Risk of SARS-CoV-2 breakthrough infection following NVX-CoV2373 and BNT162b2 vaccinations in Korean Adults: A population-based observational study.

South Korea experienced a low prevalence of SARS-CoV-2 until the emergence of the omicron in early 2022, triggering a major community epidemic. To evaluate effectiveness of NVX-CoV2373 and BNT162b2 vaccines in Korean population, we conducted an observational study utilizing individual-level case data on laboratory-confirmed SARS-CoV-2 infection, along with vaccination record. A total of 47,078 recipients of NVX-CoV2373 vaccine and 7,561 recipients of BNT162b2 vaccine were eligible for the study. Thirty days post-second doses, COVID-19 rates were 7.9% (595 out of 7561) of NVX-CoV2373 recipients and 8.6 % (647 out of 7561) of BNT162b2 recipients experienced COVID-19. NVX-CoV2373 rates increased to 9.8 % and 11.2 % at 60 and 90 days, while BNT162b2 rates were 10.5 % and 11.3 % at the same intervals. The 22-weeks risk ratios for recipients of the NVX-CoV2373 vaccine as compared with recipients of the BNT162b2 vaccine were 1.11 (95 % CI, 0.99 to 1.25) for laboratory-confirmed SARS-CoV-2 infection. Continued monitoring is essential to evaluate the duration of protection across different vaccine platforms and schedules.

Efficacy of plant-derived dietary supplements in improving overall menopausal symptoms in women: An updated systematic review and meta-analysis.

This updated systematic review and meta-analysis aims to confirm the effectiveness of plant-based supplements in improving overall menopausal symptoms and vasomotor symptoms. A systematic review of the literature was conducted by searching the PubMed/MEDLINE, Web of Science, EMBASE, and CENTRAL databases up to June 2022. Randomized placebo-controlled clinical trials that evaluated the effects of dietary supplements on menopausal symptoms were included. Outcome measures included daily hot flash frequency, Kupperman's index, Menopause Rating Scale, and Greene Climacteric Scale. Pooled data were analyzed using a fixed-effects model and expressed as a weighted mean difference with a 95% confidence interval for continuous outcomes. For qualitative assessment, 67 studies were selected. For quantitative assessment, 54 reports were obtained from 61 studies. The study participants were peri- or postmenopausal women aged 38-85, most of whom experienced hot flashes as a menopausal symptom. The investigational products included 28 soy-derived, 6 red clover-derived, and 28 other plant-derived supplements. Qualitative assessment revealed that approximately 76% of the studies were generally of fair or good quality, whereas 24% were of low quality. Meta-analysis results indicated significant improvements in all questionnaire scores, including hot flash frequency, in the dietary supplement group compared with the placebo group. Comprehensive evaluation using different questionnaire tools showed that the various plant-derived dietary supplements can significantly alleviate menopausal symptoms. However, further rigorous studies are needed to determine the association of plant-derived dietary supplements with menopausal health because of the general suboptimal quality and heterogeneous nature of current evidence.

Schisandrin A in Schisandra chinensis Upregulates the LDL Receptor by Inhibiting PCSK9 Protein Stabilization in Steatotic Model.

Schisandra chinensis extract (SCE) protects against hypocholesterolemia by inhibiting proprotein convertase subtilisin/kexin 9 (PCSK9) protein stabilization. We hypothesized that the hypocholesterolemic activity of SCE can be attributable to upregulation of the PCSK9 inhibition-associated low-density lipoprotein receptor (LDLR). Male mice were fed a low-fat diet or a Western diet (WD) containing SCE at 1% for 12 weeks. WD increased final body weight and blood LDL cholesterol levels as well as alanine transaminase and aspartate aminotransferase expression. However, SCE supplementation significantly attenuated the increase in blood markers caused by WD. SCE also attenuated WD-mediated increases in hepatic LDLR protein expression in the obese mice. In addition, SCE increased LDLR protein expression and attenuated cellular PCSK9 levels in HepG2 cells supplemented with delipidated serum (DLPS). Non-toxic concentrations of schisandrin A (SA), one of the active components of SCE, significantly increased LDLR expression and tended to decrease PCSK9 protein levels in DLPS-treated HepG2 cells. High levels of SA-mediated PCSK9 attenuation was not attributable to reduced PCSK9 gene expression, but was associated with free PCSK9 protein degradation in this cell model. Our findings show that PCSK9 secretion can be significantly reduced by SA treatment, contributing to reductions in free cholesterol levels.

Evaluation of COVID-19 vaccine effectiveness in different high-risk facility types during a period of Delta variant dominance in the Republic of Korea: a cross-sectional study.

BACKGROUND: We evaluated the effectiveness of coronavirus disease 2019 vaccination in high-risk facilities in the Republic of Korea during the period when the highly transmissible Delta variant was prevalent. Additionally, we aimed to explore any disparities in vaccine effectiveness (VE) across various types of institutions, specifically distinguishing between non-medical and medical establishments. METHODS: We examined 8 outbreak clusters covering 243 cases and 895 contacts from 8 high-risk facilities divided into 2 groups: group A (4 non-medical institutions) and group B (4 medical institutions). These clusters were observed from July 27, 2021 to October 16, 2021 for the attack rate (AR) and VE with respect to disease severity. A generalized linear model with a binomial distribution was used to determine the odds ratio (OR) for disease severity and death. RESULTS: AR was notably lower in group B (medical institutions). Furthermore, VE analysis revealed that group A exhibited higher effectivity for disease severity and death than group B. The OR for disease severity was 0.24 (95% confidence interval [CI], 0.03-2.16) for group A and 0.27 (95% CI, 0.12-0.64) for group B, with the OR for death at 0.12 (95% CI, 0.01-1.32) in group A and 0.34 (95% CI, 0.14-0.87) in group B. CONCLUSION: Although VE may vary across institutions, our findings underscore the importance of implementing vaccinations in high-risk facilities. Customized vaccination programs, tailored response plans, and competent management personnel are essential for effectively addressing and mitigating public health challenges.

Patulin Ameliorates Hypertrophied Lipid Accumulation and Lipopolysaccharide-Induced Inflammatory Response by Modulating Mitochondrial Respiration.

Patulin (PAT) is a natural mycotoxin found in decaying pome fruits. Although some toxicological studies have been conducted on PAT, recent research has highlighted its anticancer and antifungal effects. However, studies have yet to examine the effects and molecular mechanisms of PAT in other metabolic diseases. Obesity is a chronic disease caused by excessive food intake and abnormal lifestyle, leading to low-grade inflammation. Therefore, this study aimed to elucidate the effect of PAT on obesity at the cellular level. PAT treatment reduced lipid accumulation, suppressed glucose and LDL uptake, inhibited lipid deposition and triglyceride synthesis, upregulated fatty acid oxidation-related genes (Pgc1α), and downregulated adipogenic/lipogenic genes (Pparγ and C/ebpα) in hypertrophied 3T3-L1 adipocytes. Additionally, PAT treatment enhanced mitochondrial respiration and mass in differentiated adipocytes and alleviated inflammatory response in activated RAW 264.7 macrophages. Moreover, PAT treatment downregulated pro-inflammatory genes (il-6, Tnf-α, Cox-2, and inos), suppressed lipopolysaccharide (LPS)-induced increase in inflammatory mediators (IL-6, TNF-α, and NO), and restored mitochondrial oxidative function in LPS-stimulated macrophages by improving oxygen consumption and mitochondrial integrity and suppressing ROS generation. Overall, these findings suggest a potential for PAT in the prevention of lipid accumulation and inflammation-related disorders.

Risk Factors Related to COVID-19 Reinfection and Fatality During the Omicron (BA.1/BA.2) Period in Korea.

BACKGROUND: This study aimed to investigate the deaths due to coronavirus disease 2019 (COVID-19) reinfection and related risk factors. METHODS: National cohort data were collected for a six-month period when omicron BA.1/BA.2 variant was dominant in South Korea. RESULTS: The long-term care facility residents (adjusted odds ratio, 3.11; 95% confidence interval [CI], 2.98-3.25) had significantly higher risk of reinfection than the general population. The risk of reinfection was significantly lower for persons with 2 or more vaccine doses compared to the unvaccinated. The risk of death was significantly higher in the reinfection group than in the primary infection group for persons in the 60-74 years age group (adjusted relative risk [aRR], 1.62; 95% CI, 1.19-2.20), and immunocompromised group (aRR, 4.56; 95% CI, 2.34-8.90). CONCLUSION: In these data, vaccination history was significantly related to reduced COVID-19 reinfection and severe progression, and scheduled vaccinations were important even with a history of infection.

Estimating the number of severe COVID-19 cases and COVID-19-related deaths averted by a nationwide vaccination campaign in Republic of Korea.

BACKGROUND: The Korea Disease Control and Prevention Agency promotes vaccination by regularly providing information on its benefits for reducing the severity of coronavirus disease 2019 (COVID-19). This study aimed to analyze the number of averted severe COVID-19 cases and COVID-19-related deaths by age group and quantify the impact of Republic of Korea's nationwide vaccination campaign. METHODS: We analyzed an integrated database from the beginning of the vaccination campaign on February 26, 2021 to October 15, 2022. We estimated the cumulative number of severe cases and COVID-19-related deaths over time by comparing observed and estimated cases among unvaccinated and vaccinated groups using statistical modeling. We compared daily age-adjusted rates of severe cases and deaths in the unvaccinated group to those in the vaccinated group and calculated the susceptible population and proportion of vaccinated people by age. RESULTS: There were 23,793 severe cases and 25,441 deaths related to COVID-19. We estimated that 119,579 (95% confidence interval [CI], 118,901-120,257) severe COVID-19 cases and 137,636 (95% CI, 136,909-138,363) COVID-19-related deaths would have occurred if vaccination had not been performed. Therefore, 95,786 (95% CI, 94,659-96,913) severe cases and 112,195 (95% CI, 110,870-113,520) deaths were prevented as a result of the vaccination campaign. CONCLUSION: We found that, if the nationwide COVID-19 vaccination campaign had not been implemented, the number of severe cases and deaths would have been at least 4 times higher. These findings suggest that Republic of Korea's nationwide vaccination campaign reduced the number of severe cases and COVID-19 deaths.

Patulin alleviates hepatic lipid accumulation by regulating lipogenesis and mitochondrial respiration.

AIMS: The aim of this study is to evaluate the effects of patulin on hepatic lipid metabolism and mitochondrial oxidative function and elucidate the underlying molecular mechanisms. MAIN METHODS: The effects of patulin on hepatic lipid accumulation were evaluated in free fatty acid-treated AML12 or HepG2 cells through oil red O staining, triglyceride assay, real-time polymerase chain reaction, and western blotting. Alteration of mitochondrial oxidative capacity by patulin treatment was determined using Seahorse analysis to measure the oxygen consumption rate. KEY FINDINGS: The increased amounts of lipid droplets induced by free fatty acids were significantly reduced by patulin treatment. Patulin markedly activated the CaMKII/AMP-activated protein kinase (AMPK)/proliferator-activated receptor-γ coactivator (PGC)-1α signaling pathway in hepatocytes, reduced the expression of sterol regulatory element binding protein 1c (SREBP-1c) and lipogenic genes, and increased the expression of genes related to mitochondrial fatty acid oxidation. In addition, patulin treatment enhanced the mitochondrial consumption rate and increased the expression of mitochondrial oxidative phosphorylation proteins in HepG2 hepatocytes. The effects of patulin on anti-lipid accumulation; SREBP-1c, PGC-1α, and carnitine palmitoyltransferase 1 expression; and mitochondrial oxidative capacity were significantly prevented by compound C, an AMPK inhibitor. SIGNIFICANCE: Patulin is a potent inducer of the AMPK pathway, and AMPK-mediated mitochondrial activation is required for the efficacy of patulin to inhibit hepatic lipid accumulation. This study is the first to report that patulin is a promising bioactive compound that prevents the development and worsening of fatty liver diseases, including non-alcoholic fatty liver disease, by improving mitochondrial quality and lipid metabolism.

Effectiveness of Heterologous COVID-19 Vaccine Booster in Korean Elderly Population, 2022.

We conducted a cohort study to assess vaccine effectiveness (VE) of coronavirus disease 2019 vaccine combinations on severe acute respiratory syndrome coronavirus 2 critical infection and death among elderly population in Korea. From January to August 2022, VE against death for 4 doses mRNA recipients was 96.1%, whereas 1-dose viral vector + 3-dose mRNA recipients had VE of 90.8%.

A Mixture of Artemisia argyi and Saururus chinensis Improves PM2.5-Induced Cognitive Dysfunction by Regulating Oxidative Stress and Inflammatory Response in the Lung and Brain.

This study was performed to investigate the improving effect of a mixture of Artemisia argyi and Saururus chinensis (AASC) on cognitive dysfunction in mice with long-term exposure to fine particles (particulate matter smaller than 2.5 µm: PM2.5). The main compounds of AASC were identified as dicaffeoylquinic acid isomers of A. argyi and a quercetin-3-glucoside of S. chinesis. As a result of behavioral tests for the evaluation of cognitive function, it was confirmed that cognitive dysfunction was induced in the PM2.5 exposure group, and a tendency to improve in the AASC group was confirmed. Increased oxidative stress and inflammatory response and mitochondrial dysfunction were observed in the brain and lung tissues of the PM group. Damage to the brain and lung affected the accumulation of amyloid beta (Aß) in the brain. It increased Aß and induced the cholinergic dysfunction, hyperphosphorylation of the tau protein, and activation of apoptosis, leading to cognitive impairment. However, AASC suppressed brain and lung oxidative stress and inflammation, thereby suppressing brain Aß expression. Consequently, this study shows the potential that a steady intake of plant resources with antioxidant and anti-inflammatory activity could prevent cognitive impairment caused by PM2.5.

Effectiveness of A Fourth Dose of COVID-19 mRNA Vaccine in the Elderly Population During the Omicron BA.2 and BA.5 Circulation: A Nationwide Cohort Study in Korea (K-COVE).

We estimate the effectiveness of a fourth dose booster of coronavirus disease 2019 mRNA vaccine in individuals aged ≥60 years during Omicron BA.2 and BA.5 circulation in Korea. The effectiveness against critical infection was 67.7% (95% confidence interval, 50.7%-78.8%) at 31-60 days and 62.1% (95% confidence interval, 45.5%-73.7%) at 61-90 days.

Estimated Effectiveness of Prior SARS-CoV-2 BA.1 or BA.2 Infection and Booster Vaccination Against Omicron BA.5 Subvariant Infection.

This case-control study estimates the effectiveness of prior SARS-CoV-2 BA.1 or BA.2 infection and booster vaccination against Omicron BA.5 subvariant infection.

Leaves of Cedrela sinensis Attenuate Chronic Unpredictable Mild Stress-Induced Depression-like Behavior via Regulation of Hormonal and Inflammatory Imbalance.

This study aimed to evaluate the protective effects of ethyl acetate fraction from Cedrela sinensis (EFCS) against chronic unpredictable mild stress (CUMS)-induced behavioral dysfunction and stress response in C57BL/6 mice. The physiological compounds of EFCS were identified as rutin, isoquercitrin, ethyl gallate, quercitrin, kaempferol-3-O-rhamnoside, and ethyl digallate, using UPLC-Q-TOF/MSE. To evaluate the neuroprotective effect of EFCS, H2O2- and corticosterone-induced neuronal cell viability was conducted in human neuroblastoma MC-IXC cells. It was found that EFCS alleviated depression-like behavior by conducting the sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and tail suspension test (TST). EFCS inhibited mitochondrial dysfunction related to neuronal energy metabolism by regulating reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), and ATP contents in brain tissue. In addition, the administration of EFCS regulated the stress hormones in serum. EFCS regulated stress-related indicators such as CRF, ACTH, CYP11B1, and BDNF. Moreover, EFCS downregulated the inflammatory responses and apoptosis proteins such as caspase-1, TNF-α, IL-1ß, p-JNK, BAX, and p-tau in brain tissues. These results suggest that EFCS might be a potential natural plant material that alleviates CUMS-induced behavior disorder by regulating inflammation in brain tissue against CUMS-induced depression.

Effectiveness of Second mRNA COVID-19 Booster Vaccine in Immunocompromised Persons and Long-Term Care Facility Residents.

We used a nationwide population registry in South Korea to estimate the effect of a second booster dose of mRNA COVID-19 vaccine on the risk for laboratory-confirmed SARS-CoV-2 infection, critical infection, and death in immunocompromised persons and long-term care facility (LTCF) residents. During February 16-May 7, 2022, among 972,449 eligible persons, 736,439 (75.7%) received a first booster and 236,010 (24.3%) persons received a second booster. Compared with the first booster group, at 30-53 days, the second booster recipients had vaccine effectiveness (VE) against all infections of 22.28% (95% CI 19.35%-25.11%), VE against critical infection of 56.95% (95% CI 29.99%-73.53%), and VE against death of 62.96% (95% CI 34.18%-79.15%). Our findings provide real-world evidence that a second booster dose of mRNA vaccine substantially increases protection against critical infection and death in these high-risk population groups.

Korean Red Pine (Pinus densiflora) Bark Extract Attenuates Aß-Induced Cognitive Impairment by Regulating Cholinergic Dysfunction and Neuroinflammation.

In this study, we investigated the anti-amnesic effect of Korean red pine (Pinus densiflora) bark extract (KRPBE) against amyloid beta1-42 (Aß1-42)-induced neurotoxicity. We found that treatment with KRPBE improved the behavioral function in Aß-induced mice, and also boosted the antioxidant system in mice by decreasing malondialdehyde (MDA) content, increasing superoxide dismutase (SOD) activities, and reducing glutathione (GSH) levels. In addition, KRPBE improved the cholinergic system by suppressing reduced acetylcholine (ACh) content while also activating acetylcholinesterase (AChE), regulating the expression of choline acetyltransferase (ChAT), postsynaptic density protein-95 (PSD-95), and synaptophysin. KRPBE also showed an ameliorating effect on cerebral mitochondrial deficit by regulating reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and ATP levels. Moreover, KRPBE modulated the expression levels of neurotoxicity indicators Aß and phosphorylated tau (p-tau) and inflammatory cytokines TNF-α, p-IκB-α, and IL-1ß. Furthermore, we found that KRPBE improved the expression levels of neuronal apoptosis-related markers BAX and BCl-2 and increased the expression levels of BDNF and p-CREB. Therefore, this study suggests that KRPBE treatment has an anti-amnestic effect by modulating cholinergic system dysfunction and neuroinflammation in Aß1-42-induced cognitive impairment in mice.

Porphyra tenera Protects against PM2.5-Induced Cognitive Dysfunction with the Regulation of Gut Function.

To evaluate the biological effects of Porphyra tenera (P. tenera), we tried to confirm the possibility that the intake of P. tenera could modulate cognitive and intestinal functions in PM2.5-induced cognitive decline mice. P. tenera attenuated PM2.5-induced learning and memory impairment through antioxidant and anti-inflammatory effects by regulating the mitochondrial function and TLR-initiated NF-κB signaling. In addition, P. tenera effectively alleviated Aß production/tau phosphorylation by inhibiting the JNK phosphorylation. Also, the bioactive constituents of P. tenera determined the sulfated galactan, mycosporine-like amino acids (MAAs), and chlorophyll derivatives. Moreover, the bioactive compounds of P. tenera by gut fermentation protected against gut dysbiosis and intestinal tight junction damage with a decrease in inflammatory response and short-chain fatty acid production. Based on these results, our findings suggest that P. tenera with sulfated galactan and MAAs is a potential material for cognitive function improvement.

Water Extract of Ecklonia cava Protects against Fine Dust (PM2.5)-Induced Health Damage by Regulating Gut Health.

To confirm the therapeutic effect of the water extract from Ecklonia cava (WEE) against PM2.5 induced systemic health damage, we evaluated gut health with a focus on the microbiota and metabolites. Systemic damage in mice was induced through PM2.5 exposure for 12 weeks in a whole-body chamber. After exposure for 12 weeks, body weight and food intake decreased, and WEE at 200 mg/kg body weight (mpk) alleviated these metabolic efficiency changes. In addition, PM2.5 induced changes in the length of the colon and fecal water content. The administration of the WEE at 200 mpk oral dose effectively reduced changes in the colon caused by PM2.5 exposure. We also attempted to confirm whether the effect of the WEE is mediated via regulation of the microbiota-gut-brain axis in mice with PM2.5 induced systemic damage. We examined changes in the fecal microbiota and gut metabolites such as short-chain fatty acids (SCFAs) and kynurenine metabolites. In the PM2.5 exposed group, a decrease in the abundance of Lactobacillus (Family: Lactobacillaceae) and an increase in the abundance of Alistipes (Family: Rikenellaceae) were observed, and the administration of the WEE showed a beneficial effect on the gut microbiota. In addition, the WEE effectively increased the levels of SCFAs (acetate, propionate, and butyrate). Furthermore, kynurenic acid (KYNA), which is a critical neuroprotective metabolite in the gut-brain axis, was increased by the administration of the WEE. Our findings suggest that the WEE could be used as a potential therapeutic against PM2.5 induced health damage by regulating gut function.

Persimmon Water Extract Suppresses Hepatic Lipotoxicity by Regulating Lipid Metabolites.

This study was performed to investigate the effects of persimmon (Diospyros kaki) on high-fat diet (HFD)-induced hepatic lipotoxicity. The compounds of persimmon water extract (PWE) were identified as gallic acid, glucogallin, 1-O-Galloyl-(2-O-acetyl)-glu, and trihydroxy-octadecadienoic acid. The PWE was ingested by C57BL/6 mice with an HFD for 8 weeks. The PWE improved glucose tolerance and suppressed weight gain by inhibiting increases in the weight of liver and adipose tissues. The results of serum biomarker analysis showed that PWE suppressed biomarkers such as liver injury and dyslipidemia. In ex vivo tests, reduction of oxidative stress and improvement of mitochondrial dysfunction were confirmed in the liver of PWE groups. In a molecular study, it was confirmed that PWE decreased lipid accumulation, insulin resistance, inflammation, and apoptosis in the liver. Finally, in a metabolite analysis of liver tissue using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), it was confirmed that PWE has an effect on lipid metabolism. In particular, PWE reduced phosphatidylcholines (PCs) and lysophosphatidylcholines (lysoPCs). Notably, it is presumed that the reduction of lysoPCs and PCs in the PWE group is related to the improvement of liver dysfunction due to lipotoxicity.

Peanut (Arachis hypogaea) sprout prevents high-fat diet-induced cognitive impairment by improving mitochondrial function.

This study was performed to evaluate the improvement effect of the ethyl acetate fraction from peanut (Arachis hypogaea) sprout (EFPS) on high-fat diet (HFD)-induced cognitive deficits in C57BL/6 mice. Mice were randomly divided four groups (n = 13) as control (normal chow), HFD, EFPS 20 (20 mg/kg of body weight; intragastric administration) and EFPS 50 (50 mg/kg of body weight; intragastric administration) groups. HFD was provide for 15 weeks excepting control group. EFPS ameliorated cognitive dysfunction in Y-maze, passive avoidance test and Morris water maze test. EFPS significantly improved glucose tolerance and serum lipid profile, and reduced body weight. EFPS ameliorated oxidative stress by regulating MDA levels and SOD activity in liver and brain tissues. In addition, EFPS restored brain mitochondrial dysfunction related to energy metabolism. Moreover, the bioactive compounds of EFPS were identified as di-caffeic acid, caffeic acid, dihydrokaempferol-hexoside, di-p-coumaroyl tartaric acid isomer and group B soyasaponins using ultra-performance liquid chromatography-quadrupole-time-of-flight (UPLC-Q-TOF) mass spectrometry. These results show that EFPS can improve cognitive functions in HFD-induced diabetic mice.

Powdered Green Tea (Matcha) Attenuates the Cognitive Dysfunction via the Regulation of Systemic Inflammation in Chronic PM2.5-Exposed BALB/c Mice.

This study was conducted to evaluate the anti-amnesic effect of the aqueous extract of powdered green tea (matcha) (EM) in particulate matter (PM)2.5-induced systemic inflammation in BALB/c mice. EM ameliorated spatial learning and memory function, short-term memory function, and long-term learning and memory function in PM2.5-induced mice. EM protected against antioxidant deficit in pulmonary, dermal, and cerebral tissues. In addition, EM improved the cholinergic system through the regulation of acetylcholine (ACh) levels and acetylcholinesterase (AChE) activity in brain tissue, and it protected mitochondrial dysfunction by regulating the production of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and ATP contents in brain tissue. EM attenuated systemic inflammation and apoptotic signaling in pulmonary, dermal, olfactory bulb, and hippocampal tissues. Moreover, EM suppressed neuronal cytotoxicity and cholinergic dysfunction in hippocampal tissue. This study suggests that EM might be a potential substance to improve PM2.5-induced cognitive dysfunction via the regulation of systemic inflammation.