Article
Cell Biology
Juliane Bauch, Sina Vom Ort, Annika Ulc, Andreas Faissner
Summary: Recent research has demonstrated the inhibitory effects of tenascin-C (Tnc) and tenascin-R (Tnr) on the formation of myelin membranes through an ex vivo approach. In addition, the cuprizone-based acute demyelination model was successfully used to analyze the remyelination behavior in Tnc(-/-) and Tnr(-/-) mice, revealing inhibitory properties of Tnc and Tnr in myelin membrane formation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemical Research Methods
Alexander G. Ball, Maura C. Belanger, Rebecca R. Pompano
Summary: Researchers improved the slicing process of lymph nodes by washing them with digitonin, reducing tissue damage and enhancing cell viability and function. This method allows for effective observation of immune responses generated in lymph nodes during vaccination.
JOURNAL OF IMMUNOLOGICAL METHODS
(2021)
Article
Chemistry, Multidisciplinary
Hao Qin, Ruifang Zhao, Yuting Qin, Jin Zhu, Long Chen, Chunzhi Di, Xuexiang Han, Keman Cheng, Yinlong Zhang, Ying Zhao, Jian Shi, Gregory J. Anderson, Yuliang Zhao, Guangjun Nie
Summary: The development of an active lymph node accumulation system (ALAS) using click chemistry has shown promising results in enhancing the delivery of cancer vaccine components to lymph nodes, leading to improved antitumor immunity.
ADVANCED MATERIALS
(2021)
Article
Engineering, Biomedical
Matthew L. Bedell, Ziwen Wang, Katie J. Hogan, Angelica L. Torres, Hannah A. Pearce, Letitia K. Chim, K. Jane Grande-Allen, Antonios G. Mikos
Summary: Extrusion bioprinted constructs with different fiber architectures were fabricated to study their effects on encapsulated human mesenchymal stem cells' tissue-specific matrix deposition and integration. The gradient fiber (G-Fib) architecture showed increased chondral integration over time, while the segmented fiber (S-Fib) architecture was associated with significant mineralization. Both architectures demonstrated similar cartilage integration as re-inserted tissue controls. The study highlights the importance of considering spatial architecture in the engineering of multi-phasic tissue environments.
ACTA BIOMATERIALIA
(2023)
Article
Microbiology
Laurent Dembele, Jean-Francois Franetich, Valerie Soulard, Nadia Amanzougaghene, Shahin Tajeri, Teun Bousema, Geert-Jan van Gemert, Roger Le Grand, Nathalie Dereuddre-Bosquet, J. Kevin Baird, Dominique Mazier, Georges Snounou
Summary: This study found that chloroquine can potentiate the activity of 8-aminoquinoline compound primaquine against several malarial parasites in normal primary hepatocytes, but not in a hepatocarcinoma cell line.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Immunology
Mateus Eustaquio Lopes, Liliane Martins dos Santos, David Sacks, Leda Quercia Vieira, Matheus B. Carneiro
Summary: Innate immune cells play a dual role in leishmaniasis, serving as both the first line of defense against the parasite and as the main host cells for the parasite. The microbiota plays an essential role in driving macrophage activation towards a resistance phenotype against Leishmania major infection, impacting the ability to control infection and lesion healing. Host microbiota is crucial for the innate immune response against L. major infection, leading macrophages to a resistance phenotype.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Daniel Staniloaie, Constantin Budin, Danut Vasile, George Iancu, Alexandru Ilco, Daniel Iulian Voiculescu, Alexandra Florina Trandafir, Tarek Ammar, Emel Suliman, Emine Suliman, Dorin Dragos, Maria-Daniela Tanasescu
Summary: The identification of sentinel lymph nodes is valuable for disease staging and prognosis assessment in colorectal cancer. The use of methylene blue staining can improve staging and management by identifying lymph nodes with possible invasion. This study utilized in vivo and ex vivo techniques to identify sentinel nodes, with an overall identification rate of 69.26%.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2022)
Article
Oncology
Yuan Wang, Ryohichi Sugimura
Summary: Hematopoietic stem cells (HSCs) are promising for treating various hereditary and hematologic diseases by differentiating into mature blood cells. However, the low population of HSCs in cord blood and bone marrow has led to investigations on ex vivo HSC expansion. This review surveys the current techniques for HSC self-renewal and summarizes the effects of intrinsic and extrinsic factors on HSC expansion, as well as the challenges and opportunities in this field.
EXPERIMENTAL CELL RESEARCH
(2023)
Review
Oncology
James Clark, Christina Fotopoulou, Paula Cunnea, Jonathan Krell
Summary: Epithelial ovarian cancer (EOC) is a heterogeneous disease with limited treatment options. The use of patient-derived organoids (PDO) and explant tumor slices as novel research models offers the potential for personalized treatment and improved outcomes for ovarian cancer patients.
FRONTIERS IN ONCOLOGY
(2022)
Article
Immunology
Elodie Reboussin, Juliette Buffault, Francoise Brignole-Baudouin, Annabelle Reaux-Le Goazigo, Luisa Riancho, Celine Olmiere, Jose-Alain Sahel, Stephane Melik Parsadaniantz, Christophe Baudouin
Summary: This study demonstrated the neuroprotective and immunomodulatory effects of MSCs on RGCs in an ex vivo neuroretina explant model. However, co-culture with MSCs led to explant edema and the formation of an epiretinal membrane-like phenotype. The use of MSC secretome may offer the beneficial effects of MSCs without their potential adverse effects through paracrine signaling.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Manus J. Donahue, Paula M. C. Donahue, R. Sky Jones, Maria Garza, Chelsea Lee, Niral J. Patel, Andrea Cooper, Jill B. De Vis, Ingrid Meszoely, Rachelle Crescenzi
Summary: This study investigates whether in vivo imaging with CEST-Dixon can distinguish lymph nodes with metastatic involvement from those without. The results suggest that CEST-Dixon can detect a unique microenvironment in metastatic lymph nodes and has the potential for non-invasive mapping of lymph node metastasis in vivo.
MAGNETIC RESONANCE IN MEDICINE
(2023)
Article
Cell Biology
Esra Albayrak, Merve Uslu, Sezer Akgol, Emre Can Tuysuz, Fatih Kocabas
Summary: Research suggests that modulation of ubiquitination and neddylation can enhance the function of hematopoietic stem cells (HSCs) by improving their quiescence and self-renewal capacity. Inhibition of ubiquitination and neddylation can increase murine and human stem and progenitor cell compartments, as well as enhance in vitro self-renewal potential. Additionally, inhibition of these processes may trigger bone marrow HSPCs mobilization while decreasing the proliferation of other bone marrow cells. These findings highlight the importance of SKP2, ubiquitination and neddylation in HSC maintenance and expansion.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Deanna Ng, Aiman Ali, Kiera Lee, Denise Eymael, Kento Abe, Shelly Luu, Karineh Kazazian, Yi Qing Lu, Savtaj Brar, James Conner, Marco Magalhaes, Carol J. Swallow
Summary: In this study, an ex vivo human peritoneal explant model was developed to investigate the cellular and molecular mechanisms of peritoneal metastasis in gastric cancer. The model demonstrated sensitivity to molecular manipulation and can facilitate the screening of new therapies targeting peritoneal dissemination of gastric cancer.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Multidisciplinary
Ozgun Kocabiyik, Valeria Cagno, Paulo Jacob Silva, Yong Zhu, Laura Sedano, Yoshita Bhide, Joelle Mettier, Chiara Medaglia, Bruno Da Costa, Samuel Constant, Song Huang, Laurent Kaiser, Wouter L. J. Hinrichs, Anke Huckeriede, Ronan Le Goffic, Caroline Tapparel, Francesco Stellacci
Summary: This study describes a new class of broad-spectrum anti-influenza macromolecules that meet the criteria of targeting conserved viral domains and being virucidal with low toxicity. These compounds based on cyclodextrin core show effective inhibition of viruses and irreversibility of inhibition. In vitro efficacy is demonstrated against various human or avian influenza strains, as well as a 2009 pandemic strain ex vivo. Furthermore, therapeutic efficacy is shown in mice with one compound providing 90% survival when administered post-infection.
Article
Oncology
Bruno Maerkl, Bianca Grosser, Kerstin Bauer, Dmytro Vlasenko, Gerhard Schenkirsch, Andreas Probst, Bernadette Kriening
Summary: This study compared the effectiveness of OSNA in combination with ex vivo SLN mapping with conventional histology in gastric cancer cases. OSNA showed high sensitivity, specificity, and accuracy rates, and potential to increase metastases detection sensitivity.
Article
Biochemistry & Molecular Biology
Charlene Bashore, Priyadarshini Jaishankar, Nicholas J. Skelton, Jakob Fuhrmann, Brian R. Hearn, Peter S. Liu, Adam R. Renslo, Erin C. Dueber
ACS CHEMICAL BIOLOGY
(2020)
Article
Chemistry, Medicinal
Brian R. Blank, Ryan L. Gonciarz, Poulami Talukder, Jiri Gut, Jennifer Legac, Philip J. Rosenthal, Adam R. Renslo
ACS INFECTIOUS DISEASES
(2020)
Article
Infectious Diseases
Alex G. Peniche, E. Yaneth Osorio, Peter C. Melby, Bruno L. Travi
PLOS NEGLECTED TROPICAL DISEASES
(2020)
Review
Pharmacology & Pharmacy
Ryan L. Gonciarz, Eric A. Collisson, Adam R. Renslo
Summary: The recent emergence of oxidation state selective probes for cellular iron has led to a more nuanced understanding of its role in enzyme function and iron-dependent cell death. These findings suggest new therapeutics targeting ferrous iron and draw inspiration from the success of artemisinin in malaria treatment.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2021)
Article
Chemistry, Medicinal
Michael D. Sacco, Kyle Defrees, Xiujun Zhang, William Lawless, Emeka Nwanochie, Amelia Balsizer, Sophie E. Darch, Adam R. Renslo, Yu Chen
Summary: This study focuses on the development of novel tetrazole ligands with low affinity for LpxA, a critical enzyme in the lipid A biosynthesis pathway. Through structure-based design, the researchers identified 17 hit compounds and optimized two of them to discover ligand L13 with a K-D of 3.0 mu M. This research provides valuable chemical and structural information for future inhibitor discovery against this important antibacterial drug target.
ACS INFECTIOUS DISEASES
(2022)
Article
Chemistry, Medicinal
Hiroki Shimizu, Adam R. Renslo
Summary: The passive permeability of over thirty tetrapeptides mimicking the N-terminus of the pro-apoptotic protein Smac was synthesized and experimentally tested. Experimental permeability values spanned three orders of magnitude, providing useful empirical guidance for the design of more permeable Smac mimetics.
Article
Chemistry, Medicinal
Ryan L. Gonciarz, Sasank Sakhamuri, Nima Hooshdaran, Garima Kumar, Hyunjung Kim, Michael J. Evans, Adam R. Renslo
Summary: By studying models of metastatic castration-resistant prostate cancer (mCRPC), researchers found that elevated iron levels are a common feature of mCRPC. They synthesized ferrous-iron activatable drug conjugates of second and third-generation antiandrogens and found that these conjugates possessed comparable or enhanced antiproliferative activity in mCRPC cell line models. The results suggest that leveraging changes in iron metabolism may improve the tolerability and efficacy of antiandrogen therapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Brian R. Blank, Jiri Gut, Philip J. Rosenthal, Adam R. Renslo
Summary: The development of the antimalarial drug artefenomel was halted due to formulation challenges caused by its lipophilicity and low aqueous solubility. The symmetry of organic molecules influences their solubility and dissolution rates. In this study, we evaluated RLA-3107, a desymmetrized regioisomer of artefenomel, and found that it retains potent antiplasmodial activity and has improved human microsome stability and aqueous solubility compared to artefenomel. We also present in vivo efficacy data for artefenomel and its regioisomer with 12 different dosing regimens.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Markella Konstantinidou, Emira J. Visser, Edmee Vandenboorn, Sheng Chen, Priyadarshini Jaishankar, Maurits Overmans, Shubhankar Dutta, R. Jeffrey Neitz, Adam R. Renslo, Christian Ottmann, Luc Brunsveld, Michelle R. Arkin
Summary: The stabilization of protein-protein interactions (PPIs) is a promising strategy in chemical biology and drug discovery. This study presents the structure-based optimization of a nonselective fragment to develop selective and highly potent small-molecule stabilizers. Through determination of the binding modes of 37 compounds and optimization of the stabilizer's structure, potency and selectivity similar to a natural product were achieved.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Markella Konstantinidou, Emira J. Visser, Edmee Vandenboorn, Sheng Chen, Priyadarshini Jaishankar, Maurits Overmans, Shubhankar Dutta, R. Jeffrey Neitz, Adam R. Renslo, Christian Ottmann, Luc Brunsveld, Michelle R. Arkin
Summary: The stabilization of protein-protein interactions (PPIs) is a promising strategy in chemical biology and drug discovery. In this study, selective and potent small-molecule stabilizers for the 14-3-3s/ERa complex were optimized through structure-based optimization. By targeting specific amino acids and locking the conformation, the optimized covalent stabilizer achieved potency, cooperativity, and selectivity similar to a natural product. The study highlights the value of addressing structure, kinetics, and cooperativity in molecular glue development.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Medicinal
Michael D. Sacco, Kyle Defrees, Xiujun Zhang, William Lawless, Emeka Nwanochie, Amelia Balsizer, Sophie E. Darch, Adam R. Renslo, Yu Chen
Summary: In this study, a series of novel tetrazole ligands with low mu M affinity for LpxA were developed using a structure-based design approach. The results reveal potential LpxA inhibitors and provide valuable information on the binding features and protein conformational changes in response to ligand binding.
ACS INFECTIOUS DISEASES
(2022)
Article
Chemistry, Multidisciplinary
Jun Chen, Ryan L. Gonciarz, Adam R. Renslo
Summary: Sterically shielded 1,2,4-trioxolanes prepared by Griesbaum co-ozonolysis have been used as chemical sensors for labile iron in various chemical probes. Optimized conditions for co-ozonolysis have been reported in this study, allowing for efficient and highly diastereoselective reactions across an expanded range of substrates. This should enable the development of a new generation of labile iron probes with altered reaction kinetics and physicochemical properties.
Article
Chemistry, Medicinal
Adela Jilkova, Petra Rubesova, Jindrich Fanfrlik, Pavla Fajtova, Pavlina Rezacova, Jiri Brynda, Martin Lepsik, Helena Mertlikova-Kaiserova, Cory D. Emal, Adam R. Renslo, William R. Roush, Martin Horn, Conor R. Caffrey, Michael Mares
Summary: This study identified potent inhibitors of Schistosoma mansoni cathepsin B1, a validated drug target for schistosomiasis treatment. The inhibitors showed high bioactivity against the pathogen, selectivity for the target enzyme, and favorable metabolic stability. These results provide structural insights for the rational design of next-generation inhibitors for potential schistosomiasis drugs.
ACS INFECTIOUS DISEASES
(2021)
Article
Chemistry, Multidisciplinary
Ying-Chu Chen, Juan A. Oses-Prieto, Lauren E. Pope, Alma L. Burlingame, Scott J. Dixon, Adam R. Renslo
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
Article
Biology
Tyler C. Huff, Vladimir Camarena, David W. Sant, Zachary Wilkes, Derek Van Booven, Allegra T. Aron, Ryan K. Muir, Adam R. Renslo, Christopher J. Chang, Paula Monje, Gaofeng Wang
LIFE SCIENCE ALLIANCE
(2020)