Article
Biochemistry & Molecular Biology
Hosub Park, Hwangkyu Son, Hyebin Cha, Kihyuk Song, Seongsik Bang, Seungyun Jee, Hyunsung Kim, Jaekyung Myung, Su-Jin Shin, Chihwan Cha, Min Sung Chung, Seungsam Paik
Summary: This study found that low ASAP1 expression was associated with worse recurrence-free survival in invasive breast cancer, particularly in ER-positive cases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Max Von Suskil, Kazi Nasrin Sultana, Weam Othman Elbezanti, Omar S. Al-Odat, Robert Chitren, Amit K. Tiwari, Kishore B. Challagundla, Sandeep Kumar Srivastava, Subash C. Jonnalagadda, Tulin Budak-Alpdogan, Manoj K. Pandey
Summary: Multiple myeloma remains an incurable disease despite advancements in treatment, leading to aggressive relapses in patients. The cytosolic kinase BTK plays a crucial role in the survival of malignant clones and multiple myeloma stem cells, making it a promising therapeutic target. Inhibition of the BTK pathway may disrupt interactions between malignant clones and the bone marrow microenvironment in MM patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Jiakuo Liu, Chengjuan Chen, Dongmei Wang, Jie Zhang, Tiantai Zhang
Summary: Therapy based on Bruton's tyrosine kinase (BTK) inhibitors is a major treatment option for lymphoma patients, with the first generation showing remarkable progress but still facing issues like drug-resistance and serious side effects. New BTK inhibitors have been developed to address these challenges and their effects on immune-related diseases are being evaluated in clinical trials. Progress in the research and development of BTK inhibitors, focusing on structural characteristics and structure-activity relationships, has been summarized in this review.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Zhou-Peng Xiao, Min Liao, Xue-Juan Huang, Yu-Tong Wang, Xiao-Cui Lan, Xue-Ying Wang, Xi-Tao Li
Summary: In this study, a series of prodrugs of a BTK inhibitor with an insoluble 2,5-diaminopyrimidine structure were designed, synthesized, and evaluated. Different solubilizing groups were added to the parent molecule via an ester linkage. Prodrug 5a showed good aqueous solubility and could be efficiently converted to the parent in a human plasma stability study. Molecular studies supported the rational prodrug design and showed a dramatically reduced BTK kinase-inhibitory potential. These findings suggest that prodrug derivatization of the 2,5-diaminopyrimidine scaffold could be a potential strategy for advancing this series of BTK inhibitors into the therapeutic arena.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Cell Biology
Antonio Garcia-Merino
Summary: B cells play a central role in the pathogenesis of multiple sclerosis, and BTK inhibitors may serve as a non-cell-depleting alternative for B cell modulation. This review discusses the structure, signaling, and roles of BTK, along with the various inhibitors assessed in animal models and clinical trials.
Article
Oncology
Seongsik Bang, Seungyun Jee, Hwangkyu Son, Hyebin Cha, Jongmin Sim, Yeseul Kim, Hosub Park, Jaekyung Myung, Hyunsung Kim, Seungsam Paik
Summary: High expression of ASAP1 in HCC patients is associated with aggressive clinicopathological characteristics and poor clinical outcomes, indicating ASAP1 as a prognostic biomarker in HCC patients.
PATHOLOGY & ONCOLOGY RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Broto Chakrabarty, Nita Parekh
Summary: This study classifies and analyzes human ANKYRIN proteins to understand their diversity and their significance in disease association.
Review
Immunology
Charlotte McDonald, Charalampos Xanthopoulos, Efterpi Kostareli
Summary: BTK, a TEC kinase with a critical role in B-cell biology, has gained momentum as a therapeutic target in various hematological malignancies. It plays a significant role not only in lymphoproliferative disorders but also in autoimmune diseases and response to infection. Developing novel, more specific BTK inhibitors is crucial to address the rising levels of resistance and meet the unmet treatment needs of various diseases.
Article
Biochemistry & Molecular Biology
Rongrong Su, Yanyan Diao, Wenjie Sha, Dou Dou, Zhixiao Yu, Limin Leng, Zhenjiang Zhao, Zhuo Chen, Honglin Li, Yufang Xu
Summary: This study developed selective non-covalent BTK inhibitors by scaffold hopping and found that compound 2 and 4 exhibited high BTK inhibition potency. These compounds showed great ability to inhibit tumor growth in cell and animal models.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Natasha S. Clayton, Millie Fox, Jose J. Vicente-Garcia, Courtney M. Schroeder, Trevor D. Littlewood, Jonathon Wilde, Kadalmani Krishnan, Murray J. B. Brown, Claire Crafter, Helen R. Mott, Darerca Owen
Summary: Activated Cdc42-associated kinase (ACK) phosphorylates PI3K regulatory subunits, promoting cell proliferation. ACK interacts with p85 alpha in nuclear-enriched cell fractions, facilitating dimerization of the regulatory subunits.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Asim Najmi, Neelaveni Thangavel, Anugeetha Thacheril Mohanan, Marwa Qadri, Mohammed Albratty, Safeena Eranhiyil Ashraf, Safaa Fathy Saleh, Maryam Nayeem, Syam Mohan
Summary: BTK plays a crucial role in B-cell receptor signaling and is involved in B-cell malignancies and autoimmune diseases. This review examines the structural compatibility between BTK-kinase domain and its inhibitors based on recent inhibitor-bound BTK structures in the protein data bank. The study also investigates the effects of BTK on B-cell development and antibody production. Covalent inhibitors stabilize the inactive conformation of BTK by forming a bond with Cys481, while non-covalent inhibitors bind to Tyr551 in the activation kink to determine BTK selectivity. Understanding the structural complementarity of BTK and its inhibitors can aid in drug optimization and the development of therapies for B-cell malignancies and autoimmune diseases.
Article
Immunology
Alexander P. de Porto, Zhe Liu, Regina de Beer, Sandrine Florquin, Joris J. T. H. Roelofs, Onno J. de Boer, Joke M. M. den Haan, Rudi W. Hendriks, Cornelis van 't Veer, Tom van der Poll, Alex F. de Vos
Summary: The research indicates that besides regulating B cell-mediated immunity, Btk is critical for the regulation of myeloid cell-mediated, and particularly neutrophil-mediated, innate host defense against S. pneumoniae in vivo.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Christoph Heintze, Iaroslav Babenko, Jirina Zackova Suchanova, Alastair Skeffington, Benjamin M. Friedrich, Nils Kroeger
Summary: Biomineral-forming organisms produce inorganic materials with complex morphologies. This study focused on diatoms and identified new biomineralization proteins involved in silica biosynthesis. Knocking out specific genes led to aberrations in silica biogenesis, suggesting a mechanism of liquid-liquid phase separation for pore pattern morphogenesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Sayaka Okuzono, Fumihiko Fujii, Yuki Matsushita, Daiki Setoyama, Yohei Shinmyo, Ryoji Taira, Kousuke Yonemoto, Satoshi Akamine, Yoshitomo Motomura, Masafumi Sanefuji, Takeshi Sakurai, Hiroshi Kawasaki, Kihoon Han, Takahiro A. Kato, Hiroyuki Torisu, Dongchon Kang, Yusaku Nakabeppu, Yasunari Sakai, Shouichi Ohga
Summary: Epileptic seizures are common comorbidities in children with autism spectrum disorder (ASD), but little is known about the genes involved and their role in regulating neuronal excitability. This study found that Shank3, an ASD-associated gene, plays a unique role in protecting thalamocortical neurons from hyperexcitability during the early postnatal period. These findings have important implications for understanding the mechanisms underlying seizures in children with autism.
NEUROSCIENCE RESEARCH
(2023)
Article
Chemistry, Medicinal
Lin Niu, Yu-jie Lu, Xing-wang Zu, Wen Yang, Fu-kui Shen, Yan-yan Xu, Min Jiang, Yang Xie, Su-yun Li, Jie Gao, Gang Bai
Summary: This study focuses on the role of TRPV4 in fibrosis in chronic obstructive pulmonary disease (COPD) and investigates the therapeutic effect and mechanism of action of magnolol (MAG) on TRPV4. The results demonstrate that MAG disrupts the binding between phosphatidylinositol 3 kinase and TRPV4 by targeting its ankyrin repeat domain (ARD), inhibiting the membrane distribution and channel activity of TRPV4, consequently alleviating fibrosis in COPD.
PHYTOTHERAPY RESEARCH
(2023)
Article
Oncology
H. Yesid Estupinan, Qing Wang, Anna Berglof, Gerard C. P. Schaafsma, Yuye Shi, Litao Zhou, Dara K. Mohammad, Liang Yu, Mauno Vihinen, Rula Zain, C. I. Edvard Smith
Summary: Certain double mutants were found to be super-resistant to irreversible inhibitors, while reversible inhibitors showed variable patterns from resistance to no resistance, collectively demonstrating the structural constraints for different classes of inhibitors that may affect their clinical application.
Review
Cell Biology
H. Yesid Estupinan, Anna Berglof, Rula Zain, C. I. Edvard Smith
Summary: BTK inhibitors have shown efficacy in treating B-cell tumors, but are increasingly being tested for autoimmune diseases and inflammation. Adverse effects such as cardiovascular issues and bleeding can persist, while skin manifestations and diarrhea may occur early but subside.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Tea Umek, Thomas Olsson, Olof Gissberg, Osama Saher, Eman M. Zaghloul, Karin E. Lundin, Jesper Wengel, Eric Hanse, Henrik Zetterberg, Dzeneta Vizlin-Hodzic, C. I. Edvard Smith, Rula Zain
Summary: Huntington's disease is a dominantly inherited neurodegenerative disorder that affects the striatum, cerebral cortex, and other subcortical structures. The mutation in the HTT gene leads to the formation of mutant HTT protein aggregates, and reducing both mutant mRNA and protein shows promise as a treatment strategy.
NUCLEIC ACID THERAPEUTICS
(2021)
Article
Oncology
Lisa Blixt, Gordana Bogdanovic, Marcus Buggert, Yu Gao, Sophia Hober, Katie Healy, Hemming Johansson, Christian Kjellander, Sara Mravinacova, Sandra Muschiol, Peter Nilsson, Marzia Palma, Elisa Pin, C. I. Edvard Smith, Olga Stromberg, Margaret Sallberg Chen, Rula Zain, Lotta Hansson, Anders Osterborg
Summary: The study revealed that severe cases of Covid-19 were equally distributed among CLL patients, regardless of age, gender, BMI, or CLL status, except for the Cumulative Illness Rating Scale (CIRS). The mortality rate was higher in patients aged 75 and above. Despite the high hospitalization rate, there was a numerical reduction in deaths and ICU admissions during different periods of the pandemic. Most convalescent patients showed robust and durable B and/or T cell immunity, with a majority testing positive for anti-SARS-CoV-2 antibodies even six to twelve months after infection.
Article
Biochemistry & Molecular Biology
Angelica Cuapio, Caroline Boulouis, Iva Filipovic, David Wullimann, Tobias Kammann, Tiphaine Parrot, Puran Chen, Mira Akber, Yu Gao, Quirin Hammer, Benedikt Strunz, Andre Perez Potti, Olga Rivera Ballesteros, Joshua Lange, Jagadeeswara Rao Muvva, Peter Bergman, Ola Blennow, Lotta Hansson, Stephan Mielke, Piotr Nowak, Gunnar Soderdahl, Anders Osterborg, C. I. Edvard Smith, Gordana Bogdanovic, Sandra Muschiol, Fredrika Hellgren, Karin Lore, Michal J. Sobkowiak, Giorgio Gabarrini, Katie Healy, Margaret Sallberg Chen, Evren Alici, Niklas K. Bjorkstrom, Marcus Buggert, Per Ljungman, Johan K. Sandberg, Soo Aleman, Hans-Gustaf Ljunggren
Summary: This study characterized NK cells in healthy individuals and immunocompromised patients during the course of an anti-SARS-CoV-2 BNT162b2 mRNA vaccine trial. The results showed that NK cell numbers, frequencies, subsets, phenotypes, and function remained unchanged following vaccination. Furthermore, a positive correlation was observed between the frequency of a specific type of NK cells at baseline and the antibody titers after vaccination.
MOLECULAR MEDICINE
(2022)
Article
Genetics & Heredity
Ola Hammarsten, Anna Lyytikainen, Sofia Thunstrom, Torben Ek, Anders Fasth, Olov Ekwall, Sara Cajander, Emilie Wahren Borgstrom, C. I. Edvard Smith, Pegah Johansson
Summary: This study successfully measured the sensitivity of patient cells to DNA-damaging agents using an in vitro assay and found associations between different DNA repair gene variants and cell sensitivity.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Engineering, Biomedical
Jeremy P. Bost, Osama Saher, Daniel Hagey, Doste R. Mamand, Xiuming Liang, Wenyi Zheng, Giulia Corso, Oskar Gustafsson, Andre Gorgens, Ci Edvard Smith, Rula Zain, Samir El Andaloussi, Dhanu Gupta
Summary: Extracellular vesicles (EVs) are nanosized cell-derived vesicles that facilitate intercellular communication via transmitting biological cargo. The production of EVs is influenced by various pathways and external factors in the cell media, with ceramide-dependent pathway being a major contributor to engineered EV production. The study provides insights into understanding and optimizing EV production in cell culture for developing advanced methods.
ADVANCED HEALTHCARE MATERIALS
(2022)
Review
Immunology
Carl Inge Edvard Smith, Rula Zain, Anders osterborg, Marzia Palma, Marcus Buggert, Peter Bergman, Yenan Bryceson
Summary: The scarcity of plasmacytoid dendritic cells (pDCs) in patients with chronic lymphocytic leukaemia (CLL) may contribute to the severe clinical course of COVID-19 in these patients. Treatment of CLL with Bruton's tyrosine kinase (BTK) inhibitors can increase the number of pDCs.
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Alexey V. Kostarnoy, Petya G. Gancheva, Igor I. Kireev, Andrey I. Soloviev, Bernd Lepenies, Andrey Y. Kulibin, Ekaterina A. Malolina, Olga N. Scheglovitova, Alexey V. Kondratev, Maria V. Sokolova, Daria Vorobyeva, Nadezhda Filippova, Marina R. Kapkaeva, Maria A. Lagarkova, Pavel S. Metalnikova, Evgeniy Riabenko, Daniil A. Grumov, Maxim A. Bobrov, Elena Vasilieva, Boris S. Naroditsky, Alexander L. Gintsburg
Summary: Cellular lipid uptake is a fundamental physiological process, and we have discovered a previously unknown mechanism of lipid cargo uptake mediated by the receptor Mincle. Our study reveals that Mincle tightly binds a range of self-lipids and forms vesicles in the cytoplasm. Knockout of Mincle leads to a significant decrease in lipid endocytosis, suggesting it as a prospective target for disorders of lipid metabolism.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Endocrinology & Metabolism
Per-Ola Carlsson, Daniel Espes, Sofia Sisay, Lindsay C. Davies, C. I. Edvard Smith, Mathias G. Svahn
Summary: This study aimed to investigate the safety and efficacy of treatment with allogeneic Wharton's jelly-derived mesenchymal stromal cells (MSCs) in recent-onset type 1 diabetes. Results showed that treatment with ProTrans resulted in smaller decline in C-peptide levels and no change in insulin requirements, suggesting the potential to preserve beta cell function.
Article
Biochemistry & Molecular Biology
Laurent Schmied, Thuy T. Luu, Jonas N. Sondergaard, Sophia H. Hald, Stephan Meinke, Dara K. Mohammad, Sunitha B. Singh, Corinna Mayer, Giovanna Perinetti Casoni, Michael Chrobok, Heinrich Schlums, Giorgia Rota, Hieu M. Truong, Lisa S. Westerberg, Greta Guarda, Evren Alici, Arnika K. Wagner, Nadir Kadri, Yenan T. Bryceson, Mezida B. Saeed, Petter Hoglund
Summary: Natural killer (NK) cells recognize infected cells and tumors. The function of NK cells depends on balanced signaling from activating and inhibitory receptors. The subcellular localization of tyrosine phosphatase SHP-1 determines NK cell tolerance and education. Education of NK cells leads to reduced synapse accumulation of SHP-1 and augmented signaling from activating receptors.
Article
Biochemistry & Molecular Biology
Khder H. Rasul, Alamdar Hussain, Hazel Reilly, Maria Karvouni, Carin I. M. Dahlberg, Mustafa S. Al-Attar, Arnika K. Wagner, Evren Alici, Dara K. Mohammad
Summary: This study investigates the cellular processing of the TCR complex in NK cells. The findings suggest that the absence of CD3 subunits prevents surface expression of the TCR complex in NK cells. Additionally, TCR expression on the surface of NK cells gradually increases after transduction. The TCR complex in NK92 cells is shown to be functional.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Katie Healy, Elisa Pin, Puran Chen, Gunnar Soderdahl, Piotr Nowak, Stephan Mielke, Lotta Hansson, Peter Bergman, C. I. Edvard Smith, Per Ljungman, Davide Valentini, Ola Blennow, Anders Osterborg, Giorgio Gabarrini, Khaled Al-Manei, Hassan Alkharaan, Michal Jacek Sobkowiak, Jamil Yousef, Sara Mravinacova, Angelica Cuapio, Xinling Xu, Mira Akber, Karin Lore, Cecilia Hellstrom, Sandra Muschiol, Gordana Bogdanovic, Marcus Buggert, Hans-Gustaf Ljunggren, Sophia Hober, Peter Nilsson, Soo Aleman, Margaret Sallberg Chen
Summary: This study found that the mRNA BNT162b2 vaccine can induce immune responses in the saliva of immunocompromised individuals to SARS-CoV-2 spike antigens. Salivary responses were correlated with specific IgG titers and neutralizing capacity in serum, and had a high predictive power for identifying vulnerable groups for revaccination.
Article
Engineering, Biomedical
Dhanu Gupta, Oscar P. B. Wiklander, Andre Goergens, Mariana Conceicao, Giulia Corso, Xiuming Liang, Yiqi Seow, Sriram Balusu, Ulrika Feldin, Beklem Bostancioglu, Rim Jawad, Doste R. Mamand, Yi Xin Fiona Lee, Justin Hean, Imre Mager, Thomas C. Roberts, Manuela Gustafsson, Dara K. Mohammad, Helena Sork, Alexandra Backlund, Per Lundin, Antonin de Fougerolles, C. I. Edvard Smith, Matthew J. A. Wood, Roosmarijn E. Vandenbroucke, Joel Z. Nordin, Samir El-Andaloussi
Summary: This study optimized the loading of two different therapeutic protein receptors onto extracellular vesicles through genetic engineering and protein moiety screening, leading to alleviation of inflammation-related diseases.
NATURE BIOMEDICAL ENGINEERING
(2021)
Article
Hematology
Tom A. Mulder, Lucia Pena-Perez, Anna Berglof, Stephan Meinke, H. Yesid Estupinan, Kia Heimersson, Rula Zain, Robert Mansson, C. I. Edvard Smith, Marzia Palma
Summary: Ibrutinib is highly effective in chronic lymphocytic leukemia, but can cause side effects like atrial fibrillation. During treatment, significant changes in plasma biomarkers and immune cell numbers were observed, with an increase in markers associated with cardiovascular diseases potentially contributing to atrial fibrillation.