Neuroprotective Effects of Aldehyde-Reducing Composition in an LPS-Induced Neuroinflammation Model of Parkinson's Disease.

Parkinson's disease (PD) is a complex neurodegenerative disease in which neuroinflammation and oxidative stress interact to contribute to pathogenesis. This study investigates the in vivo neuroprotective effects of a patented yeast extract lysate in a lipopolysaccharide (LPS)-induced neuroinflammation model. The yeast extract lysate, named aldehyde-reducing composition (ARC), exhibited potent antioxidant and anti-aldehyde activities in vitro. Oral administration of ARC at 10 or 20 units/kg/day for 3 days prior to intraperitoneal injection of LPS (10 mg/kg) effectively preserved dopaminergic neurons in the substantia nigra (SN) and striatum by preventing LPS-induced cell death. ARC also normalized the activation of microglia and astrocytes in the SN, providing further evidence for its neuroprotective properties. In the liver, ARC downregulated the LPS-induced increase in inflammatory cytokines and reversed the LPS-induced decrease in antioxidant-related genes. These findings indicate that ARC exerts potent antioxidant, anti-aldehyde, and anti-inflammatory effects in vivo, suggesting its potential as a disease-modifying agent for the prevention and treatment of neuroinflammation-related diseases, including Parkinson's disease.

Polystyrene Microplastics Exacerbate Systemic Inflammation in High-Fat Diet-Induced Obesity.

Microplastics (MPs) are recognized as environmental pollutants with potential implications for human health. Considering the rapid increase in obesity rates despite stable caloric intake, there is a growing concern about the link between obesity and exposure to environmental pollutants, including MPs. In this study, we conducted a comprehensive investigation utilizing in silico, in vitro, and in vivo approaches to explore the brain distribution and physiological effects of MPs. Molecular docking simulations were performed to assess the binding affinity of three plastic polymers (ethylene, propylene, and styrene) to immune cells (macrophages, CD4+, and CD8+ lymphocytes). The results revealed that styrene exhibited the highest binding affinity for macrophages. Furthermore, in vitro experiments employing fluorescence-labeled PS-MPs (fPS-MPs) of 1 µm at various concentrations demonstrated a dose-dependent binding of fPS-MPs to BV2 murine microglial cells. Subsequent oral administration of fPS-MPs to high-fat diet-induced obese mice led to the co-existence of fPS-MPs with immune cells in the blood, exacerbating impaired glucose metabolism and insulin resistance and promoting systemic inflammation. Additionally, fPS-MPs were detected throughout the brain, with increased activation of microglia in the hypothalamus. These findings suggest that PS-MPs significantly contribute to the exacerbation of systemic inflammation in high-fat diet-induced obesity by activating peripheral and central inflammatory immune cells.

A Novel Aryl Hydrocarbon Receptor Antagonist HBU651 Ameliorates Peripheral and Hypothalamic Inflammation in High-Fat Diet-Induced Obese Mice.

Obesity is a chronic peripheral inflammation condition that is strongly correlated with neurodegenerative diseases and associated with exposure to environmental chemicals. The aryl hydrocarbon receptor (AhR) is a ligand-activated nuclear receptor activated by environmental chemical, such as dioxins, and also is a regulator of inflammation through interacting with nuclear factor (NF)-κB. In this study, we evaluated the anti-obesity and anti-inflammatory activity of HBU651, a novel AhR antagonist. In BV2 microglia cells, HBU651 successfully inhibited lipopolysaccharide (LPS)-mediated nuclear localization of NF-κB and production of NF-κB-dependent proinflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6. It also restored LPS-induced mitochondrial dysfunction. While mice being fed a high-fat diet (HFD) induced peripheral and central inflammation and obesity, HBU651 alleviated HFD-induced obesity, insulin resistance, glucose intolerance, dyslipidemia, and liver enzyme activity, without hepatic and renal damage. HBU651 ameliorated the production of inflammatory cytokines and chemokines, proinflammatory Ly6chigh monocytes, and macrophage infiltration in the blood, liver, and adipose tissue. HBU651 also decreased microglial activation in the arcuate nucleus in the hypothalamus. These findings suggest that HBU651 may be a potential candidate for the treatment of obesity-related metabolic diseases.

First direct-formation and properties of microspherical superstructure. Morphology of diamineplatinum(II) complexes with isonicotinate.

Uniform microspheres (30 microm) of [Pt(en)(iso)(iso.HPF(6))] (en = ethylenediamine; iso = isonicotinate) has been formed without intentional addition of any template, that is, a genuine self-assembly, and their structure, physicochemical properties, and hydrogenation-catalytic activity have been characterized.