Article
Chemistry, Analytical
Nicole Strittmatter, Frances M. Richards, Alan M. Race, Stephanie Ling, Daniel Sutton, Anna Nilsson, Yann Wallez, Jennifer Barnes, Gareth Maglennon, Aarthi Gopinathan, Rebecca Brais, Edmond Wong, Maria Paola Serra, James Atkinson, Aaron Smith, Joanne Wilson, Gregory Hamm, Timothy Johnson, Charles R. Dunlop, Brajesh P. Kaistha, Josephine Bunch, Owen J. Sansom, Zoltan Takats, Per E. Andren, Alan Lau, Simon T. Barry, Richard J. A. Goodwin, Duncan Jodrell
Summary: Gemcitabine distribution and metabolism were assessed using a multimodal imaging approach, revealing that active metabolites primarily reached tumor cell compartments, while an ATR inhibitor targeted nonviable tumor regions.
ANALYTICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
John P. McGee, Pei Su, Kenneth R. Durbin, Michael A. R. Hollas, Nicholas W. Bateman, G. Larry Maxwell, Thomas P. Conrads, Ryan T. Fellers, Rafael D. Melani, Jeannie M. Camarillo, Jared O. Kafader, Neil L. Kelleher
Summary: This study introduces a semi-automated single-ion mass spectrometry workflow for top-down tandem mass spectrometry analysis directly from tissue microenvironments. The results demonstrate that this method can identify multiple proteoforms in tumor samples within a short period of time, and effectively identify proteoform signatures in tumor and stromal regions.
NATURE COMMUNICATIONS
(2023)
Review
Chemistry, Analytical
Katerina V. Djambazova, Jacqueline M. Van Ardenne, Jeffrey M. Spraggins
Summary: Imaging mass spectrometry allows for the untargeted mapping of biomolecules directly from tissue sections, with widespread clinical applicability in disease diagnosis and classification. This review summarizes the two most widely employed IMS technologies and their advancements in biomedical applications.
TRAC-TRENDS IN ANALYTICAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Zari Saadati Nezhad, Juan Pablo Salazar, Rachel S. Pryce, Lisa M. Munter, Pierre Chaurand
Summary: Cholesterol is crucial for animal life and is dysregulated in many diseases. A new method using silver-assisted laser desorption ionization mass spectrometry imaging (AgLDI MSI) has been developed for absolute quantification of cholesterol in brain samples, providing better insight into the role of cholesterol in disease onset and progression.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Analytical
Ardalan Chaichi, Syed Mohammad Abid Hasan, Nishir Mehta, Fabrizio Donnarumma, Philip Ebenezer, Kermit K. Murray, Joseph Francis, Manas Ranjan Gartia
Summary: Post-traumatic stress disorder (PTSD) is a severe psychiatric injury that can lead to life-threatening symptoms. A novel method utilizing Raman mapping provides quantitative results on lipid alterations in the brain region affected by PTSD, offering valuable insights into the mechanisms of this disorder.
Article
Chemistry, Analytical
Alan M. Race, Daniel Sutton, Gregory Hamm, Gareth Maglennon, Jennifer P. Morton, Nicole Strittmatter, Andrew Campbell, Owen J. Sansom, Yinhai Wang, Simon T. Barry, Zoltan Takats, Richard J. A. Goodwin, Josephine Bunch
Summary: The article introduces a generic method for extracting information from different modalities using annotations from one microscopy modality and presents a fast, general multimodal registration workflow for automatic alignment of complex data sets. Experimental results demonstrate that the proposed methods help better understand tumor heterogeneity and the tumor microenvironment.
ANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Analytical
Zdravko Siketic, Iva Bogdanovic Radovic, Marko Barac, Marko Brajkovic, Marijana Popovic Hadzija
Summary: MeV SIMS is a type of secondary ion mass spectrometry (SIMS) technique that uses MeV energy ions to desorb molecules from a sample surface. This study presents a new system for molecular imaging of organic materials using a continuous analytical beam and a start trigger based on the detection of secondary electrons. The system allows for the imaging of samples with a lateral resolution of about 20 μm and the analysis of samples of any thickness. The imaging capabilities of MeV SIMS are demonstrated on various samples to show its potential applications in biology and forensic science.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Zhidan Liang, Morgan B. Giles, Mallory J. Stenslik, Maureen Marsales, James D. Ormes, Ray Seto, Wendy Zhong
Summary: This study presents a novel application of matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) for visualizing the drug release process from non-conductive polymeric LAP implants. The researchers developed a new sample surface treatment procedure to obtain homogeneous imaging of non-conductive sample surfaces. This work is the first comprehensive report of a sample preparation methodology tailored for imaging LAP at the molecular level.
ANALYTICA CHIMICA ACTA
(2022)
Article
Biochemical Research Methods
Carla Harkin, Karl W. Smith, C. Logan MacKay, Tara Moore, Simon Brockbank, Mark Ruddock, Diego F. Cobice
Summary: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. This study used mass spectrometry imaging (MSI) to localize and analyze reactive aldehydes (RAs) in the kidney tissues of a diabetic mouse model. The results identified potential biomarkers of DN and demonstrated the capability of MSI for detection and localization of poorly ionizable molecules by adapting existing chemical derivatization methods.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2022)
Review
Chemistry, Analytical
Jonatan Riber Granborg, Anne Mette Handler, Christian Janfelt
Summary: New mass spectrometry imaging (MSI) techniques are gaining importance in various stages of drug discovery and development, as well as in fundamental studies of drug delivery. MSI provides high selectivity and enables simultaneous imaging of drugs, metabolites, and endogenous biomarkers. This review focuses on the application of MSI in drug imaging, particularly in drug distribution and metabolism studies. It covers the principles of MSI, sample preparation, data analysis, and quantitative MSI. The review also presents examples of pharmaceutical applications of MSI, highlighting its contribution to obtaining information not readily obtainable by conventional analytical techniques. The paper concludes with an overview of ongoing trends in MSI and future directions.
TRAC-TRENDS IN ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Analytical
Hualei Xu, Qichen Hao, Haiqiang Liu, Lulu Chen, Ran Wu, Liang Qin, Hua Guo, Jinrong Li, Chenyu Yang, Hao Hu, Kun Xue, Jinchao Feng, Yijun Zhou, Biao Liu, Gaopeng Li, Xiaodong Wang
Summary: A new method named concentration-descending washing strategy (CDWS) with methanol (MeOH) was successfully developed to enhance the detection and imaging of endogenous proteins in tissues using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Compared to commonly used washing strategies, MeOH-CDWS significantly improved the number and intensity of protein ion signals and reduced protein delocalization, resulting in improved quality of protein images in tissue sections through MALDI-MSI.
Article
Chemistry, Multidisciplinary
Eva Illes-Toth, Oliver J. Hale, James W. Hughes, Nicole Strittmatter, Jonathan Rose, Ben Clayton, Rebecca Sargeant, Stewart Jones, Andreas Dannhorn, Richard J. A. Goodwin, Helen J. Cooper
Summary: This study demonstrates for the first time the in situ mass spectrometry analysis of a non-covalent protein-drug complex formed in vivo, and provides a direct route for target-drug characterization in early stage drug discovery by spatial mapping across liver tissue.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Deqing Zhao, Ping Yu, Bingjun Han, Fei Qiao
Summary: Mass spectrometry imaging is a rapidly developing molecular imaging technique. Air flow-assisted ionization mass spectrometry imaging (AFAI-MSI) has gained attention in the biomedical field for its features such as high sensitivity and wide coverage of metabolite detection without the need for sample pretreatment. This study established a mass spectrometry imaging method for analyzing low molecular metabolites in mango fruits using the AFAI-MSI method. The distribution of various compounds in mango tissue was analyzed, providing a convenient and direct approach for the analysis of endogenous metabolites in mango fruits.
Article
Chemistry, Analytical
Andreas Dannhorn, Stephanie Ling, Steven Powell, Eileen McCall, Gareth Maglennon, Gemma N. Jones, Andrew J. Pierce, Nicole Strittmatter, Gregory Hamm, Simon T. Barry, Josephine Bunch, Richard J. A. Goodwin, Zoltan Takats
Summary: A decontamination approach using UV-C light was presented in this study to inactivate clinically relevant pathogens without causing damage to the tissue metabolome and xenobiotics, allowing for the study of the biodistribution of endogenous metabolites. Additionally, spatially integrated abundances of ATR inhibitor ceralasertib from decontaminated human biopsies were determined using DESI-MSI.
ANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Analytical
Madisson Chabas, Olivier Pible, Jean Armengaud, Beatrice Alpha-Bazin
Summary: To accurately and rapidly identify microorganisms from complex microbiota for clinical diagnostic purposes, an innovative label-free multiplexing method for the identification of microorganisms using tandem mass spectrometry is proposed in this paper. The method involves offline reversed-phase fractionation of individual peptidomes and achieves multiplexing by mixing fractions of staged hydrophobicity. This approach enables the identification of up to 21 microorganisms in a single 60-minute run without the use of labeling reagents, providing new perspectives for high-throughput proteotyping of bacteria in large culturomics projects.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Zheng Ao, Hongwei Cai, Zhuhao Wu, Jonathan Krzesniak, Chunhui Tian, Yvonne Y. Lai, Ken Mackie, Feng Guo
Summary: The study introduces a human spinal organoid-on-a-chip device for modeling the biology and electrophysiology of human nociceptive neurons and dorsal horn interneurons. The device allows for testing nociceptive modulators and is cost-efficient, scalable, and easy to use. By integrating human sensory-spinal-cord organoids, the method shows promise for screening and validating novel therapeutics for human pain medicine discovery.
ANALYTICAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Ming Tatt Lee, Ken Mackie, Lih-Chu Chiou
Summary: This review explores the potential and contributions of activating the endocannabinoid system and peripheral neuromodulation in opioid tolerance.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Neurosciences
Miguel Garzon, June Chan, Ken Mackie, Virginia M. Pickel
Summary: Chronic administration of Delta-9-THC during adolescence can lead to adaptive changes in adult social and cognitive functions controlled by the PL-PFC. Activation of CB1Rs by Delta-9-THC can regulate memory and learning processes through M2R receptors. The study found that Delta-9-THC increases plasmalemmal expression of M2Rs in large dendrites and decreases cytoplasmic expression of M2Rs in small spines of the PL-PFC.
Article
Pharmacology & Pharmacy
Lawrence M. Carey, Zhili Xu, Gabriela Rajic, Alexandros Makriyannis, Julian Romero, Cecilia Hillard, Ken Mackie, Andrea G. Hohmann
Summary: This study suggests that CB2 activation may alleviate HIV-associated antiretroviral neuropathy and identifies a previously unreported mechanism through which CB2 activation produces antinociceptive efficacy. The study also demonstrates that a CB2 agonist can reverse established morphine tolerance and shows that CB2 localized to peripheral sensory neurons mediates the opioid tolerance sparing efficacy of CB2 agonists.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Toni Kline, Cong Xu, Faith R. Kreitzer, Dow P. Hurst, Khalil M. Eldeeb, Jim Wager-Miller, Kathleen Olivas, Seon A. Hepburn, John W. Huffman, Ken Mackie, Allyn C. Howlett, Patricia Reggio, Nephi Stella
Summary: The author synthesized fourteen novel alkylindole analogues and evaluated their activities at alkylindole-sensitive GPCRs. They found three characteristics that favor binding to alkylindole-sensitive GPCRs versus CB1R/CB2R and identified novel chemical tools for studying alkylindole-sensitive GPCRs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Toxicology
Jinhwan Lim, Hye-Lim Lee, Julie Nguyen, Joyce Shin, Samantha Getze, Caitlin Quach, Erica Squire, Kwang-Mook Jung, Stephen Mahler, Ken Mackie, Daniele Piomelli, Ulrike Luderer
Summary: Adolescent exposure to THC may cause aberrant activation of the ovarian endocannabinoid system in female mice, resulting in substantial loss of ovarian reserve in adulthood. Further investigation is needed to understand the relevance of these findings to women who frequently used cannabis during adolescence.
TOXICOLOGICAL SCIENCES
(2023)
Article
Engineering, Biomedical
Hongwei Cai, Zheng Ao, Chunhui Tian, Zhuhao Wu, Connor Kaurich, Zi Chen, Mingxia Gu, Andrea G. Hohmann, Ken Mackie, Feng Guo
Summary: Opioids may induce tolerance and hyperalgesia, but the human mechanisms underlying these effects are not well understood. Researchers have developed a novel human spinal microphysiological system (MPS) to model human nociception and opioid-induced tolerance. This system shows promising potential for studying pain etiology, screening new treatments, and validating novel therapeutics for human pain medicine.
BIOACTIVE MATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Jonah E. Zarrow, Abdul-Musawwir Alli-Oluwafuyi, Cristina M. Youwakim, Kwangho Kim, Andrew N. Jenkins, Isabelle C. Suero, Margaret R. Jones, Zahra Mashhadi, Ken Mackie, Alex G. Waterson, Amanda C. Doran, Gary A. Sulikowski, Sean S. Davies
Summary: N-Acyl-phosphatidylethanolamine hydrolyzing phospholipase D (NAPE-PLD) is an enzyme that hydrolyzes N-acyl-phosphatidylethanolamines (NAPEs) to produce N-acyl-ethanolamines (NAEs) and phosphatidic acid. Reduced NAPE-PLD activity is associated with cardiometabolic diseases, and small molecule activators of NAPE-PLD could be a potential therapeutic treatment. A series of benzothiazole phenylsulfonyl-piperidine carboxamides were identified as NAPE-PLD activators, which increased efferocytosis by macrophages. These findings suggest the importance of NAPE-PLD in regulating efferocytosis and the potential use of NAPE-PLD activators for treating cardiometabolic diseases.
ACS CHEMICAL BIOLOGY
(2023)
Article
Neurosciences
Kelsey G. Guenther, Zhili Xu, Julian Romero, Cecilia J. Hillard, Ken Mackie, Andrea G. Hohmann
Summary: CB2 agonists can suppress pathological pain in animal models without unwanted side effects associated with CB1 receptor activation. However, the specific types of pain responsive to CB2 agonists and the cell types underlying therapeutic efficacy are not fully understood.
Article
Pharmacology & Pharmacy
Axel Bernabeu, Anissa Bara, Michelle N. Murphy Green, Antonia Manduca, Jim Wager-Miller, Milene Borsoi, Olivier Lassalle, Anne-Laure Pelissier-Alicot, Pascale Chavis, Ken Mackie, Olivier J. J. Manzoni
Summary: This study reveals sex differences in the maturational trajectories of the rat prefrontal cortex (PFC). The excitability of PFC neurons is lower in adult females compared to other developmental stages. The gene expression of the endocannabinoid/vanilloid systems is sequential and sex-specific.
CANNABIS AND CANNABINOID RESEARCH
(2023)
Correction
Clinical Neurology
Mei Hu, Dexiao Zhu, Jian Zhang, Fei Gao, Jack Hashem, Philip Kingsley, Lawrence J. Marnett, Ken Mackie, Chu Chen
Article
Pharmacology & Pharmacy
Pedro Henrique Gobira, Jacob LaMar, Jade Marques, Ariandra Sartim, Kennia Silveira, Luana Santos, Gregers Wegener, Francisco S. Guimaraes, Ken Mackie, Hui-Chen Lu, Samia Joca
Summary: This study investigates the involvement of cannabinoid type 1 receptors (CB1R) in the antidepressant and psychostimulant effects induced by ketamine. The results suggest that CB1R mediate the psychostimulant side effects of ketamine, but do not play a role in its antidepressant properties. Furthermore, pharmacological blockade of CB1R has similar antidepressant effects, but does not potentiate the effects of ketamine.
CANNABIS AND CANNABINOID RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Joanna Winstone, Hana Shafique, Madeleine E. Clemmer, Ken Mackie, Jim Wager-Miller
Summary: This study found changes in BDNF mRNA expression in the hippocampus of adolescent mice exposed to THC and CBD. THC represses transcript expression for some BDNF variants, and this effect is rescued when CBD is co-administered. Sex differences were observed in specific BDNF isoforms.
CANNABIS AND CANNABINOID RESEARCH
(2023)
Article
Clinical Neurology
Mei Hu, Dexiao Zhu, Jian Zhang, Fei Gao, Jack Hashem, Philip Kingsley, Lawrence J. Marnett, Ken Mackie, Chu Chen
Summary: Traumatic brain injury is a risk factor for Alzheimer's disease and dementia. In this study, the researchers found that inhibiting monoacylglycerol lipase can reduce neuropathology caused by traumatic brain injury. The neuroprotective effects are mainly due to the inhibition of 2-arachidonoylglycerol metabolism in astrocytes, and not in neurons.
Article
Pharmacology & Pharmacy
Izaque de Sousa Maciel, Gabriel H. D. de Abreu, Claire T. Johnson, Rida Bonday, Heather B. Bradshaw, Ken Mackie, Hui-Chen Lu
Summary: The study using mice found that perinatal cannabinoid exposure affects behaviors in a sex-dependent manner, altering repetitive and hedonic behaviors. Additionally, perinatal exposure to THC or CBD prevents fluoxetine from enhancing coping behavior.
CANNABIS AND CANNABINOID RESEARCH
(2022)