Article
Neurosciences
Jessica A. Higginbotham, Rong Wang, Ben D. Richardson, Hiroko Shiina, Shi Min Tan, Mark A. Presker, David J. Rossi, Rita A. Fuchs
Summary: Systemic CB1R antagonism during cocaine-memory reconsolidation reduced drug context-induced cocaine-seeking behavior and inhibited cellular adaptations and synaptic physiology changes in the basolateral amygdala. These findings suggest that CB1R signaling modulates cellular and synaptic mechanisms in the BLA, potentially playing a crucial role in preventing relapse.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Chemistry, Physical
Xun Liu, Wei Li, Mengru Wang, Ningyu Liu, Qiang Yang, Yunjie He, Duanmin Hu, Rongying Zhu, Lichen Yin
Summary: This study presents a self-powered nanozyme that can induce the production of reactive oxygen and nitrogen species (RONS) in tumor cells through cascade reactions. The nanozymes are constructed using glucose oxidase (GOx)-templated inverse microemulsion polymerization and coated with hyaluronic acid. After intracellular delivery, the nanozymes release GOx under the action of intracellular glutathione, which decomposes glucose to generate gluconic acid and H2O2. Under acidified conditions, H2O2 efficiently oxidizes arginine residues to produce nitric oxide, and transforms into highly toxic hydroxyl radicals and superoxide anions via ferrocene-mediated Fenton reaction and Haber-Weiss cycle. Simultaneously, peroxynitrite anions are generated via the reaction between NO and center dot O-2(-), thereby provoking the RONS radical storm to effectively eradicate A549 tumor cells in vitro and in vivo. This nature-inspired enzyme-chemical dynamic therapy may provide a promising modality for anti-cancer treatment.
Article
Developmental Biology
Tomas Etcheverry, Paula Accialini, Marcos Palligas, Florencia Loureiro, Nora Saraco, Nora Martinez, Mariana Farina
Summary: The study revealed that the endocannabinoid anandamide disrupts syncytialization process, which may have an impact on pregnancy outcomes.
Article
Neurosciences
Denise L. Gaskins, Andrew R. Burke, Tammy J. Sajdyk, William A. Truitt, Amy D. Dietrich, Anantha Shekhar
Summary: Repeated exposure to stress can induce chronic anxiety states, likely through the activation of CRFR receptors in the amygdala. Selective reduction of the Sstr2 gene expression in the BLA is associated with the persistent anxiety-like phenotype observed with Ucn1-priming, and Sstr2 agonist in the BLA can block acute anxiety-inducing effects.
Article
Multidisciplinary Sciences
C. E. Matisz, M. Patel, N. S. Hong, R. J. McDonald, A. J. Gruber
Summary: Chronic inflammatory diseases are often associated with anxiety in humans. This study found that prolonged gut inflammation is sufficient to induce anxiety-related behaviors in mice. The research suggests that chronic inflammation may affect memory consolidation processes, leading to the generalization of negative associations and fearful responses in inappropriate contexts.
SCIENTIFIC REPORTS
(2022)
Article
Hematology
Anja Schmitt, Wendan Xu, Philip Bucher, Melanie Grimm, Martina Konantz, Heike Horn, Myroslav Zapukhlyak, Philipp Berning, Marc Braendle, Mohamed-Ali Jarboui, Caroline Sch Onfeld, Karsten Boldt, Andreas Rosenwald, German Ott, Michael Grau, Pavel Klener, Petra Vockova, Claudia Lengerke, Georg Lenz, Klaus Schulze-Osthoff, Stephan Hailfinger
Summary: The study demonstrates the broad antitumor effect of dimethyl fumarate (DMF) on both subtypes of DLBCL by inducing ferroptosis, especially in GCB DLBCL. In ABC DLBCL cells, DMF treatment efficiently inhibits the activity of the IKK complex and Janus kinases. Additionally, the combination of BCL-2-specific BH3 mimetic ABT-199 and an inhibitor of ferroptosis suppressor protein 1 synergize with DMF in inducing cell death in DLBCL.
Article
Neurosciences
Jaime E. Vantrease, Brittany Avonts, Mallika Padival, M. Regina DeJoseph, Janice H. Urban, J. Amiel Rosenkranz
Summary: The activity of BLA-BNST neurons mediates conditioned anticipatory anxiety-like behavior in males, but not in females. BLA-BNST projection neurons in males are more active and excitable, with a smaller after-hyperpolarization current (I-AHP) compared to other BLA neurons; while in females, BLA-BNST neurons are less excitable and have a larger I-AHP compared to other BLA neurons.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Abdeslem El Idrissi, Alejandra del Carmen Alonso
Summary: The disruption of insulin signaling and insulin resistance play a role in neurodegeneration in Alzheimer's disease. In this study, a mouse model expressing pseudo-phosphorylated tau was used to investigate the effects on neuronal excitability and insulin receptor signaling. The results showed increased excitability and decreased insulin sensitivity in the mouse model, suggesting a potential interaction between tau pathology and insulin signaling in Alzheimer's disease.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Chiara Ciminieri, Manon E. Woest, Niki L. Reynaert, Irene H. Heijink, Rene Wardenaar, Diana C. J. Spierings, Corry-Anke Brandsma, Melanie Konigshoff, Reinoud Gosens
Summary: Chronic obstructive pulmonary disease (COPD) is characterized by persistent inflammation and defective tissue repair in the lungs. This study aimed to investigate the impact of the inflammatory microenvironment on epithelial progenitors and their supporting mesenchymal niche cells in distal lung tissue repair. IL-1 beta, an inflammatory mediator increased during COPD exacerbations, was found to alter the state of fibroblasts and switch their function from supportive to inhibitory in an organoid assay. Targeting IL-1 beta intracellular signaling or C-X-C chemokine receptors 1/2 (CXCR1/2) reduced the proinflammatory response and restored organoid growth. These findings suggest that chronic inflammation contributes to the inhibition of repair in COPD.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Spencer Cesar, Lisa Willis, Kerwyn Casey Huang
Summary: Regrowth of bacteria from prolonged stationary phase is heterogeneous, with some cells rejuvenating immediately while others experience delayed or no regrowth at all. Delayed regrowth is associated with the dissolution of damaged protein aggregates, and a deep learning algorithm can distinguish cellular fates based on single images.
Article
Neurosciences
Hyeji Jung, Seungjoon Kim, Jaewon Ko, Ji Won Um
Summary: This article reviews recent research on GABAergic synaptic signaling pathways, discussing their crucial role in the formation, transmission, and plasticity of GABAergic synapses. The main outstanding issues in this field are outlined, and the association of dysregulated synaptic signaling with various brain disorders is highlighted.
CURRENT OPINION IN NEUROBIOLOGY
(2023)
Article
Neurosciences
Lucinda M. Sisk, Kristina M. Rapuano, May Conley, Abigail S. Greene, Corey Horien, Monica D. Rosenberg, Dustin Scheinost, R. Todd Constable, Charles E. Glatt, B. J. Casey, Dylan G. Gee
Summary: Research has shown that individuals carrying the FAAH C385A polymorphism gene exhibit network-level changes in brain connectivity distinct from non-carriers, which may be related to genetic variations in endocannabinoid signaling, and these genotype-associated neural differences may emerge at a younger age.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)
Article
Neurosciences
Duncan G. J. Green, Jinhee Kim, Stephen J. Kish, Rachel F. Tyndale, Matthew N. Hill, Antonio P. Strafella, Junchao Tong, Tina McCluskey, Duncan J. Westwood, Sylvain Houle, Nancy J. Lobaugh, Isabelle Boileau
Summary: This study revealed a negative correlation between levels of the endocannabinoid enzyme fatty acid amide hydrolase (FAAH) in the amygdala and functional connectivity in frontoamygdalar circuits involved in stress and affect control. The findings provide preliminary evidence supporting the role of FAAH in regulating brain circuits underlying fear and emotion processing in humans.
JOURNAL OF PSYCHIATRY & NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Rafie Belali, Seyyed Ali Mard, Seyed Esmaeil Khoshnam, Kowsar Bavarsad, Alireza Sarkaki, Yaghoob Farbood
Summary: In this study, the anti-anxiety and anti-depressant effects of the endocannabinoid anandamide (AEA) were investigated in a chronic sleep deprivation (SD) model in rats. AEA administration showed anxiolytic-like effects by increasing the time spent, distance traveled, and climbing behavior in the open-field test, and also modulated CB1R mRNA expression, cortical EEG, and inflammatory response. However, it did not exhibit anti-depressant effects in the forced swimming test.
NEUROCHEMICAL RESEARCH
(2023)
Article
Cell & Tissue Engineering
Yiwei Li, Maorong Chen, Jiliang Hu, Ren Sheng, Qirong Lin, Xi He, Ming Guo
Summary: Intracellular crowding, influenced by external physical cues, plays a significant role in regulating Wnt/beta-catenin signaling and promoting the growth of intestinal organoids. This indicates a potential link between physical cellular properties and cellular functionalities, with implications for stem cell and organoid expansion.
Article
Infectious Diseases
Elmira F. Khusnutdinova, Veronique Sinou, Denis A. Babkov, Oxana Kazakova, Jean Michel Brunel
Summary: A series of oleanolic acid derivatives with different long chain polyamines were synthesized and evaluated for their antimicrobial activities. These derivatives showed good to moderate activity against Gram-positive and Gram-negative bacteria, including the disruption of the outer bacterial membrane. Computational ADMET profiling suggested that one of the derivatives is a suitable starting point for pharmacokinetic optimization.
Article
Virology
Alexandre F. R. Stewart, Hsiao-Huei Chen
Summary: Human breast cancer incidence varies geographically. The zoonotic transmission of mouse mammary tumor virus (MMTV) from Mus musculus domesticus may explain the regional differences in breast cancer incidence. Recent developments have provided further evidence for this hypothesis, including the limited impact of genetic factors and the role of antiretroviral therapy. Economic globalization has also contributed to an increase in breast cancer incidence in Asia through the distribution of M. m. domesticus. This article revisits the evidence and proposes updated strategies for addressing MMTV transmission.
Review
Biochemistry & Molecular Biology
Jinane Tabcheh, Julia Vergalli, Anne Davin-Regli, Noha Ghanem, Jean-Marie Pages, Charbel Al-Bayssari, Jean Michel Brunel
Summary: Antibiotic resistance is increasing morbidity and mortality for non-curable infectious diseases. Novel strategies, such as effective antibiotic combinations and antibiotics with non-antibiotic activity-enhancing compounds, have emerged to combat multidrug-resistant microorganisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Neurosciences
Haley A. Vecchiarelli, Valerie Joers, Malu Gamez Tansey, Katarzyna Starowicz
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Rene Dofini Magnini, Francois Pedinielli, Julia Vergalli, Noufou Ouedraogo, Simon Remy, Adama Hilou, Jean-Michel Brunel, Jean-Marie Pages, Anne Davin-Regli
Summary: The emergence of bacterial resistance has changed the effectiveness of different antibiotic families, and research into alternative therapeutic molecules from medicinal plants is needed. This study used molecular networking and MS/MS data to characterize active molecules in natural extracts from A. senegal. The activities of different combinations of fractions and antibiotics were tested using the chessboard test. Bio-guided fractionation identified fractions with chloramphenicol activity, and LC-MS/MS analysis revealed that these fractions contained Budmunchiamines, which are macrocyclic alkaloids. This study provides a potential source of bioactive secondary metabolites related to Budmunchiamines that can restore chloramphenicol activity in enterobacterial-resistant strains with AcrB efflux pumps.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Margot Draveny, Clemence Rose, Alexis Pinet, Laurent Ferrie, Bruno Figadere, Jean-Michel Brunel, Muriel Masi
Summary: The spread of antibiotic resistance is a serious threat to global health, especially in pathogenic Gram-negative bacteria due to their robust outer membrane permeability barrier. One strategy to tackle this challenge is the use of antibiotic adjuvants, which can enhance the effectiveness of certain antibiotics. This study aimed to explore the disruption of the outer membrane in Pseudomonas aeruginosa to make it more susceptible to inactive antimicrobials with the presence of NV716. The findings suggest that outer membrane disruption alters permeation rules and expands the hydrophobicity threshold for antibacterial activity in Gram-negative bacteria.
Editorial Material
Neurosciences
Haley A. Vecchiarelli, Marie-eve Tremblay
Summary: Vasek et al. demonstrate that microglia engage in protein translation in their processes, which plays a crucial role in the number of processes and the formation of phagocytic cups. These findings shed light on the rapid response of microglia to diverse local signals in specific cellular compartments.
NATURE NEUROSCIENCE
(2023)
Article
Biology
Georgia Balsevich, Gavin N. Petrie, Daniel E. Heinz, Arashdeep Singh, Robert J. Aukema, Avery C. Hunker, Haley A. Vecchiarelli, Hiulan Yau, Martin Sticht, Roger J. Thompson, Francis S. Lee, Larry S. Zweifel, Prasanth K. Chelikani, Nils C. Gassen, Matthew N. Hill
Summary: A study found that the impact of FAAH C385A on metabolic outcomes is influenced by the environmental context. This genotype amplifies orexigenic responses and decreases anorexigenic responses, providing a potential explanation for the conflicting findings in previous human studies.
Review
Pharmacology & Pharmacy
Chloe G. McKee, Madison Hoffos, Haley A. Vecchiarelli, Marie-Eve Tremblay
Summary: As individuals age, microglia, the resident immune cells of the central nervous system (CNS), become less effective at preserving brain circuits. Increases in microglial inflammatory activity are thought to contribute to age-related declines in cognitive functions and to transitions toward mild cognitive impairment (MCI) and Alzheimer's disease (AD). Preclinical and early phase clinical trials investigating the therapeutic effects of pharmacological agents acting on microglia are currently underway, but important questions about target selectivity and microglial heterogeneity remain unanswered.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Cell Biology
Michael J. Chrusch, Selena Fu, Simon C. Spanswick, Haley A. Vecchiarelli, Payal P. Patel, Matthew N. Hill, Richard H. Dyck
Summary: Zinc plays a role in modulating synaptic plasticity, particularly in the hippocampal dentate gyrus. This study aimed to determine if vesicular zinc is important for modulating adult hippocampal neurogenesis and behavior in an experience-dependent manner. The results show that vesicular zinc is essential for enhancing adult hippocampal neurogenesis and behavior following enrichment, supporting the role of zincergic neurons in experience-dependent plasticity in the hippocampus.
Article
Infectious Diseases
Melissa M. Cadelis, Liam R. Edmeades, Dan Chen, Evangelene S. Gill, Kyle Fraser, Florent Rouvier, Marie-Lise Bourguet-Kondracki, Jean Michel Brunel, Brent R. Copp
Summary: A series of naphthyl- and biphenyl-substituted polyamine conjugates were synthesized to search for new antimicrobials and antibiotic enhancers. Longer chain variants containing 1-naphthyl and 2-naphthyl capping groups showed strong intrinsic antimicrobial properties against MRSA and Cryptococcus neoformans. Some analogues in the set were able to enhance the antibiotic action of doxycycline and erythromycin towards Pseudomonas aeruginosa and Escherichia coli, with two analogues exhibiting more than 32-fold enhancement in activity. These findings suggest the potential of α,ω-disubstituted polyamines with 1-naphthyl- and 2-naphthyl-capping groups as non-toxic antibiotic enhancers.
Article
Chemistry, Medicinal
Melissa M. Cadelis, Tim Liu, Kenneth Sue, Florent Rouvier, Marie-Lise Bourguet-Kondracki, Jean Michel Brunel, Brent R. Copp
Summary: Antibiotic resistance is a growing global health threat. One approach to overcome this is to discover and develop new antibiotic enhancers that can enhance the efficacy of existing antibiotics against resistant bacteria.
Article
Biochemistry & Molecular Biology
Melissa M. Cadelis, Jisoo Kim, Florent Rouvier, Evangelene S. Gill, Kyle Fraser, Marie-Lise Bourguet-Kondracki, Jean Michel Brunel, Brent R. Copp
Summary: In this study, a set of analogues of ianthelliformisamine C were synthesized to investigate their antimicrobial activities and enhance the action of doxycycline against Pseudomonas aeruginosa. The results showed that the longest polyamine chain analogues without bromine atoms exhibited intrinsic antimicrobial activity, while all analogues with bromine atoms were active. However, many of these longer analogues showed cytotoxic and red blood cell hemolytic properties, limiting their potential as antimicrobial lead compounds. Two non-toxic, non-halogenated analogues were found to strongly enhance the action of doxycycline against P. aeruginosa.
Article
Biochemistry & Molecular Biology
Kenneth Sue, Melissa M. Cadelis, Evangelene S. Gill, Florent Rouvier, Marie-Lise Bourguet-Kondracki, Jean Michel Brunel, Brent R. Copp
Summary: In this study, a new class of indole-3-acetamido-polyamine conjugates were synthesized and evaluated for their antimicrobial activities. The compounds showed strong growth inhibition against methicillin-resistant Staphylococcus aureus and Cryptococcus neoformans, with minimum inhibitory concentrations typically less than 0.2 μM. Some of the derivatives also exhibited enhancement of antibiotic action against Pseudomonas aeruginosa and Escherichia coli.
Article
Microbiology
Kenneth Sue, Melissa M. Cadelis, Kerrin Hainsworth, Florent Rouvier, Marie-Lise Bourguet-Kondracki, Jean Michel Brunel, Brent R. Copp
Summary: Novel pleuromutilin-polyamine conjugates with broad-spectrum antimicrobial activity targeting both Gram-positive and Gram-negative bacteria as well as fungi have been developed, showing potential for combating microbial infections.