Association Between Multiple Heavy Metal Exposures and Cholesterol Levels in Residents Living Near a Smelter Plant in Korea.

BACKGROUND: Considering the interactions between heavy metals, a comprehensive evaluation of the effects of exposure to various types of co-interacting heavy metals on health is required. This study assessed the association between dyslipidemia markers and blood mercury, lead, cadmium, iron, zinc, and nickel levels in residents of an abandoned refinery plant. METHODS: A total of 972 individuals (exposed group: 567, control group: 405) living near the Janghang refinery plant in the Republic of Korea were included. Blood mercury, lead, cadmium, iron, zinc, nickel, cholesterol, and triglyceride levels were measured. The combined effect of the six heavy metals on dyslipidemia markers was evaluated using a Bayesian kernel machine regression (BKMR) model and compared with the results of a linear regression analysis. The BKMR model results were compared using a stratified analysis of the exposed and control groups. RESULTS: In the BKMR model, the combined effect of the six heavy metals was significantly associated with total cholesterol (TC) levels both below the 45th percentile and above the 55th percentile in the total population. The combined effect range between the 25th and 75th percentiles of the six metals on TC levels was larger in the exposed group than that in the total population. In the control group, the combined effects of the changes in concentration of the six heavy metals on the TC concentration were not statistically significant. CONCLUSION: These results suggest that the cholesterol levels of residents around the Janghang refinery plant may be elevated owing to exposure to multiple heavy metals.

E-cigarettes exacerbate allergic inflammation via cytokine induction and MUC5AC/5B expression in a murine asthma model.

The effects of electronic cigarettes (e-cigarettes) vapor on inflammation and mucin secretion on asthmatics remain insufficiently explored. This study investigated the effects of e-cigarette vapor on allergic inflammation, cytokine production, and MUC5AC/5B expression in murine asthma model. Airway hyperresponsiveness was significantly higher in the e-cigarette-exposed ovalbumin (OVA) sensitization group than in the control, e-cigarette exposure, and OVA sensitization groups. The e-cigarette-exposed OVA sensitization group showed significantly greater infiltration of inflammatory cells and Th2-mediated inflammatory cytokines (interleukin-4 and -5) compared to the control, e-cigarette exposure, and OVA sensitization groups. MUC5AC mucin levels were significantly elevated in the e-cigarette exposure, OVA sensitization, and e-cigarette-exposed OVA sensitization groups, whereas MUC5B mucin levels were significantly elevated in the OVA sensitization and e-cigarette-exposed OVA sensitization groups. The results may suggest that the exposure to e-cigarette vapor in an asthmatics promoted allergic inflammation and increased mucin secretion, ultimately leading to the exacerbation of asthma.

Microscopic mechanisms for initiation and evolution of femtosecond laser-induced columnar structures above the surface level of aluminum.

A better understanding of the formation of femtosecond (fs) laser-induced surface structures is key to the control of their morphological profiles for desired surface functionalities on metals. In this work, with fs laser pulse irradiation, the two stages of formation mechanisms of the columnar structures (CSs) grown above the surface level are investigated on pure Al plates in ambient air. Here, we find that the redeposition of ablated microscale clusters following fs laser pulses of irradiation acts as the nucleation sites of CS formation, which strongly affects their location and density within the laser spot. Furthermore, we suggest their structural growths and morphological shape changes are directly associated with the competition among four laser-impact hydrodynamical phenomena: laser ablation, subsequent molten metal flow, particles' redeposition, and metal vapor condensation with continued pulse irradiation.

Association between urinary arsenic concentration and genetic polymorphisms in Korean adults.

Arsenic (As) is a human carcinogen widely distributed in the environment. This study evaluated the association between the urinary As concentration and single nucleotide polymorphisms (SNPs) in Korean adults to determine the genetic factors related to As concentration. The study included 496 participants for the genome-wide association study (GWAS) and 1483 participants for the candidate gene approach study. Participants were 19 years and older. The concentrations of total As (Tot As) and total As metabolites (Tmet As, the sum of inorganic As and their metabolites; arsenite, arsenate, monomethylarsonic, and dimethylarsinic acid) in the urine were analyzed. The GWAS identified four SNPs (rs1432523, rs3776006, rs11171747, and rs807573) associated with urinary Tot As and four SNPs (rs117605537, rs3776006, rs11171747, and rs148103384) significantly associated with urinary Tmet As concentration (P < 1 × 10-4). The candidate gene study identified two SNPs (PRDX2 rs10427027 and GLRX rs3822751) in genes related to the reduction reaction associated with urinary Tot As and Tmet As. This study suggests that genetic factors may play a role in regulating As metabolism in the human body, affecting both exposure levels and its potential health risks in the general Korean population, even at low exposure levels. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00216-x.

Complete response of metastatic BRAF V600-mutant anaplastic thyroid cancer following adjuvant dabrafenib and trametinib treatment: A case report.

BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare but aggressive type of thyroid carcinoma. BRAF V600E-mutation, which is found in 10%-50% of ATCs, is associated with poor prognosis. A recent clinical trial reported a substantial clinical benefit of concomitant treatment of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) for treating BRAF V600E-mutant ATC. However, reports on patients with ATC treated with this regimen following surgery are lacking. CASE SUMMARY: We report the case of a 63-year-old female patient diagnosed with BRAF V600E-mutant ATC. Following three surgeries-total thyroidectomy, total laryngectomy, and neck dissection-she was diagnosed with lung metastasis during follow-up. The metastatic ATC was successfully treated with dabrafenib and trametinib. The patient achieved a complete response at the 32-mo follow-up. CONCLUSION: Adjuvant chemotherapy with dabrafenib plus trametinib is efficacious for treatment and prevention of recurrent ATC with BRAF mutation following surgery.

Exposure to Hazardous Substances and Their Health Effects Among Residents Living Near Three Industrial Waste Incinerators in Korea.

BACKGROUND: This study aimed to evaluate exposure to various hazardous substances emitted by incineration facilities and their likely effect on the health for residents of Bugi-myeon, Cheongju, Korea, which has three incineration facilities. METHODS: Heavy metals, polycyclic aromatic hydrocarbons (PAHs), and dioxin concentrations in the air and soil of exposed and control areas were measured. Moreover, the exposure levels to harmful substances and its effects on health were investigated in 1,124 exposed and 232 control adults. RESULTS: PAHs and dioxin concentrations in the air in the exposed area were significantly higher than in the control area. Urinary cadmium and PAHs metabolite concentrations were significantly higher in the exposed group than in the control group. The exposure group also had a higher prevalence of depression and self-reported allergic symptoms than the control group. CONCLUSION: The possibility of residents in Bugi-myeon being exposed to hazardous substances at incineration facilities cannot be ruled out. To prevent them from further exposure to hazardous substances, it is necessary to prohibit the expansion of additional incineration facilities in this area and to implement continuous monitoring projects for residents.

C-C Motif Chemokine Receptor 3-Mediated Extracellular Signal-Regulated Kinase 1/2 and p38 Mitogen-Activated Protein Kinase Signaling: Promising Targets for Human Airway Epithelial Mucin 5AC Induction by Eotaxin-2 and Eotaxin-3.

INTRODUCTION: Eotaxin-2 and -3 of the C-C chemokine subfamily function as potent chemoattractant factors for eosinophil recruitment and various immune responses in allergic and inflammatory airway diseases. Mucin 5AC (MUC5AC), a major gel-forming secretory mucin, is overexpressed in airway inflammation. However, the association between mucin secretion and eotaxin-2/3 expression in the upper and lower airway epithelial cells has not been fully elucidated. Therefore, in this study, we investigated the effects of eotaxin-2/3 on MUC5AC expression and its potential signaling mediators. METHODS: We analyzed the effects of eotaxin-2 and -3 on NCI-H292 human airway epithelial cells and primary human nasal epithelial cells (HNEpCs) via reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting. Along with immunoblot analyses with specific inhibitors and small interfering RNA (siRNA), we explored the signaling pathway involved in MUC5AC expression following eotaxin-2/3 treatment. RESULTS: In HCI-H292 cells, eotaxin-2/3 activated the mRNA expression and protein production of MUC5AC. A specific inhibitor of C-C motif chemokine receptor 3 (CCR3), SB328437, suppressed eotaxin-2/3-induced MUC5AC expression at both the mRNA and protein levels. Eotaxin-2/3 induced the phosphorylation of extracellular signal-regulated kinase (ERK)-1/2 and p38, whereas pretreatment with a CCR3 inhibitor significantly attenuated this effect. Induction of MUC5AC expression with eotaxin-2/3 was decreased by U0126 and SB203580, specific inhibitors of ERK1/2 and p38 mitogen-activated protein kinase (MAPK), respectively. In addition, cell transfection with ERK1/2 and p38 siRNAs inhibited eotaxin-2/3-induced MUC5AC expression. Moreover, specific inhibitors (SB328437, U0126, and SB203580) attenuated eotaxin-2/3-induced MUC5AC expression in HNEpCs. CONCLUSION: Our results imply that CCR3-mediated ERK1/2 and p38 MAPK are involved in the signal transduction of eotaxin-2/3-induced MUC5AC overexpression.

Tractional Retinal Detachment in Eyes with Vitreous Hemorrhage and Proliferative Diabetic Retinopathy and Posterior Vitreous Detachment in Fellow Eye.

PURPOSE: To predict the presence of tractional retinal detachment (TRD) in eyes with dense vitreous hemorrhage (VH) and proliferative diabetic retinopathy (PDR) by evaluating the status of posterior vitreous detachment (PVD) in fellow eyes using optical coherence tomography (OCT). METHODS: A total of 44 eyes from 22 patients who underwent vitrectomy due to dense VH with PDR were enrolled. Using OCT, the PVD status in the fellow eye was divided into two groups (incomplete and complete PVD). The incomplete PVD group included eyes without PVD and eyes with partial PVD. B-scan ultrasonography was performed on eyes with dense VH to evaluate the presence of TRD. Both OCT and B-scan images were reviewed by four ophthalmologists (two novices and two experienced), and the interobserver agreement was evaluated. RESULTS: There was a difference in the interobserver agreement regarding the presence of TRD in eyes with dense VH evaluated by B scan between novice and experienced ophthalmologists (novice, κ = 0.421 vs. experienced, κ = 0.814), although there was no difference between novice and experienced ophthalmologists in the interobserver agreement regarding the status of PVD in the fellow eye evaluated by OCT (novice, κ = 1.000 vs. experienced, κ = 1.000). All observed TRD during vitrectomy occurred in eyes with incomplete PVD in the fellow eye. Logistic regression analysis revealed a statistically significant relation between TRD and the age of the patient (odds ratio [OR], 0.874; p = 0.047), and between TRD and incomplete PVD in the fellow eye evaluated by OCT (OR, 13.904; p = 0.042). CONCLUSIONS: Evaluation of the PVD status in the fellow eye using OCT may be a useful predictor for detecting the presence of TRD in eyes with dense VH and PDR.

Deep learning-based optical authentication using the structural coloration of metals with femtosecond laser-induced periodic surface structures.

Structurally colored materials present potential technological applications including anticounterfeiting tags for authentication due to the ability to controllably manipulate colors through nanostructuring. Yet, no applications of deep learning algorithms, known to discover meaningful structures in data with far-reaching optimization capabilities, to such optical authentication applications involving low-spatial-frequency laser-induced periodic surface structures (LSFLs) have been demonstrated to date. In this work, by fine-tuning one of the lightweight convolutional neural networks, MobileNetV1, we investigate the optical authentication capabilities of the structurally colorized images on metal surfaces fabricated by controlling the orientation of femtosecond LSFLs. We show that the structural color variations due to a broad range of the illumination incident angles combined with both the controlled orientations of LSFLs and differences in features captured in the image make this system suitable for deep learning-based optical authentication.

Cinnamon (Cinnamomum cassia) water extract improves diarrhea symptoms by changing the gut environment: a randomized controlled trial.

Cinnamon is a spice obtained from the bark of Cinnamomum and contains anti-inflammatory ingredients such as coumarin, cinnamaldehyde, and cinnamic acid. This study evaluated the effect of cinnamon water extract (CWE) on the symptoms of subjects with diarrhea in an 8-week randomized controlled trial. Seventy subjects with diarrhea symptoms were randomized and received three capsules of 400 mg CWE or placebo twice daily for 8 weeks. CWE intake significantly increased colonic transit time (p = 0.019) and fecal isobutyric acid (p = 0.008) and spermidine (p = 0.009) contents compared to placebo intake. In contrast, CWE decreased fecal indole (p = 0.032) and agmatine (p = 0.018) contents. Gut microbiota analysis showed increased alpha diversity and significant changes in strains such as Bifidobacterium longum ATCC 55813 (LDA = 1.38) in the CWE group compared with the placebo group. Bifidobacterium longum ATCC 55813 showed a positive correlation with colon transit time and stool phenol and spermidine contents. CWE improved diarrhea symptoms and changed the composition of stools and the gut microbiota. These results indicate that cinnamon intake relieves diarrhea symptoms through metabolic changes due to changes in intestinal microbial groups.

Clinical Trial to Reconfirm the Efficacy and Safety of Cefetamet Pivoxil Treatment in Sinusitis Patients: A Double-Blind, Randomized, Parallel Designed, Multicenter, Active Comparator Study (CASIS Study).

OBJECTIVE: To evaluate the clinical efficacy and safety of cefetamet pivoxil for the treatment of acute bacterial rhinosinusitis in Korean patients compared to treatment with cefdinir. METHODS: A prospective, multicenter, randomized double-blind, comparative study was conducted by the Departments of Otorhinolaryngology-Head and Neck Surgery at 17 hospitals or universities in the Republic of Korea from March 2017 to April 2019. A total of 309 patients were screened and 249 patients participated in the study. RESULTS: Treatment with cefetamet pivoxil for 2 weeks showed 82.4% clinical cure and improvement rates in patients with acute bacterial rhinosinusitis compared to 84.68% in those taking cefdinir for 2 weeks, showing that cefetamet pivoxil administered twice a day for 2 weeks was as effective as cefdinir 3 times a day for 2 weeks for the treatment of acute bacterial rhinosinusitis. The overall adverse reaction rates of both drugs were 10.56% in the cefetamet pivoxil group and 15.49% in the cefdinir group, without serious adverse events or drug reactions. CONCLUSIONS: Cefetamet pivoxil twice a day was as efficacious and safe as cefdinir 3 times a day for the treatment of acute bacterial rhinosinusitis, which suggested that cefetamet pivoxil may be a suitable alternative to cefdinir.

Ghrelin Downregulates Lipopolysaccharide/ Leptin-Induced MUC5AC Expression in Human Nasal Epithelial Cells.

OBJECTIVES: Obesity, which induces chronic low-grade systemic inflammation in the human body, is a known risk factor for various diseases. Recent studies have shown associations between various otorhinolaryngological diseases and obesity. In particular, inflammatory sinonasal diseases have been found to be strongly associated with obesity-related proinflammatory mediators. Many studies have been conducted to identify therapeutic agents for controlling obesity-related inflammatory airway diseases. Ghrelin, an endogenous peptide from the stomach, has anti-inflammatory and antioxidative effects in a wide range of tissues. However, the effect of ghrelin on the regulation of mucus secretion has not yet been studied in the human nasal mucosa. Therefore, we investigated the effects of ghrelin on lipopolysaccharide (LPS)/leptin-mediated MUC5AC expression and mechanisms involved in human nasal epithelial cells (HNEpCs). METHODS: In HNEpCs, the effect and signaling pathways of ghrelin on LPS/leptin-induced MUC5AC expression were examined using reverse transcription polymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassays, Western blotting, and immunofluorescence staining. RESULTS: Growth hormone secretagogue receptor 1a (GHSR1a) was expressed in the HNEpCs. Ghrelin downregulated LPS/leptin-induced MUC5AC expression, which was abolished by D-Lys-3-growth hormone-releasing peptide 6 (D-Lys-3-GHRP-6). Ghrelin significantly inhibited LPS/leptin-activated extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs). These ghrelin-mediated changes in MAPK activation were abolished by D-Lys-3-GHRP-6. These. RESULTS: showed that ghrelin inhibits LPS/leptin-induced MUC5AC overexpression by modulating the ERK1/2 and p38 MAPK pathways in HNEpCs. CONCLUSION: These findings suggest that ghrelin is a potential therapeutic agent for treating obesity-related inflammatory sinonasal diseases.

Saponin attenuates diesel exhaust particle (DEP)-induced MUC5AC expression and pro-inflammatory cytokine upregulation via TLR4/TRIF/NF-κB signaling pathway in airway epithelium and ovalbumin (OVA)-sensitized mice.

Background: Diesel exhaust particle (DEP) is a harmful kind of particulate matter known to exacerbate pre-existing respiratory diseases. Although their adverse effects on airway pathologies have been widely studied, the mechanistic analysis of signaling pathways and potential targets in reducing DEP-induced mucin secretion and pro-inflammatory cytokine production remain elusive. We, for the first time, investigated the effects of Korean Red Ginseng (KRG) extracts on mucin overproduction and airway inflammation induced by DEP. Methods: The effects of KRG and saponin on DEP-induced expression of MUC5AC and interleukin (IL)-6/8 were examined by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) in human airway epithelial NCI-H292 cells. We conducted Western blotting analysis to analyze the associated signaling pathways. To evaluate the effects of saponin treatment on DEP-induced MUC5AC expression and inflammatory cell infiltrations in ovalbumin (OVA)-sensitized mice, immunohistochemical (IHC) staining and real-time PCR were implemented. Results: The KRG extracts markedly attenuated DEP-induced MUC5AC expression in vitro by inhibiting the TLR4/TRIF/NF-κB pathway. Furthermore, KRG and saponin inhibited DEP-induced pro-inflammatory cytokine IL-6/8 production. The in vivo study revealed that saponin blocked DEP-induced inflammation, mucin production and MUC5AC expression. Conclusion: Our study revealed that KRG extracts have inhibitory effects on DEP-induced expression of MUC5AC and the production of pro-inflammatory cytokines. This finding provides novel insights into the mechanism by which saponin alleviates diesel-susceptible airway inflammation, elucidating its potential as a phytotherapeutic agent for inflammatory pathologies of airway.

Effects of Air Pollution on Chemosensory Dysfunction in COVID-19 Patients.

BACKGROUND: In some patients, coronavirus disease 2019 (COVID-19) is accompanied by loss of smell and taste, and this has been reportedly associated with exposure to air pollutants. This study investigated the relationship between the occurrence of chemosensory dysfunction in COVID-19 patients and air pollutant concentrations in Korea. METHODS: Information on the clinical symptom of chemosensory dysfunction, the date of diagnosis, residential area, age, and sex of 60,194 confirmed COVID-19 cases reported to the Korea Disease Control and Prevention Agency from January 20 to December 31, 2020 was collected. In addition, the daily average concentration of air pollutants for a week in the patients' residential area was collected from the Ministry of Environment based on the date of diagnosis of COVID-19. A binomial logistic regression model, using age and gender, standardized smoking rate, number of outpatient visits, 24-hour mean temperature and relative humidity at the regional level as covariates, was used to determine the effect of air pollution on chemosensory dysfunction. RESULTS: Symptoms of chemosensory dysfunction were most frequent among patients in their 20s and 30s, and occurred more frequently in large cities. The logistic analysis showed that the concentration of particulate matter 10 (PM10) and 2.5 (PM2.5) up to 2 days before the diagnosis of COVID-19 and the concentration of sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) at least 7 days before the diagnosis of COVID-19 affected the development of chemosensory dysfunction. In the logistic regression model adjusted for age, sex, standardized smoking rate, number of outpatient visits, and daily average temperature and relative humidity, it was found that an increase in the interquartile range of PM10, PM2.5, SO2, NO2, and CO on the day of diagnosis increased the incidence of chemosensory dysfunction 1.10, 1.10, 1.17, 1.31, and 1.19-fold, respectively. In contrast, the O3 concentration had a negative association with chemosensory dysfunction. CONCLUSION: High concentrations of air pollutants such as PM10, PM2.5, SO2, NO2, and CO on the day of diagnosis increased the risk of developing chemosensory dysfunction from COVID-19 infection. This result underscores the need to actively prevent exposure to air pollution and prevent COVID-19 infection. In addition, policies that regulate activities and products that create high amounts of harmful environmental wastes may help in promoting better health for all during COVID-19 pandemic.

Enhanced antibody responses in fully vaccinated individuals against pan-SARS-CoV-2 variants following Omicron breakthrough infection.

Omicron has become the globally dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, creating additional challenges due to its ability to evade neutralization. Here, we report that neutralizing antibodies against Omicron variants are undetected following COVID-19 infection with ancestral or past SARS-CoV-2 variant viruses or after two-dose mRNA vaccination. Compared with two-dose vaccination, a three-dose vaccination course induces broad neutralizing antibody responses with improved durability against different SARS-CoV-2 variants, although neutralizing antibody titers against Omicron remain low. Intriguingly, among individuals with three-dose vaccination, Omicron breakthrough infection substantially augments serum neutralizing activity against a broad spectrum of SARS-CoV-2 variants, including Omicron variants BA.1, BA.2, and BA.5. Additionally, after Omicron breakthrough infection, memory T cells respond to the spike proteins of both ancestral and Omicron SARS-CoV-2 by producing cytokines with polyfunctionality. These results suggest that Omicron breakthrough infection following three-dose mRNA vaccination induces pan-SARS-CoV-2 immunity that may protect against emerging SARS-CoV-2 variants of concern.

Effects of gene polymorphisms of CYP1A1, CYP1B1, EPHX1, NQO1, and NAT2 on urinary 1-nitropyrene metabolite concentrations.

Nitropyrene (1-NP) is a specific indicator of exposure to diesel exhaust and is partly metabolized to 1-aminopyrene (1-AP) and N-acetyl-1-aminopyrene (1-NAAP), which are excreted in urine. This study was conducted to evaluate the effects of gene polymorphisms of metabolic enzymes for 1-NP on the urinary concentrations of 1-AP and 1-NAAP. The study participants were 70 South Koreans who were occupationally or environmentally exposed to diesel exhaust. To evaluate 1-NP exposure levels, we sampled airborne particulate matters with a personal air sampler and measured urinary 1-AP and 1-NAAP concentrations. The genetic polymorphisms of the 1-NP metabolic enzymes (CYP1A1, CYP1B1, EPHX1, NQO1, and NAT2) were determined by direct sequencing. The mean 1-NP exposure level was 20.40 pg/m3, and the mean urinary concentrations of 1-AP and 1-NAAP were 0.074 nM and 0.213 nM, respectively. The correlation coefficient between the 1-NP exposure level and urinary 1-AP concentrations was 0.0138 and that between the 1-NP exposure level and urinary 1-NAAP concentrations was 0.1493, and neither correlation coefficient was statistically significant. The correlation coefficient between the 1-NP exposure level and urinary 1-AP concentrations showed statistically significant differences according to the CYP1A1 and CYP1B1 genotypes, and that between the 1-NP exposure level and urinary 1-NAAP concentrations was significantly different according to the CYP1A1, CYP1B1, and NAT2 genotypes. The urinary concentration of 1-NAAP is a better biomarker for exposure to 1-NP or DEPs because the former is higher, easier to measure, and more strongly correlated with 1-NP exposure levels than that of 1-AP. The relationship between 1-NP exposure and urinary 1-AP or 1-NAAP concentration depends on the single nucleotide polymorphism types of CYP1A1, CYP1B1, NQO1, and NAT2.

Particulate Matter Exposure after a Cancer Diagnosis and All-Cause Mortality in a Regional Cancer Registry-Based Cohort in South Korea.

Although particulate matter (PM) is a Group 1 carcinogen, few studies have evaluated the effect of PM exposure after a cancer diagnosis on survival. Herein, we evaluated the effect of exposure to ambient PM10 after a cancer diagnosis on survival using data from the Regional Cancer Registry cohort in Chungbuk Province, Korea. A total of 44,432 patients with cancer who survived for >1 year after being diagnosed between 2005 and 2018 were followed until 31 December 2019; there were 32,734 survivors (73.7%) and 11,698 deceased (26.3%). The average follow-up period was 67.7 months, and the cumulative average concentration of PM10 exposure of patients with cancer after a diagnosis was 49.0 µg/m3. When PM10 concentration increased by 1 standard deviation (5.2 µg/m3), the all-cause mortality risk increased 2.06-fold (95% CI: 2.02−2.11). This trend was most pronounced in the younger patient group and in patients with local-stage cancer. This study demonstrates that exposure to PM10 after cancer diagnosis might influence the survival of patients with cancer, requiring environmental preventive measures such as lower pollutant exposure.

Positive Effect of Air Purifier Intervention on Baroreflex Sensitivity and Biomarkers of Oxidative Stress in Patients with Coronary Artery Disease: A Randomized Crossover Intervention Trial.

Exposure to fine particulate matter increases the risk of cardiovascular morbidity and mortality. Few studies have tested the beneficial effect of indoor air filtration intervention in patients with cardiovascular disease. The aim of this study is to investigate the effect of air filtration on mitigating cardiovascular health in patients with coronary artery disease. This randomized, double-blind, crossover study is conducted with 38 coronary artery disease patients. The intervention consists of the following three periods: two-week active and sham air filtration interventions, with a two-week washout period. The indoor PM2.5 concentration is continuously monitored during the entire study period. We measure the blood pressure, heart rate variability, baroreflex sensitivity, autonomic function test results, and endothelial function. The two-week active air filtration intervention for two weeks reduces the average indoor concentration of PM2.5 by 33.9%. The indoor PM2.5 concentration is significantly correlated to cross-correlation baroreflex sensitivity. Active air filtration is significantly associated with a decrease in the indicator of oxidative stress represented as 8-hydroxy-2'-deoxyguanosine. This study shows that a short-term air filtration intervention improved baroreflex sensitivity and might reduce oxidative stress in coronary artery disease patients. These findings suggest that the use of an air purifier could mitigate the recurrence of cardiovascular disease events in patients with coronary artery disease.

SARS-CoV-2 Induces Expression of Cytokine and MUC5AC/5B in Human Nasal Epithelial Cell through ACE 2 Receptor.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a novel infectious respiratory disease called COVID-19, which is threatening public health worldwide. SARS-CoV-2 spike proteins connect to the angiotensin converting enzyme 2 (ACE2) receptor through the receptor binding domain and are then activated by the transmembrane protease serine subtype 2 (TMPRSS2). The ACE2 receptor is highly expressed in human nasal epithelial cells. Nasal ciliated cells are primary targets for SARS-CoV-2 replication. However, the effect of SARS-CoV-2 on the upper respiratory tract remains unknown, thus leading to the purpose of our study. We investigate the effects of SARS-CoV-2 on cytokines and mucin expression in human nasal epithelial cells. Methods: We investigated the effects of the SARS-CoV-2 spike protein receptor binding domain (RBD) on cytokines (IL-1ß, IL-6, and IL-8) and MUC5AC/5B expression via real-time PCR, ELISA, periodic acid-Schiff (PAS) staining, and immunofluorescence staining in cultured human nasal epithelial cells. Results: The mRNA expression and protein production of cytokines (IL-1ß, IL-6, and IL-8) and MUC5AC/5B were increased by SARS-CoV-2 spike protein RBD. ACE2 receptor inhibitor suppressed the expression of cytokines (IL-1ß, IL-6, and IL-8) and MUC5AC/5B induced by SARS-CoV-2 spike protein RBD. Conclusions: SARS-CoV-2 induced cytokines (IL-1ß, IL-6, and IL-8) and MUC5AC/5B expression through the ACE 2 receptor in human nasal epithelial cells. Therefore, ACE2 receptor inhibitors can be an effective therapeutic option for SARS-CoV-2 infection.

Ultrafine Diesel Exhaust Particles Induce Apoptosis of Oligodendrocytes by Increasing Intracellular Reactive Oxygen Species through NADPH Oxidase Activation.

Diesel exhaust particles (DEPs) are a main contributor to air pollution. Ultrafine DEPs can cause neurodegenerative diseases by increasing intracellular reactive oxygen species (ROS). Compared with other cells in the brain, oligodendrocytes responsible for myelination are more susceptible to oxidative stress. However, the mechanisms underlying ROS generation in oligodendrocytes and the susceptibility of oligodendrocytes to ROS by ultrafine DEPs remain unclear. Herein, we examined the effects of excessive ROS generated by NOX2, an isoform of the NADPH oxidase family, after exposure to ultrafine DEPs (200 µg/mL) on the survival of two types of oligodendrocytes-oligodendrocyte precursor cells (OPCs) and mature oligodendrocytes (mOLs)--isolated from the brain of neonatal rats. In addition, mice were exposed to ultrafine DEP suspension (20 µL, 0.4 mg/mL) via the nasal route for 1 week, after which the expression of NOX2 and cleaved caspase-3 was examined in the white matter of the cerebellum. Exposure to DEPs significantly increased NOX2 expression and ROS generation in OPCs and mOLs. OPCs and mOLs clearly exhibited viability reduction, and a significant change in p53, Bax, Bcl-2, and cleaved caspase-3 expression, after DEP exposure. In contrast, treatment with berberine (BBR), an NOX2 inhibitor, significantly mitigated these effects. In mice exposed to DEP, the presence of NOX2-positive and cleaved caspase-3-positive oligodendrocytes was demonstrated in the cerebellar white matter; NOX2 and cleaved caspase-3 expression in the cerebellum lysates was significantly increased. BBR treatment returned expression of these proteins to control levels. These results demonstrate that the susceptibility of OPCs and mOLs to ultrafine DEPs is, at least in part, caused by excessive ROS produced by NOX2 and the sequential changes in the expression of p53, Bax, Bcl-2, and cleaved caspase-3. Overall, NOX2 inhibitor enhances the survival of two types of oligodendrocytes.