Article
Environmental Sciences
Wisurumuni Arachchilage Hasitha Maduranga Karunarathne, Ilandarage Menu Neelaka Molagoda, Yung Hyun Choi, Sang Rul Park, Seungheon Lee, Gi-Young Kim
Summary: Low concentrations of BPA induce inflammation by activating the NF-kappa B signaling pathway and increasing the release of proinflammatory mediators. Molecular modeling suggests that BPA binds to the TLR4/MD2 complex to initiate downstream molecules and elicit an immune response.
ENVIRONMENTAL POLLUTION
(2021)
Article
Pharmacology & Pharmacy
Thura Tun Oo, Natticha Sumneang, Benjamin Ongnok, Busarin Arunsak, Titikorn Chunchai, Sasiwan Kerdphoo, Nattayaporn Apaijai, Wasana Pratchayasakul, Guang Liang, Nipon Chattipakorn, Siriporn C. Chattipakorn
Summary: The study demonstrated that the MD-2 inhibitor L6H21 and metformin can attenuate metabolic disturbances and restore cognitive function in a model of prediabetes induced by high-fat diet.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Immunology
Wei Zhang, Eun-Koung An, Juyoung Hwang, Jun-O Jin
Summary: The study found that LPS can directly stimulate pDCs via the TLR4/MD2 pathway and promote the activation of pDCs and cDCs. cDCs may contribute to the enhancement of IFN-alpha production in pDCs.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Hematology
Mina Noura, Ken Morita, Hiroki Kiyose, Yukiko Okuno, Hidemasa Matsuo, Asami Koyama, Yoko Nishinaka-Arai, Yasuhiko Kamikubo, Souichi Adachi
Summary: Differentiation therapy, specifically using albendazole to stimulate a differentiation axis, shows promise as a novel treatment for non-APL acute myeloid leukaemia (AML), with potential efficacy both in vitro and in vivo.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Review
Biotechnology & Applied Microbiology
Danieli F. Buccini, Beatriz C. Roriz, Julia M. Rodrigues, Octavio L. Franco
Summary: Antimicrobial peptides are important molecules in the organism's defense system. They can modulate the immune system and recognize molecules present in pathogens. Overstimulation of TLR4 can lead to uncontrolled inflammatory responses, which can be counteracted by antimicrobial peptides.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Review
Medicine, General & Internal
Jorge Cortes, Carolina Pavlovsky, Susanne Saussele
Summary: Tyrosine-kinase inhibitors have significantly altered the natural course of chronic myeloid leukaemia, allowing some patients to approach a near-normal life expectancy. Successful treatment requires understanding the patient's treatment goals, monitoring optimal response hallmarks, timely interventions, recognition of adverse events, and management of comorbidities.
Article
Medicine, General & Internal
Courtney D. Dinardo, Harry P. Erba, Sylvie D. Freeman, Andrew H. Wei
Summary: Progress in acute myeloid leukaemia treatment has seen significant improvements in scientific understanding, prognostication tools, risk assessments, and incorporation of measurable residual disease into risk assessments. Recent updates in classification and recommendations by organizations such as WHO, ICC, and European LeukemiaNet have provided enhanced guidance for prognostic stratification and treatment response assessment. There have also been advancements in treatment options, leading to improved outcomes for both newly diagnosed and relapsed patients.
Article
Multidisciplinary Sciences
Claire M. Mulvey, Lisa M. Breckels, Oliver M. Crook, David J. Sanders, Andre L. R. Ribeiro, Aikaterini Geladaki, Andy Christoforou, Nina Kocevar Britovsek, Tracey Hurrell, Michael J. Deery, Laurent Gatto, Andrew M. Smith, Kathryn S. Lilley
Summary: Protein relocalisation is crucial in the innate immune response, as demonstrated through a combination of temporal and spatial proteomics using a Bayesian framework. The study reveals dynamic proteomic changes during LPS-induced immune response, including alterations in interferon response, endo-lysosomal system, plasma membrane reorganisation, and cell migration. The data, presented as an interactive application, highlight the importance of protein relocalisation and taking a holistic perspective on immune responses driven by LPS.
NATURE COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Natticha Sumneang, Nattayaporn Apaijai, Siriporn C. Chattipakorn, Nipon Chattipakorn
Summary: MD2 plays a crucial role in cardiac inflammation and dysfunction, and its inhibitors have potential benefits for cardiac diseases such as obesity and heart failure.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Gabriele Casirati, Andrea Cosentino, Adele Mucci, Mohammed Salah Mahmoud, Iratxe Ugarte Zabala, Jing Zeng, Scott B. Ficarro, Denise Klatt, Christian Brendel, Alessandro Rambaldi, Jerome Ritz, Jarrod A. Marto, Danilo Pellin, Daniel E. Bauer, Scott A. Armstrong, Pietro Genovese
Summary: Epitope engineering of donor haematopoietic stem/progenitor cells endows haematopoietic lineages with selective resistance to CAR T cells or monoclonal antibodies, without affecting protein function or regulation, enabling the targeting of genes that are essential for leukaemia survival and reducing the risk of tumour immune escape.
Article
Multidisciplinary Sciences
Eliza Yankova, Wesley Blackaby, Mark Albertella, Justyna Rak, Etienne De Braekeleer, Georgia Tsagkogeorga, Ewa S. Pilka, Demetrios Aspris, Dan Leggate, Alan G. Hendrick, Natalie A. Webster, Byron Andrews, Richard Fosbeary, Patrick Guest, Nerea Irigoyen, Maria Eleftheriou, Malgorzata Gozdecka, Joao M. L. Dias, Andrew J. Bannister, Binje Vick, Irmela Jeremias, George S. Vassiliou, Oliver Rausch, Konstantinos Tzelepis, Tony Kouzarides
Summary: The study identified a highly potent and selective catalytic inhibitor of METTL3, STM2457, which shows potential therapeutic value in treating AML. Treatment with this inhibitor leads to reduced AML growth, increased differentiation and apoptosis, and decreased m(6)A levels on leukemogenic mRNAs. In vivo pharmacological inhibition of METTL3 results in impaired engraftment and prolonged survival in mouse models of AML.
Review
Biochemistry & Molecular Biology
Mohammad Enamul Hoque Kayesh, Michinori Kohara, Kyoko Tsukiyama-Kohara
Summary: This review discusses the importance of TLR responses in HCV infection and the mechanisms adopted by HCV to avoid immune surveillance mediated by TLRs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Xiaoling Xie, Wuju Zhang, Xuan Zhou, Zhixin Ye, Hao Wang, Yingqi Qiu, Yating Pan, Yuxing Hu, Luyao Li, Zhuanzhuan Chen, Wanwen Yang, Yao Lu, Shuxin Zou, Yuhua Li, Xiaochun Bai
Summary: AML is characterized by self-renewal and differentiation arrest of leukaemia stem cells (LSCs), leading to high relapse rates. The CDK4/6 inhibitor, abemaciclib, has been found to suppress proliferation and promote differentiation of LSCs, and when combined with the Bcl-2 inhibitor venetoclax, it exhibits synergistic anti-leukaemic effects. These findings provide strong rationale for the clinical evaluation of abemaciclib in inducing LSC differentiation and treating aggressive AML and other advanced haematological malignancies.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Immunology
Rico Feldtmann, Andreas Kuemmel, Bishwas Chamling, Anne Strohbach, Kristin Lehnert, Stefan Gross, Lisa Loerzer, Alexander Riad, Diana Lindner, Dirk Westermann, Jens Fielitz, Marcus Doerr, Stephan B. Felix
Summary: Plasma levels of myeloid differentiation factor-2 (MD-2), a co-receptor of toll-like-receptor 4 (TLR4), predict mortality independently in patients with dilated cardiomyopathy (DCM). This study shows that MD-2 contributes to immune activation and inflammatory status in DCM patients by promoting monocyte activation and endothelial cell-mediated monocyte recruitment.
Review
Pharmacology & Pharmacy
Heather A. Ogana, Samantha Hurwitz, Nathan Wei, Eliana Lee, Kayla Morris, Karina Parikh, Yong-Mi Kim
Summary: Acute myeloid leukaemia (AML) has a poor prognosis and new therapeutic strategies are needed. The bone marrow (BM) microenvironment contains niches that interact with both normal haematopoietic stem cells and AML cells. Integrins, which are adhesion molecules in the BM microenvironment, play a central role in AML. AML cells express integrins that bind to ligands in the microenvironment, leading to adhesion, intracellular signalling, and drug resistance. Targeting integrins in AML to disrupt interactions with the microenvironment is being explored as a strategy to overcome drug resistance.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
