Highly Multiplexed Immunohistochemical MALDI-MS Imaging of Biomarkers in Tissues

Journal of the American Society for Mass Spectrometry, Journal Year: 2021, Volume and Issue: 32(4), P. 977 - 988

Published: Feb. 25, 2021

Immunohistochemistry (IHC) combined with fluorescence microscopy provides an important and widely used tool for researchers pathologists to image multiple biomarkers in tissue specimens. However, multiplex IHC using standard is generally limited 3–5 different biomarkers, hyperspectral or multispectral methods 8. We report the development of a new technology based on novel photocleavable mass-tags (PC-MTs) facile antibody labeling, which enables highly multiplexed MALDI mass spectrometric imaging (MALDI-IHC). This approach significantly exceeds multiplexity both fluorescence- previous cleavable mass-tag-based methods. Up 12-plex MALDI-IHC was demonstrated mouse brain, human tonsil, breast cancer tissues specimens, reflecting known molecular composition, anatomy, pathology targeted biomarkers. Novel dual-labeled fluorescent PC-MT antibodies label-free small-molecule greatly extend capability this approach. shows promise use fields pathology, diagnostics, therapeutics, precision medicine.

Language: Английский

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Repetitive Diffuse Mild Traumatic Brain Injury Causes an Atypical Astrocyte Response and Spontaneous Recurrent Seizures

Journal of Neuroscience, Journal Year: 2019, Volume and Issue: 39(10), P. 1944 - 1963

Published: Jan. 21, 2019

Focal traumatic brain injury (TBI) induces astrogliosis, a process essential to protecting uninjured areas from secondary damage. However, astrogliosis can cause loss of astrocyte homeostatic functions and possibly contributes comorbidities such as posttraumatic epilepsy (PTE). Scar-forming astrocytes seal focal injuries off healthy tissue. It is these glial scars that are associated with originating in the cerebral cortex hippocampus. vast majority human TBIs also present diffuse caused by acceleration-deceleration forces leading tissue shearing. The resulting damage may be intrinsically different lesions would trigger scar formation. Here, we used mice both sexes model repetitive mild/concussive closed-head TBI, which only induced injury, test hypothesis respond uniquely TBI sufficient PTE. Astrocytes did not form classic characterized upregulation fibrillary acidic protein was limited. Surprisingly, an unrelated population atypical reactive lack expression, rapid sustained downregulation proteins impaired coupling. After latency period, subset developed spontaneous recurrent seizures reminiscent PTE patients. Seizing had larger compared nonseizing mice, suggesting might contribute epileptogenesis after TBI. SIGNIFICANCE STATEMENT Traumatic acquired epilepsies. Reactive have long been patients, particularly focal/lesional injury. most include nonfocal, injuries. showed for development mice. We identified response coupling while markers or formation absent. Areas were animals later this one root

Language: Английский

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Aerobic exercise upregulates the BDNF-Serotonin systems and improves the cognitive function in rats

Neurobiology of Learning and Memory, Journal Year: 2018, Volume and Issue: 155, P. 528 - 542

Published: May 23, 2018

Language: Английский

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Pan-retinal ganglion cell markers in mice, rats, and rhesus macaques

动物学研究, Journal Year: 2022, Volume and Issue: 44(0), P. 1 - 23

Published: Jan. 1, 2022

Univocal identification of retinal ganglion cells (RGCs) is an essential prerequisite for studying their degeneration and neuroprotection. Before the advent phenotypic markers, RGCs were normally identified using retrograde tracing retinorecipient areas. This invasive technique, its use precluded in higher mammals such as monkeys. In past decade, several RGC markers have been described. Here, we reviewed analyzed specificity nine used to identify all or most RGCs, i.e., pan-RGC rats, mice, macaques. The best three species terms specificity, proportion labeled, indicators viability BRN3A, expressed by vision-forming RBPMS, vision- non-vision-forming RGCs. NEUN, often was non-RGCs cell layer, therefore not RGC-specific. γ-SYN, TUJ1, NF-L labeled axons, which impaired detection somas central retina but would be good morphology. TUJ1 also non-RGCs. BM88, ERRβ, PGP9.5 are rarely they rats macaques ERRβ mice. However, BM88 suitable viability.

Language: Английский

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Nano‐Brake Halts Mitochondrial Dysfunction Cascade to Alleviate Neuropathology and Rescue Alzheimer's Cognitive Deficits

Advanced Science, Journal Year: 2023, Volume and Issue: 10(7)

Published: Jan. 26, 2023

Abstract Mitochondrial dysfunction has been recognized as the key pathogenesis of most neurodegenerative diseases including Alzheimer's disease (AD). The dysregulation mitochondrial calcium ion (Ca 2+ ) homeostasis and permeability transition pore (mPTP), is a critical upstream signaling pathway that contributes to cascade in AD pathogenesis. Herein, “two‐hit braking” therapeutic strategy synergistically halt Ca overload mPTP opening put on brake proposed. To achieve this goal, magnesium (Mg ), natural antagonist, siRNA central regulator cyclophilin D (CypD), are co‐encapsulated into designed nano‐brake; A matrix metalloproteinase 9 (MMP9) activatable cell‐penetrating peptide (MAP) anchored surface nano‐brake overcome blood‐brain barrier (BBB) realize targeted delivery cells brain. Nano‐brake treatment efficiently halts cerebrovascular endothelial cells, neurons, microglia powerfully alleviates neuropathology rescues cognitive deficits. These findings collectively demonstrate potential advanced design nanotherapeutics pathways provide powerful for modifying therapy.

Language: Английский

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NSC-derived exosomes enhance therapeutic effects of NSC transplantation on cerebral ischemia in mice

eLife, Journal Year: 2023, Volume and Issue: 12

Published: April 27, 2023

Transplantation of neural stem cells (NSCs) has been proved to promote functional rehabilitation brain lesions including ischemic stroke. However, the therapeutic effects NSC transplantation are limited by low survival and differentiation rates NSCs due harsh environment in after Here, we employed derived from human induced pluripotent together with exosomes extracted treat cerebral ischemia middle artery occlusion/reperfusion mice. The results showed that NSC-derived significantly reduced inflammatory response, alleviated oxidative stress transplantation, facilitated vivo. combination ameliorated injury tissue infarction, neuronal death, glial scarring, promoted recovery motor function. To explore underlying mechanisms, analyzed miRNA profiles potential downstream genes. Our study provided rationale for clinical application as a supportive adjuvant

Language: Английский

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Queuosine‐tRNA promotes sex‐dependent learning and memory formation by maintaining codon‐biased translation elongation speed

The EMBO Journal, Journal Year: 2023, Volume and Issue: 42(19)

Published: Aug. 23, 2023

Abstract Queuosine (Q) is a modified nucleoside at the wobble position of specific tRNAs. In mammals, queuosinylation facilitated by queuine uptake from gut microbiota and introduced into tRNA QTRT1‐QTRT2 enzyme complex. By establishing Qtrt1 knockout mouse model, we discovered that loss Q‐tRNA leads to learning memory deficits. Ribo‐Seq analysis in hippocampus ‐deficient mice revealed not only stalling ribosomes on Q‐decoded codons, but also global imbalance translation elongation speed between codons engage weak strong interactions with their cognate anticodons. While Q‐dependent molecular behavioral phenotypes were identified both sexes, female affected more severely than males. Proteomics confirmed deregulation synaptogenesis neuronal morphology. Together, our findings provide link modification brain functions reveal an unexpected role protein synthesis sex‐dependent cognitive performance.

Language: Английский

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An Antisense Oligonucleotide-Loaded Blood–Brain Barrier Penetrable Nanoparticle Mediating Recruitment of Endogenous Neural Stem Cells for the Treatment of Parkinson’s Disease

ACS Nano, Journal Year: 2023, Volume and Issue: 17(5), P. 4414 - 4432

Published: Jan. 23, 2023

Parkinson's disease (PD) is a neurodegenerative characterized by the death of dopaminergic (DA) neurons and currently cannot be cured. One selected antisense oligonucleotide (ASO) reported to effective for treatment PD. However, ASO usually intrathecally administered lumbar puncture into cerebral spinal fluid, through which risks highly invasive neurosurgery are major concerns. In this study, ZAAM, an ASO-loaded, aptamer Apt 19S-conjugated, neural stem cell membrane (NSCM)-coated nanoparticle (NP), was developed targeted NSCM facilitated blood–brain barrier (BBB) penetration NPs, both 19S promoted recruitment cells (NSCs) toward PD site DA neuron regeneration. The behavioral tests demonstrated that ZAAM improved efficacy on delivery NSCs. This work heuristic report (1) nonchemoattractant induced endogenous NSC recruitment, (2) NSCM-coated nanoparticles diseases, (3) systemic These findings provide insights development biomimetic BBB penetrable drug carriers precise diagnosis therapy central nervous system diseases.

Language: Английский

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The The Green Synthesis of Copper Oxide Nanoparticles Using the Moringa Oleifera Plant and its Subsequent Characterization for Use in Energy Storage Applications

East European Journal of Physics, Journal Year: 2023, Volume and Issue: 1, P. 162 - 172

Published: March 2, 2023

In this study, we describe the environmentally friendly synthesis of copper oxide (CuO) and its subsequent characterization for use in supercapacitors. Using extracts from dried, finely ground Moringa Oleifera as reducing/capping agent, created CuO NP. The produced NPs were then examined using X-ray Diffractometer (XRD), Ultraviolet-Visible spectroscopy, energy dispersive spectroscopy (EDS), scanning electron microscopy (SEM). Electrochemical analysis techniques like cyclic voltammetry (CV) electrochemical impedance (EIS) review utilized to look at behavior CuO-based electrodes. that followed determined green synthesize displayed supercapacitive behavior. This suggests synthesized will naturally encourage application electrodes because it has been found absorbance varies linearly with concentration, 0.6 moles highest reading 0.35 398 nm. reflection spectra demonstrate material exhibits low reflectance properties medium ultraviolet region. However, move toward visible light region, rises maximum value 16 percent short calculated crystallite sizes are follows: 0.2 mols NP, 0.3 0.4 0.5 NP 43.14 nm, 43.68 24.23 5.70 12.87 respectively, where Average D = 25.93 nm is average crystalline size across all samples. emergence cubic grains resemble nanorods tube-like holes, SEM images can be distinguished one another seen mole NPs.

Language: Английский

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Neuronal cell cycle reentry events in the aging brain are more prevalent in neurodegeneration and lead to cellular senescence

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(4), P. e3002559 - e3002559

Published: April 23, 2024

Increasing evidence indicates that terminally differentiated neurons in the brain may recommit to a cell cycle-like process during neuronal aging and under disease conditions. Because of rare existence random localization these cells brain, their molecular profiles disease-specific heterogeneities remain unclear. Through bioinformatics approach allows integrated analyses multiple single-nucleus transcriptome datasets from human samples, populations were identified selected for further characterization. Our indicated cycle-related events occur predominantly excitatory cellular senescence is likely immediate terminal fate. Quantitatively, number cycle re-engaging senescent decreased normal process, but context late-onset Alzheimer's (AD), accumulate instead. Transcriptomic profiling suggested differences tied early stage revealing presented more proinflammatory, metabolically deregulated, pathology-associated signatures disease-affected brains. Similarly, general features also observed subpopulation dopaminergic Parkinson's (PD)-Lewy body dementia (LBD) model. An extended analysis conducted mouse model validated ability this determine robust relationship between processes cross-species setting.

Language: Английский

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