Identification and validation of Atp5f1c in CD4+ T cell as a hub protein in Parkinson's disease

International Journal of Biological Macromolecules, Год журнала: 2025, Номер 297, С. 139858 - 139858

Опубликована: Янв. 14, 2025

Язык: Английский

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Structural optimization and biological evaluation of indolin-2-one derivatives as novel CDK8 inhibitors for idiopathic pulmonary fibrosis

Biomedicine & Pharmacotherapy, Год журнала: 2025, Номер 184, С. 117891 - 117891

Опубликована: Фев. 16, 2025

Язык: Английский

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Spirostanol‐Type Saponins From Allium Macrostemonis Bulbus Alleviate Chronic Unpredictable Mild Stress–Induced Depression‐Like Behavior in Mice

Journal of Food Biochemistry, Год журнала: 2025, Номер 2025(1)

Опубликована: Янв. 1, 2025

Major depressive disorder is a chronic, recurrent, and potentially life‐threatening mental that severely impacts both psychological physiological health. Allii Macrostemonis Bulbus (AMB), traditional Chinese medicinal edible plant, believed to be beneficial for mood regulation. Recent preclinical studies have demonstrated its total saponins’ antidepressant effects, though the specific active substances pathways remain unclear.We first established an in vitro model of hippocampal neuronal injury mice induced by Glu conducted preliminary screening different polarity fractions AMB’s saponins, identifying spirostanol‐type saponins (AMBN‐90) with potential. We then analyzed components used network pharmacology predict targets AMBN‐90’s effects. Next, we vivo mouse depression chronic unpredictable mild stress treated it AMBN‐90 6 weeks. Behavioral tests, HE staining, monoamine level measurements hippocampus were verify Subsequently, Western blotting molecular docking methods employed preliminarily reveal potential mechanisms. Results showed exhibited significant neuroprotective activity vitro. In , significantly improved weight loss depression‐like behaviors exposed stress, ameliorated damage, increased levels 5‐HT, DA, NE hippocampus. It also elevated brain‐derived neurotrophic factor reduced apoptosis activating PKA–CREB–BDNF pathway. Molecular superior affinity upstream proteins pathway, C‐type G protein–coupled receptors (GPCRs). Our findings suggest steroidal AMB may developed as functional foods drugs alleviating depression.

Язык: Английский

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Identifying behavior regulatory leverage over mental disorders transcriptomic network hubs toward lifestyle-dependent psychiatric drugs repurposing

Human Genomics, Год журнала: 2025, Номер 19(1)

Опубликована: Март 19, 2025

Abstract Background There is a vast prevalence of mental disorders, but patient responses to psychiatric medication fluctuate. As food choices and daily habits play fundamental role in this fluctuation, integrating machine learning with network medicine can provide valuable insights into disease systems the regulatory leverage lifestyle health. Methods This study analyzed coexpression modules MDD PTSD blood transcriptomic profile using modularity optimization method, first runner-up Disease Module Identification DREAM challenge . The top genes both were detected random forest model. Afterward, signature two predominant habitual phenotypes, diet-induced obesity smoking, identified. These transcription/translation regulating factors ( TRFs ) signals transduced toward disorders’ genes. A bipartite drugs that target TRFS together or hubs was constructed. Results research revealed one hub, CENPJ, which known influence intellectual ability. observation paves way for additional investigations potential CENPJ as novel therapeutic agents development. Additionally, most predicted associated multiple carcinomas, notable SHCBP1. SHCBP1 risk factor glioma, suggesting importance continuous monitoring patients mitigate cancer comorbidities. signaling illustrated three biomarkers co-regulated by phenotype TRFs. 6-Prenylnaringenin Aflibercept identified candidates targeting hubs: ATP6V0A1 PIGF. However, have no over Conclusion Combining biology succeeded revealing notoriously spreading PTSD. approach offers non-invasive diagnostic pipeline identifies drug targets could be repurposed under further investigation. findings contribute our understanding complex interplay between habits, interventions, thereby facilitating more targeted personalized treatment strategies.

Язык: Английский

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Combined Neurotoxic Effects of Commercial Formulations of Pyrethroid (Deltamethrin) and Neonicotinoid (Imidacloprid) Pesticides on Adult Zebrafish (Danio rerio): Behavioral, Molecular, and Histopathological Analysis

Life, Год журнала: 2025, Номер 15(4), С. 538 - 538

Опубликована: Март 25, 2025

The use of different commercial products that involve one or multiple active substances with specific targeted-pests control has become a widespread practice. Because this, severe range significant consequences been often reported. Among the most used pesticides worldwide are deltamethrin (DM) and imidacloprid (IMI). With significative effect on insect’s nervous system, DM acts voltage-gated sodium channels in nerve cell membranes, while IMI mimics acetylcholine neurotransmitter by binding irreversibly to nicotinic receptors. This study investigates neurotoxic effects sub-chronic exposure formulations (IMI) adult zebrafish, both individually combination. this contain additional ingredients commonly found pesticide products, which may contribute overall toxicity. Fish were exposed environmentally relevant concentrations these for 21 days, Behavioral, molecular, histopathological analyses conducted assess impact pesticides. Zebrafish exhibited dose-dependent behavioral alterations, particularly combined groups, including increased erratic swimming anxiety-like behavior. Gene expression analysis revealed changes neurotrophic factors (BDNF, NGF, ntf-3, ntf-4/5, ntf-6/7) their receptors (ntrk1, ntrk2a, ntrk2b, ntrk3a, ntrk3b, ngfra, ngfrb), indicating potential effects. Histopathological examination confirmed neuronal degeneration, gliosis, vacuolization, more impairments observed mixture treatments. These findings highlight aquatic environments emphasize need stricter regulations mixtures further research interactions. Our combination could trigger synergistic maximizing toxicity each compound. Thus, it is well-known practice pyrethroids neonicotinoids be together agriculture. Even so, its prevalence agriculture investigate actual human health, biodiversity, ecosystem mitigates development new strategies assessing risk and, at same time, enhancing effectiveness.

Язык: Английский

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Xanthohumol Regulates Mitophagy in Osteosarcoma Cells via AMPK‐ULK1‐FUNDC1 Signaling Pathway

Phytotherapy Research, Год журнала: 2025, Номер unknown

Опубликована: Апрель 7, 2025

ABSTRACT Osteosarcoma (OS) is the most common primary bone malignancy. The therapeutic efficacy for OS patients has remained stagnant in recent decades. Xanthohumol (XN), a flavonoid naturally found hops, demonstrated significant anticancer properties lung and breast cancer. However, its effect on underlying molecular mechanisms remains uncertain. Therefore, purpose of this study to explore relationship between XN OS. Firstly, we assessed impact cell proliferation migration using CCK‐8, wound‐healing, transwell, clonogenicity assays. Subsequently, examined mitophagy cells through flow cytometry, immunofluorescence, transmission electron microscopy, western blot analysis. Finally, constructed siRNA targeting AMPK validate pathway. In vitro, that inhibited concentration‐ time‐dependent manner. Furthermore, induced mitochondrial damage increased reactive oxygen species (ROS) levels. RNA‐seq analysis suggested potential pathway, which confirmed experimentally by showing reduced ATP levels, altered membrane potential, expression Atg5, Beclin‐1, LC3 proteins. Interestingly, inhibitor Mdivi‐1 reversed caused cells. exerted anti‐OS effects activation AMPK‐ULK1‐FUNDC1 signaling was effectively after knockdown. vivo, subcutaneous nude mouse model without any organ toxicity. emerges as promising pharmaceutical agent

Язык: Английский

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High-Resolution Tracking of Aging-Related Small Molecules: Bridging Pollutant Exposure, Brain Aging Mechanisms, and Detection Innovations

Biosensors, Год журнала: 2025, Номер 15(4), С. 242 - 242

Опубликована: Апрель 11, 2025

Brain aging is a complex process regulated by genetic, environmental, and metabolic factors, increasing evidence suggests that environmental pollutants can significantly accelerate this interfering with oxidative stress, neuroinflammation, mitochondrial function-related signaling pathways. Traditional studies have focused on the direct damage of macromolecules (e.g., proteins, DNA), while central role senescence-associated small molecules ROS, PGE2, lactate) in early regulatory mechanisms has been long neglected. In study, we innovatively proposed cascade framework "small molecule imbalance-signaling pathway dysregulation-macromolecule collapse", which reveals exacerbate dynamics brain through activation NLRP3 inflammatory vesicles inhibition HIF-1α. Meanwhile, to address technical bottleneck spatiotemporal monitoring, paper systematically reviews cutting-edge detection tools such as electrochemical sensors, genetically encoded fluorescent probes antioxidant quantum dots (AQDs). Among them, AQDs show unique advantages real-time monitoring ROS fluctuations intervention virtue their ultra-high specific surface area, controllable modification, free radical scavenging ability. By integrating multimodal techniques mechanism studies, work provides new perspective for analyzing pollutant-induced lays methodological foundation strategies based networks.

Язык: Английский

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A quantitative proteomic study reveals oxidative stress and synapse-related proteins contributed to TDCIPP exposure induced neurotoxicity

Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 271, С. 116005 - 116005

Опубликована: Янв. 22, 2024

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) has been consistently identified in various environmental media and biological specimens. Current understanding of the vivo toxicities TDCIPP is limited, especially for potential neurotoxic cognitive impairment effects. To better evaluate adverse effect chemical on learning memory, Sprague Dawley (SD) rats were administered via gavage at doses 40, 120, 360 mg/kg/day a period 90 days. Quantitative proteomic analysis, immunohistochemistry, Western blotting employed to assess alterations proteins following exposure TDCIPP. An open field test Morris Water Maze used anxiety spatial memory capacity. Administration induced impairments rats. Additionally, noteworthy decrease number neurons was observed hippocampal CA3 dentate gyrus (DG) regions. Proteomic bioinformatic analyses revealed dysregulation numerous proteins, particularly those associated with synapses (PKN1) or oxidative stress (GSTM4, NQO1, BMAL1), which further confirmed by blot analysis. In sum, caused synaptic stress-related proteins.

Язык: Английский

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Pharmacological mechanism of natural antidepressants: The role of mitochondrial quality control

Phytomedicine, Год журнала: 2024, Номер 129, С. 155669 - 155669

Опубликована: Апрель 28, 2024

Язык: Английский

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Mesenchymal stem cell-derived extracellular vesicles mitigate neuronal damage from intracerebral hemorrhage by modulating ferroptosis

Stem Cell Research & Therapy, Год журнала: 2024, Номер 15(1)

Опубликована: Авг. 13, 2024

Hemorrhagic stroke is a devastating cerebrovascular event with high rate of early mortality and long-term disability. The therapeutic potential mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) for neurological conditions, such as intracerebral hemorrhage (ICH), has garnered considerable interest, though their mechanisms action remain poorly understood.

Язык: Английский

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