Oxidized/unmodified-polyethylene microplastics neurotoxicity in mice: Perspective from microbiota-gut-brain axis

Environment International, Journal Year: 2024, Volume and Issue: 185, P. 108523 - 108523

Published: March 1, 2024

Microplastics (MPs) are inevitably oxidized in the environment, and their potential toxicity to organisms has attracted wide attention. However, neurotoxicity mechanism of polyethylene (Ox-PE) MPs remain unclear. Herein, we prepared low-density (Ox-LDPE) established a model exposure by continuously orally gavage C57BL/6 J mice with LDPE-MPs/Ox-LDPE-MPs for 28 days or without oral administration Lactobacillus plantarum DP189 galactooligosaccharides (DP189&GOS). The experimental results indicated that LDPE-MPs Ox-LDPE-MPs caused several adverse effects mice, mainly manifested behavioral changes, disruption intestinal blood–brain barrier (BBB), simultaneous oxidative stress, inflammatory reactions, pathological damage brain intestines. Brain transcriptomic analysis revealed cholinergic synaptic signaling pathways, which affect cognitive function, were significantly disrupted after Ox-LDPE-MPs. Real-time quantitative polymerase chain reaction Western Blotting further demonstrated critical genes (Slc5a7, Chat Slc18a3) proteins (Chat pathway down-regulated These alterations lead reduced acetylcholine concentration, causes dysfunction mice. Importantly, DP189&GOS interventions effectively mitigated MPs-induced microbiota alteration, improved BBB integrity, attenuated stress response, also saw rebound release acetylcholine. exert neurotoxic on inducing responses, dysregulation pathways mouse brain. That probiotic supplementation is effective attenuating Overall, this study reveals mechanisms improvement measures, necessary assess risks plastic contaminants human health.

Language: Английский

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The Role of Microglia in Brain Metastases: Mechanisms and Strategies

Aging and Disease, Journal Year: 2024, Volume and Issue: 15(1), P. 169 - 169

Published: Jan. 1, 2024

Brain metastases and related complications are one of the major fatal factors in cancer. Patients with breast cancer, lung melanoma at a high risk developing brain metastases. However, mechanisms underlying metastatic cascade remain poorly understood. Microglia, resident macrophages parenchyma, involved multiple processes associated metastasis, including inflammation, angiogenesis, immune modulation. They also closely interact cancer cells, astrocytes, other cells. Current therapeutic approaches against cancers, small-molecule drugs, antibody-coupled drugs (ADCs), immune-checkpoint inhibitors (ICIs), have compromised efficacy owing to impermeability blood-brain barrier (BBB) complex microenvironment. Targeting microglia is strategies for treating In this review, we summarize multifaceted roles highlight them as potential targets future interventions.

Language: Английский

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The immunological perspective of major depressive disorder: unveiling the interactions between central and peripheral immune mechanisms

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Jan. 19, 2025

Major depressive disorder is a prevalent mental disorder, yet its pathogenesis remains poorly understood. Accumulating evidence implicates dysregulated immune mechanisms as key contributors to disorders. This review elucidates the complex interplay between peripheral and central components underlying pathology. Peripherally, systemic inflammation, gut dysregulation, dysfunction in organs including gut, liver, spleen adipose tissue influence brain function through neural molecular pathways. Within nervous system, aberrant microglial astrocytes activation, cytokine imbalances, compromised blood-brain barrier integrity propagate neuroinflammation, disrupting neurotransmission, impairing neuroplasticity, promoting neuronal injury. The crosstalk immunity creates vicious cycle exacerbating neuropathology. Unraveling these multifaceted immune-mediated provides insights into major disorder's pathogenic basis potential biomarkers targets. Modulating both responses represent promising multidimensional therapeutic strategy.

Language: Английский

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Association of systemic immune-inflammation index with all-cause and cardiovascular mortality among adults with depression: evidence from NHANES 2005–2018

BMC Psychiatry, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 8, 2025

The relationship between the systemic immune-inflammatory index (SII) and mortality of adults with depression is uncertain. This study included who were surveyed in National Health Nutrition Examination Survey (NHANES) from 2005 to 2018. Cox proportional hazards regression models compute hazard ratios (HR) 95% confidence intervals (CI) for mortality.The restricted cubic spline(RCS), Kaplan-Meier curve analysis, time-dependent ROC subgroup sensitivity analyses also used. A total 2442 final analysis(average age: 46.51 ± 0.44 years). During a median follow-up 89 months, there 302 all-cause deaths 74 cardiovascular deaths. fully adjusted model showed that an increment 100 unit SII corresponded increased HR 1.05(95% CI,1.02,1.08, p = 0.003) 1.06(95% CI,1.02,1.10, 0.004) mortality, respectively. RCS analysis indicated J-shape positive linear association exhibited excellent efficacy predicting at 1, 3, 5 10 years. Higher levels associated risk depression. Not applicable.

Language: Английский

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Therapeutic targeting of obesity-induced neuroinflammation and neurodegeneration

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 17, 2025

Obesity is a major modifiable risk factor leading to neuroinflammation and neurodegeneration. Excessive fat storage in obesity promotes the progressive infiltration of immune cells into adipose tissue, resulting release pro-inflammatory factors such as cytokines adipokines. These inflammatory mediators circulate through bloodstream, propagating inflammation both periphery central nervous system. Gut dysbiosis, which results leaky intestinal barrier, exacerbates plays significant role linking pathogenesis neurodegeneration gut-brain/gut-brain-liver axis. Inflammatory states within brain can lead insulin resistance, mitochondrial dysfunction, autolysosomal increased oxidative stress. disruptions impair normal neuronal function subsequently cognitive decline motor deficits, similar pathologies observed neurodegenerative diseases, including Alzheimer's disease, multiple sclerosis, Parkinson's disease. Understanding underlying disease mechanisms crucial for developing therapeutic strategies address defects these metabolic pathways. In this review, we summarize provide insights different strategies, methods alter gut lifestyle changes, dietary supplementation, well pharmacological agents derived from natural sources, that target obesity-induced

Language: Английский

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