)
Article
Chemistry, Analytical
Mark Dennis Chico Retrato, Siyuan Qiu, Anna Lundquist, Aida Zuberovic Muratovic, Farshid Mashayekhy Rad, S. J. Kumari A. Ubhayasekera, Jonas Bergquist
Summary: This study describes a simple and robust method for the identification and quantification of 22 fatty acids in TPN components using gas chromatography-mass spectrometry. The method was evaluated according to the guidelines from FDA, EMA, and ICH, and demonstrated good methodological performance. The developed method has potential applications for quality assurance and control of TPN products.
ANALYTICAL METHODS
(2023)