Investigation into Drug-Induced Liver Damage Using Multimodal Mass Spectrometry Imaging.

Drug toxicity during the development of candidate pharmaceuticals is the leading cause of discontinuation in preclinical drug discovery and development. Traditionally, the cause of the toxicity is often determined by histological examination, clinical pathology, and the detection of drugs and/or metabolites by liquid chromatography-mass spectrometry (LC-MS). While these techniques individually provide information on the pathological effects of the drug and the detection of metabolites, they cannot provide specific molecular spatial information without additional experiments.

Synthesis and Characterization of Poly(ethylene furanoate)/Poly(ε-caprolactone) Block Copolymers.

Biobased poly(ethylene furanoate) (PEF)/poly(ε-caprolactone) (PCL) block copolymers have been synthesized using ring opening polymerization (ROP) of ε-caprolactone (ε-CL) in the presence of PEF in different mass ratios. An increase in intrinsic viscosity is observed for the block copolymers with higher ε-CL content due to the extension of their macromolecular chain. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MS) was employed to understand the composition and structure of the produced block copolymers.

ToF-SIMS Parallel Imaging MS/MS of Lead Soaps in Embedded Paint Cross Sections.

In the field of cultural heritage, and more specifically in oil paintings, the ability to unambiguously identify and locate metal soaps is of great interest for a better understanding of painting degradation. Here, we demonstrate the use of a Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) instrument capable of tandem mass spectrometry imaging for the unambiguous identification and localization of lead soaps in cross sections of samples of old oil paintings at high spatial resolution. It is shown that the specific fragmentation pattern of lead soaps is dictated by the loss of the lead ion and that fragmentation occurs on the hydrocarbon chains of the fatty acids.

How can MSI enhance our understanding of ASO distribution?

In the dynamic field of drug discovery and development, a comprehensive understanding of drug absorption, distribution, metabolism, excretion, and toxicity is crucial. Mass spectrometry imaging (MSI) has become a key analytical tool in the pharmaceutical industry, allowing evaluation of drug biodistribution and molecular profiles. Antisense oligonucleotides (ASOs) are emerging drug candidates for treating neurologic diseases.

Mass Spectrometry Imaging for Spatial Ingredient Classification in Plant-Based Food.

Mass spectrometry imaging (MSI) techniques enable the generation of molecular maps from complex and heterogeneous matrices. A burger patty, whether plant-based or meat-based, represents one such complex matrix where studying the spatial distribution of components can unveil crucial features relevant to the consumer experience or production process. Furthermore, the MSI data can aid in the classification of ingredients and composition.

Patient-responsive protein biomarkers for cartilage degeneration and repair identified in the infrapatellar fat pad.

Objectives: Cartilage defects (CDs) are regarded as early manifestation of osteoarthritis (OA). The infrapatellar fat pad (IPFP) is an important mediator in maintaining joint homeostasis, disease progression and tissue repair, with a crucial role of its secreted proteins. Here, we investigate the proteome of the IPFP in relation to clinical status and response to surgical treatment of CDs.

Improvements in Fast Mass Microscopy for Large-Area Samples.

Mass spectrometry imaging (MSI) is a technique that analyzes the chemical information and spatial distribution of surface analytes. Most MSI studies are conducted in microprobe mode, in which a mass spectrum is collected for each pixel to create a mass image. Thus, the spatial resolution, sample imaging area, and imaging speed are linked.

Processing Next-Generation Mass Spectrometry Imaging Data: Principal Component Analysis at Scale.

Mass spectrometry imaging (MSI) is constantly improving in spatial resolving power, throughput and mass resolution. Although beneficial, these improvements increase data set size and content. The larger data requires correspondingly fast computer-based analyses.

MALDI MSI Protocol for Spatial Bottom-Up Proteomics at Single-Cell Resolution.

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) started with spatial mapping of peptides and proteins. Since then, numerous bottom-up protocols have been developed. However, achievable spatial resolution and sample preparation with many wet steps hindered the development of single cell-level workflows for bottom-up spatial proteomics.

Lipid analysis of human primary dermal fibroblasts and epidermal keratinocytes after near-infrared exposure using mass spectrometry imaging.

Photobiomodulation (PBM) therapy is the application of near-infrared (NIR) exposure to injuries or lesions to (among others) improve wound healing, reduce inflammation, and decreases acute and chronic pain. However, the understanding of the molecular mechanism of PBM, more specifically the effects of NIR on skin cells is still lacking behind. Lipids are essential components of cellular membranes that are integral to skin structure and function.

Facilitating microplastic ingestion in aquatic models: A verified protocol for daphnia magna as a trojan horse vector.

Microplastic pollution poses a significant environmental threat due to its persistence, widespread distribution, and inherent toxic potential. Despite the increasing number of publications in this field, a standardized protocol for the laboratory intake of microplastics by has yet to be established. In this study, we introduce a verified protocol designed to facilitate the ingestion of microplastic particles (MPs) by , ranging in size from 5-55 µm.

Testing of rapid evaporative mass spectrometry for histological tissue classification and molecular diagnostics in a multi-site study.

Background: While REIMS technology has successfully been demonstrated for the histological identification of ex-vivo breast tumor tissues, questions regarding the robustness of the approach and the possibility of tumor molecular diagnostics still remain unanswered. In the current study, we set out to determine whether it is possible to acquire cross-comparable REIMS datasets at multiple sites for the identification of breast tumors and subtypes.

Methods: A consortium of four sites with three of them having access to fresh surgical tissue samples performed tissue analysis using identical REIMS setups and protocols.

Mass spectrometry imaging in plants, microbes, and food: a review.

Plant health, which affects the nutritional quality and safety of derivative food products, is influenced by symbiotic interactions with microorganisms. These interactions influence the local molecular profile at the tissue level. Therefore, studying the distribution of molecules within plants, microbes, and plant-based food is crucial to assess plant health, ensure the safety and quality of the agricultural products that become part of our food supply, and plan agricultural management practices.

Combined matrix-assisted laser desorption/ionisation-mass spectrometry imaging with liquid chromatography-tandem mass spectrometry for observing spatial distribution of lipids in whole Caenorhabditis elegans.

Rationale: Matrix-assisted laser desorption/ionisation-mass spectrometry imaging (MALDI-MSI) is a powerful label-free technique for biomolecule detection (e.g., lipids), within tissue sections across various biological species.

Biosynthesis and differential spatial distribution of the 3-deoxyanthocyanidins apigenidin and luteolinidin at the interface of a plant-cyanobacteria symbiosis exposed to cold.

Aquatic ferns of the genus Azolla (Azolla) form highly productive symbioses with filamentous cyanobacteria fixing N in their leaf cavities, Nostoc azollae. Stressed symbioses characteristically turn red due to 3-deoxyanthocyanidin (DA) accumulation, rare in angiosperms and of unknown function. To understand DA accumulation upon cold acclimation and recovery, we integrated laser-desorption-ionization mass-spectrometry-imaging (LDI-MSI), a new Azolla filiculoides genome-assembly and annotation, and dual RNA-sequencing into phenotypic analyses of the symbioses.

Inflammation-associated intramyocellular lipid alterations in human pancreatic cancer cachexia.

Background: Cancer cachexia is a multifactorial metabolic syndrome characterized by systemic inflammation and ongoing skeletal muscle loss resulting in weakness, poor quality of life, and decreased survival. Whereas lipid accumulation in skeletal muscle is associated with cancer cachexia as well as the prognosis of cancer patients, surprisingly little is known about the nature of the lipids that accumulate in the muscle during cachexia, and whether this is related to inflammation. We aimed to identify the types and distributions of intramyocellular lipids in patients with and without cancer cachexia.

Mass Spectrometry Reveals Molecular Effects of Citrulline Supplementation during Bone Fracture Healing in a Rat Model.

Bone fracture healing is a complex process in which specific molecular knowledge is still lacking. The citrulline-arginine-nitric oxide metabolism is one of the involved pathways, and its enrichment via citrulline supplementation can enhance fracture healing. This study investigated the molecular effects of citrulline supplementation during the different fracture healing phases in a rat model.

Spatial omics reveals molecular changes in focal cortical dysplasia type II.

Focal cortical dysplasia (FCD) represents a group of diverse localized cortical lesions that are highly epileptogenic and occur due to abnormal brain development caused by genetic mutations, involving the mammalian target of rapamycin (mTOR). These somatic mutations lead to mosaicism in the affected brain, posing challenges to unravel the direct and indirect functional consequences of these mutations. To comprehensively characterize the impact of mTOR mutations on the brain, we employed here a multimodal approach in a preclinical mouse model of FCD type II (Rheb), focusing on spatial omics techniques to define the proteomic and lipidomic changes.

Mass spectrometry imaging reveals flavor distribution in edible mushrooms.

Unlabelled: The spatial distribution of molecules and compounds responsible for the flavor profile of edible button mushrooms () has never been determined. The food industry is interested in knowing the localization of these compounds. Such knowledge would enable extraction of flavor compounds from a particular regions of the mushroom, which is safer for consumption compared to alternatives such as synthetic flavoring agents.

MALDI-MSI-LC-MS/MS Workflow for Single-Section Single Step Combined Proteomics and Quantitative Lipidomics.

We introduce a novel approach for comprehensive molecular profiling in biological samples. Our single-section methodology combines quantitative mass spectrometry imaging (Q-MSI) and a single step extraction protocol enabling lipidomic and proteomic liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis on the same tissue area. The integration of spatially correlated lipidomic and proteomic data on a single tissue section allows for a comprehensive interpretation of the molecular landscape.

Untargeted metabolomics for lifestyle biomarker discovery in human hair.

There is a risk of crimes remaining unsolved when no matching DNA profiles or fingermarks are found. If this is the case, forensic investigations are faced with a significant shortage of evidence and information regarding the unknown perpetrator and/or victim as well as any missing persons. However, a rather commonly found biological trace encountered at crime scenes is human hair.

Spatial Neurolipidomics at the Single Amyloid-β Plaque Level in Postmortem Human Alzheimer's Disease Brain.

Lipid dysregulations have been critically implicated in Alzheimer's disease (AD) pathology. Chemical analysis of amyloid-β (Aβ) plaque pathology in transgenic AD mouse models has demonstrated alterations in the microenvironment in the direct proximity of Aβ plaque pathology. In mouse studies, differences in lipid patterns linked to structural polymorphism among Aβ pathology, such as diffuse, immature, and mature fibrillary aggregates, have also been reported.

Spatial Metabolomics Identifies LPC(18:0) and LPA(18:1) in Advanced Atheroma With Translation to Plasma for Cardiovascular Risk Estimation.

Background: The metabolic alterations occurring within the arterial architecture during atherosclerosis development remain poorly understood, let alone those particular to each arterial tunica. We aimed first to identify, in a spatially resolved manner, the specific metabolic changes in plaque, media, adventitia, and cardiac tissue between control and atherosclerotic murine aortas. Second, we assessed their translatability to human tissue and plasma for cardiovascular risk estimation.