SREBP-1c impairs ULK1 sulfhydration-mediated autophagic flux to promote hepatic steatosis in high-fat-diet-fed mice.

A metabolic imbalance between lipid synthesis and degradation can lead to hepatic lipid accumulation, a characteristic of patients with non-alcoholic fatty liver disease (NAFLD). Here, we report that high-fat-diet-induced sterol regulatory element-binding protein (SREBP)-1c, a key transcription factor that regulates lipid biosynthesis, impairs autophagic lipid catabolism via altered H2S signaling. SREBP-1c reduced cystathionine gamma-lyase (CSE) via miR-216a, which in turn decreased hepatic H2S levels and sulfhydration-dependent activation of Unc-51-like autophagy-activating kinase 1 (ULK1). Furthermore, Cys951Ser mutation of ULK1 decreased autolysosome formation and promoted hepatic lipid accumulation in mice, suggesting that the loss of ULK1 sulfhydration was directly associated with the pathogenesis of NAFLD. Moreover, silencing of CSE in SREBP-1c knockout mice increased liver triglycerides, confirming the connection between CSE, autophagy, and SREBP-1c. Overall, our results uncover a 2-fold mechanism for SREBP-1c-driven hepatic lipid accumulation through reciprocal activation and inhibition of hepatic lipid biosynthesis and degradation, respectively.

Resistivity detection of perfluoroalkyl substances with fluorous polyaniline in an electrical lateral flow sensor.

Perfluoroalkyl substances (PFAS), known as "forever chemicals," are a growing concern in the sphere of human and environmental health. In response, rapid, reproducible, and inexpensive methods for PFAS detection in the environment and home water supplies are needed. We have developed a simple and inexpensive perfluoroalkyl acid detection method based on an electrically read lateral flow assay (e-LFA). Our method employs a fluorous surfactant formulation with undoped polyaniline (F-PANI) fabricated to create test lines for the lateral flow assay. In perfluoroalkyl acid sensing studies, an increase in conductivity of the F-PANI film is caused by acidification and doping of PANI. A conductivity enhancement by 104-fold can be produced by this method, and we demonstrate a limit of detection for perfluorooctanoic acid (PFOA) of 400 ppt and perfluorobutanoic acid of 200 ppt. This method for PFOA detection can be expanded for wide-scale environmental and at-home water testing.

Forkhead box protein D2 suppresses colorectal cancer by reprogramming enhancer interactions.

Somatic stem cells contribute to normal tissue homeostasis, and their epigenomic features play an important role in regulating tissue identities or developing disease states. Enhancers are one of the key players controlling chromatin context-specific gene expression in a spatial and temporal manner while maintaining tissue homeostasis, and their dysregulation leads to tumorigenesis. Here, epigenomic and transcriptomic analyses reveal that forkhead box protein D2 (FOXD2) is a hub for the gene regulatory network exclusive to large intestinal stem cells, and its overexpression plays a significant role in colon cancer regression. FOXD2 is positioned at the closed chromatin and facilitates mixed-lineage leukemia protein-4 (MLL4/KMT2D) binding to deposit H3K4 monomethylation. De novo FOXD2-mediated chromatin interactions rewire the regulation of p53-responsive genes and induction of apoptosis. Taken together, our findings illustrate the novel mechanistic details of FOXD2 in suppressing colorectal cancer growth and suggest its function as a chromatin-tuning factor and a potential therapeutic target for colorectal cancer.

SERS-based microdevices for use as in vitro diagnostic biosensors.

Advances in surface-enhanced Raman scattering (SERS) detection have helped to overcome the limitations of traditional in vitro diagnostic methods, such as fluorescence and chemiluminescence, owing to its high sensitivity and multiplex detection capability. However, for the implementation of SERS detection technology in disease diagnosis, a SERS-based assay platform capable of analyzing clinical samples is essential. Moreover, infectious diseases like COVID-19 require the development of point-of-care (POC) diagnostic technologies that can rapidly and accurately determine infection status. As an effective assay platform, SERS-based bioassays utilize SERS nanotags labeled with protein or DNA receptors on Au or Ag nanoparticles, serving as highly sensitive optical probes. Additionally, a microdevice is necessary as an interface between the target biomolecules and SERS nanotags. This review aims to introduce various microdevices developed for SERS detection, available for POC diagnostics, including LFA strips, microfluidic chips, and microarray chips. Furthermore, the article presents research findings reported in the last 20 years for the SERS-based bioassay of various diseases, such as cancer, cardiovascular diseases, and infectious diseases. Finally, the prospects of SERS bioassays are discussed concerning the integration of SERS-based microdevices and portable Raman readers into POC systems, along with the utilization of artificial intelligence technology.

The Efficacy and Safety of an Indocyanine Green-Macroaggregated Albumin-Hyaluronic Acid Mixture (LuminoMark™) for Surgical Localization of Recurrent Thyroid Cancer.

BACKGROUND: The recurrence of thyroid cancer poses challenges compounded by postoperative fibrosis and anatomic changes. By overcoming the limitations of current localizing dye techniques, indocyanine green-macroaggregated albumin-hyaluronic acid (ICG-MAA-HA) mixture dye promises improved localization. This study aimed to evaluate the efficacy and safety of the dye for recurrent thyroid cancer. METHODS: The nine patients in this study underwent surgery and postoperative ultrasonography. The dye was injected into recurrent lesions in all the patients preoperatively. During surgery, the lesions were confirmed with an imaging system before and after excision. If the lesion was unidentifiable with the naked eye, surgical excision was performed under the corresponding fluorescent guide. Side effects related to the dye injection and completeness of the surgery were evaluated. RESULTS: No side effects such as bleeding, skin tattooing, or pain during or after the dye injection were reported, and no discoloration occurred that interfered with the surgical field of view during surgery. In three cases (33.3 %), because it was difficult to localize metastatic lesions with the naked eye, the operation was successfully completed using an imaging system. The completeness of the surgical resection was confirmed by ultrasonography after an average of 5 months postoperatively. CONCLUSION: The study found that ICG-MAA-HA dye effectively located metastatic and recurrent thyroid cancer and had favorable results in terms of minimal procedural side effects and potential for assisting the surgeon. A large-scale multi-institutional study is necessary to prove the clinical significance regarding patient survival and disease control.

Medium-Enhanced cc[over ¯] Radiation.

We show that the same QCD formalism that accounts for the suppression of high-p_{T} hadron and jet spectra in heavy-ion collisions predicts medium-enhanced production of cc[over ¯] pairs in jets. We demonstrate that this phenomenon, which cannot be accessed by traditional jet-quenching observables, can be directly observed using D^{0}D[over ¯]^{0}-tagged jets in nuclear collisions.

Eating patterns in Korean adults, 1998-2018: increased energy contribution of ultra-processed foods in main meals and snacks.

PURPOSE: Unfavorable changes in eating patterns over time may contribute to upward trends in chronic diseases, such as obesity. We examined 20-year trends in the percentage of energy from main meals and snacks and the food sources of each eating occasion among Korean adults. METHODS: This study used nationally representative data from the 1st, 4th, and 7th Korea National Health and Nutrition Examination Surveys (1998, 2007-2009, and 2016-2018) among adults aged 20-69 years (n = 29,389). Each eating occasion (breakfast, lunch, dinner, and snacks) was defined by respondents during a 24-h dietary recall interview. To identify the food sources of each eating occasion, we used the NOVA system. The percentage of energy at each eating occasion and that from each NOVA group across survey cycles were estimated, and tests for linear trends were conducted using orthogonal polynomial contrasts in linear regression models. All analyses accounted for the complex survey design. RESULTS: After adjusting for age and sex, the percentage of energy from breakfast decreased from 25.0% in 1998 to 16.7% in 2018 (difference, - 8.2%; standard error [SE], 0.3), whereas that from dinner and snacks increased from 31.1 to 33.8% (difference, + 2.7%; SE, 0.4) and from 14.0 to 19.0% (difference, + 5.0%; SE, 0.5), respectively (all P < 0.001). At all eating occasions, the percentage of energy from minimally processed foods declined (difference, - 18.6% for breakfast; - 13.1% for lunch; - 21.1% for dinner; - 20.7% for snacks), while that from ultra-processed foods increased (difference, + 17.0% for breakfast; + 11.3% for lunch; + 18.0% for dinner; + 30.7% for snacks). When stratified by age, the given trends were shown to a greater extent in younger adults (< 50 years old) than in older adults (≥ 50 years old). CONCLUSIONS: The eating patterns of Korean adults changed from 1998 to 2018, with the greatest decrease in energy intake from breakfast and the greatest increase from snacking. At all eating occasions, the contribution of minimally processed foods declined, while that of ultra-processed foods increased, especially among younger adults.

Associations between short-term exposure to air pollution and thyroid function in a representative sample of the Korean population.

BACKGROUND: Disruption of thyroid function can profoundly affect various organ systems. However, studies on the association between air pollution and thyroid function are relatively scarce and most studies have focused on the long-term effects of air pollution among pregnant women. OBJECTIVES: This study aimed to explore the associations between short-term exposure to air pollution and thyroid function in the general population. METHODS: Data from the Korea National Health and Nutrition Examination Survey (2013-2015) were analyzed (n = 5,626). Air pollution concentrations in residential addresses were estimated using Community Multiscale Air Quality models. The moving averages of air pollution over 7 days were set as exposure variables through exploratory analyses. Linear regression and quantile g-computation models were constructed to assess the effects of individual air pollutants and air pollution mixture, respectively. RESULTS: A 10-ppb increase in NO2 (18.8-µg/m3 increase) and CO (11.5-µg/m3 increase) was associated with 2.43% [95% confidence interval (CI): 0.42, 4.48] and 0.19% (95% CI: 0.01, 0.36) higher thyroid-stimulating hormone (TSH) levels, respectively. A 10-µg/m3 increase in PM2.5 and a 10-ppb increase in O3 (19.6-µg/m3 increment) were associated with 0.87% (95% CI: 1.47, -0.27) and 0.59% (95% CI: 1.18, -0.001) lower free thyroxine (fT4) levels, respectively. A simultaneous quartile increase in PM2.5, NO2, O3, and CO levels was associated with lower fT4 but not TSH levels. CONCLUSIONS: As the subtle changes in thyroid function can affect various organ systems, the present results may have substantial public health implications despite the relatively modest effect sizes. Because this was a cross-sectional study, it is necessary to conduct further experimental or repeated-measures studies to consolidate the current results.

Factors Associated with Sugar-Sweetened Beverage Intake Among Young Children - United States, 2021.

Introduction: Because limited data exist about factors related to sugar-sweetened beverage (SSB) intake among younger children, we investigated factors associated with SSB intake among US children aged 1 to 5 years. Methods: We examined SSB intake (0, 1-3, or ≥4 times/week) by using data from the 2021 National Survey of Children's Health. We performed a multinomial logistic regression to calculate adjusted odds ratios (aORs) for select sociodemographic and household factors associated with moderate (1-3 times/week) and high (≥4 times/week) SSB intake. Results: Overall, 36% of children consumed SSBs 1 to 3 times/week and 21% consumed 4 or more times/week. Both moderate and high SSB intake were associated with child's age, child's race and ethnicity, highest caregiver education level, household income, primary household language, and frequency of family meals. For example, children who lived in households with caregiver education level of high school graduate or less were significantly more likely to have moderate (aOR, 2.06) and high (aOR, 2.81) SSB intake than those who lived in households with caregiver education level of college degree or higher. High SSB intake was also associated with marginal household food sufficiency, nonmetropolitan statistical area status, and receipt of government food benefits. Conclusion: Several sociodemographic and household factors were significantly associated with SSB intake among children aged 1 to 5 years. Public health initiatives designed to address SSB intake among young children in various settings including pediatric health care, early care and education, and the child's home could consider key associated factors.

Association between dietary carotenoid intake and breast cancer risk: a case-control study among Korean women.

The association between dietary carotenoids and breast cancer (BC) risks were inconsistent. Therefore, this study investigated the association between dietary carotenoid and BC risks among Korean women. We recruited participants from the National Cancer Centre of Korea. Odds ratios and 95% confidence intervals were calculated with a logistic regression model. There was an inverse association between dietary carotenoid subclasses and BC risks; in particular, a higher intake of ß-carotene and lutein/zeaxanthin was associated with reduced BC risks. After subgroup analysis with estrogen receptor (ER)/progesterone receptor (PR) status, there was similar trend among ER-/PR- women. We further investigated which foods contribute to the carotenoid intake. A higher intake of radish leaves, kale, and bracken was associated with lowered BC risks. Accordingly, dietary carotenoid, particularly ß-carotene and lutein/zeaxanthin, appears to be associated with a lower risk of BC among Korean women.

Thermoresponse of Odd-Even Effect in n-Alkanethiolate Self-Assembled Monolayers on Gold Substrates.

This study examines thermoresponse of odd-even effect in self-assembled monolayers (SAMs) of n-alkanethiolates (SCn , n=3-18) formed on template-stripped gold (AuTS ) using macro- and microscopic analytical techniques, contact angle goniometry (CAG) and vibrational sum frequency generation (VSFG) spectroscopy, respectively. Both CAG and VSFG analyses showed that the odd-even effect in liquid-like SAMs (n=3-9) disappeared upon heating at 50-70 °C, indicating that the heating led to increased structural disorder regardless of odd and even carbon numbers. In contrast, the opposite thermoresponse was observed for odd and even SCn molecules in wax- and solid-like SAMs (n=10-18). Namely, temperature-dependent orientational change of terminal CH3 relative to the surface normal was opposite for the odd and even molecules, thereby leading to mitigated odd-even effect. Our work offers important insights into thermoresponse of supramolecular structure in condensed organic matter.

FDG metabolic parameter-based models for predicting recurrence after upfront surgery in synchronous colorectal cancer liver metastasis.

OBJECTIVE: This study aimed to develop and validate post- and preoperative models for predicting recurrence after curative-intent surgery using an FDG PET-CT metabolic parameter to improve the prognosis of patients with synchronous colorectal cancer liver metastasis (SCLM). METHODS: In this retrospective multicenter study, consecutive patients with resectable SCLM underwent upfront surgery between 2006 and 2015 (development cohort) and between 2006 and 2017 (validation cohort). In the development cohort, we developed and internally validated the post- and preoperative models using multivariable Cox regression with an FDG metabolic parameter (metastasis-to-primary-tumor uptake ratio [M/P ratio]) and clinicopathological variables as predictors. In the validation cohort, the models were externally validated for discrimination, calibration, and clinical usefulness. Model performance was compared with that of Fong's clinical risk score (FCRS). RESULTS: A total of 374 patients (59.1 ± 10.5 years, 254 men) belonged in the development cohort and 151 (60.3 ± 12.0 years, 94 men) in the validation cohort. The M/P ratio and nine clinicopathological predictors were included in the models. Both postoperative and preoperative models showed significantly higher discrimination than FCRS (p < .05) in the external validation (time-dependent AUC = 0.76 [95% CI 0.68-0.84] and 0.76 [0.68-0.84] vs. 0.65 [0.57-0.74], respectively). Calibration plots and decision curve analysis demonstrated that both models were well calibrated and clinically useful. The developed models are presented as a web-based calculator ( https://cpmodel.shinyapps.io/SCLM/ ) and nomograms. CONCLUSIONS: FDG metabolic parameter-based prognostic models are well-calibrated recurrence prediction models with good discriminative power. They can be used for accurate risk stratification in patients with SCLM. KEY POINTS: • In this multicenter study, we developed and validated prediction models for recurrence in patients with resectable synchronous colorectal cancer liver metastasis using a metabolic parameter from FDG PET-CT. • The developed models showed good predictive performance on external validation, significantly exceeding that of a pre-existing model. • The models may be utilized for accurate patient risk stratification, thereby aiding in therapeutic decision-making.

Scientific evidence of foods that improve the lifespan and healthspan of different organisms.

Age is a risk factor for numerous diseases. Although the development of modern medicine has greatly extended the human lifespan, the duration of relatively healthy old age, or 'healthspan', has not increased. Targeting the detrimental processes that can occur before the onset of age-related diseases can greatly improve health and lifespan. Healthspan is significantly affected by what, when and how much one eats. Dietary restriction, including calorie restriction, fasting or fasting-mimicking diets, to extend both lifespan and healthspan has recently attracted much attention. However, direct scientific evidence that consuming specific foods extends the lifespan and healthspan seems lacking. Here, we synthesized the results of recent studies on the lifespan and healthspan extension properties of foods and their phytochemicals in various organisms to confirm how far the scientific research on the effect of food on the lifespan has reached.

Polar microalgae extracts protect human HaCaT keratinocytes from damaging stimuli and ameliorate psoriatic skin inflammation in mice.

BACKGROUND: Polar microalgae contain unique compounds that enable them to adapt to extreme environments. As the skin barrier is our first line of defense against external threats, polar microalgae extracts may possess restorative properties for damaged skin, but the potential of microalgae extracts as skin protective agents remains unknown. PURPOSE: This study aimed to analyze compound profiles from polar microalgae extracts, evaluate their potential as skin epithelial protective agents, and examine the underlying mechanisms. METHODS: Six different polar microalgae, Micractinium sp. (KSF0015 and KSF0041), Chlamydomonas sp. (KNM0029C, KSF0037, and KSF0134), and Chlorococcum sp. (KSF0003), were collected from the Antarctic or Arctic regions. Compound profiles of polar and non-polar microalgae extracts were analyzed using gas chromatography-mass spectrometry (GC-MS). The protective activities of polar microalgae extracts on human keratinocyte cell lines against oxidative stress, radiation, and psoriatic cytokine exposure were assessed. The potential anti-inflammatory mechanisms mediated by KSF0041, a polar microalga with protective properties against oxidative stress, ultraviolet (UV) B, and an inflammatory cytokine cocktail, were investigated using RNA-sequencing analysis. To evaluate the therapeutic activity of KSF0041, an imiquimod-induced murine model of psoriatic dermatitis was used. RESULTS: Polar microalgae contain components comparable to those of their non-polar counterparts, but also showed distinct differences, particularly in fatty acid composition. Polar microalgae extracts had a greater ability to scavenge free radicals than did non-polar microalgae and enhanced the viability of HaCaT cells, a human keratinocyte cell line, following exposure to UVB radiation or psoriatic cytokines. These extracts also reduced barrier integrity damage and decreased mRNA levels of inflammatory cytokines in psoriatic HaCaT cells. Treatment with KSF0041 extract altered the transcriptome of psoriatic HaCaT cells toward a more normal state. Furthermore, KSF0041 extract had a therapeutic effect in a mouse model of psoriasis. CONCLUSIONS: Bioactive compounds from polar microalgae extracts could provide novel therapeutics for damaged and/or inflamed skin.

Bacteria-derived metabolite, methylglyoxal, modulates the longevity of C. elegans through TORC2/SGK-1/DAF-16 signaling.

Gut microbes play diverse roles in modulating host fitness, including longevity; however, the molecular mechanisms underlying their mediation of longevity remain poorly understood. We performed genome-wide screens using 3,792 Escherichia coli mutants and identified 44 E. coli mutants that modulated Caenorhabditis elegans longevity. Three of these mutants modulated C. elegans longevity via the bacterial metabolite methylglyoxal (MG). Importantly, we found that low MG-producing E. coli mutants, Δhns E. coli, extended the lifespan of C. elegans through activation of the DAF-16/FOXO family transcription factor and the mitochondrial unfolded protein response (UPRmt). Interestingly, the lifespan modulation by Δhns did not require insulin/insulin-like growth factor 1 signaling (IIS) but did require TORC2/SGK-1 signaling. Transcriptome analysis revealed that Δhns E. coli activated novel class 3 DAF-16 target genes that were distinct from those regulated by IIS. Taken together, our data suggest that bacteria-derived MG modulates host longevity through regulation of the host signaling pathways rather than through nonspecific damage on biomolecules known as advanced glycation end products. Finally, we demonstrate that MG enhances the phosphorylation of hSGK1 and accelerates cellular senescence in human dermal fibroblasts, suggesting the conserved role of MG in controlling longevity across species. Together, our studies demonstrate that bacteria-derived MG is a novel therapeutic target for aging and aging-associated pathophysiology.

State-Specific Prevalence of Severe Obesity Among Adults in the US Using Bias Correction of Self-Reported Body Mass Index.

INTRODUCTION: Adults with severe obesity are at increased risk for poor metabolic health and may need more intensive clinical and community supports. The prevalence of severe obesity is underestimated from self-reported weight and height data. We examined severe obesity prevalence among US adults by sociodemographic characteristics and by state after adjusting for self-report bias. METHODS: Using a validated bias-correction method, we adjusted self-reported body mass index (BMI) data from the 2020 Behavioral Risk Factor Surveillance System (BRFSS) by using measured data from the National Health and Nutrition Examination Survey. We compared bias-corrected prevalence of severe obesity (BMI ≥40) with self-reported estimates by sociodemographic characteristics and state. RESULTS: Self-reported BRFSS data significantly underestimated the prevalence of severe obesity compared with bias-corrected estimates. In 2020, 8.8% of adults had severe obesity based on the bias-corrected estimates, whereas 5.3% of adults had severe obesity based on self-reported data. Women had a significantly higher prevalence of bias-corrected severe obesity (11.1%) than men (6.5%). State-level prevalence of bias-corrected severe obesity ranged from 5.5% (Massachusetts) to 13.2% (West Virginia). Based on bias-corrected estimates, 16 states had a prevalence of severe obesity greater than 10%, a level not seen in the self-reported estimates. CONCLUSION: Self-reported BRFSS data underestimated the overall prevalence of severe obesity by 40% (5.3% vs 8.8%). Accurate state-level estimates of severe obesity can help public health and health care decision makers prioritize and plan to implement effective prevention and treatment strategies for people who are at high risk for poor metabolic health.

Thermopower of Molecular Junction in Harsh Thermal Environments.

Molecular junctions can be miniaturized devices for heat-to-electricity conversion application, yet these operate only in mild thermal environments (less than 323 K) because thiol, the most widely used anchor moiety for chemisorption of active molecules onto surface of electrode, easily undergoes thermal degradation. N-Heterocyclic carbene (NHC) can be an alternative to traditional thiol anchor for producing ultrastable thermoelectric molecular junctions. Our experiments showed that the NHC-based molecular junctions withstood remarkably high temperatures up to 573 K, exhibiting consistent Seebeck effect and thermovoltage up to approximately |1900 µV|. Our work advances our understanding of molecule-electrode contact in the Seebeck effect, providing a roadmap for constructing robust and efficient organic thermoelectric devices.

High Seebeck Coefficient Achieved by Multinuclear Organometallic Molecular Junctions.

This paper describes the thermoelectric properties of molecular junctions incorporating multinuclear ruthenium alkynyl complexes that comprise Ru(dppe)2 [dppe = 1,2-bis(diphenylphosphino)ethane] fragments and diethylnyl aromatic bridging ligands with thioether anchors. Using the liquid metal technique, the Seebeck coefficient was examined as a function of metal nuclearity, oxidation state, and substituent on the organic ligand backbone. High Seebeck coefficients up to 73 µV/K and appreciable thermal stability with thermovoltage up to ∼3.3 mV at a heating temperature of 423 K were observed. An unusually high proximity of the highest occupied molecular orbital (HOMO) energy level to the Fermi level was revealed to give the remarkable thermoelectric performance as suggested by combined experiments and calculations. This work offers important insights into the development of molecular-scale devices for efficient thermoregulation and heat-to-electricity conversion.

Thermopower in Transition from Tunneling to Hopping.

The Seebeck effect of a molecular junction in a hopping regime or tunneling-to-hopping transition remains uncertain. This paper describes the Seebeck effect in molecular epitaxy films (OPIn where n = 1-9) based on imine condensation between an aryl amine and aldehyde and investigates how the Seebeck coefficient (S, µV/K) varies at the crossover region. The S value of OPIn linearly increased with increasing the molecular length (d, nm), ranging from 7.2 to 38.0 µV/K. The increasing rate changed from 0.99 to 0.38 µV·K-1 Å-1 at d = 3.4 nm (OPI4). Combined experimental and theoretical studies indicated that such a change stems from a tunneling-to-hopping transition, and the small but detectable length-dependence of thermopower in the long molecules originates from the gradual reduction of the tunneling contribution to the broadening of molecular orbital energy level, rather than its relative position to the Fermi level. Our work helps to bridge the gap between bulk and nanoscale thermoelectric systems.

Mild Oxidative Stress Induced by Sodium Arsenite Reduces Lipocalin-2 Expression Levels in Cortical Glial Cells.

Astrocytes and microglia, the most abundant glial cells in the central nervous system, are involved in maintaining homeostasis in the brain microenvironment and in the progression of various neurological disorders. Lipocalin-2 (LCN2) is a small secretory protein that can be transcriptionally upregulated via nuclear factor kappa B (NF-κB) signaling. It is synthesized and secreted by glial cells, resulting in either the restoration of damaged neural tissues or the induction of neuronal apoptosis in a context-dependent manner. It has recently been reported that when glial cells are under lipopolysaccharide-induced inflammatory stress, either reduced production or accelerated degradation of LCN2 can alleviate neurotoxicity. However, the regulatory mechanisms of LCN2 in glial cells are not yet fully understood. In this study, we used primary astroglial-enriched cells which produce LCN2 and found that the production of LCN2 could be reduced by sodium arsenite treatment. Surprisingly, the reduced LCN2 production was not due to the suppression of NF-κB signaling. Mild oxidative stress induced by sodium arsenite treatment activated antioxidant responses and downregulated Lcn2 expression without reducing the viability of astroglial-enriched cells. Intriguingly, reduced LCN2 production could not be achieved by simple activation of the nuclear factor erythroid-2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway in astroglial-enriched cells. Thus, it appears that mild oxidative stress, occurring in an Nrf2-independent manner, is required for the downregulation of Lcn2 expression. Taken together, our findings provide new insights into the regulatory mechanisms of LCN2 and suggest that mild oxidative stress may alter LCN2 homeostasis, even under neuroinflammatory conditions.