Elucidating adsorption mechanisms of benzalkonium chlorides (BACs) on polypropylene and polyethylene terephthalate microplastics (MPs): Effects of BACs alkyl chain length and MPs characteristics.

Since the onset of the COVID-19 pandemic, there has been an increase in the use of disposable plastics and disinfectants. This study systematically investigated the adsorption behavior and mechanisms of benzalkonium chlorides (BACs), commonly used disinfectants, on polypropylene (PP) and polyethylene terephthalate (PET) microplastics (MPs), considering various factors, such as characteristics of MPs, alkyl chain length of BACs, and environmental conditions. Our results demonstrated a higher adsorption capacity for PP-MPs with relatively hydrophobic properties compared to PET-MPs, where longer alkyl chains in BACs (i.e., higher octanol-water partition coefficients, Kow) significantly enhanced adsorption through hydrophobic interactions. The inverse relationship between particle size of MPs and adsorption was evident. While changes in pH minimally affected adsorption on PP-MPs, adsorption on PET-MPs increased with rising pH, highlighting the influence of pH on electrostatic interactions. Moreover, MP aging with UV/H2O2 amplified BAC adsorption on PP-MPs due to surface oxidation and fragmentation, whereas the properties of PET-MPs remained unaltered, resulting in unchanged adsorption capacities. Spectroscopy studies and density functional theory (DFT) calculations confirmed hydrophobic and electrostatic interactions as the primary adsorption mechanisms. These findings improve our understanding of MPs and BACs behavior in the environment, providing insights for environmental risk assessments related to combined pollution.

Micrandilactone C, a Nortriterpenoid Isolated from Roots of Schisandra chinensis, Ameliorates Huntington's Disease by Inhibiting Microglial STAT3 Pathways.

Huntington's disease (HD) is a neurodegenerative disease that affects the motor control system of the brain. Its pathological mechanism and therapeutic strategies have not been fully elucidated yet. The neuroprotective value of micrandilactone C (MC), a new schiartane nortriterpenoid isolated from the roots of Schisandra chinensis, is not well-known either. Here, the neuroprotective effects of MC were demonstrated in 3-nitropropionic acid (3-NPA)-treated animal and cell culture models of HD. MC mitigated neurological scores and lethality following 3-NPA treatment, which is associated with decreases in the formation of a lesion area, neuronal death/apoptosis, microglial migration/activation, and mRNA or protein expression of inflammatory mediators in the striatum. MC also inhibited the activation of the signal transducer and activator of transcription 3 (STAT3) in the striatum and microglia after 3-NPA treatment. As expected, decreases in inflammation and STAT3-activation were reproduced in a conditioned medium of lipopolysaccharide-stimulated BV2 cells pretreated with MC. The conditioned medium blocked the reduction in NeuN expression and the enhancement of mutant huntingtin expression in STHdhQ111/Q111 cells. Taken together, MC might alleviate behavioral dysfunction, striatal degeneration, and immune response by inhibiting microglial STAT3 signaling in animal and cell culture models for HD. Thus, MC may be a potential therapeutic strategy for HD.

Influence of postwashing process on the elution of residual monomers, degree of conversion, and mechanical properties of a 3D printed crown and bridge materials.

OBJECTIVES: This study aimed to determine the effects of the postwashing method and time on the mechanical properties and biocompatibility of three-dimensional (3D) printed crown and bridge resin. METHODS: DLP (digital light processing)-printed specimens produced from Nextdent crown & bridge (C&B) resins were washed separately using an ultrasonic bath and rotary washer with TPM (tripropylene glycol monomethyl ether) for 3 min, 6 min, 10 min, 20 min, and 1 h. Postcuring was applied for 30 min to each specimen after the washing process. The flexural strength, Vickers hardness, water sorption and solubility, degree of conversion (DC), elution of residual monomers, and biocompatibility of the specimens were evaluated. RESULTS: The ultrasonic bath showed greater washing efficacy by reducing the residual HEMA (2-hydroxyethyl methacrylate) from 2.0634 ppm to 0.1456 ppm and reducing the residual TEGDMA (triethylene glycol dimethacrylate) from 1.4862 ppm to 0.1484 ppm. With prolonged washing, the flexural strength significantly decreased from 129.67 ± 6.66 MPa (mean±standard deviation) to 103.17 ± 7.20 MPa, while the Vickers hardness increased slightly for the first 6 min and then decreased thereafter significantly. The DC was 87.78 ± 1.34% after 3 min and then gradually decreased with extended washing time. The cytotoxicity significantly decreases with the increment of the washing time. SIGNIFICANCE: The washing effect on the elution of residual monomers was better for an ultrasonic bath than for a rotary washer. Extending the washing time reduces the mechanical properties and cytotoxicity of the Nextdent C&B resin.

Adsorption of benzalkonium chlorides onto polyethylene microplastics: Mechanism and toxicity evaluation.

Usage of disposable plastic products and disinfectants has been skyrocketing due to the COVID-19 pandemic. The random disposal of plastic products may result in greater microplastic pollution. Benzalkonium chloride is known as one of the most common ingredients of disinfectants. In this study, the adsorption behavior of benzalkonium chlorides (BAC12, BAC14, BAC16) on polyethylene microplastics (PE-MPs) and the combined toxic effects were investigated using batch adsorption experiment and Daphnia magna. The results showed that PE-MPs had strong adsorption capacity for BACs and the adsorption capacity increased (11.03-22.77 mg g-1) with their octanol-water distribution coefficients. The effect of pH was negligible while dissolved organic matter inhibited the adsorption. A slightly inverse relationship between particle size of PE-MPs and adsorption was observed. Additionally, the MP aging with UV/H2O2 increased the adsorption of BAC12 but decreased that of relatively hydrophobic BAC14 and BAC16. The survival rate of Daphnia magna increased up to 100% in the presence of PE-MPs depending upon their adsorption capacities, suggesting that PE-MPs do not act as a carrier but rather as a scavenger for BACs. This study provides important information necessary for environmental risk assessment with regard to the combined pollution of MPs and toxic chemicals.

Ginseng gintonin attenuates the disruptions of brain microvascular permeability and microvascular endothelium junctional proteins in an APPswe/PSEN-1 double-transgenic mouse model of Αlzheimer's disease.

It has been previously indicated that gintonin, which is a novel exogenous ginseng-derived lysophosphatidic acid (LPA) receptor ligand, restores memory dysfunctions in an APPswe/PSEN-1 double-transgenic mouse model of Alzheimer's disease (AD Tg mice) by attenuating ß-amyloid plaque deposition, recovering cholinergic dysfunctions and upregulating hippocampal neurogenesis in the cortex and hippocampus. Although ß-amyloid plaque depositions in AD is accompanied with disruptions of brain microvessels, including the brain-blood barrier (BBB), it is unknown whether gintonin exerts protective effects on brain microvascular dysfunctions in AD Tg mice. In the present study, the effects of gintonin-enriched fraction (GEF) on the changes in ß-amyloid plaque depositions, brain permeability of Evans blue, and microvascular junctional proteins were investigated in AD Tg mice. Long-term oral administration of GEF reduced ß-amyloid plaque depositions in the cortex and hippocampus of AD Tg mice. GEF treatment also reduced the permeability of Evans blue through BBB and decreased immunoreactivity of platelet endothelial cell adhesion molecule-1 (a marker of BBB disruption) in the cortex and hippocampus of AD Tg mice in a dose-dependent manner. However, GEF elevated the protein expression of occludin, claudin-5 and zonula occludens-1, which are tight-junction proteins. The present results demonstrated that long-term oral GEF treatment not only attenuates ß-amyloid plaque depositions in the brain but also exhibits protective effects against microvascular disruptions in AD Tg mice. Finally, GEF exhibits anti-AD effects through attenuation of ß-amyloid plaque depositions and protection against brain microvascular damage in an AD animal model.

Korean Red Ginseng alleviates dehydroepiandrosterone-induced polycystic ovarian syndrome in rats via its antiinflammatory and antioxidant activities.

BACKGROUND: Beneficial effects of Korean Red Ginseng (KRG) on polycystic ovarian syndrome (PCOS) remains unclear. METHODS: We examined whether pretreatment (daily from 2 hours before PCOS induction) with KRG extract in water (KRGE; 75 and 150 mg/kg/day, p.o.) could exert a favorable effect in a dehydroepiandrosterone (DHEA)-induced PCOS rat model. RESULTS: Pretreatment with KRGE significantly inhibited the elevation of body and ovary weights, the increase in number and size of ovarian cysts, and the elevation of serum testosterone and estradiol levels induced by DHEA. Pretreatment with KRGE also inhibited macrophage infiltration and enhanced mRNA expression levels of chemokines [interleukin (IL)-8, monocyte chemoattractant protein-1), proinflammatory cytokines (IL-1ß, IL-6), and inducible nitric oxide synthase in ovaries induced by DHEA. It also prevented the reduction in mRNA expression of growth factors (epidermal growth factor, transforming growth factor-beta (EGF, TGF-ß)) related to inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cell pathway and stimulation of the nuclear factor erythroid-derived 2-related factor 2 pathway. Interestingly, KRGE or representative ginsenosides (Rb1, Rg1, and Rg3(s)) inhibited the activity of inflammatory enzymes cyclooxygenase-2 and iNOS, cytosolic p-IkB, and nuclear p-nuclear factor kappa-light-chain-enhancer of activated B in lipopolysaccharide-induced RAW264.7 cells, whereas they increased nuclear factor erythroid-derived 2-related factor 2 nuclear translocation. CONCLUSION: These results provide that KRGE could prevent DHEA-induced PCOS via antiinflammatory and antioxidant activities. Thus, KRGE may be used in preventive and therapeutic strategies for PCOS-like symptoms.

Transport of citrate-coated silver nanoparticles in saturated porous media.

In this study, the influences of physical and chemical factors [e.g., ionic strength (IS), pH, and flow rate] on the fate and transport of citrate-coated silver nanoparticles (AgNPs) were investigated through experiments using saturated columns. For the transport behavior of AgNPs under various conditions, retardation was confirmed with an increase in ionic strength (IS) while early elution developed with an increase in pH and flow rate. These transport experiment outcomes were simulated through Hydrus-1D, and the observed breakthrough curves were confirmed to have a significant correlation with the fitted results. Interestingly, the AgNPs and quartz sand used in this study showed a negative charge in the investigated experimental conditions. Although the reaction between AgNPs and quartz sand was expected to be unfavorable, AgNPs were observed to have been deposited onto the sand surface during the column test. To clarify the mechanism of the deposition of AgNPs even in unfavorable conditions, the interaction energy profiles were calculated based on the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. From the results, unfavorable interactions were expected in the NP-NP and NP-sand interactions in every condition. It was concluded that the deposition of AgNPs onto the sand surface under the unfavorable conditions in this study was mainly because of the physical roughness of the sand surface. Moreover, this hypothesis was supported by the zone of influence calculation in accordance with IS, the interpretation results of the fractional sand surface coverage in accordance with concentration changes of AgNPs, and series column tests.

Cerebral glucose metabolism differs according to future weight change.

The brain is known to play a central role in controlling the desire to eat. We aimed to evaluate the brain regions that might have a long-term effect on eating behavior and weight changes. We utilized the data of cognitively normal subjects who are examined by several neurologic tests, and followed-up for 36 months from Alzheimer's Disease Neuroimaging Initiative (ADNI) database, and investigated to search the brain regions that are associated with future weight change. The weight of each subject was measured on each visit at baseline (W0), 36 (W36) months after brain 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET). Percentage (%) change of weight was calculated as follows: [(W36-W0)/W0]*100. We classified each subject's change into one of three categories: weight loss, stable, and weight gain. Dynamic 3-dimensional scans of six 5-min frames were acquired 30 mins after injection of 185 MBq of FDG. Image analysis was done using Statistical Parametric Mapping 12. Ninety-six subjects were included in this study (male 54, female 42). Subjects with future weight gain showed hypometabolism in left cerebellum compared with those with future weight loss & stable. Percentage change of weight was positively associated with brain metabolism in right insula, and right caudate nucleus. In conclusion, subjects with future weight gain showed hypometabolism in left cerebellum, and percentage change of weight was positively associated with brain metabolism in right insula, and right caudate nucleus. This study raises the possibility that the brain glucose metabolism precedes the future weight change.

Development of a model (SWNano) to assess the fate and transport of TiO2 engineered nanoparticles in sewer networks.

A new model, SWNano (Sewer-Water Nano), has been developed in the present study that quantitatively simulates the spatio-temporal changes in the concentrations of TiO2 ENPs of dispersed and aggregated forms in the sewage water and sediment of a sewer network. As a brief example of SWNano applications, a small section of the entire sewer network of Seoul, Korea, was chosen to study where the sewage water was experimentally characterized. The predictions of SWNano present important findings that i) heteroaggregation is the most significant process following the advective transport among the fate and transport processes in the sewer pipes, ii) the heteroaggregation of TiO2 ENPs with SPMs in the sewage water can substantially (a few % to more than 50%) reduce the freely dispersed TiO2 ENPs depending on the magnitude of attachment efficiency, and iii) accurate determination of attachment efficiency is of critical importance in predicting the quantity of individual forms of ENPs exiting the sewer system. The predictions strongly suggest that the fate and transport of TiO2 ENPs in the sewer networks be taken into account to improve the assessment of exposure to TiO2 ENPs in the aquatic ecosystems, which warrants further development and use of models like SWNano.

Gintonin, a ginseng-derived ingredient, as a novel therapeutic strategy for Huntington's disease: Activation of the Nrf2 pathway through lysophosphatidic acid receptors.

Gintonin (GT), a ginseng-derived lysophosphatidic acid receptor ligand, regulates various cellular effects and represses inflammation. However, little is known about the potential value of GT regarding inflammation in the neurodegenerative diseases, such as Huntington's disease (HD). In this study, we investigated whether GT could ameliorate the neurological impairment and striatal toxicity in cellular or animal model of HD. Pre-, co-, and onset-treatment with GT (25, 50, or 100 mg/kg/day, p.o.) alleviated the severity of neurological impairment and lethality following 3-nitropropionic acid (3-NPA). Pretreatment with GT also attenuated mitochondrial dysfunction i.e. succinate dehydrogenase and MitoSOX activities, apoptosis, microglial activation, and mRNA expression of inflammatory mediators i.e. IL-1ß, IL-6, TNF-α, COX-2, and iNOS in the striatum after 3-NPA-intoxication. Its action mechanism was associated with lysophosphatidic acid receptors (LPARs) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway activations and the inhibition of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) signaling pathways. These beneficial effects of GT were neutralized by pre-inhibiting LPARs with Ki16425 (a LPAR1/3 antagonist). Interestingly, GT reduced cell death and mutant huntingtin (HTT) aggregates in STHdh cells. It also mitigated neurological impairment in mice with adeno-associated viral (AAV) vector serotype DJ-mediated overexpression of N171-82Q-mutant HTT in the striatum. Taken together, our findings firstly suggested that GT has beneficial effects with a wide therapeutic time-window in 3-NPA-induced striatal toxicity by antioxidant and anti-inflammatory activities through LPA. In addition, GT exerts neuroprotective effects in STHdh cells and AAV vector-infected model of HD. Thus GT might be an innovative therapeutic candidate to treat HD-like syndromes.

Prediction of Cd toxicity to Daphnia magna in the mixture of multi-walled carbon nanotubes and kaolinite.

In this study, we investigated cadmium toxicity created by adsorption kinetics in several mixtures containing two types of multi-walled carbon nanotubes (COOH-MWCNT and NH2-MWCNT) and natural kaolinite. Characteristics of two types of MWCNTs were measured by zeta potential and ATR FT-IR graphs and TEM images. The solution of CNTs and kaolinite was tested to study Cd adsorption kinetics and mechanisms of differentiation-associated toxicity using Daphnia magna in a binary system (Cd-MWCNTs and Cd-kaolinite) and a ternary system (Cd-MWCNTs-kaolinite). In the binary system, Cd removal efficiency was nearly 100% and 40% for MWCNTs and kaolinite because of surface charge, respectively, with increasing sorbent concentration. In the ternary system, the trend of adsorption rate was similar to that of binary system. In comparison with percent mortality in the binary system, the solution in the ternary system showed higher toxicity due to the interaction of MWCNTs-kaolinite coagulated particles, thereby decreasing Cd adsorption onto CNTs and kaolinites. Overall, kaolinite can affect the adsorption process of Cd on MWCNTs in negative ways, depending on adsorption state. In conclusion, our studies suggest that kaolinite differs with adsorption ability of Cd by MWCNTs, and toxicity is likely to be produced by multivariable regression in the adsorption state.

An Improved Dehydroepiandrosterone-Induced Rat Model of Polycystic Ovary Syndrome (PCOS): Post-pubertal Improve PCOS's Features.

Complete animal models investigating the pathogenesis and treatment of polycystic ovarian syndrome (PCOS) are not completely established. Although dehydroepiandrosterone (DHEA)-induced pre-pubertal rat model for PCOS has been widely used, the model exhibits weaknesses such as decreased ovary weight. Here, we report an innovative DHEA-induced PCOS model that addresses limitations of the pre-pubertal model. The 21-day-old (pre-pubertal) and 42-day-old (post-pubertal) female rats were subcutaneously injected with DHEA (60 mg/kg body weight) daily for up to 20-30 days. The post-pubertal model showed a steady increase in ovary weight and the number of ovarian cysts as well as uterine weight and thickness, which may be key features of PCOS, compared with the pre-pubertal model. Therefore, a post-pubertal PCOS model induced by DHEA may be an improved model to investigate the etiology of PCOS and development of therapeutic interventions.

Impact of surface modification on the toxicity of zerovalent iron nanoparticles in aquatic and terrestrial organisms.

Nanoscale zerovalent iron (nZVI)-based materials are increasingly being applied in environmental remediation, thereby lead to their exposure to aquatic and terrestrial biota. However, little is known regarding the toxic effects of surface-modified nZVI on multiple species in the ecosystem. In this study, we systematically compared the toxicities of different forms of nZVIs, such as bare nZVI, carboxymethyl cellulose (CMC)-stabilized nZVI, tetrapolyphosphate (TPP)-coated nZVI and bismuth (Bi)-doped nZVI, on a range of aquatic and terrestrial organisms, including bacteria (Escherichia coli and Bacillus subtilis), plant (Arabidopsis thaliana), water flea (Daphnia magna) and earthworm (Eisenia fetida). The Bi- and CMC-nZVI induced adverse biological responses across all the test systems, except E. fetida, varying from cell death in E. coli and B. subtilis to inhibition of the physiological states in D. magna and A. thaliana. The particle characterization under exposure conditions indicated that the surface modification of nZVI played a significant role in their toxicities by changing their physicochemical properties. The underlying mechanisms by which nZVI induces toxicity might be a combination of oxidative stress and another mechanism such as cell membrane disruption, chlorosis and hypoxia. Overall, our findings could provide important implications for the development of environment-friendly nanomaterials and direct further ecotoxicological researches regarding interspecies exploration.

Multitarget effects of Korean Red Ginseng in animal model of Parkinson's disease: antiapoptosis, antioxidant, antiinflammation, and maintenance of blood-brain barrier integrity.

BACKGROUND: Ginsenosides are the main ingredients of Korean Red Ginseng. They have extensively been studied for their beneficial value in neurodegenerative diseases such as Parkinson's disease (PD). However, the multitarget effects of Korean Red Ginseng extract (KRGE) with various components are unclear. METHODS: We investigated the multitarget activities of KRGE on neurological dysfunction and neurotoxicity in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. KRGE (37.5 mg/kg/day, 75 mg/kg/day, or 150 mg/kg/day, per os (p.o.)) was given daily before or after MPTP intoxication. RESULTS: Pretreatment with 150 mg/kg/day KRGE produced the greatest positive effect on motor dysfunction as assessed using rotarod, pole, and nesting tests, and on the survival rate. KRGE displayed a wide therapeutic time window. These effects were related to reductions in the loss of tyrosine hydroxylase-immunoreactive dopaminergic neurons, apoptosis, microglial activation, and activation of inflammatory factors in the substantia nigra pars compacta and/or striatum after MPTP intoxication. In addition, pretreatment with KRGE activated the nuclear factor erythroid 2-related factor 2 pathways and inhibited phosphorylation of the mitogen-activated protein kinases and nuclear factor-kappa B signaling pathways, as well as blocked the alteration of blood-brain barrier integrity. CONCLUSION: These results suggest that KRGE may effectively reduce MPTP-induced neurotoxicity with a wide therapeutic time window through multitarget effects including antiapoptosis, antiinflammation, antioxidant, and maintenance of blood-brain barrier integrity. KRGE has potential as a multitarget drug or functional food for safe preventive and therapeutic strategies for PD.

Multi-Target Protective Effects of Gintonin in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Mediated Model of Parkinson's Disease via Lysophosphatidic Acid Receptors.

Gintonin is a ginseng-derived lysophosphatidic acid receptor (LPAR) ligand. Although previous in vitro and in vivo studies demonstrated the therapeutic role of gintonin against Alzheimer's disease, the neuroprotective effects of gintonin in Parkinson's disease (PD) are still unknown. We investigated whether gintonin (50 and 100 mg/kg/day, p.o., daily for 12 days) had neuroprotective activities against neurotoxicity in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Pre-administration of 100 mg/kg gintonin displayed significantly ameliorating effects in neurological disorders (motor and welfare) as measuring using pole, rotarod, and nest building tests, and in the survival rate. These effects were associated to the reduction of the loss of tyrosine hydroxylase-positive neurons, microglial activation, activation of inflammatory mediators (interleukin-6, tumor necrosis factor, and cyclooxygenase-2), and alteration of blood-brain barrier (BBB) integrity in the substantia nigra pars compacta and/or striatum following MPTP injection. The benefits of gintonin treatment against MPTP also included the activation of the nuclear factor erythroid 2-related factor 2 pathways and the inhibition of phosphorylation of the mitogen-activated protein kinases and nuclear factor-kappa B signaling pathways. Interestingly, these neuroprotective effects of gintonin were blocked by LPAR1/3 antagonist, Ki16425. Overall, the present study shows that gintonin attenuates MPTP-induced neurotoxicity via multiple targets. Gintonin combats neuronal death, and acts as an anti-inflammatory and an anti-oxidant agent. It maintains BBB integrity. LPA receptors play a key role in gintonin-mediated anti-PD mechanisms. Finally, gintonin is a key agent for prevention and/or treatment of PD.

Adeno-Associated Viral Vector Serotype DJ-Mediated Overexpression of N171-82Q-Mutant Huntingtin in the Striatum of Juvenile Mice Is a New Model for Huntington's Disease.

Huntington's disease (HD) is an autosomal-dominant inherited neurodegenerative disorder characterized by motor, psychiatric and cognitive symptoms. HD is caused by an expansion of CAG repeats in the huntingtin (HTT) gene in various areas of the brain including striatum. There are few suitable animal models to study the pathogenesis of HD and validate therapeutic strategies. Recombinant adeno-associated viral (AAV) vectors successfully transfer foreign genes to the brain of adult mammalians. In this article, we report a novel mouse model of HD generated by bilateral intrastriatal injection of AAV vector serotype DJ (AAV-DJ) containing N171-82Q mutant HTT (82Q) and N171-18Q wild type HTT (18Q; sham). The AAV-DJ-82Q model displayed motor dysfunctions in pole and rotarod tests beginning 4 weeks after viral infection in juvenile mice (8 weeks after birth). They showed behaviors reflecting neurodegeneration. They also showed increased apoptosis, robust glial activation and upregulated representative inflammatory cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6), mediators (cyclooxygenase-2 and inducible nitric oxide synthase) and signaling pathways (nuclear factor kappa B and signal transducer and activator of transcription 3 (STAT3)) in the striatum at 10 weeks after viral infection (14 weeks after birth) via successful transfection of mutant HTT into neurons, microglia, and astrocytes in the striatum. However, little evidence of any of these events was found in mice infected with the AAV-DJ-18Q expressing construct. Intrastriatal injection of AAV-DJ-82Q might be useful as a novel in vivo model to investigate the biology of truncated N-terminal fragment (N171) in the striatum and to explore the efficacy of therapeutic strategies for HD.

Gintonin, a ginseng-derived exogenous lysophosphatidic acid receptor ligand, enhances blood-brain barrier permeability and brain delivery.

Gintonin is a ginseng-derived G-protein-coupled lysophosphatidic acid (LPA) receptor ligand. Gintonin induces [Ca2+]i transient and biological effects through LPA receptor and increases the permeability of the blood-brain barrier (BBB). However, little is known about its mechanisms on the BBB. We examined the in vitro effects of gintonin using primary human brain microvascular endothelial cells (HBMECs) and the in vivo effects of gintonin on brain delivery. Fluorescent-labeled gintonin bound to HBMECs and co-localized with the LPA1 receptor. Gintonin caused morphological changes, increased junctional spaces, and induced differential effects on junctional protein levels such as vascular endothelial-cadherin, occludin, zonula occludens 1, and claudin-5, in HBMECs. Gintonin led to the opening of gap junctions between HBMECs, and allowed Texas red-dextran to enter the cells, which was blocked by Ki16425, an LPA1/3 receptor antagonist, and Y27632, a Rho-associated kinase inhibitor. Intravenous administration of gintonin in rodents also increased the delivery of fluorescein isothiocyanate-dextran or erythropoietin to the brain. Furthermore, fluorescent-labeled gintonin bound to endothelial cells, neurons, and glia in the brain following its entry. Our findings show that gintonin facilitates entry to the brain through the paracellular pathway. Thus, gintonin may be an herbal medicine-derived candidate to overcome the BBB in drug delivery.

Effects of functionalized multi-walled carbon nanotubes on toxicity and bioaccumulation of lead in Daphnia magna.

Increased production of carbon nanotubes (CNTs) and their widespread application in industrial and consumer products have led to a rise in the release of CNTs into the aquatic environment. CNTs have a very strong adsorption affinity for various environmental contaminants; therefore, they may also influence the toxic effects of other pollutants, such as toxic metals. In this study, the effect of two different functionalized carbon nanotubes, carboxylate and polyethyleneimine modified multi-walled carbon nanotubes (C-MWCNTs and N-MWCNT, respectively) on lead toxicity and bioaccumulation was investigated with a freshwater zooplankton Daphnia magna. The acute toxicity results indicate that the different surface properties of the two types of MWCNTs have different effects on lead toxicity to D. magna. The negatively charged C-MWCNT showed a notable decrease in lead toxicity (LC50 value increased from 0.15 mg L-1 to 1.08 mg L-1 in the presence of 10 mg L-1 C-MWCNT), whereas the positively charged N-MWCNT had only a slight effect on lead toxicity (LC50 value increased from 0.15 mg L-1 to 0.16 mg L-1 in the presence of 10 mg L-1 N-MWCNT). The decrease of lead toxicity was related with the reduced bioavailability of free metal form (Pb2+) caused by greater adsorption of lead onto the MWCNTs. The present study suggests that there is a need to consider carefully the complex interaction of CNTs with toxic metals in future ecotoxicological studies.

Panax ginseng exerts antidepressant-like effects by suppressing neuroinflammatory response and upregulating nuclear factor erythroid 2 related factor 2 signaling in the amygdala.

BACKGROUND: Depression is one of the most commonly diagnosed neuropsychiatric diseases, but the underlying mechanism and medicine are not well-known. Although Panax ginseng has been reported to exert protective effects in various neurological studies, little information is available regarding its antidepressant effects. METHODS: Here, we examined the antidepressant effect and underlying mechanism of P. ginseng extract (PGE) in a chronic restraint stress (CRS)-induced depression model in mice. RESULTS: Oral administration of PGE for 14 d decreased immobility (depression-like behaviors) time in forced swim and tail suspended tests after CRS induction, which corresponded with attenuation of the levels of serum adrenocorticotropic hormone and corticosterone, as well as attenuated c-Fos expression in the amygdala. PGE enhanced messenger RNA expression level of brain-derived neurotrophic factor but ameliorated microglial activation and neuroinflammation (the level of messenger RNA and protein expression of cyclooxygenase-2 and inducible nitric oxide synthase) in the amygdala of mice after CRS induction. Interestingly, 14-d treatment with celecoxib, a selective cyclooxygenase-2 inhibitor, and Nω-nitro-L-arginine methyl ester hydrochloride, a selective inducible nitric oxide synthase inhibitor, attenuated depression-like behaviors after CRS induction. Additionally, PGE inhibited the upregulation of the nuclear factor erythroid 2 related factor 2 and heme oxygenase-1 pathways. CONCLUSION: Taken together, our findings suggest that PGE exerts antidepressant-like effect of CRS-induced depression by antineuroinflammatory and antioxidant (nuclear factor erythroid 2 related factor 2/heme oxygenase-1 activation) activities by inhibiting the hypothalamo-pituitary-adrenal axis mechanism. Further studies are needed to evaluate the potential of components of P. ginseng as an alternative treatment of depression, including clinical trial evaluation.