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Keywords = symptoms of stress

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17 pages, 962 KiB  
Article
Impact of COVID-19 on Mental Health in Nursing Students and Non-Nursing Students: A Cross-Sectional Study
by Verena Dresen, Liliane Sigmund, Siegmund Staggl, Bernhard Holzner, Gerhard Rumpold, Laura R. Fischer-Jbali, Markus Canazei and Elisabeth Weiss
Nurs. Rep. 2025, 15(8), 286; https://doi.org/10.3390/nursrep15080286 - 6 Aug 2025
Abstract
Background/Objective: Nursing and non-nursing students experience high stress levels, making them susceptible to mental health issues. This study compared stress, anxiety, and depression between these two groups after 2 years of the COVID-19 pandemic. Additionally, it explored the relationship between perceived helplessness, [...] Read more.
Background/Objective: Nursing and non-nursing students experience high stress levels, making them susceptible to mental health issues. This study compared stress, anxiety, and depression between these two groups after 2 years of the COVID-19 pandemic. Additionally, it explored the relationship between perceived helplessness, self-efficacy, and symptoms of mental stress and strain resulting from challenging internship conditions for nursing students. Methods: This cross-sectional study included 154 nursing students (mean age = 22.43 years) and 291 non-nursing students (mean age = 27.7 years). Data were collected using the Depression Anxiety Stress Scales (DASS-21), Perceived Stress Scale-10 (PSS-10), and a questionnaire on mental stress and strain. Results: Nursing students reported significantly higher scores in the DASS-21 subscales depression (ηp2 = 0.016) and anxiety (ηp2 = 0.037), and global stress (PSS-10; ηp2 = 0.029) compared to non-nursing students, but no significant difference on the DASS-21 Stress subscale. The observed group differences in the present study may be partially attributed to group differences in demographic factors. Helplessness correlated strongly with nearly all scales of mental stress and strain during internships (all p’s < 0.001), while self-efficacy showed a strong negative correlation with non-occupational difficulties, health impairment, and emotional problems (all p’s < 0.001). Conclusions: Nursing students experience elevated depression, anxiety, and perceived stress levels compared to non-nursing students. Stronger feelings of helplessness and lower confidence in their ability to overcome challenges were strongly correlated with mental stress and strain during clinical training. Targeted interventions such as cognitive behavioral training and stress management should be integrated into nursing curricula to enhance resilience and coping strategies. Full article
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33 pages, 891 KiB  
Article
Effectiveness of a Mind–Body Intervention at Improving Mental Health and Performance Among Career Firefighters
by Anthony C. Santos, Seth Long, Christopher P. Moreno and Dierdra Bycura
Int. J. Environ. Res. Public Health 2025, 22(8), 1227; https://doi.org/10.3390/ijerph22081227 - 6 Aug 2025
Abstract
Almost one in three firefighters develop mental health disorders at some point during their careers, a rate double that in the general population. Frequent exposures to potentially traumatic situations can contribute to symptoms of these disorders, two of the most common being depression [...] Read more.
Almost one in three firefighters develop mental health disorders at some point during their careers, a rate double that in the general population. Frequent exposures to potentially traumatic situations can contribute to symptoms of these disorders, two of the most common being depression and post-traumatic stress disorder (PTSD). While various psychological interventions have been implemented among this group, reports of their effectiveness include mixed results. To this end, the current study endeavored to test the effectiveness of a 12-week intervention combining occupationally-tailored high-intensity functional training (HIFT) and psychological resilience training (RES) in reducing depressive and post-traumatic stress symptoms (PTSSs), as well as increasing psychological resilience and mental wellbeing, in career firefighters. Thirty career firefighters completed four mental health measurements over 17 weeks while anthropometrics and physical performance (i.e., number of stations completed in 20 min during an eight-station simulated job-task circuit workout [T-CAC]) were measured pre- and post-intervention. Pre to post comparisons were made via repeated-measures t-tests. Significant mean differences were observed for T-CAC stations completed, PTSSs, and psychological resilience between pre- and post-intervention. In future interventions, researchers should actively engage firefighters, maximize integration with daily operations, and employ culturally-relevant practices to explore the links between physical and mental health. Full article
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13 pages, 401 KiB  
Article
The Correlation Between Cracked Teeth and National Insurance Coverage of Dental Implants in South Korea: A Retrospective Cohort Analysis
by Se Hoon Kahm, YoungHa Shim and SungEun Yang
J. Clin. Med. 2025, 14(15), 5507; https://doi.org/10.3390/jcm14155507 - 5 Aug 2025
Abstract
Background/Objectives: The expansion of National Health Insurance (NHI) coverage for dental implants in South Korea has substantially increased implant placements among older adults. While implants offer functional and esthetic benefits, their lack of periodontal ligaments alters occlusal force distribution, potentially increasing biomechanical [...] Read more.
Background/Objectives: The expansion of National Health Insurance (NHI) coverage for dental implants in South Korea has substantially increased implant placements among older adults. While implants offer functional and esthetic benefits, their lack of periodontal ligaments alters occlusal force distribution, potentially increasing biomechanical stress on adjacent or opposing teeth. This study aimed to investigate the association between the increased number of dental implants and the incidence of cracked teeth following the introduction of implant insurance. Methods: A retrospective analysis was conducted using the Clinical Data Warehouse of Seoul St. Mary’s Dental Hospital. Patients who underwent molar crown restorations between 2014 and 2022 were included. The incidence and clinical features of cracked teeth were compared before (2014–2015) and after (2016–2022) the introduction of implant insurance. Statistical analyses assessed differences in symptom presentation, pulp status, and treatment outcomes. Results: Among 5044 molars restored with crowns, 1692 were diagnosed with cracks. The incidence of cracked teeth significantly increased after NHI coverage for implants (25.5% vs. 32.6%, p < 0.001). Cases after insurance implementation showed fewer signs and symptoms at initial presentation (67.4% vs. 50.0%, p < 0.001), reduced irreversible pulpitis (37.2% vs. 25.8%, p < 0.001), and increased preservation of pulp vitality (46.9% vs. 57.8%, p < 0.001). These shifts may reflect changes in occlusal adjustment practices and earlier clinical intervention. Conclusions: The findings suggest a temporal link between increased implant placement and the rising incidence of cracked teeth. Implant-induced occlusal changes may contribute to this trend. Careful occlusal evaluation and follow-up are essential after implant placement, and further prospective studies are warranted to confirm causality and refine prevention strategies. Full article
(This article belongs to the Special Issue Research Progress in Osseointegrated Oral Implants)
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14 pages, 614 KiB  
Article
Development of Cut Scores for Feigning Spectrum Behavior on the Orebro Musculoskeletal Pain Screening Questionnaire and the Perceived Stress Scale: A Simulation Study
by John Edward McMahon, Ashley Craig and Ian Douglas Cameron
J. Clin. Med. 2025, 14(15), 5504; https://doi.org/10.3390/jcm14155504 - 5 Aug 2025
Abstract
Background/Objectives: Feigning spectrum behavior (FSB) is the exaggeration, fabrication, or false imputation of symptoms. It occurs in compensable injury with great cost to society by way of loss of productivity and excessive costs. The aim of this study is to identify feigning [...] Read more.
Background/Objectives: Feigning spectrum behavior (FSB) is the exaggeration, fabrication, or false imputation of symptoms. It occurs in compensable injury with great cost to society by way of loss of productivity and excessive costs. The aim of this study is to identify feigning by developing cut scores on the long and short forms (SF) of the Orebro Musculoskeletal Pain Screening Questionnaire (OMPSQ and OMPSQ-SF) and the Perceived Stress Scale (PSS and PSS-4). Methods: As part of pre-screening for a support program, 40 injured workers who had been certified unfit for work for more than 2 weeks were screened once with the OMPSQ and PSS by telephone by a mental health professional. A control sample comprised of 40 non-injured community members were screened by a mental health professional on four occasions under different aliases, twice responding genuinely and twice simulating an injury. Results: Differences between the workplace injured people and the community sample were compared using ANCOVA with age and gender as covariates, and then receiver operator characteristics (ROCs) were calculated. The OMPSQ and OMPSQ-SF discriminated (ρ < 0.001) between all conditions. All measures discriminated between the simulation condition and workplace injured people (ρ < 0.001). Intraclass correlation demonstrated the PSS, PSS-4, OMPSQ, and OMPSQ-SF were reliable (ρ < 0.001). Area Under the Curve (AUC) was 0.750 for OMPSQ and 0.835 for OMPSQ-SF for work-injured versus simulators. Conclusions: The measures discriminated between injured and non-injured people and non-injured people instructed to simulate injury. Non-injured simulators produced similar scores when they had multiple exposures to the test materials, showing the uniformity of feigning spectrum behavior on these measures. The OMPSQ-SF has adequate discriminant validity and sensitivity to feigning spectrum behavior, making it optimal for telephone screening in clinical practice. Full article
(This article belongs to the Section Clinical Rehabilitation)
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33 pages, 640 KiB  
Review
Future Pharmacotherapy for Bipolar Disorders: Emerging Trends and Personalized Approaches
by Giuseppe Marano, Francesco Maria Lisci, Gianluca Boggio, Ester Maria Marzo, Francesca Abate, Greta Sfratta, Gianandrea Traversi, Osvaldo Mazza, Roberto Pola, Gabriele Sani, Eleonora Gaetani and Marianna Mazza
Future Pharmacol. 2025, 5(3), 42; https://doi.org/10.3390/futurepharmacol5030042 - 4 Aug 2025
Abstract
Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse [...] Read more.
Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse rates. Methods: This paper is a narrative review aimed at synthesizing emerging trends and future directions in the pharmacological treatment of BD. Results: Future pharmacotherapy for BD is likely to shift toward precision medicine, leveraging advances in genetics, biomarkers, and neuroimaging to guide personalized treatment strategies. Novel drug development will also target previously underexplored mechanisms, such as inflammation, mitochondrial dysfunction, circadian rhythm disturbances, and glutamatergic dysregulation. Physiological endophenotypes, such as immune-metabolic profiles, circadian rhythms, and stress reactivity, are emerging as promising translational tools for tailoring treatment and reducing associated somatic comorbidity and mortality. Recognition of the heterogeneous longitudinal trajectories of BD, including chronic mixed states, long depressive episodes, or intermittent manic phases, has underscored the value of clinical staging models to inform both pharmacological strategies and biomarker research. Disrupted circadian rhythms and associated chronotypes further support the development of individualized chronotherapeutic interventions. Emerging chronotherapeutic approaches based on individual biological rhythms, along with innovative monitoring strategies such as saliva-based lithium sensors, are reshaping the future landscape. Anti-inflammatory agents, neurosteroids, and compounds modulating oxidative stress are emerging as promising candidates. Additionally, medications targeting specific biological pathways implicated in bipolar pathophysiology, such as N-methyl-D-aspartate (NMDA) receptor modulators, phosphodiesterase inhibitors, and neuropeptides, are under investigation. Conclusions: Advances in pharmacogenomics will enable clinicians to predict individual responses and tolerability, minimizing trial-and-error prescribing. The future landscape may also incorporate digital therapeutics, combining pharmacotherapy with remote monitoring and data-driven adjustments. Ultimately, integrating innovative drug therapies with personalized approaches has the potential to enhance efficacy, reduce adverse effects, and improve long-term outcomes for individuals with bipolar disorder, ushering in a new era of precision psychiatry. Full article
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27 pages, 1757 KiB  
Article
Salt Stress Mitigation and Field-Relevant Biostimulant Activity of Prosystemin Protein Fragments: Novel Tools for Cutting-Edge Solutions in Agriculture
by Martina Chiara Criscuolo, Raffaele Magliulo, Valeria Castaldi, Valerio Cirillo, Claudio Cristiani, Andrea Negroni, Anna Maria Aprile, Donata Molisso, Martina Buonanno, Davide Esposito, Emma Langella, Simona Maria Monti and Rosa Rao
Plants 2025, 14(15), 2411; https://doi.org/10.3390/plants14152411 - 4 Aug 2025
Viewed by 30
Abstract
In an increasingly challenging agricultural environment, the identification of novel tools for protecting crops from stress agents while securing marketable production is a key objective. Here we investigated the effects of three previously characterized Prosystemin-derived functional peptide fragments as protective agents against salt [...] Read more.
In an increasingly challenging agricultural environment, the identification of novel tools for protecting crops from stress agents while securing marketable production is a key objective. Here we investigated the effects of three previously characterized Prosystemin-derived functional peptide fragments as protective agents against salt stress and as biostimulants modulating tomato yield and quality traits. The treatments of tomato plants with femtomolar amounts of the peptides alleviated salt stress symptoms, likely due to an increase in root biomass up to 18% and the upregulation of key antioxidant genes such as APX2 and HSP90. In addition, the peptides exhibited biostimulant activity, significantly improving root area (up to 10%) and shoot growth (up to 9%). We validated such activities through two-year field trials carried out on industrial tomato crops. Peptide treatments confirmed their biostimulant effects, leading to a nearly 50% increase in marketable production compared to a commonly used commercial product and consistently enhancing fruit °Brix values. Full article
(This article belongs to the Section Plant Physiology and Metabolism)
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15 pages, 604 KiB  
Article
Brief Repeated Attention Training for Psychological Distress: Findings from Two Experiments
by David Skvarc, Shannon Hyder, Laetitia Leary, Shahni Watts, Marcus Seecamp, Lewis Burns and Alexa Hayley
Behav. Sci. 2025, 15(8), 1052; https://doi.org/10.3390/bs15081052 - 3 Aug 2025
Viewed by 198
Abstract
Psychological distress is understood to be maintained by attention. We performed two experiments examining the impact of attention training (AT) on psychological distress symptoms. Experiment one (N = 336) investigated what effects might be detected in a simple experimental design with longitudinal [...] Read more.
Psychological distress is understood to be maintained by attention. We performed two experiments examining the impact of attention training (AT) on psychological distress symptoms. Experiment one (N = 336) investigated what effects might be detected in a simple experimental design with longitudinal measurements, while experiment two (N = 214) examined whether using a different emotional stimulus could induce an immediate anxiolytic effect in response to AT. Attentional biases were operationalized as the target search latency correlated with mood and psychological distress scores. While limited evidence of attentional biases was found in participants with higher mood distress, correlations emerged in the experimental conditions at day thirty, indicating a relationship between task latency, stress, and changes in depression (experimental one). We found no immediate between–within-group differences in outcome when including different emotional stimuli (experiment two). Despite attentional biases being less apparent in community samples, attentional training for bias modification was effective in eliciting positive biases, leading to improved mood. Notably, participants in the control condition reported the greatest mood and psychological distress improvements, whereas changes in the experimental condition primarily pertained to attentional biases. Taken together, these findings suggest that AT tasks can improve distress, but not through changes in attentional biases. Full article
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10 pages, 237 KiB  
Article
Current Status of Mental Health in Mexico City
by Erika Sanchez, Humberto Nicolini, Jorge Villatoro, Marycarmen Bustos, María Elena Medina-Mora, Paola Mejía-Ortiz, Beatriz Robles, Diego Mondragón, Gema Ibarra, Daniela Meza and Alma Delia Genis-Mendoza
Int. J. Environ. Res. Public Health 2025, 22(8), 1217; https://doi.org/10.3390/ijerph22081217 - 2 Aug 2025
Viewed by 288
Abstract
There is limited information on the prevalence of mental health symptoms among the population of Mexico City. To provide an update and determine the prevalence of symptoms associated with various disorders in the city, a modified version of the “Screener Questionnaire” was used, [...] Read more.
There is limited information on the prevalence of mental health symptoms among the population of Mexico City. To provide an update and determine the prevalence of symptoms associated with various disorders in the city, a modified version of the “Screener Questionnaire” was used, the same instrument employed in the National Survey on Drug, Alcohol, and Tobacco Use (ENCODAT) 2016–2017. Data were collected at PILARES centers in different boroughs of Mexico City. A total of 868 questionnaires on symptoms of psychiatric disorders and the use of drugs, alcohol, and tobacco were completed. The most frequently reported symptoms were anxiety (52.67%), depression (39.34%), and post-traumatic stress disorder (44.57%). Additionally, results showed alcohol use at 15.1%, followed by tobacco (13.6%) and illicit drug use (6.8%). The prevalence of these symptoms was also compared with data from ENCODAT 2016–2017 to observe changes over the years. Full article
24 pages, 2128 KiB  
Article
Central Insulin-Like Growth Factor-1-Induced Anxiolytic and Antidepressant Effects in a Rat Model of Sporadic Alzheimer’s Disease Are Associated with the Peripheral Suppression of Inflammation
by Joanna Dunacka, Beata Grembecka and Danuta Wrona
Cells 2025, 14(15), 1189; https://doi.org/10.3390/cells14151189 - 1 Aug 2025
Viewed by 246
Abstract
(1) Insulin-like growth factor-1 (IGF-1) is a neurotrophin with anti-inflammatory properties. Neuroinflammation and stress activate peripheral immune mechanisms, which may contribute to the development of depression and anxiety in sporadic Alzheimer’s disease (sAD). This study aims to evaluate whether intracerebroventricular (ICV) premedication with [...] Read more.
(1) Insulin-like growth factor-1 (IGF-1) is a neurotrophin with anti-inflammatory properties. Neuroinflammation and stress activate peripheral immune mechanisms, which may contribute to the development of depression and anxiety in sporadic Alzheimer’s disease (sAD). This study aims to evaluate whether intracerebroventricular (ICV) premedication with IGF-1 in a rat model of streptozotocin (STZ)-induced neuroinflammation can prevent the emergence of anhedonia and anxiety-like behavior by impacting the peripheral inflammatory responses. (2) Male Wistar rats were subjected to double ICVSTZ (total dose: 3 mg/kg) and ICVIGF-1 injections (total dose: 2 µg). We analyzed the level of anhedonia (sucrose preference), anxiety (elevated plus maze), peripheral inflammation (hematological and cytometric measurement of leukocyte populations, interleukin (IL)-6), and corticosterone concentration at 7 (very early stage, VES), 45 (early stage, ES), and 90 days after STZ injections (late stage, LS). (3) We found that ICVIGF-1 administration reduces behavioral symptoms: anhedonia (ES and LS) and anxiety (VES, ES), and peripheral inflammation: number of leukocytes, lymphocytes, T lymphocytes, monocytes, granulocytes, IL-6, and corticosterone concentration (LS) in the rat model of sAD. (4) The obtained results demonstrate beneficial effects of central IGF-1 administration on neuropsychiatric symptoms and peripheral immune system activation during disease progression in the rat model of sAD. Full article
(This article belongs to the Section Cells of the Nervous System)
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16 pages, 291 KiB  
Article
General and Specific Social Trust as Predictors of Depressive Symptoms: Evidence from Post-Crisis Iceland
by Haukur Freyr Gylfason
World 2025, 6(3), 107; https://doi.org/10.3390/world6030107 - 1 Aug 2025
Viewed by 236
Abstract
Social trust has been linked to the development and severity of depression, but trust is a complex, multidimensional construct. This study examines the extent to which two distinct forms of trust, general trust and specific trust, predict depressive symptoms. Drawing on longitudinal data [...] Read more.
Social trust has been linked to the development and severity of depression, but trust is a complex, multidimensional construct. This study examines the extent to which two distinct forms of trust, general trust and specific trust, predict depressive symptoms. Drawing on longitudinal data from the Directorate of Health’s national surveys conducted in 2007 and 2009, the analysis includes responses from 3211 Icelanders selected through a stratified random sample. Depressive symptoms were assessed using the Depression, Anxiety, and Stress Scale (DASS), while specific trust captured trust in close relationships, and general trust measured broader perceptions of trustworthiness in others. The two forms of trust together explained 7.6% of the variance in depressive symptoms, with specific trust contributing a substantially greater share. Both remained significant predictors after controlling for prior depression and physical health. These findings highlight the protective role of specific trust and suggest that general trust, an indicator of broader social capital, may also help buffer against depression. The results underscore the relevance of trust as a public health resource and support continued research into social determinants of mental health in Iceland. Full article
16 pages, 321 KiB  
Review
Prevalence and Determinants of Psychological Distress in Medical Students in Spain (2010–2024): A Narrative Review
by María J. González-Calderón and José I. Baile
Psychiatry Int. 2025, 6(3), 90; https://doi.org/10.3390/psychiatryint6030090 (registering DOI) - 1 Aug 2025
Viewed by 191
Abstract
This study aims to provide a comprehensive overview of psychological distress among medical students in Spain, a growing concern given the high prevalence rates of anxiety, depression, and burnout reported across multiple medical schools and universities. To assess the scope and key characteristics [...] Read more.
This study aims to provide a comprehensive overview of psychological distress among medical students in Spain, a growing concern given the high prevalence rates of anxiety, depression, and burnout reported across multiple medical schools and universities. To assess the scope and key characteristics of this phenomenon, a thorough literature search was conducted in the PubMed, ProQuest, and Web of Science (WoS) databases. Studies published between 2010 and 2024 in peer-reviewed scientific journals, written in English or Spanish, and specifically focused on medical students enrolled in Spanish universities were considered for inclusion. A total of 14 studies were analysed. The findings indicate that psychological distress often emerges early in medical training and tends to intensify as students progress academically. Female medical students are consistently more affected, as most of the studies reviewed indicate that they exhibit higher levels of depressive symptoms, trait anxiety, and perceived stress. Some research also suggests greater levels of burnout among female students compared to their male peers. Key contributing factors include academic overload and dissatisfaction, sleep deprivation, and the use of maladaptive coping strategies. Although awareness of the issue is increasing, available evidence suggests that institutional responses remain limited, and that only a small number of universities have implemented structured mental health programmes. Overall, the results underscore the urgent need for institutional reforms in Spanish medical education to safeguard students’ mental wellbeing. Key priorities include revising curricula, implementing structured emotional support programmes, and ensuring accessible services—requiring coordinated, long-term commitment across academic, healthcare, and policy sectors. Future research should explore longitudinal trends and the effectiveness of targeted interventions. Full article
21 pages, 4988 KiB  
Article
Ozone Exposure Induces Prediabetic Symptoms Through Hepatic Glycogen Metabolism and Insulin Resistance
by Yuchai Tian, Xiaoyun Wu, Zhihua Gong, Xiaomin Liang, Huizhen Zhu, Jiyue Zhang, Yangcheng Hu, Bin Li, Pengchong Xu, Kaiyue Guo and Huifeng Yue
Toxics 2025, 13(8), 652; https://doi.org/10.3390/toxics13080652 - 31 Jul 2025
Viewed by 276
Abstract
(1) Background: Epidemiological studies link ozone (O3) exposure to diabetes risk, but mechanisms and early biomarkers remain unclear. (2) Methods: Female mice exposed to 0.5/1.0 ppm O3 were assessed for glucose tolerance and HOMA (homeostasis model assessment) index. Genes related [...] Read more.
(1) Background: Epidemiological studies link ozone (O3) exposure to diabetes risk, but mechanisms and early biomarkers remain unclear. (2) Methods: Female mice exposed to 0.5/1.0 ppm O3 were assessed for glucose tolerance and HOMA (homeostasis model assessment) index. Genes related to impaired glucose tolerance and insulin resistance were screened through the Comparative Toxicogenomics Database (CTD), and verified using quantitative real-time PCR. In addition, liver histopathological observations and the determination of basic biochemical indicators were conducted, and targeted metabolomics analysis was performed on the liver to verify glycogen levels and gene expression. In vitro validation was conducted with HepG2 and Min6 cell lines. (3) Results: Fasting blood glucose and insulin resistance were elevated following O3 exposure. Given that the liver plays a critical role in glucose metabolism, we further investigated hepatocyte apoptosis and alterations in glycogen metabolism, including reduced glycogen levels and genetic dysregulation. Metabolomics analysis revealed abnormalities in fructose metabolism and glycogen synthesis in the livers of the O3-exposed group. In vitro studies demonstrated that oxidative stress enhances both liver cell apoptosis and insulin resistance in pancreatic islet β cells. (4) Conclusions: O3 triggers prediabetes symptoms via hepatic metabolic dysfunction and hepatocyte apoptosis. The identified metabolites and genes offer potential as early biomarkers and therapeutic targets. Full article
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33 pages, 2423 KiB  
Review
Chaperone-Mediated Responses and Mitochondrial–Endoplasmic Reticulum Coupling: Emerging Insight into Alzheimer’s Disease
by Manish Kumar Singh, Minghao Fu, Sunhee Han, Jyotsna S. Ranbhise, Wonchae Choe, Sung Soo Kim and Insug Kang
Cells 2025, 14(15), 1179; https://doi.org/10.3390/cells14151179 - 31 Jul 2025
Viewed by 431
Abstract
Alzheimer’s disease (AD) is increasingly recognized as a multifactorial disorder driven by a combination of disruptions in proteostasis and organelle communication. The 2020 Lancet commission reported that approximately 10 million people worldwide were affected by AD in the mid-20th century. AD is the [...] Read more.
Alzheimer’s disease (AD) is increasingly recognized as a multifactorial disorder driven by a combination of disruptions in proteostasis and organelle communication. The 2020 Lancet commission reported that approximately 10 million people worldwide were affected by AD in the mid-20th century. AD is the most prevalent cause of dementia. By early 2030, the global cost of dementia is projected to rise by USD 2 trillion per year, with up to 85% of that cost attributed to daily patient care. Several factors have been implicated in the progression of neurodegeneration, including increased oxidative stress, the accumulation of misfolded proteins, the formation of amyloid plaques and aggregates, the unfolded protein response (UPR), and mitochondrial–endoplasmic reticulum (ER) calcium homeostasis. However, the exact triggers that initiate these pathological processes remain unclear, in part because clinical symptoms often emerge gradually and subtly, complicating early diagnosis. Among the early hallmarks of neurodegeneration, elevated levels of reactive oxygen species (ROS) and the buildup of misfolded proteins are believed to play pivotal roles in disrupting proteostasis, leading to cognitive deficits and neuronal cell death. The accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles is a characteristic feature of AD. These features contribute to chronic neuroinflammation, which is marked by the release of pro-inflammatory cytokines and chemokines that exacerbate oxidative stress. Given these interconnected mechanisms, targeting stress-related signaling pathways, such as oxidative stress (ROS) generated in the mitochondria and ER, ER stress, UPR, and cytosolic chaperones, represents a promising strategy for therapeutic intervention. This review focuses on the relationship between stress chaperone responses and organelle function, particularly the interaction between mitochondria and the ER, in the development of new therapies for AD and related neurodegenerative disorders. Full article
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17 pages, 1580 KiB  
Article
Metformin Reduces Oxidative Damage in RNASEH2-Mutant Aicardi-Goutières Cells
by Francesca Dragoni, Jessica Garau, Bartolo Rizzo, Simona Orcesi, Costanza Varesio, Rosalinda Di Gerlando, Matteo Bordoni, Eveljn Scarian, Cristina Cereda, Orietta Pansarasa and Stella Gagliardi
Genes 2025, 16(8), 922; https://doi.org/10.3390/genes16080922 (registering DOI) - 30 Jul 2025
Viewed by 214
Abstract
Background: Aicardi-Goutières Syndrome (AGS) is a rare neuroinflammatory condition characterized by early-onset symptoms that extend outside the nervous system. Due to the rarity of the disease, the pathogenesis is not well understood, and its diagnosis and treatment remain elusive. We recently demonstrated mitochondrial [...] Read more.
Background: Aicardi-Goutières Syndrome (AGS) is a rare neuroinflammatory condition characterized by early-onset symptoms that extend outside the nervous system. Due to the rarity of the disease, the pathogenesis is not well understood, and its diagnosis and treatment remain elusive. We recently demonstrated mitochondrial abnormalities and increased reactive oxygen species (ROS) levels in lymphoblastoid cell lines (LCLs) derived from RNASEH2B- and RNASEH2A-mutated AGS patients. On this background, we turned our attention to metformin, the first-choice drug for type 2 diabetes, as a possible treatment acting on oxidative stress in RNASEH2-mutant AGS cells. Methods and Results: By means of flow cytometry, we found that metformin treatment significantly decreases ROS production in RNASEH2B- and RNASEH2A-mutated AGS LCLs. Of note, metformin treatment reduces the green JC-1 monomeric signal and, concurrently, increases the red JC-1 signal in both mutated LCLs, accounting for restoration of the mitochondrial membrane potential. Immunofluorescence staining shows a decrease in 8-oxoG levels only in RNASEH2B- mutated AGS LCLs. Finally, the significant upregulation of Forkhead Box O3 (FOXO3), cytochrome C somatic (CYCS), and superoxide dismutase 2 (SOD2) mRNA levels in RNASEH2B-mutated AGS LCLs after metformin treatment points to FOXO3 signaling as a possible mechanism to reduce oxidative stress. Conclusions: In conclusion, even if these pilot results need to be confirmed on a larger cohort, we shed light on metformin treatment as a valid approach to ameliorate oxidative stress-related inflammation in AGS patients. Full article
(This article belongs to the Section Cytogenomics)
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12 pages, 451 KiB  
Article
Medical Post-Traumatic Stress Disorder Symptoms in Children and Adolescents with Chronic Inflammatory Arthritis: Prevalence and Associated Factors
by Leah Medrano, Brenda Bursch, Jennifer E. Weiss, Nicholas Jackson, Deborah McCurdy and Alice Hoftman
Children 2025, 12(8), 1004; https://doi.org/10.3390/children12081004 - 30 Jul 2025
Viewed by 204
Abstract
Background: Youth with chronic rheumatologic diseases undergo medical experiences that can lead to post-traumatic stress disorder (PTSD). Understudied in pediatric rheumatology, medical PTSD can be significantly distressing and impairing. Objective: This study explored the prevalence of medical PTSD symptoms in youth with chronic [...] Read more.
Background: Youth with chronic rheumatologic diseases undergo medical experiences that can lead to post-traumatic stress disorder (PTSD). Understudied in pediatric rheumatology, medical PTSD can be significantly distressing and impairing. Objective: This study explored the prevalence of medical PTSD symptoms in youth with chronic inflammatory arthritis and associated factors, including pain, disease activity, mental health history, and anxiety sensitivity. Methods: A cross-sectional study of 50 youth (ages 8–18) with juvenile idiopathic arthritis (JIA) and childhood-onset systemic lupus erythematous (cSLE) was conducted at a pediatric rheumatology clinic. Participants completed self-report measures assessing post-traumatic stress symptoms (CPSS-V), pain, anxiety sensitivity (CASI), pain-related self-efficacy (CSES), adverse childhood experiences (ACEs), and fibromyalgia symptoms (PSAT). Clinical data included diagnoses, disease activity, treatment history, and demographics. Results: Forty percent had trauma symptoms in the moderate or more severe range. The 14% likely meeting criteria for probable medical PTSD were older (median 17 vs. 15 years, p = 0.005), had higher pain scores (median 4 vs. 3, p = 0.008), more ACEs (median 3 vs. 1, p = 0.005), higher anxiety sensitivity scores (median 39 vs. 29, p = 0.008), and higher JIA disease activity scores (median cJADAS-10 11.5 vs. 7.5, p = 0.032). They were also more likely to report a history of depression (71 vs. 23%, p = 0.020). No associations were found with hospitalization or injected/IV medication use. Conclusions: Medical trauma symptoms are prevalent in youth with chronic inflammatory arthritis. Probable PTSD was associated with pain and psychological distress. These findings support the need for trauma-informed care in pediatric rheumatology. Full article
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