Downregulation of TRIB3 enhances the sensitivity of lung cancer cells to amino acid deprivation by suppressing AKT activation.

Tribbles pseudokinase 3 (TRIB3), a member of the mammalian Tribbles family, is implicated in multiple biological processes. This study aimed to investigate the biological functions of TRIB3 in lung cancer and its effect on amino acid-deprived lung cancer cells. TRIB3 mRNA expression was elevated in lung cancer tissues and cell lines compared to normal lung tissues and cells. TRIB3 knockdown markedly reduced the viability and proliferation of H1299 lung cancer cells. Deprivation of amino acids, particularly arginine, glutamine, lysine, or methionine, strongly increased TRIB3 expression via ATF4 activation in H1299 lung cancer cells. Knockdown of TRIB3 led to transcriptional downregulation of ATF4 and reduced AKT activation induced by amino acid deprivation, ultimately increasing the sensitivity of H1299 lung cancer cells to amino acid deprivation. Additionally, TRIB3 knockdown enhanced the sensitivity of H1299 cells to V-9302, a competitive antagonist of transmembrane glutamine flux. These results suggest that TRIB3 is a pro-survival regulator of cell viability in amino acid-deficient tumor microenvironments and a promising therapeutic target for lung cancer treatment.

Tetrahedral DNA nanostructures enhance transcription isothermal amplification for multiplex detection of non-coding RNAs.

This study introduces an innovative detection system for multiple cancer biomarkers, employing transcription isothermal amplification methods in conjunction with a tetrahedral DNA nanostructure (TDN). We demonstrate that TDN enhances various transcription isothermal amplification methods by placing DNA probes in proximity. Notably, the TDN-enhanced split T7 promoter-based isothermal transcription amplification with light-up RNA aptamer (STAR) system stands out for its optimal performance and operational simplicity, especially in identifying non-coding RNAs such as microRNAs and long non-coding RNAs (lncRNAs). Multiplex detection of lncRNAs was also achieved by generating distinct light-up RNA aptamers, each emitting unique fluorescence signals. The system effectively identified the target lncRNAs, demonstrating high sensitivity and selectivity in both cell lines and clinical samples. The system, utilizing the single enzyme T7 RNA polymerase, can be easily tailored for alternative targets by substituting target-specific sequences in DNA probes and seamlessly integrated with other isothermal amplification methods for greater sensitivity and accuracy in the detection of multiple cancer biomarkers.

Amino acid deprivation induces TXNIP expression by NRF2 downregulation.

Thioredoxin-interacting protein (TXNIP) is sensitive to oxidative stress and is involved in the pathogenesis of various metabolic, cardiovascular, and neurodegenerative disorders. Therefore, several studies have suggested that TXNIP is a promising therapeutic target for several diseases, particularly cancer and diabetes. However, the regulation of TXNIP expression under amino acid (AA)-restricted conditions is not well understood. In the present study, we demonstrated that TXNIP expression was promoted by the deprivation of AAs, especially arginine, glutamine, lysine, and methionine, in non-small cell lung cancer (NSCLC) cells. Interestingly, we determined that increased TXNIP expression induced by AA deprivation was associated with nuclear factor erythroid 2-related factor 2 (NRF2) downregulation, but not with activating transcription factor 4 (ATF4) activation. Furthermore, N-acetyl-l-cysteine (NAC), a scavenger of reactive oxygen species (ROS), suppressed TXNIP expression in NSCLC cells deprived of AA. Collectively, the induction of TXNIP expression by AA deprivation was mediated by ROS production, potentially through NRF2 downregulation. Our findings suggest that TXNIP expression may be associated with the redox homeostasis of AA metabolism and provide a possible rationale for a therapeutic strategy to treat cancer with AA restriction.

The Effect of COVID-19 Outbreak and Incidence on the Health-Related Behaviors and Depression of Gyeongnam Residents in Republic of Korea.

Background and Objectives: This study aimed to investigate whether the occurrence of COVID-19 brought about changes in the health behaviors and depression levels of residents in Gyeongnam in Republic of Korea, and whether the prevalence of COVID-19 was related to differences in health behaviors and depression levels among different regions. Materials and Methods: The researchers utilized raw data from the 2019-2020 Community Health Survey in Gyeongnam and conducted analyses using SPSS 25.0. The study included a total of 35,880 participants from 18 cities and counties in the Gyeongnam region (17,942 participants in 2019 and 17,938 participants in 2020). Results: The results of the comparative analysis between pre- and post-COVID-19 occurrence showed that, after the occurrence of COVID-19, the smoking cessation rate and monthly alcohol consumption rate among current smokers decreased, while the high-risk drinking rate increased. The rate of physical activity (walking) increased, but the prevalence of depression experiences and depressive symptoms also increased. Furthermore, the comparative analysis between areas with a higher number of COVID-19 cases and those with a lower number of cases revealed that areas with a higher number of cases had higher monthly alcohol consumption rates, as well as a higher prevalence of depression experiences and depressive symptoms. Conclusions: Considering that the occurrence and severity of COVID-19 had significant impacts on the health behaviors and depression levels of residents in Gyeongnam, this highlights the need for active intervention and management by the national and local governments in response to the occurrence and management of infectious diseases, including COVID-19, to address the health status and health behaviors of the local population.

Heavy metal exposure linked to metabolic syndrome in Korean male firefighters: FRESH cohort cross-sectional analysis.

This study aimed to identify the relationship between blood lead and Cadmium (Cd) concentrations and metabolic syndromes (MetS), including its components (central obesity, hypertriglyceridemia, low high-density lioioritein, hypertension, and hyperglycemia) among Korean firefighters. A total of 965 firefighters of the Enhancement of Safety and Health cohort were analyzed in this study. MetS was defined according to the 2005 revised National Cholesterol Education Program-Adult Treatment Panel III criteria and the Korean Society for the Study of Obesity criteria for waist circumference. The collected data were analyzed using a logistic regression model. Of the 965 participants, 190 (19.7%) had MetS. After adjusting for age, body mass index, smoking, drinking, exercise, shift duty, and main duty position, the Cd level was significantly associated with an increased risk of MetS in the Korean firefighter population (odds ratio [OR] = 1.62, 95% confidence interval [CI] 1.07, 2.46). This association was significant among non-smokers and ex-smokers (OR = 1.58, 95% CI 1.03, 2.43), non-drinkers and ex-drinkers (OR = 1.77, 95% CI 1.06, 2.94), firefighters aged 40 year or older (OR = 1.77, 95% CI 1.10, 2.86), and office administrators (OR = 3.85, 95% CI 1.42, 10.39). This outcome suggests that exposure to Cd is likely to increase risk of MetS among firefighters.

Development of a Novel DNA Aptamer Targeting Colorectal Cancer Cell-Derived Small Extracellular Vesicles as a Potential Diagnostic and Therapeutic Agent.

Colorectal cancer (CRC) as the second leading cause of global cancer deaths poses critical challenges in clinical settings. Cancer-derived small extracellular vesicles (sEVs), which are secreted by cancer cells, have been shown to mediate tumor development, invasion, and even metastasis, and have thus received increasing attention for the development of cancer diagnostic or therapeutic platforms. In the present study, the sEV-targeted systematic evolution of ligands by exponential enrichment (E-SELEX) is developed to generate a high-quality aptamer (CCE-10F) that recognizes and binds to CRC-derived sEVs. Via an in-depth investigation, it is confirmed that this novel aptamer possesses high affinity (Kd = 3.41 nm) for CRC-derived sEVs and exhibits a wide linear range (2.0 × 104 -1.0 × 106 particles µL-1 ) with a limit of detection (LOD) of 1.0 × 103 particles µL-1 . Furthermore, the aptamer discriminates CRC cell-derived sEVs from those derived from normal colon cell, human serum, and other cancer cells, showing high specificity for CRC cell-derived sEVs and significantly suppresses the critical processes of metastasis, including cellular migration, invasion, and angiogenesis, which are originally induced by sEVs themselves. These findings are highly encouraging for the potential use of the aptamer in sEV-based diagnostic and therapeutic applications.

Nebivolol Sensitizes BT-474 Breast Cancer Cells to FGFR Inhibitors.

BACKGROUND/AIM: The fibroblast growth factor receptor (FGFR) signaling pathway is abnormally activated in human cancers, including breast cancer. Therefore, targeting the FGFR signaling pathway is a potent strategy to treat breast cancer. The purpose of this study was to find drugs that could increase sensitivity to FGFR inhibitor effects in BT-474 breast cancer cells, and to investigate the combined effects and underlying mechanisms of these combinations for BT-474 breast cancer cell survival. MATERIALS AND METHODS: Cell viability was measured by MTT assay. Protein expression was determined by western blot analysis. mRNA expression was detected by Real-time PCR. Drug synergy effect was determined by isobologram analysis. RESULTS: Nebivolol, a third generation ß1-blocker, synergistically increased the sensitivity of BT-474 breast cancer cells to the potent and selective FGFR inhibitors erdafitinib (JNJ-42756493) and AZD4547. A combination of nebivolol and erdafitinib markedly reduced AKT activation. Suppression of AKT activation using specific siRNA and a selective inhibitor further enhanced cell sensitivity to combined treatment with nebivolol and erdafitinib, whereas SC79, a potent activator of AKT, reduced cell sensitivity to nebivolol and erdafitinib. CONCLUSION: Enhanced sensitivity of BT-474 breast cancer cells to nebivolol and erdafitinib was probably associated with down-regulation of AKT activation. Combined treatment with nebivolol and erdafitinib is a promising strategy for breast cancer treatment.

Cas12a/blocker DNA-based multiplex nucleic acid detection system for diagnosis of high-risk human papillomavirus infection.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) proteins are an innovative tool in molecular diagnostics owing to their high specificity and modularity for target nucleic acid sequences. However, the sequence-indiscriminate trans-cleavage activity of the Cas protein renders multiplex detection challenging. In this study, we developed a Cas12a-based multiplex detection system by designing blocker DNA complementary to reporter DNA, which enables the simultaneous detection of two genes with a single Cas protein in a single reaction. As a proof of concept, we chose high-risk human papillomavirus (HPV) 16 and 18 as the model targets and incorporated recombinase polymerase amplification (RPA) and transcription reactions to achieve high accuracy and sensitivity. Using the proposed system, we detected the genes of both HPV 16 and 18 down to 1 aM within 80 min under isothermal conditions. We validated the performance of the system in detecting genomic DNA from various cell lines and clinical samples from cervical cancer patients with high specificity. The proposed system facilitated rapid multiplex detection of high-risk HPVs in a single reaction tube with only Cas12a, thus representing a more user-friendly and economical alternative to previous Cas protein-based multiplex detection assays. The proposed system has considerable potential for point-of-care testing and could be expanded to detect various nucleic acid biomarkers.

Low-Temperature Loop-Mediated Isothermal Amplification Operating at Physiological Temperature.

Loop-mediated isothermal amplification (LAMP) is one of the most widely used isothermal amplification technologies in molecular diagnostics. However, LAMP operates at a high temperature of 65 °C; thus, operating LAMP at a lower temperature is desirable to maximize its usefulness for on-site diagnosis. In this study, we propose a new version of LAMP, termed low-temperature LAMP, which operates at the physiological temperature of 37 °C. Low-temperature LAMP differs from conventional LAMP operating at 65 °C in terms of the concentrations of MgSO4 and deoxyribonucleoside triphosphates (dNTPs), as well as the lengths of DNA probes, which are crucial for the execution of low-temperature LAMP. Under the optimal conditions, the amplification efficiency of low-temperature LAMP is comparable to that of conventional LAMP. In addition, the ligation reaction at 37 °C, which is necessary to detect actual target nucleic acids, is combined without altering the temperature, enabling the identification of miR-21, a cancer-promoting oncogenic miRNA, with high sensitivity and selectivity. The method described in this paper does not require expensive DNA modifications or special additives and would facilitate the widespread application of LAMP in facility-limited or point-of-care settings, paving the way to improvements in other isothermal-amplification-based techniques.

DNA micelle-templated copper nanoclusters for fluorescent imaging of MUC1-positive cancer cells.

DNA micelles formed by hydrophobic, self-assembly of amphiphilic DNA monomers have enormous potential in biological imaging owing to its unique and programmable, three-dimensional nanostructure. Herein, we rationally design double-stranded DNA oligonucleotides with two cholesterols that can spontaneously form the lipid-mediated DNA micelles and generate the high fluorescence signal after the formation of DNA-templated copper nanoclusters (CuNCs). Furthermore, the DNA aptamer specific to MUC1 protein, aberrantly overexpressed on the surface of cancer cells, is attached to lipid-mediated DNA micelles to confer the selectivity towards the target cancer cells. With the well-defined DNA nanostructures, the cell membrane of MUC1-positive cancer cells are stained by CuNCs exhibiting an intense, red fluorescence signal, which are clearly distinguished from MUC1-negative cancer cells. This approach may not only expand the application scope of both DNA micells and CuNCs, especially in the area of cellular imaging, but also provides a basis for developing other types of DNA nanostructures to detect target biomarkers.

Association between Disability and Edema Index Values in Rural Older Adult Osteosarcopenia Patients.

PURPOSE: This study analyzed the relationship between degree of disability and edema index [extracellular water/total body water (ECW/TBW) ratio] values in a rural population of older adult patients with osteopenia, sarcopenia, or osteosarcopenia (OS). MATERIALS AND METHODS: This study used data from the Namgaram-2 cohort. The degree of disability was measured using the World Health Organization Disability Assessment Schedule (WHODAS) 12, and ECW/TBW ratio was calculated using bioelectrical impedance analysis. Based on ECW/TBW ratio, the participants were stratified into normal (<0.391) and abnormal (≥0.391) groups, and the mean WHODAS 12 scores were compared between the two groups. Multiple regression analysis corrected for demographic factors, smoking history, hypertension, diabetes, and serological test results was also conducted. RESULTS: Significant differences in mean WHODAS 12 scores were observed in the healthy group (5.8±7.4 vs. 9.2±9.7, p=0.008), the osteopenia only group (7.4±8.7 vs. 12.9±12.0, p<0.001), and the OS group (16.0±13.2 vs. 23.1±17.1, p=0.004). However, no significant difference in mean WHODAS 12 score was observed in the sarcopenia only group (14.9±13.4 vs. 20.7±14.8, p= 0.051). There were significant differences in ECW/TBW ratio values between the abnormal and normal groups in the osteopenia only group (B=4.646 and p=0.001), the sarcopenia only group (B=5.097 and p=0.016), and the OS group (B=5.653 and p=0.043). CONCLUSION: This study found that the degree of disability is related to the edema index in older patients with osteopenia, sarcopenia, or OS. Since the edema index indicates the nutritional status of an individual, proper nutrition and fluid intake are important to reduce disability.

Knockdown of NUPR1 Enhances the Sensitivity of Non-small-cell Lung Cancer Cells to Metformin by AKT Inhibition.

BACKGROUND/AIM: Metformin is a widely used drug for type 2 diabetes mellitus and has recently attracted broad attention for its therapeutic effects on many cancers. This study aimed to investigate the molecular mechanism of metformin's anticancer activity. MATERIALS AND METHODS: Cell viability was measured by MTT assay. Gene and protein expression levels were determined by reverse transcription-polymerase chain reaction and western blot analyses, respectively. RESULTS: Metformin and phenformin markedly induced NUPR1 expression in a dose- and time-dependent manner in H1299 non-small-cell lung cancer (NSCLC) cells. The silencing of NUPR1 in H1299 NSCLC cells enhanced cell sensitivity to metformin or ionizing radiation. Our previous report showed that metformin induces AKT serine/threonine kinase (AKT) activation in an activating transcription factor 4 (ATF4)-dependent manner and that the inhibition of AKT promotes cell sensitivity to metformin in H1299 NSCLC cells. Interestingly, ATF4-induced AKT activation in H1299 NSCLC cells treated with metformin was suppressed by the knockdown of NUPR1. CONCLUSION: Targeting NUPR1 could enhance the sensitivity of H1299 NSCLC cells to metformin by AKT inhibition.

Relationship between pressure ulcer risk and sarcopenia in patients with hip fractures.

OBJECTIVE: Pressure ulcer (PU) is a frequent complication of hip fractures. PUs can develop at any time after a hip fracture but most appear within 2-4 days after surgery. The purpose of this study was to investigate the association between hip fractures due to sarcopenia and the risk of PUs in patients with hip fracture. METHOD: Between March 2017 and March 2019, patients aged ≥65 years of age with hip fractures were included in this retrospective cohort study. PU risk assessment according to the Braden Scale was performed within the first few hours after arrival at hospital. Skeletal muscle mass index (SMI) and hand grip strength were evaluated for a diagnosis of sarcopenia. RESULTS: Of the 289 patients admitted to the study institution, 180 patients were finally enrolled in the study (129 females; 51 males). In male patients, as SMI increased, so too did the Braden Scale score, which was statistically significant (p=0.02). However, there was no statistically significant difference between SMIs and Braden Scale scores in female patients (p=0.304). In male patients, there was no statistically significant difference between hand grip strength and Braden Scale score (p=0.251). However, in female patients, as hand grip strength increased, so too did the Braden Scale score; this was also statistically significant (p=0.041). CONCLUSION: In this study, decreased muscle mass and muscle weakness in patients with hip fractures were associated with increased PU risk as measured by Braden Scale scores in both males and females.

Residential Characteristics as Factors Related to Healthy Behavior Practices-Decision Tree Model Analysis Using a Community Health Survey from Korea.

In this study, we sought to identify relevant factors in healthy behavior practices, including not only individual-level variables but also regional and physical environments. Data from the Korea Community Health Survey (KCHS) of Gyeongsangnam-do in 2018 were used, with data from 16,519 of the 17,947 individuals (excluding 1428 individuals who had missing values) who participated in the survey. Healthy behavior practices were defined as meeting the criteria for all three modifiable healthy behaviors (non-smoking, moderate alcohol consumption, regular walking). A decision tree analysis was performed. In men, healthy behavior practices were lower in the unemployed population, in those aged 40−50 years, living in rural residential areas, and with stress. For women who lived in areas with small populations (<100,000 population), healthy behavior practices were below-average. Men and women who had below-average healthy behavior practices reported poor access to places for exercise and fair or poor self-rated health statuses. It is necessary to implement a health behavior practice intervention that considers not only individual characteristics but also access to local exercise facilities and residential area characteristics (urban, rural). Since age is an important variable in healthy behaviors for both men and women, customized programs that consider age should be provided.

Lead-start isothermal polymerase amplification controlled by DNAzymatic switches.

As DNA polymerases are even active at ambient temperature, there is inevitable non-specific amplification; to avoid the undesired amplification of analytes, a heat activation-based polymerase chain reaction (PCR), called hot-start PCR, is widely used to be highly precise and quantitative in detection. Unlike thermocycling amplification, isothermal amplification, compatible for point-of-care (PoC) tests, cannot be benefited by the heat-activation technique, making the method qualitative rather than quantitative. In this work, we newly developed a lead ion (Pb2+) activation technique, called lead-start isothermal amplification, allowing on-demand activation or deactivation of DNA polymerases at room temperature. We systematically correlated the DNA polymerase inhibition by the TQ30 aptamer with Pb2+-responsive strand cleavage by the GR5 DNAzyme, and relying on the type of interconnectors, Pb2+ successfully served as an initiator or a terminator of isothermal DNA amplification. Our lead-start isothermal amplification was exceptionally Pb2+-specific, dramatically increasing the enzymatic activity of DNA polymerase (>25 times) only by Pb2+ introduction. Despite one-by-one sample preparation, a number of reactions can begin and end at the same time, sharing the identical amplification conditions, and thereby allowing their quantitative analysis and comparison. Using a portable UV lamp and a smartphone camera, we also succeeded in quantifying the amounts of clinically important and human papillomavirus type 16 genes in human serum and SARS-CoV-2's nucleocapsid genes in human serum and saliva, and the limit of detection was as low as 0.1 nM, highly applicable for actual PoC tests in the field with no purification process.

Dual rolling circle amplification-enabled ultrasensitive multiplex detection of exosome biomarkers using electrochemical aptasensors.

Breast cancer is one of the leading causes of cancer-related death. An effective diagnostic system that enables early cancer detection is required for timely diagnosis and better treatment outcomes. Here, we developed an ultrasensitive electrochemical aptasensor for the multiplex detection of exosome biomarkers based on the electrochemical signals of metal ions. Specifically, a screen-printed carbon electrode (SPCE) was first modified with a multi-walled carbon nanotube (MWCNT), ionic liquid (IL), and chitosan (CHT) composite, and then gold nanoparticles (GNPs) were deposited via electrodeposition (GNPs/MWCNT-IL-CHT). To capture target exosomes, an aptamer specific for CD63, the universal exosome surface protein, was immobilized on the GNPs/MWCNT-IL-CHT/SPCE. When EpCAM or HER-2 positive exosomes were present in the sample, they could bind to EpCAM or HER-2 aptamers with primer sequences that acted as a rolling circle amplification reaction initiator, thereby generating numerous poly-guanine and poly-thymine repeats of a metal ion binding sequence, which produced strong electrochemical signals upon complexation with copper and lead ions. Using the proposed, multiplex exosome analysis system, EpCAM- and HER-2-positive exosomes were simultaneously detected with high specificity and a detection limit of 1 particle mL-1. In addition, its clinical applicability was validated via spike-and-recovery experiments using human serum samples.

Knockdown of YAP/TAZ sensitizes tamoxifen-resistant MCF7 breast cancer cells.

Although endocrine therapy with tamoxifen has improved survival in breast cancer patients, resistance to this therapy remains one of the major causes of breast cancer mortality. In the present study, we found that the expression level of YAP/TAZ in tamoxifen-resistant MCF7 (MCF7-TR) breast cancer cells was significantly increased compared with that in MCF7 cells. Knockdown of YAP/TAZ with siRNA sensitized MCF7-TR cells to tamoxifen. Furthermore, siRNA targeting PSAT1, a downstream effector of YAP/TAZ, enhanced sensitivity to tamoxifen in MCF7-TR cells. Additionally, mTORC1 activity and survivin expression were significantly decreased during cell death induced by combination treatment with YAP/TAZ or PSAT1 siRNA and tamoxifen. In conclusion, targeting the YAP/TAZ-PSAT1 axis could sensitize tamoxifen-resistant MCF7 breast cancer cells by modulating the mTORC1-survivin axis.

DNA barcode-based detection of exosomal microRNAs using nucleic acid lateral flow assays for the diagnosis of colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths worldwide. The standard methods for diagnosing CRC, endoscopy and tissue biopsy, are invasive and time-consuming. Herein, we propose a novel method for the accurate and non-invasive diagnosis of CRC based on the analysis of exosomes that are circulating in biological fluids using a DNA barcode-based nucleic acid lateral flow assay (NALFA). Our technology combines reverse transcription using a stem-loop primer with DNA barcode-based NALFA. A colorimetric signal is generated only in the presence of the target exosomal miRNA, which can be determined even with the naked eye. The proposed system successfully detected miR-92a and miR-141, which are overexpressed in CRC exosomes. Moreover, when applied to plasma samples from CRC patients, our system simultaneously detected multiple markers in one strip. By combining these markers, we achieved high analytical performance with a sensitivity and a specificity of 95.24% and 100.0%, respectively, demonstrating that the proposed assay can be a simple diagnostic platform for the detection of exosomal miRNA.

T7 Endonuclease I-mediated voltammetric detection of KRAS mutation coupled with horseradish peroxidase for signal amplification.

Rapid and selective sensing of KRAS gene mutation which plays a crucial role in the development of colorectal, pancreatic, and lung cancers is of great significance in the early diagnosis of cancers. In the current study, we developed a simple electrochemical biosensor by differential pulse voltammetry technique for the specific detection of KRAS mutation that uses the mismatch-specific cleavage activity of T7-Endonuclease I (T7EI) coupled with horseradish peroxidase (HRP) to catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) substrate in the presence of hydrogen peroxide (H2O2). In addition, we synthesized the nanocomposite composed of multi-walled carbon nanotube/chitosan-ionic liquid/gold nanoparticles (MWCNT/Chit-IL/AuNPs) on screen-printed carbon electrode surface to increase the electrode surface area and electrochemical signal. In principle, T7E1 enzyme recognized and cleaved the mismatched site formed by the presence of KRAS gene mutation, removing 5'-biotin of capture probes and subsequently reducing the differential pulse voltammetry signal compared to wild-type KRAS gene. With this proposed strategy, a limit of detection of 11.89 fM was achieved with a broad linear relationship from 100 fM to 1 µM and discriminated 0.1% of mutant genes from the wild-type target genes. This confirms that the developed biosensor is a potential platform for the detection of mutations in early disease diagnosis.

The effect of polycyclic aromatic hydrocarbons on changes in the brain structure of firefighters: An analysis using data from the Firefighters Research on Enhancement of Safety & Health study.

Polycyclic aromatic hydrocarbons (PAHs) are formed during incomplete combustion of organic matter, and firefighters are highly exposed to these toxic compounds at fire sites. Exposure to PAHs can cause cognitive decline and neurodegeneration; however, to date, few studies have examined the potential effects of PAH exposure on structural changes in the brain. We aimed to investigate the association between the four types of PAH metabolites and the corresponding changes in neuroimaging markers based on smoking status and hypertension in male firefighters. For this, we utilized the 2-year follow-up data of 301 Korean male firefighters aged over 40 years. The concentrations of four PAH metabolites in urine were measured. Subcortical volume and cortical thickness were estimated using 3 T magnetic resonance imaging of the brain. A generalized linear model was used to investigate the effects of PAHs on changes in the subcortical volume and cortical thickness. We found an association between 1-hydroxyphenathrene (1-OHPHE) and 2-hydroxyfluorene (2-OHF) and changes in several brain regions in all the study participants. Individuals who had never smoked showed significantly thinner frontal (p < 0.001), parietal (p < 0.001), temporal (p < 0.001), and cingulate lobes (p < 0.001) with 1% increase each in the urinary concentration of 1-OHPHE. Hypertension interacted with the concentration of 1-OHPHE to reduce the volume of gray matter and cause cortical thinning in the frontal, parietal, and temporal lobes. Exposure to PAHs may reduce cortical thickness and subcortical volume, which are definitive markers of neurodegeneration. Notably, hypertension can accelerate the degenerative effects of PAHs.