Elucidating the molecular pathology of DEPDC5 mutation induced mTOR-hyperactivation associated with epilepsy and autism spectrum disorder DOI Creative Commons

Mattson Jones

Published: Jan. 1, 2022

Patients harboring mutations in the gene DEPDC5 often display variations of neurological diseases including epilepsy, autism spectrum disorders (ASD) and other neuro-architectural alterations. protein has been identified as an amino acid sensor responsible for negatively regulating mechanistic target rapamycin (mTOR), a central regulator cell growth homeostasis. Often, result mTOR hyperactivity leading to abnormal neuronal phenotypes generation excitatory/inhibitory imbalances animal models. Complete knockout (KO) results death shortly after birth, while inhibition activity recovers postnatal (Marsan et al. 2016). However, heterozygous DEPDC5-KOs animals have variable their disease during adulthood indicating developmental differences between subspecies early development mechanisms which could be impactful on outcome diseases. To understand underlying development, novel primary human neural progenitor line extracted from fetal tissue was characterized proliferation differentiation. CRISPR-Cas9 induced resulted hyperphosphorylation signaling processes rapid expansion population Analysis transcriptome data deregulation amongst p53 signaling, ribosome biogenesis, nucleotide lipid synthesis well degradation pathways due loss DEPDC5. Disease datasets correlation Tuberous Sclerosis being more closely associated with also finding overlap some ASD epilepsy genes. By using inhibitor rapamycin, substantial amount deregulated network recovered reversing differentiation caused by Though we saw increased dendritic arborization subsequent decreases dendrite lengths soma sizes, failed recover these effects suggesting independent produced DEPDC5-KO. This study provides new insights relationship functional, genomic deregulatory networks it intertwines humans highlights that pathomechanisms are not fully related hyperactivation, but include processes. sheds light question why treatment only partially restores gives insight treatments patients.

Language: Английский

Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) in disease diagnosis: an overview DOI
Bharath Sampath Kumar

Analytical Methods, Journal Year: 2023, Volume and Issue: 15(31), P. 3768 - 3784

Published: Jan. 1, 2023

Illustration of critical keywords pertaining to ambient mass spectrometry imaging in disease diagnosis research.

Language: Английский

Citations

27
Reactivity of Olanzapine and Tricyclic Antidepressants on the Protective Effects of Trolox on Lipid Peroxidation Evaluated Using Fluorescence Anisotropy, Electron Paramagnetic Resonance Spectrometry, and Thermal Analysis DOI Creative Commons

Yusuke Horizumi,

Reo Tanada,

Yuya Kurosawa

et al.

ACS Chemical Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Multiacting receptor-targeting antipsychotics and tricyclic antidepressants stimulate various neurotransmitter receptors despite the different targets of postsynaptic presynaptic reuptake transporters. Their auxiliary adverse effects may be caused by multiple or modification neuronal membrane. To evaluate membrane responses to olanzapine, imipramine, desipramine, amitriptyline, lidocaine, dibucaine, we examined inhibition lipid peroxidation in egg yolk phosphatidylcholine liposomes. By contrast, their on fluidity were measured as suppressive contributions inhibitory activity Trolox oxidation. These drugs inhibit exclude harmful reactive oxygen species protective effect Trolox. The fluorescence anisotropy 1,6-diphenyl-1,3,5-hexatriene saturated phospholipid liposome-containing suggested that dibucaine enhanced fluidity. radical scavenging 2,2-diphenylpicrylhidrazyl galvinoxyl radicals was determined using electron paramagnetic resonance experiments, molecular flexibility thermograms for differential scanning calorimetry. Multiple regression analyses linear free energy relationship approach comparative investigations revealed membranous liposomes, independent drugs, induced peroxidation. We discussed how these act nervous membranes aimed identify between uncertified functions

Language: Английский

Citations

1
Applications of ambient ionization mass spectrometry in 2021: An annual review DOI
Stephanie Rankin‐Turner, James C. Reynolds, Matthew A. Turner

et al.

Analytical Science Advances, Journal Year: 2022, Volume and Issue: 3(3-4), P. 67 - 89

Published: March 20, 2022

Ambient ionization mass spectrometry (AIMS) has revolutionized the field of analytical chemistry, enabling rapid, direct analysis samples in their native state. Since inception AIMS almost 20 years ago, community driven further development this suite techniques, motivated by plentiful advantages offered addition to traditional spectrometry. Workflows can be simplified through elimination sample preparation, times significantly reduced and remote from laboratory space become a real possibility. As such, interest rapidly spread communities worldwide, techniques are increasingly being integrated with standard operations. This annual review covers applications throughout 2021, specific focus on number key fields research including disease diagnostics, forensics security, food safety testing environmental sciences. While some new introduced, is shifting novel toward efforts improve existing particularly terms reproducibility, quantification ease-of-use.

Language: Английский

Citations

25
Mass Spectrometry Imaging of Lumpectomy Specimens Deciphers Diacylglycerols as Potent Biomarkers for the Diagnosis of Breast Cancer DOI

Supratim Mondal,

Yeswanth Sthanikam,

Anubhav Kumar

et al.

Analytical Chemistry, Journal Year: 2023, Volume and Issue: 95(20), P. 8054 - 8062

Published: May 11, 2023

Detecting breast tumor markers with a fast turnaround time from frozen sections should foster intraoperative histopathology in breast-conserving surgery, reducing the need for second operation. Hence, rapid label-free discrimination of spatially resolved molecular makeup between cancer and adjacent normal tissue is growing importance. We performed desorption electrospray ionization mass spectrometry imaging (DESI-MSI) fresh-frozen excision specimens, including paired sections, obtained lumpectomy 73 patients. The results demonstrate that posits sharp metabolic upregulation diacylglycerol, lipid messenger activates protein kinase C promoting growth. identified four specific sn-1,2-diacylglycerols outperformed all other lipids simultaneously mapped by positive ion mode DESI-MSI distinguishing cancers specimens. This result contrasts several previous studies probed dysregulation glycerophospholipids, sphingolipids, free fatty acids diagnoses. A random forest-based supervised machine learning considering detected signals also deciphered highest diagnostic potential these diacylglycerols top importance scores. led us to construct classifier 100% overall prediction accuracy using parsimonious set diacylglycerol biomarkers only. pathway analysis suggested increased catabolism phosphatidylcholine contributes overexpression. These open up opportunities mapping signaling context novel therapeutic developments, assessment margin status.

Language: Английский

Citations

13
Targeting metabolic reprogramming in hepatocellular carcinoma to overcome therapeutic resistance: A comprehensive review DOI Open Access
Qi Wang, Juan Liu,

Ziye Chen

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 170, P. 116021 - 116021

Published: Dec. 20, 2023

Hepatocellular carcinoma (HCC) poses a heavy burden on human health with high morbidity and mortality rates. Systematic therapy is crucial for advanced mid-term HCC, but faces significant challenge from therapeutic resistance, weakening drug effectiveness. Metabolic reprogramming has gained attention as key contributor to resistance. Cells change their metabolism meet energy demands, adapt growth needs, or resist environmental pressures. Understanding enzyme expression patterns metabolic pathway interactions vital comprehend HCC occurrence, development, treatment Exploring pathways essential identify breakthrough points treatment. Targeting enzymes inhibitors addressing these points. Inhibitors, combined systemic drugs, can alleviate prolong overall survival offer patients chance radical resection. Advances in research methods, genomics metabolomics cells organoids, help build the network. Recent progress biomaterials nanotechnology impacts targeting effectiveness, providing new solutions This review focuses changes, interactions, inhibitors, delivery reprogramming, offering valuable references approaches

Language: Английский

Citations

12
Mass Spectrometric Imaging of Anionic Phospholipids Desorbed from Human Hippocampal Sections: Discrimination between Temporal and Nontemporal Lobe Epilepsies DOI

Supratim Mondal,

Abhijit Nandy,

Geetha Dande

et al.

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: 15(5), P. 983 - 993

Published: Feb. 14, 2024

Temporal lobe epilepsy (TLE) is one of the most common neurological disorders, often accompanied by hippocampal sclerosis. The molecular processes underlying this epileptogenesis are poorly understood. To examine lipid profile, 39 fresh frozen sections human hippocampus obtained from surgery for TLE (n = 14) and non-TLE (control group; n 25) patients were subjected to desorption electrospray ionization mass spectrometry imaging in negative ion mode. In contrast our earlier report that showed striking downregulation positively charged phospholipids (e.g., phosphatidylcholine phosphatidylethanolamine, etc.) hippocampus, study finds complementary upregulation negatively phospholipids, notably, phosphatidylserine phosphatidylglycerol. This result may point an active metabolic pool produces these anionic at expense cationic phospholipids. shift could be due dysregulation Kennedy CDP-DG pathways responsible biosynthesizing lipids. Thus, further opens up opportunities investigate hallmarks potential therapeutic targets TLE.

Language: Английский

Citations

4
Advances and Emerging Medical Applications of Direct Mass Spectrometry Technologies for Tissue Analysis DOI Creative Commons

Mary Etta King,

Monica Lin,

Meredith Spradlin

et al.

Annual Review of Analytical Chemistry, Journal Year: 2023, Volume and Issue: 16(1), P. 1 - 25

Published: March 21, 2023

Offering superb speed, chemical specificity, and analytical sensitivity, direct mass spectrometry (MS) technologies are highly amenable for the molecular analysis of complex tissues to aid in disease characterization help identify new diagnostic, prognostic, predictive markers. By enabling detection clinically actionable profiles from cells, MS have potential guide treatment decisions transform sample within clinical workflows. In this review, we highlight recent health-related developments applications that exhibit tangible accelerate research diagnosis, including oncological neurodegenerative diseases microbial infections. We focus primarily on employ tissue analysis, imaging map spatial distributions molecules situ as well handheld devices rapid vivo ex analysis.

Language: Английский

Citations

10
Identification, Clinical Values, and Prospective Pathway Signaling of Lipid Metabolism Genes in Epilepsy and AED Treatment DOI

Hong Wei,

Biao Jin,

Kangren Zhao

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Language: Английский

Citations

0
Mass Spectrometry Imaging Unveils the Fate of Azithromycin in Zebrafish: Uptake, Distribution, Transformation, and Metabolic Impact DOI
Hang Fu,

L. L. Ji,

Yanxiao Jiang

et al.

Journal of environmental chemical engineering, Journal Year: 2025, Volume and Issue: unknown, P. 117244 - 117244

Published: May 1, 2025

Language: Английский

Citations

0
Rapid Molecular Evaluation of Human Kidney Tissue Sections by In Situ Mass Spectrometry and Machine Learning to Classify the Nephrotic Syndrome DOI

Supratim Mondal,

Mithlesh Prasad Singh, Anubhav Kumar

et al.

Journal of Proteome Research, Journal Year: 2023, Volume and Issue: 22(3), P. 967 - 976

Published: Jan. 25, 2023

Nephrotic syndrome (NS) is classified based on morphological changes of glomeruli in biopsied kidney tissues evaluated by time-consuming microscopy methods. In contrast, we employed desorption electrospray ionization mass spectrometry (DESI-MS) directly renal biopsy specimens obtained from 37 NS patients to rapidly differentiate lipid profiles three prevalent forms NS: IgA nephropathy (n = 9), membranous glomerulonephritis 7), and lupus nephritis 8), along with other types glomerular diseases 13). As noted molecular heterogeneity regularly spaced tissue regions, multiple sections each specimen were collected, providing a total 973 samples for investigation. Using multivariate analysis, report differential expressions glycerophospholipids, sphingolipids, glycerolipids among the above four classes kidneys, which otherwise overlooked several past studies correlating abnormalities diseases. We developed machine learning (ML) models top 100 features using support vector machine, enabled us discriminate concerned 100% overall accuracy training, validation, holdout test set. This DESI-MS/ML-based analysis can be completed few minutes, sharp contrast daylong procedure followed conventional histopathology NS.

Language: Английский

Citations

9